Search results for: swiss albino mice

Authors: Laetitia Fourie

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Dangerous myths and stereotypes contribute to the fact that persons living with albinism are amongst the most vulnerable groups in society. The prevalence of albinism varies around the world and the World Health Organization estimates that around 1 in 5000 people in Sub-Saharan Africa are affected by this genetic disorder. Persons who are living with the condition usually experience a lack of melanin in their skin, eyes and hair that results in possible physical impairments such as poor eyesight and skin cancers. Being affected by such disorders and consequently classified as an albino, give way for unequal treatment which ultimately requires safeguarding these persons against unfair discrimination - not only on the basis of their race and color (or lack thereof), but also on the basis of their disability. The Constitution of the Republic of South Africa provides that everyone is equal before the law and prohibits unfair discrimination on the grounds of race, color and disability. This right is given effect to by the Employment Equity Act, which strives to eliminate unfair discrimination on similar grounds within any employment policy or practice. An essential non-discrimination measure that can be implemented in the labor market to achieve equality is the duty of reasonable accommodation that rests upon employers. However, reasonable accommodation is only introduced as an affirmative action measure in order to provide equal employment opportunities to the identified designated groups who include black people (defined to include Indians, Chinese and Colored), women and people with disabilities. Even though this duty exists, South African law does not elaborate on the scope of the duty, except for a Disability Code, which does not hold the force of law. Furthermore, in respect of applying affirmative action measures to people with disabilities, the law does not elaborate on the meaning of disability. Considering that persons living with albinism will find it difficult to show that they are black or disabled in order to be acknowledged as part of the designated groups, their access to reasonable accommodation will be limited to a great extent. This paper will aim to illustrate to which extent South African law currently fails to implement its international obligations as a State Party to the Conventions of the United Nations, and how these failures should be corrected in order to serve the needs of all South Africans, including albinos.

Keywords: albinism, disability, equality, South Africa, United Nations

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Authors: Suzanne Strauss, Leandi Steenkamp

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The Finnish symphonic metal band Nightwish is the brainchild of songwriter and lyricist TuomasHolopainen and the band recorded their first demonstration recording in 1996. The band has since produced nine full-length studio albums, the most recent being the 2020 album Human. :||: Nature., and has reached massive international success. The band is well known for songs about fantasy and escapism and employs many sonic, visual and branding tools and techniques to communicate these constructs to the audience. Among these, is the band’s creation of the so-called “Nightwish world and mythology” with a set of recurring characters and narratives which, in turn, creates a psychological anchor and safe space for Nightwish fans around the globe. Nature and the reverence of nature are central themes in Nightwish’s self-created mythology.Swiss psychologist Carl Jung’s theory of the collective unconscious identified a mysterious reservoir of psychological constructs common to all people, being derived from ancestral memory and experience, common to all humankind, and distinct from the individual’s personal unconscious. Furthermore, he defined archetypes as timeless collective patterns and images that springs forth from the collective unconscious. Archetypes can be actualized when they enter consciousness as images in interaction with the outside world. Archetypal patterns or images can manifest in different ways across world cultures, but follow common patterns, also known as archetypal themes and symbols. The Jungian approach to the psyche places great emphasis on nature, positing a direct link betweenthe concept of wholeness and responsible care for nature and the environment.In our proposed paper, we examine, by means of thematic content analysis, how Nightwish makes use of archetypal themes and symbols referring to nature and the environment in selected songs from their ninth full-length album Human. II Nature. Furthermore, we argue that the longing for and reverence of nature in selected Nightwish songs may serve as a type of “social intervention” and social critique on modern capitalist society. The type of social critique that the band offers is generally connoted intertextually and is not equally explicit in their songs. The band uses a unique combination of escapism, fantasy, and nature narratives to inspire a sense of wonder, enchantment, and magic in the listener. In this way, escapism, fantasy, and nature serve as postmodern frames of reference that aim to “re-enchant” the disenchanted and de-spiritualized. In this way, re-enchantment could also refer to spiritual and/or psychological healing and rebirth.

Keywords: archetypes, metal music, nature, Nightwish, social interventions

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Authors: Nicola G. G. Cecca

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In Italian IPSSEOAs, high schools that give a vocational education to students that will work in the field of Enogastronomy and Hotel Management, the course of Food Science allows the students to start and see food as a mixture of substances that they will transform during their profession. These substances are characterized not only by a chemical composition but also by a molecular structure that makes them nutritionally active. But the increasing number of new products proposed by Food Industry, the modern techniques of production and transformation, the innovative preparations required by customers have made many information reported in the most wide spread Food Science textbooks not up-to-date or too poor for the people who will work in catering sector. Often Authors offer information aged to Bohr’s Atomic Model and to the ‘Octet Rule’ proposed by G.N. Lewis to describe the Chemical Bond, without giving any reference to new as Orbital Atomic Model and Molecular Orbital Theory that, in the meantime, start to be old themselves. Furthermore, this antiquated information precludes an easy understanding of a wide range of properties of nutritive substances and many reactions in which the food constituents are involved. In this paper, our attention is pointed out to use GEOMAG™ to represent the dynamics with which the chemical bond is formed during the synthesis of the molecules. GEOMAG™ is a toy, produced by the Swiss Company Geomagword S.A., pointed to stimulate in children, aged between 6-10 years, their fantasy and their handling ability and constituted by metallic spheres and metallic magnetic bars coated by coloured plastic materials. The simulation carried out with GEOMAG™ is based on the similitude existing between the Coulomb’s force and the magnetic attraction’s force and in particular between the formulae with which they are calculated. The electrostatic force (F in Newton) that allows the formation of the chemical bond can be calculated by mean Fc = kc q1 q2/d2 where: q1 e q2 are the charge of particles [in Coulomb], d is the distance between the particles [in meters] and kc is the Coulomb’s constant. It is surprising to observe that the attraction’s force (Fm) acting between the magnetic extremities of GEOMAG™ used to simulate the chemical bond can be calculated in the same way by using the formula Fm = km m1 m2/d2 where: m1 e m2 represent the strength of the poles [A•m], d is the distance between the particles [m], km = μ/4π in which μ is the magnetic permeability of medium [N•A-2]. The magnetic attraction can be tested by students by trying to keep the magnetic elements of GEOMAG™ separate by hands or trying to measure by mean an appropriate dynamometric system. Furthermore, by using a dynamometric system to measure the magnetic attraction between the GEOMAG™ elements is possible draw a graphic F=f(d) to verify that the curve obtained during the simulation is very similar to that one hypnotized, around the 1920’s by Linus Pauling to describe the formation of H2+ in according with Molecular Orbital Theory.

Keywords: chemical bond, molecular orbital theory, magnetic attraction force, GEOMAG™

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Authors: Katerina Balounova, Jiri Pacha, Peter Ergang, Martin Vodicka, Pavlina Kvapilova

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MicroRNAs are small non-coding RNAs involved in a wide range of physiological processes. Post-transcriptional regulation of gene expression by microRNAs gives the organism a further level of control of the gene-expression program and the disruption of this microRNA regulatory mechanism seems to increase the risk of various pathophysiological conditions including tumorigenesis. To the present day, microRNAs were shown to participate in the mayor signalization pathways leading to tumorigenesis, including proliferation, cell cycle, apoptosis and metastasis formation. In addition, microRNAs have been found to play important roles in the generation and maintenance of circadian clock. These clocks generate circadian rhythms, which participate in a number of regulatory pathways. Disruption of the circadian signals seems to be associated with the development and the progression of tumours including colorectal cancer. We investigated therefore whether the diurnal profiles of miRNAs linked to tumorigenesis and regulation of circadian clock are changed during tumorigenesis. Based on published data we chose 10 microRNAs linked to tumorigenesis or circadian clock (let-7b-5p, miR 1 3p, miR 106b 5p, miR 141 3p, miR 191 5p, miR 20a 5p, miR 25 3p, miR 29a 3p, miR 34a 5p and miR 93 5p) and compared their 24-hr expression profiles in healthy and in chemically induces primary colorectal tumours of 52week-old mice. Using RT-qPCR we proved circadian rhythmicity in let-7b-5p, miR 106b 5p, miR 141 3p, miR 191 5p, miR 20a 5p, miR 25 3p, miR 29a 3p and miR 93 5p in healthy colon but not in tumours. The acrophases of miR 106b 5p, miR 141 3p, miR 191 5p, miR 20a 5p, miR 25 3p and miR 93 5p were reached around CT 24, the acrophases of let-7b-5p and miR-29a-3p were slightly shifted and reached around CT 21. In summary, our results show that circadian regulation of some colonic microRNAs is greatly affected by neoplastic transformation.

Keywords: circadian rhythm, colon, colorectal cancer, microRNA, tumorigenesis

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Authors: Changde Zhang, Qiang Zhang, Shilong Zheng, Jiawang Liu, Shanchun Guo, Qiu Zhong, Guangdi Wang

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Fulvestrant was approved by FDA to treat breast cancer as a selective estrogen receptor downregulator (SERD) with intramuscular injection administration. ZB716, a fulvestarnt-3 boronic acid, is an SERD with comparable anticancer effect to fulvestrant, but could produce good pharmacokinetic properties under oral administration with mice or rat models. To understand why ZB716 produced much better oral bioavailability, it was proposed that the boronic acid blocked the phase II direct biotransformation with the hydroxyl group on the 3 position of the aromatic ring on fulvestrant. In this study, ZB716 or fulvestrant was incubated with human liver microsome and oxidation cofactor NADPH in vitro. Their metabolites after oxidation were profiled with the Q-Exactive, a high-resolution mass spectrometer. The result showed that ZB716 blocked the forming of hydroxyl groups on its benzene ring except for the oxidation of C-B bond forming fulvestrant in its metabolites, and the concentration of fulvestrant with one more hydroxyl group found in the metabolites from incubation with fulvestrant was about 34 fold high as that formed from incubation with ZB716. Compared to fulvestrant, ZB716 is expected to be much difficult to be further bio-transformed into more hydrophilic compounds, to be difficult excreted out of blood system, and to have longer residence time in blood, which can lead to higher oral bioavailability. This study provided evidence to explain the high bioavailability of ZB716 after oral administration from the perspective of its difficulty of oxidation, a phase I biotransformation, on positions on its aromatic ring.

Keywords: biotransformation, fulvestrant, metabolite profiling, ZB716

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Authors: Haile F. Darge, Hsieh C. Tsai

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The tumor microenvironment affects the therapeutic outcomes of cancer disease. In a malignant tumor, overexpression of vascular endothelial growth factor (VEGF) provokes the production of pathologic vascular networks. This results in a hostile tumor environment that hinders anti-cancer drug activities and profoundly fuels tumor progression. In this study, we develop a strategy of sequential sustain release of the anti-angiogenic drug: Bevacizumab(BVZ), and anti-cancer drug: Doxorubicin(DOX) which had a synergistic effect on cancer treatment. Poly (D, L-Lactide)- Poly (ethylene glycol) –Poly (D, L-Lactide) (PDLLA-PEG-PDLLA) thermo-sensitive hydrogel was used as a vehicle for local delivery of drugs in a single platform. The in vitro release profiles of the drugs were investigated and confirmed a relatively rapid release of BVZ (73.56 ± 1.39%) followed by Dox (61.21 ± 0.62%) for a prolonged period. The cytotoxicity test revealed that the copolymer exhibited negligible cytotoxicity up to 2.5 mg ml-1 concentration on HaCaT and HeLa cells. The in vivo study on Hela xenograft nude mice verified that hydrogel co-loaded with BVZ and DOX displayed the highest tumor suppression efficacy for up to 36 days with pronounce anti-angiogenic effect of BVZ and with no noticeable damage on vital organs. Therefore, localized co-delivery of anti-angiogenic drug and anti-cancer drugs by the hydrogel system may be a promising approach for enhanced chemotherapeutic efficacy in cancer treatment.

Keywords: anti-angiogenesis, chemotherapy, controlled release, thermo-sensitive hydrogel

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Authors: Ioannis Boutas, Vasilios Pergialiotis, Nicolaos Salakos, George Agrogiannis, Panagiotis Konstantopoulos, Laskarina-Maria Korou, Theodoros Kalampokas, Odysseas Gregoriou, George Creatsas, Despina Perrea

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Introduction: The effect of third generation aromatase inhibitors in the lipid profile among women with breast cancer, present diversities. It has been also shown that low levels of estrogens affect liver metabolism in mice in numerous ways, such as lipid accumulation and hepatic steatosis. Materials and Methods: Forty-five female Wistar rats underwent surgical ovariectomy. The animals were anesthetized with a combination of ketamine (75 mg/kg) and xylazine (10 mg/kg) which were administered intraperitoneally. After the ovariectomy, the operated animals were randomized in three groups. The first group did not receive any drug regimen (ovariectomized control group). The second group received Anastrazole and the third group received Letrozole. Four months after the initiation of the study, the animals were euthanized and livers were dissected immediately for further histopathological analysis. The histological features were grouped into 4 broad categories: steatosis, ballooning, portal inflammation and lobular activity. A score from 0 (absence) to 3 (severe) was assigned to each parameter. Results: The liver pathology analysis revealed significant differences among groups with favored mild steatosis and ballooning among animals that received Anastrazole or Letrozole. Conclusion: The effect of Anastrazole and Letrozole on liver function have not yet been clarified. In our study mild histological liver alterations seem also to occur and these alterations should be taken in mind in future clinical studies

Keywords: anastrazole, letrozole, liver, rats

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Authors: Priti S. Tidke, Chandragouda R. Patil

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The present study was designed to investigate the effect of Magnesia phosphorica, a biochemical medicine on urine screeing, biochemical, histopathological, and electron microscopic images in ethylene glycol induced nepholithiasis in rats.Male Wistar albino rats were divided into six groups and were orally administered saline once daily (IR-sham and IR-control) or Magnesia phosphorica 100 mg/kg twice daily for 24 days.The effect of various dilutions of biochemical Mag phos3x, 6x, 30x was determined on urine output by comparing the urine volume collected by keeping individual animals in metabolic cages. Calcium oxalate urolithiasis and hyperoxaluria in male Wistar rats was induced by oral administration of 0.75% Ethylene glycol p.o. daily for 24 days. Simultaneous administration of biochemical 3x, 6x, 30xMag phos (100mg/kg p.o. twice a day) along with ethylene glycol significantly decreased calcium oxalate, urea, creatinine, Calcium, Magnesium, Chloride, Phosphorus, Albumin, Alkaline Phosphatase content in urine compared with vehicle-treated control group.After the completion of treatment period animals were sacrificed, kidneys were removed and subjected to microscopic examination for possible stone formation. Histological estimation of kidney treated with biochemical Mag phos (3x, 6x, 30xMag phos 100 mg/kg, p.o.) along with ethylene glycol inhibited the growth of calculi and reduced the number of stones in kidney compared with control group. Biochemical Mag phos of 3x dilution and its crude equivalent also showed potent diuretic and antiurolithiatic activity in ethylene glycol induced urolithiasis. A significant decrease in the weight of stones was observed after treatment in animals which received biochemical Mag phos of 3x dilution and its crude equivalent in comparison with control groups. From this study, it can be proposed that the 3x dilution of biochemical Mag phos exhibits a significant inhibitory effect on crystal growth, with the improvement of kidney function and substantiates claims on the biological activity of twelve tissue remedies which can be proved scientifically through laboratory animal studies.

Keywords: Mag phos, Magnesia phosphorica, ciochemic medicine, urolithiasis, kidney stone, ethylene glycol

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Authors: Li-Te Lin, Chia-Jung Li, Kuan-Hao Tsui

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Cuproptosis, a newly identified cell death mechanism, has attracted attention for its association with various diseases. However, the genetic interplay between cuproptosis and ovarian aging remains largely unexplored. This study aims to address this gap by analyzing datasets related to ovarian aging and cuproptosis. Spatial transcriptome analyses were conducted in the ovaries of both young and aged female mice to elucidate the role of FDX1. Comprehensive bioinformatics analyses, facilitated by R software, identified FDX1 as a potential cuproptosis-related gene with implications for ovarian aging. Clinical infertility biopsies were examined to validate these findings, showing consistent results in elderly infertile patients. Furthermore, pharmacogenomic analyses of ovarian cell lines explored the intricate association between FDX1 expression levels and sensitivity to specific small molecule drugs. Spatial transcriptome analyses revealed a significant reduction in FDX1 expression in aging ovaries, supported by consistent findings in biopsies from elderly infertile patients. Pharmacogenomic investigations indicated that modulating FDX1 could influence drug responses in ovarian-related therapies. This study pioneers the identification of FDX1 as a cuproptosis-related gene linked to ovarian aging. These findings not only contribute to understanding the mechanisms of ovarian aging but also position FDX1 as a potential diagnostic biomarker and therapeutic target. Further research may establish FDX1's pivotal role in advancing precision medicine and therapies for ovarian-related conditions.

Keywords: cuproptosis, FDX1, ovarian aging, biomarker

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Authors: Eitedal Daoud, Reda M.Daoud, Khaled Abdel-Wahhab, Maha M.Saber, Lobna Saber

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Background: Cis-platin is a widely used chemotherapeutic drug to treat many malignant disorders including head and neck malignancies. Oto-nephrotxicity is an important and dose - limiting side effect of cis - platin therapy. Nowadays, more attention had been paid to oto-toxicity caused with cis-platin. Aim of the Work: This study was designed to investigate the potential protective effect of Whey protein (WP) against cis-platin induced ototoxicity compared to the effect of N-acetylcysteine (NAC) in rats. Methodology: Male albino rats were randomly divided into 6 groups: untreated rats (control), rats orally treated with whey protein (1g/kg b.w/day) for seven executive days, rats treated orally with N-acetylcysteine (500 mg/kgb.w /day) for seven executive days, rates intoxicated intraperitoneal (ip) with cis- platin (10 mg/kgb.w. once), rats treated with whey protein (1g/kgb.w./day) for seven executive days) followed by one injection (ip) of cis-platin(10 mg/kg b.w.) one hour after the last oral administration of whey protein, rats treated with N- acetylcysteine (for seven executive days followed by one injection (ip) of cis-platin (10 mg/kgb.w) one hour after the last oral administration of N-acetylcysteine. The organ of Corti, the stria vascularis and spiral ganglia were visualized by light microscopy at different magnifications. Results: Cis-platin intoxicated animals showed a significant decrease in serum level of total antioxidant capacity (TAC),with inhibition in the activity of serum glutathione-s transferase(GST) and paraoxonnase-1 (PON-1) in comparison with control. Group treated with either NAC or WP with cis-platin showed significant elevation in the activity of both GST & PON-1 with increased serum level of TAC when compared with cis-platin intoxicated rats. Animals treated with NAC or WP with cis-platin compared to those treated with cis-platin alone showed marked degree of improvement towards control rats as there was significant drop in the serum level of cortecosterone, nitric oxide (NO), and melandialdehyde (MDA).Histopathologic, in NAC pretreated group there was no changes in stria vascularis or spiral ganglia. In group pretreated with WP, there was no histopathologic alteration detected in the organ of Corti and Reissers membrane but oedema and haemorrhage were founded in the stria vascularis in small focal manner. Conclusion: Our finding showed that Whey protein is a natural dietary supplement product proved its ability of protection of anti-oxidant system and the cochlea against cis-platin induced ototoxicity.

Keywords: anti-oxidant, cis-platin, N-acetylcysteine, ototoxicity, whey protein

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Authors: O. C. Abbah, O. Obidoa, J. Omale

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Prostate tumor is fast becoming a leading cause of morbidity and mortality in human male adults, with 50 percent of men aged 50 years and above having histological evidence of the benign tumor. The study was set out to undertake phytochemical screening and proximate analysis of the pulp of A. muricata fruit - soursop; to determine the acute toxicity of the fruit pulp extract and its effect on male albino Wistar rats with concurrent induction of experimental benign prostate hyperplasia (BPH). Eighteen rats (average weight of 100g) were used for the lethality studies and were orally administered graded doses of aqueous extracts of the fruit pulp up to 5000 mg/kg body weight. Twenty five rats weighing 150-200g were divided into five groups of five rats each for the tumor studies. The groups included four controls – Hormone control, HC, which took Testosterone, T; and Estradiol, E2 – only, in olive oil as vehicle; Vehicle control, VC; Soursop control, SC, which received the extract only; VS, Vehicle and Soursop – and the Test group, TG (500mg/kg b.w.). All rats were dosed orally. Tumor was induced with exogenous Testosterone propionate: Estradiol valerate at 300µg: 80µg/kg b.w. (respectively) in olive oil, administered subcutaneously in the inguinal region of the rats on alternate days for 21 days. Administration of the fruit pulp at graded doses up to 5000mg/kg resulted in no lethality even after 72 hours. Results from tumor studies revealed that the administration of the fruit extracts significantly (p < 0.05) reduced the relative prostate weight of the TG compared with the HC, with values of 006±0.001 and 0.010±0.003 respectively. Treatment with vehicle, soursop and vehicle with soursop caused no significant (p>0.05) change in prostate size, with their respective relative prostate weights being 0.002±0.001, 0.004±0.002 and 0.002±0.001 compared with TG. Also, treatment with A. muricata fruit extract significantly decreased (p < 0.05) serum prostate specific antigen, PSA, in TG compared with HC, with values 0.055±0.017 and 0.194±0.068 ng/ml respectively. Furthermore, A. muricata administration displayed Testosterone boosting, Estradiol lowering and consequently testosterone-estradiol ratio increasing potential at the end of the 21 days. The preventive property of soursop against experimental BPH was corroborated by histological evidence in this study. The study concludes that A. muricata fruit holds a great potential for benign prostate tumor prevention and, possibly, management.

Keywords: annona muricata, benign prostate tumor, hormone, preventive potential, soursop

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Authors: Ji Won Kim, Moo Yeol Lee, Keon Wook Kang

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GV-1001, 16 amino acid fragment of human telomerase reverse transcriptase catalytic subunit (hTERT), has been developed as an injectable cancer vaccine for many types of solid tumors showing high-level of telomerase activity. In the present study, we evaluated the anti-cancer effect of GV-1001 on androgen-receptor-positive prostate cancer. Two signaling pathways, Gs-adenylate cyclase-cAMP and Gq-IP3-Ca2+ pathways play a central role in GnRH receptor (GnRHR)-mediated activities. We found that leuprolide acetate (LA) mainly acted on Gq-mediated Ca2+ signaling, while GV-1001 preferentially acted on cAMP signaling; and both the effects were counteracted by cetrorelix, a GnRHR antagonist. We further tested whether GV-1001 affects tumor growth of human prostate cancer cells in vivo. Prostate tumor xenografts were established using LNCap, androgen receptor-positive prostate cancer cells, and the nude mice bearing tumors were subcutaneously injected with GV-1001 (0.01, 0.1, 1, 10 microg/kg/day) and LA (0.01 microg/kg/day) for 2 weeks. GV-1001 (1 and 10 microg/kg/day) significantly inhibited tumor growth of LNCap xenografts. Interestingly, mRNA expression of MMP2 and MMP9 was significantly suppressed by GV-1001 injection, but not by LA administration. Boyden chamber assay revealed that GV-1001 potently inhibited cell migration of LNCap. Our finding suggests that GV-1001 as a novel GnRHR ligand, has anti-proliferative and anti-migratory effects on androgen receptor-positive prostate cancer cells.

Keywords: GV-1001, GnRH, hTERT, prostate cancer

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Authors: Wan Liu, Haibo Wang, Cathy Huang, Zhiwu Tan, Zhiwei Chen

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The tremendous diversity of HIV-1 has been a major challenge for an effective AIDS vaccine development. Mosaic approach presents the potential for vaccine design aiming for global protection. The mosaic antigen of HIV-1 Gag allows antigenic breadth for vaccine-elicited immune response against a wider spectrum of viral strains. However, the enhancement of immune response using vaccines is dependent on the strategy used. Heterologous prime/boost regimen has been shown to elicit high levels of immune responses. Here, we investigated whether priming using plasmid DNA with electroporation followed by boosting with the live replication-competent modified vaccinia virus vector TianTan (MVTT) combined with the mosaic antigenic sequence could elicit a greater and broader antigen-specific response against HIV-1 Gag in mice. When compared to DNA or MVTT alone, or MVTT/MVTT group, DNA/MVTT group resulted in coincidentally high frequencies of broadly reactive, Gag-specific, polyfunctional, long-lived, and cytotoxic CD8+ T cells and increased anti-Gag antibody titer. Meanwhile, the vaccination could upregulate PD-1+, and Tim-3+ CD8+ T cell, myeloid-derived suppressive cells and Treg cells to balance the stronger immune response induced. Importantly, the prime/boost vaccination could help control the EcoHIV and mesothelioma AB1-gag challenge. The stronger protective Gag-specific immunity induced by a Mosaic DNA/MVTT vaccine corroborate the promise of the mosaic approach, and the potential of two acceptably safe vectors to enhance anti-HIV immunity and cancer prevention.

Keywords: DNA/MVTT vaccine, EcoHIV, mosaic antigen, mesothelioma AB1-gag

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Authors: Vanitha Varadharaj, Vijalakshmi Krishnamurthy

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Annona squamosa Linn, commonly known as Sugar apple, belonging to the family Annonaceae, is said to show varied medicinal effects, including insecticide, antiovulatory and abortifacient. The alkaloid and flavonoids present in Annona squamosa leaf has proved to have antioxidant activity. The present work has been planned to investigate the effect of ethanolic leaf extract of Annona squamosa leaf on Den Induced wistar albino rats. The study was carried out to analyze the biochemical Parmeters like Total Proteins, Bilirubin, Enzymatic and Non –Enzymatic enzymes, Marker enzymes and Tumor markers in serum and also the histopathological studies in liver is carried out in control and DEN induced rats. Supplementation of ELAS (Ethanolic Leaf Extract Of Annona squamosa) reduced the liver weight and also reduced the tumour incidence. Chemoprevention group showed near normal values of bilirubin when compared with the control rats. Total protein was decreased in the cancer bearing group and on treatment with the extract the levels of protein were restored. Both in pre and post treatment group, the activities of enzymatic antioxidants such as superoxide dismutase, catalase, and Glutathione peroxidase were increased but in pre treated animals it was more effective than post treated animals. The non- enzymatic antioxidants such as vitamin C and vitamin E were brought back to normal level significantly in post and pre treated animals. Activities of marker enzymes such as SGOT, SGPT, ALP, γ GT were significantly elevated in the serum of cancer animals and the values returned to normal after treatment with the extract suggesting the hepato protective effect of the extract. Lipid peroxide was found to be elevated in the cancer induced group. This condition was brought back to the normal in the pre and post treated animals with ELAS. Histological examination also confirmed the anti- carcinogenic potential of ELAS, Cancer induced groups had a triple fold increase in their AFP values when compared to other groups. DEN treatment increased the level of AFP expression while ELAS partially counteracted the effect of it. So the scientific validation obtained from this study may pave way to many budding scientists to find new drugs from Annona squamosa for various ailments.

Keywords: annona squamosa, biochemical parmeters, cancer, leaf extract

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Authors: Yasmin M. Attia, Hanan S. El-Abhar, Mahmoud M. Al Marzabani, Samia A. Shouman

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Background: Tamoxifen (TAM) is the most commonly used hormone therapy for the treatment of early and metastatic breast cancer. Although it significantly decreases the tumor recurrence rate and provides an overall benefit, as much as 20–30% of women still relapse during or after long-term therapy. 3-Bromopyruvate (3-BP) is a promising agent with impressive antitumor effects in several models of animal tumors and cell lines. Aim: This study was designed to investigate the combined effect of (TAM) and (3-BP) in breast cancer cells and to explore their molecular interaction via assessment of apoptotic, angiogenic, and metastatic markers. Methods: In vitro cytotoxicity study was carried out for both compounds to determine the combination regimen producing a synergistic effect and mechanistic pathways were studied using RT-PCR and western techniques. Moreover, the anti-oncolytic and anti-angiogenic potentials were assessed in mice bearing solid Ehrlich carcinoma (SEC). Results: The combined treatment significantly increased the expressions and protein levels of caspase 7, 9, and 3 and decreased of angiogenic markers VEGF, HIF-1α, and HK2 compared to cells treated with either drug individually. However, there were no significant changes in MMP-2 and MMP-9 protein levels. Interestingly, the in vivo results supported the in vitro findings; there was a decrease in the tumor volume and VEFG using immunohistochemistry in the combination-treated groups compared to either TAM or 3-BP treated one. Conclusion: 3-BP synergizes the cytotoxic effect of TAM by increasing apoptosis and decreasing angiogenesis which makes this combination a promising regimen to be applied clinically.

Keywords: tamoxifen, 3-bromopyruvate, breast cancer, cytotoxicity, angiogenesis

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

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

Keywords: bioresorbable, calcium sulfate, controlled release, NanoZolid

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Authors: Vadim Makarov, Stewart T.Cole

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PBTZ169 is novel drug candidate with high efficacy in animals models, and its combination treatment of PBTZ169 with BDQ and pyrazinamide was shown to be more efficacious than the standard treatment for tuberculosis in a mouse model. The target of PBTZ169 is famous DprE1, an essential enzyme in cell wall biosynthesis. The crystal structure of the DprE1-PBTZ169 complex reveals formation of a semimercaptal adduct with Cys387 in the active site and explains the irreversible inactivation of the enzyme. Furthermore, this drug candidate demonstrated during preclinical research ‘drug like’ properties what made it an attractive drug candidate to treat tuberculosis in humans. During first clinical trials several cohorts of the healthy volunteers were treated by the single doses of PBTZ169 as well as two weeks repeated treatment was chosen for two maximal doses. As expected PBTZ169 was well tolerated, and no significant toxicity effects were observed during the trials. The study of the metabolism shown that human metabolism of PBTZ169 is very different from microbial or animals compound transformation. So main pathway of microbial, mice and less rats metabolism connected with reduction processes, but human metabolism mainly connected with oxidation processes. Due to this difference we observed several metabolites of PBTZ169 in humans with antitubercular activity, and now we can conclude that animal antituberculosis activity of PBTZ169 is a result not only activity of the drug itself, but it is a result of the sum activity of the drug and its metabolites. Direct antimicrobial plasma activity was studied, and such activity was observed for 24 hours after human treatment for some doses. This data gets high chance for good efficacy of PBTZ169 in human for treatment TB infection. Second phase of clinical trials was started summer of 2017 and continues to the present day. Available data will be presented.

Keywords: clinical trials, DprE1, PBTZ169, metabolism

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Authors: Tzu-Hao Li, Shie-Liang Hsieh, Han-Chieh Lin, Ying-Ying Yang

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TNF superfamily-stimulated pathogenic cascades and macrophage (M1)/kupffer cells (KC) polarization are important in the pathogenesis of ischemia-reperfusion (IR) liver injury in animals with hepatic steatosis (HS). Decoy receptor 3 (DcR3) is a common upstream inhibitor of the above-mentioned pathogenic cascades. The study evaluated whether modulation of these DcR3-related cascades was able to protect steatotic liver from IR injury. Serum and hepatic DcR3 levels were lower in patients and animals with HS. Accordingly, the effects of pharmacologic and genetic DcR3 replacement on the IR-related pathogenic changes were measured. Significantly, DcR3 replacement protected IR-Zucker(HS) rats and IR-DcR3-Tg(HS) mice from IR liver injury. The beneficial effects of DcR3 replacement were accompanied by decreased serum/hepatic TNF, soluble TNF-like cytokine 1A (TL1A), Fas ligand (Fas-L) and LIGHT, T-helper-cell-1 cytokine (INF) levels, neutrophil infiltration, M1 polarization, neutrophil-macrophage/KC-T-cell interaction, hepatocyte apoptosis and improved hepatic microcirculatory failure among animals with IR-injured steatotic livers. Additionally, TL1A, Fas-L, LIGHT and TLR4/NFB signals were found to mediate the DcR3-related protective effects of steatotic livers from IR injury. Using multimodal in vivo and in vitro approaches, we found that DcR3 was a potential agent to protect steatotic livers from IR injury by simultaneous blocking the multiple IR injury-related pathogenic changes.

Keywords: Decoy 3 receptor, ischemia-reperfusion injury, M1 polarization, TNF superfamily

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Authors: Sanjeev Kumar Appicharla

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This paper presents the results of the modelling and analysis of the European Railway Traffic Management (ERTMS) safety-critical incident to raise awareness of biases in the systems engineering process on the Cambrian Railway in the UK using the RAIB 17/2019 as a primary input. The RAIB, the UK independent accident investigator, published the Report- RAIB 17/2019 giving the details of their investigation of the focal event in the form of immediate cause, causal factors, and underlying factors and recommendations to prevent a repeat of the safety-critical incident on the Cambrian Line. The Systems for Investigation of Railway Interfaces (SIRI) is the methodology used to model and analyze the safety-critical incident. The SIRI methodology uses the Swiss Cheese Model to model the incident and identify latent failure conditions (potentially less than adequate conditions) by means of the management oversight and risk tree technique. The benefits of the systems for investigation of railway interfaces methodology (SIRI) are threefold: first is that it incorporates the “Heuristics and Biases” approach advanced by 2002 Nobel laureate in Economic Sciences, Prof Daniel Kahneman, in the management oversight and risk tree technique to identify systematic errors. Civil engineering and programme management railway professionals are aware of the role “optimism bias” plays in programme cost overruns and are aware of bow tie (fault and event tree) model-based safety risk modelling techniques. However, the role of systematic errors due to “Heuristics and Biases” is not appreciated as yet. This overcomes the problems of omission of human and organizational factors from accident analysis. Second, the scope of the investigation includes all levels of the socio-technical system, including government, regulatory, railway safety bodies, duty holders, signaling firms and transport planners, and front-line staff such that lessons are learned at the decision making and implementation level as well. Third, the author’s past accident case studies are supplemented with research pieces of evidence drawn from the practitioner's and academic researchers’ publications as well. This is to discuss the role of system thinking to improve the decision-making and risk management processes and practices in the IEC 15288 systems engineering standard and in the industrial context such as the GB railways and artificial intelligence (AI) contexts as well.

Keywords: accident analysis, AI algorithm internal audit, bounded rationality, Byzantine failures, heuristics and biases approach

Procedia PDF Downloads 178

Authors: Norah Al Hokbany, Ibrahim Al Jammaz, Basem Al Otaibi, Yousif Al Malki, Subhani M. Okarvi

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Objective: The folate receptor is over-expressed in a wide variety of human tumors. Conjugates of folate have been shown to be selectively taken up by tumor cells via the folate receptor. In an attempt to develop new folate radiotracers with favorable biochemical properties for detecting folate receptor-positive cancers. Methods: we synthesized ⁶⁴Cu-NOTA- and ⁶⁴Cu-NOTAM-folate conjugates using a straightforward and simple one-step reaction. Radiochemical yields were greater than 95% (decay-corrected) with a total synthesis time of less than 20 min. Results: Radiochemical purities were always greater than 98% without high-performance liquid chromatography (HPLC) purification. These synthetic approaches hold considerable promise as a rapid and simple method for ⁶⁴Cu-folate conjugate preparation with high radiochemical yield in a short synthesis time. In vitro tests on the KB cell line showed that significant amounts of the radio conjugates were associated with cell fractions. Bio-distribution studies in nude mice bearing human KB xenografts demonstrated a significant tumor uptake and favorable bio-distribution profile for ⁶⁴Cu-NOTA- and ⁶⁴Cu-NOTAM-folate conjugate. The uptake in the tumors was blocked by the excess injection of folic acid, suggesting a receptor-mediated process. Conclusion: These results demonstrate that the ⁶⁴Cu-NOTAM-folate conjugate may be useful as a molecular probe for the detection and staging of folate receptor-positive cancers, such as ovarian cancer and their metastasis, as well as monitoring tumor response to treatment.

Keywords: folate, receptor, tumor imaging, ⁶⁴Cu-NOTA-folate, PET

Procedia PDF Downloads 91

Authors: Kim Byeong-Gon, Lee Pureun-Haneul, Hong Jisu, Jang An-Soo

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Background: Diesel exhaust particles (DEPs) lead to trigger airway hyperresponsiveness (AHR) and airway dysfunction or inflammation in respiratory systems. Whether tight junction protein changes can contribute to development or exacerbations of airway diseases remain to be clarified. Objective: The aim of this study was to observe the effect of DEP on tight junction proteins in one airway both nose and lung in a mouse model. Methods: Mice were treated with saline (Sham) and exposed to 100 μg/m³ DEPs 1 hour a day for 5 days a week for 4 weeks and 8 weeks in a closed-system chamber attached to a ultrasonic nebulizer. Airway hyperresponsiveness (AHR) was measured and bronchoalveolar lavage (BAL) fluid, nasal lavage (NAL) fluid, lung and nasal tissue was collected. The effects of DEP on tight junction proteins were estimated using western blot, immunohistochemical in lung and nasal tissue. Results: Airway hyperresponsiveness and number of inflammatory cells were higher in DEP exposure group than in control group, and were higher in 4 and 8 weeks model than in control group. The expression of tight junction proteins CLND4, -5, and -17 in both lung and nasal tissue were significantly increased in DEP exposure group than in the control group. Conclusion: These results suggesting that CLDN4, -5 and -17 may be involved in the airway both nose and lung, suggesting that air pollutants cause to disruption of epithelial and endothelial cell barriers. Acknowledgment: This research was supported by Korea Ministry of Environment (MOE) as 'The Environmental Health Action Program' (2016001360009) and Soonchunhyang University Research Fund.

Keywords: diesel exhaust particles, air pollutant, tight junction, Claudin, Airway inflammation

Procedia PDF Downloads 121

Authors: Rauza Sukma Rita, Katsuya Dezaki, Yuko Maejima, Toshihiko Yada

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Oxytocin is a nine-amino acid peptide synthesized in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus. Oxytocin promotes contraction of the uterus during birth and milk ejection during breast feeding. Although oxytocin receptors are found predominantly in the breasts and uterus of females, many tissues and organs express oxytocin receptors, including the pituitary, heart, kidney, thymus, vascular endothelium, adipocytes, osteoblasts, adrenal gland, pancreatic islets, and many cell lines. On the other hand, in pancreatic islets, oxytocin receptors are expressed in both α-cells and β-cells with stronger expression in α- cells. However, to our knowledge there are no reports yet about the effect of oxytocin on cytosolic calcium reaction on α and β-cell. This study aims to investigate the effect of oxytocin on α-cells and β-cells and its oscillation pattern. Islet of Langerhans from wild type mice were isolated by collagenase digestion. Isolated and dissociated single cells either α-cells or β-cells on coverslips were mounted in an open chamber and superfused in HKRB. Cytosolic concentration ([Ca2+]i) in single cells were measured by fura-2 microfluorimetry. After measurement of [Ca2+]i, α-cells were identified by subsequent immunocytochemical staining using an anti-glucagon antiserum. In β-cells, the [Ca2+]i increase in response to oxytocin was observed only under 8.3 mM glucose condition, whereas in α-cells, [Ca2+]i an increase induced by oxytocin was observed in both 2.8 mM and 8.3 mM glucose. The oscillation incidence was induced more frequently in β-cells compared to α-cells. In conclusion, the present study demonstrated that oxytocin directly interacts with both α-cells and β-cells and induces increase of [Ca2+]i and its specific patterns.

Keywords: α-cells, β-cells, cytosolic calcium concentration, oscillation, oxytocin

Procedia PDF Downloads 171

Authors: Austin Jiang, Richard M. Salmon, Nicholas W. Morrell, Wei Li

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BMP10 is highly expressed in the developing heart and plays essential roles in cardiogenesis. BMP10 deletion in mice results in embryonic lethality due to impaired cardiac development. In adults, BMP10 expression is restricted to the right atrium, though ventricular hypertrophy is accompanied by increased BMP10 expression in a rat hypertension model. However, reports of BMP10 activity in the circulation are inconclusive. In particular it is not known whether in vivo secreted BMP10 is active or whether additional factors are required to achieve its bioactivity. It has been shown that high-affinity binding of the BMP10 prodomain to the mature ligand inhibits BMP10 signaling activity in C2C12 cells, and it was proposed that prodomain-bound BMP10 (pBMP10) complex is latent. In this study, we demonstrated that the BMP10 prodomain did not inhibit BMP10 signaling activity in multiple endothelial cells, and that recombinant human pBMP10 complex, expressed in mammalian cells and purified under native conditions, was fully active. In addition, both BMP10 in human plasma and BMP10 secreted from the mouse right atrium were fully active. Finally, we confirmed that active BMP10 secreted from mouse right atrium was in the prodomain-bound form. Our data suggest that circulating BMP10 in adults is fully active and that the reported vascular quiescence function of BMP10 in vivo is due to the direct activity of pBMP10 and does not require an additional activation step. Moreover, being an active ligand, recombinant pBMP10 may have therapeutic potential as an endothelial-selective BMP ligand, in conditions characterized by loss of BMP9/10 signaling.

Keywords: bone morphogenetic protein 10 (BMP10), endothelial cell, signal transduction, transforming growth factor beta (TGF-B)

Procedia PDF Downloads 261

Authors: Jayden R. Hunter, Alexander J. MacQuarrie, Samantha C. Sheridan, Richard High, Carolyn Waite

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Workplace exercise programs have been recommended to improve the musculoskeletal fitness of paramedics with the aim of reducing injury rates, and while they have shown efficacy in other occupations, they have not been delivered and evaluated in Australian paramedics to our best knowledge. This study investigated the effectiveness of a 6-month workplace exercise program (MedicFit; MF) to improve paramedic fitness with or without health coach (HC) support. A group of regional Australian paramedics (n=76; 43 male; mean ± SD 36.5 ± 9.1 years; BMI 28.0 ± 5.4 kg/m²) were randomised at the station level to either exercise with remote health coach support (MFHC; n=30), exercise without health coach support (MF; n=23), or no-exercise control (CON; n=23) groups. MFHC and MF participants received a 6-month, low-moderate intensity resistance and flexibility exercise program to be performed ƒ on station without direct supervision. Available exercise equipment included dumbbells, resistance bands, Swiss balls, medicine balls, kettlebells, BOSU balls, yoga mats, and foam rollers. MFHC and MF participants were also provided with a comprehensive exercise manual including sample exercise sessions aimed at improving musculoskeletal strength and flexibility which included exercise prescription (i.e. sets, reps, duration, load). Changes to upper-body (push-ups), lower-body (wall squat) and core (plank hold) strength and flexibility (back scratch and sit-reach tests) after the 6-month intervention were analysed using repeated measures ANOVA to compare changes between groups and over time. Upper-body (+20.6%; p < 0.01; partial eta squared = 0.34 [large effect]) and lower-body (+40.8%; p < 0.05; partial eta squared = 0.08 (moderate effect)) strength increased significantly with no interaction or group effects. Changes to core strength (+1.4%; p=0.17) and both upper-body (+19.5%; p=0.56) and lower-body (+3.3%; p=0.15) flexibility were non-significant with no interaction or group effects observed. While upper- and lower-body strength improved over the course of the intervention, providing a 6-month workplace exercise program with or without health coach support did not confer any greater strength or flexibility benefits than exercise testing alone (CON). Although exercise adherence was not measured, it is possible that participants require additional methods of support such as face-to-face exercise instruction and guidance and individually-tailored exercise programs to achieve adequate participation and improvements in musculoskeletal fitness. This presents challenges for more remote paramedic stations without regular face-to-face access to suitably qualified exercise professionals, and future research should investigate the effectiveness of other forms of exercise delivery and guidance for these paramedic officers such as remotely-facilitated digital exercise prescription and monitoring.

Keywords: workplace exercise, paramedic health, strength training, flexibility training

Procedia PDF Downloads 126

Authors: Matej Patzelt, Jan Dudak, Frantisek Krejci, Jan Zemlicka, Vladimir Musil, Jitka Riedlova, Viktor Sykora, Jana Mrzilkova, Petr Zach

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Introduction: Micro-CT is well used for examination of bone structures and teeth. On the other hand visualization of the soft tissues is still limited. The goal of our study was to create a new fixation method for soft tissue imaging in micro-CT. Methodology: We used organs of 18 mice - heart, lungs, kidneys, liver and brain, which we fixated in ethanol after meticulous preparation. We fixated organs in different concentrations of ethanol and for different period of time. We used three types of ethanol concentration - 97%, 50% and ascending ethanol concentration (25%, 50%, 75%, 97% each for 12 hours). Fixated organs were scanned after 72 hours, 168 hours and 336 hours period of fixation. We scanned all specimens in micro-CT MARS (Medipix All Resolution System). Results: Ethanol method provided contrast enhancement in all studied organs in all used types of fixation. Fixation in 97% ethanol provided very fast fixation and the contrast among the tissues was visible already after 72 hours of fixation. Fixation for the period of 168 and 336 hours gave better details, especially in lung tissue, where alveoli were visualized. On the other hand, this type of fixation caused organs to petrify. Fixation in 50% ethanol provided best results in 336 hours fixation, details were visualized better than in 97% ethanol and samples were not as hard as in fixation in 97% ethanol. Best results were obtained in fixation in ascending ethanol concentration. All organs were visualized in great details, best-visualized organ was heart, where trabeculae and valves were visible. In this type of fixation, organs stayed soft for whole time. Conclusion: New ethanol method is a great option for soft tissue fixation as well as the method for enhancing contrast among tissues in organs. The best results were obtained with fixation of the organs in ascending ethanol concentration, the best visualized organ was the heart.

Keywords: x-ray imaging, small animals, ethanol, ex-vivo

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Authors: Thedy Yogasara, Fredy Agus

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In designing a product, it is currently crucial to focus not only on the product’s usability based on performance measures, but also on user experience (UX) that includes pragmatic and hedonic aspects of product use. These aspects play a significant role in fulfillment of user needs, both functionally and psychologically. Pragmatic quality refers to as product’s perceived ability to support the fulfillment of behavioral goals. It is closely linked to functionality and usability of the product. In contrast, hedonic quality is product’s perceived ability to support the fulfillment of psychological needs. Hedonic quality relates to the pleasure of ownership and use of the product, including stimulation for personal development and communication of user’s identity to others through the product. This study evaluates the pragmatic and hedonic aspects of gaming mice G600 and Razer Krait using AttrakDiff tool to create an improved design that is able to generate positive UX. AttrakDiff is a method that measures pragmatic and hedonic scores of a product with a scale between -3 to +3 through four attributes (i.e. Pragmatic Quality, Hedonic Quality-Identification, Hedonic Quality-Stimulation, and Attractiveness), represented by 28 pairs of opposite words. Based on data gathered from 15 participants, it is identified that gaming mouse G600 needs to be redesigned because of its low grades (pragmatic score: -0.838, hedonic score: 1, attractiveness score: 0.771). The redesign process focuses on the attributes with poor scores and takes into account improvement suggestions collected from interview with the participants. The redesigned mouse G600 is evaluated using the previous method. The result shows higher scores in pragmatic quality (1.929), hedonic quality (1.703), and attractiveness (1.667), indicating that the redesigned mouse is more capable of creating pleasurable experience of product use.

Keywords: AttrakDiff, hedonic aspect, pragmatic aspect, product design, user experience

Procedia PDF Downloads 139

Authors: Yiea Funk Te, Daniel Mueller, Irena Pletikosa Cvijikj

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Small and medium enterprises (SMEs) play an important role in the economy of many countries. When the overall world economy is considered, SMEs represent 95% of all businesses in the world, accounting for 66% of the total employment. Existing studies show that the current business environment is characterized as highly turbulent and strongly influenced by modern information and communication technologies, thus forcing SMEs to experience more severe challenges in maintaining their existence and expanding their business. To support SMEs at improving their competitiveness, researchers recently turned their focus on applying data mining techniques to build risk and growth prediction models. However, data used to assess risk and growth indicators is primarily obtained via questionnaires, which is very laborious and time-consuming, or is provided by financial institutes, thus highly sensitive to privacy issues. Recently, web mining (WM) has emerged as a new approach towards obtaining valuable insights in the business world. WM enables automatic and large scale collection and analysis of potentially valuable data from various online platforms, including companies’ websites. While WM methods have been frequently studied to anticipate growth of sales volume for e-commerce platforms, their application for assessment of SME risk and growth indicators is still scarce. Considering that a vast proportion of SMEs own a website, WM bears a great potential in revealing valuable information hidden in SME websites, which can further be used to understand SME risk and growth indicators, as well as to enhance current SME risk and growth prediction models. This study aims at developing an automated system to collect business-relevant data from the Web and predict future growth trends of SMEs by means of WM and data mining techniques. The envisioned system should serve as an 'early recognition system' for future growth opportunities. In an initial step, we examine how structured and semi-structured Web data in governmental or SME websites can be used to explain the success of SMEs. WM methods are applied to extract Web data in a form of additional input features for the growth prediction model. The data on SMEs provided by a large Swiss insurance company is used as ground truth data (i.e. growth-labeled data) to train the growth prediction model. Different machine learning classification algorithms such as the Support Vector Machine, Random Forest and Artificial Neural Network are applied and compared, with the goal to optimize the prediction performance. The results are compared to those from previous studies, in order to assess the contribution of growth indicators retrieved from the Web for increasing the predictive power of the model.

Keywords: data mining, SME growth, success factors, web mining

Procedia PDF Downloads 247

Authors: Bruce Wrightsman

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Construction and design are inexorably linked. Traditional building methodologies, including those using wood, comprise a series of material layers differentiated and separated from each other. This results in the separation of two agencies of building envelope (skin) separate from the structure. However, from a material performance position reliant on additional materials, this is not an efficient strategy for the building. The merits of traditional platform framing are well known. However, its enormous effectiveness within wood-framed construction has seldom led to serious questioning and challenges in defining what it means to build. There are several downsides of using this method, which is less widely discussed. The first and perhaps biggest downside is waste. Second, its reliance on wood assemblies forming walls, floors and roofs conventionally nailed together through simple plate surfaces is structurally inefficient. It requires additional material through plates, blocking, nailers, etc., for stability that only adds to the material waste. In contrast, when we look back at the history of wood construction in airplane and boat manufacturing industries, we will see a significant transformation in the relationship of structure with skin. The history of boat construction transformed from indigenous wood practices of birch bark canoes to copper sheathing over wood to improve performance in the late 18th century and the evolution of merged assemblies that drives the industry today. In 1911, Swiss engineer Emile Ruchonnet designed the first wood monocoque structure for an airplane called the Cigare. The wing and tail assemblies consisted of thin, lightweight, and often fabric skin stretched tightly over a wood frame. This stressed skin has evolved into semi-monocoque construction, in which the skin merges with structural fins that take additional forces. It provides even greater strength with less material. The monocoque, which translates to ‘mono or single shell,’ is a structural system that supports loads and transfers them through an external enclosure system. They have largely existed outside the domain of architecture. However, this uniting of divergent systems has been demonstrated to be lighter, utilizing less material than traditional wood building practices. This paper will examine the role monocoque systems have played in the history of wood construction through lineage of boat and airplane building industries and its design potential for wood building systems in architecture through a case-study examination of a unique wood construction approach. The innovative approach uses a wood monocoque system comprised of interlocking small wood members to create thin shell assemblies for the walls, roof and floor, increasing structural efficiency and wasting less than 2% of the wood. The goal of the analysis is to expand the work of practice and the academy in order to foster deeper, more honest discourse regarding the limitations and impact of traditional wood framing.

Keywords: wood building systems, material histories, monocoque systems, construction waste

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Authors: Dina Atmani-Kilani, Farah Yous, Djebbar Atmani

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The etiology of peptic ulcer is closely related to stress, excessive consumption of nonsteroidal anti-inflammatory drugs, or ethanol. Clematis flammula (Ranunculaceae) is a medicinal plant widely used by rural populations to treat inflammatory disorders. This study was designed to assess the gastroprotective potential of C. flammula extracts. Gastric ulcer was induced by stress, indomethacin, HCl / ethanol, and absolute ethanol on NMRI-type mice. The antioxidant potency of the ethanolic extract of Clematis flammula (EECF) was evaluated on catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) activities. Glutathione (GSH) and malonaldehyde (MDA) levels were also quantified. The anti-inflammatory potential was evaluated through the effect of EECF on myeloperoxidase activity (MPO) and vascular permeability. Complementary tests concerning the quantification of mucus levels, gastric motility, inhibition of ATPase H+/K+activity, as well as a histopathological study were also undertaken to explore the mechanism of action of the EECF. The EECF exhibited a significant (p <0.001) and optimal (100 mg/kg) gastroprotective effect by elevating SOD, CAT, and GSH levels, thereby minimizing the production of MDA and lowering the activity of MPO and vascular permeability. EECF also increased the rate of mucus production, decreased gastric motility, and completely suppressed the H+/K+ ATPase activity. Histopathological study confirmed the effectiveness of the extract in the prevention of peptic ulcer. The results obtained in this study demonstrated the gastro-protective effect of EECF via acidic antioxidant, anti-inflammatory, cytoprotective and anti-secretory mechanisms, which may justify its use as a substitute in peptic ulcer treatment.

Keywords: clematis flammula, superoxide dismutase, myeloperoxidase, ATPase, pump

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Authors: Katerina Bakela, Ioanna Zerva, Irene Athanassakis

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Lipopolysaccharide (LPS) is commonly used in murine sepsis models, which are largely associated with immunosuppression (incretion of MDSCs cells and Tregs, imbalance of inflammatory/anti-inflammatory cytokines) and collapse of the immune system. After adapting the LPS treatment to the needs of locally bred BALB/c mice, the present study explored the protective role of Micrococcus luteus peptidoglycan (PG) pre-activated vaccine-on chip in endotoxemia. The established protocol consisted of five daily intraperitoneal injections of 0.2mg/g LPS. Such protocol allowed longer survival, necessary in the prospect of the therapeutic treatment application. The so-called vaccine-on-chip consists of a 3-dimensional laser micro-texture Si-scaffold loaded with BALB/c mouse macrophages and activated in vitro with 1μg/ml PG, which exert its action upon subcutaneous implantation. The LPS treatment significantly decreased CD4+, CD8+, CD3z+, and CD19+ cells, while increasing myeloid-derived suppressor cells (MDSCs), CD25+, and Foxp3+ cells. These results were accompanied by increased arginase-1 activity in spleen cell lysates and production of IL-6, TNF-a, and IL-18 while acquiring severe sepsis phenotype as defined by the murine sepsis scoring. The in vivo application of PG pre-activated vaccine-on chip significantly decreased the percent of CD11b+, Gr1+, CD25+, Foxp3+ cells, and arginase-1 activity in the spleen of LPS-treated animals, while decreasing IL-6 and TNF-a in the serum, allowing survival to all animals tested and rescuing the severity of sepsis phenotype. In conclusion, these results reveal a promising mode of action of PG pre-activated vaccine-on chip in LPS endotoxemia, strengthening; thus, the use of treatment is septic patients.

Keywords: myeloid-derived suppressor cells, peptidoglycan, sepsis, Si-scaffolds

Procedia PDF Downloads 119