Development and Implementation of Workshop Management System Application to Explore Combing Multiple Design Patterns

As systems creation are becoming more complex, we face more problems that are related to system construction rather than those problems related to analysis. Design patterns represent a clear way of solving designing problems in the context of a particular computer application. Combining design patterns is one approach that is used to allow flexibility in building applications with multiple problems. The Workshop Management System application is built to demonstrate the idea of combining multiple design patterns. To support the idea, we show how to build the application by following the structures and methods that are provided by design patterns. Essentially, we show how these structures help developers to express a flexible system creation

Exploring TripAdvisor Online Reviews: The Case of George Eastman Museum

Different studies have looked at visitor related motivations and experiences under different contexts in the tourism industry. The museum-related experiences remain one of the important elements which are sought by visitors to the museums. Therefore, this study purposes to investigate and determine personal context, social context and physical contexts of George Eastman museum visitors. More importantly, the study utilised a content analysis approach in its research. The specific data about visitors to George Eastman House was obtained from the social media website TripAdvisor. The findings of the study were based on three important elements: personal context, social context and physical contexts. In the personal context based on John Falk classifications (experience seeker, explorer, facilitator, prof-hobbyist, and recharger); the experience seeker had the highest number of visitor comments about 76 reviewers, with explorer category being less represented while recharger category had the least number of visitor’s comments. On the aspect of social context, about 12% reviewers indicated the social context where the socio-cultural influence was considered one of the determinants of their museum-visit experience. Furthermore, the physical context was expressed through identified dominant themes that included mansion, the museum exhibits, and George Eastman’s personality. In both the analysis of negative and the positive dimensions of the themes, the mansion theme showed a higher positive response in the while the museum and the exhibits showed relatively a negative dimension in the analysis. Through a word cloud visualization approach memories and learning outcomes were analysed with findings indicating “Memory/impression of visit”; “Takes you back” (their experience of being drawn back into the past or into a personal memory of previous times, etc.); and most importantly, “Learn from the visit”, were the most predominant themes in memorial and learning outcomes. This study provided important insight into visitor experiences, which can be utilised by George Eastman management to understand perceptions of visitors and thus enhance their services. Furthermore, it is recommended that future studies adopt bigger samples as well as diverse contexts besides the museum in order to be able to get an in-depth insight into museum visitor’s experiences

STYLE, CONTEXT AND TRANSLATED NARRATIVES: A SOCIO-SEMIOTIC PROFILE FOR STUDYING STYLE IN TRANSLATED NARRATIVES

A translated narrative has both its structure and texture creatively reproduced in the decoding-reencoding processes. These processes of intersemiotic and interlingual transformations yield variable results influenced by language-in-context, as the broadest environment of translation, and prompted by the level of the typological and semiotic distance between texts. Translation is thus an act of communication that is separate (contextually and discursively) from, while it is still dependent (semantically) on, the original writing. Here, the translator’s style is an “imprint” that is simultaneously compelled by the creativity of the literary translation act and the existence of the targeted reader in a new socio-semiotic context (Baker, 2000; Hasan, 1986/2011, 1989; Hatim Mason, 1997; Malmkjær, 2004; Matthiessen, 2001). In response to Baker (2000), the present study aims to theoretically revisit the issue of style in narrative translation in a comparative view that takes into consideration the multiple contexts and meta-contexts of the acts of creation and translation. This comparative intersemiotic view ventures to address the complexity of narrative meaning recreation in these new acts of communication along the multi-stratal systems of language and narrative and in the light of the narrative, stylistic and socio-semiotic views of discourse and meaning

Determination of the Effects of Different Maillard Reaction Products on the Taxonomic Composition of the Gut Microbiota

The Maillard Reaction (MR) is a non-enzymatic chemical reaction which results in linkage between the amino group of amino acids and the carbonyl group of reduced sugars. This reaction generates Maillard reaction products (MRPs) which are not present naturally in foods, and are responsible for a range of colors, odors, flavors, and other sensory properties. Conflicting reports of MRPs impacts on human health are probably due to the fact that bioconversion of these digestible molecules by the gut microbiota has been marginally taken into account. This study aimed to determine the effects of different MRPs on rodent’s gut microbiota through16S rRNA amplicon sequencing over three different studies. Study 1 focused on the impact of NƐCarboxymethyllysine (CML) on the composition of mice gut microbiota and potential association with severity of experimental colitis. Study 2 focused on the impact of bread melanoidins on the composition of healthy and experimental colitis mice gut microbiota. Study 3 focused on the impact of consumption of increasing amounts of malt melanoidins on mice gut microbiota. It was found that CML induced limited changes in gut microbiota profiles of healthy mice, but was found to significantly relieve the bacterial dysbiosis imparted by one (but not the other) inflammation-inducing chemical, especially the Proteobacteria bloom. Bread crust model (high in melanoidins) showed significant decreases of Bacteroides spp. and Enterobacteriaceae, while it increased Faecalibacterium spp. Also, bread crust model limited to increase Enterobacteriaceae in colitis model. High amounts of malts rich melanoidins rapidly and persistently led to significantly different gut microbiota profiles. There was a trend for decrease of Lactobacillus and Ruminococcus and increase of Akkermansia and Bifidobacterium with higher amounts of dietary melanoidins. We concluded that CML and melanoidins are not detrimental in terms of their impact on the gut microbiota, and that they may even have prebiotic properties

Regulation of TNF-alpha gene expression by TNFAIP1 as an activator or suppressor in response to lipopolysaccharide

OBJECTIVE: To determine the link between the tumor necrosis factor induced protein 1(TNFAIP1) and TNF-alpha production in response to the P.gingivalis/LPS, and to investigate the mechanism that regulates the effect of the TNFAIP1 gene expression on TNF-alpha synthesis, using a new, simple, yet effective technique that allowed us to apply our methods on human macrophages. MATERIALS AND METHODS: We performed several experiments including: A culture of mouse RAW cells and human THP-1 cells in RPMI media supplemented with 10% FBS at 37°C in 5% CO2, Polymerase Chain reaction (PCR) using specifically designed primers and DNA cloning of TNFAIP1, transfection of the cloned TNFAIP1 cDNA into macrophages, Western blot analysis, ELISA analysis after treatment in macrophages, and GFP imaging system. RESULTS: 1. TNFAIP1 expression can reciprocally affect TNF-α production in macrophages. 2. Blocking MAPK, PI3K and JAK downregulates the TNF-alpha production. 3. The transfection of TNFAIP1 in THP-1 using a 1.5 ml Eppendorf tube generated a high transfection efficiency without the PMA treatment. 4. TNFAIP1 induces Caspase 1 gene expression in macrophages. 5. Caspase 1 induced by TNFAIP1 functions downregulation of TNF-alpha via p73. CONCLUSIONS: 1. MAP kinase, JAK, or PI3K, may be involved in TNF-α gene expression in LPS-dependent pathway. 2. TNFAIP1 expression can induce TNF-alpha production in mouse macrophages and vice versa. 3. TNFAIP1 gene expression in response to LPS is independent of NFkB-mediated signaling pathway. 4. The animal model has been confirmed by using both mouse macrophage-like cells (RAW cells) and a human macrophage-like cells (THP-1 cells). 5. The signaling pathway for the activation of TNF-alpha production in early stages is: LPS/ TNFAIP1/ PI3Kinase/AP-1/ TNF-alpha. 6. TNFAIP1 acts as a suppressor in later stage to down-regulate TNF-α gene expression via the following signaling pathway: LPS/TNF-alpha/ TNFAIP1/ Caspase 1/ Apoptotic genes/ Degradation of TNF-α/ Cell apoptosis

Venturing into a Vanishing Space: Representations of Palestine in Jewish-American and Arab Novels

This study explores the literary representation of Palestine by Jewish American and Arab novelists within the emergent geopolitics of settler colonialism, thus challenging the notion that Palestine presents a unique situation that largely defies comparative approaches. It illustrates how postcolonial theory proves necessary but insufficient to engage the cultural and political specificities of the Palestinian situation, both as fictional representation and as otherwise knowable history. Here, recent developments in theorising settler colonialism provide a useful starting point. Drawing on the work of Patrick Wolfe and Lorenzo Veracini, with its revisionary challenge to postcolonial theory in relation to the need to distinguish between settler colonialism and metropole colonialism, this thesis argues that the case of Palestine problematizes the settler colonial paradigm. Overlaps and entanglements between the supposedly distinct forms of colonialism on the ground complicate the discreteness of the settler model. Hence, the focus on Jewish-American novel serves to suggest that the Zionist settler enterprise is inseparable from American imperialism, and therefore challenges conceptualizations of a purely settler phenomenon in Palestine. The study draws together New Historicism and postcolonialism, suggesting that engagement with the intersection of these two approaches is both valid and timely. The New Historicist return to history proves central to appraisal of the forms of power that continue to condition the authority accorded to a particular version of events, and to the evaluation of the writer’s responsibility to reality as well as the measure of truth embedded even in most fictionalized versions of history. Accordingly, the structure of the thesis identifies key historical moments in the history of the Israeli-Palestinian conflict, juxtaposing Jewish-American renditions of the Zionist settler project with Arab counter-narratives. The emphasis in the thesis on historicising rhetorical appropriations and restoring a Palestinian version of events challenges the perception transfer of settler narratives, which, to the privilege of settlers’ self-origination, has long relegated Palestinian people, land, and narratives to the peripheries of history and postcolonial debates. The first three chapters focus on three signal events: the 1948 nakba, the 1967 war, and the 1980s uprising. The first chapter compares and contrasts two versions of the 1948 events as represented in Leon Uris’s The Haj (1984) and Elias Khoury’s Gate of the Sun (1998; trans. 2005). Drawing on the revisionary work of the Israeli new historians, together with Palestinian commentators, the chapter explores the 1948 Palestinian exodus in terms of settlers’ violence and logic of elimination, which Uris’s narrative conceals behind a Western civilizational discourse. Against Uris’s legitimation of the master Zionist narrative, Khoury’s novel suggests an instance of ‘writing back,’ narrating the unspoken and replacing the monologism of the official line with the multiplicity of oral history. The second chapter extends this cross-cultural research to the 1967 war, suggesting the centrality of this event to paradigmatic shifts in Palestinian historical experience and self-representation as well as in the Jewish American writer’s relation to the state of Israel. Literary representations of 1967 Palestine, including Edward Said’s Out of Place: A Memoir (2000), Halim Barakat’s Six Days (1961; trans. 1990) and Days of Dust (1969; trans. 1986), Sahar Khalifeh’s Wild Thorns (1976; trans. 2003), and Saul Bellow’s Mr Sammler’s Planet (1970) and To Jerusalem and Back: A Personal Account (1976), articulate liminality, ambivalence, and the enabling of new possibilities and fresh perspectives. Each of these writers reveals a shared concern for the politics of the local in order to escape the burdens of diasporic existence, attempting to redefine what seems to be a borderless and geographically vague existence. While post-1967 narratives affirm the rise of a new focus for Palestinian writers, the third chapter shows how the greater visibility of Palestinians in the aftermath of the 1980s uprising finds literary form in US fiction. Philip Roth’s Operation Shylock: A Confession (1993) illustrates the cultural limits that restrict a dialogic engagement with the emerging heteroglossia in US media following the appearance of a Palestinian voice and an anti-Zionist stance. However, this failed dialogism reveals how silence and dissimulation become forms of expression, unveiling the dynamics that manipulate the space permitted for Palestinians in Jewish American fiction. Recovering Palestinian literature from the margins of postcolonial studies, the final chapter charts ways of representing Palestinian (post)coloniality by drawing on the temporal and spatial specifications conceptualised in Mikhail Bakhtin’s notion of the chronotope. Raja Shehadeh’s Palestinian Walks (2008) and Susan Abulhawa’s Mornings in Jenin (2011) reinvent the traditions of walking and returning, previously manipulated in Zionist settler narratives, in order to articulate a political protest against settler colonialism and assert the legitimacy of the Palestinians’ claim to the land. Although focusing on the Palestinian case, this study seeks to open up the postcolonial to the historical and rhetorical specificities of the literature emerging from contemporary settler colonial situations, and the possible enactment of postcolonial passages in not-yet-postcolonial contexts

BISPHOSOHOGLYCERTAE MUTASE: A POTENTIAL TARGET FOR SICKLE CELL DISEASE

Bisphosphoglycerate mutase (BPGM) is a part of the erythrocyte glycolysis system. Specifically, it is a central enzyme in the Rapoport-Leubering pathway, a side glycolytic pathway involved in the regulation of the concentration of the natural allosteric effector of hemoglobin (Hb), 2,3-bisphosphoglycerate (2,3-BPG). BPGM catalyses the synthesis and hydrolysis of 2,3-BPG through its synthase and phosphatase activities. The synthase activity is the main role of BPGM, while the phosphatase activity is low and is activated by the physiological effector, 2-phosphoglycolate (2-PG) with the latter mechanism poorly understood. BPGM activity and 2,3-BPG levels in red blood cells (RBCs) have a significant role in sickle cell disease (SCD) pathology. SCD patients experience a constant state of hypoxia that results in increasing the level of 2,3-BPG as a compensatory mechanism to enhance oxygen delivery to tissues. However, the abnormal increase in 2,3-BPG in RBCs of SCD patients exacerbates the disease’s primary pathophysiology, which is the hypoxia-driven deoxygenated-sickle hemoglobin (HbS) polymerization, that in turn leads to RBCs sickling and consequent numerous downstream multi-organ adverse effects. Reducing the levels of 2,3-BPG by activating BPGM phosphatase activity using 2-PG has been proposed as a potential therapeutic approach for SCD as 2-PG was found to have an anti-sickling property. Nonetheless, the actual activation mechanism of 2-PG on the phosphatase activity or the binding mode of 2-PG to BPGM is not clear. Moreover, no drug screening studies have been performed to identify small molecules against BPGM for therapeutic purposes. The objectives of this project are to characterize the steady-state kinetics of BPGM synthase and phosphatase activities, understand the mechanism of phosphatase activation, and elucidate the atomic interaction of BPGM with 2-PG and other effectors such as citrate that can provide valuable insight into their mechanism of actions and provide a framework for developing small molecules with potential SCD therapeutic benefit. In addition, we aim to identify ligands that modulate either BPGM phosphatase and/or synthase activity to reduce 2,3-BPG concentration in RBCs. First, the steady-state kinetics of BPGM synthase and phosphatase activities were characterized using the previously reported coupled spectrophotometric synthase and phosphatase activities assays. These assays were also optimized for drug screening experiments. Both assays have limitations and proved challenging for drug screening. We also employed the colorimetric malachite green assay to study BPGM phosphatase activity, as well as for compound screening. Next, we elucidated the mechanism of phosphatase activity activation by 2-PG using kinetic and X-ray crystallography studies. The kinetic study showed the mechanism of 2-PG activation of BPGM to be mixed-type of noncompetitive and competitive, suggesting the binding of 2-PG to the active site and to an allosteric or non-catalytic site of the enzyme. The crystal structures of BPGM with 2-PG in the presence and absence of the substrate 2,3-BPG showed binding of the 2-PG and/or 3-PGA (the reaction product of 2,3-BPG) at the expected active site, and at a novel non-catalytic site at the dimer interface, in agreement with the kinetic analysis. The structural studies of BPGM also showed conformational nonequivalence of the two monomeric active sites: one site in a close catalytic conformation, and the second site in an open conformation, with the residues at the entrance of the active site, including Arg100, Arg116, and Arg117, and the C-terminus region disordered, which we propose to be induced by the dimer interface binding. In order to gain further insight into the BPGM mechanism of action, we also co-crystallized BPGM with citrate, a known BPGM phosphatase inhibitor. The co-crystal structure of BPGM with citrate showed citrate binding to only one of the dimer active sites and to the dimer interface. The kinetic and crystallographic findings suggest for the first time an allosterism or cooperativity across monomers, in which the binding of a ligand at the dimer interface induces negative cooperativity affecting the affinity of ligand binding at the second active site. In the BPGM•citrtate binary complex, an extreme form of negative cooperativity, where half of the site reactivity is observed, shows that only one active site appears to be functional. Toward the objective of identifying small molecules modulators of BPGM activity for therapeutic purposes, we identified several compounds that target the active site of BPGM using (1) in-house pharmacophore-based virtual screening and molecular docking; (2) machine learning-based molecular screening in collaboration with the pharmaceutical company Atomwise, and (3) PGM1-004A, a known inhibitor of the homologous enzyme, phosphoglycerate mutase 1 (PGAM1). The compounds were tested for their effect on BPGM synthase and phosphatase activities. Unfortunately, the compounds did not show any modulation except for PGMI-004A, which shows a dose-dependent synthase inhibition with IC50 (50±11 µM). Several attempts were made to co-crystallize BPGM with PGMI-004A but were unsuccessful. The novel allosteric site at the dimer interface was also docked against a library of compounds, which identified several potential binders. The top-scoring compounds will be obtained and tested in the near future

Potentiometric determination of stability constants and thermodynamic data for ternary Cd(II) complexes with 2-aminomethyl benzimidazole (AMBI) and other bioactive ligands

The complexing properties of 2-(aminomethyl)-benzimidazole with cadmium(II) were investigated pH-metrically at 25 oC and at ionic strength of 0.1 mol.dm-3 (NaNO3). Ternary complex formation equilibria of cadmium(II) complexes involving (AMBI) and some bio-relevant ligands (L = amino acid and peptides) have been investigated. Ternary complexes of amino acids and peptides are formed by a simultaneous mechanism. Amino acids form the complex Cd(AMBI)L, whereas amides form two complex species Cd(AMBI)L and Cd(AMBI)(LH-1). The stability of ternary complexes was quantitatively compared with their corresponding binary complexes in terms of the parameters ΔLog K, Log βStat and Log X. The effect of the side chains of amino acid ligands (ΔR) on complex formation was discussed. The values of ΔLog K indicate that the ternary complexes containing aromatic amino acids are significantly more stable than the complexes containing alkyl- and hydroxyalkyl-substituted amino acids. This may be taken as evidence for a stacking interaction between the aromatic moiety of AMBI and the aromatic side chains of the bioactive ligands. The concentration distributions of various species formed in solution were also evaluated as a function of pH. The thermodynamic parameters ΔHo, ΔGo and ΔSo calculated from the temperature dependence of the equilibrium constants were investigated for the interaction of Cd(II)-AMBI with glycine as a representative example of amino acids