Search results for: space target

Authors: Lin Zhang

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The fear of leprosy has been longstanding throughout the human history. In an era where isolation is practiced as a means of epidemic prevention, the leprosy rehabilitation group has itself become an isolated community with an entrenched metaphor. In the process of new mediatization of the leprosy isolation community, what are the relations among media literacy, the leprosy internalized stigma and social support? To address the question, the “portrait” of leprosy rehabilitation group is re-delineated through two field studies in the “post-leprosy age” in 2012 and 2020, respectively. Taking an isolation community on Si’an Leprosy Island in Dongguan City, Guangdong Province, China as the study object, it is found that new media promotes the dissolution of segregation effect of the leprosy isolation community and the cultivation of opinion leaders by breaking spatial, psychological and social segregation and by building a community of village affairs and public space in the following way: the cured patients with high new media literacy, especially those who use WeChat and other applications and largely rely on new media for information, have a low level of leprosy internalized stigma and a high level of social support, and they are often the opinion leaders inside their community; on the contrary, the cured patients with low new media literacy, a high level of leprosy internalized stigma and a low level of social support are often the followers inside their community. Such effects of dissolution and construction are reflected not only in the vertical differentiation of the same individual at different times, but also in the horizontal differentiation between different individuals at the same time.

Keywords: segregation, the leprosy rehabilitation group, new mediatization, digital empowerment, opinion leaders

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Authors: Ahmad Qabaha

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This paper teases out the ways in which the constructs of placelessness and mobility are articulated in modern exilic Palestinian literature and American expatriate writing. The mode of placelessness embodied by the characters of each of my two authors (expatriation in Paris Montparnasse for Hemingway's characters and involuntary exile in Europe for Jabra's) will be elicited from the orientations of their mobility. This paper argues that the proclivity of Hemingway's characters for centrifugal motion (moving away from the centre) is a strategy to increase their sense of freedom that space (expatriation), rather than place, secures. By contrast, the movement of Jabra's characters is centripetal (moving or tending to move towards the centre). It echoes his Palestinian characters' recurrent futile attempts to return to Palestine, and it expresses their resistance to the lures of exile. This paper asserts that the involuntarily exiled character (the Palestinian in this case) is a figure obsessed with and ache for a place, roots and 'a dwelling' from which he was uprooted - a place that defines his authentic existence and frames his understanding of the world in Martin Heidegger's, Simone Weil's and Gaston Bachelard's senses. In parallel, this paper explains that the expatriate character (the American in this case) views place as confining, restrictive and disagreeable, while mobility as a figure of freedom, resistance, wealth, self-fashioning and understanding/inhabiting the world. Place in this sense is associated with past, tradition, ideology, existence and being. Mobility is equivalent with modernity, progression, innovation, self-fashioning and freedom.

Keywords: American expatriate literature, exilic Palestinian literature, mobility, place, placelessness

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Authors: Fatemeh Haghiralsadat, Mohadese Hashemi, Elham Akhoundi Kharanaghi, Mojgan Yazdani, Mahboobe Sharafodini, Omid Javani

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Niosomes are colloidal particles formed from the self-assembly of non-ionic surfactants in aqueous medium resulting in closed bilayer structures. As a consequence of this hydrophilic and hydrophobic structure, niosomes have the capacity to entrap compounds of different solubilities. Niosomes are promising vehicle for drug delivery which protect sensitive drugs and improve the therapeutic index of drugs by restricting their action to target cells. Essential oils are complex mixtures of volatile compounds such as terpenoids, phenol-derived aromatic components that have been used for many biological properties including bactericidal, fungicidal, insecticidal, antioxidant, anti-tyrosinase and other medicinal properties. Encapsulation of essential oils in niosomes can be an attractive method to overcome their limitation such as volatility, easily decomposition by heat, humidity, light, or oxygen. Cuminum cyminum L. (Cumin) is an aromatic plant included in the Apiaceae family and is used to flavor foods, added to fragrances, and for medical preparations which is indigenous to Egypt, the Mediterranean region, Iran and India. The major components of the Cumin oil were reported as cuminaldehyde, γ -terpinene, β-pinene, p-cymene, p-mentha-1, 3-dien-7-al, and p-mentha-1, 4-dien-7-al which provide the antimicrobial and antioxidant activity. The aim of this work was to formulate Cumin essential oil-loaded niosomes to improve water solubility of natural product and evaluate its physico-chemical features and stability. Cumin oil was obtained through steam distillation using a clevenger-type apparatus and GC/MS was applied to identify the main components of the essential oil. Niosomes were prepared by using thin film hydration method and nanoparticles were characterized for particle size, dispersity index, zeta potential, encapsulation efficiency, in vitro release, and morphology.

Keywords: Cuminum cyminum L., Cumin, niosome, essential oil, encapsulation

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Authors: Pulari C. Milu Maria Anto

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Background: Cognitive Rehabilitation/Retraining has been variously used in the research literature to represent non-pharmacological interventions that target the cognitive impairments with the goal of ameliorating cognitive function and functional behaviors to optimize the quality of life. Along with adult’s cognitive impairments, the need to address acquired cognitive impairments (due to any chronic illnesses like CHD - congenital heart diseases or ALL - Acute Lymphoblastic Leukemia) among child populations is inevitable. Also, it has to be emphasized as same we consider the cognitive impairments seen in the children having neurodevelopmental disorders. Methods: All published brain image studies (Hermann, B. et al,2002, Khalil, A. et al., 2004, Follin, C. et al, 2016, etc.) and studies emphasizing cognitive impairments in attention, memory, and/or executive function and behavioral aspects (Henkin, Y. et al,2007, Bellinger, D. C., & Newburger, J. W. (2010), Cheung, Y. T., et al,2016, that could be identified were reviewed. Based on a systematic review of the literature from (2000 -2021) different brain imaging studies, increased risk of neuropsychological and psychosocial impairments are briefly described. Clinical and research gap in the area is discussed. Results:30 papers, both Indian studies and foreign publications (Sage journals, Delhi psychiatry journal, Wiley Online Library, APA PsyNet, Springer, Elsevier, Developmental medicine, and child neurology), were identified. Conclusions: In India, a very limited number of brain imaging studies and neuropsychological studies have done by indicating the cognitive deficits of a child having or undergone chronic illness. None of the studies have emphasized the relevance nor the need of implementingCR among such children, even though its high time to address but still not established yet. The review of the current evidence is to bring out an insight among rehabilitation professionals in establishing a child specific CR and to publish new findings regarding the implementation of CR among such children. Also, this study will be an awareness on considering cognitive aspects of a child having acquired cognitive deficit (due to chronic illness), especially during their critical developmental period.

Keywords: cognitive rehabilitation, neuropsychological impairments, congenital heart diseases, acute lymphoblastic leukemia, epilepsy, and neuroplasticity

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Authors: Moulay Driss Mellaoui, Khadija Zaki, Khalid Abbiche, Abdallah Imjjad, Rachid Boutiddar, Abdelouahid Sbai, Aaziz Jmiai, Souad El Issami, Al Mokhtar Lamsabhi, Hanane Zejli

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This study presents a comprehensive analysis of six isoxazolidine and isoxazoline derivatives, leveraging a multifaceted approach that combines Density Functional Theory (DFT), AdmetSAR analysis, and molecular docking simulations to explore their electronic, pharmacokinetic, and anticancer properties. Through DFT analysis, using the B3LYP-D3BJ functional and the 6-311++G(d,p) basis set, we optimized molecular geometries, analyzed vibrational frequencies, and mapped Molecular Electrostatic Potentials (MEP), identifying key sites for electrophilic attacks and hydrogen bonding. Frontier Molecular Orbital (FMO) analysis and Density of States (DOS) plots revealed varying stability levels among the compounds, with 1b, 2b, and 3b showing slightly higher stability. Chemical potential assessments indicated differences in binding affinities, suggesting stronger potential interactions for compounds 1b and 2b. AdmetSAR analysis predicted favorable human intestinal absorption (HIA) rates for all compounds, highlighting compound 3b superior oral effectiveness. Molecular docking and molecular dynamics simulations were conducted on isoxazolidine and 4-isoxazoline derivatives targeting the EGFR receptor (PDB: 1JU6). Molecular docking simulations confirmed the high affinity of these compounds towards the target protein 1JU6, particularly compound 3b, among the isoxazolidine derivatives, compound 3b exhibited the most favorable binding energy, with a g score of -8.50 kcal/mol. Molecular dynamics simulations over 100 nanoseconds demonstrated the stability and potential of compound 3b as a superior candidate for anticancer applications, further supported by structural analyses including RMSD, RMSF, Rg, and SASA values. This study underscores the promising role of compound 3b in anticancer treatments, providing a solid foundation for future drug development and optimization efforts.

Keywords: isoxazolines, DFT, molecular docking, molecular dynamic, ADMET, drugs.

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Authors: Muhammad Imran, Iqra Basit, Mobushir Riaz Khan, Sajid Rasheed Ahmad

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The present study investigates the space-time impact of climate change on the rice crop calendar in tropical Gujranwala, Pakistan. The climate change impact was quantified through the climatic variables, whereas the existing calendar of the rice crop was compared with the phonological stages of the crop, depicted through the time series of the Normalized Difference Vegetation Index (NDVI) derived from Landsat data for the decade 2005-2015. Local maxima were applied on the time series of NDVI to compute the rice phonological stages. Panel models with fixed and cross-section fixed effects were used to establish the relation between the climatic parameters and the time-series of NDVI across villages and across rice growing periods. Results show that the climatic parameters have significant impact on the rice crop calendar. Moreover, the fixed effect model is a significant improvement over cross-sectional fixed effect models (R-squared equal to 0.673 vs. 0.0338). We conclude that high inter-annual variability of climatic variables cause high variability of NDVI, and thus, a shift in the rice crop calendar. Moreover, inter-annual (temporal) variability of the rice crop calendar is high compared to the inter-village (spatial) variability. We suggest the local rice farmers to adapt this change in the rice crop calendar.

Keywords: Landsat NDVI, panel models, temperature, rainfall

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Authors: Daniel Aberdam

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Haploinsufficiency of PAX6 in humans is the main cause of congenital aniridia, a rare eye disease characterized by reduced visual acuity. Patients have also progressive disorders including cataract, glaucoma and corneal abnormalities making their condition very challenging to manage. Aniridia-related keratopathy (ARK), caused by a combination of factors including limbal stem-cell deficiency, impaired healing response, abnormal differentiation, and infiltration of conjunctival cells onto the corneal surface, affects up to 95% of patients. It usually begins in the first decade of life resulting in recurrent corneal erosions, sub-epithelial fibrosis with corneal decompensation and opacification. Unfortunately, current treatment options for aniridia patients are currently limited. Although animal models partially recapitulate this disease, there is no in vitro cellular model of AKT needed for drug/therapeutic tools screening and validation. We used genome editing (CRISPR/Cas9 technology) to introduce a nonsense mutation found in patients into one allele of the PAX6 gene into limbal stem cells. Resulting mutated clones, expressing half of the amount of PAX6 protein and thus representative of haploinsufficiency were further characterized. Sequencing analysis showed that no off-target mutations were induced. The mutated cells displayed reduced cell proliferation and cell migration but enhanced cell adhesion. Known PAX6 targets expression was also reduced. Remarkably, addition of soluble recombinant PAX6 protein into the culture medium was sufficient to activate endogenous PAX6 gene and, as a consequence, rescue the phenotype. It strongly suggests that our in vitro model recapitulates well the epithelial defect and becomes a powerful tool to identify drugs that could rescue the corneal defect in patients. Furthermore, we demonstrate that the homeotic transcription factor Pax6 is able to be uptake naturally by recipient cells to function into the nucleus.

Keywords: Pax6, crispr/cas9, limbal stem cells, aniridia, gene therapy

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Authors: Mohammad Hossein Habibi, Atena Sadat Hosseini

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Colorectal cancer is the third leading cause of cancer-related death in the world. Colorectal cancer screening, early detection, and treatment programs could benefit from the most up-to-date information on the disease's burden, given the present worldwide trend of increasing colorectal cancer incidence. Tumor recurrence and resistance are exacerbated by the presence of chemotherapy-resistant cancer stem cells that can generate rapidly proliferating tumor cells. In addition, tumor cells can evolve chemoresistance through adaptation mechanisms. In this work, we used in silico analysis to select suitable GEO datasets. In this study, we compared slow-growing cancer stem cells with high-growth colorectal cancer-derived cancer stem cells. We then evaluated the signal pathways, transcription factors, and kinases associated with these two types of cancer stem cells. A total of 980 upregulated genes and 870 downregulated genes were clustered. MAPK signaling pathway, AGE-RAGE signaling pathway in diabetic complications, Fc gamma R-mediated phagocytosis, and Steroid biosynthesis signaling pathways were observed in upregulated genes. Also, caffeine metabolism, amino sugar and nucleotide sugar metabolism, TNF signaling pathway, and cytosolic DNA-sensing pathway were involved in downregulated genes. In the next step, we evaluated the best transcription factors and kinases in two types of cancer stem cells. In this regard, NR2F2, ZEB2, HEY1, and HDGF as transcription factors and PRDM5, SMAD, CBP, and KDM2B as critical kinases in upregulated genes. On the other hand, IRF1, SPDEF, NCOA1, and STAT1 transcription factors and CTNNB1 and CDH7 kinases were regulated low expression genes. Using bioinformatics analysis in the present study, we conducted an in-depth study of colorectal cancer stem cells at low and high growth rates so that we could take further steps to detect and even target these cells. Naturally, more additional tests are needed in this direction.

Keywords: colorectal cancer, bioinformatics analysis, transcription factor, kinases, cancer stem cells

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Authors: Alexander Musyoki, Collins Odour

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Over the past few years, the bakery industry in Kenya has experienced significant growth largely in part to the increased adoption of technology and automation in their processes; more specifically due to the adoption of bakery management systems to help in running bakeries. While they have been largely responsible for the improved productivity and efficiency in bakeries, most of them are now outdated and pose more challenges than benefits. The proposed online bakery management system mentioned in this paper aims to address this by allowing bakery owners to track inventory, budget, job progress, and data analytics on each job and in doing so, promote the Sustainable Development Goals 3 and 12, which aim to ensure healthy lives and promote sustainable economic growth as the proposed benefits of these features include scalability, easy accessibility, reduced acquisition costs, better reliability, and improved functionality that will allow bakeries to become more competitive, reduce waste and track inventory more efficiently. To better understand the challenges, a comprehensive study has been performed to assess these traditional systems and try to understand if an online bakery management system can prove to be advantageous to bakery owners. The study conducted gathered feedback from bakery owners and employees in Nairobi County, Kenya using an online survey with a response rate of about 86% from the target population. The responses cited complex and hard to use bakery management systems (59.7%), lack of portability from one device to the other (58.1%) and high acquisition costs (51.6%) as the top challenges of traditional bakery management systems. On the other hand, some of the top benefits that most of the respondents would realize from the online bakery management system was better reliability (58.1%) and reduced acquisition costs (58.1%). Overall, the findings suggest that an online bakery management system has a lot of advantages over traditional systems and is likely to be well-received in the market. In conclusion, the proposed online bakery management system has the potential to improve the efficiency and competitiveness of small-sized bakeries in Nairobi County. Further research is recommended to expand the sample size and diversity of respondents and to conduct more in-depth analyses of the data collected.

Keywords: ICT, technology and automation, bakery management systems, food innovation

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Authors: Thomais Tsoulia, Arvind Y. M. Sundaram, Stine Braaen, Øyvind Haugland, Espen Rimstad, Øystein Wessel, Maria K. Dahle

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Fish red blood cells (RBC) are nucleated, and in addition to their function in gas exchange, they have been characterized as mediators of immune responses. Salmonid RBC are the major target cells of Piscineorthoreovirus (PRV), a virus associated with heart and skeletal muscle inflammation (HSMI) in farmed Atlantic salmon. The activation of antiviral response genesin RBChas previously been described in ex vivo and in vivo PRV-infection models, but not explored in the initial virus encounter phase. In the present study, mRNA transcriptome responses were explored in erythrocytes from individual fish, kept ex vivo, and exposed to purified PRV for 24 hours. The responses were compared to responses in macrophage-like salmon head kidney (SHK-1) and endothelial-like Atlantic salmon kidney (ASK) cells, none of which support PRV replication. The comparative analysis showed that the antiviral response to PRV was strongest in the SHK-1 cells, with a set of 80 significantly induced genes (≥ 2-fold upregulation). In RBC, 46 genes were significantly upregulated, while ASK cells were not significantly responsive. In particular, the transcriptome analysis of RBC revealed that PRV significantly induced interferon regulatory factor 1 (IRF1) and interferon-induced protein with tetratricopeptide repeats 5-like (IFIT9). However, several interferon-regulated antiviral genes which have previously been reported upregulated in PRV infected RBC in vivo (myxovirus resistance (Mx), interferon-stimulated gene 15 (ISG15), toll-like receptor 3 (TLR3)), were not significantly induced after 24h of virus stimulation. In contrast to RBC, these antiviral response genes were significantly upregulated in SHK-1. These results confirm that RBC are involved in the innate immune response to viruses, but with a delayed antiviral response compared to SHK-1. A notable difference is that interferon regulatory factor 1 (IRF-1) is the most strongly induced gene in RBC, but not among the significantly induced genes in SHK-1. Putative differences in the binding, recognition, and response to PRV, and any link to effects on the ability of PRV to replicate remains to be explored.

Keywords: antiviral responses, atlantic salmon, piscine orthoreovirus-1, red blood cells, RNA-seq

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Authors: Shannon Clayton

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In an effort to explore the potential transformation of North American postwar suburbs, this M.Arch thesis actively engages in the ongoing critique of modernism from the mid 20th century to the present. Contemporary urban design practice has emerged out of the reaction to orthodox modernism. Typically, new suburban development falls into one of two strategies; an attempt to replicate pre-war fabric that never existed, or a reliance on high-density to create instant urbanism. In both cases, the critical role of architecture has been grossly undervalued. Ironically, it is the denial of suburbia’s inherent modernity that has served to prevent genuine place-making. As history demonstrates, modernism is not antithetical to architecture and place. In the postwar years, a critical discussion emerged amongst architects, which sought to evolve modernism beyond functionalism. This was demonstrated through critical discussions on image, experience, and monumentality. As well as increased interest in civic space, and investigations into mat urbanism and the megastructure. The undercurrent within these explorations was a belief that the scale and complexity of modern development could become an opportunity to create urbanism, rather than squander it. This critical discourse has continued through architectural work in the Netherlands and Denmark since the early 1990s, where an emphasis on visual variety, human scale, and public interaction has been given high priority. This thesis applies principles from this ongoing dialogue, and identifies hidden potential within existing North American suburban networks. As a result, the project re-evaluates the legacy of the master plan from a contemporary perspective.

Keywords: urbanism, modernism, suburbia, place-making

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Authors: R. F. Vieira, S. A. Figueiredo, O. M. Freitas, V. F. Domingues, C. Delerue-Matos

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The presence of sulphur compounds like hydrogen sulphide and mercaptans is one of the reasons for waste-water treatment and waste management being associated with odour emissions. In this context having a quantifying method for these compounds helps in the optimization of treatment with the goal of their elimination, namely biofiltration processes. The aim of this study was the development of a method for quantification of odorous gases in waste treatment plants air samples. A method based on head space solid phase microextraction (HS-SPME) coupled with gas chromatography - flame photometric detector (GC-FPD) was used to analyse H2S and Metil Mercaptan (MM). The extraction was carried out with a 75-μm Carboxen-polydimethylsiloxane fiber coating at 22 ºC for 20 min, and analysed by a GC 2010 Plus A from Shimadzu with a sulphur filter detector: splitless mode (0.3 min), the column temperature program was from 60 ºC, increased by 15 ºC/min to 100 ºC (2 min). The injector temperature was held at 250 ºC, and the detector at 260 ºC. For calibration curve a gas diluter equipment (digital Hovagas G2 - Multi Component Gas Mixer) was used to do the standards. This unit had two input connections, one for a stream of the dilute gas and another for a stream of nitrogen and an output connected to a glass bulb. A 40 ppm H2S and a 50 ppm MM cylinders were used. The equipment was programmed to the selected concentration, and it automatically carried out the dilution to the glass bulb. The mixture was left flowing through the glass bulb for 5 min and then the extremities were closed. This method allowed the calibration between 1-20 ppm for H2S and 0.02-0.1 ppm and 1-3.5 ppm for MM. Several quantifications of air samples from inlet and outlet of a biofilter operating in a waste management facility in the north of Portugal allowed the evaluation the biofilters performance.

Keywords: biofiltration, hydrogen sulphide, mercaptans, quantification

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Authors: Andra Yount

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The purpose of this research project is to understand how focusing on movement can help English language learners acquire better reading, writing, and speaking skills. More specifically, this case study tests how Laban movement analysis, a tool often used in dance and physical education classes, contributes to advanced-level high school students’ English language acquisition at an international Swiss boarding school. This article shares theoretical bases for and findings from a teaching experiment in which LMA categories (body, effort, space, and shape) were adapted and introduced to students to encourage basic language acquisition and also cultural awareness and sensitivity. As part of the participatory action research process, data collection included pseudonym-protected questionnaires and written/video-taped responses to LMA language and task prompts. Responses from 43 participants were evaluated to determine the efficacy of using this system. Participants (ages 16-19) were enrolled in advanced English as an Additional Language (EAL) courses at a private, co-educational Swiss international boarding school. Final data analysis revealed that drawing attention to movement using LMA language as a stimulus creates better self-awareness and understanding/retention of key literary concepts and vocabulary but does not necessarily contribute to greater cultural sensitivity or eliminate the use of problematic (sexist, racist, or classist) language. Possibilities for future exploration and development are also explored.

Keywords: dance, English, Laban, pedagogy

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Authors: Syed A. Alam, Arifa Bilal

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A propagated wave of barbaric and injustice Muslims has been popularized by the International powers in the recent past to divert the winning force of Muslims in the Afghan war against Russia. It is a tactic to demolish the power of Jihaad and the religious image of Islam. The propaganda picturized that Muslims were not peaceful or trustworthy people by displaying some brutal actions of a little number of funded people. The word ‘Islam’ is titled as ‘complete codes of life’ because of the peacefulness and trustworthiness of these codes for whole lives. These codes help the whole of humanity beyond the boundaries of any religion, sect, creed, color, geography, or race to lead their lives peacefully and trustfully. The human beings who act upon these codes of life, Islam, can be called Muslims. Those people are not Muslims who do not act upon these codes of life. History is evident that the Muslims proved themselves, collectively, that they are acting upon these codes of life. In this article, an analytical study was conducted regarding popular treaties signed between Muslims and non-Muslim communities in different times and regions on different matters. The study included the treaties of Hudabiyah Treaty, Mithaq-e-Madinah, Lucknow Pact, Indus Water Pact, Air Space Violation Treaty, Gallipoli Treaty, Amity Treaty, US-Russia Peace Treaty, and Wadi Arab Peace Treaty. After critical analysis of these treaties, it can be clearly concluded that Muslims fulfilled these treatises, but non-Muslim stakeholders of these treaties broke these treaties in one aspect or many and in the start or later. It can be concluded that the history of treaties between Muslim and non-Muslim communities declared that Muslims had fulfilled these treaties and pacts, so they are more trustworthy and peaceful people.

Keywords: fulfilled treaties, Muslim and non-muslim pacts, Islam and peacefulness, Islam and treaties

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Authors: Ranjit A. Patil, Yung Liou, Yuan-Ron Ma

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It has been observed that when the size of metals such as, Au, Zn, Ag, Cu, Te, and metal oxides is reduced to several nano-meters, it starts to show further interesting properties. These new properties boost the use of nano-structures to produce attractive functional materials or used as promising building blocks in electronic devices. Present work describes the synthesis of bismuth (Bi) nanoparticles (NP’s) having uniform morphology, high crystallinity, and single phase purity by the temperature assisted pulsed laser deposition (TAPLD). Pulsed Laser deposition (PLD) technique is one of the promising methods to synthesize nano-structures. It can provide the stable nucleation sites in orders of magnitudes higher than for MBE and sputtering deposition. The desired size of purely metallic Bi NP’s of can be easily controlled by adjusting the temperature of the substrate varying from 1000 C to 250 0C. When the temperatures of the substrate raised step wise the average size of Bi NP’s appeared to be increased by maintaining the uniform distribution of NP’s on the Si surfaces. The diameter range of NP’s is ~33-84 nm shows size distribution constrained in the limited range. The EDS results show that the 0D Bi NP’s synthesized at high temperature (250 0C) at a high vacuum still remained in a metallic phase. Moreover, XRD, TEM and SAED results showed that these Bi NP’s are hexagonal in crystalline in a space group R -3 m and no traces of bismuth oxide, confirming that Bi NP’s synthesized at wide range of temperatures persisted of the pure Bi-metallic phase.

Keywords: metal nano particles, bismuth, pulsed laser deposition (PLD), nano particles, temperature assisted growth

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Authors: Salma A. El-Marasy, Rehab F. Abdel-Rahman, Reham M. Abd-Elsalam

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The burden of stroke is intensely increasing worldwide. Brain injury following transient or permanent focal cerebral ischemia develops ischemic stroke as a consequence of a complex series of pathophysiological events. The aim of this study is to evaluate the possible neuroprotective effect of a dipeptidyl peptidase-4 inhibitor, vildagliptin, independent on its insulinotropic properties in non-diabetic rats subjected to cerebral ischemia. Anaesthetized Wistar rats were subjected to either left middle cerebral artery occlusion (MCAO) or sham operation followed by reperfusion after 30 min of MCAO. The other three groups were orally administered vildagliptin at 3 dose levels (2.5, 5, 10 mg/kg) for 3 successive weeks before subjected to left focal cerebral ischemia/reperfusion and till the end of the study. Neurological deficit scores and motor activity were assessed 24h following reperfusion. 48h following reperfusion, rats were euthanized and their left brain hemispheres were harvested and used in the biochemical, histopathological, and immunohistochemical investigations. Vildagliptin pretreatment improved neurological score deficit, locomotor activity and motor coordination in MCAO rats. Moreover, vildagliptin reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), phosphotylinosital 3 kinase (PI3K), phosphorylated of protein kinase B (p-AKT), and mechanistic target of rapamycin (mTOR) brain contents in addition to reducing protein expression of caspase-3. Also, vildagliptin showed a dose-dependent attenuation in neuronal cell loss and histopathological alterations in MCAO rats. This study proves that vildagliptin exerted the neuroprotective effect in a dose-dependent manner as shown in amelioration of neuronal cell loss and histopathological damage in MCAO rats, which may be mediated by attenuating neuronal and motor deficits, it’s anti-oxidant property, activation of PI3K/AKT/mTOR pathway and its anti-apoptotic effect.

Keywords: caspase-3, cerebral ischemia, dipeptidyl peptidase-4 inhibitor, oxidative stress, PI3K/AKT/mTOR pathway, rats, vildagliptin

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Authors: Nashaat A. Deiab, Aida Radwan, Mohamed Elnagdy, Mohamed S. Yahiya, Rasha Moustafa

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This study is to evaluate and investigate the dosimetric performance of our institution's 3D treatment planning system, Elekta PrecisePLAN, for open 6MV fields including square, rectangular, variation in SSD, centrally blocked, missing tissue, square MLC and MLC shaped fields guided by the recommended QA tests prescribed in AAPM TG53, NCS report 15 test packages, IAEA TRS 430 and ESTRO booklet no.7. The study was performed for Elekta Precise linear accelerator designed for clinical range of 4, 6 and 15 MV photon beams with asymmetric jaws and fully integrated multileaf collimator that enables high conformance to target with sharp field edges. Seven different tests were done applied on solid water equivalent phantom along with 2D array dose detection system, the calculated doses using 3D treatment planning system PrecisePLAN, compared with measured doses to make sure that the dose calculations are accurate for open fields including square, rectangular, variation in SSD, centrally blocked, missing tissue, square MLC and MLC shaped fields. The QA results showed dosimetric accuracy of the TPS for open fields within the specified tolerance limits. However large square (25cm x 25cm) and rectangular fields (20cm x 5cm) some points were out of tolerance in penumbra region (11.38 % and 10.9 %, respectively). For the test of SSD variation, the large field resulted from SSD 125 cm for 10cm x 10cm filed the results recorded an error of 0.2% at the central axis and 1.01% in penumbra. The results yielded differences within the accepted tolerance level as recommended. Large fields showed variations in penumbra. These differences between dose values predicted by the TPS and the measured values at the same point may result from limitations of the dose calculation, uncertainties in the measurement procedure, or fluctuations in the output of the accelerator.

Keywords: quality assurance, dose calculation, 3D treatment planning system, photon beam

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Authors: Omolola R. Ayepola, Nicole L. Brooks, Oluwafemi O. Oguntibeju

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The liver plays an important role in the regulation of blood glucose and is a target organ of hyperglycaemia. Hyperglycemia plays a crucial role in the onset of various liver diseases and may culminate into hepatopathy if untreated. Alteration in antioxidant defense and increase in oxidative stress that results in tissue injury is characteristic of diabetes. We evaluated the protective effects of kolaviron-a biflavonoid complex, on hepatic antioxidants, lipid peroxidation and apoptosis in the liver of diabetic rats. To induce type I diabetes, rats were injected with streptozotocin intraperitoneally at a single dose of 50 mg/kg. Oral treatment of diabetic rats with kolaviron (100 mg/kg) started on the 6th day after diabetes induction and continued for 6 weeks (5 times weekly). Diabetic rats exhibited a significant increase in the peroxidation of hepatic lipids as observed from the elevated level of malondialdehyde (MDA) estimated by High-Performance Liquid Chromatography. In addition, Oxygen Radical Absorbance Capacity (ORAC), ratio of reduced to oxidized glutathione (GSH/GSSG) and catalase (CAT) activity was decreased in the liver of diabetic rats. TUNEL assay revealed increased apoptotic cell death in the liver of diabetic rats. Examination of Pancreatic beta-cells by immunohistochemical methods revealed beta cell degeneration and reduction in beta cell/ islet area in the diabetic controls. Kolaviron-treatment increased the area of insulin immunoreactive beta-cells significantly. Kolaviron attenuated lipid peroxidation and apoptosis in the liver of diabetic rats, increased CAT activity GSH levels and the resultant GSH: GSSG. The ORAC of kolaviron-treated diabetic liver was restored to near-normal values. Kolaviron protects the liver against oxidative and apoptotic damage induced by hyperglycemia. The antidiabetic effect of kolaviron may also be related to its beneficial effects on beta-cell function.

Keywords: diabetes mellitus, kolaviron, oxidative stress, liver, apoptosis

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Authors: Andy Sand, Naama Massad – Ivanir, Nadav Nitzan, Elisa Valderrama, Alfred Wegenberger, Koranit Shlosman, Rotem Shemesh, Ester Segal

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Microbial spoilage of food products is of great concern in the food industry due to the direct impact on the shelf life of foods and the risk of foodborne illness. Therefore, food packaging may serve as a crucial contribution to keep the food fresh and suitable for consumption. Active packaging solutions that have the ability to inhibit the development of microorganism in food products attract a lot of interest, and many efforts have been made to engineer and assimilate such solutions on various food products. NanoPack is an EU-funded international project aiming to develop state-of-the-art antimicrobial packaging systems for perishable foods. The project is based on natural essential oils which possess significant antimicrobial activity against many bacteria, yeasts and molds. The essential oils are encapsulated in natural aluminosilicate clays, halloysite nanotubes (HNT's), that serves as a carrier for the volatile essential oils and enable their incorporation into polymer films. During the course of the project, several polyethylene films with diverse essential oils combinations were designed based on the characteristics of their target food products. The antimicrobial activity of the produced films was examined in vitro on a broad spectrum of microorganisms including gram-positive and gram-negative bacteria, aerobic and anaerobic bacteria, yeasts and molds. The films that showed promising in vitro results were successfully assimilated on in vivo active packaging of several food products such as cheese, bread, fruits and raw meat. The results of the in vivo analyses showed significant inhibition of the microbial spoilage, indicating the strong contribution of the NanoPack packaging solutions on the extension of shelf life and reduction of food waste caused by early spoilage throughout the supply chain.

Keywords: food safety, food packaging, essential oils, nanotechnology

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Authors: Nongcebo Ngcobo

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This research explores the importance of including a multitude of voices in the cultural heritage narrative, particularly in South Africa. The Mashishing project is an extension of and builds on the existing ‘Biesje Poort project’ which is a rock art project that was funded by the National Heritage Council in 2010 - 2013. Hence, the Mashishing marking memories project applies comparable Biesje Poort project objectives, though in a different geographical area. The wider project objectives are to transfer skills, promote social cohesion and empowerment, and lastly to add to the knowledge base of the Mashishing region and the repository of the local museum in the Lydenburg museum. This study is located in the Mashishing area, in Mpumalanga, South Africa. In this area, there were no present multi-vocal heritage projects. This research assesses the Mashishing marking memories project through the culture-centered approach for communication for social change, which examines the impact that the diverse participants have on the operations of the Mashishing project and also investigates whether the culturally diverse participants facilitates or hinders effective participation within the project. Key findings of this research uncovered the significance of participation and diverse voices in the cultural heritage field. Furthermore, this study highlights how unequal power relations affect effective participation. As a result, this study encourages the importance of bringing the researcher and the participant in a safe space to facilitate mutual learning. It also encourages an exchange of roles, where the researcher shifts from being an authoritarian figure to being in the role of a listener.

Keywords: culture, heritage, participation, social change

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Authors: Mirza Adil Ahmad Mughal

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Transcendental analytics, in the critique of pure reason, combines space and time as conditions of the possibility of the phenomenon from the transcendental aesthetic with the pure magnitude-intuition notion. The property of continuity as a qualitative result of the additive magnitude brings the possibility of connecting with experience, even though only as a potential because of the a priori necessity from assumption, as syntheticity of the a priori task of a scientific method of philosophy given by Kant, which precludes the application of categories to something not empirically reducible to the content of such a category's corresponding and possible object. This continuity as the qualitative result of a priori constructed notion of magnitude lies as a fundamental assumption and property of, what in Microeconomic theory is called as, 'choice rules' which combine the potentially-empirical and practical budget-price pairs with preference relations. This latter result is the purest qualitative side of the choice rules', otherwise autonomously, quantitative nature. The theoretical, barring the empirical, nature of this qualitative result is a synthetic a priori truth, which, if at all, it should be, if the axiomatic structure of the economic theory is held to be correct. It has a potentially verifiable content as its possible object in the form of quantitative price-budget pairs. Yet, the object that serves the respective Kantian category is qualitative itself, which is utility. This article explores the validity of Kantian qualifications for this application of 'categories' to the economic structure of society.

Keywords: categories of understanding, continuity, convexity, psyche, revealed preferences, synthetic a priori

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Authors: Katyana A. Vert-Pre, James T. Thorson, Thomas Trancart, Eric Feunteun

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In marine ecosystems, spatial and temporal species structure is an important component of ecosystems’ response to anthropological and environmental factors. Although spatial distribution patterns and fish temporal series of abundance have been studied in the past, little research has been allocated to the joint dynamic spatio-temporal functional patterns in marine ecosystems and their use in multispecies management and conservation. Each species represents a function to the ecosystem, and the distribution of these species might not be random. A heterogeneous functional distribution will lead to a more resilient ecosystem to external factors. Applying a Vector-Autoregressive Spatio-Temporal (VAST) model for count data, we estimate the spatio-temporal distribution, shift in time, and abundance of 140 species of the Eastern English Chanel, Bay of Biscay and Mediterranean Sea. From the model outputs, we determined spatio-temporal clusters, calculating p-values for hierarchical clustering via multiscale bootstrap resampling. Then, we designed a functional map given the defined cluster. We found that the species distribution within the ecosystem was not random. Indeed, species evolved in space and time in clusters. Moreover, these clusters remained similar over time deriving from the fact that species of a same cluster often shifted in sync, keeping the overall structure of the ecosystem similar overtime. Knowing the co-existing species within these clusters could help with predicting data-poor species distribution and abundance. Further analysis is being performed to assess the ecological functions represented in each cluster.

Keywords: cluster distribution shift, European marine ecosystems, functional distribution, spatio-temporal model

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Authors: Heba I. Bakry

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Academic writing in the tertiary education has always been a challenge to EFL learners. This proposed study aims at investigating the academic English language needs for PhD students and candidates studying humanities and social sciences at Cairo University. The research problem arises from the fact that most of them study English as a Foreign Language (EFL) or for specific purposes (ESP) in their undergraduate years. They are hardly familiarized with the different academic genres, despite the fact that they use academic resources written in English, and they are required to publish a paper internationally. Upon understanding the conventions and constraints of academic writing, postgraduates will have the opportunity to interact with the international academic spheres conveniently. There is, thus, a need to be acquainted with the generally accepted features of the academic genres, such as academic papers and their part-genres, such as writing abstracts, in addition to other occluded genres, such as personal statements and recommendation letters. The lack of practicing many of these genres is caused by the fact that there are clear differences between the rhetoric and conventions of the students' native language, i.e., Arabic, and the target language they are learning in the academic context, i.e., English. Moreover, apart from the general culture represented ethno-linguistically, the learners' 'small' culture represented in a national setting like Cairo University is more defining than their general cultural affiliations that are associated with their nationality, race, or religion, for instance. The main research question of this proposed study is: What is the effect of teaching a genre-based EAP course on the research writing competence of PhD candidates? To reach an answer to this question, the study will attempt to answer the following sub-questions: 1. What are the Egyptian PhD candidates' EAP perceived needs? 2. What are the requisite academic research skills for Egyptian scholars? The study intends to assess the students’ needs, as a step to design and evaluate an EAP course that is based on explaining and scrutinizing a variety of academic genres. Adopting a diagnostic approach, the needs assessment uses quantitative data collected through questionnaires, and qualitative data assembled from semi-structured interviews with the students and their teachers, in addition to non-participant observations of a convenience sample.

Keywords: course design, English for academic purposes, genre-based, needs assessment

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Authors: Yifat Koren Carmi, Abed Agbarya, Hazem Khamaisi, Raymond Farah, Yelena Shechtman, Roman Korobochka, Jacob Gopas, Jamal Mahajna

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Ovarian cancer (OC), the second most common form of gynecological malignancy, has a poor prognosis and is frequently identified in its late stages. The recommended treatment for OC typically includes a platinum-based chemotherapy, like carboplatin. Nonetheless, OC treatment has proven challenging due to toxicity and development of acquired resistance to therapy. Chemoresistance is a significant obstacle to a long-lasting response in OC patients, believed to arise from alterations within the cancer cells as well as within the tumor microenvironments (TME). Malignant ascites is a presenting feature in more than one-third of OC patients. It serves as a reservoir for a complex mixture of soluble factors, metabolites, and cellular components, providing a pro-inflammatory and tumor-promoting microenvironment for the OC cells. Malignant ascites is also associated with metastasis and chemoresistance. In an attempt to elucidate the role of TME in chemoresistance of OC, we monitored the ability of soluble factors derived from ascites fluids to affect platinum sensitivity of OC cells. This research, compared ascites fluids from non-malignant cirrhotic patients to those from OC patients in terms of their ability to alter the platinum sensitivity of OC cells. Our findings indicated that exposure to OC ascites induces platinum chemoresistance on OC cells in 11 out of 13 cases (85%). In contrast, 75% of cirrhosis ascites (3 out of 4) failed to confer platinum chemoresistance to OC cells. Cytokine array analysis revealed that IL-6, and to a lesser extent HGF were enriched in OC ascites, whereas IL-22 was enriched in cirrhosis ascites. Pharmaceutical inhibitors that target the IL-6/JAK signaling pathway were mildly effective in overcoming the platinum chemoresistance induced by malignant ascites. In contrast, Crizotinib an HGF/c-MET inhibitor, and 2-hydroxyestradiol (2HE2) were effective in restoring platinum chemoresistance to OC. Our findings demonstrate the importance of OC ascites in supporting platinum chemoresistance as well as the potential of a combination therapy with Crizotinib and the estradiol metabolite 2HE2 to regain OC cells chemosensitivity.

Keywords: ovarian cancer, platinum chemoresistance, malignant ascites, tumor microenvironment, IL-6, 2-hydroxyestradiol, HGF, crizotinib

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Authors: Ugoh Kelechi Melford, Anene O.

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Introduction: Evidence has shown that there are increasing rates of new HIV and other STI infections occurring among Men who have Sex with Men (MSM) in Nigeria, with the prevalence 3 times higher than the general population as reported by the 2011 National Integrated Bio Behavioral Surveillance Survey. The poor state of health care and support services hinders our effort to control the high rates of these new infections among MSM. Methods: The Initiative for Improved Male Health (IMH-Initiative) works to provide a safe space for young MSM living with HIV to access comprehensive palliative care and support, as well as referrals for other services through drama and dance competitions. An STI assessment was conducted in IMH-Initiative’s Community Center in Calabar, for gay men and other MSM. An STI history was conducted for all clients who visited the community clinic specifically for HCT and STI counseling and referrals within a 5 month period, and their data were collated. Results: 61 MSM were diagnosed, and reported the following in the last 6 months. 49 where living with HIV. 46 had previous histories of untreated anal warts. 20 had previous histories of treated Gonorrhea by self-medication and herbs. 21 had untreated boils and rashes around the genitals. 10 clients where living with HIV, and reported untreated penile and rectal gonorrhea. All clients indicated that there were not comfortable discussing STI infections with staff of public hospitals. Conclusion: It is evident that a reasonable number of STI infections among MSM are not completely treated or ignored. This thereby increases the individual’s risk of HIV infection, and cripples HIV prevention programming in Nigeria. HIV programs targeting MSM must incorporate STI syndromic management, so as to increase access to non-stigmatized diagnosis and treatment of STIs. Also, access to STI drugs for clients cannot be overemphasized.

Keywords: MSM, IBBSS, STI, IMH

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Authors: T. Delval, C. Sauvage, Q. Jullien, R. Viano, T. Diallo, B. Collignan, G. Picinbono

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In the context of the international spread of COVID-19, the Centre Scientifique et Technique du Bâtiment (CSTB) has led a joint research with the French government authorities Hauts-de-Seine department, to analyse the risk in school spaces according to their configuration, ventilation system and spatial segmentation strategy. This paper describes the main results of this joint research. A multidisciplinary team involving experts in indoor air quality/ventilation, pedestrian movements and IT domains was established to develop a COVID risk analysis tool based on Building Information Model. The work started with specific analysis on two pilot schools in order to provide for the local administration specifications to minimize the spread of the virus. Different recommendations were published to optimize/validate the use of ventilation systems and the strategy of student occupancy and student flow segmentation within the building. This COVID expertise has been digitized in order to manage a quick risk analysis on the entire building that could be used by the public administration through an easy user interface implemented in a free BIM Management software. One of the most interesting results is to enable a dynamic comparison of different ventilation system scenarios and space occupation strategy inside the BIM model. This concurrent engineering approach provides users with the optimal solution according to both ventilation and pedestrian flow expertise.

Keywords: BIM, knowledge management, system expert, risk management, indoor ventilation, pedestrian movement, integrated design

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Authors: Kwan U. Kim, Jin Sim, Ryong Jin Jang, Sung Duk Kim

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108 years have passed since a great number of physicists explained astronomical and physical phenomena by solving geodesic equations in the Schwarzschild metric. However, when solving the geodesic equations in Schwarzschild metric, they did not correctly solve one branch of the component of space among spatial and temporal components of four-dimensional force and did not come up with physical laws correctly by means of physical analysis from the results obtained by solving the geodesic equations. In addition, they did not treat the astronomical and physical phenomena in a physical way based on the correct physical laws obtained from the solution of the geodesic equations in the Schwarzschild metric. Therefore, some former scholars mentioned that Einstein’s theoretical basis of a general theory of relativity was obscure and incorrect, but they did not give a correct physical solution to the problems. Furthermore, since the general theory of relativity has not given a quantitative solution to obscure and incorrect problems, the generalization of gravitational theory has not yet been successfully completed, although former scholars have thought of it and tried to do it. In order to solve the problems, it is necessary to explore the obscure and incorrect problems in a general theory of relativity based on the physical laws and to find out the methodology for solving the problems. Therefore, as the first step toward achieving this purpose, the right solution of the geodesic equation in the Schwarzschild metric has been presented. Next, the correct physical laws found by making a physical analysis of the results have been presented, the obscure and incorrect problems have been shown, and an analysis of them has been made based on the physical laws. In addition, the experimental verification of the physical laws found by us has been made.

Keywords: equivalence principle, general relativity, geometrodynamics, Schwarzschild, Poincaré

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Authors: S. Art-in

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This research was a survey research. The objective of this study was to study current situation and need in learning management for developing the analytical thinking of teachers in basic education of Thailand. The target group consisted of 400 teachers teaching in basic education level. They were selected by multi-stage random sampling. The instrument used in this study was the questionnaire asking current situation and need in learning management for developing the analytical thinking, 5 level rating scale. Data were analyzed by calculating the frequency, mean, standard deviation, percentage and content analysis. The research found that: 1) For current situation, the teachers provided learning management for developing analytical thinking, in overall, in “high” level. The issue with lowest level of practice: the teachers had competency in designing and establishing the learning management plan for developing the students’ analytical thinking. Considering each aspect it was found that: 1.1) the teacher aspect; the issue with lowest level of practice was: the teachers had competency in designing and establishing the learning management plan for developing the students’ analytical thinking, and 1.2) the learning management aspect for developing the students’ analytical thinking, the issue with lowest level of practice was: the learning activities provided opportunity for students to evaluate their analytical thinking process in each learning session. 2) The teachers showed their need in learning management for developing the analytical thinking, in overall, in “the highest” level. The issue with highest level of the need was: to obtain knowledge and competency in model, technique, and method for learning management or steps of learning management for developing the students’ analytical thinking. Considering each aspect it was found that: 2.1) teacher aspect; the issue with highest level of the need was: to obtain knowledge and comprehension in model, technique, and method for learning management or steps of learning management for developing the students’ analytical thinking, and 2.2) learning management aspect for developing the analytical thinking, the issue with highest level of need consisted of the determination of learning activities as problem situation, and the opportunity for students to comprehend the problem situation as well as practice their analytical thinking in order to find the answer.

Keywords: current situation and need, learning management, analytical thinking, teachers in basic education level, Thailand

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Authors: Chakrapani Pullagummi, Arun Jyothi Bheemagani, B. Chandra Sekhar Singh, Prem Kumar, A. Roja Rani

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Diabetes mellitus describes a metabolic disorder of multiple aetiology characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion and its action. The objective of present study was alloxan induced diabetes in S.D (Sprague Dawley) rats, treated with leaf extract of Andrographis paniculata and bark extract of Erythrina indica. Plant extract treated rats were analyzed biochemically and molecularly. on normal and diabetic rats. The changes in MDA (lipid peroxidation) and glucose (by GOD method) levels in blood of both normal and diabetic rat were analyzed. Diabetes induced rats were treated with methanolic extracts of Andrographis paniculata leaf and Erythrina indica bark which are of medicinal importance. Later after inducing diabetes the rats were treated with medicinal plant extracts, Andrographis paniculata leaf and Erythrina indica bark which are well known for their anti diabetic and antioxidative property in order to control the glucose and MDA levels. The blood plasma of diabetic and normal rats was analyzed for the levels of MDA (lipid peroxidation) and glucose levels. Results of this study suggested that the Andrographis paniculata leaf and Erythrina indica can be used as a potential natural antidiabetic agent for treating and postponing the appearance of complications that arise due to Diabetes. Molecular study deals with the analysis of binding mechanism of 2 selected natural compounds from Andrographis and Erythrina extracts against the novel target for type T2D namely PPAR-γ compared with Rosiglitazone (standard compound). The results revealed that most of the selected herbal lead compounds were effective targets against the receptors. These compounds showed favorable interactions with the amino acid residues thereby substantiating their proven efficacy as anti-diabetic compounds.

Keywords: andrographis paniculata, erythrina indica, alloxan, lipid peroxidation, blood glucose level, PPAR-γ

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Authors: Ian Campbell, Gillian Mitchell, Paul James, Na Li, Ella Thompson

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The genetic cause of the majority of multiple-case breast cancer families remains unresolved. Next generation sequencing has emerged as an efficient strategy for identifying predisposing mutations in individuals with inherited cancer. We are conducting whole exome sequence analysis of germ line DNA from multiple affected relatives from breast cancer families, with the aim of identifying rare protein truncating and non-synonymous variants that are likely to include novel cancer predisposing mutations. Data from more than 200 exomes show that on average each individual carries 30-50 protein truncating mutations and 300-400 rare non-synonymous variants. Heterogeneity among our exome data strongly suggest that numerous moderate penetrance genes remain to be discovered, with each gene individually accounting for only a small fraction of families (~0.5%). This scenario marks validation of candidate breast cancer predisposing genes in large case-control studies as the rate-limiting step in resolving the missing heritability of breast cancer. The aim of this study is to screen genes that are recurrently mutated among our exome data in a larger cohort of cases and controls to assess the prevalence of inactivating mutations that may be associated with breast cancer risk. We are using the Agilent HaloPlex Target Enrichment System to screen the coding regions of 168 genes in 1,000 BRCA1/2 mutation-negative familial breast cancer cases and 1,000 cancer-naive controls. To date, our interim analysis has identified 21 genes which carry an excess of truncating mutations in multiple breast cancer families versus controls. Established breast cancer susceptibility gene PALB2 is the most frequently mutated gene (13/998 cases versus 0/1009 controls), but other interesting candidates include NPSR1, GSN, POLD2, and TOX3. These and other genes are being validated in a second cohort of 1,000 cases and controls. Our experience demonstrates that beyond PALB2, the prevalence of mutations in the remaining breast cancer predisposition genes is likely to be very low making definitive validation exceptionally challenging.

Keywords: predisposition, familial, exome sequencing, breast cancer

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