Search results for: discovery of misattributed paternity

Authors: Micheale Yifter Weldemichael, Hailay Mehari Gebremedhn, Teklehaimanot Hailesslasie Teklu

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Recent developments in targeted genome editing accelerated genetic research and opened new potentials to improve crops for better yields and quality. Given the significance of cereal crops as a primary source of food for the global population, the utilization of contemporary genome editing techniques like CRISPR/Cas9 is timely and crucial. CRISPR/Cas technology has enabled targeted genomic modifications, revolutionizing genetic research and exploration. Application of gene editing through CRISPR/Cas9 in enhancing sorghum is particularly vital given the current ecological, environmental, and agricultural challenges exacerbated by climate change. As sorghum is one of the main staple foods of our region and is known to be a resilient crop with a high potential to overcome the above challenges, the application of genome editing technology will enhance the investigation of gene functionality. CRISPR/Cas9 enables the improvement of desirable sorghum traits, including nutritional value, yield, resistance to pests and diseases, and tolerance to various abiotic stresses. Furthermore, CRISPR/Cas9 has the potential to perform intricate editing and reshape the existing elite sorghum varieties, and introduce new genetic variations. However, current research primarily focuses on improving the efficacy of the CRISPR/Cas9 system in successfully editing endogenous sorghum genes, making it a feasible and successful undertaking in sorghum improvement. Recent advancements and developments in CRISPR/Cas9 techniques have further empowered researchers to modify additional genes in sorghum with greater efficiency. Successful application and advancement of CRISPR techniques in sorghum will aid not only in gene discovery and the creation of novel traits that regulate gene expression and functional genomics but also in facilitating site-specific integration events. The purpose of this review is, therefore, to elucidate the current advances in sorghum genome editing and highlight its potential in addressing food security issues. It also assesses the efficiency of CRISPR-mediated improvement and its long-term effects on crop improvement and host resistance against parasites, including tissue-specific activity and the ability to induce resistance. This review ends by emphasizing the challenges and opportunities of CRISPR technology in combating parasitic plants and proposing directions for future research to safeguard global agricultural productivity.

Keywords: CRISPR/Cas9, genome editing, quality, sorghum, stress, yield

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Authors: Mina Rabipour, Elena Pallaske, Floyd Hassenrück, Rocio Rebollido-Rios

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Protein tyrosine kinases, including Lyn kinase of the Src family kinases (SFK), regulate cell proliferation, survival, and differentiation. Lyn kinase has been implicated in various cancers, positioning it as a promising therapeutic target. However, the conserved ATP-binding pocket across SFKs makes developing selective inhibitors challenging. This study aims to address this limitation by exploring the potential for allosteric modulation of Lyn kinase, focusing on how its structural dynamics and specific oncogenic mutations impact its conformation and function. To achieve this, we combined homology modeling, molecular dynamics simulations, and data science techniques to conduct microsecond-length simulations. Our approach allowed a detailed investigation into the interplay between Lyn’s catalytic and regulatory domains, identifying key conformational states involved in allosteric regulation. Additionally, we evaluated the structural effects of Dasatinib, a competitive inhibitor, and ATP binding on Lyn active conformation. Notably, our simulations show that cancer-related mutations, specifically I364L/N and E290D/K, shift Lyn toward an inactive conformation, contrasting with the active state of the wild-type protein. This may suggest how these mutations contribute to aberrant signaling in cancer cells. We conducted a dynamical network analysis to assess residue-residue interactions and the impact of mutations on the Lyn intramolecular network. This revealed significant disruptions due to mutations, especially in regions distant from the ATP-binding site. These disruptions suggest potential allosteric sites as therapeutic targets, offering an alternative strategy for Lyn inhibition with higher specificity and fewer off-target effects compared to ATP-competitive inhibitors. Our findings provide insights into Lyn kinase regulation and highlight allosteric sites as avenues for selective drug development. Targeting these sites may modulate Lyn activity in cancer cells, reducing toxicity and improving outcomes. Furthermore, our computational strategy offers a scalable approach for analyzing other SFK members or kinases with similar properties, facilitating the discovery of selective allosteric modulators and contributing to precise cancer therapies.

Keywords: lyn tyrosine kinase, mutation analysis, conformational changes, dynamic network analysis, allosteric modulation, targeted inhibition

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Authors: Nada R. Abuknesha, John P. Morgan, Andrew J. Searle

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Information regarding post-mortem interval (PMI) in criminal investigations is vital to establish a time frame when reconstructing events. PMI is defined as the time period that has elapsed between the occurrence of death and the discovery of the corpse. Adipocere, commonly referred to as ‘grave-wax’, is formed when post-mortem adipose tissue is converted into a solid material that is heavily comprised of fatty acids. Adipocere is of interest to forensic anthropologists, as its formation is able to slow down the decomposition process. Therefore, analysing the changes in the patterns of fatty acids during the early decomposition process may be able to estimate the period of burial, and hence the PMI. The current study concerned the investigation of the fatty acid composition and patterns in buried pig fat tissue. This was in an attempt to determine whether particular patterns of fatty acid composition can be shown to be associated with the duration of the burial, and hence may be used to estimate PMI. The use of adipose tissue from the abdominal region of domestic pigs (Sus-scrofa), was used to model the human decomposition process. 17 x 20cm piece of pork belly was buried in a shallow artificial grave, and weekly samples (n=3) from the buried pig fat tissue were collected over an 11-week period. Marker fatty acids: palmitic (C16:0), oleic (C18:1n-9) and linoleic (C18:2n-6) acid were extracted from the buried pig fat tissue and analysed as fatty acid methyl esters using the gas chromatography system. Levels of the marker fatty acids were quantified from their respective standards. The concentrations of C16:0 (69.2 mg/mL) and C18:1n-9 (44.3 mg/mL) from time zero exhibited significant fluctuations during the burial period. Levels rose (116 and 60.2 mg/mL, respectively) and fell starting from the second week to reach 19.3 and 18.3 mg/mL, respectively at week 6. Levels showed another increase at week 9 (66.3 and 44.1 mg/mL, respectively) followed by gradual decrease at week 10 (20.4 and 18.5 mg/mL, respectively). A sharp increase was observed in the final week (131.2 and 61.1 mg/mL, respectively). Conversely, the levels of C18:2n-6 remained more or less constant throughout the study. In addition to fluctuations in the concentrations, several new fatty acids appeared in the latter weeks. Other fatty acids which were detectable in the time zero sample, were lost in the latter weeks. There are several probable opportunities to utilise fatty acid analysis as a basic technique for approximating PMI: the quantification of marker fatty acids and the detection of selected fatty acids that either disappear or appear during the burial period. This pilot study indicates that this may be a potential semi-quantitative methodology for determining the PMI. Ideally, the analysis of particular fatty acid patterns in the early stages of decomposition could be an additional tool to the already available techniques or methods in improving the overall processes in estimating PMI of a corpse.

Keywords: adipocere, fatty acids, gas chromatography, post-mortem interval

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Authors: Zohar Manber, Ran Elkon

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Accumulation of somatic mutations (SMs) in the genome is a major driving force of cancer development. Most SMs in the tumor's genome are functionally neutral; however, some cause damage to critical processes and provide the tumor with a selective growth advantage (termed cancer driver mutations). Current research on functional significance of SMs is mainly focused on finding alterations in protein coding sequences. However, the exome comprises only 3% of the human genome, and thus, SMs in the noncoding genome significantly outnumber those that map to protein-coding regions. Although our understanding of noncoding driver SMs is very rudimentary, it is likely that disruption of regulatory elements in the genome is an important, yet largely underexplored mechanism by which somatic mutations contribute to cancer development. The expression of most human genes is controlled by multiple enhancers, and therefore, it is conceivable that regulatory SMs are distributed across different enhancers of the same target gene. Yet, to date, most statistical searches for regulatory SMs have considered each regulatory element individually, which may reduce statistical power. The first challenge in considering the cumulative activity of all the enhancers of a gene as a single unit is to map enhancers to their target promoters. Such mapping defines for each gene its set of regulating enhancers (termed "set of regulatory elements" (SRE)). Considering multiple enhancers of each gene as one unit holds great promise for enhancing the identification of driver regulatory SMs. However, the success of this approach is greatly dependent on the availability of comprehensive and accurate enhancer-promoter (E-P) maps. To date, the discovery of driver regulatory SMs has been hindered by insufficient sample sizes and statistical analyses that often considered each regulatory element separately. In this study, we analyzed more than 2,500 whole-genome sequence (WGS) samples provided by The Cancer Genome Atlas (TCGA) and The International Cancer Genome Consortium (ICGC) in order to identify such driver regulatory SMs. Our analyses took into account the combinatorial aspect of gene regulation by considering all the enhancers that control the same target gene as one unit, based on E-P maps from three genomics resources. The identification of candidate driver noncoding SMs is based on their recurrence. We searched for SREs of genes that are "hotspots" for SMs (that is, they accumulate SMs at a significantly elevated rate). To test the statistical significance of recurrence of SMs within a gene's SRE, we used both global and local background mutation rates. Using this approach, we detected - in seven different cancer types - numerous "hotspots" for SMs. To support the functional significance of these recurrent noncoding SMs, we further examined their association with the expression level of their target gene (using gene expression data provided by the ICGC and TCGA for samples that were also analyzed by WGS).

Keywords: cancer genomics, enhancers, noncoding genome, regulatory elements

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Authors: M. A. H. Barry

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The concept of Good faith (husn al-niyyah) and fair-dealing (Nadl) are the fundamental guiding elements in all contracts and other agreements under Islamic law. The preaching of Al-Quran and Prophet Muhammad’s (Peace Be upon Him) firmly command people to act in good faith in all dealings. There are several Quran verses and the Prophet’s saying which stressed the significance of dealing honestly and fairly in all transactions. Under the English law, the good faith is not considered a fundamental requirement for the formation of a legal contract. However, the concept of Good Faith in private contracts is recognized by the civil law system and in Article 7(1) of the Convention on International Sale of Goods (CISG-Vienna Convention-1980). It took several centuries for the international trading community to recognize the significance of the concept of good faith for the international sale of goods transactions. Nevertheless, the recognition of good faith in Civil law is only confined for the commercial contracts. Subsequently to the CISG, this concept has made inroads into the private international law. There are submissions in favour of applying the good faith concept to public international law based on tacit recognition by the international conventions and International Tribunals. However, under public international law the concept of good faith is not recognized as a source of rights or obligations. This weakens the spirit of the good faith concept, particularly when determining the international disputes. This also creates a fundamental flaw because the absence of good faith application means the breaches tainted by bad faith are tolerated. The objective of this research is to evaluate, examine and analyze the application of the concept of good faith in the modern laws and identify its limitation, in comparison with Islamic concept of good faith. This paper also identifies the problems and issues connected with the non-application of this concept to public international law. This research consists of three key components (1) the preliminary inquiry (2) subject analysis and discovery of research results, and (3) examining the challenging problems, and concluding with proposals. The preliminary inquiry is based on both the primary and secondary sources. The same sources are used for the subject analysis. This research also has both inductive and deductive features. The Islamic concept of good faith covers all situations and circumstances where the bad faith causes unfairness to the affected parties, especially the weak parties. Under the Islamic law, the concept of good faith is a source of rights and obligations as Islam prohibits any person committing wrongful or delinquent acts in any dealing whether in a private or public life. This rule is applicable not only for individuals but also for institutions, states, and international organizations. This paper explains how the unfairness is caused by non-recognition of the good faith concept as a source of rights or obligations under public international law and provides legal and non-legal reasons to show why the Islamic formulation is important.

Keywords: good faith, the civil law system, the Islamic concept, public international law

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Authors: Christelle E. Chua, Alicia L. Ho

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The development of a panel of differential gene expression signatures has been of interest in the field of biomarker discovery for radiation exposure. In the absence of the availability of exposed human subjects, lymphocyte cell lines have often been used as a surrogate to human whole blood, when performing ex vivo irradiation studies. The extent of variation between different lymphocyte cell lines is currently unclear, especially with regard to the expression of extracellular miRNA. This study compares the expression profile of extracellular miRNA isolated from different lymphocyte cell lines. It also compares the profile of miRNA obtained when different exosome isolation kits are used. Lymphocyte cell lines were created using lymphocytes isolated from healthy adult males of similar racial descent (Chinese American and Chinese Singaporean) and immortalised with Epstein-Barr virus. The cell lines were cultured in exosome-free cell culture media for 72h and the cell culture supernatant was removed for exosome isolation. Two exosome isolation kits were used. Total exosome isolation reagent (TEIR, ThermoFisher) is a polyethylene glycol (PEG)-based exosome precipitation kit, while ExoSpin (ES, Cell Guidance Systems) is a PEG-based exosome precipitation kit that includes an additional size exclusion chromatography step. miRNA from the isolated exosomes were isolated using miRNEASY minikit (Qiagen) and analysed using nCounter miRNA assay (Nanostring). Principal component analysis (PCA) results suggested that the overall extracellular miRNA expression profile differed between the lymphocyte cell line originating from the Chinese American donor and the cell line originating from the Chinese Singaporean donor. As the gender, age and racial origins of both donors are similar, this may suggest that there are other genetic or epigenetic differences that account for the variation in extracellular miRNA gene expression in lymphocyte cell lines. However, statistical analysis showed that only 3 miRNA genes had a fold difference > 2 at p < 0.05, suggesting that the differences may not be of that great a significance as to impact overall conclusions drawn from different cell lines. Subsequent analysis using cell lines from other donors will give further insight into the reproducibility of results when difference cell lines are used. PCA results also suggested that the method of exosome isolation impacted the expression profile. 107 miRNA had a fold difference > 2 at p < 0.05. This suggests that the inclusion of an additional size exclusion chromatography step altered the subset of the extracellular vesicles that were isolated. In conclusion, these results suggest that extracellular miRNA can be isolated and analysed from exosomes derived from lymphocyte cell lines. However, care must be taken in the choice of cell line and method of exosome isolation used.

Keywords: biomarker, extracellular miRNA, isolation methods, lymphocyte cell line

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Authors: Nadia K. Thalji

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The shamanic odyssey of Hushahu, a courageous indigenous woman from the Amazon, reverberates with profound significance, resonating far beyond the confines of her tribal boundaries. This abstract explores Hushahu's transformative journey, which serves as a beacon of empowerment for indigenous women across the Amazon region. Hushahu's narrative unfolds against the backdrop of entrenched gender norms and colonial legacies that have historically marginalized women from spiritual leadership and ritual practices. Despite societal expectations and entrenched traditions, Hushahu boldly embraces her calling as a shaman, defying cultural constraints and challenging prevailing gender norms. Her journey represents a symbolic uprising against centuries of patriarchal dominance, offering a glimpse into the resilience and strength of indigenous women. Drawing upon Jungian psychology, Hushahu's quest can be understood as a profound exploration of the symbolic dimensions of the psyche. Through Hushahu’s initiation rituals and visionary experiences, the initiate embarks on a transformative journey of self-discovery, encountering archetypal symbols and tapping into the collective unconscious. Symbolism permeates the path, guiding Hushahu through the depths of the rainforest and illuminating the hidden realms of consciousness. Central to Hushahu's narrative is the theme of empowerment—a theme that transcends individual experience to catalyze broader social change. As Hushahu finds a voice amidst the echoes of ancestral wisdom, the journey inspires a ripple effect of empowerment throughout indigenous communities. Other women within Hushahu's tribe and neighboring societies are emboldened to challenge traditional gender roles, stepping into leadership positions and reclaiming their rightful place in spiritual practices. The resonance of Hushahu's journey extends beyond the Amazon, reverberating across cultural boundaries and igniting conversations about gender equality and indigenous rights. Through courageous defiance of cultural norms, Hushahu emerges as a symbol of resilience and empowerment, offering hope and inspiration to marginalized women around the world. In conclusion, Hushahu's shamanic journey embodies the sacred echoes of empowerment, echoing across generations and landscapes. The story serves as a testament to the enduring power of the human spirit and the transformative potential of reclaiming one's voice in the face of adversity. As indigenous women continue to rise, Hushahu's legacy stands as a beacon of hope, illuminating the path towards a more equitable and inclusive world.

Keywords: shamanic leadership, indigenous empowerment, gender norms, cultural transformation

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Authors: Michael Huber, Maximilian J. Poller, Jens Tochtermann, Wolfgang Korth, Andreas Jess, Jakob Albert

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Aside from the desulfurisation, the denitrogenation of fuels is of great importance to minimize the environmental impact of transport emissions. The oxidative reaction pathway of organic nitrogen in the catalytic oxidative denitrogenation could be successfully elucidated. This is the first time such a pathway could be traced in detail in non-microbial systems. It was found that the organic nitrogen is first oxidized to nitrate, which is subsequently reduced to molecular nitrogen via nitrous oxide. Hereby, the organic substrate serves as a reducing agent. The discovery of this pathway is an important milestone for the further development of fuel denitrogenation technologies. The United Nations aims to counteract global warming with Net Zero Emissions (NZE) commitments; however, it is not yet foreseeable when crude oil-based fuels will become obsolete. In 2021, more than 50 million barrels per day (mb/d) were consumed for the transport sector alone. Above all, heteroatoms such as sulfur or nitrogen produce SO₂ and NOx during combustion in the engines, which is not only harmful to the climate but also to health. Therefore, in refineries, these heteroatoms are removed by hy-drotreating to produce clean fuels. However, this catalytic reaction is inhibited by the basic, nitrogenous reactants (e.g., quinoline) as well as by NH3. The ion pair of the nitrogen atom forms strong pi-bonds to the active sites of the hydrotreating catalyst, which dimin-ishes its activity. To maximize the desulfurization and denitrogenation effectiveness in comparison to just extraction and adsorption, selective oxidation is typically combined with either extraction or selective adsorption. The selective oxidation produces more polar compounds that can be removed from the non-polar oil in a separate step. The extraction step can also be carried out in parallel to the oxidation reaction, as a result of in situ separation of the oxidation products (ECODS; extractive catalytic oxidative desulfurization). In this process, H8PV5Mo7O40 (HPA-5) is employed as a homogeneous polyoxometalate (POM) catalyst in an aqueous phase, whereas the sulfur containing fuel components are oxidized after diffusion from the organic fuel phase into the aqueous catalyst phase, to form highly polar products such as H₂SO₄ and carboxylic acids, which are thereby extracted from the organic fuel phase and accumulate in the aqueous phase. In contrast to the inhibiting properties of the basic nitrogen compounds in hydrotreating, the oxidative desulfurization improves with simultaneous denitrification in this system (ECODN; extractive catalytic oxidative denitrogenation). The reaction pathway of ECODS has already been well studied. In contrast, the oxidation of nitrogen compounds in ECODN is not yet well understood and requires more detailed investigations.

Keywords: oxidative reaction pathway, denitrogenation of fuels, molecular catalysis, polyoxometalate

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Authors: G. V. Manzane, S. J. Modise

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Uterine fibroids, also known as leiomyomas or myomas, are non-cancerous growths that develop in the muscular wall of the uterus during the reproductive years. The cause of uterine fibroids includes hormonal, genetic, growth factors, and extracellular matrix factors. Common symptoms of uterine fibroids include heavy and prolonged menstrual bleeding which can lead to a high risk of anemia, lower abdominal pains, pelvic pressure, infertility, and pregnancy loss. The growth of this tumor is a concern because of its negative impact on women’s health and the increase in their economic burden. Traditional medicinal plants have long been used in Africa for their potential therapeutic effects against various ailments. In this study, we aimed to identify and characterize bioactive compounds from selected African medicinal plants with potential anti-fibrotic properties using Fourier-transform infrared spectroscopy (FTIR) and gas chromatography-mass spectrometry (GCMS) analysis. Two medicinal plant species known for their traditional use in fibrosis-related conditions were selected for investigation. Aqueous extracts were prepared from the plant materials, and FTIR analysis was conducted to determine the functional groups present in the extracts. GCMS analysis was performed to identify the chemical constituents of the extracts. The FTIR analysis revealed the presence of various functional groups, such as phenols, flavonoids, terpenoids, and alkaloids, known for their potential therapeutic activities. These functional groups are associated with antioxidant, anti-inflammatory, and anti-fibrotic properties. The GCMS analysis identified several bioactive compounds, including flavonoids, alkaloids, terpenoids, and phenolic compounds, which are known for their pharmacological activities. The discovery of bioactive compounds in African medicinal plants that exhibit anti-fibrotic effects, opens up promising avenues for further research and development of potential treatments for fibrosis. This suggests the potential of these plants as a valuable source of novel therapeutic agents for treating fibrosis-related conditions. In conclusion, our study identified and characterized bioactive compounds from selected African medicinal plants using FTIR and GCMS analysis. The presence of compounds with known antifibrotic properties suggests that these plants hold promise as a potential source of natural products for the development of novel anti-fibrotic therapies.

Keywords: uterine fibroids, african medicinal plants, bioactive compounds, identify and characterized

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Authors: Hana Al-Baghaoi, Kumar Shiva Gubbiyappa, Mayuren Candasamy, Kiruthiga Perumal Vijayaraman

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Acne is a chronic inflammatory disease of the sebaceous glands characterized by areas of skin with seborrhea, comedones, papules, pustules, nodules, and possibly scarring. Propionibacterium acnes (P. acnes), plays a key role in the pathogenesis of acne. Their colonization and proliferation trigger the host’s inflammatory response leading to the production of pro-inflammatory cytokines such as interleukin-8 (IL-8) and tumour necrosis factor-α (TNF-α). The usage of honey and natural compounds to treat skin ailments has strong support in the current trend of drug discovery. The present study was carried out evaluate antimicrobial and anti-inflammatory potential of Doani Sidr honey and its fractions against P. acnes and to screen madecassoside alone and in combination with fractions of honey. The broth dilution method was used to assess the antibacterial activity. Also, ultra structural changes in cell morphology were studied before and after exposure to Sidr honey using transmission electron microscopy (TEM). The three non-toxic concentrations of the samples were investigated for suppression of cytokines IL 8 and TNF α by testing the cell supernatants in the co-culture of the human peripheral blood mononuclear cells (hPBMCs) heat killed P. acnes using enzyme immunoassay kits (ELISA). Results obtained was evaluated by statistical analysis using Graph Pad Prism 5 software. The Doani Sidr honey and polysaccharide fractions were able to inhibit the growth of P. acnes with a noteworthy minimum inhibitory concentration (MIC) value of 18% (w/v) and 29% (w/v), respectively. The proximity of MIC and MBC values indicates that Doani Sidr honey had bactericidal effect against P. acnes which is confirmed by TEM analysis. TEM images of P. acnes after treatment with Doani Sidr honey showed completely physical membrane damage and lysis of cells; whereas non honey treated cells (control) did not show any damage. In addition, Doani Sidr honey and its fractions significantly inhibited (> 90%) of secretion of pro-inflammatory cytokines like TNF α and IL 8 by hPBMCs pretreated with heat-killed P. acnes. However, no significant inhibition was detected for madecassoside at its highest concentration tested. Our results suggested that Doani Sidr honey possesses both antimicrobial and anti-inflammatory effects against P. acnes and can possibly be used as therapeutic agents for acne. Furthermore, polysaccharide fraction derived from Doani Sidr honey showed potent inhibitory effect toward P. acnes. Hence, we hypothesize that fraction prepared from Sidr honey might be contributing to the antimicrobial and anti-inflammatory activity. Therefore, this polysaccharide fraction of Doani Sidr honey needs to be further explored and characterized for various phytochemicals which are contributing to antimicrobial and anti-inflammatory properties.

Keywords: Doani sidr honey, Propionibacterium acnes, IL-8, TNF alpha

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Authors: Maciej Szelag

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The discovery of the carbon nanotubes (CNT), has led to a breakthrough in the material engineering. The CNT is characterized by very large surface area, very high Young's modulus (about 2 TPa), unmatched durability, high tensile strength (about 50 GPa) and bending strength. Their diameter usually oscillates in the range from 1 to 100 nm, and the length from 10 nm to 10-2 m. The relatively new approach is the CNT’s application in the concrete technology. The biggest problem in the use of the CNT to cement composites is their uneven dispersion and low adhesion to the cement paste. Putting the nanotubes alone into the cement matrix does not produce any effect because they tend to agglomerate, due to their large surface area. Most often, the CNT is used as an aqueous suspension in the presence of a surfactant that has previously been sonicated. The paper presents the results of investigations of the basic physical properties (apparent density, shrinkage) and mechanical properties (compression and tensile strength) of cement paste with the addition of the multiwall carbon nanotubes (MWCNT). The studies were carried out on four series of specimens (made of two different Portland Cement). Within each series, samples were made with three w/c ratios – 0.4, 0.5, 0.6 (water/cement). Two series were an unmodified cement matrix. In the remaining two series, the MWCNT was added in amount of 0.1% by cement’s weight. The MWCNT was used as an aqueous dispersion in the presence of a surfactant – SDS – sodium dodecyl sulfate (C₁₂H₂₅OSO₂ONa). So prepared aqueous solution was sonicated for 30 minutes. Then the MWCNT aqueous dispersion and cement were mixed using a mechanical stirrer. The parameters were tested after 28 days of maturation. Additionally, the change of these parameters was determined after samples temperature loading at 250°C for 4 hours (thermal shock). Measurement of the apparent density indicated that cement paste with the MWCNT addition was about 30% lighter than conventional cement matrix. This is due to the fact that the use of the MWCNT water dispersion in the presence of surfactant in the form of SDS resulted in the formation of air pores, which were trapped in the volume of the material. SDS as an anionic surfactant exhibits characteristics specific to blowing agents – gaseous and foaming substances. Because of the increased porosity of the cement paste with the MWCNT, they have obtained lower compressive and tensile strengths compared to the cement paste without additive. It has been observed, however, that the smallest decreases in the compressive and tensile strength after exposure to the elevated temperature achieved samples with the MWCNT. The MWCNT (well dispersed in the cement matrix) can form bridges between hydrates in a nanoscale of the material’s structure. Thus, this may result in an increase in the coherent cohesion of the cement material subjected to a thermal shock. The obtained material could be used for the production of an aerated concrete or using lightweight aggregates for the production of a lightweight concrete.

Keywords: cement paste, elevated temperature, mechanical parameters, multiwall carbon nanotubes, physical parameters, SDS

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Authors: Nicole C. Valdez, Vincent L. Borromeo, Conrad C. Chong, Ahmad F. Mazahery

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Breast cancer is the most prevalent cancer worldwide, where the majority of cases are estrogen-receptor positive and involve 2 receptor proteins. The binding of estrogen to estrogen receptor alpha (ERα) promotes breast cancer growth, while it's binding to estrogen-receptor beta (ERβ) inhibits tumor growth. While natural products have been a promising source of chemotherapeutic agents, the challenge remains in finding a bioactive compound that specifically targets cancer cells, minimizing side effects on normal cells. Flavonoids are natural products that act as phytoestrogens and induce the same response as estrogen. They are able to compete with estrogen for binding to ERα; however, it has a higher binding affinity for ERβ. Their abundance in nature and low toxicity make them a potential candidate for breast cancer treatment. This study aimed to determine which particular flavonoids can specifically recognize ERβ and potentially be used for breast cancer treatment through molecular docking. A total of 206 flavonoids comprised of 97 isoflavones and 109 flavanones were collected from ZINC15, while the 3D structures of ERβ and ERα were obtained from Protein Data Bank. These flavonoid subclasses were chosen as they bind more strongly to ERs due to their chemical structure. The structures of the flavonoid ligands were converted using Open Babel, while the estrogen receptor protein structures were prepared using Autodock MGL Tools. The optimal binding site was found using BIOVIA Discovery Studio Visualizer before docking all flavonoids on both ERβ and ERα through Autodock Vina. Genistein is a flavonoid that exhibits anticancer effects by binding to ERβ, so its binding affinity was used as a baseline. Eriodictyol and 4”,6”-Di-O-Galloylprunin both exceeded genistein’s binding affinity for ERβ and was lower than its binding affinity for ERα. Of the two, eriodictyol was pursued due to its antitumor properties on a lung cancer cell line and on glioma cells. It is able to arrest the cell cycle at the G2/M phase by inhibiting the mTOR/PI3k/Akt cascade and is able to induce apoptosis via the PI3K/Akt/NF-kB pathway. Protein pathway and gene analysis were also conducted using ChEMBL and PANTHER and it was shown that eriodictyol might induce anticancer effects through the ROS1, CA7, KMO, and KDM1A genes which are involved in cell proliferation in breast cancer, non-small cell lung cancer, and other diseases. The high binding affinity of eriodictyol to ERβ, as well as its potential affected genes and antitumor effects, therefore, make it a candidate for the development of new breast cancer treatment. Verification through in vitro experiments such as checking the upregulation and downregulation of genes through qPCR and checking cell cycle arrest using a flow cytometry assay is recommended.

Keywords: breast cancer, estrogen receptor, flavonoid, molecular docking

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Authors: Ahlam Ali, Katrina Lappin, Jaine Blayney, Ken Mills

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Leukaemia is the most frequently (30%) occurring type of paediatric cancer. Of these, approximately 80% are acute lymphoblastic leukaemia (ALL) with acute myeloid leukaemia (AML) cases making up the remaining 20% alongside other leukaemias. Unfortunately, children with AML do not have promising prognosis with only 60% surviving 5 years or longer. It has been highlighted recently the need for age-specific therapies for AML patients, with paediatric AML cases having a different mutational landscape compared with AML diagnosed in adult patients. Drug Repurposing is a recognized strategy in drug discovery and development where an already approved drug is used for diseases other than originally indicated. We aim to identify novel combination therapies with the promise of providing alternative more effective and less toxic induction therapy options. Our in-silico analysis highlighted ‘cell death and survival’ as an aberrant, potentially targetable pathway in paediatric AML patients. On this basis, 83 apoptotic inducing compounds were screened. A preliminary single agent screen was also performed to eliminate potentially toxic chemicals, then drugs were constructed into a pooled library with 10 drugs per well over 160 wells, with 45 possible pairs and 120 triples in each well. Seven cell lines were used during this study to represent the clonality of AML in paediatric patients (Kasumi-1, CMK, CMS, MV11-14, PL21, THP1, MOLM-13). Cytotoxicity was assessed up to 72 hours using CellTox™ Green reagent. Fluorescence readings were normalized to a DMSO control. Z-Score was assigned to each well based on the mean and standard deviation of all the data. Combinations with a Z-Score <2 were eliminated and the remaining wells were taken forward for further analysis. A well was considered ‘successful’ if each drug individually demonstrated a Z-Score <2, while the combination exhibited a Z-Score >2. Each of the ten compounds in one well (155) had minimal or no effect as single agents on cell viability however, a combination of two or more of the compounds resulted in a substantial increase in cell death, therefore the ten compounds were de-convoluted to identify a possible synergistic pair/triple combinations. The screen identified two possible ‘novel’ drug pairing, with BCL2 inhibitor ABT-737, combined with either a CDK inhibitor Purvalanol A, or AKT/ PI3K inhibitor LY294002. (ABT-737- 100 nM+ Purvalanol A- 1 µM) (ABT-737- 100 nM+ LY294002- 2 µM). Three possible triple combinations were identified (LY2409881+Akti-1/2+Purvalanol A, SU9516+Akti-1/2+Purvalanol A, and ABT-737+LY2409881+Purvalanol A), which will be taken forward for examining their efficacy at varying concentrations and dosing schedules, across multiple paediatric AML cell lines for optimisation of maximum synergy. We believe that our combination screening approach has potential for future use with a larger cohort of drugs including FDA approved compounds and patient material.

Keywords: AML, drug repurposing, ABT-737, apoptosis

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Authors: Sara E. Baumann, Megan A. Rabin, Mary Hawk, Bhimsen Devkota, Kajol Upadhyaya, Guna Raj Shrestha, Brigit Joseph, Annika Agarwal, Jessica G. Burke

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In Nepal, prevailing sociocultural norms associated with menstruation prompt adherence to stringent rules that limit participation in daily activities. Chhaupadi is a specific menstrual tradition in Nepal in which women and girls segregate themselves and follow a series of restrictions during menstruation. Despite having numerous physical and mental health implications, extant interventions have yet to sustainably address the harms associated with chhaupadi. In this study, the authors describe insights garnered from a collaboration with community members in Dailekh district, who formulated their own approaches to mitigate the adverse facets of chhaupadi. Envisaged as an entry point to improve women’s menstrual health experiences, this investigation employed an approach that uses Human-centered Design and a community-engaged approach. The authors conducted a four-day design workshop which unfolded in two phases: The Discovery Phase, to uncover chhaupadi context and key stakeholders, and the Design Phase, to design contextually relevant interventions. Diverse community-members, including those with lived experience practicing chhaupadi, developed five intervention concepts: 1) harnessing Female Community Health Volunteers as role models, for counseling, and raising awareness; 2) focusing on mothers and mother’s groups to instigate behavioral shifts; 3) engaging the broader community in behavior change efforts; 4) empowering fathers to effect change in their homes through counseling and education; and 5) training and emboldening youth to advocate for positive change through advocacy in their schools and homes. This research underscores the importance of employing multi-level approaches tailored to specific stakeholder groups, given Nepal’s rich cultural diversity. The engagement of Female Community Health Volunteers emerged as a promising yet underexplored intervention concept for chhaupadi, warranting broader implementation. Crucially, it is also imperative for interventions to prioritize tackling deleterious aspects of the chhaupadi tradition, emphasizing safety considerations, all while acknowledging chhaupadi’s entrenched cultural history; for some, there are positive aspects of the tradition that women and girls wish to preserve.

Keywords: human-centered design, menstrual health, Nepal, community-engagement, intervention development, women's health, rural health

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Authors: Alan Johnson

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This paper focuses on modern pilgrimage narratives about sites affiliated with Indian religious expressions located both within and outside India. The paper uses a multidisciplinary approach to examine poetry, personal essays, and online attestations of pilgrimage to illustrate how non-religious ideas coexist with outwardly religious ones, exemplifying a characteristically Indian form of syncretism that pre-dates Western ideas of pluralism. The paper argues that the syncretism on display in these modern creative works refutes the current exclusionary vision of India as a primordially Hindu-nationalist realm. A crucial premise of this argument is that the narrative’s intrinsic heteroglossia, so evident in India’s historically rich variety of stories and symbols, belies this reactionary version of Hindu nationalism. Equally important to this argument, therefore, is the vibrancy of Hindu sites outside India, such as the Batu Caves temple complex in Kuala Lumpur, Malaysia. The literary texts examined in this paper include, first, Arun Kolatkar’s famous 1976 collection of poems, titled Jejuri, about a visit to the pilgrimage site of the same name in Maharashtra. Here, the modern, secularized visitor from Bombay (Mumbai) contemplates the effect of the temple complex on himself and on the other, more worshipful visitors. Kolatkar’s modernist poems reflect the narrator’s typically modern-Indian ambivalence for holy ruins, for although they do not evoke a conventionally religious feeling in him, they nevertheless possess an aura of timelessness that questions the narrator’s time-conscious sensibility. The paper bookends Kolatkar’s Jejuri with considerations of an early-twentieth-century text, online accounts by visitors to the Batu Caves, and a recent, more conventional Hindu account of pilgrimage. For example, the pioneering graphic artist Mukul Chandra Dey published in 1917, My Pilgrimages to Ajanta and Bagh, in which he devotes an entire chapter to the life of the Buddha as a means of illustrating the layering of stories that is a characteristic feature of sacred sites in India. In a different but still syncretic register, Jawaharlal Nehru, India’s first prime minister, and a committed secularist proffers India’s ancient pilgrimage network as a template for national unity in his classic 1946 autobiography The Discovery of India. Narrative is the perfect vehicle for highlighting this layering of sensibilities, for a single text can juxtapose the pilgrim-narrator’s description with that of a far older pilgrimage, a juxtaposition that establishes an imaginative connection between otherwise distanced actors, and between them and the reader.

Keywords: India, literature, narrative, syncretism

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Authors: Mustafa Malki, Ewan R. Pearson

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Tools utilized by health care practitioners to flag potential adverse drug reactions secondary to drug-drug interactions ignore individual genetic variation, which has the potential to markedly alter the severity of these interactions. To our best knowledge, there have been limited published studies on the impact of genetic variation on drug-drug interactions. Therefore, our aim in this project is the discovery of previously unrecognized, clinically important drug-drug-gene interactions (DDGIs) within the list of most commonly used drug combinations in the UK. The UKBB database was utilized to identify the top most frequently prescribed drug combinations in the UK with at least one route of interaction (over than 200 combinations were identified). We have recognised 37 common and unique interacting genes considering all of our drug combinations. Out of around 600 potential genetic variants found in these 37 genes, 100 variants have met the selection criteria (common variant with minor allele frequency ≥ 5%, independence, and has passed HWE test). The association between these variants and the use of each of our top drug combinations has been tested with a case-control analysis under the log-additive model. As the data is cross-sectional, drug intolerance has been identified from the genotype distribution as presented by the lower percentage of patients carrying the risky allele and on the drug combination compared to those free of these risk factors and vice versa with drug tolerance. In GoDARTs database, the same list of common drug combinations identified by the UKBB was utilized here with the same list of candidate genetic variants but with the addition of 14 new SNPs so that we have a total of 114 variants which have met the selection criteria in GoDARTs. From the list of the top 200 drug combinations, we have selected 28 combinations where the two drugs in each combination are known to be used chronically. For each of our 28 combinations, three drug response phenotypes have been identified (drug stop/switch, dose decrease, or dose increase of any of the two drugs during their interaction). The association between each of the three phenotypes belonging to each of our 28 drug combinations has been tested against our 114 candidate genetic variants. The results show replication of four findings between both databases : (1) Omeprazole +Amitriptyline +rs2246709 (A > G) variant in CYP3A4 gene (p-values and ORs with the UKBB and GoDARTs respectively = 0.048,0.037,0.92,and 0.52 (dose increase phenotype)) (2) Simvastatin + Ranitidine + rs9332197 (T > C) variant in CYP2C9 gene (0.024,0.032,0.81, and 5.75 (drug stop/switch phenotype)) (3) Atorvastatin + Doxazosin + rs9282564 (T > C) variant in ABCB1 gene (0.0015,0.0095,1.58,and 3.14 (drug stop/switch phenotype)) (4) Simvastatin + Nifedipine + rs2257401 (C > G) variant in CYP3A7 gene (0.025,0.019,0.77,and 0.30 (drug stop/switch phenotype)). In addition, some other non-replicated, but interesting, significant findings were detected. Our work also provides a great source of information for researchers interested in DD, DG, or DDG interactions studies as it has highlighted the top common drug combinations in the UK with recognizing 114 significant genetic variants related to drugs' pharmacokinetic.

Keywords: adverse drug reactions, common drug combinations, drug-drug-gene interactions, pharmacogenomics

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Authors: Bambi Ward

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Children of Holocaust survivors have been described as inheriting their parents’ trauma as a result of ‘vicarious memory’. The term refers to a process whereby second generation Holocaust survivors subconsciously remember aspects of Holocaust trauma, despite not having directly experienced it. This can occur even when there has been a conspiracy of silence in which survivors chose not to discuss the Holocaust with their children. There are still people born in various parts of the world such as Poland, Hungary, other parts of Europe, USA, Canada and Australia, who have only learnt of their Jewish roots as adults. This discovery may occur during a parent’s deathbed confession, or when an adult child is sorting through the personal belongings of a deceased family member. Some Holocaust survivors chose to deny their Jewish heritage and raise their children as Christians. Reasons for this decision include the trauma experienced during the Holocaust for simply being Jewish, the existence of anti-Semitism, and the desire to protect one’s self and one’s family. Although there has been considerable literature written about the transgenerational impact of trauma on children of Holocaust survivors, there has been little scholarly investigation into the effects of a hidden Jewish identity on these children. This paper presents a case study of an adult child of Hungarian Holocaust survivors who was raised as a Christian. At the age of eight she was told about her family’s Jewish background, but her parents insisted that she keep this a secret, even if asked directly. She honoured their request until she turned forty. By that time she had started the challenging process of reclaiming her Jewish identity. The paper outlines the tension between family loyalty and individual freedom, and discusses the role that art and art therapy played in assisting the subject of the case study to reclaim her Jewish identity and commence writing a memoir about her spiritual journey. The main methodology used in this case study is creative practice-led research. Particular attention is paid to the utilisation of an autoethnographic approach. The autoethnographic tools used include reflective journals of the subject of the case study. These journals reflect on the subject’s collection of autobiographical data relating to her family history, and include memories, drawings, products of art therapy, diaries, letters, photographs, home movies, objects, and oral history interviews with her mother. The case study illustrates how art and art therapy benefitted a second generation Holocaust survivor who was brought up having to suppress her Jewish identity. The process allowed her to express subconscious thoughts and feelings about her identity and free herself from the burden of the long term secret she had been carrying. The process described may also be of assistance to other traumatised people who have been trying to break the silence and who are seeking to express themselves in a positive and healing way.

Keywords: art, hidden identity, holocaust, silence

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Authors: A. Anastasiou, K. S. Tingay

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Background: Discovering suitable datasets is an important part of health research, particularly for projects working with clinical data from patients organized in cohorts (cohort data), but with the proliferation of so many national and international initiatives, it is becoming increasingly difficult for research teams to locate real world datasets that are most relevant to their project objectives. We present a method for identifying healthcare institutes in the European Union (EU) which may hold haemato-oncology (HO) data. A key enabler of this research was the bibInsight platform, a scientometric data management and analysis system developed by the authors at Swansea University. Method: A PubMed search was conducted using HO clinical terms taken from previous work. The resulting XML file was processed using the bibInsight platform, linking affiliations to the Global Research Identifier Database (GRID). GRID is an international, standardized list of institutions, including the city and country in which the institution exists, as well as a category of the main business type, e.g., Academic, Healthcare, Government, Company. Countries were limited to the 28 current EU members, and institute type to 'Healthcare'. An article was considered valid if at least one author was affiliated with an EU-based healthcare institute. Results: The PubMed search produced 21,310 articles, consisting of 9,885 distinct affiliations with correspondence in GRID. Of these articles, 760 were from EU countries, and 390 of these were healthcare institutes. One affiliation was excluded as being a veterinary hospital. Two EU countries did not have any publications in our analysis dataset. The results were analysed by country and by individual healthcare institute. Networks both within the EU and internationally show institutional collaborations, which may suggest a willingness to share data for research purposes. Geographical mapping can ensure that data has broad population coverage. Collaborations with industry or government may exclude healthcare institutes that may have embargos or additional costs associated with data access. Conclusions: Data reuse is becoming increasingly important both for ensuring the validity of results, and economy of available resources. The ability to identify potential, specific data sources from over twenty thousand articles in less than an hour could assist in improving knowledge of, and access to, data sources. As our method has not yet specified if these healthcare institutes are holding data, or merely publishing on that topic, future work will involve text mining of data-specific concordant terms to identify numbers of participants, demographics, study methodologies, and sub-topics of interest.

Keywords: data reuse, data discovery, data linkage, journal articles, text mining

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Authors: Fatemeh Sadeghi, Peyman Sheikhzadeh

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Introduction: Block Sequential Regularized Expectation Maximization (BSREM) reconstruction algorithm was recently developed to suppress excessive noise by applying a relative difference penalty. The aim of this study was to investigate the effect of various strengths of noise penalization factor in the BSREM algorithm under different acquisition duration and lesion sizes in order to determine an optimum penalty factor by considering both quantitative and qualitative image evaluation parameters in clinical uses. Materials and Methods: The NEMA IQ phantom and 15 clinical whole-body patients with prostate cancer were evaluated. Phantom and patients were injected withGallium-68 Prostate-Specific Membrane Antigen(68 Ga-PSMA)and scanned on a non-time-of-flight Discovery IQ Positron Emission Tomography/Computed Tomography(PET/CT) scanner with BGO crystals. The data were reconstructed using BSREM with a β-value of 100-500 at an interval of 100. These reconstructions were compared to OSEM as a widely used reconstruction algorithm. Following the standard NEMA measurement procedure, background variability (BV), recovery coefficient (RC), contrast recovery (CR) and residual lung error (LE) from phantom data and signal-to-noise ratio (SNR), signal-to-background ratio (SBR) and tumor SUV from clinical data were measured. Qualitative features of clinical images visually were ranked by one nuclear medicine expert. Results: The β-value acts as a noise suppression factor, so BSREM showed a decreasing image noise with an increasing β-value. BSREM, with a β-value of 400 at a decreased acquisition duration (2 min/ bp), made an approximately equal noise level with OSEM at an increased acquisition duration (5 min/ bp). For the β-value of 400 at 2 min/bp duration, SNR increased by 43.7%, and LE decreased by 62%, compared with OSEM at a 5 min/bp duration. In both phantom and clinical data, an increase in the β-value is translated into a decrease in SUV. The lowest level of SUV and noise were reached with the highest β-value (β=500), resulting in the highest SNR and lowest SBR due to the greater noise reduction than SUV reduction at the highest β-value. In compression of BSREM with different β-values, the relative difference in the quantitative parameters was generally larger for smaller lesions. As the β-value decreased from 500 to 100, the increase in CR was 160.2% for the smallest sphere (10mm) and 12.6% for the largest sphere (37mm), and the trend was similar for SNR (-58.4% and -20.5%, respectively). BSREM visually was ranked more than OSEM in all Qualitative features. Conclusions: The BSREM algorithm using more iteration numbers leads to more quantitative accuracy without excessive noise, which translates into higher overall image quality and lesion detectability. This improvement can be used to shorter acquisition time.

Keywords: BSREM reconstruction, PET/CT imaging, noise penalization, quantification accuracy

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Authors: Fabiana Franceschi, Martha Cobo, Manuel Figueredo

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Bogotá, the capital of Colombia, is its largest city and one of the most polluted in Latin America due to the fast economic growth over the last ten years. Bogotá has been affected by high pollution events which led to the high concentration of PM10 and NO2, exceeding the local 24-hour legal limits (100 and 150 g/m3 each). The most important pollutants in the city are PM10 and PM2.5 (which are associated with respiratory and cardiovascular problems) and it is known that their concentrations in the atmosphere depend on the local meteorological factors. Therefore, it is necessary to establish a relationship between the meteorological variables and the concentrations of the atmospheric pollutants such as PM10, PM2.5, CO, SO2, NO2 and O3. This study aims to determine the interrelations between meteorological variables and air pollutants in Bogotá, using data mining techniques. Data from 13 monitoring stations were collected from the Bogotá Air Quality Monitoring Network within the period 2010-2015. The Principal Component Analysis (PCA) algorithm was applied to obtain primary relations between all the parameters, and afterwards, the K-means clustering technique was implemented to corroborate those relations found previously and to find patterns in the data. PCA was also used on a per shift basis (morning, afternoon, night and early morning) to validate possible variation of the previous trends and a per year basis to verify that the identified trends have remained throughout the study time. Results demonstrated that wind speed, wind direction, temperature, and NO2 are the most influencing factors on PM10 concentrations. Furthermore, it was confirmed that high humidity episodes increased PM2,5 levels. It was also found that there are direct proportional relationships between O3 levels and wind speed and radiation, while there is an inverse relationship between O3 levels and humidity. Concentrations of SO2 increases with the presence of PM10 and decreases with the wind speed and wind direction. They proved as well that there is a decreasing trend of pollutant concentrations over the last five years. Also, in rainy periods (March-June and September-December) some trends regarding precipitations were stronger. Results obtained with K-means demonstrated that it was possible to find patterns on the data, and they also showed similar conditions and data distribution among Carvajal, Tunal and Puente Aranda stations, and also between Parque Simon Bolivar and las Ferias. It was verified that the aforementioned trends prevailed during the study period by applying the same technique per year. It was concluded that PCA algorithm is useful to establish preliminary relationships among variables, and K-means clustering to find patterns in the data and understanding its distribution. The discovery of patterns in the data allows using these clusters as an input to an Artificial Neural Network prediction model.

Keywords: air pollution, air quality modelling, data mining, particulate matter

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Authors: Rebin Mzhda Mohammed, Hoshmand Ali Hama Agha

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Excess skin, often consequential to substantial weight loss or the aging process, introduces physical discomfort, obstructs daily activities, and undermines an individual's self-esteem. As these challenges become increasingly prevalent, the need to explore viable solutions grows in significance. Extra skin removal surgery, colloquially known as body contouring surgery, has emerged as a compelling intervention to ameliorate the physical and psychological burdens of excess skin. This study undertakes a comprehensive review to illuminate the intricacies of extra skin removal surgery, encompassing its diverse procedures, associated risks, benefits, and psychological implications on patients. The methodological approach adopted involves a systematic and exhaustive review of pertinent scholarly literature sourced from reputable databases, including PubMed, Google Scholar, and specialized cosmetic surgery journals. Articles are meticulously curated based on their relevance, credibility, and recency. Subsequently, data from these sources are synthesized and categorized, facilitating a comprehensive understanding of the subject matter. Qualitative analysis serves to unravel the nuanced psychological effects, while quantitative data, where available, are harnessed to underpin the study's conclusions. In terms of major findings, the research underscores the manifold advantages of extra skin removal surgery. Patients experience a notable improvement in physical comfort, amplified mobility, enhanced self-confidence, and a newfound ability to don clothing comfortably. Nonetheless, the benefits are juxtaposed with potential risks, encompassing infection, scarring, hematoma, delayed healing, and the challenge of achieving symmetry. A salient discovery is the profound psychological impact of the surgery, as patients consistently report elevated body image satisfaction, heightened self-esteem, and a substantial enhancement in overall quality of life. In summation, this research accentuates the pivotal role of extra skin removal surgery in ameliorating the intricate interplay of physical and psychological difficulties posed by excess skin. By elucidating the diverse procedures, associated risks, and psychological outcomes, the study contributes to a comprehensive and informed comprehension of the surgery's multifaceted effects. Therefore, individuals contemplating this transformative surgical option are equipped with comprehensive insights, ultimately fostering informed decision-making, guided by the expertise of medical professionals.

Keywords: extra skin removal surgery, body contouring, abdominoplasty, brachioplasty, thigh lift, body lift, benefits, risks, psychological effects

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Authors: Sofia Papadimitriou

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INTRODUCTION: The differential diagnosis between acute viral and bacterial infections is an important cost-effectiveness parameter at the stage of the treatment process in order to achieve the maximum benefits in therapeutic intervention by combining the minimum cost to ensure the proper use of antibiotics.The discovery of sensitive and robust molecular diagnostic tests in response to the role of the host in infections has enhanced the accurate diagnosis and differentiation of infections. METHOD: The study used a sample of six independent blood samples (total=756) which are associated with human proteins-proteins, each of which at the transcription stage expresses a different response in the host network between viral and bacterial infections.Τhe individual blood samples are subjected to a sequence of computer filters that identify a gene panel corresponding to an autonomous diagnostic score. The data set and the correspondence of the gene panel to the diagnostic patents a new Bangalore -Viral Bacterial (BL-VB). FINDING: We use a biomarker based on the blood of 10 genes(Panel-VB) that are an important prognostic value for the detection of viruses from bacterial infections with a weighted average AUROC of 0.97(95% CL:0.96-0.99) in eleven independent samples (sets n=898). We discovered a base with a patient score (VB 10 ) according to the table, which is a significant diagnostic value with a weighted average of AUROC 0.94(95% CL: 0.91-0.98) in 2996 patient samples from 56 public sets of data from 19 different countries. We also studied VB 10 in a new cohort of South India (BL-VB,n=56) and found 97% accuracy in confirmed cases of viral and bacterial infections. We found that VB 10 (a)accurately identifies the type of infection even in unspecified cases negative to the culture (b) shows its clinical condition recovery and (c) applies to all age groups, covering a wide range of acute bacterial and viral infectious, including non-specific pathogens. We applied our VB 10 rating to publicly available COVID 19 data and found that our rating diagnosed viral infection in patient samples. RESULTS: Τhe results of the study showed the diagnostic power of the biomarker VB 10 as a diagnostic test for the accurate diagnosis of acute infections in recovery conditions. We look forward to helping you make clinical decisions about prescribing antibiotics and integrating them into your policies management of antibiotic stewardship efforts. CONCLUSIONS: Overall, we are developing a new property of the RNA-based biomarker and a new blood test to differentiate between viral and bacterial infections to assist a physician in designing the optimal treatment regimen to contribute to the proper use of antibiotics and reduce the burden on antimicrobial resistance, AMR.

Keywords: acute infections, antimicrobial resistance, biomarker, blood transcriptome, systems biology, classifier diagnostic score

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Authors: Joao Barbosa

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After an intense dispute between the big bang cosmology and its big rival, the steady-state cosmology, some important experimental observations, such as the determination of helium abundance in the universe and the discovery of the cosmic background radiation in the 1960s were decisive for the progressive and wide acceptance of big bang cosmology and the inevitable abandonment of steady-state cosmology. But, despite solid theoretical support and those solid experimental observations favorable to big bang cosmology, Fred Hoyle, one of the proponents of the steady-state and the main opponent of the idea of the big bang (which, paradoxically, himself he baptized), never gave up and continued to fight for the idea of a stationary (or quasi-stationary) universe until the end of his life, even after decades of widespread consensus around the big bang cosmology. We can try to understand this persistent attitude of Hoyle by applying Holton’s thematic analysis to cosmology. Holton recognizes in the scientific activity a dimension that, even unconscious or not assumed, is nevertheless very important in the work of scientists, in implicit articulation with the experimental and the theoretical dimensions of science. This is the thematic dimension, constituted by themata – concepts, methodologies, and hypotheses with a metaphysical, aesthetic, logical, or epistemological nature, associated both with the cultural context and the individual psychology of scientists. In practice, themata can be expressed through personal preferences and choices that guide the individual and collective work of scientists. Thematic analysis shows that big bang cosmology is mainly based on a set of themata consisting of evolution, finitude, life cycle, and change; the cosmology of the steady-state is based on opposite themata: steady-state, infinity, continuous existence, and constancy. The passionate controversy that these cosmological views carried out is part of an old cosmological opposition: the thematic opposition between an evolutionary view of the world (associated with Heraclitus) and a stationary view (associated with Parmenides). Personal preferences seem to have been important in this (thematic) controversy, and the thematic analysis that was developed shows that Hoyle is a very illustrative example of a life-long personal commitment to some themata, in this case to the opposite themata of the big bang cosmology. His struggle against the big bang idea was strongly based on philosophical and even religious reasons – which, in a certain sense and in a Holtonian perspective, is related to thematic preferences. In this personal and persistent struggle, Hoyle always refused the way how some experimental observations were considered decisive in favor of the big bang idea, arguing that the success of this idea is based on sociological and cultural prejudices. This Hoyle’s attitude is a personal thematic attitude, in which the acceptance or rejection of what is presented as proof or scientific fact is conditioned by themata: what is a proof or a scientific fact for one scientist is something yet to be established for another scientist who defends different or even opposites themata.

Keywords: cosmology, experimental observations, fred hoyle, interpretation, life-long personal commitment, Themata

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Authors: Leigh G. Hayden, Susan E. Shepley, Cristina Passarelli, William Tingo

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Introduction: Sensory interventions are popular therapeutic and recreational approaches for people living with all stages of dementia. However, it is unknown which sensory interventions are used to achieve which outcomes across all subtypes of dementia. Methods: To address this gap, we conducted a scoping review of sensory interventions for people living with dementia. We conducted a search of the literature for any article published in English from 1 January 1990 to 1 June 2019, on any sensory or multisensory intervention targeted to people living with any kind of dementia, which reported on patient health outcomes. We did not include complex interventions where only a small aspect was related to sensory stimulation. We searched the databases Medline, CINHAL, and Psych Articles using our institutional discovery layer. We conducted all screening in duplicate to reduce Type 1 and Type 2 errors. The data from all included papers were extracted by one team member, and audited by another, to ensure consistency of extraction and completeness of data. Results: Our initial search captured 7654 articles, and the removal of duplicates (n=5329), those that didn’t pass title and abstract screening (n=1840) and those that didn’t pass full-text screening (n=281) resulted in 174 articles included. The countries with the highest publication in this area were the United States (n=59), the United Kingdom (n=26) and Australia (n=15). The most common type of interventions were music therapy (n=36), multisensory rooms (n=27) and multisensory therapies (n=25). Seven articles were published in the 1990’s, 55 in the 2000’s, and the remainder since 2010 (n=112). Discussion: Multisensory rooms have been present in the literature since the early 1990’s. However, more recently, nature/garden therapy, art therapy, and light therapy have emerged since 2008 in the literature, an indication of the increasingly diverse scholarship in the area. The least popular type of intervention is a traditional food intervention. Taste as a sensory intervention is generally avoided for safety reasons, however it shows potential for increasing quality of life. Agitation, behavior, and mood are common outcomes for all sensory interventions. However, light therapy commonly targets sleep. The majority (n=110) of studies have very small sample sizes (n=20 or less), an indicator of the lack of robust data in the field. Additional small-scale studies of the known sensory interventions will likely do little to advance the field. However, there is a need for multi-armed studies which directly compare sensory interventions, and more studies which investigate the use of layering sensory interventions (for example, adding an aromatherapy component to a lighting intervention). In addition, large scale studies which enroll people at early stages of dementia will help us better understand the potential of sensory and multisensory interventions to slow the progression of the disease.

Keywords: sensory interventions, dementia, scoping review

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Authors: Swapnil Kumar Singh

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Gamma-ray bursts (GRB's), short and intense pulses of low-energy γ rays, have fascinated astronomers and astrophysicists since their unexpected discovery in the late sixties. GRB'sare accompanied by long-lasting afterglows, and they are associated with core-collapse supernovae. The detection of delayed emission in X-ray, optical, and radio wavelength, or "afterglow," following a γ-ray burst can be described as the emission of a relativistic shell decelerating upon collision with the interstellar medium. While it is fair to say that there is strong diversity amongst the afterglow population, probably reflecting diversity in the energy, luminosity, shock efficiency, baryon loading, progenitor properties, circumstellar medium, and more, the afterglows of GRBs do appear more similar than the bursts themselves, and it is possible to identify common features within afterglows that lead to some canonical expectations. After an initial flash of gamma rays, a longer-lived "afterglow" is usually emitted at longer wavelengths (X-ray, ultraviolet, optical, infrared, microwave, and radio). It is a slowly fading emission at longer wavelengths created by collisions between the burst ejecta and interstellar gas. In X-ray wavelengths, the GRB afterglow fades quickly at first, then transitions to a less-steep drop-off (it does other stuff after that, but we'll ignore that for now). During these early phases, the X-ray afterglow has a spectrum that looks like a power law: flux F∝ E^β, where E is energy and beta is some number called the spectral index. This kind of spectrum is characteristic of synchrotron emission, which is produced when charged particles spiral around magnetic field lines at close to the speed of light. In addition to the outgoing forward shock that ploughs into the interstellar medium, there is also a so-called reverse shock, which propagates backward through the ejecta. In many ways," reverse" shock can be misleading; this shock is still moving outward from the restframe of the star at relativistic velocity but is ploughing backward through the ejecta in their frame and is slowing the expansion. This reverse shock can be dynamically important, as it can carry comparable energy to the forward shock. The early phases of the GRB afterglow still provide a good description even if the GRB is highly collimated since the individual emitting regions of the outflow are not in causal contact at large angles and so behave as though they are expanding isotropically. The majority of afterglows, at times typically observed, fall in the slow cooling regime, and the cooling break lies between the optical and the X-ray. Numerous observations support this broad picture for afterglows in the spectral energy distribution of the afterglow of the very bright GRB. The bluer light (optical and X-ray) appears to follow a typical synchrotron forward shock expectation (note that the apparent features in the X-ray and optical spectrum are due to the presence of dust within the host galaxy). We need more research in GRB and Particle Physics in order to unfold the mysteries of afterglow.

Keywords: GRB, synchrotron, X-ray, isotropic energy

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Authors: Klaus Peter Scherer, Daniel Knöll, Constantin Rieder

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Problem and Purpose: Intelligent systems are available and helpful to support the human being decision process, especially when complex surgical eye interventions are necessary and must be performed. Normally, such a decision support system consists of a knowledge-based module, which is responsible for the real assistance power, given by an explanation and logical reasoning processes. The interview based acquisition and generation of the complex knowledge itself is very crucial, because there are different correlations between the complex parameters. So, in this project (semi)automated self-learning methods are researched and developed for an enhancement of the quality of such a decision support system. Methods: For ophthalmic data sets of real patients in a hospital, advanced data mining procedures seem to be very helpful. Especially subgroup analysis methods are developed, extended and used to analyze and find out the correlations and conditional dependencies between the structured patient data. After finding causal dependencies, a ranking must be performed for the generation of rule-based representations. For this, anonymous patient data are transformed into a special machine language format. The imported data are used as input for algorithms of conditioned probability methods to calculate the parameter distributions concerning a special given goal parameter. Results: In the field of knowledge discovery advanced methods and applications could be performed to produce operation and patient related correlations. So, new knowledge was generated by finding causal relations between the operational equipment, the medical instances and patient specific history by a dependency ranking process. After transformation in association rules logically based representations were available for the clinical experts to evaluate the new knowledge. The structured data sets take account of about 80 parameters as special characteristic features per patient. For different extended patient groups (100, 300, 500), as well one target value as well multi-target values were set for the subgroup analysis. So the newly generated hypotheses could be interpreted regarding the dependency or independency of patient number. Conclusions: The aim and the advantage of such a semi-automatically self-learning process are the extensions of the knowledge base by finding new parameter correlations. The discovered knowledge is transformed into association rules and serves as rule-based representation of the knowledge in the knowledge base. Even more, than one goal parameter of interest can be considered by the semi-automated learning process. With ranking procedures, the most strong premises and also conjunctive associated conditions can be found to conclude the interested goal parameter. So the knowledge, hidden in structured tables or lists can be extracted as rule-based representation. This is a real assistance power for the communication with the clinical experts.

Keywords: an expert system, knowledge-based support, ophthalmic decision support, self-learning methods

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Authors: Malory Jonata

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Chlordecone (CLD) is an organochlorine pesticide used between 1971 and 1993 in both Guadeloupe and Martinique for the control of banana black weevil. The bishomocubane structure which characterizes this chemical compound led to high stability in organic matter and high persistence in the environment. Recently, researchers found that CLD can be degraded by isolated bacteria consortiums and, particularly, by bacteria such as Citrobacter sp 86 and Delsulfovibrio sp 86. Actually, six transformation product families of CLD are known. Moreover, the latest discovery showed that CLD was disappearing faster than first predicted in highly contaminated soil in Guadeloupe. However, the toxicity of transformation products is still unknown, and knowledge has to be deepened on the degradation ways and chemical characteristics of chlordecone and its transformation products. Microbial fuel cells (MFC) are electrochemical systems that can convert organic matter into electricity thanks to electroactive bacteria. These bacteria can exchange electrons through their membranes to solid surfaces or molecules. MFC have proven their efficiency as bioremediation systems in water and soils. They are already used for the bioremediation of several organochlorine compounds such as perchlorate, trichlorophenol or hexachlorobenzene. In this study, a three-electrodes system, inspired by MFC, is used to try to degrade chlordecone using bacteria from a mangrove swamp in Martinique. As we know, some mangrove bacteria are electroactive. Furthermore, the CLD rate seems to decline in mangrove swamp sediments. This study aims to prove that electroactive bacteria from a mangrove swamp in Martinique can degrade CLD thanks to a three-electrodes bioelectrochemical system. To achieve this goal, the tree-electrodes assembly has been connected to a potentiostat. The substrate used is mangrove water and sediments sampled in the mangrove swamp of La Trinité, a coastal city in Martinique, where CLD contamination has already been studied. Electroactive biofilms are formed by imposing a potential relative to Saturated Calomel Electrode using chronoamperometry. Moreover, their comportment has been studied by using cyclic voltametry. Biofilms have been studied under different imposed potentials, several conditions of the substrate and with or without CLD. In order to quantify the evolution of CLD rates in the substrate’s system, gas chromatography coupled with mass spectrometry (GC-MS) was performed on pre-treated samples of water and sediments after short, medium and long-term contact with the electroactive biofilms. Results showed that between -0,8V and -0,2V, the three-electrodes system was able to reduce the chemical in the substrate solution. The first GC-MS analysis result of samples spiked with CLD seems to reveal decreased CLD concentration over time. In conclusion, the designed bioelectrochemical system can provide the necessary conditions for chlordecone degradation. However, it is necessary to improve three-electrodes control settings in order to increase degradation rates. The biological pathways are yet to enlighten by biologicals analysis of electroactive biofilms formed in this system. Moreover, the electrochemical study of mangrove substrate gives new informations on the potential use of this substrate for bioremediation. But further studies are needed to a better understanding of the electrochemical potential of this environment.

Keywords: bioelectrochemistry, bioremediation, chlordecone, mangrove swamp

Procedia PDF Downloads 80

Authors: Neha Farid

Abstract:

Due to the abuse of antimicrobial medications in animal feed, the occurrence of multi-drug resistant (MDR) pathogens in foods is currently a growing public health concern on a global scale. MDR infections have the potential to penetrate the food chain by posing a serious risk to both consumers and animals. Food pathogens are those biological agents that have the tendency to cause pathogenicity in the host body upon ingestion. The major reservoirs of foodborne pathogens include food-producing fauna like cows, pigs, goats, sheep, deer, etc. The intestines of these animals are highly condensed with several different types of food pathogens. Bacterial food pathogens are the main cause of foodborne disease in humans; almost 66% of the reported cases of food illness in a year are caused by the infestation of bacterial food pathogens. When ingested, these pathogens reproduce and survive or form different kinds of toxins inside host cells causing severe infections. The genus Listeria consists of gram-positive, rod-shaped, non-spore-forming bacteria. The disease caused by Listeria monocytogenes is listeriosis or gastroenteritis, which induces fever, vomiting, and severe diarrhea in the affected body. Campylobacter jejuni is a gram-negative, curved-rod-shaped bacteria causing foodborne illness. The major source of Campylobacter jejuni is livestock and poultry; particularly, chicken is highly colonized with Campylobacter jejuni. Serious public health concerns include the widespread growth of bacteria that are resistant to antibiotics and the slowing in the discovery of new classes of medicines. The objective of this study is to provide some potential antibacterial activities with certain broad-range antibiotics and our desired bacteriocins, i.e., Enterococcus faecium from specific strains preventing microbial contamination pathways in order to safeguard the food by lowering food deterioration, contamination, and foodborne illnesses. The food pathogens were isolated from various sources of dairy products and meat samples. The isolates were tested for the presence of Listeria and Campylobacter by gram staining and biochemical testing. They were further sub-cultured on selective media enriched with the growth supplements for Listeria and Campylobacter. All six strains of Listeria and Campylobacter were tested against ten antibiotics. Campylobacter strains showed resistance against all the antibiotics, whereas Listeria was found to be resistant only against Nalidixic Acid and Erythromycin. Further, the strains were tested against the two bacteriocins isolated from Enterococcus faecium. It was found that bacteriocins showed better antimicrobial activity against food pathogens. They can be used as a potential antimicrobial for food preservation. Thus, the study concluded that natural antimicrobials could be used as alternatives to synthetic antimicrobials to overcome the problem of food spoilage and severe food diseases.

Keywords: food pathogens, listeria, campylobacter, antibiotics, bacteriocins

Procedia PDF Downloads 71

Authors: Visvaganthie Moodley

Abstract:

While rhetoric goes back as far as Aristotle who focalised its meaning as the “art of persuasion”, most scholars have focused on elocutio and dispositio canons, neglecting the rhetorical impact of multimodal texts, such as documentaries. Film documentaries are being increasingly rhetoric, often used by wildlife conservationists for influencing people to become more mindful about humanity’s connection with nature. This paper examines the award-winning film documentary, “My Octopus Teacher”, which depicts naturalist, Craig Foster’s unique discovery and relationship with a female octopus in the southern tip of Africa, the Cape of Storms in South Africa. It is anchored in Leech and Short’s (2007) framework of linguistic and stylistic categories – comprising lexical items, grammatical features, figures of speech and other rhetoric features, and cohesiveness – with particular foci on diction, anthropomorphic language, metaphors and symbolism. It also draws on Kress and van Leeuwen’s (2006) multimodal analysis to show how verbal cues (the narrator’s commentary), visual images in motion, visual images as metaphors and symbolism, and aural sensory images such as music and sound synergise for rhetoric effect. In addition, the analysis of “My Octopus Teacher” is guided by Nichol’s (2010) narrative theory; features of a documentary which foregrounds the credibility of the narrative as a text that represents real events with real people; and its modes of construction, viz., the poetic mode, the expository mode, observational mode and participatory mode, and their integration – forging documentaries as multimodal texts. This paper presents a multimodal rhetoric discussion on the sequence of salient episodes captured in the slow moving one-and-a-half-hour documentary. These are: (i) The prologue: on the brink of something extraordinary; (ii) The day it all started; (iii) The narrator’s turmoil: getting back into the ocean; (iv) The incredible encounter with the octopus; (v) Establishing a relationship; (vi) Outwitting the predatory pyjama shark; (vii) The cycle of life; and (viii) The conclusion: lessons from an octopus. The paper argues that wildlife documentaries, characterized by plausibility and which provide researchers the lens to examine the ideologies about animals and humans, offer an assimilation of the various senses – vocal, visual and audial – for engaging viewers in stylized compelling way; they have the ability to persuade people to think and act in particular ways. As multimodal texts, with its use of lexical items; diction; anthropomorphic language; linguistic, visual and aural metaphors and symbolism; and depictions of anthropocentrism, wildlife documentaries are powerful resources for promoting wildlife conservation and conscientizing people of the need for establishing a harmonious relationship with nature and humans alike.

Keywords: documentaries, multimodality, rhetoric, style, wildlife, conservation

Procedia PDF Downloads 93

Authors: Sandra Smieszek, Jonathan Haines

Abstract:

Introduction: Numerous research efforts have focused on searching for ‘longevity genes’. However, attempting to decipher the genetic component of the longevous phenotype have resulted in limited success and the mechanisms governing longevity remain to be explained. We conducted a genome-wide homozygosity analysis (GWHA) of the founder population of the Amish community in central Ohio. While genome-wide association studies using unrelated individuals have revealed many interesting longevity associated variants, these variants are typically of small effect and cannot explain the observed patterns of heritability for this complex trait. The Amish provide a large cohort of extended kinships allowing for in depth analysis via family-based approach excellent population due to its. Heritability of longevity increases with age with significant genetic contribution being seen in individuals living beyond 60 years of age. In our present analysis we show that the heritability of longevity is estimated to be increasing with age particularly on the paternal side. Methods: The present analysis integrated both phenotypic and genotypic data and led to the discovery of a series of variants, distinct for stratified populations across ages and distinct for paternal and maternal cohorts. Specifically 5437 subjects were analyzed and a subset of 893 successfully genotyped individuals was used to assess CHIP heritability. We have conducted the homozygosity analysis to examine if homozygosity is associated with increased risk of living beyond 90. We analyzed AMISH cohort genotyped for 614,957 SNPs. Results: We delineated 10 significant regions of homozygosity (ROH) specific for the age group of interest (>90). Of particular interest was ROH on chromosome 13, P < 0.0001. The lead SNPs rs7318486 and rs9645914 point to COL4A2 and our lead SNP. COL25A1 encodes one of the six subunits of type IV collagen, the C-terminal portion of the protein, known as canstatin, is an inhibitor of angiogenesis and tumor growth. COL4A2 mutations have been reported with a broader spectrum of cerebrovascular, renal, ophthalmological, cardiac, and muscular abnormalities. The second region of interest points to IRS2. Furthermore we built a classifier using the obtained SNPs from the significant ROH region with 0.945 AUC giving ability to discriminate between those living beyond to 90 years of age and beyond. Conclusion: In conclusion our results suggest that a history of longevity does indeed contribute to increasing the odds of individual longevity. Preliminary results are consistent with conjecture that heritability of longevity is substantial when we start looking at oldest fifth and smaller percentiles of survival specifically in males. We will validate all the candidate variants in independent cohorts of centenarians, to test whether they are robustly associated with human longevity. The identified regions of interest via ROH analysis could be of profound importance for the understanding of genetic underpinnings of longevity.

Keywords: regions of homozygosity, longevity, SNP, Amish

Procedia PDF Downloads 232