Search results for: macrophage targeting
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 718

Search results for: macrophage targeting

238 Metagenomic Identification of Cave Microorganisms in Lascaux and Other Périgord Caves

Authors: Lise Alonso, Audrey Dubost, Patricia Luis, Thomas Pommier, Yvan Moënne-Loccoz

Abstract:

The Lascaux Cave in South-Est France is an archeological landmark renowned for its Paleolithic paintings dating back c.18.000 years. Extensive touristic frequenting and repeated chemical treatments have resulted in the development of microbial stains on cave walls, which is a major issue in terms of art conservation. Therefore, it is of prime importance to better understand the microbiology specific to the Lascaux Cave, in comparison to regional situations. To this end, we compared the microbial community (i.e. both prokaryotic and eukaryotic microbial populations) of Lascaux Cave with three other anthropized Périgord caves as well as three pristine caves from the same area. We used state-of-the-art metagenomic analyses of cave wall samples to obtain a global view of the composition of the microbial community colonizing cave walls. We measured the relative abundance and diversity of four DNA markers targeting different fractions of the ribosomal genes of bacteria (i.e. eubacteria), archaea (i.e. archeobacteria), fungi and other micro-eukaryotes. All groups were highly abundant and diverse in all Périgord caves, as several hundred genera of microorganisms were identified in each. However, Lascaux Cave displayed a specify microbial community, which differed from those of both pristine and anthropized caves. Comparison of stains versus non-stained samples from the Passage area of the Lascaux Cave indicated that a few taxa (e.g. the Sordiaromycetes amongst fungi) were more prevalent within than outside stains, yet the main difference was in the relative proportion of the different microbial taxonomic groups and genera, which supposedly supports the biological origin of the stains. Overall, metagenomic sequencing of cave wall samples was effective to evidence the large colonization of caves by a diversified range of microorganisms. It also showed that Lascaux Cave represented a very particular situation in comparison with neighboring caves, probably in relation to the extent of disturbance it had undergone. Our results provide key baseline information to guide conservation efforts in anthropized caves such as Lascaux and pave the way to modern monitoring of ornamented caves.

Keywords: cave conservation, Lascaux cave, microbes, paleolithic paintings

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237 Aerodynamic Optimization of Oblique Biplane by Using Supercritical Airfoil

Authors: Asma Abdullah, Awais Khan, Reem Al-Ghumlasi, Pritam Kumari, Yasir Nawaz

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Introduction: This study verified the potential applications of two Oblique Wing configurations that were initiated by the Germans Aerodynamicists during the WWII. Due to the end of the war, this project was not completed and in this research is targeting the revival of German Oblique biplane configuration. The research draws upon the use of two Oblique wings mounted on the top and bottom of the fuselage through a single pivot. The wings are capable of sweeping at different angles ranging from 0° at takeoff to 60° at cruising Altitude. The top wing, right half, behaves like a forward swept wing and the left half, behaves like a backward swept wing. Vice Versa applies to the lower wing. This opposite deflection of the top and lower wing cancel out the rotary moment created by each wing and the aircraft remains stable. Problem to better understand or solve: The purpose of this research is to investigate the potential of achieving improved aerodynamic performance and efficiency of flight at a wide range of sweep angles. This will help examine the most accurate value for the sweep angle at which the aircraft will possess both stability and better aerodynamics. Explaining the methods used: The Aircraft configuration is designed using Solidworks after which a series of Aerodynamic prediction are conducted, both in the subsonic and the supersonic flow regime. Computations are carried on Ansys Fluent. The results are then compared to theoretical and flight data of different Supersonic fighter aircraft of the same category (AD-1) and with the Wind tunnel testing model at subsonic speed. Results: At zero sweep angle, the aircraft has an excellent lift coefficient value with almost double that found for fighter jets. In acquiring of supersonic speed the sweep angle is increased to maximum 60 degrees depending on the mission profile. General findings: Oblique biplane can be the future fighter jet aircraft because of its high value performance in terms of aerodynamics, cost, structural design and weight.

Keywords: biplane, oblique wing, sweep angle, supercritical airfoil

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236 Targeting Mre11 Nuclease Overcomes Platinum Resistance and Induces Synthetic Lethality in Platinum Sensitive XRCC1 Deficient Epithelial Ovarian Cancers

Authors: Adel Alblihy, Reem Ali, Mashael Algethami, Ahmed Shoqafi, Michael S. Toss, Juliette Brownlie, Natalie J. Tatum, Ian Hickson, Paloma Ordonez Moran, Anna Grabowska, Jennie N. Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan

Abstract:

Platinum resistance is a clinical challenge in ovarian cancer. Platinating agents induce DNA damage which activate Mre11 nuclease directed DNA damage signalling and response (DDR). Upregulation of DDR may promote chemotherapy resistance. Here we have comprehensively evaluated Mre11 in epithelial ovarian cancers. In clinical cohort that received platinum- based chemotherapy (n=331), Mre11 protein overexpression was associated with aggressive phenotype and poor progression free survival (PFS) (p=0.002). In the ovarian cancer genome atlas (TCGA) cohort (n=498), Mre11 gene amplification was observed in a subset of serous tumours (5%) which correlated highly with Mre11 mRNA levels (p<0.0001). Altered Mre11 levels was linked with genome wide alterations that can influence platinum sensitivity. At the transcriptomic level (n=1259), Mre11 overexpression was associated with poor PFS (p=0.003). ROC analysis showed an area under the curve (AUC) of 0.642 for response to platinum-based chemotherapy. Pre-clinically, Mre11 depletion by gene knock down or blockade by small molecule inhibitor (Mirin) reversed platinum resistance in ovarian cancer cells and in 3D spheroid models. Importantly, Mre11 inhibition was synthetically lethal in platinum sensitive XRCC1 deficient ovarian cancer cells and 3D-spheroids. Selective cytotoxicity was associated with DNA double strand break (DSB) accumulation, S-phase cell cycle arrest and increased apoptosis. We conclude that pharmaceutical development of Mre11 inhibitors is a viable clinical strategy for platinum sensitization and synthetic lethality in ovarian cancer.

Keywords: MRE11; XRCC1, ovarian cancer, platinum sensitization, synthetic lethality

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235 The Role of Zakat on Sustainable Economic Development by Rumah Zakat

Authors: Selamat Muliadi

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This study aimed to explain conceptual the role of Zakat on sustainable economic development by Rumah Zakat. Rumah Zakat is a philanthropic institution that manages zakat and other social funds through community empowerment programs. In running the program, including economic empowerment and socio health services are designed for these recipients. Rumah Zakat's connection with the establisment of Sustainable Development Goals (SDGs) which is to help impoverished recipients economically and socially. It’s an important agenda that the government input into national development, even the region. The primary goal of Zakat on sustainable economic development, not only limited to economic variables but based on Islamic principles, has comprehensive characteristics. The characteristics include moral, material, spiritual, and social aspects. In other words, sustainable economic development is closely related to improving people’s living standard (Mustahiq). The findings provide empiricial evidence regarding the positive contribution and effectiveness of zakat targeting in reducing poverty and improve the welfare of people related with the management of zakat. The purpose of this study was to identify the role of Zakat on sustainable economic development, which was applied by Rumah Zakat. This study used descriptive method and qualitative analysis. The data source was secondary data collected from documents and texts related to the research topic, be it books, articles, newspapers, journals, or others. The results showed that the role of zakat on sustainable economic development by Rumah Zakat has been quite good and in accordance with the principle of Islamic economics. Rumah Zakat programs are adapted to support intended development. The contribution of the productive program implementation has been aligned with four goals in the Sustainable Development Goals, i.e., Senyum Juara (Quality Education), Senyum Lestari (Clean Water and Sanitation), Senyum Mandiri (Entrepreneur Program) and Senyum Sehat (Free Maternity Clinic). The performance of zakat in the sustainable economic empowerment community at Rumah Zakat is taking into account dimensions such as input, process, output, and outcome.

Keywords: Zakat, social welfare, sustainable economic development, charity

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234 Preparation and in vivo Assessment of Nystatin-Loaded Solid Lipid Nanoparticles for Topical Delivery against Cutaneous Candidiasis

Authors: Rawia M. Khalil, Ahmed A. Abd El Rahman, Mahfouz A. Kassem, Mohamed S. El Ridi, Mona M. Abou Samra, Ghada E. A. Awad, Soheir S. Mansy

Abstract:

Solid lipid nanoparticles (SLNs) have gained great attention for the topical treatment of skin associated fungal infection as they facilitate the skin penetration of loaded drugs. Our work deals with the preparation of nystatin loaded solid lipid nanoparticles (NystSLNs) using the hot homogenization and ultrasonication method. The prepared NystSLNs were characterized in terms of entrapment efficiency, particle size, zeta potential, transmission electron microscopy, differential scanning calorimetry, rheological behavior and in vitro drug release. A stability study for 6 months was performed. A microbiological study was conducted in male rats infected with Candida albicans, by counting the colonies and examining the histopathological changes induced on the skin of infected rats. The results showed that SLNs dispersions are spherical in shape with particle size ranging from 83.26±11.33 to 955.04±1.09 nm. The entrapment efficiencies are ranging from 19.73±1.21 to 72.46±0.66% with zeta potential ranging from -18.9 to -38.8 mV and shear-thinning rheological Behavior. The stability studies done for 6 months showed that nystatin (Nyst) is a good candidate for topical SLN formulations. A least number of colony forming unit/ ml (cfu/ml) was recorded for the selected NystSLN compared to the drug solution and the commercial Nystatin® cream present in the market. It can be fulfilled from this work that SLNs provide a good skin targeting effect and may represent promising carrier for topical delivery of Nyst offering the sustained release and maintaining the localized effect, resulting in an effective treatment of cutaneous fungal infection.

Keywords: candida infections, hot homogenization, nystatin, solid lipid nanoparticles, stability, topical delivery

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233 A Constructivist and Strategic Approach to School Learning: A Study in a Tunisian Primary School

Authors: Slah Eddine Ben Fadhel

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Despite the development of new pedagogic methods, current teaching practices put more emphasis on the learning products than on the processes learners deploy. In school syllabi, for instance, very little time is devoted to both the explanation and analysis of strategies aimed at resolving problems by means of targeting students’ metacognitive procedures. Within a cognitive framework, teaching/learning contexts are conceived of in terms of cognitive, metacognitive and affective activities intended for the treatment of information. During these activities, learners come to develop an array of knowledge and strategies which can be subsumed within an active and constructive process. Through the investigation of strategies and metacognition concepts, the purpose is to reflect upon the modalities at the heart of the learning process and to demonstrate, similarly, the inherent significance of a cognitive approach to learning. The scope of this paper is predicated on a study where the population is a group of 76 primary school pupils who experienced difficulty with learning French. The population was divided into two groups: the first group was submitted during three months to a strategy-based training to learn French. All through this phase, the teachers centred class activities round making learners aware of the strategies the latter deployed and geared them towards appraising the steps these learners had themselves taken by means of a variety of tools, most prominent among which is the logbook. The second group was submitted to the usual learning context with no recourse whatsoever to any strategy-oriented tasks. The results of both groups point out the improvement of linguistic competences in the French language in the case of those pupils who were trained by means of strategic procedures. Furthermore, this improvement was noted in relation with the native language (Arabic), a fact that tends to highlight the importance of the interdisciplinary investigation of (meta-)cognitive strategies. These results show that strategic learning promotes in pupils the development of a better awareness of their own processes, which contributes to improving their general linguistic competences.

Keywords: constructive approach, cognitive strategies, metacognition, learning

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232 Adaptor Protein APPL2 Could Be a Therapeutic Target for Improving Hippocampal Neurogenesis and Attenuating Depressant Behaviors and Olfactory Dysfunctions in Chronic Corticosterone-induced Depression

Authors: Jiangang Shen

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Olfactory dysfunction is a common symptom companied by anxiety- and depressive-like behaviors in depressive patients. Chronic stress triggers hormone responses and inhibits the proliferation and differentiation of neural stem cells (NSCs) in the hippocampus and subventricular zone (SVZ)-olfactory bulb (OB), contributing to depressive behaviors and olfactory dysfunction. However, the cellular signaling molecules to regulate chronic stress mediated olfactory dysfunction are largely unclear. Adaptor proteins containing the pleckstrin homology domain, phosphotyrosine binding domain, and leucine zipper motif (APPLs) are multifunctional adaptor proteins. Herein, we tested the hypothesis that APPL2 could inhibit hippocampal neurogenesis by affecting glucocorticoid receptor (GR) signaling, subsequently contributing to depressive and anxiety behaviors as well as olfactory dysfunctions. The major discoveries are included: (1) APPL2 Tg mice had enhanced GR phosphorylation under basic conditions but had no different plasma corticosterone (CORT) level and GR phosphorylation under stress stimulation. (2) APPL2 Tg mice had impaired hippocampal neurogenesis and revealed depressive and anxiety behaviors. (3) GR antagonist RU486 reversed the impaired hippocampal neurogenesis in the APPL2 Tg mice. (4) APPL2 Tg mice displayed higher GR activity and less capacity for neurogenesis at the olfactory system with lesser olfactory sensitivity than WT mice. (5) APPL2 negatively regulates olfactory functions by switching fate commitments of NSCs in adult olfactory bulbs via interaction with Notch1 signaling. Furthermore, baicalin, a natural medicinal compound, was found to be a promising agent targeting APPL2/GR signaling and promoting adult neurogenesis in APPL2 Tg mice and chronic corticosterone-induced depression mouse models. Behavioral tests revealed that baicalin had antidepressant and olfactory-improving effects. Taken together, APPL2 is a critical therapeutic target for antidepressant treatment.

Keywords: APPL2, hippocampal neurogenesis, depressive behaviors and olfactory dysfunction, stress

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231 Mannosidase Alpha Class 1B Member 1 Targets F Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein and Ebola Virus Glycoprotein to Endoplasmic Reticulum-To-Lysosome-Associated Degradation by Micro-Endoplasmic Reticulum-Phagy

Authors: Yong-Hui Zheng

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Viruses hijack host machineries to propagate and spread, which disrupts cellular homeostasis and activates various counteractive mechanisms. Infection of enveloped viruses is dependent on their fusion proteins, which bind to viral receptors to allow virus entry into cells. Fusion proteins are glycoproteins and expressed in the endoplasmic reticulum (ER) by hijacking the secretory pathway. Previously, we reported that Zaire ebolavirus (EBOV)-glycoprotein (GP) expression induces ER stress, and EBOV-GP is targeted by the calnexin cycle to macro-ER-phagy for degradation. We now report that expression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/SARS2)-spike (S) protein also causes ER stress, and its expression is strongly downregulated by mannosidase alpha class 1B member 1 (MAN1B1), a class I α-mannosidase from the ER. MAN1B1 co-localizes with SARS2-S in the ER, and its downregulation of SARS2-S is blocked by inhibitors targeting lysosomes and autophagy, but not proteasomes, indicating SARS2-S degradation by autolysosomes. Notably, the SARS2-S degradation does not require the core autophagy machinery including ATG3, ATG5, ATG7, and phosphatidylinositol 3-kinase catalytic subunit type 3 (PI3KC3)/vacuolar protein sorting 34 (VPS34), and instead, it requires Beclin 1 (BECN1), a core component in the PI3KC3 complex. In addition, MAN1B1 does not trigger SARS2-S polyubiquitination, and consistently, the SARS2-S degradation does not require the autophagy receptor sequestosome 1 (SQSTM1)/p62. MAN1B1 also downregulates EBOV-GP similarly, but this degradation does not require BECN1. Collectively, we conclude that MAN1B1 downregulates viral fusions by micro-ER-phagy, and importantly, we have identified BECN1-dependent and BECN1-independent mechanisms for micro-ER-phagy.

Keywords: Micro-ER-phagy, reticulophagy, fusion proteins, ER stress

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230 Pediatric Health Nursing Research in Jordan: Evaluating the State of Knowledge and Determining Future Research Direction

Authors: Inaam Khalaf, Nadin M. Abdel Razeq, Hamza Alduraidi, Suhaila Halasa, Omayyah S. Nassar, Eman Al-Horani, Jumana Shehadeh, Anna Talal

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Background: Nursing researchers are responsible for generating knowledge that corresponds to national and global research priorities in order to promote, restore, and maintain the health of individuals and societies. The objectives of this scoping review of Jordanian literature are to assess the existing research on pediatric nursing in terms of evolution, authorship and collaborations, funding sources, methodologies, topics of research, and pediatric subjects' age groups so as to identify gaps in research. Methodology: A search was conducted using related keywords obtained from national and international databases. The reviewed literature included pediatric health articles published through December 2019 in English and Arabic, authored by nursing researchers. The investigators assessed the retrieved studies and extracted data using a data-mining checklist. Results: The review included 265 articles authored by Jordanian nursing researchers concerning children's health, published between 1987 and 2019; 95% were published between 2009 and 2019. The most commonly applied research methodology was the descriptive non-experimental method (76%). The main generic topics were health promotion and disease prevention (23%), chronic physical conditions (19%), mental health, behavioral disorders, and forensic issues (16%). Conclusion: The review findings identified a grave shortage of evidence concerning nursing care issues for children below five years of age, especially those between ages two and five years. The research priorities identified in this review resonate with those identified in international reports. Implications: Nursing researchers are encouraged to conduct more research targeting topics of national-level importance in collaboration with clinically involved nurses and international scholars.

Keywords: Jordan, scoping review, children health nursing, pediatric, adolescents

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229 Physical Activity Self-Efficacy among Pregnant Women with High Risk for Gestational Diabetes Mellitus: A Cross-Sectional Study

Authors: Xiao Yang, Ji Zhang, Yingli Song, Hui Huang, Jing Zhang, Yan Wang, Rongrong Han, Zhixuan Xiang, Lu Chen, Lingling Gao

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Aim and Objectives: To examine physical activity self-efficacy, identify its predictors, and further explore the mechanism of action among the predictors in mainland Chinese pregnant women with high risk for gestational diabetes mellitus (GDM). Background: Physical activity could protect pregnant women from developing GDM. Physical activity self-efficacy was the key predictor of physical activity. Design: A cross-sectional study was conducted from October 2021 to May 2022 in Zhengzhou, China. Methods: 252 eligible pregnant women completed the Pregnancy Physical Activity Self-efficacy Scale, the Social Support for Physical Activity Scale, the Knowledge on Physical Activity Questionnaire, the 7-item Generalized Anxiety Disorder scale, the Edinburgh Postnatal Depression Scale, and a socio-demographic data sheet. Multiple linear regression was applied to explore the predictors of physical activity self-efficacy. Structural equation modeling was used to explore the mechanism of action among the predictors. Results: Chinese pregnant women with a high risk for GDM reported a moderate level of physical activity self-efficacy. The best-fit regression analysis revealed four variables explained 17.5% of the variance in physical activity self-efficacy. Social support for physical activity was the strongest predictor, followed by knowledge of the physical activity, intention to do physical activity, and anxiety symptoms. The model analysis indicated that knowledge of physical activity could release anxiety and depressive symptoms and then increase physical activity self-efficacy. Conclusion: The present study revealed a moderate level of physical activity self-efficacy. Interventions targeting pregnant women with high risk for GDM need to include the predictors of physical activity self-efficacy. Relevance to clinical practice: To facilitate pregnant women with high risk for GDM to engage in physical activity, healthcare professionals may find assess physical activity self-efficacy and intervene as soon as possible on their first antenatal visit. Physical activity intervention programs focused on self-efficacy may be conducted in further research.

Keywords: physical activity, gestational diabetes, self-efficacy, predictors

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228 Special Single Mode Fiber Tests of Polarization Mode Dispersion Changes in a Harsh Environment

Authors: Jan Bohata, Stanislav Zvanovec, Matej Komanec, Jakub Jaros, David Hruby

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Even though there is a rapid development in new optical networks, still optical communication infrastructures remain composed of thousands of kilometers of aging optical cables. Many of them are located in a harsh environment which contributes to an increased attenuation or induced birefringence of the fibers leading to the increase of polarization mode dispersion (PMD). In this paper, we report experimental results from environmental optical cable tests and characterization in the climate chamber. We focused on the evaluation of optical network reliability in a harsh environment. For this purpose, a special thermal chamber was adopted, targeting to the large temperature changes between -60 °C and 160 C° with defined humidity. Single mode optical cable 230 meters long, having six tubes and a total number of 72 single mode optical fibers was spliced together forming one fiber link, which was afterward tested in the climate chamber. The main emphasis was put to the polarization mode dispersion (PMD) changes, which were evaluated by three different PMD measuring methods (general interferometry technique, scrambled state-of-polarization analysis and polarization optical time domain reflectometer) in order to fully validate obtained results. Moreover, attenuation and chromatic dispersion (CD), as well as the PMD, were monitored using 17 km long single mode optical cable. Results imply a strong PMD dependence on thermal changes, imposing the exceeding 200 % of its value during the exposure to extreme temperatures and experienced more than 20 dB insertion losses in the optical system. The derived statistic is provided in the paper together with an evaluation of such as optical system reliability, which could be a crucial tool for the optical network designers. The environmental tests are further taken in context to our previously published results from long-term monitoring of fundamental parameters within an optical cable placed in a harsh environment in a special outdoor testbed. Finally, we provide a correlation between short-term and long-term monitoring campaigns and statistics, which are necessary for optical network safety and reliability.

Keywords: optical fiber, polarization mode dispersion, harsh environment, aging

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227 Social Protection Reforms in Indonesia: Towards a Life Cycle Based Social Protection System

Authors: Dyah Larasati, Karishma Alize Huda, Sri Kusumastuti Rahayu, Martin Daniel Siyaranamual

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Indonesia continues to reform its social protection system to provide the needed protection for its citizen. Indonesia Social Protection consisted of social assistance programs (non-contributory/tax-financed) specifically targeted for the poor and at-risk and social security/insurance program (contributory system). The social assistance programs have mostly been implemented since 1998. The national health insurance has been implemented since 2014 and the employment social insurance since 2015. One major reform implemented has been improving the targeting performance of its major social assistance portfolios including (1) Food Assistance for the poor families (Rastra and BPNT/noncash foods assistance); (2) Education Assistance for poor children; (3) Conditional Cash Transfer for poor families (PKH); and (4) Subsidized beneficiaries of National Health Insurance (JKN-PBI) for the poor and at-risk individuals. For the Social Insurance (through BPJS Employment program), several initiatives have been implemented to expand the program contributing members, although it mostly benefits the formal sector workers. However, major gaps still exist especially for the emerging middle-income groups who typically work at the informal sectors. They have yet to get the protection needed to sustain their social and economic growth. Since 2017, TNP2K (the National Team for Poverty Reduction) under the Vice President office has led the social protection discourse as the government understands the need to address vulnerabilities across the lifecycle and prioritize support to the most at-risk population particularly the elderly, young children and people with disabilities. Discussion and advocacy to recommend for more investment is continuing in order for the government to establish a comprehensive social protection system in the near future (2020-2024) that protects children through an inclusive child benefit program; build a system to benefit more working-age adults (including individuals with disabilities) and a three-tier elderly protection as they reach 65 years.

Keywords: poverty reduction, social assistance, social insurance, social protection

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226 Protection and Immune Responses of DNA Vaccines Targeting Virulence Factors of Streptococcus iniae in Nile Tilapia (Oreochromis niloticus)

Authors: Pattanapon Kayansamruaj, Ha Thanh Dong, Nopadon Pirarat, Channarong Rodkhum

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Streptococcus iniae (SI) is a devastating pathogenic bacteria causing heavy mortality in farmed fish. The application of commercialized bacterin vaccine has been reported failures as the outbreaks of the new serotype of SI were emerged in farms after vaccination and subsequently caused severe losses. In the present study, we attempted to develop effective DNA vaccines against SI infection using Nile tilapia (Oreochromis niloticus) as an animal model. Two monovalent DNA vaccines were constructed by the insertion of coding sequences of cell wall-associated virulence factors-encoding genes, comprised of eno (α-enolase) and mtsB (hydrophobic membrane protein), into cytomegalovirus expression vector (pCI-neo). In the animal trial, 30-g Nile tilapia were injected intramuscularly with 15 µg of each vaccine (mock vaccine group was injected by naked pCI-neo) and maintained for 35 days prior challenging with pathogenic SI at the dosage of 107 CFU/fish. At 13 days post-challenge, the relative percent survival of pEno, pMtsB and mock vaccine were 57%, 45% and 27%, respectively. The expression levels of immune responses-associated genes, namely, IL1β, TNF-α, TGF-β, COX2, IL-6, IL-12 and IL-13, were investigated from the spleen of experimental animal at 7 days post-vaccination (PV) and 7 days post-challenge (PC) using quantitative RT-PCR technique. Generally, at 7 days PV, the pEno vaccinated group exhibited highest level of up-regulation (1.7 to 2.9 folds) of every gene, but TGF-β, comparing to pMtsB and mock vaccine groups. However, at 7 days PC, pEno group showed significant up-regulation (1.4 to 8.5 folds) of immune-related genes as similar as mock vaccine group, while pMtsB group had lowest level of up-regulation (0.7 to 3.3 folds). Summarily, this study indicated that the pEno and pMtsB vaccines could elicit the immune responses of the fish and the magnitude of gene expression at 7 days PV was also consistent with the protection level conferred by the vaccine.

Keywords: gene expression, DNA vaccine, Nile tilapia, Streptococcus iniae

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225 Targeting Glucocorticoid Receptor Eliminate Dormant Chemoresistant Cancer Stem Cells in Glioblastoma

Authors: Aoxue Yang, Weili Tian, Yonghe Wu, Haikun Liu

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Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Little progress has been made in therapeutic treatment of glioblastoma in the last decade despite rapid progress in molecular understanding of brain tumors1. Here we show that the stress hormone glucocorticoid is essential for the maintenance of brain tumor stem cells (BTSCs), which are resistant to conventional therapy. The glucocorticoid receptor (GR) regulates metabolic plasticity and chemoresistance of the dormant BTSC via controlling expression of GPD1 (glycerol-3-phosphate dehydrogenase 1), which is an essential regulator of lipid metabolism in BTSCs. Genomic, lipidomic and cellular analysis confirm that GR/GPD1 regulation is essential for BTSCs metabolic plasticity and survival. We further demonstrate that the GR agonist dexamethasone (DEXA), which is commonly used to control edema in glioblastoma, abolishes the effect of chemotherapy drug temozolomide (TMZ) by upregulating GPD1 and thus promoting tumor cell dormancy in vivo, this provides a mechanistic explanation and thus settle the long-standing debate of usage of steroid in brain tumor patient edema control. Pharmacological inhibition of GR/GPD1 pathway disrupts metabolic plasticity of BTSCs and prolong animal survival, which is superior to standard chemotherapy. Patient case study shows that GR antagonist mifepristone blocks tumor progression and leads to symptomatic improvement. This study identifies an important mechanism regulating cancer stem cell dormancy and provides a new opportunity for glioblastoma treatment.

Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides.

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224 Transcranial Electric Field Treatments on Redox-Toxic Iron Deposits in Transgenic Alzheimer’s Disease Mouse Models: The Electroceutical Targeting of Alzheimer’s Disease

Authors: Choi Younshick, Lee Wonseok, Lee Jaemeun, Park Sun-Hyun, Kim Sunwoung, Park Sua, Kim Eun Ho, Kim Jong-Ki

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Iron accumulation in the brain accelerates Alzheimer’s disease progression. To cure iron toxicity, we assessed the therapeutic effects of noncontact transcranial electric field stimulation to the brain on toxic iron deposits in either the Aβ-fibril structure or the Aβ plaque in a mouse model of Alzheimer’s disease (AD). A capacitive electrode-based alternating electric field (AEF) was applied to a suspension of magnetite (Fe₃O₄) to measure the field-sensitized electro-Fenton effect and resultant reactive oxygen species (ROS) generation. The increase in ROS generation compared to the untreated control was both exposure-time and AEF-frequency dependent. The frequency-specific exposure of AEF to 0.7–1.4 V/cm on a magnetite-bound Aβ-fibril or a transgenic Alzheimer’s disease (AD) mouse model revealed the removal of intraplaque ferrous magnetite iron deposit and Aβ-plaque burden together at the same time compared to the untreated control. The results of the behavioral tests show an improvement in impaired cognitive function following AEF treatment on the AD mouse model. Western blot assay found some disease-modifying biological responses, including down-regulating ferroptosis, neuroinflammation and reactive astrocytes that eventually made cognitive improvement feasible. Tissue clearing and 3D-imaging analysis revealed no induced damage to the neuronal structures of normal brain tissue following AEF treatment. In conclusion, our results suggest that the effective degradation of magnetite-bound amyloid fibrils or plaques in the AD brain by the electro-Fenton effect from electric field-sensitized magnetite offers a potential electroceutical treatment option for AD.

Keywords: electroceutical, intraplaque magnetite, alzheimer’s disease, transcranial electric field, electro-fenton effect

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223 Photoelectrical Stimulation for Cancer Therapy

Authors: Mohammad M. Aria, Fatma Öz, Yashar Esmaeilian, Marco Carofiglio, Valentina Cauda, Özlem Yalçın

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Photoelectrical stimulation of cells with semiconductor organic polymers have been shown promising applications in neuroprosthetics such as retinal prosthesis. Photoelectrical stimulation of the cell membranes can be induced through a photo-electric charge separation mechanism in the semiconductor materials, and it can alter intracellular calcium level through both stimulation of voltage-gated ion channels and increase of intracellular reactive oxygen species (ROS) level. On the other hand, targeting voltage-gated ion channels in cancer cells to induce cell apoptosis through calcium signaling alternation is an effective mechanism which has been explained before. In this regard, remote control of the voltage-gated ion channels aimed to alter intracellular calcium by using photo-active organic polymers can be novel technology in cancer therapy. In this study, we used P (ITO/Indium thin oxide)/P3HT(poly(3-hexylthiophene-2,5-diyl)) and PN (ITO/ZnO/P3HT) photovoltaic junctions to stimulate MDA-MB-231 breast cancer cells. We showed that the photo-stimulation of breast cancer cells through photo capacitive current generated by the photovoltaic junctions are able to excite the cells and alternate intracellular calcium based on the calcium imaging (at 8mW/cm² green light intensity and 10-50 ms light durations), which has been reported already to safety stimulate neurons. The control group did not undergo light treatment and was cultured in T-75 flasks. We detected 20-30% cell death for ITO/P3HT and 51-60% cell death for ITO/ZnO/P3HT samples in the light treated MDA-MB-231 cell group. Western blot analysis demonstrated poly(ADP-ribose) polymerase (PARP) activated cell death in the light treated group. Furthermore, Annexin V and PI fluorescent staining indicated both apoptosis and necrosis in treated cells. In conclusion, our findings revealed that the photoelectrical stimulation of cells (through long time overstimulation) can induce cell death in cancer cells.

Keywords: Ca²⁺ signaling, cancer therapy, electrically excitable cells, photoelectrical stimulation, voltage-gated ion channels

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222 Ophthalmic Self-Medication Practices and Associated Factors among Adult Ophthalmic Patients

Authors: Sarah Saad Alamer, Shujon Mohammed Alazzam, Amjad Khater Alanazi, Mohamed Ahmed Sankari, Jana Sameer Sendy, Saleh Al-Khaldi, Khaled Allam, Amani Badawi

Abstract:

Background: Self-medication is defined as the selection of medicines by individuals to treat self-diagnosed. There are a lot of concerns about the safety of long-term use of nonprescription ophthalmic drugs, which may lead to a variety of serious ocular complications. Topical steroids can produce severe eye-threatening complications, including the elevation of intraocular pressure (IOP) with possible development of glaucoma and infrequent optic nerve damage. In recent times, many OTC ophthalmic preparations have been possible without a prescription. Objective: In our study, we aimed to determine the prevalence of self-medication ocular topical steroid practice and associated factors among adult ophthalmic patients attending King Saud medical city. Methods: This study was conducted as a cross-sectional study, targeting participants aged 18 years old or above who had used topical steroids eye drops to determine the prevalence of self-medication ocular topical steroid practice and associated factors among adult patients attending ophthalmology clinic in King Saud Medical City (KSMC) in the central region. Results: A total of 308 responses, 92(29.8%) were using ocular topical, 58(18.8%) with prescription, 5(1.6%) without prescription, 29(9.4%) with and without prescription while 216(70.1%) did not use it. The frequency of using ocular topical steroids without a prescription among participants was 11(12%) once and 33 (35%) many times. 26(28.3%) were having complication, mostly 11(12.4%) eye infection, 8(9%) Glaucoma, 6 (6.7%) Cataracts. Reasons for self-medication ocular topical steroid practice among participants were 14 (15.2%) repeated symptoms, 11(15.2%) had heard an advice from a friend, 11 (15.2%) thought they had enough knowledge. Conclusion: Our study reveals that, even though detecting a high level of knowledge and acceptable practices and attitudes among participants, the incidence of self-medication with steroid eye drops was observed. This practice is mainly due to participants having repeated symptoms and thinking they have enough knowledge. Increasing the education level of patients on self-medication steroid eye drops practice and it is associated complications would help reduce the incidence of self-medication steroid eye drops practice.

Keywords: self-medication, ophthalmic medicine, steroid eye drop, over the counter

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221 A Realist Review of Interventions Targeting Maternal Health in Low- and Middle-income Countries

Authors: Julie Mariam Abraham, G. J. Melendez-Torres

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Background. Maternal mortality is disproportionately higher in low- and middle- income countries (LMICs) compared to other parts of the world. At the current pace of progress, the Sustainable Development Goals for maternal mortality rate will not be achieved by 2030. A variety of factors influence the increased risk of maternal complications in LMICs. These are exacerbated by socio-economic and political factors, including poverty, illiteracy, and gender inequality. This paper aims to use realist synthesis to identify the contexts, mechanisms, and outcomes (CMOs) of maternal health interventions conducted in LMICs to inform evidence-based practice for future maternal health interventions. Methods. In May 2022, we searched four electronic databases for systematic reviews of maternal health interventions in LMICs published in the last five years. We used open and axial coding of CMOs to develop an explanatory framework for intervention effectiveness. Results. After eligibility screening and full-text analysis, 44 papers were included. The intervention strategies and measured outcomes varied within reviews. Healthcare system level contextual factors were the most frequently reported, and infrastructural capacity was the most reported context. The most prevalent mechanism was increased knowledge and awareness. Discussion. Health system infrastructure must be considered in interventions to ensure effective implementation and sustainability. Healthcare-seeking behaviours are embedded within social and cultural norms, environmental conditions, family influences, and provider attitudes. Therefore, effective engagement with communities and families is important to create new norms surrounding pregnancy and delivery. Future research should explore community mobilisation and involvement to enable tailored interventions with optimal contextual fit.

Keywords: maternal mortality, service delivery and organisation, realist synthesis, sustainable development goals, overview of reviews

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220 A Six-Year Case Study Evaluating the Stakeholders’ Requirements and Satisfaction in Higher Educational Establishments

Authors: Ioannis I. Αngeli

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Worldwide and mainly in the European Union, many standards, regulations, models and systems exists for the evaluation and identification of stakeholders’ requirements of individual universities and higher education (HE) in general. All systems are targeting to measure or evaluate the Universities’ Quality Assurance Systems and the services offered to the recipients of HE, mainly the students. Numerous surveys were conducted in the past either by each university or by organized bodies to identify the students’ satisfaction or to evaluate to what extent these requirements are fulfilled. In this paper, the main results of an ongoing 6-year joint research will be presented very briefly. This research deals with an in depth investigation of student’s satisfaction, students personal requirements, a cup analysis among these two parameters and compares different universities. Through this research an attempt will be made to address four very important questions in higher education establishments (HEE): (1) Are there any common requirements, parameters, good practices or questions that apply to a large number of universities that will assure that students’ requirements are fulfilled? (2) Up to what extent the individual programs of HEE fulfil the requirements of the stakeholders? (3) Are there any similarities on specific programs among European HEE? (4) To what extent the knowledge acquired in a specific course program is utilized or used in a specific country? For the execution of the research an internationally accepted questionnaire(s) was used to evaluate up to what extent the students’ requirements and satisfaction were fulfilled in 2012 and five years later (2017). Samples of students and or universities were taken from many European Universities. The questionnaires used, the sampling method and methodology adopted, as well as the comparison tables and results will be very valuable to any university that is willing to follow the same route and methodology or compare the results with their own HHE. Apart from the unique methodology, valuable results are demonstrated from the four case studies. There is a great difference between the student’s expectations or importance from what they are getting from their universities (in all parameters they are getting less). When there is a crisis or budget cut in HEE there is a direct impact to students. There are many differences on subjects taught in European universities.

Keywords: quality in higher education, students' requirements, education standards, student's survey, stakeholder's requirements, mechanical engineering courses

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219 The Influence of Ecologically -Valid High- and Low-Volume Resistance Training on Muscle Strength and Size in Trained Men

Authors: Jason Dellatolla, Scott Thomas

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Much of the current literature pertaining to resistance training (RT) volume prescription lacks ecological validity, and very few studies investigate true high-volume ranges. Purpose: The present study sought to investigate the effects of ecologically-valid high- vs low-volume RT on muscular size and strength in trained men. Methods: This study systematically randomized trained, college-aged men into two groups: low-volume (LV; n = 4) and high-volume (HV; n = 5). The sample size was affected by COVID-19 limitations. Subjects followed an ecologically-valid 6-week RT program targeting both muscle size and strength. RT occurred 3x/week on non-consecutive days. Over the course of six weeks, LVR and HVR gradually progressed from 15 to 23 sets/week and 30 to 46 sets/week of lower-body RT, respectively. Muscle strength was assessed via 3RM tests in the squat, stiff-leg deadlift (SL DL), and leg press. Muscle hypertrophy was evaluated through a combination of DXA, BodPod, and ultrasound (US) measurements. Results: Two-way repeated-measures ANOVAs indicated that strength in all 3 compound lifts increased significantly among both groups (p < 0.01); between-group differences only occurred in the squat (p = 0.02) and SL DL (p = 0.03), both of which favored HVR. Significant pre-to-post-study increases in indicators of hypertrophy were discovered for lean body mass in the legs via DXA, overall fat-free mass via BodPod, and US measures of muscle thickness (MT) for the rectus femoris, vastus intermedius, vastus medialis, vastus lateralis, long-head of the biceps femoris, and total MT. Between-group differences were only found for MT of the vastus medialis – favoring HVR. Moreover, each additional weekly set of lower-body RT was associated with an average increase in MT of 0.39% in the thigh muscles. Conclusion: We conclude that ecologically-valid RT regimens significantly improve muscular strength and indicators of hypertrophy. When HVR is compared to LVR, HVR provides significantly greater gains in muscular strength but has no greater effect on hypertrophy over the course of 6 weeks in trained, college-aged men.

Keywords: ecological validity, hypertrophy, resistance training, strength

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218 Amelioration of Lipopolysaccharide Induced Murine Colitis by Cell Wall Contents of Probiotic Lactobacillus Casei: Targeting Immuno-Inflammation and Oxidative Stress

Authors: Vishvas N. Patel, Mehul Chorawala

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Currently, according to the authors best knowledge there are less effective therapeutic agents to limit intestinal mucosa damage associated with inflammatory bowel disease (IBD). Clinical studies have shown beneficial effects of several probiotics in patients of IBD. Probiotics are live organisms; confer a health benefit to the host by modulating immunoinflammation and oxidative stress. Although probiotics in murine and human improve disease severity, very little is known about the specific contribution of cell wall contents of probiotics in IBD. Herein, we investigated the ameliorative potential of cell wall contents of Lactobacillus casei (LC) in lipopolysaccharide (LPS)-induced murine colitis. Methods: Colitis was induced in LPS-sensitized rats by intracolonic instillation of LPS (50 µg/rat) for consecutive 14 days. Concurrently, cell wall contents isolated from 103, 106 and 109 CFU of LC was given subcutaneously to each rat for 21 days, considering sulfasalazine (100 mg/kg, p.o.) as standard. The severity of colitis was assessed by body weight loss, food intake, stool consistency, rectal bleeding, colon weight/length, spleen weight and histological analysis. Colonic inflammatory markers (myeloperoxidase (MPO) activity, C-reactive protein and proinflammatory cytokines) and oxidative stress markers (malondialdehyde, reduced glutathione and nitric oxide) were also assayed. Results: Cell wall contents of isolated from 106 and 109 CFU of LC significantly improved the severity of colitis by reducing body weight loss and diarrhea & bleeding incidence, improving food intake, colon weight/length, spleen weight and microscopic damage to the colonic mucosa. The treatment also reduced levels of inflammatory and oxidative stress markers and boosted antioxidant molecule. However, cell wall contents of isolated from 103 were ineffective. Conclusion: In conclusion, cell wall contents of LC attenuate LPS-induced colitis by modulating immuno-inflammation and oxidative stress.

Keywords: probiotics, Lactobacillus casei, immuno-inflammation, oxidative stress, lipopolysaccharide, colitis

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217 In-silico DFT Study, Molecular Docking, ADMET Predictions, and DMS of Isoxazolidine and Isoxazoline Analogs with Anticancer Properties

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

Abstract:

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

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

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216 The Grand Technological Promise in Norwegian Child Welfare Services: Social Workers’ Experiences and Expectations

Authors: Ida Bruheim Jensen, Hulda Mjöll Gunnarsdottir, Ingunn T. Ellingsen

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Digital government is often seen as an enabler or even driver of transformation of public administration, with the objective of creating public value. The increasing use of digital solutions in public services comes with great expectations of new and/or more efficient service provision. Digitalizing public sector services involve multi-level implementation. It involves national policy negotiations and decisions of digital government solutions. It involves co-creation/-production of ideas where planning, design, and implementation involves several groups of actors targeting end-users. Norway is among the most digitalised countries in the world, and Government spendings on digital technologies in public services are high compared to other OECD countries. This contribution studies an ongoing digital transformation in the Norwegian child welfare services. DigiBarnevern (Digi child welfare) is a nationwide project promising better and more efficient child welfare services through various digital technologies. The digitalization process, which is managed by the state and municipalities, is still in its early stages, and as of 2022, only a few services are operative. Digital technologies such as DigiBarnevern are implemented with promises of qualitatively improving child protection work, making the services more effective, foster user participation, and increase availability. There is limited research on the implications of using digital technologies in child protection work. We aim to present findings from an ongoing research project (2022-2024). Drawing on data from focus group interviews with social workers in 5 municipal child welfare services in Norway, we explore social workers’ experiences and expectations towards using digital technologies in child welfare services. Technological solutions may change the services and child protection work in numerous ways. Potential points of departure for discussion are how technologies may change the relationships between social workers, children, youth, and their families, how technologies can alter and obscure responsibilities, and how technologies may demand digital competence among social workers and service recipients.

Keywords: child welfare, social work, technology, digitalisation

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215 Computational Team Dynamics in Student New Product Development Teams

Authors: Shankaran Sitarama

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Teamwork is an extremely effective pedagogical tool in engineering education. New Product Development (NPD) has been an effective strategy of companies to streamline and bring innovative products and solutions to customers. Thus, Engineering curriculum in many schools, some collaboratively with business schools, have brought NPD into the curriculum at the graduate level. Teamwork is invariably used during instruction, where students work in teams to come up with new products and solutions. There is a significant emphasis of grade on the semester long teamwork for it to be taken seriously by students. As the students work in teams and go through this process to develop the new product prototypes, their effectiveness and learning to a great extent depends on how they function as a team and go through the creative process, come together, and work towards the common goal. A core attribute of a successful NPD team is their creativity and innovation. The team needs to be creative as a group, generating a breadth of ideas and innovative solutions that solve or address the problem they are targeting and meet the user’s needs. They also need to be very efficient in their teamwork as they work through the various stages of the development of these ideas resulting in a POC (proof-of-concept) implementation or a prototype of the product. The simultaneous requirement of teams to be creative and at the same time also converge and work together imposes different types of tensions in their team interactions. These ideational tensions / conflicts and sometimes relational tensions / conflicts are inevitable. Effective teams will have to deal with the Team dynamics and manage it to be resilient enough and yet be creative. This research paper provides a computational analysis of the teams’ communication that is reflective of the team dynamics, and through a superimposition of latent semantic analysis with social network analysis, provides a computational methodology of arriving at patterns of visual interaction. These team interaction patterns have clear correlations to the team dynamics and provide insights into the functioning and thus the effectiveness of the teams. 23 student NPD teams over 2 years of a course on Managing NPD that has a blend of engineering and business school students is considered, and the results are presented. It is also correlated with the teams’ detailed and tailored individual and group feedback and self-reflection and evaluation questionnaire.

Keywords: team dynamics, social network analysis, team interaction patterns, new product development teamwork, NPD teams

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214 Re-Emergence of Religious Militancy in Pakistan after Return of Afghan Taliban to Power Corridors in Afghanistan (2021-2022)

Authors: Syed Sibtain Hussain Shah

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The Afghan Taliban returned to power corridors in Afghanistan in August 2021 after waging a twenty-year insurgency in the country. U.S.-led forces completed their withdrawal from Afghanistan on August 30, 2021, but the Taliban took control of the whole country till August 15, 2021. At the same time, some of the militant groups such as Tehrik-e-Taliban Pakistan (TTP) and Islamic State Khurasan (IS-K) reappeared in Pakistan’s borders and other areas and by increasing attacks on the armed forces of Pakistan and minorities communities. These groups once again created a crucial challenge to the internal security of the country. Since mid of 2021, many of the terrorist incidents in the countries specified in the areas of Pakistan bordering Afghanistan were committed by TTP and IS-K. The aim of this paper is to investigate the reappearance of TTP and IS-K in 2021 and 2022 as a crucial threat to the internal security of Pakistan. The author will particularly probe threats to the security of military personnel and their installations and threats to human security, including danger to religious minority communities in the different areas of the country, including border areas such as Waziristan, which was once a hub of TTP and other militant groups in the 2000s. The author will employ the relevant method and appropriate theories of security studies, such as religious extremism and terrorism, in this study. TTP, inspired by the Afghan Taliban, initially emerged in Pakistan in 2007 and this group has so far targeted various religious and ethnic communities and government installations in Pakistan. The group is not only against Pakistan’s government policies, but it also committed terrorist attacks on the communities of the other Muslim sects and as well as non-Muslim communities. Most of the prominent figures of this violent group disappeared or escaped to Afghanistan after military actions, such as the larger “Zarb-e-Azb” operation in Pakistan in 2015. IS-K, which established its branch of Khurasan covering Pakistan and Afghanistan in 2015, with its main formation in Iraq and Syria in 2015, by targeting religious minorities such as Shia Muslims, has so far created a vital security challenge for the security of the country.

Keywords: Pakistan, Afghanistan, Afghan Taliban, Pakistani Taliban, Islamic state Khorasan, security threat

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213 Caregiver Training Results in Accurate Reporting of Stool Frequency

Authors: Matthew Heidman, Susan Dallabrida, Analice Costa

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Background:Accuracy of caregiver reported outcomes is essential for infant growth and tolerability study success. Crying/fussiness, stool consistencies, and other gastrointestinal characteristics are important parameters regarding tolerability, and inter-caregiver reporting can see a significant amount of subjectivity and vary greatly within a study, compromising data. This study sought to elucidate how caregiver reported questions related to stool frequency are answered before and after a short amount of training and how training impacts caregivers’ understanding, and how they would answer the question. Methods:A digital survey was issued for 90 daysin the US (n=121) and 30 days in Mexico (n=88), targeting respondents with children ≤4 years of age. Respondents were asked a question in two formats, first without a line of training text and second with a line of training text. The question set was as follows, “If your baby had stool in his/her diaper and you changed the diaper and 10 min later there was more stool in the diaper, how many stools would you report this as?” followed by the same question beginning with “If you were given the instruction that IF there are at least 5 minutes in between stools, then it counts as two (2) stools…”.Four response items were provided for both questions, 1) 2 stools, 2) 1stool, 3) it depends on how much stool was in the first versus the second diaper, 4) There is not enough information to be able to answer the question. Response frequencies between questions were compared. Results: Responses to the question without training saw some variability in the US, with 69% selecting “2 stools”,11% selecting “1 stool”, 14% selecting “it depends on how much stool was in the first versus the second diaper”, and 7% selecting “There is not enough information to be able to answer the question” and in Mexico respondents selected 9%, 78%, 13%, and 0% respectively. However, responses to the question after training saw more consolidation in the US, with 85% of respondents selecting“2 stools,” representing an increase in those selecting the correct answer. Additionally in Mexico, with 84% of respondents selecting “1 episode” representing an increase in the those selecting the correct response. Conclusions: Caregiver reported outcomes are critical for infant growth and tolerability studies, however, they can be highly subjective and see a high variability of responses without guidance. Training is critical to standardize all caregivers’ perspective regarding how to answer questions accurately in order to provide an accurate dataset.

Keywords: infant nutrition, clinical trial optimization, stool reporting, decentralized clinical trials

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212 One-Step Synthesis and Characterization of Biodegradable ‘Click-Able’ Polyester Polymer for Biomedical Applications

Authors: Wadha Alqahtani

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In recent times, polymers have seen a great surge in interest in the field of medicine, particularly chemotherapeutics. One recent innovation is the conversion of polymeric materials into “polymeric nanoparticles”. These nanoparticles can be designed and modified to encapsulate and transport drugs selectively to cancer cells, minimizing collateral damage to surrounding healthy tissues, and improve patient quality of life. In this study, we have synthesized pseudo-branched polyester polymers from bio-based small molecules, including sorbitol, glutaric acid and a propargylic acid derivative to further modify the polymer to make it “click-able" with an azide-modified target ligand. Melt polymerization technique was used for this polymerization reaction, using lipase enzyme catalyst NOVO 435. This reaction was conducted between 90- 95 °C for 72 hours. The polymer samples were collected in 24-hour increments for characterization and to monitor reaction progress. The resulting polymer was purified with the help of methanol dissolving and filtering with filter paper then characterized via NMR, GPC, FTIR, DSC, TGA and MALDI-TOF. Following characterization, these polymers were converted to a polymeric nanoparticle drug delivery system using solvent diffusion method, wherein DiI optical dye and chemotherapeutic drug Taxol can be encapsulated simultaneously. The efficacy of the nanoparticle’s apoptotic effects were analyzed in-vitro by incubation with prostate cancer (LNCaP) and healthy (CHO) cells. MTT assays and fluorescence microscopy were used to assess the cellular uptake and viability of the cells after 24 hours at 37 °C and 5% CO2 atmosphere. Results of the assays and fluorescence imaging confirmed that the nanoparticles were successful in both selectively targeting and inducing apoptosis in 80% of the LNCaP cells within 24 hours without affecting the viability of the CHO cells. These results show the potential of using biodegradable polymers as a vehicle for receptor-specific drug delivery and a potential alternative for traditional systemic chemotherapy. Detailed experimental results will be discussed in the e-poster.

Keywords: chemotherapeutic drug, click chemistry, nanoparticle, prostat cancer

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211 Applications and Development of a Plug Load Management System That Automatically Identifies the Type and Location of Connected Devices

Authors: Amy Lebar, Kim L. Trenbath, Bennett Doherty, William Livingood

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Plug and process loads (PPLs) account for 47% of U.S. commercial building energy use. There is a huge potential to reduce whole building consumption by targeting PPLs for energy savings measures or implementing some form of plug load management (PLM). Despite this potential, there has yet to be a widely adopted commercial PLM technology. This paper describes the Automatic Type and Location Identification System (ATLIS), a PLM system framework with automatic and dynamic load detection (ADLD). ADLD gives PLM systems the ability to automatically identify devices as they are plugged into the outlets of a building. The ATLIS framework takes advantage of smart, connected devices to identify device locations in a building, meter and control their power, and communicate this information to a central database. ATLIS includes five primary capabilities: location identification, communication, control, energy metering and data storage. A laboratory proof of concept (PoC) demonstrated all but the data storage capabilities and these capabilities were validated using an office building scenario. The PoC can identify when a device is plugged into an outlet and the location of the device in the building. When a device is moved, the PoC’s dashboard and database are automatically updated with the new location. The PoC implements controls to devices from the system dashboard so that devices maintain correct schedules regardless of where they are plugged in within a building. ATLIS’s primary technology application is improved PLM, but other applications include asset management, energy audits, and interoperability for grid-interactive efficient buildings. A system like ATLIS could also be used to direct power to critical devices, such as ventilators, during a brownout or blackout. Such a framework is an opportunity to make PLM more widespread and reduce the amount of energy consumed by PPLs in current and future commercial buildings.

Keywords: commercial buildings, grid-interactive efficient buildings (GEB), miscellaneous electric loads (MELs), plug loads, plug load management (PLM)

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210 Enhanced Cytotoxic Effect of Expanded NK Cells with IL12 and IL15 from Leukoreduction Filter on K562 Cell Line Exhibits Comparable Cytotoxicity to Whole Blood

Authors: Abdulbaset Mazarzaei

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Natural killer (NK) cells are innate immune effectors that play a pivotal role in combating tumors and infected cells. In recent years, the therapeutic potential of NK cells has gained significant attention due to their remarkable cytotoxic ability. This study focuses on investigating the cytotoxic effect of expanded NK cells enriched with interleukin 12 (IL12) and interleukin 15 (IL15), derived from the leukoreduction filter, on the K562 cell line. Firstly, NK cells were isolated from whole blood samples obtained from healthy volunteers. These cells were subsequently expanded ex vivo using a combination of feeder cells, IL12, and IL15. The expanded NK cells were then harvested and assessed for their cytotoxicity against K562, a well-established human chronic myelogenous leukemia cell line. The cytotoxicity was evaluated using flow cytometry assay. Results demonstrate that the expanded NK cells significantly exhibited enhanced cytotoxicity against K562 cells compared to non-expanded NK cells. Interestingly, the expanded NK cells derived specifically from IL12 and IL15-enriched leukoreduction filters showed a robust cytotoxic effect similar to the whole blood-derived NK cells. These findings suggest that IL12 and IL15 in the leukoreduction filter are crucial in promoting NK cell cytotoxicity. Furthermore, the expanded NK cells displayed relatively similar cytotoxicity profiles to whole blood-derived NK cells, indicating their comparable capability in targeting and eliminating tumor cells. This observation is of significant relevance as expanded NK cells from the leukoreduction filter could potentially serve as a readily accessible and efficient source for adoptive immunotherapy. In conclusion, this study highlights the significant cytotoxic effect of expanded NK cells enriched with IL12 and IL15 obtained from the leukoreduction filter on the K562 cell line. Moreover, it emphasizes that these expanded NK cells exhibit comparable cytotoxicity to whole blood-derived NK cells. These findings reinforce the potential clinical utility of using expanded NK cells from the leukoreduction filter as an effective strategy in adoptive immunotherapy for the treatment of cancer. Further studies are warranted to explore the broader implications of this approach in clinical settings.

Keywords: natural killer (NK) cells, Cytotoxicity, Leukoreduction filter, IL-12 and IL-15 Cytokines

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209 The ICC, International Criminal Justice and International Politics

Authors: Girma Y. Iyassu Menelik

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The international community has gone through indescribable atrocities resulting from acts of war. These atrocities turned Europe and Africa into a wilderness of bloodshed and crime. In the period 1960- 1970s Africa witnessed unprecedented and well-documented assaults on life and property. This necessitated the adoption, signing and ratification of the International Criminal Court, establishment of the International Court of Justice which is a great achievement for the protection and fulfilling of human rights in the context of international political instability. The ICC came as an important opportunity to advance justice for serious crimes committed in violation of international law. Thus the Rome statute has become a formidable contribution to peace and security. There are concerns that the ICC is targeting African states. However, the ICC cannot preside over cases that are not parties to the Rome statute unless the UN Security council refers the situation or the relevant state asks the court to become involved. The instable international political situation thus deals with criminal prosecutions where amnesty is not permissible or is strongly repudiated. The court has become important justice instruments for states that are unable or unwilling to fulfill their obligation to address legacies of massive human rights violations. The ICJ as a court has a twofold role; to settle legal disputes submitted to it by states, and to give advisory opinions on legal questions referred to it by duly authorized United Nations organs and specialized agencies. All members of the UN are ipso facto parties to the statute of the ICJ. The court gives advisory opinion on any legal question. These courts are the most appropriate fora to pronounce on international crimes and are in a better position to know and apply international law. Cases that have been brought to the courts include Rwanda’s genocide, Liberia’s Charles Taylor etc. The receptiveness and cooperation of the local populations are important to the courts and if the ICC and ICJ can provide appropriate protections for the physical and economic safety of victims then peace and human rights observance can be attained. This paper will look into the effectiveness and impediments of these courts in handling criminal and injustices in international politics as while as what needs to be done to strengthen the capacity of these courts.

Keywords: ICC, international politics, justice, UN security council, violence, protection, fulfilling

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