Search results for: mechanisms

Authors: Elif Tugce Aksun Tumerkan

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Fluorescent proteins (FPs) have become very popular since green fluorescent protein discovered from crystal jellyfish. It is known that Anthozoa species have a wide range of chromophore organisms, and the initial crystal structure for non-fluorescent chromophores obtained from the reef-building coral has been determined. There are also differently coloured pigments in non-bioluminescent Anthozoa zooxanthellate and azooxanthellate which are frequently members of the GFP-like protein family. The development of fluorescent proteins (FPs) and their applications is an outstanding example of basic science leading to practical biotechnological and medical applications. Fluorescent proteins have several applications in science and are used as important indicators in molecular biology and cell-based research. With rising interest in cell biology, FPs have used as biosensor indicators and probes in pharmacology and cell biology. Using fluorescent proteins in genetically encoded metabolite sensors has many advantages than chemical probes for metabolites such as easily introduced into any cell or organism in any sub-cellular localization and giving chance to fixing to fluoresce of different colours or characteristics. There are different factors effects to signalling mechanism when they used as a biosensor. While there are wide ranges of research have been done on the significance and applications of fluorescent proteins, the cell signalling response of FPs and target cell are less well understood. In this study, it was aimed to clarify the response of adaptive mechanisms of coral species such as pH, temperature and symbiotic relationship and target cells properties on the signalling capacity. Corals are a rich natural source of fluorescent proteins that change with environmental conditions such as light, heat stress and injury. Adaptation mechanism of coral species to these types of environmental variations is important factor due to FPs properties have affected by this mechanism. Since fluorescent proteins obtained from nature, their own ecological property like the symbiotic relationship is observed very commonly in coral species and living conditions have the impact on FPs efficiency. Target cell properties also have an effect on signalling and visualization. The dynamicity of detector that used for reading fluorescence and the level of background fluorescence are key parameters for the quality of the fluorescent signal. Among the factors, it can be concluded that coral species adaptive characteristics have the strongest effect on FPs signalling capacity.

Keywords: biosensor, cell biology, environmental conditions, fluorescent protein, sea anemone

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Authors: Joseph Fitoussi, Mohammadali Shirinbayan, Abbas Tcharkhtchi

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Due to material flow during processing, short fiber reinforced composites structures obtained by injection or compression molding generally present strong spatial microstructure variation. On the other hand, quasi-static, dynamic, and fatigue behavior of these materials are highly dependent on microstructure parameters such as fiber orientation distribution. Indeed, because of complex damage mechanisms, SFRC structures design is a key challenge for safety and reliability. In this paper, we propose a micromechanical model allowing prediction of damage behavior of real structures as a function of microstructure spatial distribution. To this aim, a statistical damage criterion including strain rate and fatigue effect at the local scale is introduced into a Mori and Tanaka model. A critical local damage state is identified, allowing fatigue life prediction. Moreover, the multi-scale model is coupled with an experimental intrinsic link between damage under monotonic loading and fatigue life in order to build an abacus giving Tsai-Wu failure criterion parameters as a function of microstructure and targeted fatigue life. On the other hand, the micromechanical damage model gives access to the evolution of the anisotropic stiffness tensor of SFRC submitted to complex thermomechanical loading, including quasi-static, dynamic, and cyclic loading with temperature and amplitude variations. Then, the latter is used to fill out microstructure dependent material cards in finite element analysis for design optimization in the case of complex loading history. The proposed methodology is illustrated in the case of a real automotive component made of sheet molding compound (PSA 3008 tailgate). The obtained results emphasize how the proposed micromechanical methodology opens a new path for the automotive industry to lighten vehicle bodies and thereby save energy and reduce gas emission.

Keywords: short fiber reinforced composite, structural design, damage, micromechanical modelling, fatigue, strain rate effect

Procedia PDF Downloads 107

Authors: Ahmed Bahieldin, Ahmed Atef, Jamal S. M. Sabir, Nour O. Gadalla, Sherif Edris, Ahmed M. Alzohairy, Nezar A. Radhwan, Mohammed N. Baeshen, Ahmed M. Ramadan, Hala F. Eissa, Sabah M. Hassan, Nabih A. Baeshen, Osama Abuzinadah, Magdy A. Al-Kordy, Fotouh M. El-Domyati, Robert K. Jansen

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Wild salt-tolerant barley (Hordeum spontaneum) is the ancestor of cultivated barley (Hordeum vulgare or H. vulgare). Although the cultivated barley genome is well studied, little is known about genome structure and function of its wild ancestor. In the present study, RNA-Seq analysis was performed on young leaves of wild barley treated with salt (500 mM NaCl) at four different time intervals. Transcriptome sequencing yielded 103 to 115 million reads for all replicates of each treatment, corresponding to over 10 billion nucleotides per sample. Of the total reads, between 74.8 and 80.3% could be mapped and 77.4 to 81.7% of the transcripts were found in the H. vulgare unigene database (unigene-mapped). The unmapped wild barley reads for all treatments and replicates were assembled de novo and the resulting contigs were used as a new reference genome. This resultedin94.3 to 95.3%oftheunmapped reads mapping to the new reference. The number of differentially expressed transcripts was 9277, 3861 of which were uni gene-mapped. The annotated unigene- and de novo-mapped transcripts (5100) were utilized to generate expression clusters across time of salt stress treatment. Two-dimensional hierarchical clustering classified differential expression profiles into nine expression clusters, four of which were selected for further analysis. Differentially expressed transcripts were assigned to the main functional categories. The most important groups were ‘response to external stimulus’ and ‘electron-carrier activity’. Highly expressed transcripts are involved in several biological processes, including electron transport and exchanger mechanisms, flavonoid biosynthesis, reactive oxygen species (ROS) scavenging, ethylene production, signaling network and protein refolding. The comparisons demonstrated that mRNA-Seq is an efficient method for the analysis of differentially expressed genes and biological processes under salt stress.

Keywords: electron transport, flavonoid biosynthesis, reactive oxygen species, rnaseq

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Authors: Md. Kausar Alam, Ramin Motamed

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The damaging effects of liquefaction-induced ground movements have been frequently observed in past earthquakes, such as the 2010-2011 Canterbury Earthquake Sequence (CES) in New Zealand and the 2011 Tohoku earthquake in Japan. To reduce the consequences of soil liquefaction at shallow depths, various ground improvement techniques have been utilized in engineering practice, among which this research is focused on experimentally evaluating the press-in sheet piling technique. The press-in sheet pile technique eliminates the vibration, hammering, and noise pollution associated with dynamic sheet pile installation methods. Unfortunately, there are limited experimental studies on the press-in sheet piling technique for liquefaction mitigation using 1g shake table tests in which all the controlling mechanisms of liquefaction-induced foundation settlement, including sand ejecta, can be realistically reproduced. In this study, a series of moderate scale 1g shake table experiments were conducted at the University of Nevada, Reno, to evaluate the performance of this technique in liquefiable soil layers. First, a 1/5 size model was developed based on a recent UC San Diego shaking table experiment. The scaled model has a density of 50% for the top crust, 40% for the intermediate liquefiable layer, and 85% for the bottom dense layer. Second, a shallow foundation is seated atop an unsaturated sandy soil crust. Third, in a series of tests, a sheet pile with variable embedment depth is inserted into the liquefiable soil using the press-in technique surrounding the shallow foundations. The scaled models are subjected to harmonic input motions with amplitude and dominant frequency properly scaled based on the large-scale shake table test. This study assesses the performance of the press-in sheet piling technique in terms of reductions in the foundation movements (settlement and tilt) and generated excess pore water pressures. In addition, this paper discusses the cost-effectiveness and carbon footprint features of the studied mitigation measures.

Keywords: excess pore water pressure, foundation settlement, press-in sheet pile, soil liquefaction

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Authors: Alina Beraudi, Simona Catalani, Dalila De Pasquale, Eva Bianconi, Umberto Santoro, Susanna Stea, Pietro Apostoli

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Recently the European Community, in line with the international scientific community such as with the Consensus Statement, has determined to stop the use of metal-on-metal big head stemmed hip prosthesis. Among the factors accounted as responsible for the high failure rates of these hip implants are the release and accumulation of metal ions. Many studies have correlated the presence of these ions, besides other factors, with the induction of oxidative stress response. In our study on 12 subjects, we observed the patient specific capability to eliminate metal ions after revision surgery. While for cobalt all the patients were able to completely excrete cobalt ions within 5-7 months after metal-on-metal bearing removal, for chromium ions it didn’t happen. If on the one hand the toxicokinetic differences between the two types of ions are confirmed by toxicological and occupational studies, on the other hand, this peculiar way of exposition represents a novel and important point of view. Thus, two different approaches were performed to better understand the subject specific capability to transport metal ions (albumin study) and to manage the response to them (heme-oxygenase-1 study): - a mutational screening of ALBUMIN gene was conducted in 30 MoM prosthetic patients resulting in the absence of nucleotidic changes compared with the ALB reference sequence. To this study was also added the analysis of expression of modified albumin protein; - a gene and protein expression study on 44 patients of heme-oxygenase-1, that is one of the most important antioxidant enzyme induced by metallic ions, was performed. This study resulted in no statistically significant differences in the expression of the gene and protein heme-oxygenase-1 between prosthetic and non-prosthetic patients, as well as between patients with high and low ions levels. Our results show that the protein studied (albumin and heme-oxygenase-1) seem to be not involved in determining chromium and cobalt ions level. On the other hand, achromium and cobalt elimination rates are different, but similar in all patients analyzed, suggesting that this process could be not patient-related. We support the importance of researching more about ions transport within the organism once released by hip prosthesis, about the chemical species involved, the districts where they are contained and the mechanisms of elimination, not excluding the existence of a subjective susceptibility to these metals ions.

Keywords: chromium, cobalt, hip prosthesis, individual susceptibility

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Authors: Seyedahmad Hosseini, Mohammadjavad Sotoudeheian

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Introduction: Allergic asthma is a heterogeneous immuno-inflammatory disease based on Th-2-mediated inflammation. Histopathologic abnormalities of the airways characteristic of asthma include epithelial damage and subepithelial collagen deposition. Objectives: Human bronchial epithelial cell genome expression of TNF‑α, IL‑6, ICAM‑1, VCAM‑1, nuclear factor (NF)‑κB signaling pathways up-regulate during inflammatory cascades. Moreover, immunofluorescence assays confirmed the nuclear translocation of NF‑κB p65 during inflammatory responses. An absolute LDH leakage assays suggestedLPS-inducedcells injury, and the associated mechanisms are co-incident events. LPS-induced phosphorylation of ERKand JNK causes inflammation in epithelial cells through inhibition of ERK and JNK activation and NF-κB signaling pathway. Furthermore, the inhibition of NF-κB mRNA expression and the nuclear translocation of NF-κB lead to anti-inflammatory events. Likewise, activation of SUMF2 which inhibits IL-13 and reduces Th2-cytokines, NF-κB, and IgE levels to ameliorate asthma. On the other hand, TNFα-induced mucus production reduced NF-κB activation through inhibition of the activation status of Rac1 and IκBα phosphorylation. In addition, bradykinin B2 receptor (B2R), which mediates airway remodeling, regulates through NF-κB. Bronchial B2R expression is constitutively elevated in allergic asthma. In addition, certain NF-κB -dependent chemokines function to recruit eosinophils in the airway. Besides, bromodomain containing 4 (BRD4) plays a significant role in mediating innate immune response in human small airway epithelial cells as well as transglutaminase 2 (TG2), which is detectable in saliva. So, the guanine nucleotide-binding regulatory protein α-subunit, Gα16, expresses a κB-driven luciferase reporter. This response was accompanied by phosphorylation of IκBα. Furthermore, expression of Gα16 in saliva markedly enhanced TNF-α-induced κB reporter activity. Methods: The applied method to form NF-κB activation is the electromobility shift assay (EMSA). Also, B2R-BRD4-TG2 complex detection by immunoassay method within saliva with EMSA of NF-κB activation may be a novel biomarker for asthma diagnosis and follow up. Conclusion: This concept introduces NF-κB signaling pathway as potential asthma biomarkers and promising targets for the development of new therapeutic strategies against asthma.

Keywords: NF-κB, asthma, saliva, T-helper

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Authors: R. A. Shahmiri, O. Standard, J. Hart, C. C. Sorrell

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Yttrium stabilized tetragonal zirconium polycrystalline (Y-TZP) has been used as a dental biomaterial. The strength and toughness of zirconia can be accounted for by its toughening mechanisms, such as crack deflection, zone shielding, contact shielding, and crack bridging. Prevention of crack propagation is of critical importance in high-fatigue situations, such as those encountered in mastication and para-function. However, the poor translucency of Y-TZP means that it may not meet the aesthetic requirements due to its white/grey appearance in polycrystalline form. To improve optical property of the Zirconia, precise evaluation of its refractive index is of significance. Zirconia`s optical properties need to be studied more in depth. Number of studies assumed, scattered light is isotropically distributed over all angles from biological media when defining optical parameters. Nevertheless, optical behaviour of real biological material depends on angular scattering of light by anisotropy material. Therefore, the average cosine of the scattering angle (which represent recovery phase function in the scattering angular distribution) usually characterized by anisotropy material. It has been identified that yttrium anti-sites present in the space charge layer have no significant role in the absorption of light in the visible range. Addition of cation dopant to polycrystalline zirconia results in segregate to grain boundaries and grain growth. Intrinsic and extrinsic properties of ZrO2 and their effect on optical properties need to be investigated. Intrinsic properties such as chemical composition, defect structure (oxygen vacancy), phase configuration (porosity, second phase) and distribution of phase need to be studied to comprehend their effect on refraction index, absorption/reflection and scattering. Extrinsic properties such as surface structure, thickness, underlying tooth structure, cement layer (type, thickness), and light source (natural, curing, artificial) of ZrO2 need to be studied to understand their effect on colour and translucency of material. This research reviewed effect of stabilization of tetragonal zirconia on optical property of zirconia for dental application.

Keywords: optical properties, zirconia dental biomaterial, chemical composition, phase composition

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Authors: E. C. Swart, E. Kunneke

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Background: Disparities in food security exist between communities and households across the country, reflecting continuing social and economic inequalities. The purpose of this study was to investigate the presence of food insecurity amongst UWC students. Method: Cross-sectional study recruited 200 students via email and cellphone from an ICS generated list of randomly selected students aged 18-25. Data collection took place during the first two weeks of term 3. Individual appointments were made with consenting participants and conducted in English by trained BSc Dietetics students. Data was analysed using SPSS. The hunger scale used by Stats SA (October 2010) was used. Dietary intake was assessed using a single 24hr recall. Results: Sixty-three percent of the students reported that they do experience some food insecurity whilst 14.5% reported to go hungry due to inadequate access to food. Coping mechanisms during periods of food insecurity include: Asking a friend, neighbour, family member (40%); Borrow (15%); Steal (none); Casual jobs (12%). Anthropometric status of students did not differ statistically significantly by food security status. A statistically significantly greater proportion of Xhosa speaking students reported inadequate money for food. Students residing in residences off campus appear to be least food secure in terms of money available and limiting food intake, whilst those residing at home are less food insecure. Similar proportions of students who receive bursaries or whose parents are paying reported going hungry whilst those who supports themselves never goes hungry. Mean nutrient intake during the previous 24 hours of students who reported inadequate resources to buy food, who eat less due to inadequate resources and who goes hungry only differed statistically significantly for Vitamin B (go hungry) and for fibre (money shortage). In general the nutrient intake is lower for those who reported to eat less and go hungry except for added sugar, vitamin A and folate (go hungry), and energy, fibre, iron, riboflavin and folate (eat less). For students who reported to have inadequate money to buy food, the mean nutrient intake was higher except for calcium and thiamin. The mean body mass index of this group of students was also higher even though the difference was not statistically significant. Conclusion: Hunger is present on campus however a single 24hr recall did not confirm statistically significant lower nutrient intakes for students who reported different levels of food insecurity.

Keywords: anthropometry, dietary intake, nutritional status, students

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Authors: Anna Tokajuk, Agnieszka Zakrzeska, Ewa Chabielska, Halina Car

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Whey is a by-product generated mainly in the production of cheese and casein. Powder forms of whey are used widely in the food industry as well as a high-protein food for infants, for convalescents, by athletes and especially by bodybuilders to increase muscle mass during exercise. Whey protein concentrate-80 (WPC-80) is a source of bioactive peptides with beneficial effects on the cardiovascular system. It is known that whey proteins health beneficial properties include antidiabetic, blood pressure lowering, improving cardiovascular system function, antibacterial, antiviral and other effects. To study its influence on the development of thrombosis, venous thrombosis model was performed according to the protocol featured by Reyers with modification by Chabielska and Gromotowicz. Male Wistar-Crl: WI (Han) rats from researched groups were supplemented with two doses of WPC-80 (0.3 or 0.5 g/kg) for 7, 14 or 21 days and after these periods, one-hour venous thrombosis model was performed. Control group received 0.9 % NaCl solution and was sham operated. The statistical significance of results was computed by Mann – Whitney’s test. We observed that thrombus weight was decreased in animals obtaining WPC-8080 and that was statistically significant in 14 and 21-day supplemented groups. Blood count parameters did not differ significantly in rats with and without thrombosis induction whether they were fed with WPC-80 or not. Moreover, the number of platelets (PLT) was within the normal range in each group. The examined coagulation parameters in rats of the control groups were within normal limits. After WPC-80 supplementation there was the tendency to prolonged activated partial thromboplastin time (aPTT), but in comparison, the results did not turn out significant. In animals that received WPC-80 0.3 g·kg-1 for 21 days with and without induced thrombosis, prothrombin time (PT) and an international normalized ratio (INR) was somewhat decreased, remaining within the normal range, but the nature and significance of this observation are beyond the framework of the current study. Additionally, fibrinogen and thrombin time (TT) did not differ significantly between groups. Therefore the exact effect of WPC-80 on coagulation system is still elusive and requires further thorough research including mechanisms of action. Determining the potential clinical application of WPC-80 requires the selection of the optimal dose and duration of supplementation.

Keywords: antithrombotic, rats, venous thrombosis, WPC-80

Procedia PDF Downloads 118

Authors: Chloe Richards, Adrian Delgado Ollero, Yan Delaure, Fiona Regan

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Growing concern about the natural environment has accelerated the search for non-toxic, but at the same time, economically reasonable, antifouling materials. Bioinspired surfaces, due to their nano and micro topographical antifouling capabilities, provide a hopeful approach to the design of novel antifouling surfaces. Biological organisms are known to have highly evolved and complex topographies, demonstrating antifouling potential, i.e. shark skin. Previous studies have examined the antifouling ability of topographic patterns, textures and roughness scales found on natural organisms. One of the mechanisms used to explain the adhesion of cells to a substrate is called attachment point theory. Here, the fouling organism experiences increased attachment where there are multiple attachment points and reduced attachment, where the number of attachment points are decreased. In this study, an attempt to characterize the microtopography of the common brill fish, Scophthalmus rhombus, was undertaken. Scophthalmus rhombus is a small flatfish of the family Scophthalmidae, inhabiting regions from Norway to the Mediterranean and the Black Sea. They reside in shallow sandy and muddy coastal areas at depths of around 70 – 80 meters. Six engineered surfaces (inspired by the Brill fish scale) produced by a 2-photon polymerization (2PP) process were evaluated for their potential as an antifouling solution for incorporation onto tidal energy blades. The micro-textures were analyzed for their AF potential under both static and dynamic laboratory conditions using two laboratory grown diatom species, Amphora coffeaeformis and Nitzschia ovalis. The incorporation of a surface topography was observed to cause a disruption in the growth of A. coffeaeformis and N. ovalis cells on the surface in comparison to control surfaces. This work has demonstrated the importance of understanding cell-surface interaction, in particular, topography for the design of novel antifouling technology. The study concluded that biofouling can be controlled by physical modification, and has contributed significant knowledge to the use of a successful novel bioinspired AF technology, based on Brill, for the first time.

Keywords: attachment point theory, biofouling, Scophthalmus rhombus, topography

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Authors: Zdzisław Kobos, Robert Jędrys, Zbigniew Wochyński

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Motor activity and good health are sine qua non determinants of a proper practice of the profession, especially aviation. Therefore, candidates to the aviation are selected according their psychomotor ability by both specialist medical commissions. Moreover, they must past an examination of the physical fitness. During the studies in the air force academy, eye-hand coordination is formed in two stages. The future aircraft pilots besides all-purpose physical education must practice specialist training on SAGI. Training includes: looping, aerowheel, and gyroscope. Aim of the training on the above listed apparatuses is to form eye-hand coordination during the tasks in the air. Such coordination is necessary to perform various figures in the real flight. Therefore, during the education of the future pilots, determinants of the effective ways of this important parameter of the human body functioning are sought for. Several studies of the sport psychology indicate an important role of the temperament as a factor determining human behavior during the task performance and acquiring operating skills> Polish psychologist Jan Strelau refers to the basic, relatively constant personality features which manifest themselves in the formal characteristics of the human behavior. Temperament, being initially determined by the inborn physiological mechanisms, changes in the course of maturation and some environmental factors and concentrates on the energetic level and reaction characteristics in time. Objectives. This study aimed at seeking a relationship between temperamental features and eye-hand coordination formation during training on SAGI. Material and Methods: Group of 30 students of pilotage was examined in two situations. The first assessment of the eye-hand coordination level was carried out before the beginning of a 30-hour training on SAGI. The second assessment was carried out after training completion. Training lasted for 2 hours once a week. Temperament was evaluated with The Formal Characteristics of Behavior − Temperament Inventory (FCB-TI) developed by Bogdan Zawadzki and Jan Strelau. Eye-hand coordination was assessed with a computer version of the Warsaw System of Psychological Tests. Results: It was found that the training on SAGI increased the level of eye-hand coordination in the examined students. Conclusions: Higher level of the eye-hand coordination was obtained after completion of the training. Moreover, a relationship between eye-hand coordination level and selected temperamental features was statistically significant.

Keywords: temperament, eye-hand coordination, pilot, SAGI

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Authors: Akterono Budiyati, Gita Kusumo, Teguh Putra, Fritzie Rexana, Antonius Kurniawan, Aru Sudoyo, Ahmad Utomo, Andi Utama

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The presence of the programmed death ligand-1 (PD-L1) has been used in multiple clinical trials and approved as biomarker for selecting patients more likely to respond to immune checkpoint inhibitors. However, the expression of PD-L1 is regulated in different ways, which leads to a different significance of its presence. Positive PD-L1 within tumors may result from two mechanisms, induced PD-L1 expression by T-cell presence or genetic mechanism that lead to constitutive PD-L1 expression. Amplification of PD-L1 genes was found as one of genetic mechanism which causes an increase in PD-L1 expression. In case of colorectal cancer (CRC), targeting immune checkpoint inhibitor has been recommended for patients with microsatellite instable (MSI). Although the correlation between PD-L1 expression and MSI status has been widely studied, so far the precise mechanism of PD-L1 gene activation in CRC patients, particularly in MSI population have yet to be clarified. In this present study we have profiled 61 archived formalin fixed paraffin embedded CRC specimens of patients from Medistra Hospital, Jakarta admitted in 2010 - 2016. Immunohistochemistry was performed to measure expression of PD-L1 in tumor cells as well as MSI status using antibodies against PD-L1 and MMR (MLH1, MSH2, PMS2 and MSH6), respectively. PD-L1 expression was measured on tumor cells with cut off of 1% whereas loss of nuclear MMR protein expressions in tumor cells but not in normal or stromal cells indicated presence of MSI. Subset of PD-L1 positive patients was then assessed for copy number variations (CNVs) using single Tube TaqMan Copy Number Assays Gene CD247PD-L1. We also observed KRAS mutation to profile possible genetic mechanism leading to the presence or absence of PD-L1 expression. Analysis of 61 CRC patients revealed 15 patients (24%) expressed PD-L1 on their tumor cell membranes. The prevalence of surface membrane PD-L1 was significantly higher in patients with MSI (87%; 7/8) compared to patients with microsatellite stable (MSS) (15%; 8/53) (P=0.001). Although amplification of PD-L1 gene was not found among PD-L1 positive patients, low-level amplification of PD-L1 gene was commonly observed in MSS patients (75%; 6/8) than in MSI patients (43%; 3/7). Additionally, we found 26% of CRC patients harbored KRAS mutations (16/61), so far the distribution of KRAS status did not correlate with PD-L1 expression. Our data suggest genetic mechanism through amplification of PD-L1 seems not to be the mechanism underlying upregulation of PD-L1 expression in CRC patients. However, further studies are warranted to confirm the results.

Keywords: colorectal cancer, gene amplification, microsatellite instable, programmed death ligand-1

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Authors: Varsha Salian, Shama Rao, N. Narendra, B. Mohana Kumar

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Evolving evidence proposes the existence of a highly tumorigenic subpopulation of undifferentiated, self-renewing cancer stem cells, responsible for exhibiting resistance to conventional anti-cancer therapy, recurrence, metastasis and heterogeneous tumor formation. Importantly, the mechanisms exploited by cancer stem cells to resist chemotherapy are very less understood. Oral squamous cell carcinoma (OSCC) is one of the most regularly diagnosed cancer types in India and is associated commonly with alcohol and tobacco use. Therefore, the isolation and in vitro characterization of cancer stem-like cells from patients with OSCC is a critical step to advance the understanding of the chemoresistance processes and for designing therapeutic strategies. With this, the present study aimed to establish and characterize cancer stem-like cells in vitro from OSCC. The primary cultures of cancer stem-like cell lines were established from the tissue biopsies of patients with clinical evidence of an ulceroproliferative lesion and histopathological confirmation of OSCC. The viability of cells assessed by trypan blue exclusion assay showed more than 95% at passage 1 (P1), P2 and P3. Replication rate was performed by plating cells in 12-well plate and counting them at various time points of culture. Cells had a more marked proliferative activity and the average doubling time was less than 20 hrs. After being cultured for 10 to 14 days, cancer stem-like cells gradually aggregated and formed sphere-like bodies. More spheroid bodies were observed when cultured in DMEM/F-12 under low serum conditions. Interestingly, cells with higher proliferative activity had a tendency to form more sphere-like bodies. Expression of specific markers, including membrane proteins or cell enzymes, such as CD24, CD29, CD44, CD133, and aldehyde dehydrogenase 1 (ALDH1) is being explored for further characterization of cancer stem-like cells. To summarize the findings, the establishment of OSCC derived cancer stem-like cells may provide scope for better understanding the cause for recurrence and metastasis in oral epithelial malignancies. Particularly, identification and characterization studies on cancer stem-like cells in Indian population seem to be lacking thus provoking the need for such studies in a population where alcohol consumption and tobacco chewing are major risk habits.

Keywords: cancer stem-like cells, characterization, in vitro, oral squamous cell carcinoma

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Authors: Sasibhushan Yengala, Nelson Muthu, Subramani Kanagaraj

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The abstract reports on the design related to a modular and affordable standing cum sitting device to meet the requirements of paraplegic patients of the different physiques. Paraplegic patients need the assistance of an external arrangement to the lower limbs and trunk to help patients adopt the correct posture while standing abreast gravity. This support can be from a tilt table or a standing frame which the patient can use to stay in a vertical posture. Standing frames are devices fitting to support a person in a weight-bearing posture. Commonly, these devices support and lift the end-user in shifting from a sitting position to a standing position. The merits of standing for a paraplegic patient with a spinal injury are numerous. Even when there is limited control on muscles that ordinarily support the user using the standing frame in a vertical position, the standing stance improves the blood pressure, increases bone density, improves resilience and scope of motion, and improves the user's feelings of well-being by letting the patient stand. One limitation with standing frames is that these devices are typically function definitely; cannot be used for different purposes. Therefore, users are often compelled to purchase more than one of these devices, each being purposefully built for definite activities. Another concern frequent in standing frames is manoeuvrability; it is crucial to provide a convenient adjustment scope for all users. Thus, there is a need to provide a standing frame with multiple uses that can be economical for a larger population. There is also a need to equip added readjustment means in a standing frame to lessen the shear and to accommodate a broad range of users. The proposed Versatile Standing cum Sitting Device (VSD) is designed to change from standing to a comfortable sitting position using a series of mechanisms. First, a locking mechanism is provided to lock the VSD in a standing stance. Second, a dampening mechanism is provided to make sure that the VSD shifts from a standing to a sitting position gradually when the lock mechanism gets disengaged. An adjustment option is offered for the height of the headrest via the use of lock knobs. This device can be used in clinics for rehabilitation purposes irrespective of patient's anthropometric data due to its modular adjustments. It can facilitate the patient's daily life routine while in therapy and giving the patient the comfort to sit when tired. The device also provides the availability of rehabilitation to a common person.

Keywords: paraplegic, rehabilitation, spinal cord injury, standing frame

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Authors: Ndibarefinia Tobin

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The UK construction industry has been under pressure for many years to produce economical buildings which offer value for money, not only during the construction phase, but more importantly, during the full life of the building. Whole life costing is considered as an economic analysis tool that takes into account the total investment cost in and ownership, operation and subsequent disposal of a product or system to which the whole life costing method is being applied. In spite of its importance, the practice is still crippled by the lack of tangible evidence, ‘know-how’ skills and knowledge of the practice i.e. the lack of professionals with the knowledge and training on the use of the practice in construction project, this situation is compounded by the absence of available data on whole life costing from relevant projects, lack of data collection mechanisms and so on. The aforementioned problems has forced many construction organisations to adopt project enhancement initiatives to boost their performance on the use of whole life costing techniques so as to produce economical buildings which offer value for money during the construction stage also the whole life of the building/asset. The management of knowledge in whole life costing is considered as one of the many project enhancement initiative and it is becoming imperative in the performance and sustainability of an organisation. Procuring building projects using whole life costing technique is heavily reliant on the knowledge, experience, ideas and skills of workers, which comes from many sources including other individuals, electronic media and documents. Due to the diversity of knowledge, capabilities and skills of employees that vary across an organisation, it is significant that they are directed and coordinated efficiently so as to capture, retrieve and share knowledge in order to improve the performance of the organisation. The implementation of knowledge management concept has different levels in each organisation. Measuring the maturity level of knowledge management in whole life costing practice will paint a comprehensible picture of how knowledge is managed in construction organisations. Purpose: The purpose of this study is to identify knowledge management maturity in UK construction organisations adopting whole life costing in construction project. Design/methodology/approach: This study adopted a survey method and conducted by distributing questionnaires to large construction companies that implement knowledge management activities in whole life costing practice in construction project. Four level of knowledge management maturity was proposed on this study. Findings: From the results obtained in the study shows that 34 contractors at the practiced level, 26 contractors at managed level and 12 contractors at continuously improved level.

Keywords: knowledge management, whole life costing, construction industry, knowledge

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Authors: Setareh Orak

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Wetlands are essential guardians of global ecosystems, yet they remain vulnerable to increasing human interference and environmental stress. The Miankaleh wetland in northern Iran, designated as a Ramsar Convention site, represents a critical habitat known for its rich biodiversity and essential ecological functions. Despite the existence of national and international environmental laws aimed at preserving such critical ecosystems, the regulatory frameworks in place often fall short in terms of enforcement, monitoring, and overall effectiveness. Unfortunately, this wetland is undergoing severe degradation due to overexploitation, industrial contamination, unsustainable tourism, and land-use alterations. This study aims to assess the strengths and limitations of these regulations and examine their practical impacts on Miankaleh’s ecological health. Adopting a multi-method research approach, this study relies on a combination of case study analysis, legal and literature reviews, environmental data examination, stakeholder interviews, and comparative assessments. Through these methodologies, we scrutinize current national policies, international conventions, and their enforcement mechanisms, revealing the primary areas where they fail to protect Miankaleh effectively. The analysis is supported by two satellite maps linked to our tables, offering detailed visual representations of changes in land use, vegetation, and pollution sources over recent years. By connecting these visual data with quantitative measures, the study provides a comprehensive perspective on how human activities and regulatory shortcomings are contributing to environmental degradation. In conclusion, this study’s insights into the limitations of current environmental legislation and its recommendations for enhancing both policy and public engagement underscore the urgent need for integrated, multi-level efforts in conserving the Miankaleh wetland. Through strengthened legal frameworks, better enforcement, increased public awareness, and international cooperation, the hope is to establish a model of conservation that not only preserves Miankaleh but also serves as a template for protecting similar ecologically sensitive areas worldwide.

Keywords: wetlands, tourism, industrial pollution, land use changes, Ramsar convention

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Authors: Leyla Sattarzadeh, Shahin Fathi Molk Kian, Maghsoud Peeri, Mohammadali Azarbaijani, Hasan Matin Homaee

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Inflammation by various mechanisms may cause atherosclerosis. Systemic circulating inflammatory markers such as C-reactive protein (CRP), pro-inflammatory cytokines such as Interleukin-6 (IL-6), vascular inflammatory markers as adhesion molecules like Intracellular Adhesion Molecule-1 (ICAM-1) and Vascular Cell Adhesion Molecule-1 (VCAM-1) are the predictors of cardiovascular diseases. Regarding the conflicting results about the effect of different patterns of resistance exercise training on these inflammatory markers, present study aimed to examine the effect of different patterns of eight week resistance exercise training on CRP, IL-6, ICAM-1 and VCAM-1 levels in healthy untrained women. 56 healthy volunteered untrained female university students (aged: 21 ± 3 yr., Body Mass Index: 21.5 ± 3.5 kg/m²) were selected purposefully and divided into four groups. At the end of training protocol and after subject drop during the protocol, upper body exercise training (n=11), lower body (n=12) and whole body resistance exercise training group (n=11) completed the eight weeks of training period although the control group (n=7) did anything. Blood samples gathered pre and post-experimental period and CRP, IL-6, ICAM-1 and VCAM-1 levels were evaluated using special laboratory kits, then the difference of pre and post values of each indices analyzed using one-way analysis of variance (α < 0.05). The results of one way ANOVA for difference of pre and post values of CRP, ICAM-1 and VCAM-1 showed no significant changes due to the exercise training, but there were significant differences between groups about IL-6. Tukey post- hoc test indicated that there is significant difference between the differences of pre and post values of IL-6 between lower body exercise training group and control group, and eight weeks of lower body exercise training lead to significant changes in IL-6 values. There were no changes in anthropometric indices. The findings show that the different patterns of upper, lower and whole body exercise training by involving the different amounts of muscles altered the IL-6 values in lower body exercise training group probably because of engaging the bigger amount of muscles, but showed any significant changes about CRP, ICAM-1 and VCAM-1 probably due to intensity and duration of exercise or the lower levels of these markers at baseline of healthy people.

Keywords: resistance training, C-reactive protein, interleukin-6, intracellular adhesion molecule-1, vascular cell adhesion molecule-1

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Authors: Ahmed E. Hodaib, Mohamed A. Hashem

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In engineering applications, a design has to be as fully perfect as possible in some defined case. The designer has to overcome many challenges in order to reach the optimal solution to a specific problem. This process is called optimization. Generally, there is always a function called “objective function” that is required to be maximized or minimized by choosing input parameters called “degrees of freedom” within an allowed domain called “search space” and computing the values of the objective function for these input values. It becomes more complex when we have more than one objective for our design. As an example for Multi-Objective Optimization Problem (MOP): A structural design that aims to minimize weight and maximize strength. In such case, the Pareto Optimal Frontier (POF) is used, which is a curve plotting two objective functions for the best cases. At this point, a designer should make a decision to choose the point on the curve. Engineers use algorithms or iterative methods for optimization. In this paper, we will discuss the Evolutionary Algorithms (EA) which are widely used with Multi-objective Optimization Problems due to their robustness, simplicity, suitability to be coupled and to be parallelized. Evolutionary algorithms are developed to guarantee the convergence to an optimal solution. An EA uses mechanisms inspired by Darwinian evolution principles. Technically, they belong to the family of trial and error problem solvers and can be considered global optimization methods with a stochastic optimization character. The optimization is initialized by picking random solutions from the search space and then the solution progresses towards the optimal point by using operators such as Selection, Combination, Cross-over and/or Mutation. These operators are applied to the old solutions “parents” so that new sets of design variables called “children” appear. The process is repeated until the optimal solution to the problem is reached. Reliable and robust computational fluid dynamics solvers are nowadays commonly utilized in the design and analyses of various engineering systems, such as aircraft, turbo-machinery, and auto-motives. Coupling of Computational Fluid Dynamics “CFD” and Multi-Objective Evolutionary Algorithms “MOEA” has become substantial in aerospace engineering applications, such as in aerodynamic shape optimization and advanced turbo-machinery design.

Keywords: mathematical optimization, multi-objective evolutionary algorithms "MOEA", computational fluid dynamics "CFD", aerodynamic shape optimization

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Authors: Ana Bermudez de Castro Muela, Xiomara Santos Salas, Silvia Cayon Somacarrera

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The aim of this review is to explain what is the intracranial hypotension and its main causes, and also to approach to the diagnostic management in the different clinical situations, understanding radiological findings, and physiopathological substrate. An approach to the diagnostic management is presented: what are the guidelines to follow, the different tests available, and the typical findings. We review the myelo-CT and myelo-RM studies in patients with suspected CSF fistula or hypotension of unknown cause during the last 10 years in three centers. Signs of intracranial hypotension (subdural hygromas/hematomas, pachymeningeal enhancement, venous sinus engorgement, pituitary hyperemia, and lowering of the brain) that are evident in baseline CT and MRI are also sought. The intracranial hypotension is defined as a lower opening pressure of 6 cmH₂O. It is a relatively rare disorder with an annual incidence of 5 per 100.000, with a female to male ratio 2:1. The clinical features it’s an orthostatic headache, which is defined as development or aggravation of headache when patients move from a supine to an upright position and disappear or typically relieve after lay down. The etiology is a decrease in the amount of cerebrospinal fluid (CSF), usually by loss of it, either spontaneous or secondary (post-traumatic, post-surgical, systemic disease, post-lumbar puncture etc.) and rhinorrhea and/or otorrhea may exist. The pathophysiological mechanisms of hypotension and CSF hypertension are interrelated, as a situation of hypertension may lead to hypotension secondary to spontaneous CSF leakage. The diagnostic management of intracranial hypotension in our center includes, in the case of being spontaneous and without rhinorrhea and/or otorrhea and according to necessity, a range of available tests, which will be performed from less to more complex: cerebral CT, cerebral MRI and spine without contrast and CT/MRI with intrathecal contrast. If we are in a situation of intracranial hypotension with the presence of rhinorrhea/otorrhea, a sample can be obtained for the detection of b2-transferrin, which is found in the CSF physiologically, as well as sinus CT and cerebral MRI including constructive interference steady state (CISS) sequences. If necessary, cisternography studies are performed to locate the exact point of leakage. It is important to emphasize the significance of myelo-CT / MRI to establish the diagnosis and location of CSF leak, which is indispensable for therapeutic planning (whether surgical or not) in patients with more than one lesion or doubts in the baseline tests.

Keywords: cerebrospinal fluid, neuroradiology brain, magnetic resonance imaging, fistula

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Authors: A. Díaz-Roa, P. I. Silva Junior, F. J. Bello

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Sarconesiopsis magellanica (Diptera: Calliphoridae) is a medically important necrophagous fly which is used for establishing the post-mortem interval. Dipterous maggots release diverse proteins and peptides contained in larval excretion and secretion (ES) products playing a key role in digestion. The most important mechanism for combating infection using larval therapy depends on larval ES. These larvae are protected against infection by a diverse spectrum of antimicrobial peptides (AMPs), one already known like lucifensin. Special interest in these peptides has also been aroused regarding understanding their role in wound healing since they degrade necrotic tissue and kill different bacteria during larval therapy. The action of larvae on wounds occurs through 3 mechanisms of action: removal of necrotic tissue, stimulation of granulation tissue, and antibacterial action of larval ES. Some components of the ES include calcium, urea, allantoin ammonium bicarbonate and reducing the viability of Gram positive and Gram negative bacteria. The Lucilia sericata fly larvae have been the most used, however, we need to evaluate new species that could potentially be similar or more effective than fly above. This study was thus aimed at identifying and characterizing S. magellanica AMPs contained in ES products for the first time and compared them with the common fly used L. sericata. These products were obtained from third-instar larvae taken from a previously established colony. For the first analysis, ES fractions were separate by Sep-Pak C18 disposable columns (first step). The material obtained was fractionated by RP-HPLC by using Júpiter C18 semi-preparative column. The products were then lyophilized and their antimicrobial activity was characterized by incubation with different bacterial strains. The first chromatographic analysis of ES from L. sericata gives 6 fractions with antimicrobial activity against Gram-positive bacteria Micrococus luteus, and 3 fractions with activity against Gram-negative bacteria Pseudomonae aeruginosa while the one from S. magellanica gaves 1 fraction against M. luteus and 4 against P. aeruginosa. Maybe one of these fractions could correspond to the peptide already known from L. sericata. These results show the first work for supporting further experiments aimed at validating S. magellanica use in larval therapy. We still need to search if we find some new molecules, by making mass spectrometry and ‘de novo sequencing’. Further studies are necessary to identify and characterize them to better understand their functioning.

Keywords: antimicrobial peptides, larval therapy, Lucilia sericata, Sarconesiopsis magellanica

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Authors: A. Mostaani, M. P. Pereira, B. F. Rolfe

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The increasing application of Advanced High Strength Steel (AHSS) in the automotive industry to fulfill crash requirements has introduced higher levels of wear in stamping dies and parts. Therefore, understanding wear behaviour in sheet metal forming is of great importance as it can help to reduce the high costs currently associated with tool wear. At the contact between the die and the sheet, the tips of hard tool asperities interact with the softer sheet material. Understanding the deformation that occurs during this interaction is important for our overall understanding of the wear mechanisms. For these reasons, the scratching of a perfectly plastic material by a rigid indenter has been widely examined in the literature; with finite element modelling (FEM) used in recent years to further understand the behaviour. The ‘wear mode diagram’ has been commonly used to classify the deformation regime of the soft work-piece during scratching, into three modes: ploughing, wedge formation, and cutting. This diagram, which is based on 2D slip line theory and upper bound method for perfectly plastic work-piece and rigid indenter, relates different wear modes to attack angle and interfacial strength. This diagram has been the basis for many wear studies and wear models to date. Additionally, it has been concluded that galling is most likely to occur during the wedge formation mode. However, there has been little analysis in the literature of how the material behaviour and deformation conditions associated with metal forming processes influence the wear behaviour. Therefore, the first aim of this work is first to use a commercial FEM package (Abaqus/Explicit) to build a 3D model to capture wear modes during scratching with indenters with different attack angles and different interfacial strengths. The second goal is to utilise the developed model to understand how wear modes might change in the presence of bulk deformation of the work-piece material as a result of the metal forming operation. Finally, the effect of the work-piece material properties, including strain hardening, will be examined to understand how these influence the wear modes and wear behaviour. The results show that both strain hardening and substrate deformation can change the critical attack angle at which the wedge formation regime is activated.

Keywords: finite element, pile-up, scratch test, wear mode

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Authors: Ezzati Givi M., Hoveizi E., Nezhad Marani N.

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Platinum-based anticancer therapeutics are the most widely used drugs in clinical chemotherapy but have major limitations and various side effects in clinical applications. Gonadotoxicity and sterility is one of the most common complications for cancer survivors, which seem to be drug-specific and dose-related. Therefore, many efforts have been dedicated to discovering a new structure of platinum-based anticancer agents with improved therapeutic index, fewer side effects. In this regard, new Pt(II)-phosphane complexes containing heterocyclic thionate ligands (PCTL) have been synthesized, which show more potent antitumor activities in comparison to cisplatin. Cisplatin, the best leading metal-based antitumor drug in the field, induces testicular toxicity on Leydig and Sertoli cells leading to serious side effects such as azoospermia and infertility. Therefore in the present study, we aimed to investigate the cytotoxicity effect of PCTL on mice TM4 Sertoli cells with particular emphasis on the role of autophagy in comparison to cisplatin. In this study, an MTT assay was performed to evaluate the IC50 of PCTL and to analyze the TM3 Leydig cell's viability. Cells morphology was evaluated via invert microscope and Changing in morphology for nuclei swelling or autophagic vacuoles formation were assessed by DAPI and MDC staining. Testosterone production in the culture medium was measured using an ELISA kit. Finally, the expression of Autophagy-related genes, Atg5, Beclin1 and p62, were analyzed by qPCR. Based on the obtained results by MTT, the IC50 value of PCTL was 50 μM in TM3 cells and cytotoxic effects was in a dose- and time-dependent manner. Cells morphological changes investigated by inverted microscopy, DAPI, and MDC staining which showed the cytotoxic concentrations of PCTL was significantly higher than cisplatin in the treated TM3 Leydig cells. The results of PCR showed a lack of expression of the p62, Atg5 and Beclin1 gene in TM3 cells treated with PCTL in comparison to cisplatin and control groups. It should be noted that the effects of 25 μM PCTL concentration on TM3 cells have been associated with increased testosterone production and secretion, which requires further study to explain the possible causes and involved molecular mechanisms. The results of the study showed that the PCTL had less-lethal effects on TM3 cells in comparison to cisplatin and probably did not induce autophagy in TM3 cells.

Keywords: platinum-based anticancer agents, cisplatin, Leydig TM3 cells, autophagy

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Authors: Md. Mustakimur Rahman

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On the one hand, while dealing with temporally distant international crimes (TDICs), prosecutors are likely to encounter many defendants suffering from severe physical or mental disorders. The concept of a defendant's "fitness," on the other hand, is based on the notion that an alleged perpetrator must be protected from a conviction resulting from a lack of participation or competence in making proper judgments. As a result, if a defendant is temporarily or permanently mentally ill, going through a formal criminal trial may be highly unlikely. TheExtraordinary Chambers in the Courts of Cambodia(ECCC), for example, arrested and tried IengThirth for crimes against humanity, grave breaches of the 1949 Geneva Conventions, and genocide. Still, the Trial Chamber found her incompetent to stand trial and released her in 2011. Although the prosecution had a lot of evidence against her, she was free from prosecution. It suggests that alleged war criminals may be granted immunity due to their unfitness, implying that unfitness is a hurdle to combating impunity. Given the absence of a formal criminal trial, international criminal law (ICL) should take steps to address this issue. ICL, according to Mark A. Drumbl, has yet to develop its penology; hence it borrows penological rationales from domestic criminal law. For example, international crimes tribunals such as the Nuremberg Tribunal and the Tokyo Tribunal, ad hoc tribunals have used retribution, utilitarianism, and rehabilitation as punishment justifications. On the other hand, like in the case of IengThirth, a criminal trial may not always be feasible. As a result, instead of allowing impunity, this paper proposes informal trials. This paper, for example, suggests two approaches to dealing with unfit defendants: 1) trial without punishment and 2) punishment without trial. Trial without punishment is a unique method of expressing condemnation without incarceration. "Expressivism has a broader basis than communication of punishment and sentencing," says Antony Duff. According to Drumbl, we can untangle our understanding of punishment from "the iconic preference for jailhouses" to include a larger spectrum of non-incarcerative measures like "recrimination, shame, consequence, and sanction." Non-incarcerative measures allow offenders to be punished without going through a formal criminal trial. This strategy denotes accountability for unlawful behavior. This research concludes that in many circumstances, prosecuting elderly war crimes suspects is difficult or unfeasible, but their age or illness should not be grounds for impunity. They should be accountable for their heinous activities through criminal trials or other mechanisms.

Keywords: international criminal law, international criminal punishment, international crimes tribunal, temporally distant international crimes

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Authors: Moustafa Osman Mohammed

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Integration sustainability outcomes give attention to construction ecology in the design review of urban environments to comply with Earth’s System that is composed of integral parts of the (i.e., physical, chemical and biological components). Naturally, exchange patterns of industrial ecology have consistent and periodic cycles to preserve energy flows and materials in Earth’s System. When engineering topology is affecting internal and external processes in system networks, it postulated the valence of the first-level spatial outcome (i.e., project compatibility success). These instrumentalities are dependent on relating the second-level outcome (i.e., participant security satisfaction). Construction ecology approach feedback energy from resources flows between biotic and abiotic in the entire Earth’s ecosystems. These spatial outcomes are providing an innovation, as entails a wide range of interactions to state, regulate and feedback “topology” to flow as “interdisciplinary equilibrium” of ecosystems. The interrelation dynamics of ecosystems are performing a process in a certain location within an appropriate time for characterizing their unique structure in “equilibrium patterns”, such as biosphere and collecting a composite structure of many distributed feedback flows. These interdisciplinary systems regulate their dynamics within complex structures. These dynamic mechanisms of the ecosystem regulate physical and chemical properties to enable a gradual and prolonged incremental pattern to develop a stable structure. The engineering topology of construction ecology for integration sustainability outcomes offers an interesting tool for ecologists and engineers in the simulation paradigm as an initial form of development structure within compatible computer software. This approach argues from ecology, resource savings, static load design, financial other pragmatic reasons, while an artistic/architectural perspective, these are not decisive. The paper described an attempt to unify analytic and analogical spatial modeling in developing urban environments as a relational setting, using optimization software and applied as an example of integrated industrial ecology where the construction process is based on a topology optimization approach.

Keywords: construction ecology, industrial ecology, urban topology, environmental planning

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Authors: Fatimah Abd Elghani, Raymonde Szargel, Vered Shani, Hazem Safory, Haya Hamza, Mor Savyon, Ruth Rott, Rina Bandopadhyay, Simone Engelender

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Background: PINK1 is a mitochondrial kinase mutated in some familial cases of Parkinson’s disease. Down regulation of PINK1 results in abnormal mitochondrial morphology and altered membrane potential. Although PINK1 has a predicted mitochondrial import sequence, it’s cellular, and submitochondrial localization remains unclear, in part because it is rapidly degraded. In this work, we investigated the mechanisms involved in PINK1 degradation and how this may affect PINK1 stability and function, with implications for mitochondrial function in PD. In addition, pharmacological inhibition of proteasome activity was shown to lead to PINK1 accumulation, indicating that PINK1 degradation depends on the ubiquitin-proteasome system (UPS). Methods: Using co-immunoprecipitation assays, we identified E3 ubiquitin ligase SIAH1 as a PINK1-interacting protein in HEK293 cells as well as on rat brain tissues. In addition, we determined the effect of SIAH 1, SIAH2 and Parkin on PINK1 steady-state levels by Western blot analysis, and checked their possibility to ubiquitinate and mediate PINK1 degradation through the proteasome carried out in vivo ubiquitination experiments. Results: We have obtained results showing that SIAH-1 interacts with and ubiquitinates PINK1. The ubiquitination promoted by SIAH-1 leads to the proteasomal degradation of PINK1. We confirmed these findings by knocking down SIAH-1 and observing important accumulation of PINK1 in cells. Besides, we found that SIAH-1 decreases PINK1 steady-state levels but not the E3 ligase Parkin. We also investigated the interaction of SIAH-1 with PINK1 disease mutants and its ability to promote their ubiquitination and degradation. Although, no clear difference in the ability of SIAH-1 to promote the degradation of PINK1 disease mutants was observed. It is possible that dysfunction of proteasomal activity in the disease may lead to the accumulation and aggregation of ubiquitinated PINK1 in patients with PINK1 mutations, with possible implications to the pathogenesis of PD. Conclusions: Here, we demonstrated that SIAH-1 ubiquitinates and promotes the degradation of PINK1. In addition, SIAH-1 represents now a target that may help the improvement of mitophagy in PD. Further investigations needed to understand how mitophagy is regulated by PINK1-SIAH-1 axis to provide targets for future therapeutics.

Keywords: PD, Parkinson's disease, PINK1, PTEN-induced kinase1, SIAH, seven in absentia homolog, SN, substantia nigra

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Authors: Sonia Saddiqui, Maya Marcus

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UTS STEAMpunk Girls is an educational program for young women (aged 12-16), to empower them to be more informed and active members of the 21st century workforce. With the number of STEM graduates on the decline, especially among young women, an additional aim of the program is to trial a STEAM (Science, Technology, Engineering, Arts/Humanities/Social Sciences, Mathematics), inter-disciplinary approach to improving STEM engagement. In-line with UNESCO’s recent focus on promoting ‘transversal competencies’ in future graduates, the program utilised co-design, project-based learning, entrepreneurial processes, and inter-disciplinary learning. The program consists of two phases. Taking a participatory design approach, the first phase (co-design workshops) provided valuable insight into student perspectives around engaging young women in STEM and inter-disciplinary thinking. The workshops positioned 26 young women from three schools as subject matter experts (SMEs), providing a platform for them to share their opinions, experiences and findings around the STEAM disciplines. The second (pilot) phase put the co-design phase findings into practice, with 64 students from four schools working in groups to articulate problems with real-world implications, and utilising design-thinking to solve them. The pilot phase utilised project-based learning to engage young women in entrepreneurial and STEAM frameworks and processes. Scalable program design and educational resources were trialed to determine appropriate mechanisms for engaging young women in STEM and in STEAM thinking. Across both phases, data was collected via longitudinal surveys to obtain pre-program, baseline attitudinal information, and compare that against post-program responses. Preliminary findings revealed students’ improved understanding of the STEM disciplines, industries and professions, improved awareness of STEAM as a concept, and improved understanding regarding inter-disciplinary and design thinking. Program outcomes will be of interest to high-school educators in both STEM and the Arts, Humanities and Social Sciences fields, and will hopefully inform future programmatic approaches to introducing inter-disciplinary STEAM learning in STEM curriculum.

Keywords: co-design, STEM, STEAM, project-based learning, inter-disciplinary

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Authors: Bartosz Olszanski, Zbigniew Nosal, Jacek Rokicki

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An experimental study of cold-jet (nitrogen) reaction control jet system has been carried out to investigate the flow control efficiency for low to moderate jet pressure ratios (total jet pressure p0jet over free stream static pressure in the wind tunnel p∞) and different angles of attack for infinite Mach number equal to 2. An investigation of jet influence was conducted on a flat plate geometry placed in the test section of intermittent supersonic wind tunnel of Department of Aerodynamics, WUT. Various convergent jet nozzle geometries to obtain different jet momentum ratios were tested on the same test model geometry. Surface static pressure measurements, Schlieren flow visualizations (using continuous and photoflash light source), load cell measurements gave insight into the supersonic crossflow interaction for different jet pressure and jet momentum ratios and their influence on the efficiency of side jet control as described by the amplification factor (actual to theoretical net force generated by the control nozzle). Moreover, the quasi-steady numerical simulations of flow through the same wind tunnel geometry (convergent-divergent nozzle plus test section) were performed using ANSYS Fluent basing on Reynolds-Averaged Navier-Stokes (RANS) solver incorporated with k-ω Shear Stress Transport (SST) turbulence model to assess the possible spurious influence of test section walls over the jet exit near field area of interest. The strong bow shock, barrel shock, and Mach disk as well as lambda separation region in front of nozzle were observed as images taken by high-speed camera examine the interaction of the jet and the free stream. In addition, the development of large-scale vortex structures (counter-rotating vortex pair) was detected. The history of complex static pressure pattern on the plate was recorded and compared to the force measurement data as well as numerical simulation data. The analysis of the obtained results, especially in the wake of the jet showed important features of the interaction mechanisms between the lateral jet and the flow field.

Keywords: flow visualization techniques, pressure measurements, reaction control jet, supersonic cross flow

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Authors: Abhishek Ranka

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Rock-cut Architecture is a manifestation of human endurance in constructing magnificent structures by sculpting and cutting entire hills. Cave Architecture in India form an important part of rock-cut development and is among the most prolific examples of rock-cut architecture in the world. There are more than 1500 rock-cut caves in various regions of India. Among them mostly are located in western India, more particularly in the state of Maharashtra. Some of the rock-cut caves are located in the central region of India, which is presently known as Malawa (Madhya Pradesh). The region is dominated by the vidhyachal hill ranges toward the west, dotted with the coarse laterite rock. Dhamnar Caves have been excavated in the central region of Mandsaur Dist. With a combination of shared sacred faiths. The earliest rock-cut activity began in the north, in Bihar, where caves were excavated in the Barabar and the Nagarjuni hills during the Mauryan period (3rd century BCE). The rock-cut activity then shifts to the central part of India in Madhya Pradesh, where the caves at Dhamnar, Bagh, Udayagiri, Poldungar, etc. excavated between 3rdto 9ᵗʰ CE. The rock-cut excavation continued to flourish in Madhya Pradesh till 10ᵗʰ century CE, simultaneously with monolithic Hindu temples. Dhamnar caves fall into four architectural typologies: the Lena caves, Chaitya caves, Viharas & Lena-Chaityagriha caves. The Buddhist rock-cutting activity in central India is divisible into two phases. In the first phase (2ndBCE-3rd CE), the Buddha image is conspicuously absent. After a lapse of about three centuries, activity begins again, and the Buddha images this time are carved. The former group belongs to the Hinayana (Lesser Vehicle) phase and the latter to the Mahayana (Greater Vehicle). Dhamnar caves has an elaborate facades, pillar capitals, and many more creative sculptures in various postures. These caves were excavated against the background of invigorating trade activities and varied socio-religious or Socio Cultural contexts. These caves also highlights the wealthy and varied patronage provided by the dynasties of the past. This paper speaks about the appraisal of the rock cut mechanisms, design strategies, and approaches while promoting a scope for further research in conservation practices. Rock-cut sites, with their physical setting and various functional spaces as a sustainable habitat for centuries, has a heritage footprint with a researchquotient.

Keywords: rock-cut architecture, buddhism, hinduism, Iconography, and architectural typologies, Jainism

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Authors: Jana Soler Libran

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The primary aim of this paper is to analyze the relationship between power and knowledge suggested in Michel Foucault's theory. Taking into consideration the role of power in knowledge production, the goal is to evaluate to what extent genealogy can be presented as a practical method for epistemic resistance. To do so, the methodology used consists of a revision of Foucault’s literature concerning the topic discussed. In this sense, conceptual analysis is applied in order to understand the effect of the double dimension of power on knowledge production. In its negative dimension, power is conceived as an organ of repression, vetoing certain instances of knowledge considered deceitful. In opposition, in its positive dimension, power works as an organ of the production of truth by means of institutionalized discourses. This double declination of power leads to the first main findings of the present analysis: no truth or knowledge can lie outside power’s action, and power is constituted through accepted forms of knowledge. To second these statements, Foucaultian discourse formations are evaluated, presenting external exclusion procedures as paradigmatic practices to demonstrate how power creates and shapes the validity of certain epistemes. Thus, taking into consideration power’s mechanisms to produce and reproduce institutionalized truths, this paper accounts for the Foucaultian praxis of genealogy as a method to reveal power’s intention, instruments, and effects in the production of knowledge. In this sense, it is suggested to consider genealogy as a practice which, firstly, reveals what instances of knowledge are subjugated to power and, secondly, promotes aforementioned peripherical discourses as a form of epistemic resistance. In order to counterbalance these main theses, objections to Foucault’s work from Nancy Fraser, Linda Nicholson, Charles Taylor, Richard Rorty, Alvin Goldman, or Karen Barad are discussed. In essence, the understanding of the Foucaultian relationship between power and knowledge is essential to analyze how contemporary discourses are produced by both traditional institutions and new forms of institutionalized power, such as mass media or social networks. Therefore, Michel Foucault's practice of genealogy is relevant, not only for its philosophical contribution as a method to uncover the effects of power in knowledge production but also because it constitutes a valuable theoretical framework for political theory and sociological studies concerning the formation of societies and individuals in the contemporary world.

Keywords: epistemic resistance, Foucault’s genealogy, knowledge, power, truth

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Authors: Qirat Naz, Abasiokpon Udoakah

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In developed countries, global migration is diversifying. The minority ethnic population, including refugees and asylum seekers who, fled their home countries due to war, terrorism, oppression, or natural disasters, and returning home is dangerous for them. They need sanctuary and peaceful environment in host countries. They begin the process of acculturation, in which a person adopts the social mores and behavioral patterns of the dominant culture, yet they still have unique multicultural needs that the dominant society fails to address. The aim of this research is to provide a holistic understanding of the living experiences of a minority population, particularly migrants, including asylum seekers and refugees, in the health and social care system of South Wales. The purpose of this study is to investigate three research objectives: the multicultural health care needs of minorities, as well as the barriers to seeking health and social care facilities. There are Welsh policies for promoting cultural competence in the health and social care sectors; this research will explore the implications and impact of these policies on the target population. This research study will be conducted using qualitative research methods, tools, and techniques. This research is an inductive approach to coming up with a grounded theory. The sample will be divided into two groups: migrants and professionals providing any kind of services to migrants; each group will contain 30 participants. Interpretive phenomenological analysis would be utilized during the process of coding and developing the main themes of this research. The positionality of the researcher would be minimized by unloaded and open-ended questions, researcher’s work experience in research, continuous evaluation of her positionality, daily base reflection of fieldwork and seeking the help of male and female gatekeepers. The research findings would be based on emic perspective, and by documenting the emic perspective of minorities, this research will contribute to the knowledge of appropriate channels, including organizations, academics, and policymakers, to discover possible solutions and coping mechanisms to deal with the challenges and meet the multicultural demands of minorities. This research will provide a more in-depth understanding of minorities and will help to promote the diversity of health and social care in South Wales.

Keywords: migration, migrants, cultural competence, cultural barriers, healthcare challenges

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