Search results for: sterol regulatory element binding proteins

Authors: Mahani Razali, Nordin Mamat

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The purpose of this research is to identify the teacher’s role and parent’s participation to develop children`s socio emotion through play activities. This research is based on three main objectives which are to identify children`s socio emotion during play activities, teacher’s role and parent’s participation to develop children`s socio emotion. This qualitative study was carried out among 25 pre-school children, three teachers and three parents as the research sample. On the other hand, parent’s support was obtained from their discussions, supervisions and communication at home. The data collection procedures involved structured observation which was to identify socio emotional development element among pre-school children through play activities; as for semi-structured interviews, it was done to study the perception of the teachers and parents on the acquired socio emotional development among the children. Besides, documentation analysis method was used as to triangulate acquired information with observations and interviews. In this study, the qualitative data analysis was tabulated in descriptive manner with frequency and percentage format. This study primarily focused on five main socio emotional elements among the pre-school children: 1) Cooperation, 2) Confidence and Courage, 3) Ability to communicate, 4) patience, and 5) Tolerance. The findings of this study were presented in the form of case to case manner from the researches sample. Findings revealed that the children showed positive outcomes on the socio emotional development during their play. Both teachers and parents showed positive perceptions towards the acquired socio emotional development during their play activities. In conclusion, this research summarizes that teacher’s role and parent’s support can improve children`s socio emotional development through play activities. As a whole, this research highlighted the significance of play activities as to stimulate socio emotional development among the pre-school children.

Keywords: social emotional, children, play activities, stimulating

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Authors: Adnan I. O. Zaid

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Zinc aluminum alloys are versatile materials which are widely used in manufacturing several parts in the automobile and aircraft industries. The effect of grain refinement of these alloys by rare earth elements on their mechanical characteristics is scarce. The equal channel angular pressing is relatively recent method for producing severe plastic deformation in materials subjected to it resulting in refinement of their structure and enhancement of their mechanical characteristics. The phase diagram of these alloys indicates that large dendrites of large grain size can be formed during their solidification of the cast which tends to deteriorate their mechanical strength and surface quality. To overcome this problem they are normally grain refined by either titanium or titanium + boron to their melt prior to solidification. In this paper, comparison between the effect of adding either titanium, (Ti), titanium+boron, (Ti+B), or Molybdenum, Mo, to zinc-aluminum22, alloy, (ZA22) on its metallurgical and mechanical characteristics in the cast condition and after pressing by the ECAP process is investigated. It was found that addition of either Ti, Ti+B, or Mo to the ZA22 alloy in the cast condition resulted in refining of their structure being more refined by the addition of Mo, then .Ti+B and less refining by Ti addition. Furthermore, the ECAP process resulted in further refinement of the alloy micro structure except in case of Ti+B addition where poisoning i.e. coarsening of the grains has occurred. Regarding the addition of these element on the mechanical behavior; it was found that addition of Ti Or Ti+B resulted in little enhancement of the alloy strength factor and its flow stress at 20% true strain; whereas, the addition of resulted in deteriorating of its mechanical behavior as % decrease in the strength factor and % in its flow stress of 20%. As for the strain hardening index; addition of any of these elements resulted in decreasing the strain hardening index.

Keywords: addition, grain refinement, mechanical characteristics, microstructure, rare earth elements, ZA-22, Zinc- aluminum alloy

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Authors: Farrah Putri Salmanida, Mei-Li Wu, Rika Wahyuningtyas, Wen-Bin Chung, Hso-Chi Chaung, Ko-Tung Chang

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Within the field of immunotherapy, oncolytic virotherapy (OVT) employs dual approaches that directly eliminate tumor cells while preserving healthy ones and indirectly reprogram the tumor microenvironment (TME) to elicit antitumor responses. Within the TME, tumor associated macrophages (TAMs) manifest characteristics akin to those of anti-inflammatory M2 macrophages, thus earning the designation of M2-like TAMs. In prior research, two antigens denoted as A1 (g6Ld10T) and A3 (ORF6L5), derived from a complete sequence of ORF5 with partial sequence of ORF6 in Porcine Reproductive and Respiratory Syndrome Virus Genotype 2 (PRRSV-2), demonstrated the capacity to repolarize M2-type porcine alveolar macrophages (PAMs) into M1 phenotypes. In this study, we sought for utilizing OVT strategies by introducing A1 or A3 on TAMs to endow them with the anti-tumor traits of M1 macrophages while retaining their capacity to target cancer cells. Upon exposing human THP-1-derived M2 macrophages to a cross-species test with 2 µg/ml of either A1 or A3 for 24 hours, real time PCR revealed that A3, but not A1, treated cells exhibited upregulated gene expressions of M1 markers (CCR7, IL-1ß, CCL2, Cox2, CD80). These cells reacted to virus-derived antigen, as evidenced by increased expression of pattern-recognition receptors TLR3, TLR7, and TLR9, subsequently providing feedback in the form of type I interferon responses like IFNAR1, IFN-ß, IRF3, IRF7, OAS1, Mx1, and ISG15. Through an MTT assay, only after 15 µg/ml of A3 treatment could the cell viability decrease, with a predicted IC50 of 16.96 µg/ml. Interestingly, A3 caused dose-dependent toxicity to a rat C6 glial cancer cell line even at doses as low as 2.5 µg/ml and reached its IC50 at 9.419 µg/ml. Using Annexin V/7AAD staining and PCR test, we deduced that a significant proportion of C6 cells were undergoing the early apoptosis phase predominantly through the intrinsic apoptosis cascade involving Bcl-2 family proteins. Following this stage, we conducted a test on A3’s repolarization ability, which revealed a significant rise in M1 gene expression markers, such as TNF, CD80, and IL-1ß, in M2-like TAMs generated in vitro from murine RAW264.7 macrophages grown with conditioned medium of 4T1 breast cancer cells. This was corroborated by the results of transcriptome analysis, which revealed that the primary subset among the top 10 to top 30 significantly upregulated differentially expressed genes (DEGs) dominantly consisted of M1 macrophages profiles, including Ccl3, Ccl4, Csf3, TNF, Bcl6b, Stc1, and Dusp2. Our findings unveiled the remarkable potential of the PRRSV-derived antigen A3 to repolarize macrophages while also being capable of selectively inducing apoptosis in cancerous cells. While further in vivo study is needed for A3, it holds promise as an adjuvant by its dual effects in cancer therapy modalities.

Keywords: cancer cell apoptosis, interferon responses, macrophage repolarization, recombinant protein

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Authors: Veenu Bala, Yashpal S. Chhonker, Bhavana Kushwaha, Rabi S. Bhatta, Gopal Gupta, Vishnu L. Sharma

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According to UNAIDS 2013 estimate nearly 52% of all individuals living with HIV are now women of reproductive age (15–44 years). Seventy-five percent cases of HIV acquisition are through heterosexual contacts and sexually transmitted infections (STIs), attributable to unsafe sexual behaviour. Each year, an estimated 500 million people acquire atleast one of four STIs: chlamydia, gonorrhoea, syphilis and trichomoniasis. Trichomonas vaginalis (TV) is exclusively sexually transmitted in adults, accounting for 30% of STI cases and associated with pelvic inflammatory disease (PID), vaginitis and pregnancy complications in women. TV infection resulted in impaired vaginal milieu, eventually favoring HIV transmission. In the absence of an effective prophylactic HIV vaccine, prevention of new infections has become a priority. It was thought worthwhile to integrate HIV prevention and reproductive health services including unintended pregnancy protection for women as both are related with unprotected sex. Initially, nonoxynol-9 (N-9) had been proposed as a spermicidal agent with microbicidal activity but on the contrary it increased HIV susceptibility due to surfactant action. Thus, to accomplish an urgent need of novel woman controlled non-detergent microbicidal spermicides benzenepropanamine analogues have been synthesized. At first, five benzenepropanamine-dithiocarbamate hybrids have been synthesized and evaluated for their spermicidal, anti-Trichomonas and anti-fungal activities along with safety profiling to cervicovaginal cells. In order to further enhance the scope of above study benzenepropanamine was hybridized with thiourea as to introduce anti-HIV potential. The synthesized hybrid molecules were evaluated for their reverse transcriptase (RT) inhibition, spermicidal, anti-Trichomonas and antimicrobial activities as well as their safety against vaginal flora and cervical cells. simulated vaginal fluid (SVF) stability and pharmacokinetics of most potent compound versus N-9 was examined in female Newzealand (NZ) rabbits to observe its absorption into systemic circulation and subsequent exposure in blood plasma through vaginal wall. The study resulted in the most promising compound N-butyl-4-(3-oxo-3-phenylpropyl) piperazin-1-carbothioamide (29) exhibiting better activity profile than N-9 as it showed RT inhibition (72.30 %), anti-Trichomonas (MIC, 46.72 µM against MTZ susceptible and MIC, 187.68 µM against resistant strain), spermicidal (MEC, 0.01%) and antifungal activity (MIC, 3.12–50 µg/mL) against four fungal strains. The high safety against vaginal epithelium (HeLa cells) and compatibility with vaginal flora (lactobacillus), SVF stability and least vaginal absorption supported its suitability for topical vaginal application. Docking study was performed to gain an insight into the binding mode and interactions of the most promising compound, N-butyl-4-(3-oxo-3-phenylpropyl) piperazin-1-carbothioamide (29) with HIV-1 Reverse Transcriptase. The docking study has revealed that compound (29) interacted with HIV-1 RT similar to standard drug Nevirapine. It may be concluded that hybridization of benzenepropanamine and thiourea moiety resulted into novel lead with multiple activities including RT inhibition. A further lead optimization may result into effective vaginal microbicides having spermicidal, anti-Trichomonas, antifungal and anti-HIV potential altogether with enhanced safety to cervico-vaginal cells in comparison to Nonoxynol-9.

Keywords: microbicidal, nonoxynol-9, reverse transcriptase, spermicide

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Authors: Maryam Hajrezaie, Mahmood Ameen Abdulla, Nazia Abdul Majid, Hapipa Mohd Ali, Pouya Hassandarvish, Maryam Zahedi Fard

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Background: Colon cancer is one of the most prevalent cancers in the world and is the third leading cause of death among cancers in both males and females. The incidence of colon cancer is ranked fourth among all cancers but varies in different parts of the world. Cancer chemoprevention is defined as the use of natural or synthetic compounds capable of inducing biological mechanisms necessary to preserve genomic fidelity. Andrographolide is the major labdane diterpenoidal constituent of the plant Andrographis paniculata (family Acanthaceae), used extensively in the traditional medicine. Extracts of the plant and their constituents are reported to exhibit a wide spectrum of biological activities of therapeutic importance. Laboratory animal model studies have provided evidence that Andrographolide play a role in inhibiting the risk of certain cancers. Objective: Our aim was to evaluate the chemopreventive efficacy of the Andrographolide in the AOM induced rat model. Methods: To evaluate inhibitory properties of andrographolide on colonic aberrant crypt foci (ACF), five groups of 7-week-old male rats were used. Group 1 (control group) were fed with 10% Tween 20 once a day, Group 2 (cancer control) rats were intra-peritoneally injected with 15 mg/kg Azoxymethan, Gropu 3 (drug control) rats were injected with 15 mg/kg azoxymethan and 5-Flourouracil, Group 4 and 5 (experimental groups) were fed with 10 and 20 mg/kg andrographolide each once a day. After 1 week, the treatment group rats received subcutaneous injections of azoxymethane, 15 mg/kg body weight, once weekly for 2 weeks. Control rats were continued on Tween 20 feeding once a day and experimental groups 10 and 20 mg/kg andrographolide feeding once a day for 8 weeks. All rats were sacrificed 8 weeks after the azoxymethane treatment. Colons were evaluated grossly and histopathologically for ACF. Results: Administration of 10 mg/kg and 20 mg/kg andrographolide were found to be effectively chemoprotective, as evidenced microscopily and biochemically. Andrographolide suppressed total colonic ACF formation up to 40% to 60%, respectively, when compared with control group. Pre-treatment with andrographolide, significantly reduced the impact of AOM toxicity on plasma protein and urea levels as well as on plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and gamma-glutamyl transpeptidase (GGT) activities. Grossly, colorectal specimens revealed that andrographolide treatments decreased the mean score of number of crypts in AOM-treated rats. Importantly, rats fed andrographolide showed 75% inhibition of foci containing four or more aberrant crypts. The results also showed a significant increase in glutathione (GSH), superoxide dismutase (SOD), nitric oxide (NO), and Prostaglandin E2 (PGE2) activities and a decrease in malondialdehyde (MDA) level. Histologically all treatment groups showed a significant decrease of dysplasia as compared to control group. Immunohistochemical staining showed up-regulation of Hsp70 and down-regulation of Bax proteins. Conclusion: The current study demonstrated that Andrographolide reduce the number of ACF. According to these data, Andrographolide might be a promising chemoprotective activity, in a model of AOM-induced in ACF.

Keywords: chemopreventive, andrographolide, colon cancer, aberrant crypt foci (ACF)

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Authors: Yasser Aboel-Magd

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This research addresses the critical issue of accessibility for individuals with special needs and the broader implications of disability on one's ability to lead an independent and integrated life within society. It highlights the consequences of injury, illness, or disability not only on the physical level but also on psychological, social, educational, economic, and functional aspects of life. The study emphasizes the importance of inclusive design in urban spaces, reflecting on how a society's treatment of individuals with disabilities serves as a measure of its progress. The research delves into the challenges faced by people with special needs in the Kingdom, where, despite advancements in various sectors, there is a noticeable lack of accommodating public opportunities for this significant demographic. It argues for the necessity of a Saudi building code that considers the needs of a diverse population during the design phase. The paper discusses the role of urban space as a fundamental element in urban formation and its impact on the societal integration of individuals with special needs. The study explores a variety of inclusive design principles, ranging from physical features like ramps and tactile paving to digital and cognitive accessibility measures such as screen readers, closed captions, plain language, and visual aids. It also considers the impact of wayfinding and appropriate lighting design on the orientation and assistance of individuals within urban spaces at the lowest cost. The researchers connect inclusive design with sustainable practices, advocating for environments that are not only environmentally friendly but also adaptable and lasting. The paper concludes with the assertion that the integration of accessibility, universal design, and sustainability signifies a society's commitment to inclusivity and the empowerment of all individuals, paving the way for a future where everyone can participate fully and independently in society.

Keywords: accessibility, inclusive design, Saudi building code, disability inclusion, socioeconomic progress

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Authors: Reza Miresmaeili, Asghar Heydari Astaraee, Fereshteh Dolati

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In the present study, an analytical model based on dislocation density model was developed to simulate grain refinement in surface mechanical attrition treatment (SMAT). The correlation between SMAT time and development in plastic strain on one hand, and dislocation density evolution, on the other hand, was established to simulate the grain refinement in SMAT. A dislocation density-based constitutive material law was implemented using VUHARD subroutine. A random sequence of shots is taken into consideration for multiple impacts model using Python programming language by utilizing a random function. The simulation technique was to model each impact in a separate run and then transferring the results of each run as initial conditions for the next run (impact). The developed Finite Element (FE) model of multiple impacts describes the coverage evolution in SMAT. Simulations were run to coverage levels as high as 4500%. It is shown that the coverage implemented in the FE model is equal to the experimental coverage. It is depicted that numerical SMAT coverage parameter is adequately conforming to the well-known Avrami model. Comparison between numerical results and experimental measurements for residual stresses and depth of deformation layers confirms the performance of the established FE model for surface engineering evaluations in SMA treatment. X-ray diffraction (XRD) studies of grain refinement, including resultant grain size and dislocation density, were conducted to validate the established model. The full width at half-maximum in XRD profiles can be used to measure the grain size. Numerical results and experimental measurements of grain refinement illustrate good agreement and show the capability of established FE model to predict the gradient microstructure in SMA treatment.

Keywords: dislocation density, grain refinement, severe plastic deformation, simulation, surface mechanical attrition treatment

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Authors: Aleksandra Bylinska, Samantha Slight-Webb, Kevin Thomas, Miles Smith, Susan Macwana, Nicolas Dominguez, Eliza Chakravarty, Joan T. Merrill, Judith A. James, Joel M. Guthridge

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Background: Systemic Lupus Erythematosus (SLE) is an interferon-related autoimmune disease characterized by B cell dysfunction. One of the main hallmarks is a loss of tolerance to self-antigens leading to increased levels of autoantibodies against nuclear components (ANAs). However, up to 20% of healthy ANA+ individuals will not develop clinical illness. SLE is more prevalent among women and minority populations (African, Asian American and Hispanics). Moreover, African Americans have a stronger interferon (IFN) signature and develop more severe symptoms. The exact mechanisms involved in ethnicity-dependent B cell dysregulation and the progression of autoimmune disease from ANA+ healthy individuals to clinical disease remains unclear. Methods: Peripheral blood mononuclear cells (PBMCs) from African (AA) and European American (EA) ANA- (n=12), ANA+ (n=12) and SLE (n=12) individuals were assessed by multimodal scRNA-Seq/CITE-Seq methods to examine differential gene signatures in specific B cell subsets. Library preparation was done with a 10X Genomics Chromium according to established protocols and sequenced on Illumina NextSeq. The data were further analyzed for distinct cluster identification and differential gene signatures in the Seurat package in R and pathways analysis was performed using Ingenuity Pathways Analysis (IPA). Results: Comparing all subjects, 14 distinct B cell clusters were identified using a community detection algorithm and visualized with Uniform Manifold Approximation Projection (UMAP). The proportion of each of those clusters varied by disease status and ethnicity. Transitional B cells trended higher in ANA+ healthy individuals, especially in AA. Ribonucleoprotein high population (HNRNPH1 elevated, heterogeneous nuclear ribonucleoprotein, RNP-Hi) of proliferating Naïve B cells were more prevalent in SLE patients, specifically in EA. Interferon-induced protein high population (IFIT-Hi) of Naive B cells are increased in EA ANA- individuals. The proportion of memory B cells and plasma cells clusters tend to be expanded in SLE patients. As anticipated, we observed a higher signature of cytokine-related pathways, especially interferon, in SLE individuals. Pathway analysis among AA individuals revealed an NRF2-mediated Oxidative Stress response signature in the transitional B cell cluster, not seen in EA individuals. TNFR1/2 and Sirtuin Signaling pathway genes were higher in AA IFIT-Hi Naive B cells, whereas they were not detected in EA individuals. Interferon signaling was observed in B cells in both ethnicities. Oxidative phosphorylation was found in age-related B cells (ABCs) for both ethnicities, whereas Death Receptor Signaling was found only in EA patients in these cells. Interferon-related transcription factors were elevated in ABCs and IFIT-Hi Naive B cells in SLE subjects of both ethnicities. Conclusions: ANA+ healthy individuals have altered gene expression pathways in B cells that might drive apoptosis and subsequent clinical autoimmune pathogenesis. Increases in certain regulatory pathways may delay progression to SLE. Further, AA individuals have more elevated activation pathways that may make them more susceptible to SLE.

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Authors: Mehmet Akköse

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Concern about seismic safety of concrete dams have been growing around the world, partly because the population at risk in locations downstream of major dams continues to expand and also because it is increasingly evident that the seismic design concepts in use at the time most existing dams were built were inadequate. Most of the investigations in the past have been conducted on large dams, typically above 100m high. A large number of concrete dams in our country and in other parts of the world are less than 50m high. Most of these dams were usually designed using pseudo-static methods, ignoring the dynamic characteristics of the structure as well as the characteristics of the ground motion. Therefore, it is important to carry out investigations on seismic behavior this category of dam in order to assess and evaluate the safety of existing dams and improve the knowledge for different high dams to be constructed in the future. In this study, size effects on structural performance of concrete gravity dams subjected to near and far-fault ground motions are investigated including dam-water-foundation interaction. For this purpose, a benchmark problem proposed by ICOLD (International Committee on Large Dams) is chosen as a numerical application. Structural performance of the dam having five different heights is evaluated according to damage criterions in USACE (U.S. Army Corps of Engineers). It is decided according to their structural performance if non-linear analysis of the dams requires or not. The linear elastic dynamic analyses of the dams to near and far-fault ground motions are performed using the step-by-step integration technique. The integration time step is 0.0025 sec. The Rayleigh damping constants are calculated assuming 5% damping ratio. The program NONSAP modified for fluid-structure systems with the Lagrangian fluid finite element is employed in the response calculations.

Keywords: concrete gravity dams, Lagrangian approach, near and far-fault ground motion, USACE damage criterions

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Authors: Anierudh Vishwanathan

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This paper suggests a new design of the crankshaft system that would help to use a low revving engine for applications requiring the use of a high revving engine operating at the same power by converting the extra or unnecessary torque obtained from a low revving engine into angular velocity of the crankshaft of the engine hence, improve the fuel economy of the vehicle because of the fact that low revving engines run more effectively on lean air fuel mixtures accompanied with less wear and tear of the engine due to lesser rubbing of the piston rings with the cylinder walls. If the crankshaft with the proposed design is used in a low revving engine, then it will give the same torque and speed as that given by a high revving engine operating at the same power but the new engine will give better fuel economy. Hence the new engine will give the benefits of a low revving engine as well as a high revving engine. The proposed crankshaft design will be achieved by changing the design of the crankweb in such a way that it functions both as a counterweight as well as a helical gear that can transfer power to the secondary gear shaft which will be incorporated in the crankshaft system. The crankshaft and the secondary gear shaft will be operating at an overdrive ratio. The crankshaft will now be a two shaft system instead of a single shaft system. The newly designed crankshaft will be mounted on the bearings instead of being connected to the flywheel of the engine. This newly designed crankshaft will transmit power to the secondary shaft which will rotate the flywheel and then the rotary motion will be transmitted to the transmission system as usual. In this design, the concept of power transmission will be incorporated in the crankshaft system. In the paper, the crankshaft and the secondary shafts have been designed in such a way that at any instant of time only half the number of crankwebs will be meshed with the secondary shaft. For example, during one revolution of the crankshaft, if for the first half of revolution; first, second, seventh and eighth crankwebs are meshing with the secondary shaft then for the next half revolution, third, fourth, fifth and sixth crankwebs will mesh with the secondary shaft. This paper also analyses the proposed crankshaft design for safety against fatigue failure. Finite element analysis of the crankshaft has been done and the resultant stresses have been calculated.

Keywords: low revving, high revving, secondary shaft, partial meshing

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Authors: Deepak Loura

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Production and productivity of several crops in the country continue to be adversely affected by biotic (e.g., Insect-pests and diseases) and abiotic (e.g., water temperature and salinity) stresses. Over-dependence on pesticides and other chemicals is economically non-viable for the resource-poor farmers of our country. Further, pesticides can potentially affect human and environmental safety. While traditional breeding techniques and proper- management strategies continue to play a vital role in crop improvement, we need to judiciously use biotechnology approaches for the development of genetically modified crops addressing critical problems in the improvement of crop plants for sustainable agriculture. Modern biotechnology can help to increase crop production, reduce farming costs, and improve food quality and the safety of the environment. Genetic engineering is a new technology which allows plant breeders to produce plants with new gene combinations by genetic transformation of crop plants for improvement of agronomic traits. Advances in recombinant DNA technology have made it possible to have genes between widely divergent species to develop genetically modified or genetically engineered plants. Plant genetic engineering provides the strength to harness useful genes and alleles from indigenous microorganisms to enrich the gene pool for developing genetically modified (GM) crops that will have inbuilt (inherent) resistance to insect pests, diseases, and abiotic stresses. Plant biotechnology has made significant contributions in the past 20 years in the development of genetically engineered or genetically modified crops with multiple benefits. A variety of traits have been introduced in genetically engineered crops which include (i) herbicide resistance. (ii) pest resistance, (iii) viral resistance, (iv) slow ripening of fruits and vegetables, (v) fungal and bacterial resistance, (vi) abiotic stress tolerance (drought, salinity, temperature, flooding, etc.). (vii) quality improvement (starch, protein, and oil), (viii) value addition (vitamins, micro, and macro elements), (ix) pharmaceutical and therapeutic proteins, and (x) edible vaccines, etc. Multiple genes in transgenic crops can be useful in developing durable disease resistance and a broad insect-control spectrum and could lead to potential cost-saving advantages for farmers. The development of transgenic to produce high-value pharmaceuticals and the edible vaccine is also under progress, which requires much more research and development work before commercially viable products will be available. In addition, molecular-aided selection (MAS) is now routinely used to enhance the speed and precision of plant breeding. Newer technologies need to be developed and deployed for enhancing and sustaining agricultural productivity. There is a need to optimize the use of biotechnology in conjunction with conventional technologies to achieve higher productivity with fewer resources. Therefore, genetic modification/ engineering of crop plants assumes greater importance, which demands the development and adoption of newer technology for the genetic improvement of crops for increasing crop productivity.

Keywords: biotechnology, plant genetic engineering, genetically modified, biotic, abiotic, disease resistance

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Authors: Hassan Beigi Rizi, Harold Auradou, Lamine Hattali

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Various industries, including civil engineering, automotive, aerospace, and biomedical fields, are currently seeking novel and innovative high-performance lightweight materials to reduce energy consumption. Inspired by the structure of Euplectella Aspergillum Glass Sponges (EA-sponge), 2D unit cells were created and fabricated using a Fused Filament Fabrication (FFF) process with Polylactic acid (PLA) filaments. The stiffness and strength of bio-inspired EA-sponge lattices were investigated both experimentally and numerically under uniaxial tensile loading and are compared to three standard square lattices with diagonal struts (Designs B and C) and non-diagonal struts (Design D) reinforcements. The aim is to establish predictive scaling laws models and examine the deformation mechanisms involved. The results indicated that for the EA-sponge structure, the relative moduli and yield strength scaled linearly with relative density, suggesting that the deformation mechanism is stretching-dominated. The Finite element analysis (FEA), with periodic boundary conditions for volumetric homogenization, confirms these trends and goes beyond the experimental limits imposed by the FFF printing process. Therefore, the stretching-dominated behavior, investigated from 0.1 to 0.5 relative density, demonstrate that the study of EA-sponge structure can be exploited for the realization of square lattice topologies that are stiff and strong and have attractive potential for lightweight structural applications. However, the FFF process introduces an accuracy limitation, with approximately 10% error, making it challenging to print structures with a relative density below 0.2. Future work could focus on exploring the impact of different printing materials on the performance of EA-sponge structures.

Keywords: bio-inspiration, lattice structures, fused filament fabrication, scaling laws

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Authors: Elena Mugarza, Stephanie Glendinning, Ross Stirling, Colin Davies

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The effects of climate change and increased rainfall events on UK-based infrastructure are observable, with an increasing number being reported on in the national press. The fatal derailment at Stonehaven in 2020 prompted a wider review of Network Rail-owned earthworks assets. The event was indicated by the Rail Accident Investigation Branch (RAIB) to be caused by mis-installed drainage on the adjacent cutting. The slope failure on Snake Pass (public highway A57) was reportedly caused by significant water ingress following numerous storm events and resulted in the road’s closure for several months. This problem is only projected to continue with greater intensity and more prolonged rainfall events forecasted in the future. Subsequently, this project is designed to evaluate effective drainage trench design within infrastructure embankments, considering the capillary barrier phenomenon that may govern their deterioration and resultant failure. Theoretically, the differential between grain sizes of the embankment clays and gravels, customarily used in drainage trenches, would have a limiting effect on infiltration. As such, it is anticipated that the inclusion of an additional material with an intermediate grain size should improve the hydraulic conductivity across the drainage boundary. Multiple drainage designs will be studied using instrumentation within the drain and surrounding clays. Data from the real-world installation at the BIONICS embankment will be collected and compared with laboratory and Finite Element (FE) simulations. This research aims to reduce the risk of infrastructure slope failures by improving the resilience of earthwork drainage and lessening the consequential impact on transportation networks.

Keywords: earthworks, slope drainage, transportation slopes, deterioration, capillary barriers, field study

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Authors: Ginger Egberts, Marianne Schaaphok, Fred Vermolen, Paul van Zuijlen

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A few years ago, a promising morphoelastic model was developed for the simulation of contraction formation after burn injuries. Contraction can lead to a serious reduction in physical mobility, like a reduction in the range-of-motion of joints. If this is the case in a healing burn wound, then this is referred to as a contracture that needs medical intervention. The morphoelastic model consists of a set of partial differential equations describing both a chemical part and a mechanical part in dermal wound healing. These equations are solved with the numerical finite element method (FEM). In this method, many calculations are required on each of the chosen elements. In general, the more elements, the more accurate the solution. However, the number of elements increases rapidly if simulations are performed in 2D and 3D. In that case, it not only takes longer before a prediction is available, the computation also becomes more expensive. It is therefore important to investigate alternative possibilities to generate the same results, based on the input parameters only. In this study, a surrogate neural network has been designed to mimic the results of the one-dimensional morphoelastic model. The neural network generates predictions quickly, is easy to implement, and there is freedom in the choice of input and output. Because a neural network requires extensive training and a data set, it is ideal that the one-dimensional FEM code generates output quickly. These feed-forward-type neural network results are very promising. Not only can the network give faster predictions, but it also has a performance of over 99%. It reports on the relative surface area of the wound/scar, the total strain energy density, and the evolutions of the densities of the chemicals and mechanics. It is, therefore, interesting to investigate the applicability of a neural network for the two- and three-dimensional morphoelastic model for contraction after burn injuries.

Keywords: biomechanics, burns, feasibility, feed-forward NN, morphoelasticity, neural network, relative surface area wound

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Authors: Noor Ul Huda, Mushtaq Ahmed, Nadia Mushtaq, Naila Sher, Rahmat Ali Khan

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Purpose: The green synthesis of AgNPs has been favored over chemical synthesis due to their distinctive properties such as high dispersion, surface-to-volume ratio, low toxicity, and easy preparation. In the present work, the biosynthesis of AgNPs (KE-AgNPs) was carried out in one step by using the traditionally used plant Kickxia elatine (KE) extract and then investigated its enzyme inhibiting activity against rat’s brain acetylcholinesterase (AChE) in vitro. Methods: KE-AgNPs were synthesized from 1mM AgNO₃ using KE extract and characterized by UV–spectroscopy, SEM, EDX, XRD, and FTIR analysis. Rat’s brain acetylcholinesterase (AChE) inhibition activity was evaluated by the standard protocol. Results: UV–spectrum at 416 nm confirmed the formation of KE-AgNPs. X-ray diffraction (XRD) pattern presented 2θ values corresponding to the crystalline nature of KE-AgNPs with an average size of 42.47nm. The scanning electron microscope (SEM) analysis confirmed the presence of spherical-shaped and huge density KE-AgNPs with a size of 50nm. Fourier transform infrared spectroscopy (FT-IR) suggested that the functional groups present in KE extract and on the surface of KE-AgNPs are responsible for the stability of biosynthesized NPs. Energy dispersive X-ray (EDX) displayed an intense sharp peak at 3.2 keV, presenting that Ag was the chief element with 61.67%. Both KE extract and KE-AgNPs showed good and potent anti-AChE activity, with higher inhibition potential at a concentration of 175 µg/ml. Statistical analysis showed that both KEE and AgNPs exhibited non-competitive type inhibition against AChE, i.e., Vmax decreased (34.17-68.64% and 22.29- 62.10%) in the concentration-dependent mode for KEE and KE-AgNPs respectively and while Km values remained constant. Conclusions: KEE and KE-AgNPs can be considered an inhibitor of rats’ brain AChE, and the synthesis of KE-AgNPs-based drugs can be used as a cheaper and alternative option against diseases such as Alzheimer’s disease.

Keywords: Kickxia elatine, AgNPs, brain homogenate, acetylcholinesterase, kinetics

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Authors: Babatunde Joel Todowede

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It is a public knowledge that lack of quality and qualitative education breeds problems besetting Nigeria as a nation today. This paper entitled “Quality and Qualitative Education for all, panacea for insecurity and political unrest in Nigeria” seeks to explore how quality and qualitative education for all will tends to put an end to insecurity and political unrest in Nigeria as a Nation. It may be pertinent to note at this juncture that the development of any modern society or nation is primarily hinged on the functionality of its educational system. There is no developed nation in the world today, which does not owe its advancement to quality and qualitative education. In other words, Education is a vital instrument in the nation’s economic competitiveness, in its people, and in its communities. Hence, Education is not luxury to be cut in difficult economic times – it is an essential element of growth. In fact, education is the bedrock of any society that hopes to be numbered among the developed economies in the world. Nigeria, as a nation, has made continual efforts to assume its rightful place in education on the African continent, but has not been quite lucky. Interestingly however, Quality and Qualitative Education for all will come about if all stakeholders in the Education Sector perform their roles with skill and efficiency. Education is a very sensitive area, hence, needs to be passionate about education, and focused on building a future for the sector.” Quality and qualitative education instill significant core values in every student, which shape them into mature, caring and independent individuals. These values include commitment, collaboration, integrity, responsibility and respect. By imbibing these values in every aspect of their life, they are able to contribute their skills and talents while supporting each other in attaining their lifelong goals. This paper identified lack of proper education as the bane of insecurity and political unrest in the Country and urged the government to review the policy in a way that there will be quality and standard to check insurgency in the Country. More so, until the fallen standard of education in Nigeria is fixed to engage out of school children, the incessant attack on innocent Nigerians, particularly in the North East may get worse.

Keywords: quality and qualitative education, panacea, insecurity, political unrest

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Authors: Deybith Venegas-Rojas, Jens Budde, Dominik Nörz, Manfred Jücker, Hoc Khiem Trieu

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Microfluidics is a promising approach for biomedicine cell culture experiments with microfluidic bioreactors (MBR), which can provide high precision in volume and time control over mass transport and microenvironments in small-scale studies. Nevertheless, shear stress and oxygen concentration are important factors that affect the microenvironment and then the cell culture. It is presented a novel MBR design in which differences in geometry, shear stress, and oxygen concentration were studied and optimized for cell culture. The aim is to mimic the in vivo condition with biocompatible materials and continuous perfusion of nutrients, a healthy shear stress, and oxygen concentration. The design consists of a capture system of PDMS micropillars which keep cells in place, so it is not necessary any hydrogel or complicated scaffolds for cells immobilization. Besides, the design allows continuous supply with nutrients or even any other chemical for cell experimentation. Finite element method simulations were used to study and optimize the effect of parameters such as flow rate, shear stress, oxygen concentration, micropillars shape, and dimensions. The micropillars device was fabricated with microsystem technology such as soft-lithography, deep reactive ion etching, self-assembled monolayer, replica molding, and oxygen plasma bonding. Eight different geometries were fabricated and tested, with different flow rates according to the simulations. During the experiments, it was observed the effect of micropillars size, shape, and configuration for stability and shear stress control when increasing flow rate. The device was tested with several successful HepG2 3D cell cultures. With this MBR, the aforementioned parameters can be controlled in order to keep a healthy microenvironment according to specific necessities of different cell types, with no need of hydrogels and can be used for a wide range of experiments with cells.

Keywords: cell culture, micro-bioreactor, microfluidics, micropillars, oxygen concentration, shear stress

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Authors: K. Sridhar Reddy, M. Amaranatha Reddy, Nilanjan Mitra

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Short paneled concrete pavement (SPCP) with shorter panel size can be an alternative to the conventional jointed plain concrete pavements (JPCP) at the same cost as the asphalt pavements with all the advantages of concrete pavement with reduced thickness, less chance of mid-slab cracking and or dowel bar locking so common in JPCP. Cast-in-situ short concrete panels (short slabs) laid on a strong foundation consisting of a dry lean concrete base (DLC), and cement treated subbase (CTSB) will reduce the thickness of the concrete slab to the order of 180 mm to 220 mm, whereas JPCP was with 280 mm for the same traffic. During the construction of SPCP test sections on two Indian National Highways (NH), it was observed that the joints remain uncracked after a year of traffic. The undoweled and uncracked joints load transfer variability and joint behavior are of interest with anticipation on its long-term performance of the SPCP. To investigate the effects of undoweled and uncracked joints on short slabs, the present study was conducted. A multilayer linear elastic analysis using 3D finite element package for different panel sizes with different thicknesses resting on different types of solid elastic foundation with and without temperature gradient was developed. Surface deflections were obtained from 3D FE model and validated with measured field deflections from falling weight deflectometer (FWD) test. Stress analysis indicates that flexural stresses in short slabs are decreased with a decrease in panel size and increase in thickness. Detailed evaluation of stress analysis with the effects of curling behavior, the stiffness of the base layer and a variable degree of load transfer, is underway.

Keywords: joint behavior, short slabs, uncracked joints, undoweled joints, 3D numerical simulation

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Authors: Noe Brice Nkoumbou Kaptchouang, Pierre-Guy Vincent, Yann Monerie

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The present work addresses the modelling and the simulation of crack initiation and propagation in ductile materials which failed by void nucleation, growth, and coalescence. One of the current research frameworks on crack propagation is the use of cohesive-volumetric approach where the crack growth is modelled as a decohesion of two surfaces in a continuum material. In this framework, the material behavior is characterized by two constitutive relations, the volumetric constitutive law relating stress and strain, and a traction-separation law across a two-dimensional surface embedded in the three-dimensional continuum. Several cohesive models have been proposed for the simulation of crack growth in brittle materials. On the other hand, the application of cohesive models in modelling crack growth in ductile material is still a relatively open field. One idea developed in the literature is to identify the traction separation for ductile material based on the behavior of a continuously-deforming unit cell failing by void growth and coalescence. Following this method, the present study proposed a semi-analytical cohesive model for ductile material based on a micromechanical approach. The strain localization band prior to ductile failure is modelled as a cohesive band, and the Gurson-Tvergaard-Needleman plasticity model (GTN) is used to model the behavior of the cohesive band and derived a corresponding traction separation law. The numerical implementation of the model is realized using the non-smooth contact method (NSCD) where cohesive models are introduced as mixed boundary conditions between each volumetric finite element. The present approach is applied to the simulation of crack growth in nuclear ferritic steel. The model provides an alternative way to simulate crack propagation using the numerical efficiency of cohesive model with a traction separation law directly derived from porous continuous model.

Keywords: ductile failure, cohesive model, GTN model, numerical simulation

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Authors: Anthony Quansah, Tresor Ntaryamira, Shula Mushota

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Models for geotechnical centrifuge testing are usually made from re-formed soil, allowing for comparisons with naturally occurring soil deposits. However, there is a fundamental omission in this process because the natural soil is deposited in layers creating a unique structure. Nonlinear dynamics of clay material deposit is an essential part of changing the attributes of ground movements when subjected to solid seismic loading, particularly when diverse intensification conduct of speeding up and relocation are considered. The paper portrays a review of axis shaking table tests and numerical recreations to explore the offshore clay deposits subjected to seismic loadings. These perceptions are accurately reenacted by DEEPSOIL with appropriate soil models and parameters reviewed from noteworthy centrifuge modeling researches. At that point, precise 1-D site reaction investigations are performed on both time and recurrence spaces. The outcomes uncover that for profound delicate clay is subjected to expansive quakes, noteworthy increasing speed lessening may happen close to the highest point of store because of soil nonlinearity and even neighborhood shear disappointment; nonetheless, huge enhancement of removal at low frequencies are normal in any case the forces of base movements, which proposes that for dislodging touchy seaward establishments and structures, such intensified low-recurrence relocation reaction will assume an essential part in seismic outline. This research shows centrifuge as a tool for creating a layered sample important for modelling true soil behaviour (such as permeability) which is not identical in all directions. Currently, there are limited methods for creating layered soil samples.

Keywords: seismic analysis, layered modeling, terotechnology, finite element modeling

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Authors: Mark Andrew

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Geopolitical tensions are at a thirty-year high, and the pace of technological innovation is driving asymmetry in force capabilities between nation states and between non-state actors. Technology futures are a vital component of defence capability growth, and investments in technology futures need to be informed by accurate and reliable forecasts of the options for ‘systems of systems’ innovation, development, and deployment. This paper describes a method for forecasting technology futures developed through an analysis of four key systems’ development stages, namely: technology domain categorisation, scanning results examining novel systems’ signals and signs, potential system-of systems’ implications in warfare theatres, and political ramifications in terms of funding and development priorities. The method has been applied to several technology domains, including physical systems (e.g., nano weapons, loitering munitions, inflight charging, and hypersonic missiles), biological systems (e.g., molecular virus weaponry, genetic engineering, brain-computer interfaces, and trans-human augmentation), and information systems (e.g., sensor technologies supporting situation awareness, cyber-driven social attacks, and goal-specification challenges to proliferation and alliance testing). Although the current application of the method has been team-centred using paper-based rapid prototyping and iteration, the application of autonomous language models (such as GPT-3) is anticipated as a next-stage operating platform. The importance of forecasting accuracy and reliability is considered a vital element in guiding technology development to afford stronger contingencies as ideological changes are forecast to expand threats to ecology and earth systems, possibly eclipsing the traditional vulnerabilities of nation states. The early results from the method will be subjected to ground truthing using longitudinal investigation.

Keywords: forecasting, technology futures, uncertainty, complexity

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Authors: Chao-Ton Su, Li-Fei Chen

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The parameter design is crucial to improving the uniformity of a product or process. In the product design stage, parameter design aims to determine the optimal settings for the parameters of each element in the system, thereby minimizing the functional deviations of the product. In the process design stage, parameter design aims to determine the operating settings of the manufacturing processes so that non-uniformity in manufacturing processes can be minimized. The parameter design, trying to minimize the influence of noise on the manufacturing system, plays an important role in the high-tech companies. Taiwan has many well-known high-tech companies, which show key roles in the global economy. Quality remains the most important factor that enables these companies to sustain their competitive advantage. In Taiwan however, many high-tech companies face various quality problems. A common challenge is related to root causes and defect patterns. In the R&D stage, root causes are often unknown, and defect patterns are difficult to classify. Additionally, data collection is not easy. Even when high-volume data can be collected, data interpretation is difficult. To overcome these challenges, high-tech companies in Taiwan use more advanced quality improvement tools. In addition to traditional statistical methods and quality tools, the new trend is the application of powerful tools, such as neural network, fuzzy theory, data mining, industrial engineering, operations research, and innovation skills. In this study, several examples of optimizing the parameter settings for the manufacturing process in Taiwan’s tech companies will be presented to illustrate proposed approach’s effectiveness. Finally, a discussion of using traditional experimental design versus the proposed approach for process optimization will be made.

Keywords: quality engineering, parameter design, neural network, genetic algorithm, experimental design

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Authors: Sudeshna Chandra, Christian Gäbler, Christian Schliebe, Heinrich Lang

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Highly branched dendrimers provide structural homogeneity, controlled composition, comparable size to biomolecules, internal porosity and multiple functional groups for conjugating reactions. Electro-active dendrimers containing multiple redox units have generated great interest in their use as electrode modifiers for development of biosensors. The electron transfer between the redox-active dendrimers and the biomolecules play a key role in developing a biosensor. Ferrocenes have multiple and electrochemically equivalent redox units that can act as electron “pool” in a system. The ferrocenyl-terminated polyamidoamine dendrimer is capable of transferring multiple numbers of electrons under the same applied potential. Therefore, they can be used for dual purposes: one in building a film over the electrode for immunosensors and the other for immobilizing biomolecules for sensing. Electrochemical immunosensor, thus developed, exhibit fast and sensitive analysis, inexpensive and involve no prior sample pre-treatment. Electrochemical amperometric immunosensors are even more promising because they can achieve a very low detection limit with high sensitivity. Detection of the cancer biomarkers at an early stage can provide crucial information for foundational research of life science, clinical diagnosis and prevention of disease. Elevated concentration of biomarkers in body fluid is an early indication of some type of cancerous disease and among all the biomarkers, IgG is the most common and extensively used clinical cancer biomarkers. We present an IgG (=immunoglobulin) electrochemical immunosensor using a newly synthesized redox-active ferrocenyl dendrimer of generation 2 (G2Fc) as glassy carbon electrode material for immobilizing the antibody. The electrochemical performance of the modified electrodes was assessed in both aqueous and non-aqueous media using varying scan rates to elucidate the reaction mechanism. The potential shift was found to be higher in an aqueous electrolyte due to presence of more H-bond which reduced the electrostatic attraction within the amido groups of the dendrimers. The cyclic voltammetric studies of the G2Fc-modified GCE in 0.1 M PBS solution of pH 7.2 showed a pair of well-defined redox peaks. The peak current decreased significantly with the immobilization of the anti-goat IgG. After the immunosensor is blocked with BSA, a further decrease in the peak current was observed due to the attachment of the protein BSA to the immunosensor. A significant decrease in the current signal of the BSA/anti-IgG/G2Fc/GCE was observed upon immobilizing IgG which may be due to the formation of immune-conjugates that blocks the tunneling of mass and electron transfer. The current signal was found to be directly related to the amount of IgG captured on the electrode surface. With increase in the concentration of IgG, there is a formation of an increasing amount of immune-conjugates that decreased the peak current. The incubation time and concentration of the antibody was optimized for better analytical performance of the immunosensor. The developed amperometric immunosensor is sensitive to IgG concentration as low as 2 ng/mL. Tailoring of redox-active dendrimers provides enhanced electroactivity to the system and enlarges the sensor surface for binding the antibodies. It may be assumed that both electron transfer and diffusion contribute to the signal transformation between the dendrimers and the antibody.

Keywords: ferrocenyl dendrimers, electrochemical immunosensors, immunoglobulin, amperometry

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Authors: L.L. Costa, A. M. G. Brito, S. Khan, L. Schaeffer

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Microstructure resulting from the forging process is studied as a function of variables such as temperature, deformation, austenite grain size and cooling rate. The purpose of this work is to study the thermomechanical behavior of DIN 42CrMo4 (AISI 4140) steel maintained at the temperatures of 900°, 1000°, 1100° and 1200°C for the austenization times of 22, 66 and 200 minutes each and subsequently forged. These samples were quenched in water in order to study the austenite grain and to investigate the microstructure instead of quenching the annealed samples after forging they were cooled down naturally in the air. The morphologies and properties of the materials such as hardness; prepared by these two different routes have been compared. In addition to the forging experiments, the numerical simulation using the finite element model (FEM), microhardness profiles and metallography images have been presented. Forging force vs position curves has been compared with metallographic results for each annealing condition. The microstructural phenomena resulting from the hot conformation proved that longer austenization time and higher temperature decrease the forging force in the curves. The complete recrystallization phenomenon (static, dynamic and meta dynamic) was observed at the highest temperature and longest time i.e., the samples austenized for 200 minutes at 1200ºC. However, higher hardness of the quenched samples was obtained when the temperature was 900ºC for 66 minutes. The phases observed in naturally cooled samples were exclusively ferrite and perlite, but the continuous cooling diagram indicates the presence of austenite and bainite. The morphology of the phases of naturally cooled samples has shown that the phase arrangement and the previous austenitic grain size are the reasons to high hardness in obtained samples when temperature were 900ºC and 1100ºC austenization times of 22 and 66 minutes, respectively.

Keywords: austenization time, thermomechanical effects, forging process, steel AISI 4140

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Authors: Milica Carević, Katarina Banjanac, Marija ĆOrović, Ana Milivojević, Nevena Prlainović, Aleksandar Marinković, Dejan Bezbradica

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Nowadays, considering the growing awareness of functional food beneficial effects on human health, due attention is dedicated to the research in the field of obtaining new prominent products exhibiting improved physiological and physicochemical characteristics. Therefore, different approaches to valuable bioactive compounds synthesis have been proposed. β-Galactosidase, for example, although mainly utilized as hydrolytic enzyme, proved to be a promising tool for these purposes. Namely, under the particular conditions, such as high lactose concentration, elevated temperatures and low water activities, reaction of galactose moiety transfer to free hydroxyl group of the alternative acceptor (e.g. different sugars, alcohols or aromatic compounds) can generate a wide range of potentially interesting products. Up to now, galacto-oligosaccharides and lactulose have attracted the most attention due to their inherent prebiotic properties. The goal of this study was to obtain a novel product sorbitol galactoside, using the similar reaction mechanism, namely transgalactosylation reaction catalyzed by β-galactosidase from Aspergillus oryzae. By using sugar alcohol (sorbitol) as alternative acceptor, a diverse mixture of potential prebiotics is produced, enabling its more favorable functional features. Nevertheless, an introduction of alternative acceptor into the reaction mixture contributed to the complexity of reaction scheme, since several potential reaction pathways were introduced. Therefore, the thorough optimization using response surface method (RSM), in order to get an insight into different parameter (lactose concentration, sorbitol to lactose molar ratio, enzyme concentration, NaCl concentration and reaction time) influences, as well as their mutual interactions on product yield and productivity, was performed. In view of product yield maximization, the obtained model predicted optimal lactose concentration 500 mM, the molar ratio of sobitol to lactose 9, enzyme concentration 0.76 mg/ml, concentration of NaCl 0.8M, and the reaction time 7h. From the aspect of productivity, the optimum substrate molar ratio was found to be 1, while the values for other factors coincide. In order to additionally, improve enzyme efficiency and enable its reuse and potential continual application, immobilization of β-galactosidase onto tailored silica nanoparticles was performed. These non-porous fumed silica nanoparticles (FNS)were chosen on the basis of their biocompatibility and non-toxicity, as well as their advantageous mechanical and hydrodinamical properties. However, in order to achieve better compatibility between enzymes and the carrier, modifications of the silica surface using amino functional organosilane (3-aminopropyltrimethoxysilane, APTMS) were made. Obtained support with amino functional groups (AFNS) enabled high enzyme loadings and, more importantly, extremely high expressed activities, approximately 230 mg proteins/g and 2100 IU/g, respectively. Moreover, this immobilized preparation showed high affinity towards sorbitol galactoside synthesis. Therefore, the findings of this study could provided a valuable contribution to the efficient production of physiologically active galactosides in immobilized enzyme reactors.

Keywords: β-galactosidase, immobilization, silica nanoparticles, transgalactosylation

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Authors: Chang-Hui Shen, Michelle Esposito, Andrew J. Shen, Michael Adejokun, Diana Laterman

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The packaging of DNA into nucleosomes is critical to genomic compaction, yet it can leave gene promoters inaccessible to activator proteins or transcription machinery and thus prevents transcriptional initiation. Both chromatin remodelers and histone acetylases (HATs) are the two main transcription co-activators that can reconfigure chromatin structure for transcriptional activation. Ino80p is the core component of the INO80 remodeling complex. Recently, it was shown that Ino80p dissociates from the yeast INO1 promoter after induction. However, when certain HATs were deleted or mutated, Ino80p accumulated at the promoters during gene activation. This suggests a link between HATs’ presence and Ino80p’s dissociation. However, it has yet to be demonstrated that Ino80p can be acetylated. To determine if Ino80p can be acetylated, wild-type Saccharomyces cerevisiae cells carrying Ino80p engineered with a double FLAG tag (MATa INO80-FLAG his3∆200 leu2∆0 met15∆0 trp1∆63 ura3∆0) were grown to mid log phase, as were non-tagged wild type (WT) (MATa his3∆200 leu2∆0 met15∆0 trp1∆63 ura3∆0) and ino80∆ (MATa ino80∆::TRP1 his3∆200 leu2∆0 met15∆0 trp1∆63 ura3∆0) cells as controls. Cells were harvested, and the cell lysates were subjected to immunoprecipitation (IP) with α-FLAG resin to isolate Ino80p. These eluted IP samples were subjected to SDS-PAGE and Western blot analysis. Subsequently, the blots were probed with the α-FLAG and α-acetyl lysine antibodies, respectively. For the blot probed with α-FLAG, one prominent band was shown in the INO80-FLAG cells, but no band was detected in the IP samples from the WT and ino80∆ cells. For the blot probed with the α-acetyl lysine antibody, we detected acetylated Ino80p in the INO80-FLAG strain while no bands were observed in the control strains. As such, our results showed that Ino80p can be acetylated. This acetylation can explain the co-activator’s recruitment patterns observed in current gene activation models. In yeast INO1, it has been shown that Ino80p is recruited to the promoter during repression, and then dissociates from the promoter once de-repression begins. Histone acetylases, on the other hand, have the opposite pattern of recruitment, as they have an increased presence at the promoter as INO1 de-repression commences. This Ino80p recruitment pattern significantly changes when HAT mutant strains are studied. It was observed that instead of dissociating, Ino80p accumulates at the promoter in the absence of functional HATs, such as Gcn5p or Esa1p, under de-repressing processes. As such, Ino80p acetylation may be required for its proper dissociation from the promoters. The remodelers’ dissociation mechanism may also have a wide range of implications with respect to transcriptional initiation, elongation, or even repression as it allows for increased spatial access to the promoter for the various transcription factors and regulators that need to bind in that region. Our findings here suggest a previously uncharacterized interaction between Ino80p and other co-activators recruited to promoters. As such, further analysis of Ino80p acetylation not only will provide insight into the role of epigenetic modifications in transcriptional activation, but also gives insight into the interactions occurring between co-activators at gene promoters during gene regulation.

Keywords: acetylation, chromatin remodeler, epigenetic modification, Ino80p

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Authors: Sundaram Arulmozhiraja, Kanade Shimizu, Yuta Yamamoto, Satoshi Ichikawa, Maenaka Katsumi, Hiroaki Tokiwa

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Drug discovery is shifting from small molecule based drugs targeting local active site to middle molecules (MM) targeting large, flat, and groove-shaped binding sites, for example, protein-protein interface because at least half of all targets assumed to be involved in human disease have been classified as “difficult to drug” with traditional small molecules. Hence, MMs such as peptides, natural products, glycans, nucleic acids with various high potent bioactivities become important targets for drug discovery programs in the recent years as they could be used for ‘undruggable” intracellular targets. Cell membrane permeability is one of the key properties of pharmacodynamically active MM drug compounds and so evaluating this property for the potential MMs is crucial. Computational prediction for cell membrane permeability of molecules is very challenging; however, recent advancement in the molecular dynamics simulations help to solve this issue partially. It is expected that MMs with high membrane permeability will enable drug discovery research to expand its borders towards intracellular targets. Further to understand the chemistry behind the permeability of MMs, it is necessary to investigate their conformational changes during the permeation through membrane and for that their interactions with the membrane field should be studied reliably because these interactions involve various non-bonding interactions such as hydrogen bonding, -stacking, charge-transfer, polarization dispersion, and non-classical weak hydrogen bonding. Therefore, parameters-based classical mechanics calculations are hardly sufficient to investigate these interactions rather, quantum mechanical (QM) calculations are essential. Fragment molecular orbital (FMO) method could be used for such purpose as it performs ab initio QM calculations by dividing the system into fragments. The present work is aimed to study the cell permeability of middle molecules using molecular dynamics simulations and FMO-QM calculations. For this purpose, a natural compound syringolin and its analogues were considered in this study. Molecular simulations were performed using NAMD and Gromacs programs with CHARMM force field. FMO calculations were performed using the PAICS program at the correlated Resolution-of-Identity second-order Moller Plesset (RI-MP2) level with the cc-pVDZ basis set. The simulations clearly show that while syringolin could not permeate the membrane, its selected analogues go through the medium in nano second scale. These correlates well with the existing experimental evidences that these syringolin analogues are membrane-permeable compounds. Further analyses indicate that intramolecular -stacking interactions in the syringolin analogues influenced their permeability positively. These intramolecular interactions reduce the polarity of these analogues so that they could permeate the lipophilic cell membrane. Conclusively, the cell membrane permeability of various middle molecules with potent bioactivities is efficiently studied using molecular dynamics simulations. Insight of this behavior is thoroughly investigated using FMO-QM calculations. Results obtained in the present study indicate that non-bonding intramolecular interactions such as hydrogen-bonding and -stacking along with the conformational flexibility of MMs are essential for amicable membrane permeation. These results are interesting and are nice example for this theoretical calculation approach that could be used to study the permeability of other middle molecules. This work was supported by Japan Agency for Medical Research and Development (AMED) under Grant Number 18ae0101047.

Keywords: fragment molecular orbital theory, membrane permeability, middle molecules, molecular dynamics simulation

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Authors: Chris Phan, Yong Seok Park

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The Toyota Camry is one of the best-selling cars in America. It is economical, reliable, and most importantly, safe. These attributes allowed the Camry to be the trustworthy choice when choosing dependable vehicle. However, a new finding brought question to the Camry’s safety. Since 1997, the Camry received a “good” rating on its moderate overlap front crash test through the Insurance Institute of Highway Safety. In 2012, the Insurance Institute of Highway Safety introduced a frontal small overlap crash test into the overall evaluation of vehicle occupant safety test. The 2012 Camry received a “poor” rating on this new test, while the 2015 Camry redeemed itself with a “good” rating once again. This study aims to find a possible solution that Toyota implemented to reduce the severity of a frontal small overlap crash in the Camry during a mid-cycle update. The purpose of this study is to analyze and evaluate the performance of various A-pillar shapes as energy absorbing structures in improving passenger safety in a frontal crash. First, A-pillar structures of the 2012 and 2015 Camry were modeled using CAD software, namely SolidWorks. Then, a crash test simulation using ANSYS software, was applied to the A-pillars to analyze the behavior of the structures in similar conditions. Finally, the results were compared to safety values of cabin intrusion to determine the crashworthy behaviors of both A-pillar structures by measuring total deformation. This study highlights that it is possible that Toyota improved the shape of the A-pillar in the 2015 Camry in order to receive a “good” rating from the IIHS safety evaluation once again. These findings can possibly be used to increase safety performance in future vehicles to decrease passenger injury or fatality.

Keywords: A-pillar, Crashworthiness, Design Synthesis, Finite Element Analysis

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Authors: Sanyka Banerjee, Saikat Nandi, P. K. Dan

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Synchronizers as an integral part of gearbox is a key element in the transmission system in automotive. The performance of synchronizer affects transmission efficiency and driving comfort. Synchronizing mechanism as a major component of transmission system must be capable of preventing vibration and noise in the gears. Gear shifting efficiency improvement with an aim to achieve smooth, quick and energy efficient power transmission remains a challenge for the automotive industry. Performance of the synchronizer is dependent on the features and characteristics of its sub-components and therefore analysis of the contribution of such characteristics is necessary. An important exercise involved is to identify all such characteristics or factors which are associated with the modeling and analysis and for this purpose the literature was reviewed, rather extensively, to study the mathematical models, formulated considering such. It has been observed that certain factors are rather common across models; however, there are few factors which have specifically been selected for individual models, as reported. In order to obtain a more realistic model, an attempt here has been made to identify and assimilate practically all possible factors which may be considered in formulating the model more comprehensively. A simulation study, formulated as a block model, for such analysis has been carried out in a reliable environment like MATLAB. Lower synchronization time is desirable and hence, it has been considered here as the output factors in the simulation modeling for evaluating transmission efficiency. An improved synchronizer model requires optimized values of sub-component design parameters. A parametric optimization utilizing Taguchi’s design of experiment based response data and their analysis has been carried out for this purpose. The effectiveness of the optimized parameters for the improved synchronizer performance has been validated by the simulation study of the synchronizer block model with improved parameter values as input parameters for better transmission efficiency and driver comfort.

Keywords: design of experiments, modeling, parametric optimization, simulation, synchronizer

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Authors: Demet Ozgur-Unluakin, Busenur Turkali, S. Caglar Aksezer

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Since the age of industrialization, maintenance has always been a very crucial element for all kinds of factories and plants. With today’s increasingly developing technology, the system structure of such facilities has become more complicated, and even a small operational disruption may return huge losses in profits for the companies. In order to reduce these costs, effective maintenance planning is crucial, but at the same time, it is a difficult task because of the complexity of systems. The most important aspect of correct maintenance planning is to understand the structure of the system, not to ignore the dependencies among the components and as a result, to model the system correctly. In this way, it will be better to understand which component improves the system more when it is maintained. Undoubtedly, proactive maintenance at a scheduled time reduces costs because the scheduled maintenance prohibits high losses in profits. But the necessity of corrective maintenance, which directly affects the situation of the system and provides direct intervention when the system fails, should not be ignored. When a fault occurs in the system, if the problem is not solved immediately and proactive maintenance time is awaited, this may result in increased costs. This study proposes various maintenance methods with different efficiency measures under corrective maintenance strategy on a subsystem of a thermal power plant. To model the dependencies between the components, dynamic Bayesian Network approach is employed. The proposed maintenance methods aim to minimize the total maintenance cost in a planning horizon, as well as to find the most appropriate component to be attacked on, which improves the system reliability utmost. Performances of the methods are compared under corrective maintenance strategy. Furthermore, sensitivity analysis is also applied under different cost values. Results show that all fault effect methods perform better than the replacement effect methods and this conclusion is also valid under different downtime cost values.

Keywords: dynamic Bayesian networks, maintenance, multi-component systems, reliability

Procedia PDF Downloads 128