Search results for: target receptor

Authors: Hua Li, Hongwu Deng

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The turbine blade's leading edge is usually cooled by jet impingement cooling technology due to the heaviest heat load. For a rotating turbine blade, however, the channel orientation (β, the angle between the jet direction and the rotating plane) could play an important role in influencing the flow field and heat transfer. Therefore, in this work, the effects of channel orientation (from 90° to 180°) on heat transfer in a jet impingement cooling channel are experimentally investigated. Furthermore, the investigations are conducted under an isothermal boundary condition. Both the jet-to-target surface distance and jet-to-jet spacing are three times the jet hole diameter. The jet Reynolds number is 5,000, and the maximum jet rotation number reaches 0.24. The results show that the rotation-induced variations of heat transfer are different in each channel orientation. In the cases of 90°≤β≤135°, a vortex generated in the low-radius region of the supply channel changes the mass-flowrate distribution in each jet hole. Therefore, the heat transfer in the low-radius region decreases with the rotation number, whereas the heat transfer in the high-radius region increases, indicating that a larger temperature gradient in the radial direction could appear in the turbine blade's leading edge. When 135°<β≤180°; however, the heat transfer of the entire stagnant zone decreases with the rotation number. The rotation-induced jet deflection is the primary factor that weakens the heat transfer, and jets cannot reach the target surface at high rotation numbers. For the downstream regions, however, the heat transfer is enhanced by 50%-80% in every channel orientation because the dead zone is broken by the rotation-induced secondary flow in the impingement channel.

Keywords: heat transfer, jet impingement cooling, channel orientation, high rotation number, isothermal boundary

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Authors: Li-Te Lin, Chia-Jung Li, Kuan-Hao Tsui

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Cuproptosis, a newly identified cell death mechanism, has attracted attention for its association with various diseases. However, the genetic interplay between cuproptosis and ovarian aging remains largely unexplored. This study aims to address this gap by analyzing datasets related to ovarian aging and cuproptosis. Spatial transcriptome analyses were conducted in the ovaries of both young and aged female mice to elucidate the role of FDX1. Comprehensive bioinformatics analyses, facilitated by R software, identified FDX1 as a potential cuproptosis-related gene with implications for ovarian aging. Clinical infertility biopsies were examined to validate these findings, showing consistent results in elderly infertile patients. Furthermore, pharmacogenomic analyses of ovarian cell lines explored the intricate association between FDX1 expression levels and sensitivity to specific small molecule drugs. Spatial transcriptome analyses revealed a significant reduction in FDX1 expression in aging ovaries, supported by consistent findings in biopsies from elderly infertile patients. Pharmacogenomic investigations indicated that modulating FDX1 could influence drug responses in ovarian-related therapies. This study pioneers the identification of FDX1 as a cuproptosis-related gene linked to ovarian aging. These findings not only contribute to understanding the mechanisms of ovarian aging but also position FDX1 as a potential diagnostic biomarker and therapeutic target. Further research may establish FDX1's pivotal role in advancing precision medicine and therapies for ovarian-related conditions.

Keywords: cuproptosis, FDX1, ovarian aging, biomarker

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Authors: Kheireddine El-Boubbou

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Drug delivery to target human acute myeloid leukemia (AML) using a nanoparticulate chemotherapeutic formulation that can deliver drugs selectively to AML cancer is hugely needed. In this work, we report the development of a nanoformulation made of polymeric-stabilized multifunctional magnetic iron oxide nanoparticles (PMNP) loaded with the anticancer drug Doxorubicin (Dox) as a promising drug carrier to treat AML. Dox@PMNP conjugates simultaneously exhibited high drug content, maximized fluorescence, and excellent release properties. Nanoparticulate uptake and cell death following addition of Dox@PMNPs were then evaluated in different types of human AML target cells, as well as on normal human cells. While the unloaded MNPs were not toxic to any of the cells, Dox@PMNPs were found to be highly toxic to the different AML cell lines, albeit at different inhibitory concentrations (IC₅₀ values), but showed very little toxicity towards the normal cells. In comparison, free Dox showed significant potency concurrently to all the cell lines, suggesting huge potentials for the use of Dox@PMNPs as selective AML anticancer cargos. Live confocal imaging, fluorescence and electron microscopy confirmed that Dox is indeed delivered to the nucleus in relatively short periods of time, causing apoptotic cell death. Importantly, this targeted payload may potentially enhance the effectiveness of the drug in AML patients and may further allow physicians to image leukemic cells exposed to Dox@PMNPs using MRI.

Keywords: magnetic nanoparticles, drug delivery, acute myeloid leukemia, iron oxide, cancer nanotherapy

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Authors: Jerry Fiave, Dacosta Aboagye, Stephen Ayisi-Addo, Mabel Kissiwah Asafo, Felix Osei-Sarpong, Ebenezer Kye-Mensah, Renee Opare-Otoo

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Background: Acceptability and preference of social and behaviour change (SBC) materials by target audiences is an important determinant of effective health communication outcomes. In Ghana, however, pre-test and post-test studies on acceptability and preference of specific SBC materials for specific audiences are rare. The aim of this study was therefore to assess the acceptability and preference of printed posters on COVID-19 related stigma as suitable SBC materials for health workers to influence behaviours that promote uptake of HIV-focused services. Methods: A total of 218 health workers who provide HIV-focused services were purposively sampled in 16 polyclinics where the posters were distributed in the Greater Accra region of Ghana. Data was collected in March 2021 using an adapted self-administered questionnaire in Google forms deployed via WhatsApp to participants. The data were imported into SPSS version 27 where chi-square test and regression analyses were performed to establish association as well as strength of association between variables respectively. Results: A total of 142 participants (physicians, nurses, midwives, lab scientists, health promoters, diseases control officers) made up of 85(60%) females and 57(40%) males responded to the questionnaire, giving a response rate of 65.14%. Only 88 (61.97%) of the respondents were exposed to the posters. The majority of those exposed said the posters were informative [82(93.18%)], relevant [85(96.59%)] and attractive [83(94.32%)]. They [82(93.20%)] also rated the material as acceptable with no statistically significant association between category of health worker and acceptability of the posters (X =1.631, df=5, p=0.898). However, participants’ most preferred forms of material on COVID-19 related stigma were social media [38(26.76%)], television [33(23.24%)], SMS [19(13.38%)], and radio [18(12.70%)]. Clinical health workers were 4.88 times more likely to prefer online or electronic versions of SBC materials than nonclinical health workers [AOR= 4.88 (95% CI= 0.31-0.98), p=0.034]. Conclusions: Printed posters on COVID-19 related stigma are acceptable SBC materials in communicating behaviour change messages that target health workers in promoting uptake of HIV-focused services. Posters are however, not among the most preferred materials for health workers. It is therefore recommended that material assessment studies are conducted to inform the development of acceptable and preferred materials for target audiences.

Keywords: acceptability, AIDS, HIV, posters, preference, SBC, stigma, social and behaviour change communication

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Authors: M. Mousavi-Daramoroudi, H. Yousefnia, F. Abbasi-Davani, S. Zolghadri

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Dosimetry is an indispensable and precious factor in patient treatment planning to minimize the absorbed dose in vital tissues. In this study, compartmental model was used in order to estimate the human absorbed dose of ¹⁷⁷Lu-DOTATOC from the biodistribution data in wild type rats. For this purpose, ¹⁷⁷Lu-DOTATOC was prepared under optimized conditions and its biodistribution was studied in male Syrian rats up to 168 h. Compartmental model was applied to mathematical description of the drug behaviour in tissue at different times. Dosimetric estimation of the complex was performed using radiation absorbed dose assessment resource (RADAR). The biodistribution data showed high accumulation in the adrenal and pancreas as the major expression sites for somatostatin receptor (SSTR). While kidneys as the major route of excretion receive 0.037 mSv/MBq, pancreas and adrenal also obtain 0.039 and 0.028 mSv/MBq. Due to the usage of this method, the points of accumulated activity data were enhanced, and further information of tissues uptake was collected that it will be followed by high (or improved) precision in dosimetric calculations.

Keywords: compartmental modeling, human absorbed dose, ¹⁷⁷Lu-DOTATOC, Syrian rats

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Authors: Shailendra Kumar Mishra

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In this paper, we focus on how contextual factors like the physical presence of other perceivers and then developed induced emotional empathy towards a person with disabilities may reduce the automatic negative stereotypes and then response towards that person. We demonstrated in study 1 that negative attitude based on negative stereotypes assessed on ATDP-test questionnaires on five points Linkert-scale are significantly less negative when participants were tested with a group of perceivers and then tested alone separately by applying 3 (positive, indifferent, and negative attitude levels) X 2 (physical presence condition and alone) factorial design of ANOVA test. In the second study, we demonstrate, by applying regression analysis, in the presence of other perceivers, whether in a small group, participants showed more induced emotional empathy through stronger prosociality towards a high distress target like a person with disabilities in comparison of that of other stigmatized persons such as racial biased or gender-biased people. Thus results show that automatic affective response in the form of induced emotional empathy in perceiver and contextual factors like the presence of other perceivers automatically activate stronger prosocial norms and egalitarian goals towards physically challenged persons in comparison to other stigmatized persons like racial or gender-biased people. This leads to less negative attitudes and behaviour towards a person with disabilities.

Keywords: contextual factors, high distress target, induced emotional empathy, stronger prosociality

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Authors: Khalid El Asri

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Culture influences lexicalization of salient concepts in a society. Hence, languages often have different degrees of equivalence regarding lexical items of different fields. The present study focuses on the field of emotions in English and Moroccan Arabic. Findings of a comparative study that involved fifty English emotions revealed that Moroccan Arabic has equivalence of some English emotion terms, partial equivalence of some emotion terms, and no equivalence for some other terms. It is hypothesized then that emotion terms that have near equivalence in Moroccan Arabic will be easier to acquire for EFL learners, while partially equivalent terms will be difficult to acquire, and those that have no equivalence will be even more difficult to acquire. In order to test these hypotheses, the participants (104 advanced Moroccan EFL learners and 104 native speakers of English) were given two tests: the first is a receptive one in which the participants were asked to choose, among four emotion terms, the term that is appropriate to fill in the blanks for a given situation indicating certain kind of feelings. The second test is a productive one in which the participants were asked to give the emotion term that best described the feelings of the people in the situations given. The results showed that conceptually equivalent terms do not pose any problems for Moroccan EFL learners since they can link the concept to an already existing linguistic category; whereas the results concerning the acquisition of partially equivalent terms indicated that this type of emotion terms were difficult for Moroccan EFL learners to acquire, because they need to restructure the boundaries of the target linguistic categories by expanding them when the term includes other range of meanings that are not subsumed in the L1 term. Surprisingly however, the results concerning the case of non-equivalence revealed that Moroccan EFL learners could internalize the target L2 concepts that have no equivalence in their L1. Thus, it is the category of emotion terms that have partial equivalence in the learners’ L1 that pose problems for them.

Keywords: acquisition, culture, emotion terms, lexical equivalence

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Authors: Bhuvanesh Baniya

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Alzheimer disease is illnesses that are responsible for neuronal cell death and resulting in lifelong cognitive problems. Due to their unclear mechanism, there are no effective drugs available for the treatment. For a long time, herbal drugs have been used as a role model in the field of the drug discovery process. Holy basil in the Indian medicinal system (Ayurveda) is used for several neuronal disorders like insomnia and memory loss for decades. This study aims to identify active components of holy basil as potential inhibitors for the treatment of Alzheimer disease. To fulfill this objective, the Network pharmacology approach, gene ontology, pharmacokinetics analysis, molecular docking, and molecular dynamics simulation (MDS) studies were performed. A total of 7 active components in holy basil, 12 predicted neurodegenerative targets of holy basil, and 8063 Alzheimer-related targets were identified from different databases. The network analysis showed that the top ten targets APP, EGFR, MAPK1, ESR1, HSPA4, PRKCD, MAPK3, ABL1, JUN, and GSK3B were found as significant target related to Alzheimer disease. On the basis of gene ontology and topology analysis results, APP was found as a significant target related to Alzheimer’s disease pathways. Further, the molecular docking results to found that various compounds showed the best binding affinities. Further, MDS top results suggested could be used as potential inhibitors against APP protein and could be useful for the treatment of Alzheimer’s disease.

Keywords: holy basil, network pharmacology, neurodegeneration, active phytochemicals, molecular docking and simulation

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Authors: Sikander Nawaz Khan

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Natural disasters like flood, earthquake, cyclone, volcanic eruption and others are causing immense losses to the property and lives every year. Current status and actual loss information of natural hazards can be determined and also prediction for next probable disasters can be made using different remote sensing and mapping technologies. Global Positioning System (GPS) calculates the exact position of damage. It can also communicate with wireless sensor nodes embedded in potentially dangerous places. GPS provide precise and accurate locations and other related information like speed, track, direction and distance of target object to emergency responders. Remote Sensing facilitates to map damages without having physical contact with target area. Now with the addition of more remote sensing satellites and other advancements, early warning system is used very efficiently. Remote sensing is being used both at local and global scale. High Resolution Satellite Imagery (HRSI), airborne remote sensing and space-borne remote sensing is playing vital role in disaster management. Early on Geographic Information System (GIS) was used to collect, arrange, and map the spatial information but now it has capability to analyze spatial data. This analytical ability of GIS is the main cause of its adaption by different emergency services providers like police and ambulance service. Full potential of these so called 3S technologies cannot be used in alone. Integration of GPS and other remote sensing techniques with GIS has pointed new horizons in modeling of earth science activities. Many remote sensing cases including Asian Ocean Tsunami in 2004, Mount Mangart landslides and Pakistan-India earthquake in 2005 are described in this paper.

Keywords: disaster mitigation, GIS, GPS, remote sensing

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Authors: Sara Pereira-Nogueira, Tim Worbs, Marc Permanyer-Bosser, Reinhold Förster

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While the entry mechanism of lymphocytes into the lymph node via the blood are well described, it is still largely unknown how cells enter lymph nodes that arrive via afferent lymphatics. In order to address this, our group has established a micro-injection technique in mice through which cells are delivered directly into the lymphatic vessel immediately afferent to the popliteal lymph node. Injected cells can then be tracked via multi-colour fluorescence or 2-photon microscopy, and their localization can be analysed within the popliteal or downstream lymph nodes by immunohistology. Since naïve B cells express the chemokine receptor CXCR5 we intra-lymphatically co-injected B cells derived from wildtype and Cxcr5-deficient mice. While CXCR5 does not play a role in guiding B cells out of the subcapsular sinus, it affects their positioning within the lymph node parenchyma, since CXCR5-deficient B cells are impaired in migrating into the B cell follicle. The knowledge obtained by studying B-cell migration may prove beneficial in clinical settings regarding tumor metastasis or autoimmune diseases.

Keywords: afferent lymphatics, B cell migration, chemokine, intra-lymphatic injection

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Authors: Swati Gautam, Salman Akhtar, S. P. Jaiswar, Amita Jain

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Background: FGTB is now a major global health problem mostly in developing countries including India. In humans, Mycobacterium Tuberculosis (M.tb) is a causating agent of infection. High index of suspicion is required for early diagnosis due to asymptomatic presentation of FGTB disease. In macrophages Toll Like Receptor-2 (TLR-2) is one which mediated host’s immune response to M.tb. The expression of TLR-2 on macrophages is important to determine the fate of innate immune responses to M.tb. TLR-2 have two work. First its high expression on macrophages worsen the outer of infection and another side, it maintains M.tb to its dormant stage avoids activation of M.tb from latent phase. Single Nucleotide Polymorphism (SNP) of TLR-2 gene plays an important role in susceptibility to TB among different populations and subsequently, in the development of infertility. Methodology: This Case-Control study was done in the Department of Obs and Gynae and Department of Microbiology at King George’s Medical University, U.P, Lucknow, India. Total 300 subjects (150 Cases and 150 Controls) were enrolled in the study. All subjects were enrolled only after fulfilling the given inclusion and exclusion criteria. Inclusion criteria: Age 20-35 years, menstrual-irregularities, positive on Acid-Fast Bacilli (AFB), TB-PCR, (LJ/MGIT) culture in Endometrial Aspiration (EA). Exclusion criteria: Koch’s active, on ATT, PCOS, and Endometriosis fibroid women, positive on Gonococal and Chlamydia. Blood samples were collected in EDTA tubes from cases and healthy control women (HCW) and genomic DNA extraction was carried out by salting-out method. Genotyping of TLR2 genetic variants (Arg753Gln and Arg677Trp) were performed by using single amplification refractory mutation system (ARMS) PCR technique. PCR products were analyzed by electrophoresis on 1.2% agarose gel and visualized by gel-doc. Statistical analysis of the data was performed using the SPSS 16.3 software and computing odds ratio (OR) with 95% CI. Linkage Disequiliribium (LD) analysis was done by SNP stats online software. Results: In TLR-2 (Arg753Gln) polymorphism significant risk of FGTB observed with GG homozygous mutant genotype (OR=13, CI=0.71-237.7, p=0.05), AG heterozygous mutant genotype (OR=13.7, CI=0.76-248.06, p=0.03) however, G allele (OR=1.09, CI=0.78-1.52, p=0.67) individually was not associated with FGTB. In TLR-2 (Arg677Trp) polymorphism a significant risk of FGTB observed with TT homozygous mutant genotype (OR= 0.020, CI=0.001-0.341, p < 0.001), CT heterozygous mutant genotype (OR=0.53, CI=0.33-0.86, p=0.014) and T allele (OR=0.463, CI=0.32-0.66, p < 0.001). TT mutant genotype was only found in FGTB cases and frequency of CT heterozygous more in control group as compared to FGTB group. So, CT genotype worked as protective mutation for FGTB susceptibility group. In haplotype analysis of TLR-2 genetic variants, four possible combinations, i.e. (G-T, A-C, G-C, and A-T) were obtained. The frequency of haplotype A-C was significantly higher in FGTB cases (0.32). Control group did not show A-C haplotype and only found in FGTB cases. Conclusion: In conclusion, study showed a significant association with both genetic variants of TLR-2 of FGTB disease. Moreover, the presence of specific associated genotype/alleles suggest the possibility of disease severity and clinical approach aimed to prevent extensive damage by disease and also helpful for early detection of disease.

Keywords: ARMS, EDTA, FGTB, TLR

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Authors: Hamidreza Hoshyarmanesh, Hosein Madieh, Sanju Lama, Yaser Maddahi, Garnette R. Sutherland, Kourosh Zareinia

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This paper illustrates the concept of an algorithm to register specified markers on the neuroArm surgical manipulators, an image-guided MR-compatible tele-operated robot for microsurgery and stereotaxy. Two range-finding algorithms, namely time-of-flight and phase-shift, are evaluated for registration and supervisory control. The time-of-flight approach is implemented in a semi-field experiment to determine the precise position of a tiny retro-reflective moving object. The moving object simulates a surgical tool tip. The tool is a target that would be connected to the neuroArm end-effector during surgery inside the magnet bore of the MR imaging system. In order to apply flight approach, a 905-nm pulsed laser diode and an avalanche photodiode are utilized as the transmitter and receiver, respectively. For the experiment, a high frequency time to digital converter was designed using a field-programmable gate arrays. In the phase-shift approach, a continuous green laser beam with a wavelength of 530 nm was used as the transmitter. Results showed that a positioning error of 0.1 mm occurred when the scanner-target point distance was set in the range of 2.5 to 3 meters. The effectiveness of this non-contact approach exhibited that the method could be employed as an alternative for conventional mechanical registration arm. Furthermore, the approach is not limited by physical contact and extension of joint angles.

Keywords: 3D laser scanner, intraoperative MR imaging, neuroArm, real time registration, robot-assisted surgery, supervisory control

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Authors: M. Mousavi-Daramoroudi, H. Yousefnia, F. Abbasi-Davani, S. Zolghadri, S. Kakaei

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Despite the appropriate characteristics of ¹⁷⁷Lu and DOTATOC, to our best knowledge, the therapeutic benefit of ¹⁷⁷Lu-DOTATOC complex in breast cancer has not been reported until now. In this study, biodistribution of ¹⁷⁷Lu-DOTA-TOC in mouse tumor model for evaluation of possible utilization of this complex in breast cancer treatment was investigated.¹⁷⁷Lu was prepared with the specific activity of 2.6-3 GBq.mg^-1 and radionuclidic purity higher than 99%. The radiolabeled complex was prepared in the optimized conditions with the radiochemical purity higher than 99%. The final solution was injected to the BALB/c mice with adenocarcinoma breast cancer. The biodistribution results showed major accumulation in the kidneys as the major excretion route and the somatostatin receptor-positive tissues such as pancreas compared with the other tissues. Also, significant uptake was observed in tumor even in longer time after injection. According to the results obtained in this research study, somatostatin receptors expressed in breast cancers can be targeted with DOTATOC analogues especially with ¹⁷⁷Lu-DOTATOC as an ideal therapeutic agent.

Keywords: ¹⁷⁷Lu, adenocarcinoma breast cancer, DOTATOC, BALB/c mice

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Authors: Ping Li, Bing Feng, Junpu Zhao, Xudong Xie, Dangpeng Xu, Kuixing Zheng, Qihua Zhu, Xiaofeng Wei

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In laser driven inertial confinement fusion (ICF), the control of the temporal shape of the laser pulse is a key point to ensure an optimal interaction of laser-target. One of the main difficulties in controlling the temporal shape is the foot part control accuracy of high contrast pulse. Based on the analysis of pulse perturbation in the process of amplification and frequency conversion in high power lasers, an approach of beam spatio-temporal multiplexing is proposed to improve the control precision of high contrast pulse. In the approach, the foot and peak part of high contrast pulse are controlled independently, which propagate separately in the near field, and combine together in the far field to form the required pulse shape. For high contrast pulse, the beam area ratio of the two parts is optimized, and then beam fluence and intensity of the foot part are increased, which brings great convenience to the control of pulse. Meanwhile, the near field distribution of the two parts is also carefully designed to make sure their F-numbers are the same, which is another important parameter for laser-target interaction. The integrated calculation results show that for a pulse with a contrast of up to 500, the deviation of foot part can be improved from 20% to 5% by using beam spatio-temporal multiplexing approach with beam area ratio of 1/20, which is almost the same as that of peak part. The research results are expected to bring a breakthrough in power balance of high power laser facility.

Keywords: inertial confinement fusion, laser pulse control, beam spatio-temporal multiplexing, power balance

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Authors: Francesca Carta, Giovanna Linfante, Laura Agneni, Debora Radicchia, Camilla Micheletta, Angelo Del Cimmuto

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Overtaking competence mismatches and fostering career pathways congruent with the individual skills profile would significantly contribute to fighting unemployment. The aim of this paper is to examine the usefulness and efficiency of qualitative tools in supporting and improving the quality of caseworkers’ activities during the jobseekers’ profile analysis and career guidance process. The selected target groups are long-term and middle term unemployed, job seekers, young people at the end of the vocational training pathway and unemployed woman with social disadvantages. The experimentation is conducted in Italy at public employment services in 2017. In the framework of Italian labour market reform, the experimentation represents the first step to develop a customized qualitative model profiling; the final general object is to improve the public employment services quality. The experimentation tests the transferability of an OECD self-assessment competences tool in the Italian public employment services. On one hand, the first analysis results will indicate the user’s perception concerning the tool’s application and their different competence levels (literacy, numeracy, problem solving, career interest, subjective well-being and health, behavioural competencies) with reference to the specific target. On the other hand, the experimentation outcomes will show caseworkers understanding regarding the tool’s usability and efficiency for career guidance and reskilling and upskilling programs.

Keywords: career guidance, evaluation competences, reskilling pathway, unemployment

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Authors: Raptis Sotirios

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Health and social care (HSc) services planning and scheduling are facing unprecedented challenges due to the pandemic pressure and also suffer from unplanned spending that is negatively impacted by the global financial crisis. Data-driven can help to improve policies, plan and design services provision schedules using algorithms assist healthcare managers’ to face unexpected demands using fewer resources. The paper discusses services packing using statistical significance tests and machine learning (ML) to evaluate demands similarity and coupling. This is achieved by predicting the range of the demand (class) using ML methods such as CART, random forests (RF), and logistic regression (LGR). The significance tests Chi-Squared test and Student test are used on data over a 39 years span for which HSc services data exist for services delivered in Scotland. The demands are probabilistically associated through statistical hypotheses that assume that the target service’s demands are statistically dependent on other demands as a NULL hypothesis. This linkage can be confirmed or not by the data. Complementarily, ML methods are used to linearly predict the above target demands from the statistically found associations and extend the linear dependence of the target’s demand to independent demands forming, thus groups of services. Statistical tests confirm ML couplings making the prediction also statistically meaningful and prove that a target service can be matched reliably to other services, and ML shows these indicated relationships can also be linear ones. Zero paddings were used for missing years records and illustrated better such relationships both for limited years and in the entire span offering long term data visualizations while limited years groups explained how well patients numbers can be related in short periods or can change over time as opposed to behaviors across more years. The prediction performance of the associations is measured using Receiver Operating Characteristic(ROC) AUC and ACC metrics as well as the statistical tests, Chi-Squared and Student. Co-plots and comparison tables for RF, CART, and LGR as well as p-values and Information Exchange(IE), are provided showing the specific behavior of the ML and of the statistical tests and the behavior using different learning ratios. The impact of k-NN and cross-correlation and C-Means first groupings is also studied over limited years and the entire span. It was found that CART was generally behind RF and LGR, but in some interesting cases, LGR reached an AUC=0 falling below CART, while the ACC was as high as 0.912, showing that ML methods can be confused padding or by data irregularities or outliers. On average, 3 linear predictors were sufficient, LGR was found competing RF well, and CART followed with the same performance at higher learning ratios. Services were packed only if when significance level(p-value) of their association coefficient was more than 0.05. Social factors relationships were observed between home care services and treatment of old people, birth weights, alcoholism, drug abuse, and emergency admissions. The work found that different HSc services can be well packed as plans of limited years, across various services sectors, learning configurations, as confirmed using statistical hypotheses.

Keywords: class, cohorts, data frames, grouping, prediction, prob-ability, services

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Authors: Hong Su, Qiuju Yan, Wei Du, En Hu, Zhaoyu Yang, Wei Zhang, Yusheng Li, Tao Tang, Wang yang, Shushan Zhao

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Osteoarthritis (OA) is a severe chronic inflammatory disease. As the main active component of Astragalus mongholicus Bunge, a classic traditional ethnic herb, calycosin exhibits anti-inflammatory action and its mechanism of exact targets for OA have yet to be determined. In this study, we established an anterior cruciate ligament transection (ACLT) mouse model. Mice were randomized to sham, OA, and calycosin groups. Cartilage synthesis markers type II collagen (Col-2) and SRY-Box Transcription Factor 9 (Sox-9) increased significantly after calycosin gavage. While cartilage matrix degradation index cyclooxygenase-2 (COX-2), phosphor-epidermal growth factor receptor (p-EGFR), and matrix metalloproteinase-9 (MMP9) expression were decreased. With the help of network pharmacology and molecular docking, these results were confirmed in chondrocyte ATDC5 cells. Our results indicated that the calycosin treatment significantly improved cartilage damage, this was probably attributed to reversing the imbalance between chondrocyte synthesis and catabolism.

Keywords: calycosin, osteoarthritis, network pharmacology, molecular docking, inflammatory, cyclooxygenase 2

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Authors: Gail Louw, Helena Boshoff, Taeksun Song, Clifton Barry

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Drug resistance in Mycobacterium tuberculosis is primarily attributed to mutations in target genes. These mutations incur a fitness cost and result in bacterial generations that are less fit, which subsequently acquire compensatory mutations to restore fitness. We hypothesize that mutations in specific drug target genes influence bacterial metabolism and cellular function, which affects its ability to develop subsequent resistance to additional agents. We aim to determine whether the sequential acquisition of drug resistance and specific mutations in a well-defined clinical M. tuberculosis strain promotes or limits the development of additional resistance. In vitro mutants resistant to pretomanid, linezolid, moxifloxacin, rifampicin and kanamycin were generated from a pan-susceptible clinical strain from the Beijing lineage. The resistant phenotypes to the anti-TB agents were confirmed by the broth microdilution assay and genetic mutations were identified by targeted gene sequencing. Growth of mono-resistant mutants was done in enriched medium for 14 days to assess in vitro fitness. Double resistant mutants were generated against anti-TB drug combinations at concentrations 5x and 10x the minimum inhibitory concentration. Subsequently, mutation frequencies for these anti-TB drugs in the different mono-resistant backgrounds were determined. The initial level of resistance and the mutation frequencies observed for the mono-resistant mutants were comparable to those previously reported. Targeted gene sequencing revealed the presence of known and clinically relevant mutations in the mutants resistant to linezolid, rifampicin, kanamycin and moxifloxacin. Significant growth defects were observed for mutants grown under in vitro conditions compared to the sensitive progenitor. Mutation frequencies determination in the mono-resistant mutants revealed a significant increase in mutation frequency against rifampicin and kanamycin, but a significant decrease in mutation frequency against linezolid and sutezolid. This suggests that these mono-resistant mutants are more prone to develop resistance to rifampicin and kanamycin, but less prone to develop resistance against linezolid and sutezolid. Even though kanamycin and linezolid both inhibit protein synthesis, these compounds target different subunits of the ribosome, thereby leading to different outcomes in terms of fitness in the mutants with impaired cellular function. These observations showed that oxazolidinone treatment is instrumental in limiting the development of multi-drug resistance in M. tuberculosis in vitro.

Keywords: oxazolidinones, mutations, resistance, tuberculosis

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Authors: Fadila Hadjeris

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The study aims at investigating the functions of English-Arabic code switching in English as a foreign language classroom oral discourse and the extent to which they can contribute to the flow of classroom interaction. It also seeks to understand the views, beliefs, and perceptions of teachers and learners towards this practice. We hypothesized that code switching is a communicative strategy which facilitates classroom interaction. Due to this fact, both teachers and learners support its use. The study draws on a key body of literature in bilingualism, second language acquisition, and classroom discourse in an attempt to provide a framework for considering the research questions. It employs a combination of qualitative and quantitative research methods which include classroom observations and questionnaires. The analysis of the recordings shows that teachers’ code switching to Arabic is not only used for academic and classroom management reasons. Rather, the data display instances in which code switching is used for social reasons. The analysis of the questionnaires indicates that teachers and pupils have different attitudes towards this phenomenon. Teachers reported their deliberate switching during EFL teaching, yet the majority was against this practice. According to them, the use of the mother has detrimental effects on the acquisition and the practice of the target language. In contrast, pupils showed their preference to their teachers’ code switching because it enhances and facilitates their understanding. These findings support the fact that the shift to pupils’ mother tongue is a strategy which aids and facilitates the teaching and the learning of the target language. This, in turn, necessitates recommendations which are suggested to teachers and course designers.

Keywords: bilingualism, codeswitching, classroom interaction, classroom discourse, EFL learning/ teaching, SLA

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Authors: Alina Goldberg Cavalleri, Sara Franco Ortega, Nawaporn Onkokesung, Richard Dale, Melissa Brazier-Hicks, Robert Edwards

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Non-target site based resistance (NTSR) to herbicides in weeds is a polygenic trait associated with the upregulation of proteins involved in xenobiotic detoxification and translocation we have termed the xenome. Among the xenome proteins, ABC transporters play a key role in enhancing herbicide metabolism by effluxing conjugated xenobiotics from the cytoplasm into the vacuole. The importance of ABC transporters is emphasized by the fact that they often contribute to multidrug resistance in human cells and antibiotic resistance in bacteria. They also play a key role in insecticide resistance in major vectors of human diseases and crop pests. By surveying available databases, transcripts encoding ABCs have been identified as being enhanced in populations exhibiting NTSR in several weed species. Based on a transcriptomics data in black grass (Alopecurus myosuroides, Am), we have identified three proteins from the ABC-C subfamily that are upregulated in NTSR populations. ABC-C transporters are poorly characterized proteins in plants, but in Arabidopsis localize to the vacuolar membrane and have functional roles in transporting glutathionylated (GSH)-xenobiotic conjugates. We found that the up-regulation of AmABCs strongly correlates with the up-regulation of a glutathione transferase termed AmGSTU2, which can conjugate GSH to herbicides. The expression profile of the ABC transcripts was profiled in populations of black grass showing different degree of resistance to herbicides. This, together with a phylogenetic analysis, revealed that AmABCs cluster in different groups which might indicate different substrate and roles in the herbicide resistance phenotype in the different populations

Keywords: black grass, herbicide, resistance, transporters

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Authors: Endalew Fufa Kufi

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The research investigated the role of stakeholders such as students, teachers and administrators in the practices of good governance in higher education by looking into the special contributions of top-officials, teachers and students in ensuring workable ties and productive interchanges in Adama Science and Technology University. Attention was given to participation, fairness and exemplariness as key indicators of good governance. The target university was chosen for its familiarity for the researcher to get dependable data, access to respondent and management of the processing of data. Descriptive survey design was used for the purpose of describing concerned roles the stakeholders in the university governance in order to reflect on the nature of participation of the practices. Centres of the research were administration where supportive groups such as central administrators and underlying service-givers had parts and academia where teachers and students were target. Generally, 60 teachers, 40 students and 15 administrative officers were referents. Data were collected in the form of self-report through open-ended questionnaires. The findings indicated that, while vertical interchanges in terms of academic and administrative routines were had normal flow on top-down basis, planned practices of stakeholders in decision-making and reasonably communicating roles and changes in decisions with top-officials were not efficiently practiced. Moreover, the practices of good modelling were not witnessed to have existed to the fullest extent. Rather, existence of a very wide gap between the academic and administrative staffs was witnessed as was reflected the case between teachers and students. The implication was such that for shortage in participative atmosphere and weaning of fairness in governance, routine practices have been there as the vicious circles of governance.

Keywords: governance, participative, stakeholders, transformative, role-assumption

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Authors: Mekdes Getu Chekol, Biniam Tedros Kahsay, Rahwa Berihu Haile

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The main objective of this study is to investigate the marketing strategy practice in the Case of St. George Brewery Factory in Addis Ababa. One of the core activities in a Business Company to stay in business is having a well-developed marketing strategy. It assessed how the marketing strategies were practiced in the company to achieve its goals aligned with segmentation, target market, positioning, and the marketing mix elements to satisfy customer requirements. Using primary and secondary data, the study is conducted by using both qualitative and quantitative approaches. The primary data was collected through open and closed-ended questionnaires. Considering the size of the population is small, the selection of the respondents was carried out by using a census. The finding shows that the company used all the 4 Ps of the marketing mix elements in its marketing strategies and provided quality products at affordable prices by promoting its products by using high and effective advertising mechanisms. The product availability and accessibility are admirable with the practices of both direct and indirect distribution channels. On the other hand, the company has identified its target customers, and the company’s market segmentation practice is geographical location. Communication effectiveness between the marketing department and other departments is very good. The adjusted R2 model explains 61.6% of the marketing strategy practice variance by product, price, promotion, and place. The remaining 38.4% of variation in the dependent variable was explained by other factors not included in this study. The result reveals that all four independent variables, product, price, promotion, and place, have a positive beta sign, proving that predictor variables have a positive effect on that of the predicting dependent variable marketing strategy practice. Even though the marketing strategies of the company are effectively practiced, there are some problems that the company faces while implementing them. These are infrastructure problems, economic problems, intensive competition in the market, shortage of raw materials, seasonality of consumption, socio-cultural problems, and the time and cost of awareness creation for the customers. Finally, the authors suggest that the company better develop a long-range view and try to implement a more structured approach to attain information about potential customers, competitor’s actions, and market intelligence within the industry. In addition, we recommend conducting the study by increasing the sample size and including different marketing factors.

Keywords: marketing strategy, market segmentation, target marketing, market positioning, marketing mix

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Authors: Afaf Alhusayni, Elizabeth Sheppard, Asiyya Jaffrani, Peter Mitchell, Lauren Marsh

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Introduction: Previous research has found that people make systematic judgments about others based on small glimpses of their behavior. Furthermore, autistic people are consistently judged more negatively than non-autistic people in terms of favourability and approachability. Objectives: This project focuses on a hitherto unstudied type of judgment that is highly relevant within a university context, judgments about academic performance. This is particularly important as autistic university students are less likely to complete their degrees than neurotypical students. Methods: Twenty-five neurotypical perceivers (21 females - 4 males) viewed a series of 4s video clips featuring an individual ‘target’ displaying natural behavior. Nine of these targets were autistic and nine were neurotypical. Perceivers were asked to rate each target on four aspects related to university life (motivation, success, grades, and happiness). Results: Autistic targets were judged more negatively on all aspects compared to neurotypical targets. Conclusions: This study concludes that neurotypical perceivers negatively judge the academic performance of autistic students. This suggests that autistic university students face unfavorable scrutiny and judgment, which may negatively impact their academic success. Implications: These initial findings provide important evidence that autistic people are negatively stigmatized within education environments. Further work is needed to ascertain the extent to which these negative judgments may feed into attainment gaps for autistic students. This information is useful for the education department, government, and social care organizations, enabling change in the provision of support for autistic students.

Keywords: autistic person perception, academic performance, stigma and judgment, higher education

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Authors: Laleh Golamrej Eliasi, Mahsa Tahzibi, Mohammad Torkashvand Moradabadi

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TheIranian Ear, Throat, Nose, Head, and Neck Research Center has estimated that three to five percent of Iran’s population has moderate to profound hearing disorders. The prevalence of hearing loss in provincial centers is equal to 4.7 per thousand live births (362 cases). The deaf community has limited access to information and health services due to language and communication barriers. Communication and language limitations isolate and limit deaf people from social media, health services, and communication with caregivers and health providers.Limitedcommunicationwith the deaf has led to a lack of knowledge and information about domestic violence against the deaf (DVAD) in this target group in Iran. To fill this knowledge gap, deaf living in Iranwere selected as the target group to assess their views on DVAD. This study is implemented in the socio-ecological approach framework to assess the impacts of individual characteristics, interpersonal relationships, community, and society components on DVAD. Semi-structured interviews with the Iranian deaf and Content analysis are used to find the participants’ point of view on DVAD, its risk factors, and the reduction approach to DVAD. The main purpose is to obtain information about participants' views on the subject. The findings can be used to improve culturally safe social work knowledge and practices with a bottom-up approach to reduce DV and increase their well-being. Therefore, this research can have important effects on the sustainable development of services and supports the welfare and inclusion of the deaf.

Keywords: domestic violence, Iranian deaf, social work, content analysis

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Authors: Saulutė Juzelėnienė, Skirmantė Šarkauskienė

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In this paper, it is aimed to analyse the multimodal representations of the concepts of LOVE and PASSION in Lithuanian graphic novel “Gertrūda”, by Gerda Jord. The research is based on the earlier findings by Forceville (2005), Eerden (2009) as well as insights made by Shihara and Matsunaka (2009) and Kövecses (2000). The domains of target and source of LOVE and PASSION metaphors in comics are expressed by verbal and non-verbal cues. The analysis of non-verbal cues adopts the concepts of rune and indexes. A pictorial rune is a graphic representation of an object that does not exist in reality in comics, such as lines, dashes, text "balloons", and pictorial index – a graphically represented object of reality, a real symptom expressing a certain emotion, such as a wide smile, furrowed eyebrows, etc. Indexes are often hyperbolized in comics. The research revealed that most frequent source domains are CLOSINESS/UNITY, NATURAL/ PHYSICAL FORCE, VALUABLE OBJECT, PRESSURE. The target is the emotion of LOVE/PASSION which belongs to a more abstract domain of psychological experience. In this kind of metaphor, the picture can be interpreted as representing the emotion of happiness. Data are taken from Lithuanian comic books and Internet sites, where comics have been presented. The data and the analysis we are providing in this article aims to reveal that there are pictorial metaphors that manifest conceptual metaphors that are also expressed verbally and that methodological framework constructed for the analysis in the papers by Forceville at all is applicable to other emotions and culture specific pictorial manifestations.

Keywords: multimodal metaphor, conceptual metaphor, comics, graphic novel, concept of love/passion

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Authors: Kadiri Kayode Ibrahim, Kadiri Omowunmi

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The research study was concerned with an evaluation of the effect of marketing strategy on the performance of SMEs in Abuja. This was achieved, specifically, through the examination of the effect of disaggregated components of Marketing Strategy (Product, Price, Promotion, Placement and Process) on Sales Volume (as a proxy for performance). The study design was causal in nature, with the use of quantitative methods involving a cross-sectional survey carried out with the administration of a structured questionnaire. A multistage sample of 398 respondents was utilized to provide the primary data used in the study. Subsequently, path analysis was employed in processing the obtained data and testing formulated hypotheses. Findings from the study indicated that all modeled components of marketing strategy were positive and statistically significant determinants of performance among businesses in the zone. It was, therefore, recommended that SMEs invest in continuous product innovation and development that are in line with the needs and preferences of the target market, as well as adopt a dynamic pricing strategy that considers both cost factors and market conditions. It is, therefore, crucial that businesses in the zone adopt marker communication measures that would stimulate brand awareness and increase engagement, including the use of social media platforms and content marketing. Additionally, owner-managers should ensure that their products are readily available to their target customers through an emphasis on availability and accessibility measures. Furthermore, a commitment to consistent optimization of internal operations is crucial for improved productivity, reduced costs, and enhanced customer satisfaction, which in turn will positively impact their overall performance.

Keywords: product, price, promotion, placement

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Authors: Sabahattin Comertpay, Sandra Pastorino, Rosanna Mezzapelle, Mika Tanji, Oriana Strianese, Andrea Napolitano, Tracey Weigel, Joseph Friedberg, Paul Sugarbaker, Thomas Krausz, Ena Wang, Amy Powers, Giovanni Gaudino, Harvey I. Pass, Fatmagul Ozcelik, Barbara L. Parsons, Haining Yang, Michele Carbone

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Tumors are thought to be monoclonal in origin. This paradigm arose decades ago, primarily from the study of hematopoietic malignancies and sarcomas. The clonal origin of malignant mesothelioma (MM), a deadly cancer resistant to the current therapies, has not been investigated. Examination of the pleura from patients with MM shows often the presence of multiple pleural nodules, raising the question of whether they represent independent or metastatic growth processes. To investigate the clonality patterns of MM, we used the HUMARA (Human Androgen Receptor) assay to examine 14 sporadic and 2 familial Malignant Mesotheliomas (MM). Of 16 specimens studied, 15 were informative and 14/15 revealed two electrophoretically distinct methylated HUMARA alleles, indicating a polyclonal origin for these tumors. This discovery has important clinical implications, because an accurate assessment of tumor clonality is key to the design of novel molecular strategies for the treatment of MM.

Keywords: malignant mesothelioma, clonal origin, HUMARA, sarcomas

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Authors: Regina M. Chiechio, Rémi Leguevél, Helene Solhi, Marie Madeleine Gueguen, Stephanie Dutertre, Xavier, Jean-Pierre Bazureau, Olivier Mignen, Pascale Even-Hernandez, Paolo Musumeci, Maria Jose Lo Faro, Valerie Marchi

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Thanks to their ultra-small size, high electron density, and low toxicity, gold nanoclusters (Au NCs) have unique photoelectrochemical and luminescence properties that make them very interesting for diagnosis bio-imaging and theranostics. These applications require control of their delivery and interaction with cells; for this reason, the surface chemistry of Au NCs is essential to determine their interaction with the targeted biological objects. Here we demonstrate their ability as markers of pancreatic tumor cells. By functionalizing the surface of the NCs with a recognition peptite (U11), the nanostructures are able to preferentially bind to pancreatic cancer cells via a receptor (uPAR) overexpressed by these cells. Furthermore, the NCs can mark even the nucleus without the need of fixing the cells. These nanostructures can therefore be used as a non-toxic, multivalent luminescent platform, capable of selectively recognizing tumor cells for bioimaging, drug delivery, and radiosensitization.

Keywords: gold nanoclusters, luminescence, biomarkers, pancreatic cancer, biomedical applications, bioimaging, fluorescent probes, drug delivery

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Authors: Wilailuk Meepracha

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The results of the study on the project evaluation to develop the competencies, capabilities, and skills in repairing computers of people in Jompluak Local Municipality, Bang Khonthi District, Samut Songkram Province showed that the overall result was good (4.33). When considering on each aspect, it was found that the highest one was on process evaluation (4.60) followed by product evaluation (4.50) and the least one was on feeding factor (3.97). When considering in details, it was found that: 1) the context aspect was high (4.23) with the highest item on the arrangement of the training situation (4.67) followed by the appropriateness of the target (4.30) and the least aspect was on the project cooperation (3.73). 2) The evaluation of average overall primary factor or feeding factor showed high value (4.23) while the highest aspect was on the capability of the trainers (4.47) followed by the suitable venue (4.33) while the least aspect was on the insufficient budget (3.47). 3) The average result of process evaluation was very high (4.60). The highest aspect was on the follow-op supervision (4.70) followed by responsibility of each project staffs (4.50) while the least aspect was on the present situation and the problems of the community (4.40). 4) The overall result of the product evaluation was very high (4.50). The highest aspect was on the diversity of the activities and the community integration (4.67) followed by project target achievement (4.63) while the least aspect was on continuation and regularity of the activities (4.33). The trainees reported high satisfaction on the project management at very high level (43.33%) while 40% reported high level and 16.67% reported moderate level. Suggestions for the project were on the additional number of the computer sets (37.78%) followed by longer training period especially on computer skills (43.48%).

Keywords: project evaluation, competency development, the capability on computer repairing and computer skills

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Authors: Johannes Günther

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Time Sensitive Networking (TSN), standardized in the IEEE 802.1 standard, has been lent increasing attention in the context of mission critical systems. Such mission critical systems, e.g., in the automotive domain, aviation, industrial, and smart factory domain, are responsible for coordinating complex functionalities in real time. In many of these contexts, a reliable data exchange fulfilling hard time constraints and quality of service (QoS) conditions is of critical importance. TSN standards are able to provide guarantees for deterministic communication behaviour, which is in contrast to common best-effort approaches. Therefore, the superior QoS guarantees of TSN may aid in the development of new technologies, which rely on low latencies and specific bandwidth demands being fulfilled. TSN extends existing Ethernet protocols with numerous standards, providing means for synchronization, management, and overall real-time focussed capabilities. These additional QoS guarantees, as well as management mechanisms, lead to an increased attack surface for potential malicious attackers. As TSN guarantees certain deadlines for priority traffic, an attacker may degrade the QoS by delaying a packet beyond its deadline or even execute a denial of service (DoS) attack if the delays lead to packets being dropped. However, thus far, security concerns have not played a major role in the design of such standards. Thus, while TSN does provide valuable additional characteristics to existing common Ethernet protocols, it leads to new attack vectors on networks and allows for a range of potential attacks. One answer to these security risks is to deploy defense mechanisms according to a moving target defense (MTD) strategy. The core idea relies on the reduction of the attackers' knowledge about the network. Typically, mission-critical systems suffer from an asymmetric disadvantage. DoS or QoS-degradation attacks may be preceded by long periods of reconnaissance, during which the attacker may learn about the network topology, its characteristics, traffic patterns, priorities, bandwidth demands, periodic characteristics on links and switches, and so on. Here, we implemented and tested several MTD-like defense strategies against different attacker models of varying capabilities and budgets, as well as collaborative attacks of multiple attackers within a network, all within the context of TSN networks. We modelled the networks and tested our defense strategies on an OMNET++ testbench, with networks of different sizes and topologies, ranging from a couple dozen hosts and switches to significantly larger set-ups.

Keywords: network security, time sensitive networking, moving target defense, cyber security

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