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Authors: Petra Hofmann, Dana Koniel, Jussi Luukkanen, Walter Nieminen, Lea Hannola, Ilkka Donoghue

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The Covid-19 pandemic forced people to isolate and become physically less connected. The pandemic hasnot only reshaped people’s behaviours and needs but also accelerated digital transformation (DT). DT of cities has become an imperative with the outlook of converting them into smart cities in the future. Embedding digital infrastructure and smart city initiatives as part of the normal design, construction, and operation of cities provides a unique opportunity to improve connection between people. Internet of Things (IoT) is an emerging technology and one of the drivers in DT. It has disrupted many industries by introducing different services and business models, and IoT solutions are being applied in multiple fields, including smart cities. As IoT and data are fundamentally linked together, IoT solutions can only create value if the data generated by the IoT devices is analysed properly. Extracting relevant conclusions and actionable insights by using established techniques, data analytics contributes significantly to the growth and success of IoT applications and investments. Companies must grasp DT and be prepared to redesign their offerings and business models to remain competitive in today’s marketplace. As there are many IoT solutions available today, the amount of data is tremendous. The challenge for companies is to understand what solutions to focus on and how to prioritise and which data to differentiate from the competition. This paper explains how IoT and data analytics can impact competitive advantage and how companies should approach IoT and data analytics to translate them into concrete offerings and solutions in the smart city context. The study was carried out as a qualitative, literature-based research. A case study is provided to validate the preservation of company’s competitive advantage through smart city solutions. The results of the researchcontribution provide insights into the different factors and considerations related to creating competitive advantage through IoT and data analytics deployment in the smart city context. Furthermore, this paper proposes a framework that merges the factors and considerations with examples of offerings and solutions in smart cities. The data collected through IoT devices, and the intelligent use of it, can create a competitive advantage to companies operating in smart city business. Companies should take into consideration the five forces of competition that shape industries and pay attention to the technological, organisational, and external contexts which define factors for consideration of competitive advantages in the field of IoT and data analytics. Companies that can utilise these key assets in their businesses will most likely conquer the markets and have a strong foothold in the smart city business.

Keywords: internet of things, data analytics, smart cities, competitive advantage

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Authors: Caroline Kim

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Scholars have long disputed the relationship between the origins of language and human behavior. Historically, behaviorist psychologist B. F. Skinner argued that language is one instance of the general stimulus-response phenomenon that characterizes the essence of human behavior. Another, more recent approach argues, by contrast, that language is an innate cognitive faculty and does not arise from behavior, which might develop and reinforce linguistic facility but is not its source. Pinker, among others, proposes that linguistic defects arise from damage to the brain, both congenital and acquired in life. Much of his argument is based on case studies in which damage to the Broca’s and Wernicke’s areas of the brain results in loss of the ability to produce coherent grammatical expressions when speaking or writing; though affected speakers often utter quite fluent streams of sentences, the words articulated lack discernible semantic content. Pinker concludes on this basis that language is an innate component of specific, classically language-correlated regions of the human brain. Taking a notorious 1970s case of linguistic maladaptation, this paper queries the dominant materialist paradigm of language-correlated regions. Susan “Genie” Wiley was physically isolated from language interaction in her home and beaten by her father when she attempted to make any sort of sound. Though without any measurable resulting damage to the brain, Wiley was never able to develop the level of linguistic facility normally achieved in adulthood. Having received a negative reinforcement of language acquisition from her father and lacking the usual language acquisition period, in adulthood Wiley was able to develop language only at a quite limited level in later life. From a contemporary behaviorist perspective, this case confirms the possibility of language deficiency without brain pathology. Wiley’s potential language-determining areas in the brain were intact, and she was exposed to language later in her life, but she was unable to achieve the normal level of communication skills, deterring socialization. This phenomenon and others like it in the case limited literature on linguistic maladaptation pose serious clinical, scientific, and indeed philosophical difficulties for both of the major competing theories of language acquisition, innateness, and linguistic stimulus-response. The implications of such cases for future research in language acquisition are explored, with a particular emphasis on the interaction of innate capacity and stimulus-based development in early childhood.

Keywords: behaviorism, innateness hypothesis, language, Susan "Genie" Wiley

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Authors: Atsuko Okazaki, Jurg Ott

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Some genetic diseases (‘digenic traits’) are due to the interaction between two DNA variants. For example, certain forms of Retinitis Pigmentosa (a genetic form of blindness) occur in the presence of two mutant variants, one in the ROM1 gene and one in the RDS gene, while the occurrence of only one of these mutant variants leads to a completely normal phenotype. Detecting such digenic traits by genetic methods is difficult. A common approach to finding disease-causing variants is to compare 100,000s of variants between individuals with a trait (cases) and those without the trait (controls). Such genome-wide association studies (GWASs) have been very successful but hinge on genetic effects of single variants, that is, there should be a difference in allele or genotype frequencies between cases and controls at a disease-causing variant. Frequent pattern mining (FPM) methods offer an avenue at detecting digenic traits even in the absence of single-variant effects. The idea is to enumerate pairs of genotypes (genotype patterns) with each of the two genotypes originating from different variants that may be located at very different genomic positions. What is needed is for genotype patterns to be significantly more common in cases than in controls. Let Y = 2 refer to cases and Y = 1 to controls, with X denoting a specific genotype pattern. We are seeking association rules, ‘X → Y’, with high confidence, P(Y = 2|X), significantly higher than the proportion of cases, P(Y = 2) in the study. Clearly, generally available FPM methods are very suitable for detecting disease-associated genotype patterns. We use fpgrowth as the basic FPM algorithm and built a framework around it to enumerate high-frequency digenic genotype patterns and to evaluate their statistical significance by permutation analysis. Application to a published dataset on opioid dependence furnished results that could not be found with classical GWAS methodology. There were 143 cases and 153 healthy controls, each genotyped for 82 variants in eight genes of the opioid system. The aim was to find out whether any of these variants were disease-associated. The single-variant analysis did not lead to significant results. Application of our FPM implementation resulted in one significant (p < 0.01) genotype pattern with both genotypes in the pattern being heterozygous and originating from two variants on different chromosomes. This pattern occurred in 14 cases and none of the controls. Thus, the pattern seems quite specific to this form of substance abuse and is also rather predictive of disease. An algorithm called Multifactor Dimension Reduction (MDR) was developed some 20 years ago and has been in use in human genetics ever since. This and our algorithms share some similar properties, but they are also very different in other respects. The main difference seems to be that our algorithm focuses on patterns of genotypes while the main object of inference in MDR is the 3 × 3 table of genotypes at two variants.

Keywords: digenic traits, DNA variants, epistasis, statistical genetics

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Authors: Michio Kurosu

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Alterations in glycosylation not only directly impact cell growth and survival but also facilitate tumor-induced immunomodulation and eventual metastasis. Identification of cell type-specific glycoconjugates (tumor markers) has led to the discovery of new assay systems for certain cancers via immunodetection reagents. N- and O-linked glycans are the most abundant forms of glycoproteins. Recent studies of cancer immunotherapy are based on the immunogenicity of truncated O-glycan chains (e.g., Tn, sTn, T, and sLea/x). The prevalence of N-linked glycan changes in the development of tumor cells is known; however, therapeutic antibodies against N-glycans have not yet been developed. This is due to the lack of specificity of N-linked glycans between normal/healthy and cancer cells. Abnormal branching of N-linked glycans has been observed, particularly in solid cancer cells. While the discovery of drug-like glycosyltransferase inhibitors that block the biosynthesis of specific branching has a very low likelihood of success, altered glycosylation levels can be exploited by suppressing N-glycan biosynthesis through the inhibition of dolichyl-phosphate N-acetylglucosaminephosphotransferase1 (DPAGT1) activity. Inhibition of DPAGT1 function leads to changes of O-glycosylation on proteins associated with mitochondria and zinc finger binding proteins (indirect effects). On the basis of dynamic crosstalk between DPAGT1 and Snail/Slung/ZEB1 (a family of transcription factors that promote the repression of the adhesion molecules), we have developed pharmacologically acceptable selective DPAGT1 inhibitors. Tunicamycin kills a wide range of cancer and healthy cells in a non-selective manner. In sharp contrast, our DPAGT1 inhibitors display strong cytostatic effects against 16 solid cancers, which require the overexpression of DPAGT1 in their progression but do not affect the cell viability of healthy cells. The identified DPAGT1 inhibitors possess impressive anti-metastatic ability in various solid cancer cell lines and induce their mitochondrial structural changes, resulting in apoptosis. A prototype DPAGT1 inhibitor, APPB has already been proven to shrink solid tumors (e.g., pancreatic cancers, triple-negative breast cancers) in vivo while suppressing metastases and has strong synergistic effects when combined with current cytotoxic drugs (e.g., paclitaxel). At this conference, our discovery of selective DPAGT1 inhibitors with drug-like properties and proof-of-pharmaceutical concept studies of a novel DPAGT1 inhibitor are presented.

Keywords: DPAGT1 inhibitors, anti-metastatic drugs, natural product based drug designs, cytostatic effects

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Authors: Somayeh Fani, Mahmood Ameen Abdulla

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Costus speciosus is an important Malaysian medicinal plant commonly used traditionally in the treatment of many aliments. The present investigation is designed to elucidate preventive effects of ethanolic extracts of C. speciosus rhizome against absolute ethanol-induced gastric mucosal injury in Sprague-Dawley rats. Five groups of rats were orally pre-treated with vehicle, carboxymethylcellulose (CMC) as normal control group (Group 1), ethanol as ulcer control group (Group 2), omeprazole 20 mg/kg (reference group) (Group 3), and 250 and 500 mg/kg of C. speciosus extract (experimental groups) (Group 4 and 5), respectively. An hour later, CMC was given orally to Group 1 rats and absolute ethanol was given orally to Group 2-5 rats to generate gastric mucosal injury. After an additional hour, the rats were sacrificed. Grossly, ulcer control group exhibited severe of gastric mucosal hemorrhagic injury and increased in ulcer area, whereas groups pre-treated with omeprazole or plant’s rhizomes exhibited the significant reduction of gastric mucosal injury. Significant increase in the pH and mucous of gastric content was observed in rats re-treated with C. speciosus rhizome. Histology, ulcer control rats, demonstrated remarkable disruption of gastric mucosa, increased in edema and inflammatory cells infiltration of submucosal layer compared to rats pre-treated with rhizomes extract. Periodic acid Schiff staining for glycoprotein, rats pre-fed with C. speciosus C. displayed remarkably intense uptake of magenta color by glandular gastric mucosa compared with ulcer control rats. Immunostaining of gastric epithelium, rats pre-treatment with rhizome extract provide evidence of up-regulation of HSP70 and down-regulation of Bax proteins compared to ulcer control animals. Gastric tissue homogenate, C. speciosus significantly increased the activity of superoxide dismutase (SOD), and catalase (CAT), increased the level of non-protein sulfhydryl (NP-SH) and decreased the level of lipid peroxidation after ethanol administration. Acute toxicity test did not show any signs of toxicity. The mechanisms implicated the gasrtoprotective property of C. speciosus depend upon the antisecretory activity, increased in gastric mucus glycoprotein, up-regulation of HSP70 protein and down-regulation of Bax proteins, reduction in the lipid peroxidation and increase in the level of NP-SH and antioxidant enzymes activity in gastic homogenate.

Keywords: antioxidant, Costus speciosus, gastric ulcer, histology, omeprazole

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Authors: Rui Wang, Luodi Yu, Dan Huang, Hsuan-Chih Chen, Yang Zhang, Suiping Wang

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Enhanced discrimination of pure tones but diminished discrimination of speech pitch (i.e., lexical tone) were found in children with autism who speak a tonal language (Mandarin), suggesting a speech-specific impairment of pitch perception in these children. However, in tonal languages, both lexical tone and vowel are phonemic cues and integrally dependent on each other. Therefore, it is unclear whether the presence of phonemic vowel dimension contributes to the observed lexical tone deficits in Mandarin-speaking children with autism. The current study employed a multi-feature oddball paradigm to examine how vowel and tone dimensions contribute to the neural responses for syllable change detection and involuntary attentional orienting in school-age Mandarin-speaking children with autism. In the oddball sequence, syllable /da1/ served as the standard stimulus. There were three deviant stimulus conditions, representing tone-only change (TO, /da4/), vowel-only change (VO, /du1/), and change of tone and vowel simultaneously (TV, /du4/). EEG data were collected from 25 children with autism and 20 age-matched normal controls during passive listening to the stimulation. For each deviant condition, difference waveform measuring mismatch negativity (MMN) was derived from subtracting the ERP waveform to the standard sound from that to the deviant sound for each participant. Additionally, the linear summation of TO and VO difference waveforms was compared to the TV difference waveform, to examine whether neural sensitivity for TV change detection reflects simple summation or nonlinear integration of the two individual dimensions. The MMN results showed that the autism group had smaller amplitude compared with the control group in the TO and VO conditions, suggesting impaired discriminative sensitivity for both dimensions. In the control group, amplitude of the TV difference waveform approximated the linear summation of the TO and VO waveforms only in the early time window but not in the late window, suggesting a time course from dimensional summation to nonlinear integration. In the autism group, however, the nonlinear TV integration was already present in the early window. These findings suggest that speech perception atypicality in children with autism rests not only in the processing of single phonemic dimensions, but also in the dimensional integration process.

Keywords: autism, event-related potentials , mismatch negativity, speech perception

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Authors: Josephine Muchiri, Makena Muriithi

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Adverse mental health consequences are experienced by those that have been touched by Intimate Partner Violence (IPV), whether directly or indirectly. These negative effects are felt not only in the short term but in years to come. It is important to examine the prevalence and co-occurrence of mental disorders in order to provide strategic interventions for women who have experienced IPV. The aim of this study was to examine the prevalence and comorbidity of post-traumatic stress disorder (PTSD), Depression, and Anxiety among women who had experienced intimate Partner violence in two selected informal settlements in Nairobi County, Kenya. Participants were 116 women (15-60 years) selected through purposive and snowball sampling from the low social, economic settlements (Kawangware and Kibera) in Nairobi, Kenya. A social demographic questionnaire and the Woman Abuse Screening Tool (WAST) were used to collect data on intimate partner violence experiences. The PTSD Checklist for DSM-5 (PCL-5), Beck’s Depression Inventory, and the Beck’s Anxiety Inventory assessed for post-traumatic stress disorder, depression, and anxiety, respectively. Data analysis was conducted using the Statistical Package for Social Sciences (SPSS) version 29, utilizing descriptive and correlation analyses. Findings indicated that the women had undergone various forms of abuse from their intimate partners, which were physical abuse 111(92.5%), sexual abuse 70(88.6%), and verbal abuse 92(93.9%). The prevalence of the mental disorders was PTSD 47(32.4%); M= 44.11, S.D =14.67, depression was the highest at n=131(90.3%; M=33.37±9.98) with the levels of depression having varying prevalence rates where severe depression had the highest representation [moderate: n= 35; 24.1%, severe: n=69 (47.6%) and extremely severe: n=27(18.6%)]. Anxiety had the second highest prevalence of n=99 (68.8%; M= 28.55±13.63) with differing prevalence rates in the levels of anxiety which were normal anxiety: 45(31.3%), moderate anxiety n=62(43.1%) and severe anxiety: n=37(25.7%). Regarding comorbidities, the Pearson correlation test showed that there was a significant (p=0.000) positive relationship between PTSD and depression (r=0.379; p=.000), PTSD and anxiety (r=0.624; p=.000), and depression and anxiety (r=0.386; p=.000) such that increase in one disorder concomitantly led to increase of the other two disorders; hence comorbidity of the three disorders was ascertained. Conclusion: The study asserted the adverse impacts of IPV on women’s mental well-being, where the prevalence of PTSD, depression, and anxiety was established. Almost all the women had depressive symptoms; whereas more than half had anxiety and slightly more than a third had PTSD. Regarding the severity levels of anxiety and depression, almost half of the women with depression had severe depression whereas moderate anxiety was more prevalent for those with anxiety. The three disorders were found to co-occur where comorbidities of PTSD and anxiety had the highest probability of co-occurrence. It is thus recommended that mental health interventions with a focus on the three disorders be offered for women undergoing IPV.

Keywords: anxiety, comorbidity, depression, intimate partner violence, post-traumatic stress disorder

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Authors: Elif Gencturk, Ekin Yurdakul, Ahmet Y. Celik, Senol Mutlu, Kutlu O. Ulgen

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Yeast cells are generally used as a model system of eukaryotes due to their complex genetic structure, rapid growth ability in optimum conditions, easy replication and well-defined genetic system properties. Thus, yeast cells increased the knowledge of the principal pathways in humans. During fermentation, carbohydrates (hexoses and pentoses) degrade into some toxic by-products such as 5-hydroxymethylfurfural (5-HMF or HMF) and furfural. HMF influences the ethanol yield, and ethanol productivity; it interferes with microbial growth and is considered as a potent inhibitor of bioethanol production. In this study, yeast single cell behavior under HMF application was monitored by using a continuous flow single phase microfluidic platform. Microfluidic device in operation is fabricated by hot embossing and thermo-compression techniques from cyclo-olefin polymer (COP). COP is biocompatible, transparent and rigid material and it is suitable for observing fluorescence of cells considering its low auto-fluorescence characteristic. The response of yeast cells was recorded through Red Fluorescent Protein (RFP) tagged Nop56 gene product, which is an essential evolutionary-conserved nucleolar protein, and also a member of the box C/D snoRNP complexes. With the application of HMF, yeast cell proliferation continued but HMF slowed down the cell growth, and after HMF treatment the cell proliferation stopped. By the addition of fresh nutrient medium, the yeast cells recovered after 6 hours of HMF exposure. Thus, HMF application suppresses normal functioning of cell cycle but it does not cause cells to die. The monitoring of Nop56 expression phases of the individual cells shed light on the protein and ribosome synthesis cycles along with their link to growth. Further computational study revealed that the mechanisms underlying the inhibitory or inductive effects of HMF on growth are enriched in functional categories of protein degradation, protein processing, DNA repair and multidrug resistance. The present microfluidic device can successfully be used for studying the effects of inhibitory agents on growth by single cell tracking, thus capturing cell to cell variations. By metabolic engineering techniques, engineered strains can be developed, and the metabolic network of the microorganism can thus be manipulated such that chemical overproduction of target metabolite is achieved along with the maximum growth/biomass yield.  

Keywords: COP, HMF, ribosome biogenesis, thermoplastic microbioreactor, yeast

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Authors: Maria Barbano Acevedo-Gomez, Elena Sonsoles Rodriguez-Lopez, Sofia Olivia Calvo-Moreno, Angel Basas-Garcia, Cristophe Ramirez

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Introduction: Urinary incontinence (UI) is defined as the involuntary leakage of urine. In persons who practice sport, its prevalence is 36.1% (95% CI 26.5%-46.8%) and varies as it seems to depend on the intensity of exercise, movements, and impact on the ground. Such high impact sports are likely to generate higher intra-abdominal pressures and leading to pelvic floor muscle weakness. Even though the emphasis of this research is on female athletes, all women should perform pelvic floor muscle exercises as a part of their general physical exercise. Pelvic floor exercises are generally considered the first treatment against urinary incontinence. Objective: The main objective of the present study was to determine the knowledge of the pelvic floor and of the UI in elite athletes and know if they incorporate pelvic floor strengthening in their training. Methods: This was an observational study conducted on 754 elite athletes. After collecting questions about the pelvic floor, UI, and sport-related data, participants completed the questionnaire International Consultation on Incontinence Questionnaire-UI Short-Form (ICIQ-SF). Results: 57.3% of the athletes reflect not having knowledge of their pelvic floor, 48.3% do not know what strengthening exercises are, and around 90% have never practiced them. 78.1% (n=589) of all elite athletes do not include pelvic floor exercises in their training. Of the elite athletes surveyed, 33% had UI according to ICIQ-SF (mean age 23.75 ± 7.74 years). In response to the question 'Do you think you have or have had UI?', Only 9% of the 754 elite athletes admitted they presently had UI, and 13.3% indicated they had had UI at some time. However, 22.7% (n=171) reported they had experienced urine leakage while training. Of the athletes who indicated they did not have UI in the ICIQ-SF, 25.7% stated they did experience urine leakage during training (χ² [1] = 265.56; p < 0.001). Further, 12.3% of the athletes who considered they did not have UI and 60% of those who admitted they had had UI on some occasion stated they had suffered some urine leakage in the past 3 months (χ² [1] = 287.59; p < 0.001). Conclusions: There is a lack of knowledge about UI in sport. Through the use of validated questionnaires, we observed a UI prevalence of 33%, and 22.7% reported they experienced urine leakage while training. These figures contrast with only 9% of athletes who reported they had or had in the past had UI. This discrepancy could reflect the great lack of knowledge about UI in sports and that sometimes an athlete may consider that urine leakage is normal and a consequence of the demands of training. These data support the idea that coaches, physiotherapists, and other professionals involved in maximizing the performance of athletes should include pelvic floor muscle exercises in their training programs. Measures such as this could help to prevent UI during training and could be a starting point for future studies designed to develop adequate prevention and treatment strategies for this embarrassing problem affecting young athletes, both male and female.

Keywords: athletes, pelvic floor, performance, prevalence, sport, training, urinary incontinence

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Authors: Elena Maria Scalisi

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The increasing production and the use of TiO₂ nanoparticles (NPs) have inevitably led to their release into the environment, thereby posing a threat to organisms and also for human. Human exposure to TiO₂-NPs may occur during both manufacturing and use. TiO₂-NPs are common in consumer products for dermal application, toothpaste, food colorants, and nutritional supplements, then oral exposure may occur during use of such products. Into the body, TiO₂-NPs thanks to their small size (<100 nm), can, through testicular blood barrier inducing effect on testis and then on male reproductive health. The nanoscale size of TiO₂ increase the surface-to-volume ratio making them more reactive in a cell, then TiO₂ NPs increase their ability to produce reactive oxygen species (ROS). In male germ cells, ROS may have important implications in maintaining the normal functions of mature spermatozoa at physiological levels, moreover, in spermatozoa they are important signaling molecules for their hyperactivation and acrosome reaction. Nevertheless, an excess of ROS by external inputs such as NPs can increased the oxidative stress (OS), which results in damage DNA and apoptosis. The aim of our study has been investigate the impact of TiO₂ NPs on human spermatozoa, evaluating DNA damage and the expression of proteins involved in cell stress. According WHO guidelines 2021, we have exposed human spermatozoa in vitro to TiO₂ NP at concentrations 50 ppm, 100 ppm, 250 ppm, and 500 ppm for 1 hour (at 37°C and CO₂ at 5%). DNA damage was evaluated by Sperm Chromatin Dispersion Test (SCD) and TUNEL assay; moreover, we have evaluated the expression of biomarkers of oxidative stress like Heat Shock Protein 70 (HSP70) and Metallothioneins (MTs). Also, sperm parameters as motility viability have been evaluated. Our results not report a significant reduction in motility of spermatozoa at the end of the exposure. On the contrary, the progressive motility was increased at the highest concentration (500 ppm) and was statistically significant compared to control (p <0.05). Also, viability was not changed by exposure to TiO₂-NPs (p <0.05). However, increased DNA damage was observed at all concentrations, and the TUNEL assay highlighted the presence of single strand breaks in the DNA. The spermatozoa responded to the presence of TiO₂-NPs with the expression of Hsp70, which have a protective function because they allow the maintenance of cellular homeostasis in stressful/ lethal conditions. A positivity for MTs was observed mainly for the concentration of 4 mg/L. Although the biological and physiological function of the metallothionein (MTs) in the male genital organs is unclear, our results highlighted that the MTs expressed by spermatozoa maintain their biological role of detoxification from metals. Our results can give additional information to the data in the literature on the toxicity of TiO₂-NPs and reproduction.

Keywords: human spermatozoa, DNA damage, TiO₂-NPs, biomarkers

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Authors: Agnieszka H. Ludwig-Slomczynska, Michal T. Seweryn, Przemyslaw Kapusta, Ewelina Pitera, Katarzyna Cyganek, Urszula Mantaj, Lucja Dobrucka, Ewa Wender-Ozegowska, Maciej T. Malecki, Pawel Wolkow

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Obesity results from an imbalance between energy intake and its expenditure. Genome-Wide Association Study (GWAS) analyses have led to discovery of only about 100 variants influencing body mass index (BMI), which explain only a small portion of genetic variability. Analysis of gene epistasis gives a chance to discover another part. Since it was shown that interaction and communication between nuclear and mitochondrial genome are indispensable for normal cell function, we have looked for epistatic interactions between the two genomes to find their correlation with BMI. Methods: The analysis was performed on 366 T1DM patients using Illumina Infinium OmniExpressExome-8 chip and followed by imputation on Michigan Imputation Server. Only genes which influence mitochondrial functioning (listed in Human MitoCarta 2.0) were included in the analysis – variants of nuclear origin (MAF > 5%) in 1140 genes and 42 mitochondrial variants (MAF > 1%). Gene expression analysis was performed on GTex data. Association analysis between genetic variants and BMI was performed with the use of Linear Mixed Models as implemented in the package 'GENESIS' in R. Analysis of association between mRNA expression and BMI was performed with the use of linear models and standard significance tests in R. Results: Among variants involved in epistasis between mitochondria and nucleus we have identified one in mitochondrial transcription factor, TFB2M (rs6701836). It interacted with mitochondrial variants localized to MT-RNR1 (p=0.0004, MAF=15%), MT-ND2 (p=0.07, MAF=5%) and MT-ND4 (p=0.01, MAF=1.1%). Analysis of the interaction between nuclear variant rs6701836 (nuc) and rs3021088 localized to MT-ND2 mitochondrial gene (mito) has shown that the combination of the two led to BMI decrease (p=0.024). Each of the variants on its own does not correlate with higher BMI [p(nuc)=0.856, p(mito)=0.116)]. Although rs6701836 is intronic, it influences gene expression in the thyroid (p=0.000037). rs3021088 is a missense variant that leads to alanine to threonine substitution in the MT-ND2 gene which belongs to complex I of the electron transport chain. The analysis of the influence of genetic variants on gene expression has confirmed the trend explained above – the interaction of the two genes leads to BMI decrease (p=0.0308). Each of the mRNAs on its own is associated with higher BMI (p(mito)=0.0244 and p(nuc)=0.0269). Conclusıons: Our results show that nuclear-mitochondrial epistasis can influence BMI in T1DM patients. The correlation between transcription factor expression and mitochondrial genetic variants will be subject to further analysis.

Keywords: body mass index, epistasis, mitochondria, type 1 diabetes

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Authors: R. Zhankina, U. Zhanbyrbekuly, A. Tamadon, M. Askarov, R. Sherkhanov, D. Akhmetov, D. Saipiyeva, N. Keulimzhaev

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Male infertility affects about 15% of couples of reproductive age. Approximately 10–15% have azoospermia who have previously been diagnosed with male infertility. Azoospermia is regarded as the absence of spermatozoa in the ejaculate and is found in 10-15% of infertile men. Non-obstructive azoospermia is considered a cause of male infertility that is not amenable to drug therapy. Patients with non-obstructive azoospermia are unable to have their "own" children and have only options for adoption or use of donor sperm. Advances in assisted reproductive technologies such as intracytoplasmic sperm injection in vitro fertilization have significantly changed the management of patients with non-obstructive azoospermia. Advances in biotechnology have increased the options for treating patients with non-obstructive azoospermia. Mesenchymal stem cell therapy has been recognized as a new option for infertility treatment. Material and methods of the study: After obtaining informed consent, 5 patients diagnosed with non-obstructive azoospermia were included in an open, non-randomized study. The age of the patients ranged from 24 to 35 years. The examination was carried out before the start of treatment, which included biochemical blood tests, hormonal profile levels (luteinizing hormone, follicle-stimulating hormone, testosterone, prolactin, inhibin B); tests for tumor markers; genetic research. All studies were carried out in compliance with the requirements of Protocol No. 8 dated 06/09/20, approved by the Local Ethical Commission of NJSC "Astana Medical University". The control examination of patients was carried out after 6 months, by re-taking the program and hormonal profile (testosterone, luteinizing hormone, follicle-stimulating hormone, prolactin, inhibin B). Before micro-TESE of the testis, all 5 patients underwent myeloexfusion in the operating room. During the micro-TESE, autotransplantation of mesenchymal stem cells into the testicular network, previously cultured in a cell technology laboratory for 2 weeks, was performed. Results of the study: in all patients, the levels of total testosterone increased, the level of follicle-stimulating hormone decreased, the levels of luteinizing hormone returned to normal, the level of inhibin B increased. IVF with a positive result; another patient (20%) had spermatogenesis cells. Non-obstructive azoospermia and mesenchymal stem cells Conclusions: The positive results of this work serve as the basis for the application of a new cellular therapeutic approach for the treatment of non-obstructive azoospermia using mesenchymal stem cells.

Keywords: cell therapy, regenerative medicine, male infertility, mesenchymal stem cells

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Authors: Emma Plante, Charles Ekwunwa, Diego Illanes

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Introduction: Serum Sickness-Like Reaction (SSLR) is an inflammatory immune response characterized by a rash, polyarthralgias, and fever. SSLR usually occurs in response to a new medication (most commonly antibiotics, anticonvulsants, or antiinflammatory agents) and is believed to involve the formation of drug-specific immune complexes. Here we present a case of a 16-year-old female patient who developed an SSLR in response to the D-mannose-containing over-the-counter supplement, Uqora, used to promote bladder health. Methodology: The methodology for this study included a thorough literature search for other cases of SSLR associated with D-Mannose containing products. Data collection was performed through a review of the patient’s medical record, including history, physical examination, relevant laboratory results, and treatment plan. Findings: A 16-year-old female with a history of overactive bladder and anemia presented with a diffuse urticarial rash, headaches, joint pain, and swelling for three days. Her medications included oral contraceptive pills, iron, mirabegron, UQora, and a probiotic. Physical examination revealed a diffuse urticarial rash, and her musculoskeletal exam revealed swelling and tenderness in her wrists. Her CBC, basic metabolic panel, liver function panel, lyme titers, and urinalysis were all within normal limits. The patient was referred to an allergist, who diagnosed her with SSLR. All medications were discontinued, and she was treated with a 7-day course of prednisone and cetirizine. Her symptoms resolved, and her medications were slowly resumed sequentially over several months. However, UQora triggered a recurrence of her symptoms, and it was identified as the culprit medication. Consequently, UQora was permanently discontinued, and the patient has remained symptom-free. Conclusion: This case report describes the first documented case of SSLR caused by UQora (active ingredient D-mannose). D-Mannose is a monosaccharide found in many plants and fruits, and it is commonly used to prevent urinary tract infections. While the clinical features and timeline, in this case, were typical of SSLR, UQora as the trigger was highly unusual. Clinicians should be aware of the diverse triggers of SSLR and the importance of prompt identification and management to enhance patient safety. It is possible D-mannose was not the trigger, and further research is necessary to better understand the potential therapeutic applications of D-mannose, as well as the potential risks and interactions.

Keywords: serum sickness-like reaction, d-mannose, hypersensitivity reaction, urticaria

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Authors: Neeraj Vij, Christian Leber, Kenneth Schmidt

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Introduction: Total knee arthroplasty is a common procedure. It is well known that the biomechanics of the knee do not fully return to their normal state. Motion analysis has been used to study the biomechanics of the knee after total knee arthroplasty. The purpose of this scoping review is to summarize the current use of gait analysis in total knee arthroplasty and to identify the preoperative motion analysis parameters for which a systematic review aimed at determining the reliability and validity may be warranted. Materials and Methods: This IRB-exempt scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist strictly. Five search engines were searched for a total of 279 articles. Articles underwent a title and abstract screening process followed by full-text screening. Included articles were placed in the following sections: the role of gait analysis as a research tool for operative decisions, other research applications for motion analysis in total knee arthroplasty, gait analysis as a tool in predicting radiologic outcomes, gait analysis as a tool in predicting clinical outcomes. Results: Eleven articles studied gait analysis as a research tool in studying operative decisions. Motion analysis is currently used to study surgical approaches, surgical techniques, and implant choice. Five articles studied other research applications for motion analysis in total knee arthroplasty. Other research applications for motion analysis currently include studying the role of the unicompartmental knee arthroplasty and novel physical therapy protocols aimed at optimizing post-operative care. Two articles studied motion analysis as a tool for predicting radiographic outcomes. Preoperative gait analysis has identified parameters than can predict postoperative tibial component migration. 15 articles studied motion analysis in conjunction with clinical scores. Conclusions: There is a broad range of applications within the research domain of total knee arthroplasty. The potential application is likely larger. However, the current literature is limited by vague definitions of ‘gait analysis’ or ‘motion analysis’ and a limited number of articles with preoperative and postoperative functional and clinical measures. Knee adduction moment, knee adduction impulse, total knee range of motion, varus angle, cadence, stride length, and velocity have the potential for integration into composite clinical scores. A systematic review aimed at determining the validity, reliability, sensitivities, and specificities of these variables is warranted.

Keywords: motion analysis, joint replacement, patient-reported outcomes, knee surgery

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Authors: Anamika Paul, Sudipto Sarkar

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The flow behaviour of non-Newtonian fluid is quite complicated, although both the pseudoplastic (n < 1, n being the power index) and dilatant (n > 1) fluids under this category are used immensely in chemical and process industries. A limited research work is carried out for flow over a bluff body in non-Newtonian flow environment. In the present numerical simulation we control the vortices of a square cylinder by placing an upstream vertical splitter plate for pseudoplastic (n=0.8), Newtonian (n=1) and dilatant (n=1.2) fluids. The position of the upstream plate is also varied to calculate the critical distance between the plate and cylinder, below which the cylinder vortex shedding suppresses. Here the Reynolds number is considered as Re = 150 (Re = U∞a/ν, where U∞ is the free-stream velocity of the flow, a is the side of the cylinder and ν is the maximum value of kinematic viscosity of the fluid), which comes under laminar periodic vortex shedding regime. The vertical plate is having a dimension of 0.5a × 0.05a and it is placed at the cylinder centre-line. Gambit 2.2.30 is used to construct the flow domain and to impose the boundary conditions. In detail, we imposed velocity inlet (u = U∞), pressure outlet (Neumann condition), symmetry (free-slip boundary condition) at upper and lower domain. Wall boundary condition (u = v = 0) is considered both on the cylinder and the splitter plate surfaces. The unsteady 2-D Navier Stokes equations in fully conservative form are then discretized in second-order spatial and first-order temporal form. These discretized equations are then solved by Ansys Fluent 14.5 implementing SIMPLE algorithm written in finite volume method. Here, fine meshing is used surrounding the plate and cylinder. Away from the cylinder, the grids are slowly stretched out in all directions. To get an account of mesh quality, a total of 297 × 208 grid points are used for G/a = 3 (G being the gap between the plate and cylinder) in the streamwise and flow-normal directions respectively after a grid independent study. The computed mean flow quantities obtained from Newtonian flow are agreed well with the available literatures. The results are depicted with the help of instantaneous and time-averaged flow fields. Qualitative and quantitative noteworthy differences are obtained in the flow field with the changes in rheology of fluid. Also, aerodynamic forces and vortex shedding frequencies differ with the gap-ratio and power index of the fluid. We can conclude from the present simulation that fluent is capable to capture the vortex dynamics of unsteady laminar flow regime even in the non-Newtonian flow environment.

Keywords: CFD, critical gap-ratio, splitter plate, wake-wake interactions, dilatant, pseudoplastic

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Authors: María Barbaño Acevedo Gómez, Elena Sonsoles Rodríguez López, Sofía Olivia Calvo Moreno, Ángel Basas García, Christophe RamíRez Parenteau

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Introduction: Urinary incontinence (UI) is defined as the involuntary leakage of urine. In persons who practice sport, its prevalence is 36.1% (95% CI 26.5% –46.8%) and varies as it seems to depend on the intensity of exercise, movements and impact on the ground. Such high impact sports are likely to generate higher intra-abdominal pressures and leading to pelvic floor muscle weakness. Although physical exercise reduces the risk of suffering from many diseases the mentality of an elite athlete is not to optimize their health, achieving their goals can put their health at risk. Furthermore, feeling or suffering from any discomfort during training seems to be normal within the elite sport demands. Objective: The main objective of the present study was to know the effects of UI in sports performance in athletes. Methods: This was an observational study conducted in 754 elite athletes. After collecting questions about pelvic floor, UI and sport-related data, participants completed the questionnaire International Consultation on Incontinence Questionnaire-UI Short- Form (ICIQ-SF) and ISI (index of incontinence severity). Results: 48.8% of the athletes declare having losses also in rest, preseason and / or competition (χ2 [3] = 3.64; p = 0.302), being the competition period (29.1%) the most frequent where suffer from urine leakage. Of the elite athletes surveyed, 33% had UI according ICIQ-SF (mean age 23.75 ± 7.74 years). Elite athletes with UI (5.31 ± 1.07 days) dedicate significantly more days per week to training [M = 0.28; 95% CI = 0.08-0.48; t (752) = 2.78; p = 0.005] than those without UI. Regarding frequency, 59.7% lose urine once a week, 25.6% lose urine more than 3 times a week, and 14.7% daily. Based on the amount, approximately 15% claim to lose a moderate and abundant. Athletes with the highest number of urine leaks during their training, the UI affects them more in their daily life (r = 0.259; p = 0.001), they present a greater number of losses in their day to day (r = 0.341; p <0.001 ) and greater severity of UI (r = 0.341; p <0.001). Conclusions: Athletes consider that UI affects them negatively in their daily routine, 30.9% affirm having a severity between moderate and severe in their daily routine, and 29.1% loss urine in competition period. An interesting fact is that more than half of the samples collected were elite athletes who compete at the highest level (Olympic Games, World and European Championship), the dedication to sport occupies a big piece in their life. The most frequent period where athletes suffers urine leakage is in competition and there are many emotions that athletes manage to get their best performance, if we add urine losses in that moments it is possible that their performance could be affected.

Keywords: athletes, performance, prevalence, sport, training, urinary incontinence

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Authors: Wing Mui Winnie So, Tian Luo, Zeyu Han

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To fully explore and develop the potentials of gifted students systematically and strategically by providing them with opportunities to receive education at appropriate levels, schools in Hong Kong are encouraged to adopt the "Three-Tier Implementation Model" to plan and implement the school-based gifted education, with Level Three refers to the provision of learning opportunities for the exceptionally gifted students in the form of specialist training outside the school setting by post-secondary institutions, non-government organisations, professional bodies and technology enterprises. Due to the growing concern worldwide about low interest among students in pursuing STEM (Science, Technology, Engineering, and Mathematics) careers, cultivating and boosting STEM career interest has been an emerging research focus worldwide. Although numerous studies have explored its critical contributors, little research has examined the effectiveness of comprehensive interventions such as “Studying with STEM professional”. This study aims to examine the effect on gifted students’ career interest during their participation in an off-school support programme designed and supervised by a team of STEM educators and STEM professionals from a university. Gifted students were provided opportunities and tasks to experience STEM career topics that are not included in the school syllabus, and to experience how to think and work like a STEM professional in their learning. Participants involved 40 primary school students joining the intervention programme outside the normal school setting. Research methods included adopting the STEM career interest survey and drawing tasks supplemented with writing before and after the programme, as well as interviews before the end of the programme. The semi-structured interviews focused on students’ views regarding STEM professionals; what’s it like to learn with a STEM professional; what’s it like to work and think like a STEM professional; and students’ STEM identity and career interest. The changes in gifted students’ STEM career interest and its well-recognised significant contributors, for example, STEM stereotypes, self-efficacy for STEM activities, and STEM outcome expectation, were collectively examined from the pre- and post-survey using T-test. Thematic analysis was conducted for the interview records to explore how studying with STEM professional intervention can help students understand STEM careers; build STEM identity; as well as how to think and work like a STEM professional. Results indicated a significant difference in STEM career interest before and after the intervention. The influencing mechanism was also identified from the measurement of the related contributors and the analysis of drawings and interviews. The potential of off-school support programme supervised by STEM educators and professionals to develop gifted students’ STEM career interest is argued to be further unleashed in future research and practice.

Keywords: gifted students, STEM career, STEM education, STEM professionals

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Authors: Umut Kokbas, Mustafa Nisari

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Immunoglobulins, also known as antibodies, are glycoprotein molecules produced by activated B cells that transform into plasma cells and result in them. Antibodies are critical molecules of the immune response to fight, which help the immune system specifically recognize and destroy antigens such as bacteria, viruses, and toxins. Immunoglobulin classes differ in their biological properties, structures, targets, functions, and distributions. Five major classes of antibodies have been identified in mammals: IgA, IgD, IgE, IgG, and IgM. Evaluation of the immunoglobulin isotype can provide a useful insight into the complex humoral immune response. Evaluation and knowledge of immunoglobulin structure and classes are also important for the selection and preparation of antibodies for immunoassays and other detection applications. The immunoglobulin test measures the level of certain immunoglobulins in the blood. IgA, IgG, and IgM are usually measured together. In this way, they can provide doctors with important information, especially regarding immune deficiency diseases. Hypogammaglobulinemia (HGG) is one of the main groups of primary immunodeficiency disorders. HGG is caused by various defects in B cell lineage or function that result in low levels of immunoglobulins in the bloodstream. This affects the body's immune response, causing a wide range of clinical features, from asymptomatic diseases to severe and recurrent infections, chronic inflammation and autoimmunity Transient infant hypogammaglobulinemia (THGI), IgM deficiency (IgMD), Bruton agammaglobulinemia, IgA deficiency (SIgAD) HGG samples are a few. Most patients can continue their normal lives by taking prophylactic antibiotics. However, patients with severe infections require intravenous immune serum globulin (IVIG) therapy. The IgE level may rise to fight off parasitic infections, as well as a sign that the body is overreacting to allergens. Also, since the immune response can vary with different antigens, measuring specific antibody levels also aids in the interpretation of the immune response after immunization or vaccination. Immune deficiencies usually occur in childhood. In Immunology and Allergy clinics, apart from the classical methods, it will be more useful in terms of diagnosis and follow-up of diseases, if it is fast, reliable and especially in childhood hypogammaglobulinemia, sampling from children with a method that is more convenient and uncomplicated. The antibodies were attached to the electrode surface via the poly hydroxyethyl methacrylamide cysteine nanopolymer. It was used to evaluate the anodic peak results obtained in the electrochemical study. According to the data obtained, immunoglobulin determination can be made with a biosensor. However, in further studies, it will be useful to develop a medical diagnostic kit with biomedical engineering and to increase its sensitivity.

Keywords: biosensor, immunosensor, immunoglobulin, infection

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Authors: Ludmila Vucolova

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The thought is a process that underlies consciousness and cognition and understanding its origin and processes is a longstanding goal of many academic disciplines. By integrating over twenty novel ideas and hypotheses of this theoretical proposal, we can speculate that thought is an emergent property of coded neural events, translating the electro-chemical interactions of the body with its environment—the objects of sensory stimulation, X, and Y. The latter is a self- generated feedback entity, resulting from the arbitrary pattern of the motion of a body’s motor repertory (M). A culmination of these neural events gives rise to a thought: a state of identity between an observed object X and a symbol Y. It manifests as a “state of awareness” or “state of knowing” and forms our perception of the physical world. The values of the variables of a construct—X (object), S1 (sense for the perception of X), Y (object), S2 (sense for perception of Y), and M (motor repertory that produces Y)—will specify the particular conscious percept at any given time. The proposed principle of interaction between the elements of a construct (X, Y, S1, S2, M) is universal and applies for all modes of communication (normal, deaf, blind, deaf and blind people) and for various language systems (Chinese, Italian, English, etc.). The particular arrangement of modalities of each of the three modules S1 (5 of 5), S2 (1 of 3), and M (3 of 3) defines a specific mode of communication. This multifaceted paradigm demonstrates a predetermined pattern of relationships between X, Y, and M that passes from generation to generation. The presented analysis of a cognitive experience encompasses the key elements of embodied cognition theories and unequivocally accords with the scientific interpretation of cognition as the mental action or process of acquiring knowledge and understanding through thought, experience, and the senses, and cognition means thinking and awareness. By assembling the novel ideas presented in twelve sections, we can reveal that in the invisible “chaos”, there is an order, a structure with landmarks and principles of operations and mental processes (thoughts) are physical and have a biological basis. This innovative proposal explains the phenomenon of mental imagery; give the first insight into the relationship between mental states and brain states, and support the notion that mind and body are inseparably connected. The findings of this theoretical proposal are supported by the current scientific data and are substantiated by the records of the evolution of language and human intelligence.

Keywords: agent, awareness, cognitive, element, experience, feedback, first person, imagery, language, mental, motor, object, sensory, symbol, thought

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Authors: Christopher R. Triggle, Hong Ding, Khaled Machaca, Gnanapragasam Arunachalam

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The antidiabetic drug, metformin, has been in clinical use for over 50 years and remains the first choice drug for the treatment of type two diabetes. In addition to its effectiveness as an oral anti-hyperglycaemic drug metformin also possesses vasculoprotective effects that are assumed to be secondary to its ability to reduce insulin resistance and control glycated hemoglobin levels; however, recent data from our laboratory indicate that metformin also has direct vasoprotective effects that are mediated, at least in part, via the anti-ageing gene, SIRT1. Diabetes is a major risk factor for the development of cardiovascular disease (CVD) and it is also well established that tobacco use further enhances the risk of CVD; however, it is not known whether treatment with metformin can offset the negative effects of diabetes and tobacco use on cardiac function. The current study was therefore designed to investigate 1: the effects of hyperglycaemia (HG) either alone or in the presence of elevated fatty acids (palmitate) and nicotine on the protein expression levels of the deacetylase sirtuin 1 (the protein product of SIRT1), anti-apoptotic Bcl-2, pro-apoptotic BIM and the pro-apoptotic, tumour suppressor protein, acetylated p53 in cardiomyocytes. 2: the ability of metformin to prevent the detrimental effects of HG, palmitate and nicotine on cardiomyocyte survival. Cell culture protocols were designed using a rat cardiomyocyte cell line, H9c2, either under normal glycaemic (NG) conditions of 5.5mM glucose, or hyperglycaemic conditions (HG) of 25mM glucose with, or without, added palmitate (250μM) or nicotine (1.0mM) for 24h. Immuno-blotting was used to detect the expression of sirtuin 1, Bcl-2, BIM, acetylated (Ac)-p53, p53 with β-actin used as the reference protein. Exposure to HG, palmitate, or nicotine alone significantly reduced expression of sirtuin1, Bcl-2 and raised the expression levels of acetylated p53 and BIM; however, the combination of HG, palmitate and nicotine had a synergistic effect to significantly suppress the expression levels of sirtuin 1 and Bcl-2, but further enhanced the expression of Ac-p53, and BIM. The inclusion of 1000μM, but not 50μM, metformin in the H9c2 cell culture protocol prevented the effects of HG, palmitate and nicotine on the pro-apoptotic pathways. Collectively these data indicate that metformin, in addition to its anti-hyperglycaemic and vasculoprotective properties, also has direct cardioprotective actions that offset the negative effects of hyerglycaemia, elevated free fatty acids and nicotine on cardiac cell survival. These data are of particular significance for the treatment of patients with diabetes who are also smokers as the inclusion of metformin in their therapeutic treatment plan should help reduce cardiac-related morbidity and mortality.

Keywords: apoptosis, cardiac muscle, diabetes, metformin, nicotine

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Authors: Kar Yue Chan

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Cantonese opera is a valuable heritage originated from South China, and started to span its influence across the area to Hong Kong, and became extremely popular back in the 1950s to the 1970s. It has also been honoured and recognized as one treasurable item on the Intangible Cultural Heritage of Humanity on the Representative List of UNESCO since 2009. A certain level of difficulty is encountered when one identifies the gender roles and representations from a usual performance of Cantonese opera, as conventional practices of Cantonese opera display to the audience that many of the male hero roles are played by female upon the prior knowledge of all audience, and it is understandable for them as well because in the past there were insufficient male actors and performers on the market. Female actresses, in some senses, are more capable to sing near-male voices, and their appearances in heroic operatic attires are more appreciated by general audience. Therefore, perspectives of 'feminine representation' and the 'Reception Theory' in literature are conducive to analyzing such phenomenon. In spite of some 'normal' performances with romantic love stories or historical accounts involving often a talented intellectual and a beautiful wise lady (in Chinese caizi jiaren 才子佳人), in which the male role is actually male and the female role is actually female, there have still been some opera titles specifically manifesting these extreme gender associations by putting together displacement of gender roles in the same performance in view of such chaotic complication. On top of all other factors, translators dealing with any operatic texts face plenty of challenges upon transferring Cantonese operatic performances into English. It is found that translators need to deal with cultural elements embedded in the lyrics; the form (which is as delicate as those deriving from classical Chinese poetry); the gender misplacements that affect the mood and tone of the lyrics that much when they are in the process of translating. Some lyrics and tunes are specifically designed for a particular gender role to perform, while some others are more generic; both of which require different and specific translation strategies. After scrutinizing the various sources of reference, readers of this paper should be well informed of a significance which lies in the refined nature of the poetic form and content that signifies in the way the distinguished gender voice segregation of the discourse from which the lyrics are derived, and definitely also through the on-stage performability aspect of the task. In order to produce a relatively short and concise translated version which fits performance needs, all of the above factors will be looked at in this paper with relevant examples and analysis.

Keywords: Cantonese opera, translation, chaotic gender, performance

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Authors: Tatsuhiko Aizawa, Hiroshi Morita

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The tool steels such as SKD11 and SKH51 have been utilized as punch and die substrates for cold stamping, forging, and fine blanking processes. The heat-treated SKD11 punches with the hardness of 700 HV wrought well in the stamping of SPCC, normal steel plates, and non-ferrous alloy such as a brass sheet. However, they suffered from severe damage in the fine blanking process of smaller holes than 1.5 mm in diameter. Under the high aspect ratio of punch length to diameter, an elastoplastic bucking of slender punches occurred on the production line. The heat-treated punches had a risk of chipping at their edges. To be free from those damages, the blanking punch must have sufficient rigidity and strength at the same time. In the present paper, the small-hole blanking punch with a dual toughness structure was proposed to provide a solution to this engineering issue in production. The low-temperature plasma nitriding process was utilized to form the nitrogen supersaturated thick layer into the original SKD11 punch. Through the plasma nitriding at 673 K for 14.4 ks, the nitrogen supersaturated layer, with the thickness of 50 μm and without nitride precipitates, was formed as a high nitrogen steel (HNS) layer surrounding the original SKD11 punch. In this two-zone structured SKD11 punch, the surface hardness increased from 700 HV for the heat-treated SKD11 to 1400 HV. This outer high nitrogen SKD11 (HN-SKD11) layer had a homogeneous nitrogen solute depth profile with a nitrogen solute content plateau of 4 mass% till the border between the outer HN-SKD11 layer and the original SKD11 matrix. When stamping the brass sheet with the thickness of 1 mm by using this dually toughened SKD11 punch, the punch life was extended from 500 K shots to 10000 K shots to attain a much more stable production line to yield the brass American snaps. Furthermore, with the aid of the masking technique, the punch side surface layer with the thickness of 50 μm was modified by this high nitrogen super-saturation process to have a stripe structure where the un-nitrided SKD11 and the HN-SKD11 layers were alternatively aligned from the punch head to the punch bottom. This flexible structuring promoted the mechanical integrity of total rigidity and toughness as a punch with an extremely small diameter.

Keywords: high nitrogen supersaturation, semi-dry cold stamping, solid solution hardening, tool steel dies, low temperature nitriding, dual toughness structure, extremely small diameter punch

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Authors: Pamela R. Jackson, Andrea Hawkins-Daarud, Cassandra R. Rickertsen, Kamala Clark-Swanson, Scott A. Whitmire, Kristin R. Swanson

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Glioblastoma Multiforme (GBM), the most common primary brain tumor, often presents with hyperintensity on T2-weighted or T2-weighted fluid attenuated inversion recovery (T2/FLAIR) magnetic resonance imaging (MRI). This hyperintensity corresponds with vasogenic edema, however there are likely many infiltrating tumor cells within the hyperintensity as well. While MRIs do not directly indicate tumor cells, MRIs do reflect the microenvironmental water abnormalities caused by the presence of tumor cells and edema. The inherent heterogeneity and resulting MRI features of GBMs complicate assessing disease response. To understand how hyperintensity on T2/FLAIR MRI may correlate with edema in the extracellular space (ECS), a multi-compartmental MRI signal equation which takes into account tissue compartments and their associated volumes with input coming from a mathematical model of glioma growth that incorporates edema formation was explored. The reasonableness of two possible extracellular space schema was evaluated by varying the T2 of the edema compartment and calculating the possible resulting T2s in tumor and peripheral edema. In the mathematical model, gliomas were comprised of vasculature and three tumor cellular phenotypes: normoxic, hypoxic, and necrotic. Edema was characterized as fluid leaking from abnormal tumor vessels. Spatial maps of tumor cell density and edema for virtual tumors were simulated with different rates of proliferation and invasion and various ECS expansion schemes. These spatial maps were then passed into a multi-compartmental MRI signal model for generating simulated T2/FLAIR MR images. Individual compartments’ T2 values in the signal equation were either from literature or estimated and the T2 for edema specifically was varied over a wide range (200 ms – 9200 ms). T2 maps were calculated from simulated images. T2 values based on simulated images were evaluated for regions of interest (ROIs) in normal appearing white matter, tumor, and peripheral edema. The ROI T2 values were compared to T2 values reported in literature. The expanding scheme of extracellular space is had T2 values similar to the literature calculated values. The static scheme of extracellular space had a much lower T2 values and no matter what T2 was associated with edema, the intensities did not come close to literature values. Expanding the extracellular space is necessary to achieve simulated edema intensities commiserate with acquired MRIs.

Keywords: extracellular space, glioblastoma multiforme, magnetic resonance imaging, mathematical modeling

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Authors: S. Sansone-Casaburi

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The pandemic that the world is going through is causing important changes in the daily life of all cities, which can translate into opportunities to rearrange pending situations. Among others: the town-city relationship and sustainability. On the one hand, the city continues to be the center of attention, and the countryside is assumed as the supplier of food. However, the temporary closure of cities highlighted the importance of the rural environment, and many people are reassessing this context as an alternative for life. Furthermore, the countryside is not simply the home and the center of activity of the people who inhabit it, but rather constitutes the active group of all citizens, both rural and urban. On the other hand, the pandemic is the opportunity to meet sustainable development goals. Sustainable development is understood as the capital to be transferred to future generations made up of three types of wealth: natural capital (environment), human capital (people, relationships, culture), and artificial or built capital, made up of buildings and infrastructure, or by cities and towns. The 'new normal' can mean going back to the countryside, but not to a merely agricultural place but to a sustainable, affordable, and healthy place, which, with the appropriate infrastructures, allows work from a distance, a new post-COVID-19 modality. The contribution of the research is towards the recovery of traditional villages from the perspective of populations that have managed to maintain their vitality with innovative solutions. It is assumed that innovation is a path for the recovery of traditional villages, so we ask: what conditions are necessary for innovation to be successful and sustainable? In the research, several variables were found, among which culture is named, so the objective of this article is to understand Uruena, a town in the province of Valladolid, which with only 182 inhabitants houses five museums and twelve bookstores that make up the first Villa del Libro in Spain. The methodology used is mixed: inductive and deductive and the results were specified in determining the formula of innovative peoples in culture: PIc = Pt + C [E (Aec) + S (pp) + A (T + s + t + enc)]. Where the innovative villages in culture PIc are the result of traditional villages Pt that from a cultural innovation C, integrates into the economic, economic and cultural activities E (Aec); in the social sphere, the public and private actors S (pp); and in the environmental (A), Territory (T), services (s), technology (t) and natural and built spaces (enc). The results of this analysis will focus on determining what makes the structure of innovative peoples sustainable and understanding what variables make up that structure to verify if they can be applied in other contexts and repower abandoned places to provide a solution for people who migrate to this context. That is, learn from what has been done to replicate it in similar cases.

Keywords: culture as innovation, depopulation, sustainability, traditional villages

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Authors: Michael Russelle S. Alvarez, Noel S. Quiming, Francisco M. Heralde

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This study aims to: a) obtain ethanolic (95% EtOH) and aqueous extracts of Selaginella elmeri, Christella dentata, Elatostema sinnatum, Curculigo capitulata, Euphorbia hirta, Murraya koenigii, Alpinia speciosa, Cymbopogon citratus, Eucalyptus globulus, Jatropha curcas, Psidium guajava, Gliricidia sepium, Ixora coccinea and Capsicum frutescens and screen them for larvicidal activities against Aedes aegypti (Linn.) and Aedes albopictus (Skuse) larvae; b) to fractionate the most active extract and determine the most active fraction; c) to determine the larvicidal properties of the most active extract and fraction against by computing their percentage mortality, LC50, and LC90 after 24 and 48 hours of exposure; and d) to determine the nature of the components of the active extracts and fractions using phytochemical screening. Ethanolic (95% EtOH) and aqueous extracts of the selected plants will be screened for potential larvicidal activity against Ae. aegypti and Ae. albopictus using standard procedures and 1% malathion and a Piper nigrum based ovicide-larvicide by the Department of Science and Technology as positive controls. The results were analyzed using One-Way ANOVA with Tukey’s and Dunnett’s test. The most active extract will be subjected to partial fractionation using normal-phase column chromatography, and the fractions subsequently screened to determine the most active fraction. The most active extract and fraction were subjected to dose-response assay and probit analysis to determine the LC50 and LC90 after 24 and 48 hours of exposure. The active extracts and fractions will be screened for phytochemical content. The ethanolic extracts of C. citratus, E. hirta, I. coccinea, G. sepium, M. koenigii, E globulus, J. curcas and C. frutescens exhibited significant larvicidal activity, with C. frutescens being the most active. After fractionation, the ethyl acetate fraction was found to be the most active. Phytochemical screening of the extracts revealed the presence of alkaloids, tannins, indoles and steroids. A formulation using talcum powder–300 mg fraction per 1 g talcum powder–was made and again tested for larvicidal activity. At 2 g/L, the formulation proved effective in killing all of the test larvae after 24 hours.

Keywords: larvicidal activity screening, partial purification, dose-response assay, capsicum frutescens

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Authors: Gaweł Magdalena, Lipkowska Anna, Olbert Magdalena, Frąckiewicz Ewelina, Librowski Tadeusz, Nowak Gabriel, Pilc Andrzej

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Heme oxygenase-1 (HO-1), also known as heat shock protein 32 (HSP32), has been shown to be implicated in cytoprotection in various organs. Its activation plays a significant role in acute and chronic inflammation, protecting cells from oxidative injury and apoptosis. This inducible isoform of HO catalyzes the first and rate-limiting step in heme degradation to produce equimolar quantities of biologically active products: carbon monoxide (CO), free iron and biliverdin. CO has been reported to possess anti-apoptotic properties. Moreover, it inhibits the production of proinflammatory cytokines and stimulates the synthesis of the anti-inflammatory interleukin-10 (IL-10), as well as promotes vasodilatation at sites of inflammation. The second product of catalytic HO-1 activity, free cytotoxic iron, is promptly sequestered into the iron storage protein ferritin, which lowers the pro-oxidant state of the cell. The third product, biliverdin, is subsequently converted by biliverdin reductase into the bile pigment bilirubin, the most potent endogenous antioxidant among the constituents of human serum, which modulates immune effector functions and suppresses inflammatory response. Furthermore, being one of the so-called stress proteins, HO-1 adaptively responds to different stressors, such as reactive oxygen species (ROS), inflammatory cytokines and heavy metals and thus protects cells against such conditions as ischemia, hemorrhagic shock, heat shock or hypoxia. It is suggested that pharmacologic modulation of HO-1 may represent an effective strategy for prevention of stress and drug-induced gastrointestinal toxicity. HO-1 is constitutively expressed in normal gastric, intestinal and colonic mucosa and up-regulated during inflammation. It has been proven that HO-1 up-regulated by hemin, heme and cobalt-protoporphyrin ameliorates experimental colitis. In addition, the up-regulation of HO-1 partially explains the mechanism of action of 5-aminosalicylic acid (5-ASA), which is used clinically as an anti-colitis agent. In 2009 Ueda et al. has reported for the first time that mucosal protection by Polaprezinc, a chelate compound of zinc and L-carnosine used as an anti-ulcer drug in Japan, is also attributed to induction of HO-1 in the stomach. Since then, inducers of HO-1 are desired subject of research, as they may constitute therapeutically effective anti-ulcer drugs.

Keywords: heme oxygenase-1, gastric lesions, gastroprotection, Polaprezinc

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Authors: Anjali Roy, Mirza S. Baig

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Atherosclerosis is a chronic inflammatory disease characterized by the formation of lipid rich plaque enriched with necrotic core, modified lipid accumulation, smooth muscle cells, endothelial cells, leucocytes and macrophages. Macrophage foam cells play a critical role in the occurrence and development of inflammatory atherosclerotic plaque. Foam cells are the fat-laden macrophages in the initial stage atherosclerotic lesion formation. Foam cells are an indication of plaque build-up, or atherosclerosis, which is commonly associated with increased risk of heart attack and stroke as a result of arterial narrowing and hardening. The mechanisms that drive atherosclerotic plaque progression remain largely unknown. Dissecting the molecular mechanism involved in process of macrophage foam cell formation will help to develop therapeutic interventions for atherosclerosis. To investigate the mechanism, we studied the role of nitric oxide synthase 1(NOS1)-mediated nitric oxide (NO) on low-density lipoprotein (LDL) uptake by bone marrow derived macrophages (BMDM). Using confocal microscopy, we found that incubation of macrophages with NOS1 inhibitor, TRIM (1-(2-Trifluoromethylphenyl) imidazole) or L-NAME (N omega-nitro-L-arginine methyl ester) prior to LDL treatment significantly reduces the LDL uptake by BMDM. Further, addition of NO donor (DEA NONOate) in NOS1 inhibitor treated macrophages recovers the LDL uptake. Our data strongly suggest that NOS1 derived NO regulates LDL uptake by macrophages and foam cell formation. Moreover, we also checked proinflammatory cytokine mRNA expression through real time PCR in BMDM treated with LDL and copper oxidized LDL (OxLDL) in presences and absences of inhibitor. Normal LDL does not evoke cytokine expression whereas OxLDL induced proinflammatory cytokine expression which significantly reduced in presences of NOS1 inhibitor. Rapid NOS-1-derived NO and its stable derivative formation act as signaling agents for inducible NOS-2 expression in endothelial cells, leading to endothelial vascular wall lining disruption and dysfunctioning. This study highlights the role of NOS1 as critical players of foam cell formation and would reveal much about the key molecular proteins involved in atherosclerosis. Thus, targeting NOS1 would be a useful strategy in reducing LDL uptake by macrophages at early stage of disease and hence dampening the atherosclerosis progression.

Keywords: atherosclerosis, NOS1, inflammation, oxidized LDL

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Authors: Mai Abdul Latif, Yuntian Feng

Abstract:

Applied Element Method (AEM) is a method that was developed to aid in the analysis of the collapse of structures. Current available methods cannot deal with structural collapse accurately; however, AEM can simulate the behavior of a structure from an initial state of no loading until collapse of the structure. The elements in AEM are connected with sets of normal and shear springs along the edges of the elements, that represent the stresses and strains of the element in that region. The elements are rigid, and the material properties are introduced through the spring stiffness. Nonlinear dynamic analysis has been widely modelled using the finite element method for analysis of progressive collapse of structures; however, difficulties in the analysis were found at the presence of excessively deformed elements with cracking or crushing, as well as having a high computational cost, and difficulties on choosing the appropriate material models for analysis. The Applied Element method is developed and coded to significantly improve the accuracy and also reduce the computational costs of the method. The scheme works for both linear elastic, and nonlinear cases, including elasto-plastic materials. This paper will focus on elastic and elasto-plastic material behaviour, where the number of springs required for an accurate analysis is tested. A steel cantilever beam is used as the structural element for the analysis. The first modification of the method is based on the Gaussian Quadrature to distribute the springs. Usually, the springs are equally distributed along the face of the element, but it was found that using Gaussian springs, only up to 2 springs were required for perfectly elastic cases, while with equal springs at least 5 springs were required. The method runs on a Newton-Raphson iteration scheme, and quadratic convergence was obtained. The second modification is based on adapting the number of springs required depending on the elasticity of the material. After the first Newton Raphson iteration, Von Mises stress conditions were used to calculate the stresses in the springs, and the springs are classified as elastic or plastic. Then transition springs, springs located exactly between the elastic and plastic region, are interpolated between regions to strictly identify the elastic and plastic regions in the cross section. Since a rectangular cross-section was analyzed, there were two plastic regions (top and bottom), and one elastic region (middle). The results of the present study show that elasto-plastic cases require only 2 springs for the elastic region, and 2 springs for the plastic region. This showed to improve the computational cost, reducing the minimum number of springs in elasto-plastic cases to only 6 springs. All the work is done using MATLAB and the results will be compared to models of structural elements using the finite element method in ANSYS.

Keywords: applied element method, elasto-plastic, Gaussian springs, nonlinear

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Authors: Tayo P. Ogundunmade, Adedayo A. Adepoju

Abstract:

Terrorist attacks in liberal democracies bring about a few pessimistic results, for example, sabotaged public support in the governments they target, disturbing the peace of a protected environment underwritten by the state, and a limitation of individuals from adding to the advancement of the country, among others. Hence, seeking for techniques to understand the different factors involved in terrorism and how to deal with those factors in order to completely stop or reduce terrorist activities is the topmost priority of the government in every country. This research aim is to develop an efficient deep learning-based predictive model for the prediction of future terrorist activities in Nigeria, addressing low-quality prediction accuracy problems associated with the existing solution methods. The proposed predictive AI-based model as a counterterrorism tool will be useful by governments and law enforcement agencies to protect the lives of individuals in society and to improve the quality of life in general. A Heterogeneous Bayesian Neural Network (HETBNN) model was derived with Gaussian error normal distribution. Three primary transfer functions (HOTTFs), as well as two derived transfer functions (HETTFs) arising from the convolution of the HOTTFs, are namely; Symmetric Saturated Linear transfer function (SATLINS ), Hyperbolic Tangent transfer function (TANH), Hyperbolic Tangent sigmoid transfer function (TANSIG), Symmetric Saturated Linear and Hyperbolic Tangent transfer function (SATLINS-TANH) and Symmetric Saturated Linear and Hyperbolic Tangent Sigmoid transfer function (SATLINS-TANSIG). Data on the Terrorist activities in Nigeria gathered through questionnaires for the purpose of this study were used. Mean Square Error (MSE), Mean Absolute Error (MAE) and Test Error are the forecast prediction criteria. The results showed that the HETFs performed better in terms of prediction and factors associated with terrorist activities in Nigeria were determined. The proposed predictive deep learning-based model will be useful to governments and law enforcement agencies as an effective counterterrorism mechanism to understand the parameters of terrorism and to design strategies to deal with terrorism before an incident actually happens and potentially causes the loss of precious lives. The proposed predictive AI-based model will reduce the chances of terrorist activities and is particularly helpful for security agencies to predict future terrorist activities.

Keywords: activation functions, Bayesian neural network, mean square error, test error, terrorism

Procedia PDF Downloads 162

Authors: Nareshkumar Harale, B. B. Meshram

Abstract:

The continued exponential growth of successful cyber intrusions against today’s businesses has made it abundantly clear that traditional perimeter security measures are no longer adequate and effective. We evolved the network trust architecture from trust-untrust to Zero-Trust, With Zero Trust, essential security capabilities are deployed in a way that provides policy enforcement and protection for all users, devices, applications, data resources, and the communications traffic between them, regardless of their location. Information exchange over the Internet, in spite of inclusion of advanced security controls, is always under innovative, inventive and prone to cyberattacks. TCP/IP protocol stack, the adapted standard for communication over network, suffers from inherent design vulnerabilities such as communication and session management protocols, routing protocols and security protocols are the major cause of major attacks. With the explosion of cyber security threats, such as viruses, worms, rootkits, malwares, Denial of Service attacks, accomplishing efficient and effective intrusion detection and prevention is become crucial and challenging too. In this paper, we propose a design and analysis model for next generation network intrusion detection and protection system as part of layered security strategy. The proposed system design provides intrusion detection for wide range of attacks with layered architecture and framework. The proposed network intrusion classification framework deals with cyberattacks on standard TCP/IP protocol, routing protocols and security protocols. It thereby forms the basis for detection of attack classes and applies signature based matching for known cyberattacks and data mining based machine learning approaches for unknown cyberattacks. Our proposed implemented software can effectively detect attacks even when malicious connections are hidden within normal events. The unsupervised learning algorithm applied to network audit data trails results in unknown intrusion detection. Association rule mining algorithms generate new rules from collected audit trail data resulting in increased intrusion prevention though integrated firewall systems. Intrusion response mechanisms can be initiated in real-time thereby minimizing the impact of network intrusions. Finally, we have shown that our approach can be validated and how the analysis results can be used for detecting and protection from the new network anomalies.

Keywords: network intrusion detection, network intrusion prevention, association rule mining, system analysis and design

Procedia PDF Downloads 226