Search results for: molecular mechanisms of cancer
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 6294

Search results for: molecular mechanisms of cancer

3084 Cryotopic Macroporous Polymeric Matrices for Regenerative Medicine and Tissue Engineering Applications

Authors: Archana Sharma, Vijayashree Nayak, Ashok Kumar

Abstract:

Three-dimensional matrices were fabricated from blend of natural-natural polymers like carrageenan-gelatin and synthetic -natural polymers such as PEG- gelatin (PEG of different molecular weights (2,000 and 6,000) using two different crosslinkers; glutaraldehyde and EDC-NHS by cryogelation technique. Blends represented a feasible approach to design 3-D scaffolds with controllable mechanical, physical and biochemical properties without compromising biocompatibility and biodegradability. These matrices possessed interconnected porous structure, good mechanical strength, biodegradable nature, constant swelling kinetics, ability to withstand high temperature and visco-elastic behavior. Hemocompatibility of cryogel matrices was determined by coagulation assays and hemolytic activity assay which demonstrated that these cryogels have negligible effects on coagulation time and have excellent blood compatibility. In vitro biocompatibility (cell-matrix interaction) inferred good cell adhesion, proliferation, and secretion of ECM on matrices. These matrices provide a microenvironment for the growth, proliferation, differentiation and secretion of ECM of different cell types such as IMR-32, C2C12, Cos-7, rat bone marrow derived MSCs and human bone marrow MSCs. Hoechst 33342 and PI staining also confirmed that the cells were uniformly distributed, adhered and proliferated properly on the cryogel matrix. An ideal scaffold used for tissue engineering application should allow the cells to adhere, proliferate and maintain their functionality. Neurotransmitter analysis has been done which indicated that IMR-32 cells adhered, proliferated and secreted neurotransmitters when they interacted with these matrices which showed restoration of their functionality. The cell-matrix interaction up to molecular level was also evaluated so to check genotoxicity and protein expression profile which indicated that these cryogel matrices are non-genotoxic and maintained biofunctionality of cells growing on these matrices. All these cryogels, when implanted subcutaneously in balb/c mice, showed no adverse systemic or local toxicity effects at implantation site. There was no significant increase in inflammatory cell count has otherwise been observed after scaffold implantation. These cryogels are supermacroporous and this porous structure allows cell infiltration and proliferation of host cells. This showed the integration and presence of infiltrated cells into the cryogel implants. Histological analysis confirmed that the implanted cryogels do not have any adverse effect in spite of host immune system recognition at the site of implantation, on its surrounding tissues and other vital host organs. In vivo biocompatibility study after in vitro biocompatibility analysis has also concluded that these synthesized cryogels act as important biological substitutes, more adaptable and appropriate for transplantation. Thus, these cryogels showed their potential for soft tissue engineering applications.

Keywords: cryogelation, hemocompatibility, in vitro biocompatibility, in vivo biocompatibility, soft tissue engineering applications

Procedia PDF Downloads 226
3083 Effectiveness of the Use of Polycarboxylic Ether Superplasticizers in High Performance Concrete Containing Silica Fume

Authors: Alya Harichane, Badreddine Harichane

Abstract:

The incorporation of polycarboxylate ether superplasticizer (PCE) and silica fume (SF) in high-performance concretes (HPC) leads to the achievement of remarkable rheological and mechanical improvements. In the fresh state, PCEs are adsorbed on cement particles and dispersants, in turn promoting the workability of the concrete. Silica fume enables a very well compacted concrete to be obtained, which is characterized by high mechanical parameters in its hardened state. Some PCEs are incompatible with silica fume, which can result in the loss of slump and in poor rheological behavior. The main objective of the research is the study of the influence of three types of PCEs, which all have a different molecular architecture, on the rheological and mechanical behavior of high-performance concretes containing 10% of SF as a partial replacement of cement. The results show that the carboxylic density of PCE has an influence on its compatibility with SF.

Keywords: polycarboxylate-ether superplasticizer, rheology, compressive strength, high-performance concrete, silica fume

Procedia PDF Downloads 77
3082 Regulation of Desaturation of Fatty Acid and Triglyceride Synthesis by Myostatin through Swine-Specific MEF2C/miR222/SCD5 Pathway

Authors: Wei Xiao, Gangzhi Cai, Xingliang Qin, Hongyan Ren, Zaidong Hua, Zhe Zhu, Hongwei Xiao, Ximin Zheng, Jie Yao, Yanzhen Bi

Abstract:

Myostatin (MSTN) is the master regulator of double muscling phenotype with overgrown muscle and decreased fatness in animals, but its action mode to regulate fat deposition remains to be elucidated. In this study a swin-specific pathway through which MSTN acts to regulate the fat deposition was deciphered. Deep sequenincing of the mRNA and miRNA of fat tissues of MSTN knockout (KO) and wildtype (WT) pigs discovered the positive correlation of myocyte enhancer factor 2C (MEF2C) and fat-inhibiting miR222 expression, and the inverse correlation of miR222 and stearoyl-CoA desaturase 5 (SCD5) expression. SCD5 is rodent-absent and expressed only in pig, sheep and cattle. Fatty acid spectrum of fat tissues revealed a lower percentage of oleoyl-CoA (18:1) and palmitoleyl CoA (16:1) in MSTN KO pigs, which are the catalyzing products of SCD5-mediated desaturation of steroyl CoA (18:0) and palmitoyl CoA (16:0). Blood metrics demonstrated a 45% decline of triglyceride (TG) content in MSTN KO pigs. In light of these observations we hypothesized that MSTN might act through MEF2C/miR222/SCD5 pathway to regulate desaturation of fatty acid as well as triglyceride synthesis in pigs. To this end, real-time PCR and Western blotting were carried out to detect the expression of the three genes stated above. These experiments showed that MEF2C expression was up-regulated by nearly 2-fold, miR222 up-regulated by nearly 3-fold and SCD5 down-regulated by nearly 50% in MSTN KO pigs. These data were consistent with the expression change in deep sequencing analysis. Dual luciferase reporter was then used to confirm the regulation of MEF2C upon the promoter of miR222. Ecotopic expression of MEF2C in preadipocyte cells enhanced miR222 expression by 3.48-fold. CHIP-PCR identified a putative binding site of MEF2C on -2077 to -2066 region of miR222 promoter. Electrophoretic mobility shift assay (EMSA) demonstrated the interaction of MEF2C and miR222 promoter in vitro. These data indicated that MEF2C transcriptionally regulates the expression of miR222. Next, the regulation of miR222 on SCD5 mRNA as well as its physiological consequences were examined. Dual luciferase reporter testing revealed the translational inhibition of miR222 upon the 3´ UTR (untranslated region) of SCD5 in preadipocyte cells. Transfection of miR222 mimics and inhibitors resulted in the down-regulation and up-regulation of SCD5 in preadipocyte cells respectively, consistent with the results from reporter testing. RNA interference of SCD5 in preadipocyte cells caused 26.2% reduction of TG, in agreement with the results of TG content in MSTN KO pigs. In summary, the results above supported the existence of a molecular pathway that MSTN signals through MEF2C/miR222/SCD5 to regulate the fat deposition in pigs. This swine-specific pathway offers potential molecular markers for the development and breeding of a new pig line with optimised fatty acid composition. This would benefit human health by decreasing the takeup of saturated fatty acid.

Keywords: fat deposition, MEF2C, miR222, myostatin, SCD5, pig

Procedia PDF Downloads 131
3081 Empowering Youth-Led Cooperatives for Sustainable Development: A Pathway to Inclusive Growth in Malawi

Authors: Ulemu Maseko

Abstract:

In Malawi, empowering youth-led cooperatives is a pivotal strategy for fostering sustainable development and nurturing inclusive growth. The study delves into the pressing need to understand the impact and potential of youth-led cooperatives in driving socio-economic progress within the country. Through a mixed-methods approach encompassing qualitative interviews, surveys, and case studies, this research investigates the role of these cooperatives in promoting entrepreneurship, community engagement, and sustainable practices among young individuals. The results underscore the significant contribution of youth-led cooperatives towards economic empowerment and social inclusion in Malawi, highlighting their capacity to address local challenges effectively. The study concludes that supporting and investing in youth-led cooperatives is imperative for advancing sustainable development goals and achieving inclusive growth. Recommendations include tailored support mechanisms, capacity-building programs, and strategic partnerships to enhance the resilience and scalability of youth-led cooperative initiatives in Malawi.

Keywords: youth-led cooperatives, sustainable development, Malawi, empowerment

Procedia PDF Downloads 29
3080 Arbutin-loaded Butylglyceryl Dextran Nanoparticles for Topical Delivery

Authors: Mohammad F. Bostanudin, Tan S. Fei, Azwan M. Lazim

Abstract:

Toward the development of colloidal systems that are able to enhance permeation across the skin, a material combining the non-toxic and non-immunogenic of dextran with alkylglycerols permeation enhancing property has been designed. To this purpose, a range of butylglyceryl dextrans (DEX-OX4) were synthesized via functionalization with n-butylglycidyl ether and the successful functionalization was confirmed by NMR and FT-IR spectroscopies, along with GPC with a degree of modification in the range 6.3–35.7 %. A reduced viscosity and an increased molecular weight of DEX-OX4 were also recorded when compared to that of the native dextran. DEX-OX4 was further formulated into nanocarriers and loaded with α-arbutin prior to be investigated for their particle size, morphology, stability, loading ability, and release profiles. The resulting nanoparticles were found to be close-to-spherical and relatively stable at pH 5 and 7, with size 180–220 nm (ζ-potential -22 to -25 mV), and a loading degree of 11.7 %. Lack of toxicity at application-relevant concentrations and increased permeation across skin biological membrane model were demonstrated by nanoparticles in-vitro results against immortalized skin human keratinocytes cells (HaCaT).

Keywords: butylglycerols, dextran, nanoparticles, transdermal

Procedia PDF Downloads 125
3079 The Journey of a Malicious HTTP Request

Authors: M. Mansouri, P. Jaklitsch, E. Teiniker

Abstract:

SQL injection on web applications is a very popular kind of attack. There are mechanisms such as intrusion detection systems in order to detect this attack. These strategies often rely on techniques implemented at high layers of the application but do not consider the low level of system calls. The problem of only considering the high level perspective is that an attacker can circumvent the detection tools using certain techniques such as URL encoding. One technique currently used for detecting low-level attacks on privileged processes is the tracing of system calls. System calls act as a single gate to the Operating System (OS) kernel; they allow catching the critical data at an appropriate level of detail. Our basic assumption is that any type of application, be it a system service, utility program or Web application, “speaks” the language of system calls when having a conversation with the OS kernel. At this level we can see the actual attack while it is happening. We conduct an experiment in order to demonstrate the suitability of system call analysis for detecting SQL injection. We are able to detect the attack. Therefore we conclude that system calls are not only powerful in detecting low-level attacks but that they also enable us to detect high-level attacks such as SQL injection.

Keywords: Linux system calls, web attack detection, interception, SQL

Procedia PDF Downloads 360
3078 Machine Learning Automatic Detection on Twitter Cyberbullying

Authors: Raghad A. Altowairgi

Abstract:

With the wide spread of social media platforms, young people tend to use them extensively as the first means of communication due to their ease and modernity. But these platforms often create a fertile ground for bullies to practice their aggressive behavior against their victims. Platform usage cannot be reduced, but intelligent mechanisms can be implemented to reduce the abuse. This is where machine learning comes in. Understanding and classifying text can be helpful in order to minimize the act of cyberbullying. Artificial intelligence techniques have expanded to formulate an applied tool to address the phenomenon of cyberbullying. In this research, machine learning models are built to classify text into two classes; cyberbullying and non-cyberbullying. After preprocessing the data in 4 stages; removing characters that do not provide meaningful information to the models, tokenization, removing stop words, and lowering text. BoW and TF-IDF are used as the main features for the five classifiers, which are; logistic regression, Naïve Bayes, Random Forest, XGboost, and Catboost classifiers. Each of them scores 92%, 90%, 92%, 91%, 86% respectively.

Keywords: cyberbullying, machine learning, Bag-of-Words, term frequency-inverse document frequency, natural language processing, Catboost

Procedia PDF Downloads 133
3077 Closed Loop Large Bowel Obstruction Due to Appendiceal Signet Cell Carcinoma

Authors: Joshua Teo, Leo Phan

Abstract:

Signet cell carcinoma of the appendix is the rarest and the most aggressive subtype of appendiceal malignancy, typically with non-specific presentations. We describe a case of a 62-year-old male with large bowel obstruction and CT demonstrating dilated large bowels from caecum to proximal sigmoid colon with pneumoperitoneum. Intra-operatively, closed-loop obstruction caused by dense adherence of sigmoid colon to caecum was noted, which had resulted in caecal perforation. Histopathology study indicated primary appendiceal malignancy of signet cell morphology with intra-peritoneal spread to the sigmoid colon. Large bowel obstruction from appendiceal malignancy has rarely been reported, and a similar presentation has not been described in the existing literature. When left-sided large bowel obstruction is suspected to be caused by a malignant stricture, it is essential to consider transperitoneal spread of appendiceal malignancy as potential aetiology, particularly in the elderly.

Keywords: appendiceal carcinoma, large bowel obstruction, signet ring cell cancer, caecal perforation

Procedia PDF Downloads 223
3076 Evaluation of Dynamic Log Files for Different Dose Rates in IMRT Plans

Authors: Saad Bin Saeed, Fayzan Ahmed, Shahbaz Ahmed, Amjad Hussain

Abstract:

The aim of this study is to evaluate dynamic log files (Dynalogs) at different dose rates by dose-volume histograms (DVH) and used as a (QA) procedure of IMRT. Seven patients of phase one head and neck cancer with similar OAR`s are selected randomly. Reference plans of dose rate 300 and 600 MU/Min with prescribed dose of 50Gy in 25 fractions for each patient is made. Dynalogs produced by delivery of reference plans processed by in-house MATLAB program which produces new field files contain actual positions of multi-leaf collimators (MLC`s) instead of planned positions in reference plans. Copies of reference plans are used to import new field files generated by MATLAB program and renamed as Dyn.plan. After dose calculations of Dyn.plans for different dose rates, DVH, and multiple linear regression tools are used to evaluate reference and Dyn.plans. The results indicate good agreement of correlation between different dose rate plans. The maximum dose difference among PTV and OAR`s are found to be less than 5% and 9% respectively. The study indicates the potential of dynalogs to be used as patient-specific QA of IMRT at different dose rate.

Keywords: IMRT, dynalogs, dose rate, DVH

Procedia PDF Downloads 537
3075 Users’ Information Disclosure Determinants in Social Networking Sites: A Systematic Literature Review

Authors: Wajdan Al Malwi, Karen Renaud, Lewis Mackenzie

Abstract:

The privacy paradox describes a phenomenon whereby there is no connection between stated privacy concerns and privacy behaviours. We need to understand the underlying reasons for this paradox if we are to help users to preserve their privacy more effectively. In particular, the Social Networking System (SNS) domain offers a rich area of investigation due to the risks of unwise information disclosure decisions. Our study thus aims to untangle the complicated nature and underlying mechanisms of online privacy-related decisions in SNSs. In this paper, we report on the findings of a Systematic Literature Review (SLR) that revealed a number of factors that are likely to influence online privacy decisions. Our deductive analysis approach was informed by Communicative Privacy Management (CPM) theory. We uncovered a lack of clarity around privacy attitudes and their link to behaviours, which makes it challenging to design privacy-protecting SNS platforms and to craft legislation to ensure that users’ privacy is preserved.

Keywords: privacy paradox, self-disclosure, privacy attitude, privacy behavior, social networking sites

Procedia PDF Downloads 158
3074 Biofilm Formation Due to the Proteome Changes Of Enterococcus Faecium in Response to Sub-Mic of Gentamicin

Authors: Amin Abbasi, Mahdi Asghari Ozma

Abstract:

Background and Objective:Enterococcus faecium is a normal flora of the human gastrointestinal tract that causes infection in the host body under conditions such as biofilm formation, in which the use of antibiotics causes changes in these pathogenic mechanisms. In this study, we aimed to evaluate comprehensively the changes in E.faecium when exposed to sub-MIC of the gentamicin,especiallythe biofilm formation rate. Materials and Methods: For this study, the keywords "Enterococcus faecium ", "Biofilm", and "Gentamicin" in the databases PubMed, Google Scholar, Sid, and MagIran between 2015 and 2021 were searched, and 14 articles were chosen, studied, and analyzed. Results: Gentamicin significantly had increased biofilm formation in most of the isolates in the studies. Increased expression of the genes (efaA and esp) and proteins involved in biofilm formation and decreased expression of the genes (gelE and cylA) involved in spreading and proteins involved in metabolism and cell division in E.faecium were the most significant cause of the biofilm formation, which were increased in sub-MIC gentamicin-treated situation. Conclusion: Inadequate use of gentamicin intensify biofilm formation of E.faecium, which can make the treatment of infections caused by this bacterium difficult.

Keywords: biofilm, enterococcus faecium, gentamicin, proteome

Procedia PDF Downloads 112
3073 Characterization of Platelet Mitochondrial Metabolism in COVID-19 Caused Acute Respiratory Distress Syndrome (ARDS)

Authors: Anna Höfer, Johannes Herrmann, Patrick Meybohm, Christopher Lotz

Abstract:

Mitochondria are pivotal for energy supply and regulation of cellular functions. Deficiencies of mitochondrial metabolism have been implicated in diverse stressful conditions including infections. Platelets are key mediators for thrombo-inflammation during development and resolution of acute respiratory distress syndrome (ARDS). Previous data point to an exhausted platelet phenotype in critically-ill patients with coronavirus 19 disease (COVID-19) impacting the course of disease. The objective of this work was to characterize platelet mitochondrial metabolism in patients suffering from COVID-19 ARDSA longitudinal analysis of platelet mitochondrial metabolism in 24 patients with COVID-19 induced ARDS compared to 35 healthy controls (ctrl) was performed. Blood samples were analyzed at two time points (t1=day 1; t2=day 5-7 after study inclusion). The activity of mitochondrial citrate synthase was photometrically measured. The impact of oxidative stress on mitochondrial permeability was assessed by a photometric calcium-induced swelling assay and the activity of superoxide dismutase (SOD) by a SOD assay kit. The amount of protein carbonylation and the activity of mitochondria complexes I-IV were photometrically determined. Levels of interleukins (IL)-1α, IL-1β and tumor necrosis factor (TNF-) α were measured by a Multiplex assay kit. Median age was 54 years, 63 % were male and BMI was 29.8 kg/m2. SOFA (12; IQR: 10-15) and APACHE II (27; IQR: 24-30) indicated critical illness. Median Murray Score was 3.4 (IQR: 2.8-3.4), 21/24 (88%) required mechanical ventilation and V-V ECMO support in 14/24 (58%). Platelet counts in ARDS did not change during ICU stay (t1: 212 vs. t2: 209 x109/L). However, mean platelet volume (MPV) significantly increased (t1: 10.6 vs. t2: 11.9 fL; p<0.0001). Citrate synthase activity showed no significant differences between ctrl and ARDS patients. Calcium induced swelling was more pronounced in patients at t1 compared to t2 and to ctrl (50µM; t1: 0.006 vs. ctrl: 0.016 ΔOD; p=0.001). The amount of protein carbonylation as marker for irreversible proteomic modification constantly increased during ICU stay and compared to ctrl., without reaching significance. In parallel, superoxid dismutase activity gradually declined during ICU treatment vs. ctrl (t2: - 29 vs. ctrl.: - 17 %; p=0.0464). Complex I analysis revealed significantly stronger activity in ARDS vs. ctrl. (t1: 0.633 vs. ctrl.: 0.415 ΔOD; p=0.0086). There were no significant differences in complex II, III or IV activity in platelets from ARDS patients compared to ctrl. IL-18 constantly increased during the observation period without reaching significance. IL-1α and TNF-α did not differ from ctrl. However, IL-1β levels were significantly elevated in ARDS (t1: 16.8; t2: 16.6 vs. ctrl.: 12.4 pg/mL; p1=0.0335, p2=0.0032). This study reveals new insights in platelet mitochondrial metabolism during COVID-19 caused ARDS. it data point towards enhanced platelet activity with a pronounced turnover rate. We found increased activity of mitochondria complex I and evidence for enhanced oxidative stress. In parallel, protective mechanisms against oxidative stress were narrowed with elevated levels of IL-1β likely causing a pro-apoptotic environment. These mechanisms may contribute to platelet exhaustion in ARDS.

Keywords: acute respiratory distress syndrome (ARDS), coronavirus 19 disease (COVID-19), oxidative stress, platelet mitochondrial metabolism

Procedia PDF Downloads 62
3072 [Keynote Talk]: Software Reliability Assessment and Fault Tolerance: Issues and Challenges

Authors: T. Gayen

Abstract:

Although, there are several software reliability models existing today there does not exist any versatile model even today which can be used for the reliability assessment of software. Complex software has a large number of states (unlike the hardware) so it becomes practically difficult to completely test the software. Irrespective of the amount of testing one does, sometimes it becomes extremely difficult to assure that the final software product is fault free. The Black Box Software Reliability models are found be quite uncertain for the reliability assessment of various systems. As mission critical applications need to be highly reliable and since it is not always possible to ensure the development of highly reliable system. Hence, in order to achieve fault-free operation of software one develops some mechanism to handle faults remaining in the system even after the development. Although, several such techniques are currently in use to achieve fault tolerance, yet these mechanisms may not always be very suitable for various systems. Hence, this discussion is focused on analyzing the issues and challenges faced with the existing techniques for reliability assessment and fault tolerance of various software systems.

Keywords: black box, fault tolerance, failure, software reliability

Procedia PDF Downloads 427
3071 Analysis of Mechanotransduction-Induced Microalgae under Direct Membrane Distortion

Authors: Myung Kwon Cho, Seul Ki Min, Gwang Heum Yoon, Jung Hyun Joo, Sang Jun Sim, Hwa Sung Shin

Abstract:

Mechanotransduction is a mechanism that external mechanical stimulation is converted to biochemical activity in the cell. When applying this mechanism to the unicellular green algae Chlamydomonas reinhardtii, the dramatic result that the accumulation of intracellular lipid was up to 60% of dry weight basis occurred. Furthermore, various variations in cellular physiology occurred, but there is a lack of the development of the system and related research for applying that technology to control the mechanical stress and facilitate molecular analyses. In this study, applying a mechanical stress to microalgae, the microfluidic device system that finely induced direct membrane distortion of microalgae. Cellular membrane distortion led to deflagellation, calcium influx and lipid accumulation in microalgae. In conclusion, cytological studies such as mechanotransduction can be actualized by using this system and membrane distortion is a promising inducer for biodiesel production.

Keywords: mechanotransduction, microalgae, membrane distortion, biodiesel

Procedia PDF Downloads 324
3070 Paradigms of Assessment, Valuation and Quantification to Trade Ecosystem Services: A Review Focusing on Mangroves and Wetlands

Authors: Rama Seth, Luise Noring, Pratim Majumdar

Abstract:

Based on an extensive literature review, this paper presents distinct approaches to value, quantify and trade ecosystem services, with particular emphasis on services provided by mangroves and wetlands. Building on diverse monetary and market-based systems for the improved allocation of natural resources, such trading and exchange-based methods can help tackle the degradation of ecosystem services in a more targeted and structured manner than achievable with stand-alone policy and administrative regulations. Using various threads of literature, the paper proposes a platform that serves as the skeletal foundation for developing an efficient global market for ecosystem services trading. The paper bridges a significant research and practice gap by recommending how to establish an equilibrium in the biosphere via trading mechanisms while also discovering other research gaps and future research potential in the domain of ecosystem valuation.

Keywords: environment, economics, mangroves, wetlands, markets, ESG, global capital, climate investments, valuation, ecosystem services

Procedia PDF Downloads 255
3069 The Obstacles of Applying Electronic Administration at the University of Tabuk from Its Academic Leaders' Perspectives

Authors: Saud Eid Alanazi

Abstract:

The study aimed at recognizing the obstacles of applying of Electronic Administration (e-administration), which refers to any of a number of mechanisms which convert what in a traditional office are paper processes into electronic processes, with the goal being to create a paperless office and improve productivity and performance at the University of Tabuk from its Academic Leaders' Perspectives. The sample of the study consisted of (98) members from deans, vice deans and head of departments from different specialization, gender and position. For achieving the aim of the study, a questionnaire was developed including (45) items distributed into three domains (administrative, human and technical obstacles) . By using appropriate statistical methods to analyze the information, the results indicated that the administrative obstacles domain came in the first rank with a high degree, and the human and technical obstacles came at the second rank with a moderate degree. The study also showed that there were no statistically significant differences attributed to the variables of the members (specialization, gender and position).

Keywords: administration, electronic administration, obstacles, technology, universities

Procedia PDF Downloads 390
3068 Defective Autophagy Leads to the Resistance to PP2 in ATG5 Knockout Cells Generated by CRISPR-Cas9 Endonuclease

Authors: Sung-Hee Hwang, Michael Lee

Abstract:

Upregulated Src activity has been implicated in a variety of cancers. Thus, Src family tyrosine kinase (SFK) inhibitors are often effective cancer treatments. Here, we investigate the role of autophagy in ATG5 knockout cell lines generated by the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas mediated genome editing. The CRISPR-associated protein Cas9 is an RNA-guided DNA endonuclease that uses RNA–DNA complementarity to identify target sites for sequence specific double-stranded DNA (dsDNA) cleavage. Interestingly, ATG5 KO cells clearly showed a greater proliferation rate than WT NIH 3T3 cells, implying that autophagy induction is cytotoxic. Also, the clonogenic survival of ATG5 KO cells was greater than WT cells. The MTT assay revealed that the cytotoxic effect of PP2 was weaker on ATG5 knockout cells than that WT cells. The conversion of non-autophagic LC3-I to autophagic LC3-II and RT-PCR confirmed the functional gene knockout. Furthermore, Cyto-ID autophagy assay also revealed that PP2 failed to induce autophagy in ATG5 knockout cells. Together, our findings suggest that the resistance to PP2 in ATG5 knockout cells is associated with defective autophagy.

Keywords: ATG5 knockout, Autophagy, CRISPR/Cas9, PP2

Procedia PDF Downloads 348
3067 Plasma Collagen XVIII in Response to Intensive Aerobic Running and Aqueous Extraction of Black Crataegus Elbursensis in Male Rats

Authors: A. Abdi, A. Abbasi Daloee, A. Barari

Abstract:

Aim: The adaptations that occur in human body after doing exercises training are a factor to help healthy people stay away from certain diseases. One of the main adaptations is a change in blood circulation, especially in vessels. The increase of capillary density is dependent on the balance between angiogenic and angiostatic factors. Most studies show that the changes made to angiogenic developmental factors resulted from physical exercises indicate the low level of stimulators compared with inhibitors. It is believed that the plasma level of VEGF-A, the important angiogenic factor, is reduced after physical exercise. Findings indicate that the extract of crataegus plant reduces the platelet-derived growth factor receptor (PDGFR) autophosphorylation in human's fibroblast. More importantly, crataegus (1 to 100 mg in liter) clearly leads to the inhibition of PDGFR autophosphorylation in vascular smooth muscle cells (VSMCs). Angiogenesis is a process that can be classified into physiological and pathophysiological forms. collagen XVIII is a part of extracellular protein and heparan sulfate proteoglycans in vascular epithelial and endothelial basement membrane cause the release of endostatin from noncollagenous collagen XVIII. Endostatin inhibits the growth of endothelial cells, inhibits angiogenesis, weakens different types of cancer, and the growth of tumors. The purpose of the current study was to investigate the effect of intensive aerobic running with or without aqueous extraction of black Crataegus elbursensis on Collagen XVIII in male rats. Design: Thirty-two Wistar male rats (4-6 weeks old, 125-135 gr weight) were acquired from the Pasteur's Institute (Amol, Mazandaran), and randomly assigned into control (n = 16) and training (n = 16) groups. Rats were further divided into saline-control (SC) (n=8), saline-training (ST) (n=8), crataegus pentaegyna extraction -control (CPEC) (n=8), and crataegus pentaegyna extraction - training (CPET) (n=8). The control (SC and CPEC) groups remained sedentary; whereas the training groups underwent a high running exercise program. plasma were excised and immediately frozen in liquid nitrogen. Statistical analysis was performed using a one way analysis of variance and Tukey test. Significance was accepted at P = 0.05. Results: The results show that aerobic exercise group had the highest concentration collagen XVIII compared to other groups and then respectively black crataegus, training-crataegus and control groups. Conclusion: In general, researchers in this study concluded that the increase of collagen XVIII (albeit insignificant) as a result of physical activity and consumption of black crataegus extract could possibly serve as a regional inhibitor of angiogenesis and another evidence for the anti-cancer effects of physical activities. Since the research has not managed in this study to measure the amount of plasma endostatin, it is suggested that both indices are measured with important angiogenic factors so that we can have a more accurate interpretation of changes to angiogenic and angiostatic factors resulted from physical exercises.

Keywords: aerobic running, Crataegus elbursensis, Collagen XVIII

Procedia PDF Downloads 326
3066 Synthesis of Carboxylate Gemini Surfactant

Authors: Rui Wang, Shanfa Tang, Yuanwu Dong, Siyao Wang

Abstract:

A carboxylate Gemini surfactant N, N`-bis (3-chloro-2 -hydroxypropane-N-dodecyl secondary amine) p-phenylenediamine diacetate sodium (GD12-P-12) was synthesized by substitution and ring-opening reaction from p-phenylenediamine, sodium chloroacetate, epichlorohydrin, and dodecylamine. The synthesis conditions were optimized by controlling variables. The structure of GD12-P-12 was characterized by FT-IR and 1H NMR, and its foam performance, interfacial tension, viscosity was evaluated. The results show that the molecular structure of the synthesized product is consistent with that of the target product, the GD12-P-12 can reduce the oil-water interfacial tension to 7.49×10⁻³mN/m (ultra-low interfacial tension level) in 20min. GD12-P-12 surfactant has excellent foam performance, ultra-low interfacial tension, good temperature-resistant viscosity-increasing properties, has good application prospect in foam flooding.

Keywords: gemini surfactant, optimization of synthesis conditions, foam performance, low interfacial tension

Procedia PDF Downloads 123
3065 Comparison of Psychological Well-Being, Hope, and Health Concern in Leukemia Patients before and After Receiving Stem Cells

Authors: Tahereh Yavari, Sara Norozi Far

Abstract:

The aim of this study was to compare psychological well-being, hope, and health concerns in leukemia patients before and after receiving stem cells. The statistical population of the present study was made up of leukemia patients in Tehran, and the research sample was among the patients referred to the Bone Marrow Transplant Center of Shariati Hospital in Tehran, and they were placed in two experimental and control groups (15 people in each group), which were selected by purposive sampling method. In order to collect the data for the research, three psychological well-being questionnaires were used by Riff (2002), Schneider's Hope Scale (SHS), and Schneider's Health Concern Questionnaire (HCQ). In order to analyze the data in this research, according to the "pre-test-post-test design with a control group," covariance analysis was used. Based on the research findings, it was concluded that receiving stem cells increases hope and psychological well-being in leukemia patients and significantly reduces health concerns.

Keywords: psychological well-being, hope, health concerns, blood cancer, stem cells

Procedia PDF Downloads 91
3064 Influence of Silica Surface Hydrophilicity on Adsorbed Water and Isopropanol Studied by in-situ NMR

Authors: Hyung T. Kwak, Jun Gao, Yao An, Alfred Kleinhammes, Yue Wu

Abstract:

Surface wettability is a crucial factor in oil recovery. In oil industry, the rock wettability involves the interplay between water, oil, and solid surface. Therefore, studying the interplay between adsorptions of water and hydrocarbon molecules on solid surface would be very informative for understanding rock wettability. Here we use the in-situ Nuclear Magnetic Resonance (NMR) gas isotherm technique to study competitive adsorptions of water and isopropanol, an intermediate step from hydrocarbons. This in-situ NMR technique obtains information on thermodynamic properties such as the isotherm, molecular dynamics via spin relaxation measurements, and adsorption kinetics such as how fast the system can reach thermal equilibrium after changes of vapor pressures. Using surfaces of silica glass beads, which can be modified from hydrophilic to hydrophobic, we obtained information on the influence of surface hydrophilicity on the state of surface water via obtained thermodynamic and dynamic properties.

Keywords: Wettability, NMR, Gas Isotherm, Hydrophilicity, adsorption

Procedia PDF Downloads 180
3063 Relay Mining: Verifiable Multi-Tenant Distributed Rate Limiting

Authors: Daniel Olshansky, Ramiro Rodrıguez Colmeiro

Abstract:

Relay Mining presents a scalable solution employing probabilistic mechanisms and crypto-economic incentives to estimate RPC volume usage, facilitating decentralized multitenant rate limiting. Network traffic from individual applications can be concurrently serviced by multiple RPC service providers, with costs, rewards, and rate limiting governed by a native cryptocurrency on a distributed ledger. Building upon established research in token bucket algorithms and distributed rate-limiting penalty models, our approach harnesses a feedback loop control mechanism to adjust the difficulty of mining relay rewards, dynamically scaling with network usage growth. By leveraging crypto-economic incentives, we reduce coordination overhead costs and introduce a mechanism for providing RPC services that are both geopolitically and geographically distributed.

Keywords: remote procedure call, crypto-economic, commit-reveal, decentralization, scalability, blockchain, rate limiting, token bucket

Procedia PDF Downloads 56
3062 Estimation and Utilization of Landfill Gas from Egyptian Municipal Waste: A Case Study

Authors: Ali A. Hashim Habib, Ahmed A. Abdel-Rehim

Abstract:

Assuredly, massive amounts of wastes that are not utilized and dumped in uncontrolled dumpsites will be one of the major sources of diseases, fires, and emissions. With easy steps and minimum effort, energy can be produced from these gases. The present work introduces an experimental and theoretical analysis to estimate the amount of landfill gas and the corresponding energy which can be produced based on actual Egyptian municipal wastes composition. Two models were utilized and compared, EPA (Environmental Protection Agency) model and CDM (Clean Development Mechanisms) model to estimate methane generation rates and total CH4 emissions based on a particular landfill. The results showed that for every ton of municipal waste, 140 m3 of landfill gas can be produced. About 800 kW of electricity for a minimum of 24 years can be generated form one million ton of municipal waste. A total amount of 549,025 ton of carbon emission can be avoided during these 24 years.

Keywords: energy from landfill gases, landfill biogas, methane emission, municipal solid waste, renewable energy sources

Procedia PDF Downloads 226
3061 Nutritional Benefits of Soy: An Implication for Health Education

Authors: Mbadugha Esther Ifeoma

Abstract:

Soybeans, like other legumes are rich in nutrients. However, the nutrient profile of soybeans differs in some important ways from most other legumes. Among other nutrients, soy is high in protein, carbohydrates, and fibers, is rich in vitamins, minerals and unsaturated fatty acids and is low in saturated fatty acids. Because of its high nutritional value, it has been rated to be equivalent to meats, eggs and milk. Soy has many health benefits including prevention of coronary heart disease, prevention of cancer growth, improvement of cognitive function, promotion of bone health, prevention of obesity, prevention of type II diabetes and promotion of growth of normal floras in the colon. Soybean consumption is also associated with some side effects which include allergy, flatulence and abdominal discomfort. Nurses/health care providers should therefore, educate clients on the precautionary measures to be taken in preparing soy food products in order to reduce to the barest minimum the side effects, while encouraging them to include soy as part of their daily meals for optimal health and vitality.

Keywords: health benefit, health education, nutritional benefit, soybeans

Procedia PDF Downloads 493
3060 PARP1 Links Transcription of a Subset of RBL2-Dependent Genes with Cell Cycle Progression

Authors: Ewelina Wisnik, Zsolt Regdon, Kinga Chmielewska, Laszlo Virag, Agnieszka Robaszkiewicz

Abstract:

Apart from protecting genome, PARP1 has been documented to regulate many intracellular processes inter alia gene transcription by physically interacting with chromatin bound proteins and by their ADP-ribosylation. Our recent findings indicate that expression of PARP1 decreases during the differentiation of human CD34+ hematopoietic stem cells to monocytes as a consequence of differentiation-associated cell growth arrest and formation of E2F4-RBL2-HDAC1-SWI/SNF repressive complex at the promoter of this gene. Since the RBL2 complexes repress genes in a E2F-dependent manner and are widespread in the genome in G0 arrested cells, we asked (a) if RBL2 directly contributes to defining monocyte phenotype and function by targeting gene promoters and (b) if RBL2 controls gene transcription indirectly by repressing PARP1. For identification of genes controlled by RBL2 and/or PARP1,we used primer libraries for surface receptors and TLR signaling mediators, genes were silenced by siRNA or shRNA, analysis of gene promoter occupation by selected proteins was carried out by ChIP-qPCR, while statistical analysis in GraphPad Prism 5 and STATISTICA, ChIP-Seq data were analysed in Galaxy 2.5.0.0. On the list of 28 genes regulated by RBL2, we identified only four solely repressed by RBL2-E2F4-HDAC1-BRM complex. Surprisingly, 24 out of 28 emerged genes controlled by RBL2 were co-regulated by PARP1 in six different manners. In one mode of RBL2/PARP1 co-operation, represented by MAP2K6 and MAPK3, PARP1 was found to associate with gene promoters upon RBL2 silencing, which was previously shown to restore PARP1 expression in monocytes. PARP1 effect on gene transcription was observed only in the presence of active EP300, which acetylated gene promoters and activated transcription. Further analysis revealed that PARP1 binding to MA2K6 and MAPK3 promoters enabled recruitment of EP300 in monocytes, while in proliferating cancer cell lines, which actively transcribe PARP1, this protein maintained EP300 at the promoters of MA2K6 and MAPK3. Genome-wide analysis revealed a similar distribution of PARP1 and EP300 around transcription start sites and the co-occupancy of some gene promoters by PARP1 and EP300 in cancer cells. Here, we described a new RBL2/PARP1/EP300 axis which controls gene transcription regardless of the cell type. In this model cell, cycle-dependent transcription of PARP1 regulates expression of some genes repressed by RBL2 upon cell cycle limitation. Thus, RBL2 may indirectly regulate transcription of some genes by controlling the expression of EP300-recruiting PARP1. Acknowledgement: This work was financed by Polish National Science Centre grants nr DEC-2013/11/D/NZ2/00033 and DEC-2015/19/N/NZ2/01735. L.V. is funded by the National Research, Development and Innovation Office grants GINOP-2.3.2-15-2016-00020 TUMORDNS, GINOP-2.3.2-15-2016-00048-STAYALIVE and OTKA K112336. AR is supported by Polish Ministry of Science and Higher Education 776/STYP/11/2016.

Keywords: retinoblastoma transcriptional co-repressor like 2 (RBL2), poly(ADP-ribose) polymerase 1 (PARP1), E1A binding protein p300 (EP300), monocytes

Procedia PDF Downloads 211
3059 Numerical Model for Investigation of Recombination Mechanisms in Graphene-Bonded Perovskite Solar Cells

Authors: Amir Sharifi Miavaghi

Abstract:

It is believed recombination mechnisms in graphene-bonded perovskite solar cells based on numerical model in which doped-graphene structures are employed as anode/cathode bonding semiconductor. Moreover, th‌‌‌‌e da‌‌‌‌‌rk-li‌‌‌‌‌ght c‌‌‌‌urrent d‌‌‌‌ens‌‌‌‌ity-vo‌‌‌‌‌‌‌ltage density-voltage cu‌‌‌‌‌‌‌‌‌‌‌rves are investigated by regression analysis. L‌‌‌oss m‌‌‌‌echa‌‌‌‌nisms suc‌‌‌h a‌‌‌‌‌‌s ba‌‌‌‌ck c‌‌‌ontact b‌‌‌‌‌arrier, d‌‌‌‌eep surface defect i‌‌‌‌n t‌‌‌‌‌‌‌he adsorbent la‌‌‌yer is det‌‌‌‌‌ermined b‌‌‌y adapting th‌‌‌e sim‌‌‌‌‌ulated ce‌‌‌‌‌ll perfor‌‌‌‌‌mance to t‌‌‌‌he measure‌‌‌‌ments us‌‌‌‌ing the diffe‌‌‌‌‌‌rential evolu‌‌‌‌‌tion of th‌‌‌‌e global optimization algorithm. T‌‌‌‌he performance of t‌‌‌he c‌‌‌‌ell i‌‌‌‌n the connection proc‌‌‌‌‌ess incl‌‌‌‌‌‌udes J-V cur‌‌‌‌‌‌ves that are examined at di‌‌‌‌‌fferent tempe‌‌‌‌‌‌‌ratures an‌‌‌d op‌‌‌‌en cir‌‌‌‌cuit vol‌‌‌‌tage (V) und‌‌‌‌er differ‌‌‌‌‌ent light intensities as a function of temperature. Ba‌‌‌‌sed o‌‌‌n t‌‌‌he prop‌‌‌‌osed nu‌‌‌‌‌merical mod‌‌‌‌el a‌‌‌‌nd the acquired lo‌‌‌‌ss mecha‌‌‌‌‌‌nisms, our approach can be used to improve the efficiency of the solar cell further. Due to the high demand for alternative energy sources, solar cells are good alternatives for energy storage using the photovoltaic phenomenon.

Keywords: numerical model, recombination mechanism, graphen, perovskite solarcell

Procedia PDF Downloads 72
3058 Study on the Neurotransmitters and Digestion of Amino Acids Affecting Psychological Chemical Imbalance

Authors: Yoonah Lee, Richard Kyung

Abstract:

With technological advances in the computational biomedical field, the ability to measure neurotransmitters’ chemical imbalances that affect depression and anxiety has been established. By comparing the thermodynamics stability of amino acid supplements, such as glutamine, tyrosine, phe-nylalanine, and methionine, this research analyzes mood-regulating neurotransmitters, amino acid supplements, and antipsychotic substances (ie. Reserpine molecule and CRF complexes) in relation to depression and anxiety and suggests alternative complexes that are low in energy to act as more efficient treatments for mood disorders. To determine a molecule’s thermodynamic stability, this research examines the molecular energy using Avogadro, a software for building virtual molecules and calculating optimized geometry using GAFF (General Amber Force Field) and UFF (Universal Force Field). The molecules, built using Avogadro, is analyzed using their theoretical values and atomic properties.

Keywords: amino acids, anxiety, depression, neurotransmitters

Procedia PDF Downloads 164
3057 School Students’ Career Guidance in the Context of Inclusive Education in Kazakhstan: Experience and Perspectives

Authors: Laura Butabayeva, Svetlana Ismagulova, Gulbarshin Nogaibayeva, Maiya Temirbayeva, Aidana Zhussip

Abstract:

The article presents the main results of the study conducted within the grant project «Organizational and methodological foundations for ensuring the inclusiveness of school students’ career guidance» (2022-2024). The main aim of the project is to study the issue of the absence of developed mechanisms, coordinating the activities of all stakeholders in preparing school students for conscious career choice, taking into account their individual opportunities and special educational needs. To achieve the aim of the project, according to the implementation plan, the analysis of foreign and national literature on the studied problem, as well as the study of the state of school students’ career guidance and their socialization in the context of inclusive education were conducted, the international experience on this issue was explored. The analysis of the national literature conducted by the authors has shown the State’s annual increase in the number of students with special educational needs as well as the rapid demand of labour market, influencing their professional self-determination in modern society. The participants from 5 State’s regions, including students, their parents, general secondary schools administration and educators, as well as employers, took part in the study, taking into account the geographical location: south, north, west, centre, and the cities of republican significance. To ensure the validity of the study’s results, the triangulation method was utilised, including both qualitative and quantitative methods. The data were analysed independently and compared with each other. Ethical principles were considered during all stages of the study. The characteristics of the system of career guidance in the modern school, the role and the involvement of stakeholders in the system of career guidance, the opinions of educators on school students’ preparedness for career choice, and the factors impeding the effectiveness of career guidance in schools were examined. The problem of stakeholders’ disunity and inconsistency, causing the systemic labor market distortions, the growth of low-skilled labor, and the unemployed, including people with special educational needs, were revealed. The other issue identified by the researchers was educators’ insufficient readiness for students’ career choice preparation in the context of inclusive education. To study cutting-edge experience in organizing a system of career guidance for young people and develop mechanisms coordinating the actions of all stakeholders in preparing students for career choice, the institutions of career guidance in France, Japan, and Germany were explored by the researchers. To achieve the aim of the project, the systemic contemporary model of school students’ professional self-determination, considering their individual opportunities and special educational needs, has been developed based on the study results and international experience. The main principles of this model are consistency, accessibility, inclusiveness, openness, coherence, continuity. The perspectives of students’ career guidance development in the context of inclusive education have been suggested.

Keywords: career guidance, inclusive education, model of school students’ professional self-determination, psychological and pedagogical support, special educational needs

Procedia PDF Downloads 58
3056 Derivation of Generic Kinematic Equations of Above-Knee Prosthetic Legs Using DH Parameters

Authors: Serdar Kucuk, Redwan Alqasemi

Abstract:

In this paper, the generic kinematic equations of 1-Degrees-Of-Freedom (DOF), 2-DOF, and 3-DOF above-knee prosthetic legs are derived using the mathematical tools used in science of robotics. As it is known, since the human leg performs rotational motions in the knee joint and foot-ankle joint, the axial rotational motions in the above-knee prosthetic legs are performed by using one or more revolute joints. When deriving the kinematic equations of the 1-DOF, 2-DOF, and 3-DOF above-knee prosthetic legs, the foot-ankle is treated as if there were a fixed non-rotating joint, a revolute joint, and a universal joint, respectively. The kinematic equations of the prosthetic legs presented in this article are obtained using DH method. The main advantages of this method are the easy physical interpretation of robot mechanisms and the use of 4x4 homogeneous transformation matrices, which are widely used in the literature. It is thought that the equations presented in this article contribute positively to the design, control, simulation and hence easy production of above-knee prosthetic legs.

Keywords: robotic above-knee prosthetic legs, generic kinematic equations, revolute and universal joints, DH method

Procedia PDF Downloads 12
3055 Genistein Suppresses Doxorubicin Associated Genotoxicity in Human Lymphocytes

Authors: Tanveer Beg, Yasir H. Siddique, Gulshan Ara, Asfar S. Azmi, Mohammad Afzal

Abstract:

Doxorubicin is a well-known DNA intercalating chemotherapy drug that is widely used for treatment of different cancers. Its clinical utility is limited due to the observed genotoxic side effects on healthy cells suggesting that newer combination and genoprotective regimens are urgently needed for the management of doxorubicin chemotherapy. Some dietary phytochemicals are well known for their protective mechanism of action and genistein from soy is recognized as an anti-oxidant with similar properties. Therefore, the present study investigates the effect of genistein against the genotoxic doses of doxorubicin by assessing chromosomal aberrations, sister chromatid exchanges, cell cycle kinetics, cell viability, apoptosis, and DNA damage markers in cultured human lymphocytes. Our results reveal that genistein treatment significantly suppresses genotoxic damage induced by doxorubicin. It is concluded that genistein has the potential to reduce the genotoxicity induced by anti-cancer drugs, thereby reducing the chances of developing secondary tumors during the therapy.

Keywords: apoptosis, DNA damage markers, doxorubicin, genistein, genotoxicity, human lymphocyte culture

Procedia PDF Downloads 361