Search results for: modulation recognition
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2158

Search results for: modulation recognition

418 TNF Modulation of Cancer Stem Cells in Renal Clear Cell Carcinoma

Authors: Rafia S. Al-lamki, Jun Wang, Simon Pacey, Jordan Pober, John R. Bradley

Abstract:

Tumor necrosis factor alpha (TNF), signaling through TNFR2, may act an autocrine growth factor for renal tubular epithelial cells. Clear cell renal carcinomas (ccRCC) contain cancer stem cells (CSCs) that give rise to progeny which form the bulk of the tumor. CSCs are rarely in cell cycle and, as non-proliferating cells, resist most chemotherapeutic agents. Thus, recurrence after chemotherapy may result from the survival of CSCs. Therapeutic targeting of both CSCs and the more differentiated bulk tumor populations may provide a more effective strategy for treatment of RCC. In this study, we hypothesized that TNFR2 signaling will induce CSCs in ccRCC to enter cell cycle so that treatment with ligands that engage TNFR2 will render CSCs susceptible to chemotherapy. To test this hypothesis, we have utilized wild-type TNF (wtTNF) or specific muteins selective for TNFR1 (R1TNF) or TNFR2 (R2TNF) to treat either short-term organ cultures of ccRCC and adjacent normal kidney (NK) tissue or cultures of CD133+ cells isolated from ccRCC and adjacent NK, hereafter referred to as stem cell-like cells (SCLCs). The effect of cyclophosphamide (CP), currently an effective anticancer agent, was tested on CD133+SCLCs from ccRCC and NK before and after R2TNF treatment. Responses to TNF were assessed by flow cytometry (FACS), immunofluorescence, and quantitative real-time PCR, TUNEL, and cell viability assays. Cytotoxic effect of CP was analyzed by Annexin V and propidium iodide staining with FACS. In addition, we assessed the effect of TNF on isolated SCLCs differentiation using a three-dimensional (3D) culture system. Clinical samples of ccRCC contain a greater number SCLCs compared to NK and the number of SCSC increases with higher tumor grade. Isolated SCLCs show expression of stemness markers (oct4, Nanog, Sox2, Lin28) but not differentiation markers (cytokeratin, CD31, CD45, and EpCAM). In ccRCC organ cultures, wtTNF and R2TNF increase CD133 and TNFR2 expression and promote cell cycle entry whereas wtTNF and R1TNF increase TNFR1 expression and promote cell death of SCLCs. Similar findings are observed in SCLCs isolated from NK but the effect was greater in SCLCs isolated from ccRCC. Application of CP distinctly triggered apoptotic and necrotic cell death in SLCSs pre-treatment with R2TNF as compared to CP treatment alone, with SCLCs from ccRCC more sensitive to CP compared to SLCS from NK. Furthermore, TNF promotes differentiation of SCLCs to an epithelial phenotype in 3D cultures, confirmed by cytokeratin expression and loss of stemness markers Nanog and Sox2. The differentiated cells show positive expression of TNF and TNFR2. These findings provide evidence that selective engagement of TNFR2 drive CSCs to cell proliferation/differentiation, and targeting of cycling cells with TNFR2 agonist in combination with anti-cancer agents may be a potential therapy for RCC.

Keywords: cancer stem cells, ccRCC, cell cycle, cell death, TNF, TNFR1, TNFR2, CD133

Procedia PDF Downloads 262
417 An Analysis of the Representation of the Translator and Translation Process into Brazilian Social Networking Groups

Authors: Érica Lima

Abstract:

In the digital era, in which we have an avalanche of information, it is not new that the Internet has brought new modes of communication and knowledge access. Characterized by the multiplicity of discourses, opinions, beliefs and cultures, the web is a space of political-ideological dimensions where people (who often do not know each other) interact and create representations, deconstruct stereotypes, and redefine identities. Currently, the translator needs to be able to deal with digital spaces ranging from specific software to social media, which inevitably impact on his professional life. One of the most impactful ways of being seen in cyberspace is the participation in social networking groups. In addition to its ability to disseminate information among participants, social networking groups allow a significant personal and social exposure. Such exposure is due to the visibility of each participant achieved not only on its personal profile page, but also in each comment or post the person makes in the groups. The objective of this paper is to study the representations of translators and translation process on the Internet, more specifically in publications in two Brazilian groups of great influence on the Facebook: "Translators/Interpreters" and "Translators, Interpreters and Curious". These chosen groups represent the changes the network has brought to the profession, including the way translators are seen and see themselves. The analyzed posts allowed a reading of what common sense seems to think about the translator as opposed to what the translators seem to think about themselves as a professional class. The results of the analysis lead to the conclusion that these two positions are antagonistic and sometimes represent conflict of interests: on the one hand, the society in general consider the translator’s work something easy, therefore it is not necessary to be well remunerated; on the other hand, the translators who know how complex a translation process is and how much it takes to be a good professional. The results also reveal that social networking sites such as Facebook provide more visibility, but it takes a more active role from the translator to achieve a greater appreciation of the profession and more recognition of the role of the translator, especially in face of increasingly development of automatic translation programs.

Keywords: Facebook, social representation, translation, translator

Procedia PDF Downloads 148
416 Perinatal Ethanol Exposure Modifies CART System in Rat Brain Anticipated for Development of Anxiety, Depression and Memory Deficits

Authors: M. P. Dandekar, A. P. Bharne, P. T. Borkar, D. M. Kokare, N. K. Subhedar

Abstract:

Ethanol ingestion by the mother ensue adverse consequences for her offspring. Herein, we examine the behavioral phenotype and neural substrate of the offspring of the mother on ethanol. Female rats were fed with ethanol-containing liquid diet from 8 days prior of conception and continued till 25 days post-parturition to coincide with weaning. Behavioral changes associated with anxiety, depression and learning and memory were assessed in the offspring, after they attained adulthood (day 85), using elevated plus maze (EPM), forced swim (FST) and novel object recognition tests (NORT), respectively. The offspring of the alcoholic mother, compared to those of the pair-fed mother, spent significantly more time in closed arms of EPM and showed more immobility time in FST. Offspring at the age of 25 and 85 days failed to discriminate between novel versus familiar object in NORT, thus reflecting anxiogenic, depressive and amnesic phenotypes. Neuropeptide cocaine- and amphetamine-regulated transcript peptide (CART) is known to be involved in central effects of ethanol and hence selected for the current study. Twenty-five days old pups of the alcoholic mother showed significant augmentation in CART-immunoreactivity in the cells of Edinger-Westphal (EW) nucleus and lateral hypothalamus. However, a significant decrease in CART-immunoreactivity was seen in nucleus accumbens shell (AcbSh), lateral part of bed nucleus of the stria terminalis (BNSTl), locus coeruleus (LC), hippocampus (CA1, CA2 and CA3), and arcuate nucleus (ARC) of the pups and/or adults offspring. While no change in the CART-immunoreactive fibers of AcbSh and BNSTl, CA2 and CA3 was noticed in the 25 days old pups, the CART-immunoreactive cells in EW and paraventricular nucleus (PVN), and fibers in the central nucleus of amygdala of 85 days old offspring remained unaffected. We suggest that the endogenous CART system in these discrete areas, among other factors, may be a causal to the abnormalities in the next generation of an alcoholic mother.

Keywords: anxiety, depression, CART, ethanol, immunocytochemistry

Procedia PDF Downloads 395
415 Opportunities for Lesbian/Gay/Bisexual/Transgender/Queer/Questioning Tourism in Vietnam

Authors: Eric D. Olson

Abstract:

The lesbian/gay/bisexual/transgender/queer/questioning tourist (LGBTQ+) travels more frequently, spends more money on travel, and is more likely to travel internationally compared to their straight/heterosexual counterparts. For Vietnam, this represents a huge opportunity to increase international tourism, considering social advancements and recognition of the LGBTQ+ have greatly increased in the past few years in Vietnam. For example, Vietnam’s Health Ministry confirmed in 2022 that same-sex attraction and being transgender is not a mental health condition. A robust hospitality ecosystem of LGBTQ+ tourism suppliers already exists in Vietnam catering to LGBTQ+ tourists (e.g., Gay Hanoi Tours, VietPride). Vietnam is a safe and welcoming destination with incredible nature, cosmopolitan cities, and friendly people; however, there is a dearth of academic and industry research that has examined how LGBTQ+ international tourists perceive Vietnam as an LGBTQ+ friendly destination. To rectify this gap, this research examines Vietnam as an LGBTQ+ destination in order to provide government officials, destination marketers, and industry practitioners with insight into this increasingly visible tourist market segment. A self-administered survey instrument was administered to n=375 international LGBTQ+ tourists to examine their perceptions of Vietnam. A factor analysis found three categories of LGBTQ+ factors of visitation to Vietnam: safety and security (Eigenvalue = 4.12, variance = 32.45, α = .82); LGBTQ+ attractions (Eigenvalue = 3.65 variance = 24.23, α = .75); and friendly interactions (Eigenvalue = 3.71, variance = 10.45, α = .96). Multiple regression was used to examine LGBTQ+ visitation factors and intention to visit Vietnam, F=12.20 (2, 127), p < .001, R2 = .56. Safety and security (β = 0.42, p < .001), LGBTQ+ attractions (β = 0.61, p < .001) and friendly interactions (β = 0.42, p < .001) are predictors to visit Vietnam. Results are consistent with previous research that highlight safety/security is of utmost importance to the community when traveling. Attractions, such as LGBTQ+ tours, suppliers, and festivals can also be used as a pull factor in encouraging tourism. Implications/limitations will be discussed.

Keywords: tourism, LGBTQ, vietnam, regression

Procedia PDF Downloads 67
414 Corporate Governance and Corporate Social Responsibility: Research on the Interconnection of Both Concepts and Its Impact on Non-Profit Organizations

Authors: Helene Eller

Abstract:

The aim of non-profit organizations (NPO) is to provide services and goods for its clientele, with profit being a minor objective. By having this definition as the basic purpose of doing business, it is obvious that the goal of an organisation is to serve several bottom lines and not only the financial one. This approach is underpinned by the non-distribution constraint which means that NPO are allowed to make profits to a certain extent, but not to distribute them. The advantage is that there are no single shareholders who might have an interest in the prosperity of the organisation: there is no pie to divide. The gained profits remain within the organisation and will be reinvested in purposeful projects. Good governance is mandatory to support the aim of NPOs. Looking for a measure of good governance the principals of corporate governance (CG) will come in mind. The purpose of CG is direction and control, and in the field of NPO, CG is enlarged to consider the relationship to all important stakeholders who have an impact on the organisation. The recognition of more relevant parties than the shareholder is the link to corporate social responsibility (CSR). It supports a broader view of the bottom line: It is no longer enough to know how profits are used but rather how they are made. Besides, CSR addresses the responsibility of organisations for their impact on society. When transferring the concept of CSR to the non-profit area it will become obvious that CSR with its distinctive features will match the aims of NPOs. As a consequence, NPOs who apply CG apply also CSR to a certain extent. The research is designed as a comprehensive theoretical and empirical analysis. First, the investigation focuses on the theoretical basis of both concepts. Second, the similarities and differences are outlined and as a result the interconnection of both concepts will show up. The contribution of this research is manifold: The interconnection of both concepts when applied to NPOs has not got any attention in science yet. CSR and governance as integrated concept provides a lot of advantages for NPOs compared to for-profit organisations which are in a steady justification to show the impact they might have on the society. NPOs, however, integrate economic and social aspects as starting point. For NPOs CG is not a mere concept of compliance but rather an enhanced concept integrating a lot of aspects of CSR. There is no “either-nor” between the concepts for NPOs.

Keywords: business ethics, corporate governance, corporate social responsibility, non-profit organisations

Procedia PDF Downloads 240
413 Analysis of Maternal Death Surveillance and Response: Causes and Contributing Factors in Addis Ababa, Ethiopia, 2022

Authors: Sisay Tiroro Salato

Abstract:

Background: Ethiopia has been implementing the maternal death surveillance and response system to provide real-time actionable information, including causes of death and contributing factors. Analysis of maternal mortality surveillance data was conducted to identify the causes and underlying factors in Addis Ababa, Ethiopia. Methods: We carried out a retrospective surveillance data analysis of 324 maternal deaths reported in Addis Ababa, Ethiopia, from 2017 to 2021. The data were extracted from the national maternal death surveillance and response database, including information from case investigation, verbal autopsy, and facility extraction forms. The data were analyzed by computing frequency and presented in numbers, proportions, and ratios. Results: Of 324 maternal deaths, 92% died in the health facilities, 6.2% in transit, and 1.5% at home. The mean age at death was 28 years, ranging from 17 to 45. The maternal mortality ratio per 100,000 live births was 77for the five years, ranging from 126 in 2017 to 21 in 2021. The direct and indirect causes of death were responsible for 87% and 13%, respectively. The direct causes included obstetric haemorrhage, hypertensive disorders in pregnancy, puerperal sepsis, embolism, obstructed labour, and abortion. The third delay (delay in receiving care after reaching health facilities) accounted for 57% of deaths, while the first delay (delay in deciding to seek health care) and the second delay (delay in reaching health facilities) and accounted for 34% and 24%, respectively. Late arrival to the referral facility, delayed management after admission, andnon-recognition of danger signs were underlying factors. Conclusion: Over 86% of maternal deaths were attributed by avoidable direct causes. The majority of women do try to reach health services when an emergency occurs, but the third delays present a major problem. Improving the quality of care at the healthcare facility level will help to reduce maternal death.

Keywords: maternal death, surveillance, delays, factors

Procedia PDF Downloads 113
412 Toward Indoor and Outdoor Surveillance using an Improved Fast Background Subtraction Algorithm

Authors: El Harraj Abdeslam, Raissouni Naoufal

Abstract:

The detection of moving objects from a video image sequences is very important for object tracking, activity recognition, and behavior understanding in video surveillance. The most used approach for moving objects detection / tracking is background subtraction algorithms. Many approaches have been suggested for background subtraction. But, these are illumination change sensitive and the solutions proposed to bypass this problem are time consuming. In this paper, we propose a robust yet computationally efficient background subtraction approach and, mainly, focus on the ability to detect moving objects on dynamic scenes, for possible applications in complex and restricted access areas monitoring, where moving and motionless persons must be reliably detected. It consists of three main phases, establishing illumination changes in variance, background/foreground modeling and morphological analysis for noise removing. We handle illumination changes using Contrast Limited Histogram Equalization (CLAHE), which limits the intensity of each pixel to user determined maximum. Thus, it mitigates the degradation due to scene illumination changes and improves the visibility of the video signal. Initially, the background and foreground images are extracted from the video sequence. Then, the background and foreground images are separately enhanced by applying CLAHE. In order to form multi-modal backgrounds we model each channel of a pixel as a mixture of K Gaussians (K=5) using Gaussian Mixture Model (GMM). Finally, we post process the resulting binary foreground mask using morphological erosion and dilation transformations to remove possible noise. For experimental test, we used a standard dataset to challenge the efficiency and accuracy of the proposed method on a diverse set of dynamic scenes.

Keywords: video surveillance, background subtraction, contrast limited histogram equalization, illumination invariance, object tracking, object detection, behavior understanding, dynamic scenes

Procedia PDF Downloads 256
411 Slave Museums and a Site of Democratic Pedagogy: Engagement, Healing and Tolerance

Authors: Elaine Stavro

Abstract:

In our present world where acts of incivility, intolerance and anger towards minority communities is on the rise, the ways museum practices cultivate ethical generosity is of interest. Democratic theorists differ as to how they believe respect can be generated through active participation. Allowing minority communities a role in determining what artifacts will be displayed and how they will be displayed has been an important step in generating respect. In addition, the rise of indigenous museums, slave museums and curators who represent these communities, contribute to the communication of their history of oppression. These institutional practices have been supplemented by the handling of objects, recognition stories and multisensory exhibitions. Psychoanalysis, object relations theorists believe that the handling of objects: amenable objects and responsive listeners will trigger the expression of anomie, alienation and traumatizing experiences. Not only memorializing but engaging with one’s lose in a very personal way can facilitate the process of mourning. Manchester Museum (UK) gathered together Somalian refugees, who in the process of handling their own objects and those offered at the museum, began to tell their stories. Democratic theorists (especially affect theorists or vital materialists or Actor Network theorists) believe that things can be social actants- material objects have agentic capacities that humans should align with. In doing so, they challenge social constructivism that attributes power to interpreted things, but like them they assume an openness or responsiveness to Otherness can be cultivated. Rich sensory experiences, corporeal engagement (devices that involve bodily movement or objects that involve handling) auditory experiences (songs) all contribute to improve one’s responsiveness and openness to Others. This paper will focus specifically on slave museums/ and exhibits in the U.K, the USA., South Africa to explore and evaluate their democratic strategies in cultivating tolerant practices via the various democratic avenues outlined above.

Keywords: democratic pedagogy, slave exhibitions, affect/emotion, object handling

Procedia PDF Downloads 460
410 Development of Doctoral Education in Armenia (1990 - 2023)

Authors: Atom Mkhitaryan, Astghik Avetisyan

Abstract:

We analyze the developments of doctoral education in Armenia since 1990 and the management process. Education and training of highly qualified personnel are increasingly seen as a fundamental platform that ensures the development of the state. Reforming the national institute for doctoral studies (aspirantura) is aimed at improving the quality of human resources in science, optimizing research topics in accordance with the priority areas of development of science and technology, increasing publication and innovative activities, bringing national science and research closer to the world level and achieving international recognition. We present a number of defended dissertations in Armenia during the last 30 years, the dynamics and the main trends of the development of the academic degree awarding system. We discuss the possible impact of reforming the system of training and certification of highly qualified personnel on the organization of third–level doctoral education (doctoral schools) and specialized / dissertation councils in Armenia. The results of the SWOT analysis of doctoral education and academic degree awarding processes in Armenia are shown. The article presents the main activities and projects aimed at using the advantages and strong points of the National Academy network in order to improve the quality of doctoral education and training. The paper explores the mechanisms of organizational, methodological and infrastructural support for research and innovation activities of doctoral students and young scientists. There are also suggested approaches to the organization of strong networking between research institutes and foreign universities for training and certification of highly qualified personnel. The authors define the role of ISEC in the management of doctoral studies and the establishment of a competitive third-level education for the sphere of research and development in Armenia.

Keywords: doctoral studies, academic degree, PhD, certification, highly qualified personnel, dissertation, research and development, innovation, networking, management of doctoral school

Procedia PDF Downloads 63
409 Towards Innovation Performance among University Staff

Authors: Cheng Sim Quah, Sandra Phek Lin Sim

Abstract:

This study examined how individuals in their respective teams contributed to innovation performance besides defining the term of innovation in their own respective views. This study also identified factors that motivated University staff to contribute to the innovation products. In addition, it examined whether there is a significant relationship between professional training level and the length of service among university staff towards innovation and to what extent do the two variables contributed towards innovative products. The significance of this study is that it revealed the strengths and weaknesses of the university staff when contributing to innovation performance. Stratified-random sampling was employed to determine the samples representing the population of lecturers in the study, involving 123 lecturers in one of the local universities in Malaysia. The method employed to analyze the data is through categorizing into themes for the open-ended questions besides using descriptive and inferential statistics for the quantitative data. This study revealed that two types of definition for the term “innovation” exist among the university staff, namely, creation of new product or new approach to do things as well as value-added creative way to upgrade or improve existing process and service to be more efficient. This study found that the most prominent factor that propel them towards innovation is to improve the product in order to benefit users, followed by self-satisfaction and recognition. This implies that the staff in the organization viewed the creation of innovative products as a process of growth to fulfill the needs of others and also to realize their personal potential. This study also found that there was only a significant relationship between the professional training level and the length of service of 4-6 years among the university staff. The rest of the groups based on the length of service showed that there was no significant relationship with the professional training level towards innovation. Moreover, results of the study on directional measures depicted that the relationship for the length of service of 4 - 6 years with professional training level among the university staff is quite weak. This implies that good organization management lies on the shoulders of the key leaders who enlighten the path to be followed by the staff.

Keywords: innovation, length of service, performance, professional training level, motivation

Procedia PDF Downloads 320
408 Ambient Electrospray Deposition: An Efficient Technique to Immobilize Laccase on Cheap Electrodes With Unprecedented Reuse and Storage Performances

Authors: Mattea Carmen Castrovilli, Antonella Cartoni

Abstract:

Electrospray ionisation (ESI), a well-established technique widely used to produce ion beams of biomolecules in mass spectrometry (ESI-MS), can be used for ambient soft landing of enzymes on a specific substrate. In this work, we show how the ambient electrospray deposition (ESD) technique can be successfully exploited for manufacturing a promising, green-friendly electrochemical amperometric laccase-based biosensor with unprecedented reuse and storage performance. These biosensors have been manufactured by spraying a laccase solution of 2μg/μL at 20% of methanol on a commercial carbon screen printed electrode (C-SPE) using a custom ESD set-up. The laccase-based ESD biosensor has been tested against catechol compounds in the linear range 2-100 μM, with a limit of detection of 1.7 μM, without interference from cadmium, chrome, arsenic, and zinc and without any memory effects, but showing a matrix effect in lake and well water. The ESD biosensor shows enhanced performances compared to the ones fabricated with other immobilization methods, like drop-casting. Indeed, it retains 100% activity up to two months of storage at ambient conditions without any special care and working stability up to 63 measurements on the same electrode just prepared and 20 on a one-year-old electrode subjected to redeposition together with a 100% resistance to use of the same electrode in subsequent days. The ESD method is a one-step, environmentally friendly method that allows the deposition of the bio-recognition layer without using any additional chemicals. The promising results in terms of storage and working stability also obtained with the more fragile lactate oxidase enzyme suggest these improvements should be attributed to the ESD technique rather than to the bioreceptor, highlighting how the ESD could be useful in reducing pollution from disposable devices. Acknowledgment: The understanding at the molecular level of this promising biosensor by using different spectroscopies, microscopies and analytical techniques is the subject of our PRIN 2022 project ESILARANTE.

Keywords: reuse, storage performance, immobilization, electrospray deposition, biosensor, laccase, catechol detection, green chemistry

Procedia PDF Downloads 62
407 Radiation Safety Factor of Education and Research Institution in Republic of Korea

Authors: Yeo Ryeong Jeon, Pyong Kon Cho, Eun Ok Han, Hyon Chul Jang, Yong Min Kim

Abstract:

This study surveyed on recognition related to radiation safety for radiation safety managers and workers those who have been worked in Republic of Korea education and research institution. At present, South Korea has no guideline and manual of radiation safety for education and research institution. Therefore, we tried to find an educational basis for development of radiation safety guideline and manual. To check the level of knowledge, attitude, and behavior about radiation safety, we used the questionnaire that consisted of 29 questions against knowledge, attitude and behavior, 4 questions against self-efficacy and expectation based on four factors (radiation source, human, organizational and physical environment) of the Haddon's matrix. Responses were collected between May 4 and June 30, 2015. We analyzed questionnaire by means of IBM SPSS/WIN 15 which well known as statistical package for social science. The data were compared with mean, standard deviation, Pearson's correlation, ANOVA (analysis of variance) and regression analysis. 180 copies of the questionnaire were returned from 60 workplaces. The overall mean results for behavior level was relatively lower than knowledge and attitude level. In particular, organizational environment factor on the radiation safety management indicated the lowest behavior level. Most of the factors were correlated in Pearson’s correlation analysis, especially between knowledge of human factors and behavior of human factors (Pearson’s correlation coefficient 0.809, P<.01). When analysis performed in line with the main radiation source type, institutions where have been used only opened RI (radioisotope) behavior level was the lowest among all subjects. Finally, knowledge of radiation source factor (β=0.556, P<.001) and human factor(β=0.376, P<.001) had the greatest impact in terms of behavior practice. Radiation safety managers and workers think positively about radiation safety management, but are poorly informed organizational environment of their institution. Thus, each institution need to efforts to settlement of radiation safety culture. Also, pedagogical interventions for improving knowledge on radiation safety needs in terms of safety accident prevention.

Keywords: radiation safety management, factor analysis, SPSS, republic of Korea

Procedia PDF Downloads 364
406 Systematic Identification and Quantification of Substrate Specificity Determinants in Human Protein Kinases

Authors: Manuel A. Alonso-Tarajano, Roberto Mosca, Patrick Aloy

Abstract:

Protein kinases participate in a myriad of cellular processes of major biomedical interest. The in vivo substrate specificity of these enzymes is a process determined by several factors, and despite several years of research on the topic, is still far from being totally understood. In the present work, we have quantified the contributions to the kinase substrate specificity of i) the phosphorylation sites and their surrounding residues in the sequence and of ii) the association of kinases to adaptor or scaffold proteins. We have used position-specific scoring matrices (PSSMs), to represent the stretches of sequences phosphorylated by 93 families of kinases. We have found negative correlations between the number of sequences from which a PSSM is generated and the statistical significance and the performance of that PSSM. Using a subset of 22 statistically significant PSSMs, we have identified specificity determinant residues (SDRs) for 86% of the corresponding kinase families. Our results suggest that different SDRs can function as positive or negative elements of substrate recognition by the different families of kinases. Additionally, we have found that human proteins with known function as adaptors or scaffolds (kAS) tend to interact with a significantly large fraction of the substrates of the kinases to which they associate. Based on this characteristic we have identified a set of 279 potential adaptors/scaffolds (pAS) for human kinases, which is enriched in Pfam domains and functional terms tightly related to the proposed function. Moreover, our results show that for 74.6% of the kinase– pAS association found, the pAS colocalize with the substrates of the kinases they are associated to. Finally, we have found evidence suggesting that the association of kinases to adaptors and scaffolds, may contribute significantly to diminish the in vivo substrate crossed- specificity of protein kinases. In general, our results indicate the relevance of several SDRs for both the positive and negative selection of phosphorylation sites by kinase families and also suggest that the association of kinases to pAS proteins may be an important factor for the localization of the enzymes with their set of substrates.

Keywords: kinase, phosphorylation, substrate specificity, adaptors, scaffolds, cellular colocalization

Procedia PDF Downloads 343
405 Morphology and Risk Factors for Blunt Aortic Trauma in Car Accidents: An Autopsy Study

Authors: Ticijana Prijon, Branko Ermenc

Abstract:

Background: Blunt aortic trauma (BAT) includes various morphological changes that occur during deceleration, acceleration and/or body compression in traffic accidents. The various forms of BAT, from limited laceration of the intima to complete transection of the aorta, depends on the force acting on the vessel wall and the tolerance of the aorta to injury. The force depends on the change in velocity, the dynamics of the accident and of the seating position in the car. Tolerance to aortic injury depends on the anatomy, histological structure and pathomorphological alterations due to aging or disease of the aortic wall.An overview of the literature and medical documentation reveals that different terms are used to describe certain forms of BAT, which can lead to misinterpretation of findings or diagnoses. We therefore, propose a classification that would enable uniform systematic screening of all forms of BAT. We have classified BAT into three morphologycal types: TYPE I (intramural), TYPE II (transmural) and TYPE III (multiple) aortic ruptures with appropriate subtypes. Methods: All car accident casualties examined at the Institute of Forensic Medicine from 2001 to 2009 were included in this retrospective study. Autopsy reports were used to determine the occurrence of each morphological type of BAT in deceased drivers, front seat passengers and other passengers in cars and to define the morphology of BAT in relation to the accident dynamics and the age of the fatalities. Results: A total of 391 fatalities in car accidents were included in the study. TYPE I, TYPE II and TYPE III BAT were observed in 10,9%, 55,6% and 33,5%, respectively. The incidence of BAT in drivers, front seat and other passengers was 36,7%, 43,1% and 28,6%, respectively. In frontal collisions, the incidence of BAT was 32,7%, in lateral collisions 54,2%, and in other traffic accidents 29,3%. The average age of fatalities with BAT was 42,8 years and of those without BAT 39,1 years. Conclusion: Identification and early recognition of the risk factors of BAT following a traffic accident is crucial for successful treatment of patients with BAT. Front seat passengers over 50 years of age who have been injured in a lateral collision are the most at risk of BAT.

Keywords: aorta, blunt trauma, car accidents, morphology, risk factors

Procedia PDF Downloads 513
404 Identifying the Challenges of Implementing Nationwide E-Government Services in Underdeveloped Countries: Sudan as a Case Study

Authors: Mohamed Abdalla Khalil Mahmoud, Omnia Haidar Suliman

Abstract:

Information and Communication technologies have revolutionized the way services are developed and offered to customers and have achieved evident success in a variety of vital sectors and widely contributed to the growth and resilience of the economy worldwide. Consequently, governments, especially of developing countries, have turned their attention to examine possible ways to utilize contemporary technology advances to offer essential governmental services to citizens, especially in areas where government agencies are not present. This paper investigates the challenges that impede governments of developing countries to provide basic services to its constituents nationwide. Sudan, as a case study, has taken major steps to provide essential governmental services via electronic channels. However, these services are still not widely used by the citizens, resulting in waste of financial and human resources and efforts that could have been invested more appropriately. This paper examines the challenges that hinder the Sudan’s government in their pursuit of availing its services via electronic channels. Different categories of e-government challenges, such as organizational, technological, social and, demographic, and financial and economic, have been explored in order to pinpoint the major challenges. A structured questionnaire is used to survey the target population of e-government professionals and executives who have direct involvement in the implementation of this nationwide endeavor in Sudan. The survey has successfully identified the main challenges that have high impact on the government’s effort to offer its services via electronic channels, such as Lack of coordination between public and private sectors and Lack of the benefits recognition of the e-government program. The findings of this paper can be used as a solid foundation for improving the way governmental services are offered to citizens in Sudan, resulting in a successful investment of financial and human resources and benefiting the targeted customers of all types.

Keywords: citizen, digital, e-channels, public sector, Sudan, technology

Procedia PDF Downloads 71
403 Cannabis Sativa L as Natural Source of Promising Anti-Alzheimer Drug Candidates: A Comprehensive Computational Approach Including Molecular Docking, Molecular Dynamics, Admet and MM-PBSA Studies

Authors: Hassan Nour, Nouh Mounadi, Oussama Abchir, Belaidi Salah, Samir Chtita

Abstract:

Cholinesterase enzymes are biological catalysts essential for the transformation of acetylcholine, which is a neurotransmitter implicated in memory and learning, into acetic acid and choline, altering the neurotransmission process in Alzheimer’s disease patients. Therefore, inhibition of cholinesterase enzymes is a relevant strategy for the symptomatic treatment of Alzheimer’s disease. The current investigation aims to explore potential Cholinesterase (ChE) inhibitors through a comprehensive computational approach. Forty-nine phytoconstituents extracted from Cannabis sativa L were in-silico screened using molecular docking, pharmacokinetic and toxicological analysis to evaluate their possible inhibitory effect towards the cholinesterase enzymes. Two phytoconstituents belonging to cannabinoid derivatives were revealed to be promising candidates for Alzheimer therapy by acting as cholinesterase inhibitors. They have exhibited high binding affinities towards the cholinesterase enzymes and showed their ability to interact with key residues involved in cholinesterase enzymatic activity. In addition, they presented good ADMET profiles allowing them to be promising oral drug candidates. Furthermore, molecular dynamics (MD) simulations were executed to explore their interactions stability under mimetic biological conditions and thus support our findings. To corroborate the docking results, the binding free energy corresponding to the more stable ligand-ChE complexes was re-estimated by applying the MM-PBSA method. MD and MM-PBSA studies affirmed that the ligand-ChE recognition is spontaneous reaction leading to stable complexes. The conducted investigations have led to great findings that would strongly guide the pharmaceutical industries towards the rational development of potent anti-Alzheimer agents.

Keywords: alzheimer’s disease, molecular docking, cannabis sativa l, cholinesterase inhibitors

Procedia PDF Downloads 73
402 3d Property Modelling of the Lower Acacus Reservoir, Ghadames Basin, Libya

Authors: Aimen Saleh

Abstract:

The Silurian Lower Acacus sandstone is one of the main reservoirs in North West Libya. Our aim in this study is to grasp a robust understanding of the hydrocarbon potential and distribution in the area. To date, the depositional environment of the Lower Acacus reservoir still open to discussion and contradiction. Henceforth, building three dimensional (3D) property modelling is one way to support the analysis and description of the reservoir, its properties and characterizations, so this will be of great value in this project. The 3D model integrates different data set, these incorporates well logs data, petrophysical reservoir properties and seismic data as well. The finalized depositional environment model of the Lower Acacus concludes that the area is located in a deltaic transitional depositional setting, which ranges from a wave dominated delta into tide dominated delta type. This interpretation carried out through a series of steps of model generation, core description and Formation Microresistivity Image tool (FMI) interpretation. After the analysis of the core data, the Lower Acacus layers shows a strong effect of tidal energy. Whereas these traces found imprinted in different types of sedimentary structures, for examples; presence of some crossbedding, such as herringbones structures, wavy and flaser cross beddings. In spite of recognition of some minor marine transgression events in the area, on the contrary, the coarsening upward cycles of sand and shale layers in the Lower Acacus demonstrate presence of a major regressive phase of the sea level. However, consequently, we produced a final package of this model in a complemented set of facies distribution, porosity and oil presence. And also it shows the record of the petroleum system, and the procedure of Hydrocarbon migration and accumulation. Finally, this model suggests that the area can be outlined into three main segments of hydrocarbon potential, which can be a textbook guide for future exploration and production strategies in the area.

Keywords: Acacus, Ghadames , Libya, Silurian

Procedia PDF Downloads 143
401 Associated Risks of Spontaneous Lung Collapse after Shoulder Surgery: A Literature Review

Authors: Fiona Bei Na Tan, Glen Wen Kiat Ho, Ee Leen Liow, Li Yin Tan, Sean Wei Loong Ho

Abstract:

Background: Shoulder arthroscopy is an increasingly common procedure. Pneumothorax post-shoulder arthroscopy is a rare complication. Objectives: Our aim is to highlight a case report of pneumothorax post shoulder arthroscopy and to conduct a literature review to evaluate the possible risk factors associated with developing a pneumothorax during or after shoulder arthroscopy. Case Report: We report the case of a 75-year-old male non-smoker who underwent left shoulder arthroscopy without regional anaesthesia and in the left lateral position. The general anaesthesia and surgery were uncomplicated. The patient was desaturated postoperatively and was found to have a pneumothorax on examination and chest X-ray. A chest tube drain was inserted promptly into the right chest. He had an uncomplicated postoperative course. Methods: PubMed Medline and Cochrane database search was carried out using the terms shoulder arthroplasty, pneumothorax, pneumomediastinum, and subcutaneous emphysema. We selected full-text articles written in English. Results: Thirty-two articles were identified and thoroughly reviewed. Based on our inclusion and exclusion criteria, 14 articles, which included 20 cases of pneumothorax during or after shoulder arthroscopy, were included. Eighty percent (16/20) of pneumothoraxes occurred postoperatively. In the articles that specify the side of pneumothorax, 91% (10/11) occur on the ipsilateral side of the arthroscopy. Eighty-eight percent (7/8) of pneumothoraxes occurred when subacromial decompression was performed. Fifty-six percent (9/16) occurred in patients placed in the lateral decubitus position. Only 30% (6/20) occurred in current or ex-smokers, and only 25% (5/20) had a pre-existing lung condition. Overall, of the articles that posit a mechanism, 75% (9/12) deem the pathogenesis to be multifactorial. Conclusion: The exact mechanism of pneumothorax is currently unknown. Awareness of this complication and timely recognition are important to prevent life-threatening sequelae. Surgeons should have a low threshold to obtain diagnostic plain radiographs in the event of clinical suspicion.

Keywords: rotator cuff repair, decompression, pressure, complication

Procedia PDF Downloads 66
400 Overall Assessment of Human Research and Ethics Committees in the United Arab Emirates

Authors: Mahera Abdulrahman, Satish Chandrasekhar Nair

Abstract:

Growing demand for human health research in the United Arab Emirates (UAE) has prompted the need to develop a robust research ethics oversight, particularly given the large unskilled-worker immigrant population and the elderly citizens utilizing health services. Examination of the structure, function, practices and outcomes of the human research ethics committees (HREC) was conducted using two survey instruments, reliable and validated. Results indicate that in the absence of a national ethics regulatory body, the individual emirate’s governed 21 HRECs covering health facilities and academic institutions in the UAE. Among the HRECs, 86% followed International Council for Harmonization-Good Clinical Practice guidelines, 57% have been in operation for more than five years, 81% reviewed proposals within eight weeks, 48% reviewed for clinical and scientific merit apart from ethics, and 43% handled more than 50 research proposals per year. However, researcher recognition, funding transparency, adverse event reporting systems were widespread in less than one-third of all HRECs. Surprisingly, intellectual property right was not included as a research output. Research was incorporated into the vision and mission statements of many (62%) organizations and, mechanisms such as research publications, collaborations, and recognitions were employed as key performance indicators to measure research output. In spite, resources to generate research output such as dedicated budget (19%), support staff (19%) and continuous training and mentoring program for medical residents and HREC members were somehow lacking. HREC structure and operations in the UAE are similar to other regions of the world, resources allocation for efficient, quality monitoring, continuous training, and the creation of a clinical research network are needed to strengthen the clinical research enterprise to scale up for the future. It is anticipated that the results of this study will benefit investigators, regulators, pharmaceutical sponsors and the policy makers in the region.

Keywords: institutional review board, ethics committee, human research ethics, United Arab Emirates (UAE)

Procedia PDF Downloads 224
399 Force Sensor for Robotic Graspers in Minimally Invasive Surgery

Authors: Naghmeh M. Bandari, Javad Dargahi, Muthukumaran Packirisamy

Abstract:

Robot-assisted minimally invasive surgery (RMIS) has been widely performed around the world during the last two decades. RMIS demonstrates significant advantages over conventional surgery, e.g., improving the accuracy and dexterity of a surgeon, providing 3D vision, motion scaling, hand-eye coordination, decreasing tremor, and reducing x-ray exposure for surgeons. Despite benefits, surgeons cannot touch the surgical site and perceive tactile information. This happens due to the remote control of robots. The literature survey identified the lack of force feedback as the riskiest limitation in the existing technology. Without the perception of tool-tissue contact force, the surgeon might apply an excessive force causing tissue laceration or insufficient force causing tissue slippage. The primary use of force sensors has been to measure the tool-tissue interaction force in real-time in-situ. Design of a tactile sensor is subjected to a set of design requirements, e.g., biocompatibility, electrical-passivity, MRI-compatibility, miniaturization, ability to measure static and dynamic force. In this study, a planar optical fiber-based sensor was proposed to mount at the surgical grasper. It was developed based on the light intensity modulation principle. The deflectable part of the sensor was a beam modeled as a cantilever Euler-Bernoulli beam on rigid substrates. A semi-cylindrical indenter was attached to the bottom surface the beam at the mid-span. An optical fiber was secured at both ends on the same rigid substrates. The indenter was in contact with the fiber. External force on the sensor caused deflection in the beam and optical fiber simultaneously. The micro-bending of the optical fiber would consequently result in light power loss. The sensor was simulated and studied using finite element methods. A laser light beam with 800nm wavelength and 5mW power was used as the input to the optical fiber. The output power was measured using a photodetector. The voltage from photodetector was calibrated to the external force for a chirp input (0.1-5Hz). The range, resolution, and hysteresis of the sensor were studied under monotonic and harmonic external forces of 0-2.0N with 0 and 5Hz, respectively. The results confirmed the validity of proposed sensing principle. Also, the sensor demonstrated an acceptable linearity (R2 > 0.9). A minimum external force was observed below which no power loss was detectable. It is postulated that this phenomenon is attributed to the critical angle of the optical fiber to observe total internal reflection. The experimental results were of negligible hysteresis (R2 > 0.9) and in fair agreement with the simulations. In conclusion, the suggested planar sensor is assessed to be a cost-effective solution, feasible, and easy to use the sensor for being miniaturized and integrated at the tip of robotic graspers. Geometrical and optical factors affecting the minimum sensible force and the working range of the sensor should be studied and optimized. This design is intrinsically scalable and meets all the design requirements. Therefore, it has a significant potential of industrialization and mass production.

Keywords: force sensor, minimally invasive surgery, optical sensor, robotic surgery, tactile sensor

Procedia PDF Downloads 230
398 Connecting Life and Learning: Transformative Learning to Increase Student Engagement

Authors: Kashi Raj Pandey

Abstract:

Transformative learning is a form of learning rooted in learners' life experiences and their inherent love for learning. It emphasizes the importance of incorporating students' everyday work through the use of learning diaries and reflective journals. It encourages learners to take a proactive role in their own improvement, fostering creativity and promoting informed discussions about the learning process. Reflecting on the personal experience with English language learning in a rural village in Nepal where rote memorization was the prevailing teaching method, this traditional approach hindered a deeper understanding of the language, prompting the author to recognize the need for more effective pedagogy. In this study, the author delved into the cultural contextualization of English language learning, taking into account learners' backgrounds. The study’s findings highlighted the importance of equity, inclusion, mutuality, and social justice in the classroom, emphasizing the significance of integrating students' lived experiences into the pedagogical approach. This, in turn, can encourage students to engage in profound and collaborative learning practices within the realm of English language education. Upon successfully implementing the research findings, including the eight key conditions of transformative learning, in multiple classrooms, the author collaborated with international educationists and government stakeholders in Nepal. The purpose was to disseminate the research findings, conduct teacher training workshops, and systematically enhance Nepali students’ English language learning. These methods have already demonstrated a significant improvement in student engagement within the same school where the author once learned English as a child. This study aims to explore teachers’ decision-making process regarding the transition from traditional teaching methods to interactive ones, which have gained national recognition within the ESL/EFL teaching community in Nepal. By sharing these experiences, it is expected that other teachers will also contemplate adopting transformative learning pedagogy in their own classrooms.

Keywords: reflection, student engagement, pedagogy, transformative learning

Procedia PDF Downloads 80
397 Environmental Degradation and Biodiversity Loss in Bangladesh

Authors: Mohammad Atiqur Rahman

Abstract:

The study aimed at inventorying the threatened biodiversity of Bangladesh and assessing the rate of loss of biodiversity caused due to environmental degradation for conservation management. The impact assessment of environmental depletion and rate of biodiversity loss determination have been made by a long term field investigation, examination of preserved herbarium specimens and survey of relevant floristic literature following the IUCN’s threatened criteria of assessing Red List Plants under the Flora Bangladesh Project. Biodiversity of Bangladesh, as evaluated, has been affected to a large extent during the last four and half decades due to spontaneous environmental degradation caused by frequent occurrence of cyclonic storms and tidal bores since 1970 and flooding, draught, unilateral diversion of trans-boundary waters by operating Farakka Barrage since 1975, indiscriminate destruction and over exploitation of natural resources, unplanned development and industrialization, overpopulation etc. Depletion of world’s largest mangrove biodiversity in Sundarbans, coastal and island biodiversity in southern part, agro-biodiversity and agro-fisheries all over the country, Haor and wetland biodiversity of plain lands, terrestrial and forest biodiversity in central and eastern hilly part of Bangladesh, as assessed, have greatly been occurred at a higher rate due to environmental degradation which in turn affect directly or indirectly the economy, food security and environmental health of the country. Complete inventory of 30 plant families resulted in the recognition of 45.18% species of Bangladesh as threatened environmentally and 13.23% species as possibly extinct from the flora since these have neither been reported or could be traced in the field for more than 100 years. The rate of extinction is determined to be 2.65% per 20 years. Hence the study indicates that the loss of biodiversity and environmental degradation in Bangladesh occurring at an alarming rate. The study focuses on the issues of environment, the extent of loss of different plant biodiversities in Bangladesh, prioritizing and implementing national conservation strategies for sustainable management of the environment.

Keywords: Bangladesh, biodiversity, conservation, environmental management

Procedia PDF Downloads 251
396 Empowering 21st Century Students with Self-Employability Skill Competencies in an Era of Uncertainties of Paid Employment Jobs

Authors: Pac Ordu

Abstract:

The paper was conceived on the premise that employment of tertiary education graduates has become an endemic problem in Nigeria. Recognizing the objective of current education as schooling for paid employment, the paper identified that the basic objective of present-day education should be schooling to become self-employed. While schooling to become a successful employee was identified as the focus for the older generation, schooling to become self-employed was defined as the focus for 21st-century teaching and learning. Hence, the paper condemned the inability of curriculum implementers to teach creative trends to enable students to acquire practical skills and small business operation-oriented competencies. A review of some disciplines was made to show the new trend of education that would empower Nigerian students with small business enterprise operation skills for self-employment on graduation. This was further made to draw the attention of institutions and curriculum designers to the need for our curriculum to be functional in line with demands of the innovative economic environment. The paper also noted that at periods of recession with its attendant effects, was the best period for students of entrepreneurship to dream and create their small business enterprises. It highlighted the role of Federal College of Education (Technical) Omoku, Rivers State, Nigeria and the national recognition it has received for developing an innovative, practical model of teaching entrepreneurship education in Nigeria Colleges of Education system. In order to equip students for economic survival on graduation, the introduction of innovative teaching can only be successful if lecturers shift their focus away from the conventional emphasis on theory to students’ energy quotients. While the paper obviously recommended that lecturers should be creative and teach outside the curriculum box, it further recommended that students should use this period of their studentship to dream, create and operate their own small business enterprises.

Keywords: 21st century students, curriculum, entrepreneurship, hands-on-training, innovative

Procedia PDF Downloads 116
395 An Approach to Autonomous Drones Using Deep Reinforcement Learning and Object Detection

Authors: K. R. Roopesh Bharatwaj, Avinash Maharana, Favour Tobi Aborisade, Roger Young

Abstract:

Presently, there are few cases of complete automation of drones and its allied intelligence capabilities. In essence, the potential of the drone has not yet been fully utilized. This paper presents feasible methods to build an intelligent drone with smart capabilities such as self-driving, and obstacle avoidance. It does this through advanced Reinforcement Learning Techniques and performs object detection using latest advanced algorithms, which are capable of processing light weight models with fast training in real time instances. For the scope of this paper, after researching on the various algorithms and comparing them, we finally implemented the Deep-Q-Networks (DQN) algorithm in the AirSim Simulator. In future works, we plan to implement further advanced self-driving and object detection algorithms, we also plan to implement voice-based speech recognition for the entire drone operation which would provide an option of speech communication between users (People) and the drone in the time of unavoidable circumstances. Thus, making drones an interactive intelligent Robotic Voice Enabled Service Assistant. This proposed drone has a wide scope of usability and is applicable in scenarios such as Disaster management, Air Transport of essentials, Agriculture, Manufacturing, Monitoring people movements in public area, and Defense. Also discussed, is the entire drone communication based on the satellite broadband Internet technology for faster computation and seamless communication service for uninterrupted network during disasters and remote location operations. This paper will explain the feasible algorithms required to go about achieving this goal and is more of a reference paper for future researchers going down this path.

Keywords: convolution neural network, natural language processing, obstacle avoidance, satellite broadband technology, self-driving

Procedia PDF Downloads 251
394 Implementing Quality Function Deployment Tool for a Customer Driven New Product Development in a Kuwait SME

Authors: Asma AlQahtani, Jumana AlHadad, Maryam AlQallaf, Shoug AlHasan

Abstract:

New product development (NPD) is the complete process of bringing a new product to the customer by integrating the two broad divisions; one involving the idea generation, product design and detail engineering; and the other involving market research and marketing analysis. It is a common practice for companies to undertake some of these tasks simultaneously (concurrent engineering) and also consider them as an ongoing process (continuous development). The current study explores the framework and methodology for a new product development process utilizing the Quality Function Deployment (QFD) tool for bringing the customer opinion into the product development process. An elaborate customer survey with focus groups in the region was carried out to ensure that customer requirements are integrated into new products as early as the design stage including identifying the recognition of need for the new product. A QFD Matrix (House of Quality) was prepared that links customer requirements to product engineering requirements and a feasibility study and risk assessment exercise was carried out for a Small and Medium Enterprise (SME) in Kuwait for development of the new product. SMEs in Kuwait, particularly in manufacturing sector are mainly focused on serving the local demand, and often lack of product quality adversely affects the ability of the companies to compete on a regional/global basis. Further, lack of focus on identifying customer requirements often deters SMEs to envisage the idea of a New Product Development. The current study therefore focuses in utilizing QFD Matrix right from the conceptual design to detail design and to some extent, extending the link this to design of the manufacturing system. The outcome of the project resulted in a development of the prototype for a new molded product which can ensure consistency between the customer’s requirements and the measurable characteristics of the product. The Engineering Economics and Cost studies were also undertaken to analyse the viability of the new product, the results of which was also linked to the successful implementation of the initial QFD Matrix.

Keywords: Quality Function Deployment, QFD Matrix, new product development, NPD, Kuwait SMEs, prototype development

Procedia PDF Downloads 414
393 Use of Zikani’s Ribosome Modulating Agents for Treating Recessive Dystrophic & Junctional Epidermolysis Bullosa with Nonsense Mutations

Authors: Mei Chen, Yingping Hou, Michelle Hao, Soheil Aghamohammadzadeh, Esteban Terzo, Roger Clark, Vijay Modur

Abstract:

Background: Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a genetic skin condition characterized by skin tearing and unremitting blistering upon minimal trauma. Repeated blistering, fibrosis, and scarring lead to aggressive squamous cell carcinoma later in life. RDEB is caused by mutations in the COL7A1 gene encoding collagen type VII (C7), the major component of anchoring fibrils mediating epidermis-dermis adherence. Nonsense mutations in the COL7A1 gene of a subset of RDEB patients leads to premature termination codons (PTC). Similarly, most Junctional Epidermolysis Bullosa (JEB) cases are caused by nonsense mutations in the LAMB3 gene encoding the β3 subunit of laminin 332. Currently, there is an unmet need for the treatment of RDEB and JEB. Zikani Therapeutics has discovered an array of macrocyclic compounds with ring structures similar to macrolide antibiotics that can facilitate readthrough activity of nonsense mutations in the COL7A1 and LAMB3 genes by acting as Ribosome Modulating Agents (RMAs). The medicinal chemistry synthetic advancements of these macrocyclic compounds have allowed targeting the human ribosome while preserving the structural elements responsible for the safety and pharmacokinetic profile of clinically used macrolide antibiotics. Methods: C7 expression was used as a measure of readthrough activity by immunoblot assays in two primary human fibroblasts from RDEB patients (R578X/R578X and R163X/R1683X-COL7A1). Similarly, immunoblot assays in C325X/c.629-12T > A-LAMB3 keratinocytes were used to measure readthrough activity for JEB. The relative readthrough activity of each compound was measured relative to Gentamicin. An imaging-based fibroblast migration assay was used as an assessment of C7 functionality in RDEB-fibroblasts over 16-20 hrs. The incubation period for the above experiments was 48 hrs for RDEB fibroblasts and 72 hours for JEB keratinocytes. Results: 9 RMAs demonstrated increased protein expression in both patient RDEB fibroblasts. The highest readthrough activity at tested concentrations without cytotoxicities increased protein expression up to 179% of Gentamicin (400 µg/ml), with favored readthrough activity in R163X/R1683X-COL7A1 fibroblasts. Concurrent with protein expression, fibroblast hypermotility phenotype observed in RDEB was rescued by reducing motility by ~35% to WT levels (the same level as 690 µM Gentamicin treated cells). Laminin β3 expression was also shown to be increased by 6 RMAs in keratinocytes to 33-83% of (400 µg/ml) Gentamicin. Conclusions: To date, 9 RMAs have been identified that enhance the expression of functional C7 in a mutation-dependent manner in two different RDEB patient fibroblast backgrounds (R578X/R578X and R163X/R1683X-COL7A1). A further 6 RMAs have been identified that enhance the readthrough of C325X-LAMB3 in JEB patient keratinocytes. Based on the clinical trial conducted by us with topical gentamycin in 2017, Zikani’s RMAs achieve clinically significant levels of read-through for the treatment of recessive dystrophic and Junctional Epidermolysis Bullosa.

Keywords: epidermolysis bullosa, nonsense mutation, readthrough, ribosome modulation

Procedia PDF Downloads 98
392 The Use of Coronary Calcium Scanning for Cholesterol Assessment and Management

Authors: Eva Kirzner

Abstract:

Based on outcome studies published over the past two decades, in 2018, the ACC/AHA published new guidelines for the management of hypercholesterolemia that incorporate the use of coronary artery calcium (CAC) scanning as a decision tool for ascertaining which patients may benefit from statin therapy. This use is based on the recognition that the absence of calcium on CAC scanning (i.e., a CAC score of zero) usually signifies the absence of significant atherosclerotic deposits in the coronary arteries. Specifically, in patients with a high risk for atherosclerotic cardiovascular disease (ASCVD), initiation of statin therapy is generally recommended to decrease ASCVD risk. However, among patients with intermediate ASCVD risk, the need for statin therapy is less certain. However, there is a need for new outcome studies that provide evidence that the management of hypercholesterolemia based on these new ACC/AHA recommendations is safe for patients. Based on a Pub-Med and Google Scholar literature search, four relevant population-based or patient-based cohort studies that studied the relationship between CAC scanning, risk assessment or mortality, and statin therapy that were published between 2017 and 2021 were identified (see references). In each of these studies, patients were assessed for their baseline risk for atherosclerotic cardiovascular disease (ASCVD) using the Pooled Cohorts Equation (PCE), an ACC/AHA calculator for determining patient risk based on assessment of patient age, gender, ethnicity, and coronary artery disease risk factors. The combined findings of these four studies provided concordant evidence that a zero CAC score defines patients who remain at low clinical risk despite the non-use of statin therapy. Thus, these new studies confirm the use of CAC scanning as a safe tool for reducing the potential overuse of statin therapy among patients with zero CAC scores. Incorporating these new data suggest the following best practice: (1) ascertain ASCVD risk according to the PCE in all patients; (2) following an initial attempt trial to lower ASCVD risk with optimal diet among patients with elevated ASCVD risk, initiate statin therapy for patients who have a high ASCVD risk score; (3) if the ASCVD score is intermediate, refer patients for CAC scanning; and (4) and if the CAC score is zero among the intermediate risk ASCVD patients, statin therapy can be safely withheld despite the presence of an elevated serum cholesterol level.

Keywords: cholesterol, cardiovascular disease, statin therapy, coronary calcium

Procedia PDF Downloads 115
391 Neuroprotective Effect of Chrysin on Thioacetamide-Induced Hepatic Encephalopathy in Rats: Role of Oxidative Stress and TLR-4/NF-κB Pathway

Authors: S. A. El-Marasy, S. A. El Awdan, R. M. Abd-Elsalam

Abstract:

This study aimed to investigate the possible neuroprotective effect of chrysin on thioacetamide (TAA)-induced hepatic encephalopathy in rats. Also, the effect of chrysin on motor impairment, cognitive deficits, oxidative stress, neuroinflammation, apoptosis and histopathological damage was assessed. Male Wistar rats were randomly allocated into five groups. The first group received the vehicle (distilled water) for 21 days and is considered as normal group. While the second one received intraperitoneal dose of TAA (200 mg/kg) at three alternative days during the third week of the experiment to induce HE and is considered as control group. The other three groups were orally administered chrysin for 21 days (25, 50, 100 mg/kg) and starting from day 17; rats received intraperitoneal dose of TAA (200 mg/kg) at three alternative days. Then behavioral, biochemical, histopathological and immunohistochemical analyses were assessed. Then behavioral, biochemical, histopathological and immunohistochemical analyses were assessed. Chrysin reversed TAA-induced motor coordination in rotarod test, cognitive deficits in object recognition test (ORT) and attenuated serum ammonia, hepatic liver enzymes, reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), reduced nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6) brain contents. Chrysin administration also reduced Toll-4 receptor (TLR-4) gene expression, caspase-3 protein expression, hepatic necrosis and astrocyte swelling. This study depicts that chrysin exerted neuroprotective effect in TAA-induced HE rats, evidenced by improvement of cognitive deficits, motor incoordination and histopathological changes such as astrocyte swelling and vacuolization; hallmarks in HE, via reducing hyperammonemia, ameliorating hepatic function, in addition to its anti-oxidant, inactivation of TLR-4/NF-κB inflammatory pathway, and anti-apoptotic effects.

Keywords: chrysin, hepatic encephalopathy, oxidative stress, rats, thioacetamide, TLR4/NF-κB pathway

Procedia PDF Downloads 161
390 Cannabis Sativa L as Natural Source of Promising Anti-Alzheimer Drug Candidates: A Comprehensive Computational Approach Including Molecular Docking, Molecular Dynamics, ADMET and MM-PBSA Studies

Authors: Hassan Nour, Nouh Mounadi, Oussama Abchir, Belaidi Salah, Samir Chtita

Abstract:

Cholinesterase enzymes are biological catalysts essential for the transformation of acetylcholine, which is a neurotransmitter implicated in memory and learning, into acetic acid and choline, altering the neurotransmission process in Alzheimer’s disease patients. Therefore, inhibition of cholinesterase enzymes is a relevant strategy for the symptomatic treatment of Alzheimer’s disease. The current investigation aims to explore potential cholinesterase (ChE) inhibitors through a comprehensive computational approach. Forty-nine phytoconstituents extracted from Cannabis sativa L. were in-silico screened using molecular docking and pharmacokinetic and toxicological analysis to evaluate their possible inhibitory effect on the cholinesterase enzymes. Two phytoconstituents belonging to cannabinoid derivatives were revealed to be promising candidates for Alzheimer's therapy by acting as cholinesterase inhibitors. They have exhibited high binding affinities towards the cholinesterase enzymes and showed their ability to interact with key residues involved in cholinesterase enzymatic activity. In addition, they presented good ADMET profiles allowing them to be promising oral drug candidates. Furthermore, molecular dynamics (MD) simulations were executed to explore their interaction stability under mimetic biological conditions and thus support our findings. To corroborate the docking results, the binding free energy corresponding to the more stable ligand-ChE complexes was re-estimated by applying the MM-PBSA method. MD and MM-PBSA studies affirmed that the ligand-ChE recognition is a spontaneous reaction leading to stable complexes. The conducted investigations have led to great findings that would strongly guide the pharmaceutical industries toward the rational development of potent anti-Alzheimer agents.

Keywords: Alzheimer’s disease, molecular docking, Cannabis sativa L., cholinesterase inhibitors, molecular dynamics, ADMET, MM-PBSA

Procedia PDF Downloads 83
389 The Intersection of Disability, Race and Gender in Keah Brown's 'The Pretty One'

Authors: Mehena Fedoul

Abstract:

This paper examines the intersection of race, gender, and disability through a Critical disability race theory and black feminist disability perspective in Keah Brown's memoir, "The Pretty One." The background of the study highlights the significance of intersectionality in understanding the multifaceted experiences of individuals who navigate multiple marginalized identities. The study contributes to the underrepresented field of disability studies from a Critical race and black feminist perspectives, shedding light on the unique challenges and resilience of black disabled women. The study employs a qualitative analysis of Keah Brown's memoir as a primary text. Drawing on intersectionality theory and black feminist disability scholarship, the analysis focuses on how Brown's memoir illuminates the ways in which her race, gender, and disability intersect and shape her lived experiences. The analysis reveals how Brown's memoir challenges traditional notions of disability, beauty, and empowerment through her unapologetic celebration of her blackness, femaleness, and disability. The major findings of the study indicate that Brown's memoir provides a powerful narrative of the complexity, uniqueness and richness of the lived experiences of black disabled women. It demonstrates how the intersectionality of race, gender, and disability shapes Brown's identity, body image, relationships, and societal interactions. The paper also highlights how Brown's memoir emphasizes the importance of inclusivity and intersectionality in understanding and addressing the challenges faced by black disabled women. In conclusion, this study offers a critical analysis of the intersection of race, gender, and disability in Keah Brown's memoir, "The Pretty One," from a black feminist disability perspective. It contributes to the growing body of literature that recognizes the significance of intersectionality in understanding the experiences of marginalized individuals in the disability community. The study underscores the need for more inclusive and intersectional perspectives in disability studies and advocates for greater recognition of the voices and experiences of black disabled women in academic and societal discourse.

Keywords: Intersectionality, black feminism, disability studies, keah brown

Procedia PDF Downloads 82