Search results for: human and viral genes
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 9311

Search results for: human and viral genes

6371 A Hybrid Traffic Model for Smoothing Traffic Near Merges

Authors: Shiri Elisheva Decktor, Sharon Hornstein

Abstract:

Highway merges and unmarked junctions are key components in any urban road network, which can act as bottlenecks and create traffic disruption. Inefficient highway merges may trigger traffic instabilities such as stop-and-go waves, pose safety conditions and lead to longer journey times. These phenomena occur spontaneously if the average vehicle density exceeds a certain critical value. This study focuses on modeling the traffic using a microscopic traffic flow model. A hybrid traffic model, which combines human-driven and controlled vehicles is assumed. The controlled vehicles obey different driving policies when approaching the merge, or in the vicinity of other vehicles. We developed a co-simulation model in SUMO (Simulation of Urban Mobility), in which the human-driven cars are modeled using the IDM model, and the controlled cars are modeled using a dedicated controller. The scenario chosen for this study is a closed track with one merge and one exit, which could be later implemented using a scaled infrastructure on our lab setup. This will enable us to benchmark the results of this study obtained in simulation, to comparable results in similar conditions in the lab. The metrics chosen for the comparison of the performance of our algorithm on the overall traffic conditions include the average speed, wait time near the merge, and throughput after the merge, measured under different travel demand conditions (low, medium, and heavy traffic).

Keywords: highway merges, traffic modeling, SUMO, driving policy

Procedia PDF Downloads 106
6370 Enzyme Producing Psyhrophilic Pseudomonas app. Isolated from Poultry Meats

Authors: Ali Aydin, Mert Sudagidan, Aysen Coban, Alparslan Kadir Devrim

Abstract:

Pseudomonas spp. (specifically, P. fluorescens and P. fragi) are considered the principal spoilage microorganisms of refrigerated poultry meats. The higher the level psychrophilic spoilage Pseudomonas spp. on carcasses at the end of processing lead to decrease the shelf life of the refrigerated product. The aim of the study was the identification of psychrophilic Pseudomonas spp. having proteolytic and lipolytic activities from poultry meats by 16S rRNA and rpoB gene sequencing, investigation of protease and lipase related genes and determination of proteolytic activity of Pseudomonas spp. In the of isolation procedure, collected chicken meat samples from local markets and slaughterhouses were homogenized and the lysates were incubated on Standard method agar and Skim Milk agar for selection of proteolytic bacteria and tributyrin agar for selection of lipolytic bacteria at +4 °C for 7 days. After detection of proteolytic and lipolytic colonies, the isolates were firstly analyzed by biochemical tests such as Gram staining, catalase and oxidase tests. DNA gene sequencing analysis and comparison with GenBank revealed that 126 strong enzyme Pseudomonas spp. were identified as predominantly P. fluorescens (n=55), P. fragi (n=42), Pseudomonas spp. (n=24), P. cedrina (n=2), P. poae (n=1), P. koreensis (n=1), and P. gessardi (n=1). Additionally, protease related aprX gene was screened in the strains and it was detected in 69/126 strains, whereas, lipase related lipA gene was found in 9 Pseudomonas strains. Protease activity was determined using commercially available protease assay kit and 5 strains showed high protease activity. The results showed that psychrophilic Pseudomonas strains were present in chicken meat samples and they can produce important levels of proteases and lipases for food spoilage to decrease food quality and safety.

Keywords: Pseudomonas, chicken meat, protease, lipase

Procedia PDF Downloads 387
6369 A Contemporary Gender Predominance: A Honduran Textile Manufacturing Diagnose

Authors: Jesús David Argueta Moreno, Taria Ruiz, Cesar Ortega

Abstract:

This qualitative investigation represents the first stage of the human capital engineering analysis, along the small and medium textile manufacturing companies, located on the city of Tegucigalpa, Honduras where the symptoms of the local manufacturing industry´s describe a severe gender displacement phenomenon. The evaluation of this phenomena, intends to trigger the Honduran small and medium technology manufactures into a collective performance, analysis through the development of a sectorial diagnose and the creation of a manufacturers guide, personalized. In accordance to the Honduran textile manufacturing needs, in order to strengthen their personnel capacities and thereby smoothen the gender equilibrium on this particular sector. It is worth mentioning, that on the last decade, the female gender has gathered positive statistics upon Central American job market´s, were the local business landscape describes a significant displacement of the Honduran female operators over the male gender workers that has significantly diminished their employment predominance. On the other hand, this study aims to evaluate the main features that impact on the job market local gender supplanting. On the other hand, this document aims to holistically describe the Honduran manufacturing context, as well as the current textile operator qualifications, in order to infer over the most proper human resources enforcement approaches/techniques on the industry.

Keywords: gender predominance, manufacturing, higher education institutions, emerging trends

Procedia PDF Downloads 430
6368 Analysis and Design of Exo-Skeleton System Based on Multibody Dynamics

Authors: Jatin Gupta, Bishakh Bhattacharya

Abstract:

With the aging process, many people start suffering from the problem of weak limbs resulting in mobility disorders and loss of sensory and motor function of limbs. Wearable robotic devices are viable solutions to help people suffering from these issues by augmenting their strength. These robotic devices, popularly known as exoskeletons aides user by providing external power and controlling the dynamics so as to achieve desired motion. Present work studies a simplified dynamic model of the human gait. A four link open chain kinematic model is developed to describe the dynamics of Single Support Phase (SSP) of the human gait cycle. The dynamic model is developed integrating mathematical models of the motion of inverted and triple pendulums. Stance leg is modeled as inverted pendulum having single degree of freedom and swing leg as triple pendulum having three degrees of freedom viz. thigh, knee, and ankle joints. The kinematic model is formulated using forward kinematics approach. Lagrangian approach is used to formulate governing dynamic equation of the model. For a system of nonlinear differential equations, numerical method is employed to obtain system response. Reference trajectory is generated using human body simulator, LifeMOD. For optimal mechanical design and controller design of exoskeleton system, it is imperative to study parameter sensitivity of the system. Six different parameters viz. thigh, shank, and foot masses and lengths are varied from 85% to 115% of the original value for the present work. It is observed that hip joint of swing leg is the most sensitive and ankle joint of swing leg is the least sensitive one. Changing link lengths causes more deviation in system response than link masses. Also, shank length and thigh mass are most sensitive parameters. Finally, the present study gives an insight on different factors that should be considered while designing a lower extremity exoskeleton.

Keywords: lower limb exoskeleton, multibody dynamics, energy based formulation, optimal design

Procedia PDF Downloads 200
6367 Antibacterial Evaluation, in Silico ADME and QSAR Studies of Some Benzimidazole Derivatives

Authors: Strahinja Kovačević, Lidija Jevrić, Miloš Kuzmanović, Sanja Podunavac-Kuzmanović

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In this paper, various derivatives of benzimidazole have been evaluated against Gram-negative bacteria Escherichia coli. For all investigated compounds the minimum inhibitory concentration (MIC) was determined. Quantitative structure-activity relationships (QSAR) attempts to find consistent relationships between the variations in the values of molecular properties and the biological activity for a series of compounds so that these rules can be used to evaluate new chemical entities. The correlation between MIC and some absorption, distribution, metabolism and excretion (ADME) parameters was investigated, and the mathematical models for predicting the antibacterial activity of this class of compounds were developed. The quality of the multiple linear regression (MLR) models was validated by the leave-one-out (LOO) technique, as well as by the calculation of the statistical parameters for the developed models and the results are discussed on the basis of the statistical data. The results of this study indicate that ADME parameters have a significant effect on the antibacterial activity of this class of compounds. Principal component analysis (PCA) and agglomerative hierarchical clustering algorithms (HCA) confirmed that the investigated molecules can be classified into groups on the basis of the ADME parameters: Madin-Darby Canine Kidney cell permeability (MDCK), Plasma protein binding (PPB%), human intestinal absorption (HIA%) and human colon carcinoma cell permeability (Caco-2).

Keywords: benzimidazoles, QSAR, ADME, in silico

Procedia PDF Downloads 375
6366 Biophysical Assessment of the Ecological Condition of Wetlands in the Parkland and Grassland Natural Regions of Alberta, Canada

Authors: Marie-Claude Roy, David Locky, Ermias Azeria, Jim Schieck

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It is estimated that up to 70% of the wetlands in the Parkland and Grassland natural regions of Alberta have been lost due to various land-use activities. These losses include ecosystem function and services they once provided. Those wetlands remaining are often embedded in a matrix of human-modified habitats and despite efforts taken to protect them the effects of land-uses on wetland condition and function remain largely unknown. We used biophysical field data and remotely-sensed human footprint data collected at 322 open-water wetlands by the Alberta Biodiversity Monitoring Institute (ABMI) to evaluate the impact of surrounding land use on the physico-chemistry characteristics and plant functional traits of wetlands. Eight physio-chemistry parameters were assessed: wetland water depth, water temperature, pH, salinity, dissolved oxygen, total phosphorus, total nitrogen, and dissolved organic carbon. Three plant functional traits were evaluated: 1) origin (native and non-native), 2) life history (annual, biennial, and perennial), and 3) habitat requirements (obligate-wetland and obligate-upland). Intensity land-use was quantified within a 250-meter buffer around each wetland. Ninety-nine percent of wetlands in the Grassland and Parkland regions of Alberta have land-use activities in their surroundings, with most being agriculture-related. Total phosphorus in wetlands increased with the cover of surrounding agriculture, while salinity, total nitrogen, and dissolved organic carbon were positively associated with the degree of soft-linear (e.g. pipelines, trails) land-uses. The abundance of non-native and annual/biennial plants increased with the amount of agriculture, while urban-industrial land-use lowered abundance of natives, perennials, and obligate wetland plants. Our study suggests that land-use types surrounding wetlands affect the physicochemical and biological conditions of wetlands. This research suggests that reducing human disturbances through reclamation of wetland buffers may enhance the condition and function of wetlands in agricultural landscapes.

Keywords: wetlands, biophysical assessment, land use, grassland and parkland natural regions

Procedia PDF Downloads 333
6365 Development of Lectin-Based Biosensor for Glycoprofiling of Clinical Samples: Focus on Prostate Cancer

Authors: Dominika Pihikova, Stefan Belicky, Tomas Bertok, Roman Sokol, Petra Kubanikova, Jan Tkac

Abstract:

Since aberrant glycosylation is frequently accompanied by both physiological and pathological processes in a human body (cancer, AIDS, inflammatory diseases, etc.), the analysis of tumor-associated glycan patterns have a great potential for the development of novel diagnostic approaches. Moreover, altered glycoforms may assist as a suitable tool for the specificity and sensitivity enhancement in early-stage prostate cancer diagnosis. In this paper we discuss the construction and optimization of ultrasensitive sandwich biosensor platform employing lectin as glycan-binding protein. We focus on the immunoassay development, reduction of non-specific interactions and final glycoprofiling of human serum samples including both prostate cancer (PCa) patients and healthy controls. The fabricated biosensor was measured by label-free electrochemical impedance spectroscopy (EIS) with further lectin microarray verification. Furthermore, we analyzed different biosensor interfaces with atomic force microscopy (AFM) in nanomechanical mapping mode showing a significant differences in the altitude. These preliminary results revealing an elevated content of α-2,3 linked sialic acid in PCa patients comparing with healthy controls. All these experiments are important step towards development of point-of-care devices and discovery of novel glyco-biomarkers applicable in cancer diagnosis.

Keywords: biosensor, glycan, lectin, prostate cancer

Procedia PDF Downloads 372
6364 Employee Happiness: The Influence of Providing Consumers with an Experience versus an Object

Authors: Wilson Bastos, Sigal G. Barsade

Abstract:

Much of what happens in the marketplace revolves around the provision and consumption of goods. Recent research has advanced a useful categorization of these goods—as experiential versus material—and shown that, from the consumers’ perspective, experiences (e.g., a theater performance) are superior to objects (e.g., an electronic gadget) in offering various social and psychological benefits. A common finding in this growing research stream is that consumers gain more happiness from the experiences they have than the objects they own. By focusing solely on those acquiring the experiential or material goods (the consumers), prior research has remained silent regarding another important group of individuals—those providing the goods (the employees). Do employees whose jobs are primarily focused on offering consumers an experience (vs. object) also gain more happiness from their occupation? We report evidence from four experiments supporting an experiential-employee advantage. Further, we use mediation and moderation tests to unearth the mechanism responsible for this effect. Results reveal that work meaningfulness is the primary driver of the experiential-employee advantage. Overall, our findings suggest that employees find it more meaningful to provide people with an experience as compared to a material object, which in turn shapes the happiness they derive from their jobs. We expect this finding to have implications on human development, and to be of relevance to researchers and practitioners interested in how to advance human condition in the workplace.

Keywords: employee happiness, experiential versus material jobs, work meaningfulness

Procedia PDF Downloads 271
6363 Genetic Polymorphism of Milk Protein Gene and Association with Milk Production Traits in Local Latvian Brown Breed Cows

Authors: Daina Jonkus, Solvita Petrovska, Dace Smiltina, Lasma Cielava

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The beta-lactoglobulin and kappa-casein are milk proteins which are important for milk composition. Cows with beta-lactoglobulin and kappa-casein gene BB genotypes have highest milk crude protein and fat content. The aim of the study was to determinate the frequencies of milk protein gene polymorphisms in local Latvian Brown (LB) cows breed and analyze the influence of beta-lactoglobulin and kappa-casein genotypes to milk productivity traits. 102 cows’ genotypes of milk protein genes were detected using Polymerase Chain Reaction and Restriction Fragment Length Polymorphism (PCR-RFLP) and electrophoresis on 3% agarose gel. For beta-lactoglobulin were observed 2 types of alleles A and B and for kappa-casein 3 types: A, B and E. Highest frequency in beta-lactoglobulin gene was observed for B allele – 0.926. Molecular analysis of beta-lactoglobulin gene shows 86.3% of individuals are homozygous by B allele and animals are with genotypes BB and 12.7% of individuals are heterozygous with genotypes AB. The highest milk yield 4711.7 kg was for 1st lactation cows with AB genotypes, whereas the highest milk protein content (3.35%) and fat content (4.46 %) was for BB genotypes. Analysis of the kappa-casein locus showed a prevalence of the A allele – 0.750. The genetic variant of B was characterized by a low frequency – 0.240. Moreover, the frequency of E occurred in the LB cows’ population with very low frequency – 0.010. 54.9 % of cows are homozygous with genotypes AA, and only 4.9 % are homozygous with genotypes BB. 32.8 % of individuals are heterozygous with genotypes AB, and 2.0 % are with AE. The highest milk productivity was for 1st lactation cows with AB genotypes: milk yield 4620.3 kg, milk protein content 3.39% and fat content 4.53 %. According to the results, in local Latvian brown there are only 2.9% of cows are with BB-BB genotypes, which is related to milk coagulation ability and affected cheese production yield. Acknowledgment: the investigation is supported by VPP 2014-2017 AgroBioRes Project No. 3 LIVESTOCK.

Keywords: beta-lactoglobulin, cows, genotype frequencies, kappa-casein

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6362 Walls against Legal Identity: A Qualitative Study on Children of Refugees without Birth Registration in Malaysia

Authors: Rodziana M. Razali, Tamara J. Duraisingham

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Malaysia is not a signatory to the 1951 Refugee Convention and its 1967 Protocol despite receiving the largest share of refugee inflows in Southeast Asia aside from Thailand. In Peninsular Malaysia, the majority of refugees and asylum seekers are from Myanmar, with Rohingya refugees recording the highest number compared to all other ethnicities. In the eastern state of Sabah, the presence of refugees who have long established themselves in the state is connected to those who escaped military persecution in southern Philippines in the 1970’s and 1980’s. A combination of legal and non-legal factors has created and sustained an adverse atmosphere of deprivation of legal identity for children of migrants including refugees born in Malaysia. This paper aims to qualitatively analyse the barriers to birth registration as the cornerstone of every person’s legal identity for children of refugees born in this country, together with the associated human rights implications. Data obtained through semi-structured interviews with refugees in Kota Kinabalu, Sabah and Rohingya refugees in Peninsular Malaysia shall be studied alongside secondary sources. Results show that births out of medical facilities, suspension of birth records, illiteracy, lack of awareness on the importance and procedures of birth registration, inability to meet documentary requirements, as well as fear of immigration enforcement, are the key factors hindering birth registration. These challenges exist against the backdrop of restrictive integration policy to avoid destabilising demographic and racial balance, political sentiment stirring xenophobic prejudices, as well as other economic and national security considerations. With no proof of their legal identity, the affected children grow up in a legal limbo, facing multiple human rights violations across generations. This research concludes that the country’s framework and practice concerning birth registration is in need of serious reform and improvement to reflect equality and universality of access to its birth registration system. Such would contribute significantly towards meeting its commitments to the post-2015 sustainable development agenda that pledges to 'Leave no one behind', as well as its recently announced National Human Rights Action Plan.

Keywords: birth registration, children, Malaysia, refugees

Procedia PDF Downloads 171
6361 SUMOylation Enhances Nurr1/1a Mediated Transactivation in a Neuronal Cell Type

Authors: Jade Edey, Andrew Bennett, Gareth Hathway

Abstract:

Nuclear receptor-related 1 protein (also known as Nurr1 or NR4A2) is an orphan nuclear receptor which plays a vital role in the development, survival and maintenance of dopaminergic (DA) neurons particularly in the substantia nigra (SN). Increasing research has investigated Nurr1’s additional role within microglia and astrocytes where it has been suggested to act as a negative regulator of inflammation; potentially offering neuroprotection. Considering both DA neurodegeneration and neuroinflammation are commonly accepted constituents of Parkinson’s Disease (PD), understanding the mechanisms by which Nurr1 regulates inflammatory processes could provide an attractive therapeutic target. Nurr1 regulates inflammation via a transrepressive mechanism possibly dependent upon SUMOylation. In addition, Nurr1 can transactivate numerous genes involved in DA synthesis, such as Tyrosine Hydroxylase (TH). A C-terminal splice variant of Nurr1, Nurr-1a, has been reported in both neuronal and glial cells. However, research into its transcriptional activity is minimal. We employed in vitro methods such as SUMO-Pulldown experiments alongside Luciferase reporter assays to investigate the SUMOylation status and transactivation capabilities of Nurr1 and Nurr-1a respectively. The SUMO-Pulldown assay demonstrated Nurr-1a undergoes significantly more SUMO modification than its full-length variant. Consequently, despite having less transcriptional activation than Nurr1, Nurr1a may play a more prominent role in repression of microglial inflammation. Contrary to published literature we also identified that SUMOylation enhances transcriptional activation by Nurr1 and Nurr1a. SUMOylation-dependent increases in Nurr1 and Nurr1a transcriptional activation were only evident in neuronal SHSY5Y cells but not in HEK293 cells. This research provides novel insight into the regulation of Nurr-1a and indicates differential effects of SUMOylation dependent regulation in neuronal and inflammatory cells.

Keywords: nuclear receptors, Parkinson’s disease, inflammation, transcriptional regulation

Procedia PDF Downloads 154
6360 The Role of People in Continuing Airworthiness: A Case Study Based on the Royal Thai Air Force

Authors: B. Ratchaneepun, N.S. Bardell

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It is recognized that people are the main drivers in almost all the processes that affect airworthiness assurance. This is especially true in the area of aircraft maintenance, which is an essential part of continuing airworthiness. This work investigates what impact English language proficiency, the intersection of the military and Thai cultures, and the lack of initial and continuing human factors training have on the work performance of maintenance personnel in the Royal Thai Air Force (RTAF). A quantitative research method based on a cross-sectional survey was used to gather data about these three key aspects of “people” in a military airworthiness environment. 30 questions were developed addressing the crucial topics of English language proficiency, impact of culture, and human factors training. The officers and the non-commissioned officers (NCOs) who work for the Aeronautical Engineering Divisions in the RTAF comprised the survey participants. The survey data were analysed to support various hypotheses by using a t-test method. English competency in the RTAF is very important since all of the service manuals for Thai military aircraft are written in English. Without such competency, it is difficult for maintenance staff to perform tasks and correctly interpret the relevant maintenance manual instructions; any misunderstandings could lead to potential accidents. The survey results showed that the officers appreciated the importance of this more than the NCOs, who are the people actually doing the hands-on maintenance work. Military culture focuses on the success of a given mission, and leverages the power distance between the lower and higher ranks. In Thai society, a power distance also exists between younger and older citizens. In the RTAF, such a combination tends to inhibit a just reporting culture and hence hinders safety. The survey results confirmed this, showing that the older people and higher ranks involved with RTAF aircraft maintenance believe that the workplace has a positive safety culture and climate, whereas the younger people and lower ranks think the opposite. The final area of consideration concerned human factors training and non-technical skills training. The survey revealed that those participants who had previously attended such courses appreciated its value and were aware of its benefits in daily life. However, currently there is no regulation in the RTAF to mandate recurrent training to maintain such knowledge and skills. The findings from this work suggest that the people involved in assuring the continuing airworthiness of the RTAF would benefit from: (i) more rigorous requirements and standards in the recruitment, initial training and continuation training regarding English competence; (ii) the development of a strong safety culture that exploits the uniqueness of both the military culture and the Thai culture; and (iii) providing more initial and recurrent training in human factors and non-technical skills.

Keywords: aircraft maintenance, continuing airworthiness, military culture, people, Royal Thai Air Force

Procedia PDF Downloads 130
6359 Material Response Characterisation of a PolyJet 3D Printed Human Infant Skull

Authors: G. A. Khalid, R. Prabhu, W. Whittington, M. D. Jones

Abstract:

To establish a causal relationship of infant head injury consequences, this present study addresses the necessary challenges of cranial geometry and the physical response complexities of the paediatric head tissues. Herein, we describe a new approach to characterising and understanding infant head impact mechanics by developing printed head models, using high resolution clinical postmortem imaging, to provide the most complete anatomical representation currently available, and biological material response data-matched polypropylene polymers, to replicate the relative mechanical response properties of immature cranial bone, sutures and fontanelles. Additive manufacturing technology was applied to creating a physical polymeric model of a newborn infant skull, using PolyJet printed materials. Infant skull materials responses, were matched by a response characterisation study, utilising uniaxial tensile testing (1 mm min-1 loading rate), to determine: the stiffness, ultimate tensile strength and maximum strain of rigid and rubber additively manufactured acrylates. The results from the mechanical experiments confirm that the polymeric materials RGD835 Vero White Plus (White), representing the frontal and parietal bones; RGD8510- DM Rigid Light Grey25 (Grey), representing the occipital bone; and FLX9870-DM (Black) representing the suture and fontanelles, were found to show a close stiffness -correlation (E) at ambient temperatures. A 3D physical model of infant head was subsequently printed from the matched materials and subsequently validated against results obtained from a series of Post Mortem Human Surrogate (PMHS) tests. A close correlation was demonstrated between the model impact tests and the PMHS. This study, therefore, represents a key step towards applying printed physical models to understanding head injury biomechanics and is useful in the efforts to predict and mitigate head injury consequences in infants, whether accidental or by abuse.

Keywords: infant head trauma, infant skull, material response, post mortem human subjects, polyJet printing

Procedia PDF Downloads 140
6358 Automation of AAA Game Development using AI and Procedural Generation

Authors: Paul Toprac, Branden Heng, Harsheni Siddharthan, Allison Tseng, Sarah Abraham, Etienne Vouga

Abstract:

The goal of this project was to evaluate and document the capabilities and limitations of AI tools for empowering small teams to create high budget, high profile (AAA) 3D games typically developed by large studios. Two teams of novice game developers attempted to create two different games using AI and Unreal Engine 5.3. First, the teams evaluated 60 AI art, design, sound, and programming tools by considering their capability, ease of use, cost, and license restrictions. Then, the teams used a shortlist of 13 AI tools for game development. During this process, the following tools were found to be the most productive: (1) ChatGPT 4.0 for both game and narrative concepting and documentation; (2) Dall-E 3 and OpenArt for concept art; (3) Beatoven for music drafting; (4) Epic PCG for level design; and (5) ChatGPT 4.0 and Github Copilot for generating simple code and to complement human-made tutorials as an additional learning resource. While current generative AI may appear impressive at first glance, the assets they produce fall short of AAA industry standards. Generative AI tools are helpful when brainstorming ideas such as concept art and basic storylines, but they still cannot replace human input or creativity at this time. Regarding programming, AI can only effectively generate simple code and act as an additional learning resource. Thus, generative AI tools are at best tools to enhance developer productivity rather than as a system to replace developers.

Keywords: AAA games, AI, automation tools, game development

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6357 Evaluation of ROS Mediated Apoptosis Induced by Tuber Extract of Dioscorea Bulbifera on Human Breast Adenocarcinoma

Authors: Debasmita Dubey, Rajesh Kumar Meher, Smruti Pragya Samal, Pradeep Kumar Naik

Abstract:

Background: To determine antioxidant properties and anticancer activity by ROS and mitochondrial transmembrane potential mediated apoptosis against MCF7, MDA-MB-231, cell line. Methods: Leaf sample was extracted using methanol by microwave digestion technique. The antioxidant properties of the methanolic extract were determined by a DPPH scavenging assay. In vitro anticancer activity, mitochondrial transmembrane potential, apoptosis activity and DNA fragmentation study, as well as intracellular ROS activity of most potential leaf extract, were also determined by using the MDA-MB-231cell line. In vivo animal toxicity study was carried out using mice model. Results: Methanolic leaf extract has shown the highest antioxidant, as well as anticancer activity, is based on the assay conducted. For the identification of active phytochemicals from methanolic extract, High-resolution mass spectroscopy-LCMS was used. In vitro cytotoxicity study against MCF-7 and MDA-MB-231 cell line and IC 50 value was found to be 37.5µg/ml. From histopathological studies, no toxicity in liver and kidney tissue was identified. Conclusion: This plant tuber can be used as a regular diet to reduce the chance of breast cancer. Further, more studies should be conducted to isolate and identify the responsible compound.

Keywords: human breast adenocarcinoma, ROS, mitochondrial transmembrane, apoptosis

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6356 Communicating Through Symbolisms in Anthropoligical Medicine with Reference to Traditional Performances of Wayang Kulit, Main Puteri and Kuda Kepang

Authors: M. G. Nasuruddin, S. Ishak

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In anthropological medicine (traditional therapeutic healing) symbolic interface are used to connect with the cognitive and metacognitive mechanisms to activate conscious and unconscious response of patients or other recipients. At the same time they are used to communicate with the inhabitants of the nether world to whom are ascribed almost all cases of psychosomatic illness. The symbols, which are cultural specific, are divided into verbal and non-verbal forms of communication. The verbal forms are chanting of mantra and doa and the invocation to invoke the spirits while the non-verbal ones are the physical materials such as the offerings, props and decorative elements, music, movements, olfactory sensation and the performance space. The process of communication through these symbols is affected by the Shaman who is a link or intermediary between the healer (Shaman) and the patients and between the healer and the spirits of the nether world. The paper also examines the scientific perspective of the traditional healing through the use of these symbols. The response to these symbols as external stimuli is embedded in the genes that are linked to the hereditary factor in the person’s DNA. When the patients are tuned in to external stimuli such as music, chanting and singing (sonic orders), it can triggers a response from the brain, which may activate its inner pharmacy by releasing drugs such as dopamine and/or opiodsto ameliorate pain and counter depression, anxiety and create a feel good feeling. These symbols act like placebo, evoking the power of the mind over the body and triggering the innate self-healing energy. At the same time they could also be used as nocebo, for example black magic, which has the opposite effect of placebo. In whatever capacity they operate these symbols, which are either visual or auditory, is an integral part of anthropological medicine. For they communicate and conjure emotional responses that are conducive to healing by activating the internal brain pharmacy.

Keywords: communication, healing, placebo, nacebo, symbol

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6355 Epidemiological, Clinical and Bacteriological Profile of Human Brucellosis in the District of Tunis

Authors: Jihene Bettaieb, Ghassen kharroubi, Rym mallekh, Ines Cherif, Taoufik Atawa, Kaouther Harrabech

Abstract:

Brucellosis is a major worldwide zoonosis. It is a reportable condition in Tunisia where the disease remains endemic, especially in rural areas. The aim of this study was to describe the epidemiological, clinical, and bacteriological profile of human brucellosis cases notified in the district of Tunis. It was a retrospective descriptive study of cases reported in the district of Tunis through the national surveillance system between the 1st January and 31th December 2017. During the study period, 133 brucellosis confirmed cases were notified. The mean age was 37.5 ± 18.0 years, and 54.9% of cases were males. More than four-fifths (82.7%) of cases were reported in spring and summer with a peak in the month of May (36 cases). Fever and sweats were the most common symptoms; they occurred in 95% and 72% of cases, respectively. Osteoarticular complications occurred in 10 cases, meningitis in one case and endocarditis in one other case. Wright agglutination test and Rose Bengale test were positive in 100% and 91% of cases, respectively. While blood culture was positive in 9 cases and PCR in 2 cases. Brucella melitensis was the only identified specie (9 cases). Almost all cases (99.2%) reported the habit of consuming raw dairy products. Only 5 cases had a suspect contact with animals; among them, 3 persons were livestock breeders. The transmission was essentially due to raw dairy product consumption. It is important to enhance preventive measures to control animal Brucellosis and to educate the population regarding the risk factors of the disease.

Keywords: brucellosis, risk factors, surveillance system, Tunisia

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6354 TNFRSF11B Gene Polymorphisms A163G and G11811C in Prediction of Osteoporosis Risk

Authors: I. Boroňová, J.Bernasovská, J. Kľoc, Z. Tomková, E. Petrejčíková, D. Gabriková, S. Mačeková

Abstract:

Osteoporosis is a complex health disease characterized by low bone mineral density, which is determined by an interaction of genetics with metabolic and environmental factors. Current research in genetics of osteoporosis is focused on identification of responsible genes and polymorphisms. TNFRSF11B gene plays a key role in bone remodeling. The aim of this study was to investigate the genotype and allele distribution of A163G (rs3102735) osteoprotegerin gene promoter and G1181C (rs2073618) osteoprotegerin first exon polymorphisms in the group of 180 unrelated postmenopausal women with diagnosed osteoporosis and 180 normal controls. Genomic DNA was isolated from peripheral blood leukocytes using standard methodology. Genotyping for presence of different polymorphisms was performed using the Custom Taqman®SNP Genotyping assays. Hardy-Weinberg equilibrium was tested for each SNP in the groups of participants using the chi-square (χ2) test. The distribution of investigated genotypes in the group of patients with osteoporosis were as follows: AA (66.7%), AG (32.2%), GG (1.1%) for A163G polymorphism; GG (19.4%), CG (44.4%), CC (36.1%) for G1181C polymorphism. The distribution of genotypes in normal controls were follows: AA (71.1%), AG (26.1%), GG (2.8%) for A163G polymorphism; GG (22.2%), CG (48.9%), CC (28.9%) for G1181C polymorphism. In A163G polymorphism the variant G allele was more common among patients with osteoporosis: 17.2% versus 15.8% in normal controls. Also, in G1181C polymorphism the phenomenon of more frequent occurrence of C allele in the group of patients with osteoporosis was observed (58.3% versus 53.3%). Genotype and allele distributions showed no significant differences (A163G: χ2=0.270, p=0.605; χ2=0.250, p=0.616; G1181C: χ2= 1.730, p=0.188; χ2=1.820, p=0.177). Our results represents an initial study, further studies of more numerous file and associations studies will be carried out. Knowing the distribution of genotypes is important for assessing the impact of these polymorphisms on various parameters associated with osteoporosis. Screening for identification of “at-risk” women likely to develop osteoporosis and initiating subsequent early intervention appears to be most effective strategy to substantially reduce the risks of osteoporosis.

Keywords: osteoporosis, real-time PCR method, SNP polymorphisms

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6353 Artificial Intelligence Approach to Water Treatment Processes: Case Study of Daspoort Treatment Plant, South Africa

Authors: Olumuyiwa Ojo, Masengo Ilunga

Abstract:

Artificial neural network (ANN) has broken the bounds of the convention programming, which is actually a function of garbage in garbage out by its ability to mimic the human brain. Its ability to adopt, adapt, adjust, evaluate, learn and recognize the relationship, behavior, and pattern of a series of data set administered to it, is tailored after the human reasoning and learning mechanism. Thus, the study aimed at modeling wastewater treatment process in order to accurately diagnose water control problems for effective treatment. For this study, a stage ANN model development and evaluation methodology were employed. The source data analysis stage involved a statistical analysis of the data used in modeling in the model development stage, candidate ANN architecture development and then evaluated using a historical data set. The model was developed using historical data obtained from Daspoort Wastewater Treatment plant South Africa. The resultant designed dimensions and model for wastewater treatment plant provided good results. Parameters considered were temperature, pH value, colour, turbidity, amount of solids and acidity. Others are total hardness, Ca hardness, Mg hardness, and chloride. This enables the ANN to handle and represent more complex problems that conventional programming is incapable of performing.

Keywords: ANN, artificial neural network, wastewater treatment, model, development

Procedia PDF Downloads 149
6352 Contextual Toxicity Detection with Data Augmentation

Authors: Julia Ive, Lucia Specia

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Understanding and detecting toxicity is an important problem to support safer human interactions online. Our work focuses on the important problem of contextual toxicity detection, where automated classifiers are tasked with determining whether a short textual segment (usually a sentence) is toxic within its conversational context. We use “toxicity” as an umbrella term to denote a number of variants commonly named in the literature, including hate, abuse, offence, among others. Detecting toxicity in context is a non-trivial problem and has been addressed by very few previous studies. These previous studies have analysed the influence of conversational context in human perception of toxicity in controlled experiments and concluded that humans rarely change their judgements in the presence of context. They have also evaluated contextual detection models based on state-of-the-art Deep Learning and Natural Language Processing (NLP) techniques. Counterintuitively, they reached the general conclusion that computational models tend to suffer performance degradation in the presence of context. We challenge these empirical observations by devising better contextual predictive models that also rely on NLP data augmentation techniques to create larger and better data. In our study, we start by further analysing the human perception of toxicity in conversational data (i.e., tweets), in the absence versus presence of context, in this case, previous tweets in the same conversational thread. We observed that the conclusions of previous work on human perception are mainly due to data issues: The contextual data available does not provide sufficient evidence that context is indeed important (even for humans). The data problem is common in current toxicity datasets: cases labelled as toxic are either obviously toxic (i.e., overt toxicity with swear, racist, etc. words), and thus context does is not needed for a decision, or are ambiguous, vague or unclear even in the presence of context; in addition, the data contains labeling inconsistencies. To address this problem, we propose to automatically generate contextual samples where toxicity is not obvious (i.e., covert cases) without context or where different contexts can lead to different toxicity judgements for the same tweet. We generate toxic and non-toxic utterances conditioned on the context or on target tweets using a range of techniques for controlled text generation(e.g., Generative Adversarial Networks and steering techniques). On the contextual detection models, we posit that their poor performance is due to limitations on both of the data they are trained on (same problems stated above) and the architectures they use, which are not able to leverage context in effective ways. To improve on that, we propose text classification architectures that take the hierarchy of conversational utterances into account. In experiments benchmarking ours against previous models on existing and automatically generated data, we show that both data and architectural choices are very important. Our model achieves substantial performance improvements as compared to the baselines that are non-contextual or contextual but agnostic of the conversation structure.

Keywords: contextual toxicity detection, data augmentation, hierarchical text classification models, natural language processing

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6351 Interaction of Phytochemicals Present in Green Tea, Honey and Cinnamon to Human Melanocortin 4 Receptor

Authors: Chinmayee Choudhury

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Human Melanocortin 4 Receptor (HMC4R) is one of the most potential drug targets for the treatment of obesity which controls the appetite. A deletion of the residues 88-92 in HMC4R is sometimes the cause of severe obesity in the humans. In this study, two homology models are constructed for the normal as well as mutated HMC4Rs and some phytochemicals present in Green Tea, Honey and Cinnamon have been docked to them to study their differential binding to the normal and mutated HMC4R as compared to the natural agonist α- MSH. Two homology models have been constructed for the normal as well as mutated HMC4Rs using the Modeller9v7. Some of the phytochemicals present in Green Tea, Honey, and Cinnamon, which have appetite suppressant activities are constructed, minimized and docked to these normal and mutated HMC4R models using ArgusLab 4.0.1. The mode of binding of the phytochemicals with the Normal and Mutated HMC4Rs have been compared. Further, the mode of binding of these phytochemicals with that of the natural agonist α- Melanocyte Stimulating Hormone(α-MSH) to both normal and mutated HMC4Rs have also been studied. It is observed that the phytochemicals Kaempherol, Epigallocatechin-3-gallate (EGCG) present in Green Tea and Honey, Isorhamnetin, Chlorogenic acid, Chrysin, Galangin, Pinocambrin present in Honey, Cinnamaldehyde, Cinnamyl acetate and Cinnamyl alcohol present in Cinnamon have capacity to form more stable complexes with the Mutated HMC4R as compared to α- MSH. So they may be potential agonists of HMC4R to suppress the appetite.

Keywords: HMC4R, α-MSH, docking, photochemical, appetite suppressant, homology modelling

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6350 Reconstruction of Performace-Based Budgeting in Indonesian Local Government: Application of Soft Systems Methodology in Producing Guideline for Policy Implementation

Authors: Deddi Nordiawan

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Effective public policy creation required a strong budget system, both in terms of design and implementation. Performance-based Budget is an evolutionary approach with two substantial characteristics; first, the strong integration between budgeting and planning, and second, its existence as guidance so that all activities and expenditures refer to measurable performance targets. There are four processes in the government that should be followed in order to make the budget become performance-based. These four processes consist of the preparation of a vision according to the bold aspiration, the formulation of outcome, the determination of output based on the analysis of organizational resources, and the formulation of Value Creation Map that contains a series of programs and activities. This is consistent with the concept of logic model which revealed that the budget performance should be placed within a relational framework of resources, activities, outputs, outcomes and impacts. Through the issuance of Law 17/2003 regarding State Finance, local governments in Indonesia have to implement performance-based budget. Central Government then issued Government Regulation 58/2005 which contains the detail guidelines how to prepare local governments budget. After a decade, implementation of performance budgeting in local government is still not fully meet expectations, though the guidance is completed, socialization routinely performed, and trainings have also been carried out at all levels. Accordingly, this study views the practice of performance-based budget at local governments as a problematic situation. This condition must be approached with a system approach that allows the solutions from many point of views. Based on the fact that the infrastructure of budgeting has already settled, the study then considering the situation as complexity. Therefore, the intervention needs to be done in the area of human activity system. Using Soft Systems Methodology, this research will reconstruct the process of performance-based budget at local governments is area of human activity system. Through conceptual models, this study will invite all actors (central government, local government, and the parliament) for dialogue and formulate interventions in human activity systems that systematically desirable and culturally feasible. The result will direct central government in revise the guidance to local government budgeting process as well as a reference to build the capacity building strategy.

Keywords: soft systems methodology, performance-based budgeting, Indonesia, public policy

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6349 A Study on Coronary Artery Dominance and Divisions of Main Trunk of Left Coronary Artery in Adult Human Cadaveric Hearts of South Indian Population

Authors: Chethan Purushothama

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Coronary artery disease is one of the major causes of death in developing countries. The coronary arteries show wide range of variations and these variations have not been dealt with different population groups. The present study aims to focus on the pattern and variations of coronary artery in south Indian population. The study was performed to analyze the coronary artery dominance and divisions of main trunk of left coronary artery in 81 isolated adult human cadaveric hearts of South Indian population. The specimens were fixed in 10% formalin and were dissected manually. In our specimens, 74.1% of the hearts were right dominant, 11.1% were left dominant, and 14.8% were co-dominant. Bifurcation, trifurcation, and quadrifurcation of main trunk of left coronary artery were seen in 49.4%, 48.1%, and 2.5% cases respectively. The right dominant hearts had bifurcation, trifurcation and quadrifurcation of main trunk of left coronary artery in 46.7%, 50% and 3.3% hearts respectively. The left dominant hearts had bifurcation and trifurcation of main trunk of left coronary artery in 55.6% and 44.4% cases respectively. The co-dominant hearts had bifurcation and trifurcation of main trunk of left coronary artery in 58.3% and 41.7% respectively. Quadrifurcation of main trunk of left coronary artery were seen only in right dominant hearts. We believe that the data obtained from the present study are important to the interventional cardiologists and radiologists. The details obtained will also be helpful for the clinical anatomists.

Keywords: bifurcation, coronary artery, trifurcation, quadrifurcation

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6348 From Edible Products to Disinfecting Currency Notes

Authors: Aniruddha Hore, Saptarshi Mitra, Sandip Ghosh, Sujoy Bose, Avijit Ghosh

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The Indian rupee is the official currency of India. With time, science and technology got advanced, and our society is slowly making its way to a cashless mode of transaction. But as India is still a developing country, a large part of our society still depends on transaction through cash. During times of pandemics, we came to understand that everything that we touch is not safe from microbial contamination. The Indian currency is also not an exception. The Indian currency is the modern-day medium of harmful bacterial as well as other microbial contaminations resulting in diseases in human bodies. Therefore, the need came to make the currency disinfectant to give our people a healthier lifestyle. The main focus of the study is to develop a solution that, when applied to the currency notes, will kill the persisting bacteria or microbes present in the notes. So various natural edible products were used in order to prepare the solution, which is highly effective against the presence of harmful bacteria such as E. coli and S. aureus. The antibacterial activity of these natural ingredients is not unknown to us, so extracts from those products were mixed together to form a solution which was made the Indian currency notes antibacterial for 20min approx. The solution was creating a layer on the surface of currency notes, therefore, making it antibacterial for a given duration of time, i.e., no bacterial growth was seen during the time period of 20 minutes, therefore, making it safe for the usage of human hands.

Keywords: Indian currency, antibacterial property of Indian currency, surface coating, currency disinfectant

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6347 Exercise and Aging Process Related to Oxidative Stress

Authors: B. Dejanova, S. Petrovska, L. Todorovska, J. Pluncevic, S. Mancevska, V. Antevska, E. Sivevska, I. Karagjozova

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Introduction: Aging process is mainly related to endothelial function which may be impaired by oxidative stress (OS). Exercise is known to be beneficial to aging process, which may improve health and prevent appearance of chronic diseases in elderly. The aim of the study was to investigate the OS markers related to exercise. Methods: A number of 80 subjects (healthy volunteers) were examined (38 male and 32 female), divided in 3 age groups: group I ≤ 30 years (n=24); group II – 31-50 years (n=24); group III - ≥ 51 year (n=32). Each group was divided to subgroups of sedentary subjects (SS) and subjects who exercise (SE). Group I: SS (n=11), SE (n=13); group II: SS (n=13), SE (n=10); group III: SS (n=23) SE (n=9). Lipid peroxidation (LP) as a fluorimetric method with thiobarbituric acid was used to estimate OS. Antioxidative status was determined by cell antioxidants such as enzymes - superoxide dismutase (SOD), glutathione peroxidase (GPx) and glucose 6 phosphate (G-6-PD); and by extra cell antioxidants such as glutathione reductase (GR), nitric oxide (NO) and total antioxidant capacity (TAC). Results: Increased values of LP were noticed along the aging process: group I – 3.30±0.3 µmol/L; group II – 3.91±0.2 µmol/L; group III – 3.94±0.8 µmol/L (p<0.05), while no statistical significance was found between male and female subjects. Statistical significance for OS was not found between SS and SE in group I as it was found in group II (p<0.05) and in group III (p<0.01). No statistical significance was found for all cell antioxidants and GR within the groups, while NO and TAC showed lower values in SS compared to SE in II (p<0.05) and in group III (p<0.05). Discussion and conclusion: Aging process showed increased OS which may be either due to impaired function of scavengers of free radicals or due to their enormous production. Well balanced exercise might be one of the factors that keep the integrity of blood vessel endothelium which slows down the aging process. Possible mechanism of exercise beneficial influence is shear stress by upregulation of genes coding for nitric oxide bioavailability. Thus, due to obtained results we may conclude that OS is found to be diminished in the subject groups who perform exercise.

Keywords: oxidative stress, aging process, exercise, endothelial function

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6346 Effect of Far Infrared and Endothelial Cell Growth Supplement on Human Umbilical Vascular Endothelial Cells

Authors: Ming-Tzu Tsai, Jui-Ting Hsu, Chia-Chieh Lin, Feng-Tsai Chiang, Cheng-Chin Huang

Abstract:

Far infrared (FIR), an invisible and short electromagnetic waves ranges from 6-14 μm also defines as the “growth ray.” Although the mechanism of FIR is still unknown, most data have suggested that FIR could accelerate the skin microcirculation by elevating the blood flow and nitric-oxide (NO) synthesis. In this present work, the effect of FIR irradiation and endothelial cell growth supplement (ECGS) on human umbilical vascular endothelial cells (HUVECs) was evaluated. To understand whether the cell viability and NO production of HUVECs affected by NO, cells with/without ECGS were treated in the presence or absence of L-NAME, an eNOS inhibitor. For FIR exposure, FIR-emitted ceramic powders consisted of a variety of well-mixed metal oxides were developed. The results showed that L-NAME did had a strong effect on the inhibition of NO production, especially in the ECGS-treated group. However, the cell viability of each group was rarely affected in the presence of L-NAME. Cells with the incubation of ECGS showed much higher cell viability compared to the control. Moreover, NO production of HUVECs exposed to FIR irradiation was significantly inhibited in the presence of L-NAME. It suggested that NO could play a role modulating the downstream signals of HUVECs during FIR exposure.

Keywords: far-infrared irradiation (FIR), nitric oxide (NO), endothelial nitric oxide synthase (eNOS), endothelial cell growth supplement (ECGS)

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6345 Identifying Knowledge Gaps in Incorporating Toxicity of Particulate Matter Constituents for Developing Regulatory Limits on Particulate Matter

Authors: Ananya Das, Arun Kumar, Gazala Habib, Vivekanandan Perumal

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Regulatory bodies has proposed limits on Particulate Matter (PM) concentration in air; however, it does not explicitly indicate the incorporation of effects of toxicities of constituents of PM in developing regulatory limits. This study aimed to provide a structured approach to incorporate toxic effects of components in developing regulatory limits on PM. A four-step human health risk assessment framework consists of - (1) hazard identification (parameters: PM and its constituents and their associated toxic effects on health), (2) exposure assessment (parameters: concentrations of PM and constituents, information on size and shape of PM; fate and transport of PM and constituents in respiratory system), (3) dose-response assessment (parameters: reference dose or target toxicity dose of PM and its constituents), and (4) risk estimation (metric: hazard quotient and/or lifetime incremental risk of cancer as applicable). Then parameters required at every step were obtained from literature. Using this information, an attempt has been made to determine limits on PM using component-specific information. An example calculation was conducted for exposures of PM2.5 and its metal constituents from Indian ambient environment to determine limit on PM values. Identified data gaps were: (1) concentrations of PM and its constituents and their relationship with sampling regions, (2) relationship of toxicity of PM with its components.

Keywords: air, component-specific toxicity, human health risks, particulate matter

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6344 Re-identification Risk and Mitigation in Federated Learning: Human Activity Recognition Use Case

Authors: Besma Khalfoun

Abstract:

In many current Human Activity Recognition (HAR) applications, users' data is frequently shared and centrally stored by third parties, posing a significant privacy risk. This practice makes these entities attractive targets for extracting sensitive information about users, including their identity, health status, and location, thereby directly violating users' privacy. To tackle the issue of centralized data storage, a relatively recent paradigm known as federated learning has emerged. In this approach, users' raw data remains on their smartphones, where they train the HAR model locally. However, users still share updates of their local models originating from raw data. These updates are vulnerable to several attacks designed to extract sensitive information, such as determining whether a data sample is used in the training process, recovering the training data with inversion attacks, or inferring a specific attribute or property from the training data. In this paper, we first introduce PUR-Attack, a parameter-based user re-identification attack developed for HAR applications within a federated learning setting. It involves associating anonymous model updates (i.e., local models' weights or parameters) with the originating user's identity using background knowledge. PUR-Attack relies on a simple yet effective machine learning classifier and produces promising results. Specifically, we have found that by considering the weights of a given layer in a HAR model, we can uniquely re-identify users with an attack success rate of almost 100%. This result holds when considering a small attack training set and various data splitting strategies in the HAR model training. Thus, it is crucial to investigate protection methods to mitigate this privacy threat. Along this path, we propose SAFER, a privacy-preserving mechanism based on adaptive local differential privacy. Before sharing the model updates with the FL server, SAFER adds the optimal noise based on the re-identification risk assessment. Our approach can achieve a promising tradeoff between privacy, in terms of reducing re-identification risk, and utility, in terms of maintaining acceptable accuracy for the HAR model.

Keywords: federated learning, privacy risk assessment, re-identification risk, privacy preserving mechanisms, local differential privacy, human activity recognition

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6343 Development of selective human matrix metalloproteinases-9 (hMMP-9) inhibitors as potent diabetic wound healing agents

Authors: Geetakshi Arora, Danish Malhotra

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Diabetic wounds are serious health issues and often fail to heal, leading to limb amputation that makes the life of the patient miserable. Delayed wound healing has been characterized by an increase in matrix metalloproteinase-9 (MMP-9). Thus research throughout the world has been going on to develop selective MMP-9 inhibitors for aiding diabetic wound healing. Bioactive constituents from natural sources always served as potential leads in drug development with high rates of success. Considering the need for novel selective MMP-9 inhibitors and the importance of natural bioactive compounds in drug development, we have screened a library of bioactive constituents from plant sources that were effective in diabetic wound healing on human MMP-9 (hMMP-9) using molecular docking studies. Screened constituents are ranked according to their dock score, ∆G value (binding affinity), and Ligand efficiency evaluated from FleXX docking and Hyde scoring modules available with drug designing platform LeadIT. Rhamnocitrin showed the highest correlation between dock score, ∆G value (binding affinity), and Ligand efficiency was further explored for binding interactions with hMMP-9. The overall study suggest that Rhamnocitrin is sufficiently decorated with both hydrophilic and hydrophobic substitutions that perfectly block hMMP-9 and act as a potential lead in the design and development of selective hMMP-9 inhibitors.

Keywords: MMP-9, diabetic wound, molecular docking, phytoconstituents

Procedia PDF Downloads 126
6342 Implementation of Cord- Blood Derived Stem Cells in the Regeneration of Two Experimental Models: Carbon Tetrachloride and S. Mansoni Induced Liver Fibrosis

Authors: Manal M. Kame, Zeinab A. Demerdash, Hanan G. El-Baz, Salwa M. Hassan, Faten M. Salah, Wafaa Mansour, Olfat Hammam

Abstract:

Cord blood (CB) derived Unrestricted Somatic Stem Cells (USSCs) with their multipotentiality hold great promise in liver regeneration. This work aims at evaluation of the therapeutic potentiality of USSCs in two experimental models of chronic liver injury induced either by S. mansoni infection in balb/c mice or CCL4 injection in hamsters. Isolation, propagation, and characterization of USSCs from CB samples were performed. USSCs were induced to differentiate into osteoblasts, adipocytes and hepatocyte-like cells. Cells of the third passage were transplanted in two models of liver fibrosis: (1) Twenty hamsters were induced to liver fibrosis by repeated i. p. injection of 100 μl CCl4 /hamster for 8 weeks. This model was designed as; 10 hamsters with liver fibrosis and treated with i.h. injection of 3x106 USSCs (USSCs transplanted group), 10 hamsters with liver fibrosis (pathological control group), and 10 hamsters with healthy livers (normal control group). (2) Murine chronics S.mansoni model: twenty mice were induced to liver fibrosis with S. mansoni ceracariae (60 cercariae/ mouse) using the tail immersion method and left for 12 weeks. This model was designed as; 10 mice with liver fibrosis were transplanted with i. v. injection of 1×106 USCCs (USSCs transplanted group). Other 2 groups were designed as in hamsters model. Animals were sacrificed 12 weeks after USSCs transplantation, and their liver sections were examined for detection of human hepatocyte-like cells by immunohistochemistry staining. Moreover, liver sections were examined for fibrosis level, and fibrotic indices were calculated. Sera of sacrificed animals were tested for liver functions. CB USSCs, with fibroblast-like morphology, expressed high levels of CD44, CD90, CD73 and CD105 and were negative for CD34, CD45, and HLA-DR. USSCs showed high expression of transcripts for Oct4 and Sox2 and were in vitro differentiated into osteoblasts, adipocytes. In both animal models, in vitro induced hepatocyte-like cells were confirmed by cytoplasmic expression of glycogen, alpha-fetoprotein, and cytokeratin18. Livers of USSCs transplanted group showed engraftment with human hepatocyte-like cells as proved by cytoplasmic expression of human alpha-fetoprotein, cytokeratin18, and OV6. In addition, livers of this group showed less fibrosis than the pathological control group. Liver functions in the form of serum AST & ALT level and serum total bilirubin level were significantly lowered in USSCs transplanted group than pathological control group (p < 0.001). Moreover, the fibrotic index was significantly lower (p< 0.001) in USSCs transplanted group than pathological control group. In addition liver sections, of i. v. injection of 1×106 USCCs of mice, stained with either H&E or sirius red showed diminished granuloma size and a relative decrease in hepatic fibrosis. Our experimental liver fibrosis models transplanted with CB-USSCs showed liver engraftment with human hepatocyte-like cells as well as signs of liver regeneration in the form of improvement in liver function assays and fibrosis level. These data provide hope that human CB- derived USSCs are introduced as multipotent stem cells with great potentiality in regenerative medicine & strengthens the concept of cellular therapy for the treatment of liver fibrosis.

Keywords: cord blood, liver fibrosis, stem cells, transplantation

Procedia PDF Downloads 309