Search results for: artificial animal intelligence

Authors: Babak Forouraghi

Abstract:

A genetic circuit is a collection of interacting genes and proteins that enable individual cells to implement and perform vital biological functions such as cell division, growth, death, and signaling. In cell engineering, synthetic gene circuits are engineered networks of genes specifically designed to implement functionalities that are not evolved by nature. These engineered networks enable scientists to tackle complex problems such as engineering cells to produce therapeutics within the patient's body, altering T cells to target cancer-related antigens for treatment, improving antibody production using engineered cells, tissue engineering, and production of genetically modified plants and livestock. Construction of computational models to realize genetic circuits is an especially challenging task since it requires the discovery of flow of genetic information in complex biological systems. Building synthetic biological models is also a time-consuming process with relatively low prediction accuracy for highly complex genetic circuits. The primary goal of this study was to investigate the utility of a pre-trained bidirectional encoder transformer that can accurately predict gene expressions in genetic circuit designs. The main reason behind using transformers is their innate ability (attention mechanism) to take account of the semantic context present in long DNA chains that are heavily dependent on spatial representation of their constituent genes. Previous approaches to gene circuit design, such as CNN and RNN architectures, are unable to capture semantic dependencies in long contexts as required in most real-world applications of synthetic biology. For instance, RNN models (LSTM, GRU), although able to learn long-term dependencies, greatly suffer from vanishing gradient and low-efficiency problem when they sequentially process past states and compresses contextual information into a bottleneck with long input sequences. In other words, these architectures are not equipped with the necessary attention mechanisms to follow a long chain of genes with thousands of tokens. To address the above-mentioned limitations of previous approaches, a transformer model was built in this work as a variation to the existing DNA Bidirectional Encoder Representations from Transformers (DNABERT) model. It is shown that the proposed transformer is capable of capturing contextual information from long input sequences with attention mechanism. In a previous work on genetic circuit design, the traditional approaches to classification and regression, such as Random Forrest, Support Vector Machine, and Artificial Neural Networks, were able to achieve reasonably high R2 accuracy levels of 0.95 to 0.97. However, the transformer model utilized in this work with its attention-based mechanism, was able to achieve a perfect accuracy level of 100%. Further, it is demonstrated that the efficiency of the transformer-based gene expression classifier is not dependent on presence of large amounts of training examples, which may be difficult to compile in many real-world gene circuit designs.

Keywords: transformers, generative ai, gene expression design, classification

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Authors: Mohamad F. Jamiluddin, Emeline Sarry, Ana Bejanariu, Cécile Bauche

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Introduction: Over 360 million people are chronically infected with hepatitis B virus (HBV), of whom 1 million die each year from HBV-associated liver cirrhosis or hepatocellular carcinoma. Current treatment options for chronic hepatitis B depend on interferon-α (IFNα) or nucleos(t)ide analogs, which control virus replication but rarely eliminate the virus. Treatment with PEG-IFNα leads to a sustained antiviral response in only one third of patients. After withdrawal of the drugs, the rebound of viremia is observed in the majority of patients. Furthermore, the long-term treatment is subsequently associated with the appearance of drug resistant HBV strains that is often the cause of the therapy failure. Among the new therapeutic avenues being developed, therapeutic vaccine aimed at inducing immune responses similar to those found in resolvers is of growing interest. The high prevalence of chronic hepatitis B necessitates the design of better vaccination strategies capable of eliciting broad-spectrum of cell-mediated immunity(CMI) and humoral immune response that can control chronic hepatitis B. Induction of HBV-specific T cells and B cells by therapeutic vaccination may be an innovative strategy to overcome virus persistence. Lentiviral vectors developed and optimized by THERAVECTYS, due to their ability to transduce non-dividing cells, including dendritic cells, and induce CMI response, have demonstrated their effectiveness as vaccination tools. Method: To develop a HBV therapeutic vaccine that can induce a broad but specific immune response, we generated recombinant lentiviral vector carrying IRES(Internal Ribosome Entry Site)-containing bicistronic constructs which allow the coexpression of two vaccine products, namely HBV T- cell epitope vaccine and HBV virus like particle (VLP) vaccine. HBV T-cell epitope vaccine consists of immunodominant cluster of CD4 and CD8 epitopes with spacer in between them and epitopes are derived from HBV surface protein, HBV core, HBV X and polymerase. While HBV VLP vaccine is a HBV core protein based chimeric VLP with surface protein B-cell epitopes displayed. In order to evaluate the immunogenicity, mice were immunized with lentiviral constructs by intramuscular injection. The T cell and antibody immune responses of the two vaccine products were analyzed using IFN-γ ELISpot assay and ELISA respectively to quantify the adaptive response to HBV antigens. Results: Following a single administration in mice, lentiviral construct elicited robust antigen-specific IFN-γ responses to the encoded antigens. The HBV T- cell epitope vaccine demonstrated significantly higher T cell immunogenicity than HBV VLP vaccine. Importantly, we demonstrated by ELISA that antibodies are induced against both HBV surface protein and HBV core protein when mice injected with vaccine construct (p < 0.05). Conclusion: Our results highlight that THERAVECTYS lentiviral vectors may represent a powerful platform for immunization strategy against chronic hepatitis B. Our data suggests the likely importance of Lentiviral vector based novel bicistronic construct for further study, in combination with drugs or as standalone antigens, as a therapeutic lentiviral based HBV vaccines. THERAVECTYS bicistronic HBV vaccine will be further evaluated in animal efficacy studies.

Keywords: chronic hepatitis B, lentiviral vectors, therapeutic vaccine, virus-like particle

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Authors: Claudia Trillo

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Regional innovation eco-ecosystems are composed of a variety of interconnected urban innovation eco-systems, mutually reinforcing each other and making the whole territorial system successful. Combining principles drawn from the new economic growth theory and from the socio-constructivist approach to the economic growth, with the new geography of innovation emerging from the networked nature of innovation districts, this paper explores the spatial configuration of urban innovation districts, with the aim of unveiling replicable spatial patterns and transferable portfolios of urban policies. While some authors suggest that cities should be considered ideal natural clusters, supporting cross-fertilization and innovation thanks to the physical setting they provide to the construction of collective knowledge, still a considerable distance persists between regional development strategies and urban policies. Moreover, while public and private policies supporting entrepreneurship normally consider innovation as the cornerstone of any action aimed at uplifting the competitiveness and economic success of a certain area, a growing body of literature suggests that innovation is non-neutral, hence, it should be constantly assessed against equity and social inclusion. This paper draws from a robust qualitative empirical dataset gathered through 4-years research conducted in Boston to provide readers with an evidence-based set of recommendations drawn from the lessons learned through the investigation of the chosen innovation districts in the Boston area. The evaluative framework used for assessing the overall performance of the chosen case studies stems from the Habitat III Sustainable Development Goals rationale. The concept of inclusive growth has been considered essential to assess the social innovation domain in each of the chosen cases. The key success factors for the development of the Boston innovation ecosystem can be generalized as follows: 1) a quadruple helix model embedded in the physical structure of the two cities (Boston and Cambridge), in which anchor Higher Education (HE) institutions continuously nurture the Entrepreneurial Environment. 2) an entrepreneurial approach emerging from the local governments, eliciting risk-taking and bottom-up civic participation in tackling key issues in the city. 3) a networking structure of some intermediary actors supporting entrepreneurial collaboration, cross-fertilization and co-creation, which collaborate at multiple-scales thus enabling positive spillovers from the stronger to the weaker contexts. 4) awareness of the socio-economic value of the built environment as enabler of cognitive networks allowing activation of the collective intelligence. 5) creation of civic-led spaces enabling grassroot collaboration and cooperation. Evidence shows that there is not a single magic recipe for the successful implementation of place-based and social innovation-driven strategies. On the contrary, the variety of place-grounded combinations of micro and macro initiatives, embedded in the social and spatial fine grain of places and encompassing a diversity of actors, can create the conditions enabling places to thrive and local economic activities to grow in a sustainable way.

Keywords: innovation-driven sustainable Eco-systems , place-based sustainable urban development, sustainable innovation districts, social innovation, urban policie

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Authors: Rachana Tank, Donald. M. Lyall, Kristin Flegal, Joey Ward, Jonathan Cavanagh

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Alzheimer’s research UK estimates by 2050, 2 million individuals will be living with Late Onset Alzheimer’s disease (LOAD). However, individuals experience considerable cognitive deficits and brain pathology over decades before reaching clinically diagnosable LOAD and studies have utilised gene candidate studies such as genome wide association studies (GWAS) and polygenic risk (PGR) scores to identify high risk individuals and potential pathways. This investigation aims to determine whether high genetic risk of LOAD is associated with worse brain MRI and cognitive performance in healthy older adults within the UK Biobank cohort. Previous studies investigating associations of PGR for LOAD and measures of MRI or cognitive functioning have focused on specific aspects of hippocampal structure, in relatively small sample sizes and with poor ‘controlling’ for confounders such as smoking. Both the sample size of this study and the discovery GWAS sample are bigger than previous studies to our knowledge. Genetic interaction between loci showing largest effects in GWAS have not been extensively studied and it is known that APOE e4 poses the largest genetic risk of LOAD with potential gene-gene and gene-environment interactions of e4, for this reason we  also analyse genetic interactions of PGR with the APOE e4 genotype. High genetic loading based on a polygenic risk score of 21 SNPs for LOAD is associated with worse brain MRI and cognitive outcomes in healthy individuals within the UK Biobank cohort. Summary statistics from Kunkle et al., GWAS meta-analyses (case: n=30,344, control: n=52,427) will be used to create polygenic risk scores based on 21 SNPs and analyses will be carried out in N=37,000 participants in the UK Biobank. This will be the largest study to date investigating PGR of LOAD in relation to MRI. MRI outcome measures include WM tracts, structural volumes. Cognitive function measures include reaction time, pairs matching, trail making, digit symbol substitution and prospective memory. Interaction of the APOE e4 alleles and PGR will be analysed by including APOE status as an interaction term coded as either 0, 1 or 2 e4 alleles. Models will be adjusted partially for adjusted for age, BMI, sex, genotyping chip, smoking, depression and social deprivation. Preliminary results suggest PGR score for LOAD is associated with decreased hippocampal volumes including hippocampal body (standardised beta = -0.04, P = 0.022) and tail (standardised beta = -0.037, P = 0.030), but not with hippocampal head. There were also associations of genetic risk with decreased cognitive performance including fluid intelligence (standardised beta = -0.08, P<0.01) and reaction time (standardised beta = 2.04, P<0.01). No genetic interactions were found between APOE e4 dose and PGR score for MRI or cognitive measures. The generalisability of these results is limited by selection bias within the UK Biobank as participants are less likely to be obese, smoke, be socioeconomically deprived and have fewer self-reported health conditions when compared to the general population. Lack of a unified approach or standardised method for calculating genetic risk scores may also be a limitation of these analyses. Further discussion and results are pending.

Keywords: Alzheimer's dementia, cognition, polygenic risk, MRI

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Authors: Nahla Elsherbiny, Ahmed Ahmed, Hamada Mohammed, Mohamed Ali

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Background: The enterococci may be considered as opportunistic agents particularly in immunocompromised patients. It is one of the top three pathogens causing many healthcare associated infections (HAIs). Resistance to several commonly used antimicrobial agents is a remarkable characteristic of most species which may carry various genes contributing to virulence. Objectives: to determine the prevalence of enterococci species in different intensive care units (ICUs) causing health care-associated infections (HAIs), intestinal carriage and environmental contamination. Also, to study the antimicrobial susceptibility pattern of the isolates with special reference to vancomycin resistance. In addition to phenotypic and genotypic detection of gelatinase, cytolysin and biofilm formation among isolates. Patients and Methods: This study was carried out in the infection control laboratory at Assiut University Hospitals over a period of one year. Clinical samples were collected from 285 patients with various (HAIs) acquired after admission to different ICUs. Rectal swabs were taken from 14 cases for detection of enterococci carriage. In addition, 1377 environmental samples were collected from the surroundings of the patients. Identification was done by conventional bacteriological methods and confirmed by analytical profile index (API). Antimicrobial sensitivity testing was performed by Kirby Bauer disc diffusion method and detection of vancomycin resistance was done by agar screen method. For the isolates, phenotypic detection of cytolysin, gelatinase production and detection of biofilm by tube method, Congo red method and microtiter plate. We performed polymerase chain reaction (PCR) for detection of some virulence genes (gelE, cylA, vanA, vanB and esp). Results: Enterococci caused 10.5% of the HAIs. Respiratory tract infection was the predominant type (86.7%). The commonest species were E.gallinarum (36.7%), E.casseliflavus (30%), E.faecalis (30%), and E.durans (3.4 %). Vancomycin resistance was detected in a total of 40% (12/30) of those isolates. The risk factors associated with acquiring vancomycin resistant enterococci (VRE) were immune suppression (P= 0.031) and artificial feeding (P= 0.008). For the rectal swabs, enterococci species were detected in 71.4% of samples with the predominance of E. casseliflavus (50%). Most of the isolates were vancomycin resistant (70%). Out of a total 1377 environmental samples, 577 (42%) samples were contaminated with different microorganisms. Enterococci were detected in 1.7% (10/577) of total contaminated samples, 50% of which were vancomycin resistant. All isolates were resistant to penicillin, ampicillin, oxacillin, ciprofloxacin, amikacin, erythromycin, clindamycin and trimethoprim-sulfamethaxazole. For the remaining antibiotics, variable percentages of resistance were reported. Cytolysin and gelatinase were detected phenotypically in 16% and 48 % of the isolates respectively. The microtiter plate method showed the highest percentages of detection of biofilm among all isolated species (100%). The studied virulence genes gelE, esp, vanA and vanB were detected in 62%, 12%, 2% and 12% respectively, while cylA gene was not detected in any isolates. Conclusions: A significant percentage of enterococci was isolated from patients and environments in the ICUs. Many virulence factors were detected phenotypically and genotypically among isolates. The high percentage of resistance, coupled with the risk of cross transmission to other patients make enterococci infections a significant infection control issue in hospitals.

Keywords: antimicrobial resistance, enterococci, ICUs, virulence factors

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Authors: Byron Baron

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Typical of the Mediterranean region, the Maltese islands exhibit calcareous soils containing low organic carbon content and high salinity, in addition to being relatively shallow. This has lead to the common practice of applying copious amounts of artificial fertilisers as well as other chemical inputs, together with the use of ground water having high salinity. Such intensive agricultural activities, over a prolonged time period, on such land has lead further to the loss of any soil fertility, together with direct negative impacts on the quality of fresh water reserves and the local ecosystem. The aim of this study was to investigate whether the natural resources on the island would be sufficient to apply ecological intensification i.e. the use of natural processes to replace anthropological inputs without any significant loss in food production. This was implementing through a sustainable agricultural system based on permaculture practices. Ecological intensification following permaculture principles was implemented for two years in order to capture the seasonal changes in duplicate. The areas dedicated to wild plants were only trimmed back to avoid excessive seeding but never mowing. A number of local staple crops were grown throughout this period, also in duplicate. Concomitantly, a number of practices were implemented following permaculture principles such as reducing land tilling, applying only natural fertiliser, mulching, monitoring of soil parameters using sensors, no use of herbicides or pesticides, and precision irrigation linked to a desalination system. Numerous environmental parameters were measured at regular intervals so as to quantify any improvements in ecological conditions. Crop output was also measured as kilos of produce per area. The results clearly show that over the two year period, the variety of wild plant species increased, the number of visiting pollinators increased, there were no pest infestations (although an increase in the number of pests was observed), and a slight improvement in overall soil health was also observed. This was obviously limited by the short duration of the testing implementation. Dedicating slightly less than 15% of total land area to wild plants in the form of borders around plots of crops assisted pollination and provided a foraging area for gleaning bats (measured as an increased number of feeding buzzes) whilst not giving rise to any pest infestations and no apparent yield losses or ill effects to the crops. Observed increases in crop yields were not significant. The study concluded that with the right support for the initial establishment of a healthy ecosystem and controlled intervention, the available natural resources on the island can substantially improve the condition of the local agricultural land area, resulting is a more prolonged economical output with greater ecological sustainability. That being said, more comprehensive and long-term monitoring is required in order to fully validate these results and design a sustainable agriculture system that truly achieves the best outcome for the Maltese context.

Keywords: ecological intensification, soil health, sustainable agriculture, permaculture

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Authors: Ashlie Latiolais

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Architecture, as a discipline, is on a trajectory of extension beyond the boundaries of buildings and, more increasingly, is coupled with research that connects to alternative and typically disjointed disciplines. A “both/and” approach and (expanded) definition of architecture, as depicted here, expands the margins that contain the profession. Figuratively, architecture is a series of edges, events, and occurrences that establishes a choreography or stage by which humanity exists. The way in which architecture controls and suggests the movement through these spaces, being within a landscape, city, or building, can be viewed as a datum by which the “dance” of everyday life occurs. This submission views the realm of architecture through the lens of movement and dance as a cross-fertilizer of collaboration, tectonic, and spatial geometry investigations. “Designing on digital programs puts architects at a distance from the spaces they imagine. While this has obvious advantages, it also means that they lose the lived, embodied experience of feeling what is needed in space—meaning that some design ideas that work in theory ultimately fail in practice.” By studying the body in motion through real-time performance, a more holistic understanding of architectural space surfaces and new prospects for theoretical teaching pedagogies emerge. The atypical intersection rethinks how architecture is considered, created, and tested, similar to how “dance artists often do this by thinking through the body, opening pathways and possibilities that might not otherwise be accessible” –this is the essence of this poster submission as explained through unFOLDED, a creative performance work. A new languageismaterialized through unFOLDED, a dynamic occupiable installation by which architecture is investigated through dance, movement, and body analysis. The entry unfolds a collaboration of an architect, dance choreographer, musicians, video artist, and lighting designers to re-create one of the first documented avant-garde performing arts collaborations (Matisse, Satie, Massine, Picasso) from the Ballet Russes in 1917, entitled Parade. Architecturally, this interdisciplinary project orients and suggests motion through structure, tectonic, lightness, darkness, and shadow as it questions the navigation of the dark space (stage) surrounding the installation. Artificial light via theatrical lighting and video graphics brought the blank canvas to life – where the sensitive mix of musicality coordinated with the structure’s movement sequencing was certainly a challenge. The upstage light from the video projections created both flickered contextual imagery and shadowed figures. When the dancers were either upstage or downstage of the structure, both silhouetted figures and revealed bodies are experienced as dancer-controlled installation manipulations occurred throughout the performance. The experimental performance, through structure, prompted moving (dancing) bodies in space, where the architecture served as a key component to the choreography itself. The tectonic of the delicate steel structure allowed for the dancers to interact with the installation, which created a variety of spatial conditions – the contained box of three-dimensional space, to a wall, and various abstracted geometries in between. The development of this research unveils the new role of an Architect as a Choreographer of the built environment.

Keywords: dance, architecture, choreography, installation, architect, choreographer, space

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Authors: Inna Kornienko, Svetlana Guryeva, Anatoly Shekhter, Elena Petersen

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Transplantation is an effective treatment option for patients suffering from different end-stage diseases. However, it is plagued by a constant shortage of donor organs and the subsequent need of a lifelong immunosuppressive therapy for the patient. Currently some researchers look towards using of pig organs to replace human organs for transplantation since the matrix derived from porcine organs is a convenient substitute for the human matrix. As an initial step to create a new ex vivo tissue engineered model, optimized protocols have been created to obtain organ-specific acellular matrices and evaluated their potential as tissue engineered scaffolds for culture of normal cells and tumor cell lines. These protocols include decellularization by perfusion in a bioreactor system and immersion-agitation on an orbital shaker with use of various detergents (SDS, Triton X-100) and freezing. Complete decellularization – in terms of residual DNA amount – is an important predictor of probability of immune rejection of materials of natural origin. However, the signs of cellular material may still remain within the matrix even after harsh decellularization protocols. In this regard, the matrices obtained from tissues of low-immunogenic pigs with α3Galactosyl-tranferase gene knock out (GalT-KO) may be a promising alternative to native animal sources. The research included a study of induced effect of frozen and fresh fragments of GalT-KO skin on healing of full-thickness plane wounds in 80 rats. Commercially available wound dressings (Ksenoderm, Hyamatrix and Alloderm) as well as allogenic skin were used as a positive control and untreated wounds were analyzed as a negative control. The results were evaluated on the 4th day after grafting, which corresponds to the time of start of normal wound epithelization. It has been shown that a non-specific immune response in models treated with GalT-Ko pig skin was milder than in all the control groups. Research has been performed to measure technical skin characteristics: stiffness and elasticity properties, corneometry, tevametry, and cutometry. These metrics enabled the evaluation of hydratation level, corneous layer husking level, as well as skin elasticity and micro- and macro-landscape. These preliminary data may contribute to development of personalized transplantable organs from GalT-Ko pigs with significantly limited potential of immune rejection. By applying growth factors to a decellularized skin sample it is possible to achieve various regenerative effects based on the particular situation. In this particular research BMP2 and Heparin-binding EGF-like growth factor have been used. Ideally, a bioengineered organ must be biocompatible, non-immunogenic and support cell growth. Porcine organs are attractive for xenotransplantation if severe immunologic concerns can be bypassed. The results indicate that genetically modified pig tissues with knock-outed α3Galactosyl-tranferase gene may be used for production of low-immunogenic matrix suitable for transplantation.

Keywords: decellularization, low-immunogenic, matrix, scaffolds, transplants

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Authors: Erica Cochran Hameen, Bobuchi Ken-Opurum, Mounica Guturu

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The United Stated (U.S.) populous spends the majority of their time indoors in spaces where building codes and voluntary sustainability standards provide clear Indoor Environmental Quality (IEQ) metrics. The existing sustainable building standards and codes are aimed towards improving IEQ, health of occupants, and reducing the negative impacts of buildings on the environment. While they address the post-occupancy stage of buildings, there are fewer standards on the pre-occupancy stage thereby placing a large labor population in environments much less regulated. Construction personnel are often exposed to a variety of uncomfortable and unhealthy elements while on construction sites, primarily thermal, visual, acoustic, and air quality related. Construction site power generators, equipment, and machinery generate on average 9 decibels (dBA) above the U.S. OSHA regulations, creating uncomfortable noise levels. Research has shown that frequent exposure to high noise levels leads to chronic physiological issues and increases noise induced stress, yet beyond OSHA no other metric focuses directly on the impacts of noise on contractors’ well-being. Research has also associated natural light with higher productivity and attention span, and lower cases of fatigue in construction workers. However, daylight is not always available as construction workers often perform tasks in cramped spaces, dark areas, or at nighttime. In these instances, the use of artificial light is necessary, yet lighting standards for use during lengthy tasks and arduous activities is not specified. Additionally, ambient air, contaminants, and material off-gassing expelled at construction sites are one of the causes of serious health effects in construction workers. Coupled with extreme hot and cold temperatures for different climate zones, health and productivity can be seriously compromised. This research evaluates the impact of existing green building metrics on construction and risk management, by analyzing two codes and nine standards including LEED, WELL, and BREAM. These metrics were chosen based on the relevance to the U.S. construction industry. This research determined that less than 20% of the sustainability context within the standards and codes (texts) are related to the pre-occupancy building sector. The research also investigated the impact of construction personnel’s health and well-being on construction management through two surveys of project managers and on-site contractors’ perception of their work environment on productivity. To fully understand the risks of limited Environmental and Health Quality metrics for contractors (EHQ) this research evaluated the connection between EHQ factors such as inefficient lighting, on construction workers and investigated the correlation between various site coping strategies for comfort and productivity. Outcomes from this research are three-pronged. The first includes fostering a discussion about the existing conditions of EQH elements, i.e. thermal, lighting, ergonomic, acoustic, and air quality on the construction labor force. The second identifies gaps in sustainability standards and codes during the pre-occupancy stage of building construction from ground-breaking to substantial completion. The third identifies opportunities for improvements and mitigation strategies to improve EQH such as increased monitoring of effects on productivity and health of contractors and increased inclusion of the pre-occupancy stage in green building standards.

Keywords: construction contractors, health and well-being, environmental quality, risk management

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Authors: Rebecca Laycock

Abstract:

Many Urban Agriculture (UA) initiatives, including community/allotment gardens, Community Supported Agriculture, and community/social farms, depend on volunteers. However, initiatives supported or run by volunteers are often faced with a high turnover of labour as a result of the involvement of episodic volunteers (a term describing ad hoc, one-time, and seasonal volunteers), leading to challenges with maintaining project continuity and retaining skills/knowledge within the initiative. This is a notable challenge given that food growing is a knowledge intensive activity where the fruits of labour appear months or sometimes years after investment. Participatory Action Research (PAR) is increasingly advocated for in the field of UA as a solution-oriented approach to research, providing concrete results in addition to advancing theory. PAR is a cyclical methodological approach involving researchers and stakeholders collaboratively 'identifying' and 'theorising' an issue, 'planning' an action to address said issue, 'taking action', and 'reflecting' on the process. Through iterative cycles and prolonged engagement, the theory is developed and actions become better tailored to the issue. The demand for PAR in UA research means that understanding how to use PAR with episodic volunteers is of critical importance. The aim of this paper is to explore (1) the challenges of doing PAR in UA initiatives with episodic volunteers, and (2) how PAR can be harnessed to advance sustainable development of UA through theoretically-informed action. A 2.5 year qualitative PAR study on three English case study student-led food growing initiatives took place between 2014 and 2016. University UA initiatives were chosen as exemplars because most of their volunteers were episodic. Data were collected through 13 interviews, 6 workshops, and a research diary. The results were thematically analysed through eclectic coding using Computer-Assisted Qualitative Data Analysis Software (NVivo). It was found that the challenges of doing PAR with transient participants were (1) a superficial understanding of issues by volunteers because of short term engagement, resulting in difficulties ‘identifying’/‘theorising’ issues to research; (2) difficulties implementing ‘actions’ given those involved in the ‘planning’ phase often left by the ‘action’ phase; (3) a lack of capacity of participants to engage in research given the ongoing challenge of maintaining participation; and (4) that the introduction of the researcher acted as an ‘intervention’. The involvement of a long-term stakeholder (the researcher) changed the group dynamics, prompted critical reflections that had not previously taken place, and improved continuity. This posed challenges for providing a genuine understanding the episodic volunteering PAR initiatives, and also challenged the notion of what constitutes an ‘intervention’ or ‘action’ in PAR. It is recommended that researchers working with episodic volunteers using PAR should (1) adopt a first-person approach by inquiring into the researcher’s own experience to enable depth in theoretical analysis to manage the potentially superficial understandings by short-term participants; and (2) establish safety mechanisms to address the potential for the research to impose artificial project continuity and knowledge retention that will end when the research does. Through these means, we can more effectively use PAR to conduct solution-oriented research about UA.

Keywords: community garden, continuity, first-person research, higher education, knowledge retention, project management, transience, university

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Authors: Babak Forouraghi

Abstract:

A genetic circuit is a collection of interacting genes and proteins that enable individual cells to implement and perform vital biological functions such as cell division, growth, death, and signaling. In cell engineering, synthetic gene circuits are engineered networks of genes specifically designed to implement functionalities that are not evolved by nature. These engineered networks enable scientists to tackle complex problems such as engineering cells to produce therapeutics within the patient's body, altering T cells to target cancer-related antigens for treatment, improving antibody production using engineered cells, tissue engineering, and production of genetically modified plants and livestock. Construction of computational models to realize genetic circuits is an especially challenging task since it requires the discovery of the flow of genetic information in complex biological systems. Building synthetic biological models is also a time-consuming process with relatively low prediction accuracy for highly complex genetic circuits. The primary goal of this study was to investigate the utility of a pre-trained bidirectional encoder transformer that can accurately predict gene expressions in genetic circuit designs. The main reason behind using transformers is their innate ability (attention mechanism) to take account of the semantic context present in long DNA chains that are heavily dependent on the spatial representation of their constituent genes. Previous approaches to gene circuit design, such as CNN and RNN architectures, are unable to capture semantic dependencies in long contexts, as required in most real-world applications of synthetic biology. For instance, RNN models (LSTM, GRU), although able to learn long-term dependencies, greatly suffer from vanishing gradient and low-efficiency problem when they sequentially process past states and compresses contextual information into a bottleneck with long input sequences. In other words, these architectures are not equipped with the necessary attention mechanisms to follow a long chain of genes with thousands of tokens. To address the above-mentioned limitations, a transformer model was built in this work as a variation to the existing DNA Bidirectional Encoder Representations from Transformers (DNABERT) model. It is shown that the proposed transformer is capable of capturing contextual information from long input sequences with an attention mechanism. In previous works on genetic circuit design, the traditional approaches to classification and regression, such as Random Forrest, Support Vector Machine, and Artificial Neural Networks, were able to achieve reasonably high R2 accuracy levels of 0.95 to 0.97. However, the transformer model utilized in this work, with its attention-based mechanism, was able to achieve a perfect accuracy level of 100%. Further, it is demonstrated that the efficiency of the transformer-based gene expression classifier is not dependent on the presence of large amounts of training examples, which may be difficult to compile in many real-world gene circuit designs.

Keywords: machine learning, classification and regression, gene circuit design, bidirectional transformers

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Authors: Lise Paesen, Marielle Leijten

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People diagnosed with probable Alzheimer disease suffer from an impairment of their language capacities; a gradual impairment which affects both their spoken and written communication. Our study aims at characterising the language decline in DAT patients with the use of congeneric elicited writing tasks. Within these tasks, a descriptive text has to be written based upon images with which the participants are confronted. A randomised set of images allows us to present the participants with a different task on every encounter, thus allowing us to avoid a recognition effect in this iterative study. This method is a revision from previous studies, in which participants were presented with a larger picture depicting an entire scene. In order to create the randomised set of images, existing pictures were adapted following strict criteria (e.g. frequency, AoA, colour, ...). The resulting data set contained 50 images, belonging to several categories (vehicles, animals, humans, and objects). A pre-test was constructed to validate the created picture set; most images had been used before in spoken picture naming tasks. Hence the same reaction times ought to be triggered in the typed picture naming task. Once validated, the effectiveness of the descriptive tasks was assessed. First, the participants (n=60 students, n=40 healthy elderly) performed a typing task, which provided information about the typing speed of each individual. Secondly, two descriptive writing tasks were carried out, one simple and one complex. The simple task contains 4 images (1 animal, 2 objects, 1 vehicle) and only contains elements with high frequency, a young AoA (<6 years), and fast reaction times. Slow reaction times, a later AoA (≥ 6 years) and low frequency were criteria for the complex task. This task uses 6 images (2 animals, 1 human, 2 objects and 1 vehicle). The data were collected with the keystroke logging programme Inputlog. Keystroke logging tools log and time stamp keystroke activity to reconstruct and describe text production processes. The data were analysed using a selection of writing process and product variables, such as general writing process measures, detailed pause analysis, linguistic analysis, and text length. As a covariate, the intrapersonal interkey transition times from the typing task were taken into account. The pre-test indicated that the new images lead to similar or even faster reaction times compared to the original images. All the images were therefore used in the main study. The produced texts of the description tasks were significantly longer compared to previous studies, providing sufficient text and process data for analyses. Preliminary analysis shows that the amount of words produced differed significantly between the healthy elderly and the students, as did the mean length of production bursts, even though both groups needed the same time to produce their texts. However, the elderly took significantly more time to produce the complex task than the simple task. Nevertheless, the amount of words per minute remained comparable between simple and complex. The pauses within and before words varied, even when taking personal typing abilities (obtained by the typing task) into account.

Keywords: Alzheimer's disease, experimental design, language decline, writing process

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Authors: Adrienn Kiss, Karoly Zauer, Gyorgy Keglevich, Rita Molnarne Bernath

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Ginger (Zingiber officinale) is a perennial plant from Southeast Asia, widely used as a spice, herb, and medicine for many illnesses since its beneficial health effects were observed thousands of years ago. Among the compounds found in ginger, zingerone [4-hydroxy-3- methoxyphenyl-2-butanone] deserves special attention: it has an anti-inflammatory and antispasmodic effect, it can be used in case of diarrheal disease, helps to prevent the formation of blood clots, has antimicrobial properties, and can also play a role in preventing the Alzheimer's disease. Ferulic acid [(E)-3-(4-hydroxy-3-methoxyphenyl)-prop-2-enoic acid] is another cinnamic acid derivative in ginger, which has promising properties. Like many phenolic compounds, ferulic acid is also an antioxidant. Based on the results of animal experiments, it is assumed to have a direct antitumoral effect in lung and liver cancer. It also deactivates free radicals that can damage the cell membrane and the DNA and helps to protect the skin against UV radiation. The aim of this work was to synthesize these two compounds by new methods. A few of the reactions were based on the hydrogenation of dehydrozingerone [4-(4-Hydroxy-3-methoxyphenyl)-3-buten-2-one] to zingerone. Dehydrozingerone can be synthesized by a relatively simple method from acetone and vanillin with good yield (80%, melting point: 41 °C). Hydrogenation can be carried out chemically, for example by the reaction of zinc and acetic acid, or Grignard magnesium and ethyl alcohol. Another way to complete the reduction is the electrochemical pathway. The electrolysis of dehydrozingerone without diaphragm in aqueous media was attempted to produce ferulic acid in the presence of sodium carbonate and potassium iodide using platinum electrodes. The electrolysis of dehydrozingerone in the presence of potassium carbonate and acetic acid to prepare zingerone was carried out similarly. Ferulic acid was expected to be converted to dihydroferulic acid [3-(4-Hydroxy-3-methoxyphenyl)propanoic acid] in potassium hydroxide solution using iron electrodes, separating the anode and cathode space with a Soxhlet paper sheath impregnated with saturated magnesium chloride solution. For this reaction, ferulic acid was synthesized from vanillin and malonic acid in the presence of pyridine and piperidine (yield: 88.7%, melting point: 173°C). Unfortunately, in many cases, the expected transformations did not happen or took place in low conversions, although gas evolution occurred. Thus, a deeper understanding of these experiments and optimization are needed. Since both compounds are found in different plants, they can also be obtained by alkaline extraction or steam distillation from distinct plant parts (ferulic acid from ground bamboo shoots, zingerone from grated ginger root). The products of these reactions are rich in several other organic compounds as well; therefore, their separation must be solved to get the desired pure material. The products of the reactions described above were characterized by infrared spectral data and melting points. The use of these two simple methods may be informative for the formation of the products. In the future, we would like to study the ferulic acid and zingerone content of other plants and extract them efficiently. The optimization of electrochemical reactions and the use of other test methods are also among our plans.

Keywords: ferulic acid, ginger, synthesis, zingerone

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Authors: Vahid Saatchian, Seyyed Farideh Hadavi

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The main aim of this study was developing the collaboration model of physical education and sport sciences faculties with service section of sport industrial.The research methods of this study was a qualitative. So researcher with of identifying the priority list of collaboration between colleges and service section of sport industry and according to sampling based of subjective and snowball approach, conducted deep interviews with 22 elites that study around the field of research topic. indeed interviews were analyzed through qualitative coding (open, axial and selective) with 5 category such as causal condition, basic condition, intervening conditions, action/ interaction and strategy. Findings exposed that in causal condition 10 labels appeared. So because of heterogeneity of labes, researcher categorized in total subject. In basic condition 59 labels in open coding identified this categorized in 14 general concepts. Furthermore with composition of the declared category and relationship between them, 5 final and internal categories (culture, intelligence, marketing, environment and ultra-powers) were appeared. Also an intervening condition in the study includes 5 overall scopes of social factors, economic, cultural factors, and the management of the legal and political factors that totally named macro environment. Indeed for identifying strategies, 8 areas that covered with internal and external challenges relationship management were appeared. These are including, understanding, outside awareness, manpower, culture, integrated management, the rules and regulations and marketing. Findings exposed 8 labels in open coding which covered the internal and external of challenges of relation management of two sides and these concepts were knowledge and awareness, external view, human source, madding organizational culture, parties’ thoughts, unit responsible for/integrated management, laws and regulations and marketing. Eventually the consequences categorized in line of strategies and were at scope of the cultural development, general development, educational development, scientific development, under development, international development, social development, economic development, technology development and political development that consistent with strategies. The research findings could help the sport managers witch use to scientific collaboration management and the consequences of this in those sport institutions. Finally, the consequences that identified as a result of the devopmental strategies include: cultural, governmental, educational, scientific, infrastructure, international, social, economic, technological and political that is largely consistent with strategies. With regard to the above results, enduring and systematic relation with long term cooperation between the two sides requires strategic planning were based on cooperation of all stakeholders. Through this, in the turbulent constantly changing current sustainable environment, competitive advantage for university and industry obtained. No doubt that lack of vision and strategic thinking for cooperation in the planning of the university and industry from its capability and instead of using the opportunity, lead the opportunities to problems.

Keywords: university and industry collaboration, sport industry, physical education and sport science college, service section of sport industry

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Authors: Felix Lankester, Alicia Davis, Safari Kinung'hi, Catherine Bunga, Shayo Alkara, Imam Mzimbiri, Jonathan Yoder, Sarah Cleaveland, Guy H. Palmer

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Achieving the London Declaration goal of a 90% reduction in neglected tropical diseases (NTDs) by 2030 requires cost-effective strategies that attain high and comprehensive coverage. The first objective of this trial was to assess the impact on cost and coverage of employing a novel integrative One Health approach linking two NTD control programs: mass drug administration (MDA) for soil-transmitted helminths in humans (STH) and mass dog rabies vaccination (MDRV). The second objective was to compare the coverage achieved by the MDA, a community-wide deworming intervention, with that of the existing national primary school-based deworming program (NSDP), with particular focus on the proportion of primary school-age children reached and their school enrolment status. Our approach was unconventional because, in line with the One Health approach to disease control, it coupled the responsibilities and resources of the Ministries responsible for human and animal health into one program with the shared aim of preventing multiple NTDs. The trial was carried out in hard-to-reach pastoral communities comprising 24 villages of the Ngorongoro District, Tanzania, randomly allocated to either Arm A (MDA and MDRV), Arm B (MDA only) or Arm C (MDRV only). Objective one: The percentage of people in each target village that received treatment through MDA in Arms A and B was 63% and 65%, respectively (χ2 = 1, p = 0.32). The percentage of dogs vaccinated in Arm A and C was 70% and 81%, respectively (χ2 =9, p = 0.003). It took 33% less time for a single person and a dog to attend the integrated delivery than two separate events. Cost per dose (including delivery) was lower under the integrated strategy, with delivery of deworming and rabies vaccination reduced by $0.13 (54%) and $0.85 (19%) per dose, respectively. Despite a slight reduction in the proportion of village dogs vaccinated in the integrated event, both the integrated and non-integrated strategies achieved the target threshold of 70% required to eliminate rabies. Objective two: The percentages of primary school age children enrolled in school that was reached by this trial (73%) and the existing NSDP (80%) were not significantly different (F = 0.9, p = 0.36). However, of the primary school age children treated in this trial, 46% were not enrolled in school. Furthermore, 86% of the people treated would have been outside the reach of the NSDP because they were not primary school age or were primary school age children not enrolled in school. The comparable reach, the substantial reductions in cost per dose delivered and the decrease in participants’ time support this integrated One Health approach to control multiple NTDs. Further, the recorded level of non-enrolment at primary school suggests that, in remote areas, school-based delivery strategies could miss a large fraction of school-age children and that programs that focus delivery solely at the level of the primary school will miss a substantial proportion of both primary school age children as well as other individuals from the community. We have shown that these populations can be effectively reached through extramural programs.

Keywords: canine mediated human rabies, integrated health interventions, mass drug administration, neglected tropical disease, One Health, soil-transmitted helminths

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Authors: Tamal Roy, Anuradha Bhat

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Cognitive abilities aid fishes in foraging, avoiding predators & locating mates. Factors like predation pressure & habitat complexity govern learning & memory in fishes. This study aims to compare spatial learning & memory across four natural populations of zebrafish. Zebrafish, a small cyprinid inhabits a diverse range of freshwater habitats & this makes it amenable to studies investigating role of native environment in spatial cognitive abilities. Four populations were collected across India from waterbodies with contrasting ecological conditions. Habitat complexity of the water-bodies was evaluated as a combination of channel substrate diversity and diversity of vegetation. Experiments were conducted on populations under controlled laboratory conditions. A square shaped spatial testing arena (maze) was constructed for testing the performance of adult zebrafish. The square tank consisted of an inner square shaped layer with the edges connected to the diagonal ends of the tank-walls by connections thereby forming four separate chambers. Each of the four chambers had a main door in the centre. Each chamber had three sections separated by two windows. A removable coloured window-pane (red, yellow, green or blue) identified each main door. A food reward associated with an artificial plant was always placed inside the left-hand section of the red-door chamber. The position of food-reward and plant within the red-door chamber was fixed. A test fish would have to explore the maze by taking turns and locate the food inside the right-side section of the red-door chamber. Fishes were sorted from each population stock and kept individually in separate containers for identification. At a time, a test fish was released into the arena and allowed 20 minutes to explore in order to find the food-reward. In this way, individual fishes were trained through the maze to locate the food reward for eight consecutive days. The position of red door, with the plant and the reward, was shuffled every day. Following training, an intermission of four days was given during which the fishes were not subjected to trials. Post-intermission, the fishes were re-tested on the 13th day following the same protocol for their ability to remember the learnt task. Exploratory tendencies and latency of individuals to explore on 1st day of training, performance time across trials, and number of mistakes made each day were recorded. Additionally, mechanism used by individuals to solve the maze each day was analyzed across populations. Fishes could be expected to use algorithm (sequence of turns) or associative cues in locating the food reward. Individuals of populations did not differ significantly in latencies and tendencies to explore. No relationship was found between exploration and learning across populations. High habitat-complexity populations had higher rates of learning & stronger memory while low habitat-complexity populations had lower rates of learning and much reduced abilities to remember. High habitat-complexity populations used associative cues more than algorithm for learning and remembering while low habitat-complexity populations used both equally. The study, therefore, helped understand the role of natural ecology in explaining variations in spatial learning abilities across populations.

Keywords: algorithm, associative cue, habitat complexity, population, spatial learning

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Authors: Rodriguez Diego, Del Valle Martin, Hargreaves Matias, Riveros Jose Luis

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Nutrient deficiencies due to a diet low in quantitative and qualitative terms, are prevalent throughout the developing world, especially in sub-Saharan Africa. Children and women of childbearing age are especially vulnerable. Limited availability, access and intake of animal foods at home and lack of knowledge about their value in the diet and the role they play in health, contribute to poor diet quality. Poor bioavailability of micronutrients in diets based on foods high in fiber and phytates, the low content of some micronutrients in these foods are further factors to consider. Goats are deeply embedded in almost every Sub-Saharan African rural culture, generally kept for their milk, meat, hair or leather. Goats have played an important role in African social life, especially in food security. Goat meat has good properties for human wellbeing, with a special role in lower income households. It has a high-quality protein (20 protein g/100 meat g) including all essential amino acids, good unsaturated/satured fatty acids relationship, and it is an important B-vitamin source with high micronutrients bioavailability. Mozambique has major food security problems, with poor food access and utilization, undiversified diets, chronic poverty and child malnutrition. Our objective was to design a nutritional intervention based on a dietary diversification, nutritional education, cultural beliefs and local resources, aimed to strengthen food security of children at Barrio Broma village (15°43'58.78"S; 32°46'7.27"E) in Chitima, Mozambique. Two surveys were conducted first of socio-productive local databases and then to 100 rural households about livelihoods, food diversity and anthropometric measurements in children under 5 years. Our results indicate that the main economic activity is goat production, based on a native breed with two deliveries per year in the absence of any management. Adult goats weighted 27.2±10.5 kg and raised a height of 63.5±3.8 cm. Data showed high levels of poverty, with a food diversity score of 2.3 (0-12 points), where only 30% of households consume protein and 13% iron, zinc, and B12 vitamin. The main constraints to food security were poor access to water and low income to buy food. Our dietary intervention was based on improving diet quality by increasing the access to dried goat meat, fresh vegetables, and legumes, and its utilization by a nutritional education program. This proposal was based on local culture and living conditions characterized by the absence of electricity power and drinkable water. The drying process proposed would secure the food maintenance under local conditions guaranteeing food safety for a longer period. Additionally, an ancient local drying technique was rescued and used. Moreover, this kind of dietary intervention would be the most efficient way to improve the infant nutrition by delivering macro and micronutrients on time to these vulnerable populations.

Keywords: child malnutrition, dietary diversification, food security, goat meat

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Authors: Ririh Rahma Ratinghayu, Jayu Pramudya, Nur Aini Masruroh, Shi-Woei Lin

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This research studies pricing strategy in cooperative setting of hotel duopoly selling perishable product under fixed capacity constraint by using the perspective of managers. In hotel revenue management, competitor’s average room rate and occupancy rate should be taken into manager’s consideration in determining pricing strategy to generate optimum revenue. This information is not provided by business intelligence or available in competitor’s website. Thus, Information Sharing (IS) among players might result in improved performance of pricing strategy. IS is widely adopted in the logistics industry, but IS within hospitality industry has not been well-studied. This research put IS as one of cooperative game schemes, besides Mutual Price Setting (MPS) scheme. In off-peak season, hotel manager arranges pricing strategy to offer promotion package and various kinds of discounts up to 60% of full-price to attract customers. Competitor selling homogenous product will react the same, then triggers a price war. Price war which generates lower revenue may be avoided by creating collaboration in pricing strategy to optimize payoff for both players. In MPS cooperative game, players collaborate to set a room rate applied for both players. Cooperative game may avoid unfavorable players’ payoff caused by price war. Researches on horizontal cooperative game in logistics show better performance and payoff for the players, however, horizontal cooperative game in hotel revenue management has not been demonstrated. This paper aims to develop hotel revenue management models under duopoly cooperative schemes (IS & MPS), which are compared to models under non-cooperative scheme too. Each scheme has five models, Capacity Allocation Model; Demand Model; Revenue Model; Optimal Price Model; and Equilibrium Price Model. Capacity Allocation Model and Demand Model employs self-hotel and competitor’s full and discount price as predictors under non-linear relation. Optimal price is obtained by assuming revenue maximization motive. Equilibrium price is observed by interacting self-hotel’s and competitor’s optimal price under reaction equation. Equilibrium is analyzed using game theory approach. The sequence applies for three schemes. MPS Scheme differently aims to optimize total players’ payoff. The case study in which theoretical models are applied observes two hotels offering homogenous product in Indonesia during a year. The Capacity Allocation, Demand, and Revenue Models are built using multiple regression and statistically tested for validation. Case study data confirms that price behaves within demand model in a non-linear manner. IS Models can represent the actual demand and revenue data better than Non-IS Models. Furthermore, IS enables hotels to earn significantly higher revenue. Thus, duopoly hotel players in general, might have reasonable incentives to share information horizontally. During off-peak season, MPS Models are able to predict the optimal equal price for both hotels. However, Nash equilibrium may not always exist depending on actual payoff of adhering or betraying mutual agreement. To optimize performance, horizontal cooperative game may be chosen over non-cooperative game. Mathematical models can be used to detect collusion among business players. Empirical testing can be used as policy input for market regulator in preventing unethical business practices potentially harming society welfare.

Keywords: horizontal cooperative game theory, hotel revenue management, information sharing, mutual price setting

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Authors: Sami El Khatib, Agnès Leroux, Jean-Louis Merlin, François Guillemin, Marie-Ange D’Hallewin

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Photodynamic therapy (PDT) is a treatment modality based on the cytotoxic effect occurring on the target tissues by interaction of a photosensitizer with light in the presence of oxygen. One of the major advances in PDT can be attributed to the use of topical aminolevulinic (ALA) to induce Protoporphyrin IX (PpIX) for the treatment of early stage cancers as well as diagnosis. ALA is a precursor of the heme synthesis pathway. Locally delivered to the target tissue ALA overcomes the negative feedback exerted by heme and promotes the transient formation of PpIX in situ to reach critical effective levels in cells and tissue. Whereas early steps of the heme pathway occur in the cytosol, PpIX synthesis is shown to be held in the mitochondrial membranes and PpIX fluorescence is expected to accumulate in close vicinity of the initial building site and to progressively diffuse to the neighboring cytoplasmic compartment or other lipophylic organelles. PpIX is known to be highly reactive and will be degraded when irradiated with light. PpIX photobleaching is believed to be governed by a singlet oxygen mediated mechanism in the presence of oxidized amino acids and proteins. PpIX photobleaching and subsequent spectral phototransformation were described widely in tumor cells incubated in vitro with ALA solution, or ex vivo in human and porcine mucosa superfused with hexylaminolevulinate (hALA). PpIX photobleaching was also studied in vivo, using animal models such as normal or tumor mice skin and orthotopic rat bladder model. Hexyl aminolevulinate a more potent lipophilic derivative of ALA was proposed as an adjunct to standard cystoscopy in the fluorescence diagnosis of bladder cancer and other malignancies. We have previously reported the effectiveness of hALA mediated PDT of rat bladder cancer. Although normal and tumor bladder epithelium exhibit similar fluorescence intensities after intravesical instillation of two hALA concentrations (8 and 16 mM), the therapeutic response at 8mM and 20J/cm2 was completely different from the one observed at 16mM irradiated with the same light dose. Where the tumor is destroyed, leaving the underlying submucosa and muscle intact after an 8 mM instillation, 16mM sensitization and subsequent illumination results in the complete destruction of the underlying bladder wall but leaves the tumor undamaged. The object of the current study is to try to unravel the underlying mechanism for this apparent contradiction. PpIX extraction showed identical amounts of photosensitizer in tumor bearing bladders at both concentrations. Photobleaching experiments revealed mono-exponential decay curves in both situations but with a two times faster decay constant in case of 16mM bladders. Fluorescence microscopy shows an identical fluorescence pattern for normal bladders at both concentrations and tumor bladders at 8mM with bright spots. Tumor bladders at 16 mM exhibit a more diffuse cytoplasmic fluorescence distribution. The different response to PDT with regard to the initial pro-drug concentration can thus be attributed to the different cellular localization.

Keywords: bladder cancer, hexyl-aminolevulinate, photobleaching, confocal fluorescence microscopy

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Authors: Iñaki Iturria, Pasquale Russo, Montserrat Nacher-Vázquez, Giuseppe Spano, Paloma López, Miguel Angel Pardo

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Introduction: It is known that some Lactic Acid Bacteria (LAB) present an interesting probiotic effect. Probiotic bacteria stimulate host resistance to microbial pathogens and thereby aid in immune response, and modulate the host's immune responses to antigens with a potential to down-regulate hypersensitivity reactions. Therefore, probiotic therapy is valuable against intestinal infections and may be beneficial in the treatment of Inflammatory Bowel Disease (IBD). Several in vitro tests are available to evaluate the probiotic potential of a LAB strain. However, an in vivo model is required to understand the interaction between the host immune system and the bacteria. During the last few years, zebrafish (Danio rerio) has gained interest as a promising vertebrate model in this field. This organism has been extensively used to study the interaction between the host and the microbiota, as well as the host immune response under several microbial infections. In this work, we report on the use of the zebrafish model to investigate in vivo the colonizing ability and the immunomodulatory effect of probiotic LAB. Methods: Lactobacillus strains belonging to different LAB species were fluorescently tagged and used to colonize germ-free zebrafish larvae gastrointestinal tract (GIT). Some of the strains had a well-documented probiotic effect (L. acidophilus LA5); while others presented an exopolysaccharide (EPS) producing phenotype, thus allowing evaluating the influence of EPS in the colonization and immunomodulatory effect. Bacteria colonization was monitored for 72 h by direct observation in real time using fluorescent microscopy. CFU count per larva was also evaluated at different times. The immunomodulatory effect was assessed analysing the differential expression of several innate immune system genes (MyD88, NF-κB, Tlr4, Il1β and Il10) by qRT- PCR. The anti-inflammatory effect was evaluated using a chemical enterocolitis zebrafish model. The protective effect against a pathogen was also studied. To that end, a challenge test was developed using a fluorescently tagged pathogen (Vibrio anguillarum-GFP+). The progression of the infection was monitored up to 3 days using a fluorescent stereomicroscope. Mortality rates and CFU counts were also registered. Results and conclusions: Larvae exposed to EPS-producing bacteria showed a higher fluorescence and CFU count than those colonized with no-EPS phenotype LAB. In the same way, qRT-PCR results revealed an immunomodulatory effect on the host after the administration of the strains with probiotic activity. A downregulation of proinflammatory cytoquines as well as other cellular mediators of inflammation was observed. The anti-inflammatory effect was found to be particularly marked following exposure to LA% strain, as well as EPS producing strains. Furthermore, the challenge test revealed a protective effect of probiotic administration. As a matter of fact, larvae fed with probiotics showed a decrease in the mortality rate ranging from 20 to 35%. Discussion: In this work, we developed a promising model, based on the use of gnotobiotic zebrafish coupled with a bacterial fluorescent tagging in order to evaluate the probiotic potential of different LAB strains. We have successfully used this system to monitor in real time the colonization and persistence of exogenous LAB within the gut of zebrafish larvae, to evaluate their immunomodulatory effect and for in vivo competition assays. This approach could bring further insights into the complex microbial-host interactions at intestinal level.

Keywords: gnotobiotic, immune system, lactic acid bacteria, probiotics, zebrafish

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Authors: M. Reza Hashemi, Chris Small, Scott Hayward

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The Northeast Coast of the US faces damaging effects of coastal flooding and winds due to Atlantic tropical and extratropical storms each year. Historically, several large storm events have produced substantial levels of damage to the region; most notably of which were the Great Atlantic Hurricane of 1938, Hurricane Carol, Hurricane Bob, and recently Hurricane Sandy (2012). The objective of this study was to develop an integrated modeling system that could be used as a forecasting/hindcasting tool to evaluate and communicate the risk coastal communities face from these coastal storms. This modeling system utilizes the ADvanced CIRCulation (ADCIRC) model for storm surge predictions and the Simulating Waves Nearshore (SWAN) model for the wave environment. These models were coupled, passing information to each other and computing over the same unstructured domain, allowing for the most accurate representation of the physical storm processes. The coupled SWAN-ADCIRC model was validated and has been set up to perform real-time forecast simulations (as well as hindcast). Modeled storm parameters were then passed to a coastal risk assessment tool. This tool, which is generic and universally applicable, generates spatial structural damage estimate maps on an individual structure basis for an area of interest. The required inputs for the coastal risk model included a detailed information about the individual structures, inundation levels, and wave heights for the selected region. Additionally, calculation of wind damage to structures was incorporated. The integrated coastal risk assessment system was then tested and applied to Charlestown, a small vulnerable coastal town along the southern shore of Rhode Island. The modeling system was applied to Hurricane Sandy and a synthetic storm. In both storm cases, effect of natural dunes on coastal risk was investigated. The resulting damage maps for the area (Charlestown) clearly showed that the dune eroded scenarios affected more structures, and increased the estimated damage. The system was also tested in forecast mode for a large Nor’Easters: Stella (March 2017). The results showed a good performance of the coupled model in forecast mode when compared to observations. Finally, a nearshore model XBeach was then nested within this regional grid (ADCIRC-SWAN) to simulate nearshore sediment transport processes and coastal erosion. Hurricane Irene (2011) was used to validate XBeach, on the basis of a unique beach profile dataset at the region. XBeach showed a relatively good performance, being able to estimate eroded volumes along the beach transects with a mean error of 16%. The validated model was then used to analyze the effectiveness of several erosion mitigation methods that were recommended in a recent study of coastal erosion in New England: beach nourishment, coastal bank (engineered core), and submerged breakwater as well as artificial surfing reef. It was shown that beach nourishment and coastal banks perform better to mitigate shoreline retreat and coastal erosion.

Keywords: ADCIRC, coastal flooding, storm surge, coastal risk assessment, living shorelines

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Authors: Ron Dick, P. S. D. V. Prasadarao, Glenn Coltman

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Agenesis of the corpus callosum (ACC) is a failure to develop corpus callosum - the large bundle of fibers of the brain that connects the two cerebral hemispheres. It can occur as a partial or complete absence of the corpus callosum. In the general population, its estimated prevalence rate is 1 in 4000 and a wide range of genetic, infectious, vascular, and toxic causes have been attributed to this heterogeneous condition. The diagnosis of ACC is often achieved by neuroimaging procedures. Though persons with ACC can perform normally on intelligence tests they generally present with a range of neuropsychological and social deficits. The deficit profile is characterized by poor coordination of motor movements, slow reaction time, processing speed and, poor memory. Socially, they present with deficits in communication, language processing, the theory of mind, and interpersonal relationships. The present paper illustrates the role of neuropsychological assessment with implications to psychosocial management in a case of agenesis of the corpus callosum. Method: A 27-year old left handed Caucasian male with a history of ACC was self-referred for a neuropsychological assessment to assist him in his employment options. Parents noted significant difficulties with coordination and balance at an early age of 2-3 years and he was diagnosed with dyspraxia at the age of 14 years. History also indicated visual impairment, hypotonia, poor muscle coordination, and delayed development of motor milestones. MRI scan indicated agenesis of the corpus callosum with ventricular morphology, widely spaced parallel lateral ventricles and mild dilatation of the posterior horns; it also showed colpocephaly—a disproportionate enlargement of the occipital horns of the lateral ventricles which might be affecting his motor abilities and visual defects. The MRI scan ruled out other structural abnormalities or neonatal brain injury. At the time of assessment, the subject presented with such problems as poor coordination, slowed processing speed, poor organizational skills and time management, and difficulty with social cues and facial expressions. A comprehensive neuropsychological assessment was planned and conducted to assist in identifying the current neuropsychological profile to facilitate the formulation of a psychosocial and occupational rehabilitation programme. Results: General intellectual functioning was within the average range and his performance on memory-related tasks was adequate. Significant visuospatial and visuoconstructional deficits were evident across tests; constructional difficulties were seen in tasks such as copying a complex figure, building a tower and manipulating blocks. Poor visual scanning ability and visual motor speed were evident. Socially, the subject reported heightened social anxiety, difficulty in responding to cues in the social environment, and difficulty in developing intimate relationships. Conclusion: Persons with ACC are known to present with specific cognitive deficits and problems in social situations. Findings from the current neuropsychological assessment indicated significant visuospatial difficulties, poor visual scanning and problems in social interactions. His general intellectual functioning was within the average range. Based on the findings from the comprehensive neuropsychological assessment, a structured psychosocial rehabilitation programme was developed and recommended.

Keywords: agenesis, callosum, corpus, neuropsychology, psychosocial, rehabilitation

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Authors: Fouzia Arif, Arif S. Mohammad, Hifsa Altaf, Lubna Raees

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Introduction: The term "disability", refers to any condition that impedes the completion of daily tasks using traditional methods. In developing countries like Pakistan, disable population is usually excluded from the mainstream. In squatter settlements the situation is more critical. Sultanabad is one of the squatter settlements of Karachi. Purpose of case study is to improve the health of disabled children’s, and create awareness among the parents and community. Through a household visit, Shiraz, a young disabled boy of 15.5 years old was identified. Her mother articulated that her son was living normally and happily with his parents two years back. When he was 13 years old and student of class 8th, both his legs were traumatized in a Railway Train Accident while playing cricket. He got both femoral shaft fractured severely. He was taken to Jinnah Post Graduate Medical Centre (JPMC) where his left leg was amputated at above knee level and right leg was opened & fixed by reduction internally, luckily bone healed moderately with the passage of time. Methods: In Squatter settlements of Karachi Sultanabad, a survey was conducted in two sectors. Disability screening questionnaire was developed, collaboration with community through household visits, outreach sessions 23cases of disabled were identified who were socialized through sports, Musical program and get-together was organized with stockholder for creating awareness among community and parent’s. Collaboration was established with different NGOs, Government, stakeholders and community support for establishment of Physiotherapy Center. During home visit it was identified that Shiraz was on bed since last 1 year, his family could not afforded cost of physiotherapist and medical consultation due to poverty. Parents counseling was done mentioning that Shiraz needed to take treatment. After motivation his parents agreed for treatment. He was consulted by an orthopedic surgeon in AKUH, Who referred to DMC University of Health Science for rehabilitation service. There he was assessed and referred for Community Based Physiotherapy Centre Sultanabad. Physiotherapist visited home along with Coordinator for Special children and assessed him regularly, planned Physiotherapy treatment for abdominal, high muscles strutting exercise foot muscles strengthening exercise, knee mobilization weight bearing from partial to full weight gradually, also strengthen exercise were given for residual limb as the boy was dependent on it. He was also provided by an artificial leg and training was done. Result: Shiraz is now fully mobile, he can walk independently even out of home, functional ability progress improved and dependency factors reduced. It was difficult but not impossible. We all have sympathy but if we have empathy then we can rehabilitate the community in a better way. His parents are very happy and also the community is surprised to see him in such better condition. Conclusion: Combined efforts of physiotherapist, Coordinator of special children, community and parents made a drastic change in Shiraz’s case by continuously motivating him for better outcome. He is going to school regularly without support. Since he belongs to a poor family he faces financial constraints for education and clinical follow ups regularly.

Keywords: femoral shaft fracture, trauma, orthopedic surgeon, physiotherapy treatment

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Authors: Kakali Roy, Sahana P. Raju, Subhra Dhar, Sandipan Dhar

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Introduction: Xeroderma pigmentosa (XP) is a rare inherited (autosomal recessive) disease resulting from impairment in DNA repair that involves recognition and repair of ultraviolet radiation (UVR) induced DNA damage in the nucleotide excision repair pathway. Which results in increased photosensitivity, UVR induced damage to skin and eye, increased susceptibility of skin and ocular cancer, and progressive neurodegeneration in some patients. XP is present worldwide, with higher incidence in areas having frequent consanguinity. Being extremely rare, there is limited literature on XP and associated complications. Here, the clinico-pathological experience (spectrum of clinical presentation, histopathological findings of malignant skin lesions, and progression) of managing 8 cases of XP is presented. Methodology: A retrospective study was conducted in a pediatric tertiary care hospital in eastern India during a ten-year period from 2013 to 2022. A clinical diagnosis was made based on severe sun burn or premature photo-aging and/or onset of cutaneous malignancies at early age (1st decade) in background of consanguinity and autosomal recessive inheritance pattern in family. Results: The mean age of presentation was 1.2 years (range of 7month-3years), while three children presented during their infancy. Male to female ratio was 5:3, and all were born of consanguineous marriage. They presented with dermatological manifestations (100%) followed by ophthalmic (75%) and/or neurological symptoms (25%). Patients had normal skin at birth but soon developed extreme sensitivity to UVR in the form of exaggerated sun tanning, burning, and blistering on minimal sun exposure, followed by abnormal skin pigmentation like freckles and lentiginosis. Subsequently, over time there was progressive xerosis, atrophy, wrinkling, and poikiloderma. Six patients had varied degree of ocular involvement, while three of them had severe manifestation, including madarosis, tylosis, ectropion, Lagopthalmos, Pthysis bulbi, clouding and scarring of the cornea with complete or partial loss of vision, and ophthalmic malignancies. 50% (n=4) cases had skin and ocular pre-malignant (actinic keratosis) and malignant lesions, including melanoma and non melanoma skin cancer (NMSC) like squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) in their early childhood. One patient had simultaneous occurrence of multiple malignancies together (SCC, BCC, and melanoma). Subnormal intelligence was noticed as neurological feature, and none had sensory neural hearing loss, microcephaly, neuroregression, or neurdeficit. All the patients had been being managed by a multidisciplinary team of pediatricians, dermatologists, ophthalmologists, neurologists and psychiatrists. Conclusion: Although till date there is no complete cure for XP and the disease is ultimately fatal. But increased awareness, early diagnosis followed by persistent vigorous protection from UVR, and regular screening for early detection of malignancies along with psychological support can drastically improve patients’ quality of life and life expectancy. Further research is required on formulating optimal management of XP, specifically the role and possibilities of gene therapy in XP.

Keywords: childhood malignancies, dermato-pathological findings, eastern India, Xeroderma pigmentosa

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Authors: Ashleigh Williams

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Micro- and nanoplastics’ (MNLPs) omnipresence and ecological accumulation is evident when surveying recent environmental impact studies. For example, in 2014 it was estimated that at least 52.3 trillion plastic microparticles are floating at sea, and scientists have even found plastics present remote Arctic ice and snow (5,6). Plastics have even found their way into precipitation, with more than 1000 tons of microplastic rain precipitating onto the Western United States in 2020. Even more recent studies evaluating the chemical safety of reusable plastic bottles found that hundreds of chemicals leached into the control liquid in the bottle (ddH2O, ph = 7) during a 24-hour time period. A consequence of the increased abundance in plastic waste in the air, land, and water every year is the bioaccumulation of MNLPs in ecosystems and trophic niches of the animal food chain, which could potentially cause increased direct and indirect exposure of humans to MNLPs via inhalation, ingestion, and dermal contact. Though the detrimental, toxic effects of MNLPs have been established in marine biota, much less is known about the potentially hazardous health effects of chronic MNLP ingestion in humans. Recent data indicate that long-term exposure to MNLPs could cause possible inflammatory and dysbiotic effects. However, toxicity seems to be largely dose-, as well as size-dependent. In addition, the transcytotic uptake of MNLPs through the intestinal epithelia in humans remain relatively unknown. To this point, the goal of the current study was to investigate the mechanisms of micro- and nanoplastic uptake and transcytosis of Polystyrene (PE) in human stem-cell derived, physiologically relevant in vitro intestinal model systems, and to compare the relative effect of particle size (30 nm, 100 nm, 500 nm and 1 µm), and concentration (0 µg/mL, 250 µg/mL, 500 µg/mL, 1000 µg/mL) on polystyrene MNLP uptake, transcytosis and intestinal epithelial model integrity. Observational and quantitative data obtained from confocal microscopy, immunostaining, transepithelial electrical resistance (TEER) measurements, cryosectioning, and ELISA cytokine assays of the proinflammatory cytokines Interleukin-6 and Interleukin-8 were used to evaluate the localization and transcytosis of polystyrene MNPs and its impact on epithelial integrity in human-derived intestinal in vitro model systems. The effect of Microfold (M) cell induction on polystyrene micro- and nanoparticle (MNP) uptake, transcytosis, and potential inflammation was also assessed and compared to samples grown under standard conditions. Microfold (M) cells, link the human intestinal system to the immune system and are the primary cells in the epithelium responsible for sampling and transporting foreign matter of interest from the lumen of the gut to underlying immune cells. Given the uptake capabilities of Microfold cells to interact both specifically and nonspecific to abiotic and biotic materials, it was expected that M- cell induced in vitro samples would have increased binding, localization, and potentially transcytosis of Polystyrene MNLPs across the epithelial barrier. Experimental results of this study would not only help in the evaluation of the plastic toxicity, but would allow for more detailed modeling of gut inflammation and the intestinal immune system.

Keywords: nanoplastics, enteroids, intestinal barrier, tissue engineering, microfold (M) cells

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Authors: Alexander Vandesompele, Joni Dambre

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The diversity in dendritic arborization, as first illustrated by Santiago Ramon y Cajal, has always suggested a role for dendrites in the functionality of neurons. In the past decades, thanks to new recording techniques and optical stimulation methods, it has become clear that dendrites are not merely passive electrical components. They are observed to integrate inputs in a non-linear fashion and actively participate in computations. Regardless, in simulations of neural networks dendritic structure and functionality are often overlooked. Especially in a machine learning context, when designing artificial neural networks, point neuron models such as the leaky-integrate-and-fire (LIF) model are dominant. These models mimic the integration of inputs at the neuron soma, and ignore the existence of dendrites. In this work, the LIF point neuron model is extended with a simple form of dendritic computation. This gives the LIF neuron increased capacity to discriminate spatiotemporal input sequences, a dendritic functionality as observed in another study. Simulations of the spiking neurons are performed using the Bindsnet framework. In the common LIF model, incoming synapses are independent. Here, we introduce a dependency between incoming synapses such that the post-synaptic impact of a spike is not only determined by the weight of the synapse, but also by the activity of other synapses. This is a form of short term plasticity where synapses are potentiated or depressed by the preceding activity of neighbouring synapses. This is a straightforward way to prevent inputs from simply summing linearly at the soma. To implement this, each pair of synapses on a neuron is assigned a variable,representing the synaptic relation. This variable determines the magnitude ofthe short term plasticity. These variables can be chosen randomly or, more interestingly, can be learned using a form of Hebbian learning. We use Spike-Time-Dependent-Plasticity (STDP), commonly used to learn synaptic strength magnitudes. If all neurons in a layer receive the same input, they tend to learn the same through STDP. Adding inhibitory connections between the neurons creates a winner-take-all (WTA) network. This causes the different neurons to learn different input sequences. To illustrate the impact of the proposed dendritic mechanism, even without learning, we attach five input neurons to two output neurons. One output neuron isa regular LIF neuron, the other output neuron is a LIF neuron with dendritic relationships. Then, the five input neurons are allowed to fire in a particular order. The membrane potentials are reset and subsequently the five input neurons are fired in the reversed order. As the regular LIF neuron linearly integrates its inputs at the soma, the membrane potential response to both sequences is similar in magnitude. In the other output neuron, due to the dendritic mechanism, the membrane potential response is different for both sequences. Hence, the dendritic mechanism improves the neuron’s capacity for discriminating spa-tiotemporal sequences. Dendritic computations improve LIF neurons even if the relationships between synapses are established randomly. Ideally however, a learning rule is used to improve the dendritic relationships based on input data. It is possible to learn synaptic strength with STDP, to make a neuron more sensitive to its input. Similarly, it is possible to learn dendritic relationships with STDP, to make the neuron more sensitive to spatiotemporal input sequences. Feeding structured data to a WTA network with dendritic computation leads to a significantly higher number of discriminated input patterns. Without the dendritic computation, output neurons are less specific and may, for instance, be activated by a sequence in reverse order.

Keywords: dendritic computation, spiking neural networks, point neuron model

Procedia PDF Downloads 101

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

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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 285

Authors: Abhisek Chakrabarty, Subhraprakash Mandal

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Flash flood is one of the catastrophic natural hazards in the mountainous region of India. The recent flood in the Mandakini River in Kedarnath (14-17th June, 2013) is a classic example of flash floods that devastated Uttarakhand by killing thousands of people.The disaster was an integrated effect of high intensityrainfall, sudden breach of Chorabari Lake and very steep topography. Every year in Himalayan Region flash flood occur due to intense rainfall over a short period of time, cloud burst, glacial lake outburst and collapse of artificial check dam that cause high flow of river water. In Sikkim-Derjeeling Himalaya one of the probable flash flood occurrence zone is Teesta Watershed. The Teesta River is a right tributary of the Brahmaputra with draining mountain area of approximately 8600 Sq. km. It originates in the Pauhunri massif (7127 m). The total length of the mountain section of the river amounts to 182 km. The Teesta is characterized by a complex hydrological regime. The river is fed not only by precipitation, but also by melting glaciers and snow as well as groundwater. The present study describes an attempt to model surface runoff in upper Teesta basin, which is directly related to catastrophic flood events, by creating a system based on GIS technology. The main object was to construct a direct unit hydrograph for an excess rainfall by estimating the stream flow response at the outlet of a watershed. Specifically, the methodology was based on the creation of a spatial database in GIS environment and on data editing. Moreover, rainfall time-series data collected from Indian Meteorological Department and they were processed in order to calculate flow time and the runoff volume. Apart from the meteorological data, background data such as topography, drainage network, land cover and geological data were also collected. Clipping the watershed from the entire area and the streamline generation for Teesta watershed were done and cross-sectional profiles plotted across the river at various locations from Aster DEM data using the ERDAS IMAGINE 9.0 and Arc GIS 10.0 software. The analysis of different hydraulic model to detect flash flood probability ware done using HEC-RAS, Flow-2D, HEC-HMS Software, which were of great importance in order to achieve the final result. With an input rainfall intensity above 400 mm per day for three days the flood runoff simulation models shows outbursts of lakes and check dam individually or in combination with run-off causing severe damage to the downstream settlements. Model output shows that 313 Sq. km area were found to be most vulnerable to flash flood includes Melli, Jourthang, Chungthang, and Lachung and 655sq. km. as moderately vulnerable includes Rangpo,Yathang, Dambung,Bardang, Singtam, Teesta Bazarand Thangu Valley. The model was validated by inserting the rain fall data of a flood event took place in August 1968, and 78% of the actual area flooded reflected in the output of the model. Lastly preventive and curative measures were suggested to reduce the losses by probable flash flood event.

Keywords: flash flood, GIS, runoff, simulation model, Teesta river basin

Procedia PDF Downloads 281

Authors: Suman Chaudhary, Rupinder K. Kanwar, Jagat R. Kanwar

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Azadirachta indica, also known as Neem belonging to the mahogany family is actively gaining interest in the era of modern day medicine due to its extensive applications in homeopathic medicine such as Ayurveda and Unani. More than 140 phytochemicals have been extracted from neem leaves, seed, bark and flowers for agro-medicinal applications. Among the various components, neem leaf protein (NLP) is currently the most investigated active ingredient, due to its immunomodulatory activities against tumor growth. However, these therapeutic ingredients of neem are susceptible to degradation and cannot withstand the drastic pH changes under physiological environment, and therefore, there is an urgent need of an alternative strategy such as a nano-delivery system to exploit its medicinal benefits. This study hypothesizes that guar gum (GG) derived biodegradable nano-carrier based encapsulation of NLP will improve its stability, specificity and sensitivity, thus facilitating targeted anti-cancer therapeutics. GG is a galactomannan derived from the endosperm of the guar beans seeds. Synthesis of guar nanocapsules (NCs) was performed using nanoprecipitation technique where the GG was encapsulated with NLP. Preliminary experiments conducted to characterize the NCs confirmed spherical morphology with a narrow size distribution of 30-40 nm. Differential scanning colorimetric analysis (DSC) validated the stability of these NCs even at a temperature range of 50-60°C which was well within the physiological and storage conditions. Thermogravimetric (TGA) analysis indicated high decomposition temperature of these NCs ranging upto 350°C. Additionally, Fourier Transform Infrared spectroscopy (FTIR) and the SDS-PAGE data acquired confirmed the successful encapsulation of NLP in the NCs. The anti-cancerous therapeutic property of this NC was tested on colon cancer cells (caco-2) as they are one of the most prevalent form of cancer. These NCs (both NLP loaded and void) were also tested on human intestinal epithelial cells (FHs 74) cells to evaluate their effect on normal cells. Cytotoxicity evaluation of the NCs in the cell lines confirmed that the IC50 for NLP in FHs 74 cells was ~2 fold higher than in caco-2 cells, indicating that this nanoformulation system possessed biocompatible anti-cancerous properties Immunoconfocal microscopy analysis confirmed the time dependent internalization of the NCs within 6h. Recent findings performed using Annexin V and PI staining indicated a significant increase (p ≤ 0.001) in the early and late apoptotic cell population when treated with the NCs signifying the role of NLP in inducing apoptosis in caco-2 cells. This was further validated using Western blot, Polymerase chain reaction (PCR) and Fluorescence activated cell sorter (FACS) aided protein expressional analysis which presented a downregulation of survivin, an anti-apoptotic cell marker and upregulation of Bax/Bcl-2 ratio (pro-apoptotic indicator). Further, both the NLP NC and unencapsulated NLP treatment destabilized the mitochondrial membrane potential subsequently facilitating the release of the pro-apoptotic caspase cascade initiator, cytochrome-c. Future studies will be focused towards granting specificity to these NCs towards cancer cells, along with a comprehensive analysis of the anti-cancer potential of this naturally occurring compound in different cancer and in vivo animal models, will validate the clinical application of this unprecedented protein therapeutic.

Keywords: anti-tumor, guar gum, nanocapsules, neem leaf protein

Procedia PDF Downloads 147

Authors: Robert Miller, Fred Soltero, Sandra Allan, Denise Bonilla

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The Tropical Bont Tick (TBT), Amblyomma variegatum, was introduced to the Caribbean in the mid-1700s. Since it has spread throughout the Caribbean dispersed by cattle egrets (Bubulcus ibis). Tropical Bont Ticks vector many pathogens to livestock and humans. However, only the livestock diseases heartwater, Ehrlichia (Cowdria) ruminantium, and dermatophilosis, Dermatophilus congolensis, are associated with TBT in the Caribbean. African tick bite fever (Rickettsia africae) is widespread in Caribbean TBT but human cases are rare. The Caribbean Amblyomma Programme (CAP) was an effort led by the Food and Agricultural Organization to eradicate TBTs from participating islands. This 10-year effort successfully eradicated TBT from many islands. However, most are reinfested since its termination. Pheromone technology has been developed to aid in TBT control. Although not part of the CAP treatment scheme, this research established that pheromones in combination with pesticide greatly improves treatment efficiencies. Additionally, pheromone combined with CO₂ traps greatly improves active surveillance success. St. Croix has a history of TBT outbreaks. Passive surveillance detected outbreaks in 2016 and in May of 2021. Surveillance efforts are underway to determine the extent of TBT on St Croix. Puerto Rico is the next island in the archipelago and is at a greater risk of re-infestation due to active outbreaks in St Croix. Tropical Bont Ticks were last detected in Puerto Rico in the 1980s. The infestation started on the small Puerto Rican island of Vieques, the closest landmass to St Croix, and spread to the main island through cattle movements. This infestation was eradicated with the help of the Tropical Cattle Tick (TCT), Rhipicephalus (Boophilus) microplus, eradication program. At the time, large percentages of Puerto Rican cattle were treated for ticks along with the necessary material and manpower mobilized for the effort. Therefore, a shift of focus from the TCT to TBT prevented its establishment in Puerto Rico. Currently, no large-scale treatment of TCTs occurs in Puerto Rico. Therefore, the risk of TBT establishment is now greater than it was in the 1980s. From Puerto Rico, the risk of TBT movement to the American continent increases significantly. The establishment of TBTs in the Americas would cause $1.2 billion USD in losses to the livestock industry per year. The USDA Agricultural Research Service recently worked with the USDA Animal Health Inspection Service and the Puerto Rican Department of Agriculture to modernize the management of the TCT. This modernized program uses safer pesticides and has successfully been used to eradicate pesticide-susceptible and -resistant ticks throughout the island. The objective of this work is to prevent the infestation of Puerto Rico by TBTs by combining the current TCT management efforts with TBT surveillance in Vieques. The combined effort is designed to eradicate TCT from Vieques while using the treated cattle as trap animals for TBT using pheromone impregnated tail tags attached to treated animals. Additionally, active surveillance using CO₂-baited traps combined with pheromone will be used to actively survey the environment for free-living TBT. Knowledge gained will inform TBT control efforts in St. Croix.

Keywords: Amblyomma variegatum, caribbean, eradication, Rhipicephalus (boophilus) microplus, pheromone

Procedia PDF Downloads 145