Search results for: probability density function (PDF)
136 Biophysical and Structural Characterization of Transcription Factor Rv0047c of Mycobacterium Tuberculosis H37Rv
Authors: Md. Samsuddin Ansari, Ashish Arora
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Every year 10 million people fall ill with one of the oldest diseases known as tuberculosis, caused by Mycobacterium tuberculosis. The success of M. tuberculosis as a pathogen is because of its ability to persist in host tissues. Multidrug resistance (MDR) mycobacteria cases increase every day, which is associated with efflux pumps controlled at the level of transcription. The transcription regulators of MDR transporters in bacteria belong to one of the following four regulatory protein families: AraC, MarR, MerR, and TetR. Phenolic acid decarboxylase repressor (PadR), like a family of transcription regulators, is closely related to the MarR family. Phenolic acid decarboxylase repressor (PadR) was first identified as a transcription factor involved in the regulation of phenolic acid stress response in various microorganisms (including Mycobacterium tuberculosis H37Rv). Recently research has shown that the PadR family transcription factors are global, multifunction transcription regulators. Rv0047c is a PadR subfamily-1 protein. We are exploring the biophysical and structural characterization of Rv0047c. The Rv0047 gene was amplified by PCR using the primers containing EcoRI and HindIII restriction enzyme sites cloned in pET-NH6 vector and overexpressed in DH5α and BL21 (λDE3) cells of E. coli following purification with Ni2+-NTA column and size exclusion chromatography. We did DSC to know the thermal stability; the Tm (transition temperature) of protein is 55.29ºC, and ΔH (enthalpy change) of 6.92 kcal/mol. Circular dichroism to know the secondary structure and conformation and fluorescence spectroscopy for tertiary structure study of protein. To understand the effect of pH on the structure, function, and stability of Rv0047c we employed spectroscopy techniques such as circular dichroism, fluorescence, and absorbance measurements in a wide range of pH (from pH-2.0 to pH-12). At low and high pH, it shows drastic changes in the secondary and tertiary structure of the protein. EMSA studies showed the specific binding of Rv0047c with its own 30-bp promoter region. To determine the effect of complex formation on the secondary structure of Rv0047c, we examined the CD spectra of the complex of Rv0047c with promoter DNA of rv0047. The functional role of Rv0047c was characterized by over-expressing the Rv0047c gene under the control of hsp60 promoter in Mycobacterium tuberculosis H37Rv. We have predicted the three-dimensional structure of Rv0047c using the Swiss Model and Modeller, with validity checked by the Ramachandra plot. We did molecular docking of Rv0047c with dnaA, through PatchDock following refinement through FireDock. Through this, it is possible to easily identify the binding hot-stop of the receptor molecule with that of the ligand, the nature of the interface itself, and the conformational change undergone by the protein pattern. We are using X-crystallography to unravel the structure of Rv0047c. Overall the studies show that Rv0047c may have transcription regulation along with providing an insight into the activity of Rv0047c in the pH range of subcellular environment and helps to understand the protein-protein interaction, a novel target to kill dormant bacteria and potential strategy for tuberculosis control.Keywords: mycobacterium tuberculosis, phenolic acid decarboxylase repressor, Rv0047c, Circular dichroism, fluorescence spectroscopy, docking, protein-protein interaction
Procedia PDF Downloads 121135 Nursing Experience in Caring for a Patient with Terminal Gastric Cancer and Abdominal Aortic Aneurysm
Authors: Pei-Shan Liang
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Objective: This article explores the nursing experience of caring for a patient with terminal gastric cancer complicated by an abdominal aortic aneurysm. The patient experienced physical discomfort due to the disease, initially unable to accept the situation, leading to anxiety, and eventually accepting the need for surgery. Methods: The nursing period was from June 6 to June 10, 2024. Through observation, direct care, conversations, and physical assessments, and using Gordon's eleven functional health patterns for a one-on-one holistic assessment, interdisciplinary team meetings were held with the critical care team and family. Three nursing health issues were identified: pain related to the disease and invasive procedures, anxiety related to uncertainty about disease recovery, and decreased cardiac tissue perfusion related to hemodynamic instability. Results: Open communication techniques and empathetic care were employed to establish a trusting nurse-patient relationship, and patient-centered nursing interventions were developed. Pain was assessed using a 10-point pain scale, and pain medications were adjusted by a pharmacist. Initially, Fentanyl 500mcg with pump run at 1ml/hr was administered, later changed to Ultracet 37.5mg/325mg, 1 tablet every 6 hours orally, reducing the pain score to 3. Lavender aromatherapy and listening to crystal music were used as distractions to alleviate pain, allowing the patient to sleep uninterrupted for at least 7 hours. The patient was encouraged to express feelings and fears through LINE messages or drawings, and a psychologist was invited to provide support. Family members were present at least twice a day for over an hour each time, reducing psychological distress and uncertainty about the prognosis. According to the Beck Anxiety Inventory, the anxiety score dropped from 17 (moderate anxiety) to 6 (no anxiety). Focused nursing care was implemented with close monitoring of vital signs maintaining systolic blood pressure between 112-118 mmHg to ensure adequate myocardial perfusion. The patient was encouraged to get out of bed for postoperative rehabilitation and to strengthen cardiopulmonary function. A chest X-ray showed no abnormalities, and breathing was smooth with Triflow use, maintaining at least 5 seconds with 2 balls four times a day, and SpO2 >96%. Conclusion: The care process highlighted the importance of addressing psychological care in addition to maintaining life when the patient’s condition changes. The presence of family often provided the greatest source of comfort for the patient, helping to reduce anxiety and pain. Nurses must play multiple roles, including advocate, coordinator, educator, and consultant, using various communication techniques and fostering hope by listening to and accepting the patient’s emotional responses. It is hoped that this report will provide a reference for clinical nursing staff and contribute to improving the quality of care.Keywords: intensive care, gastric cancer, aortic aneurysm, quality of care
Procedia PDF Downloads 24134 Pharmacokinetics and Safety of Pacritinib in Patients with Hepatic Impairment and Healthy Volunteers
Authors: Suliman Al-Fayoumi, Sherri Amberg, Huafeng Zhou, Jack W. Singer, James P. Dean
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Pacritinib is an oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1, and CSF1R. In clinical studies, pacritinib was well tolerated with clinical activity in patients with myelofibrosis. The most frequent adverse events (AEs) observed with pacritinib are gastrointestinal (diarrhea, nausea, and vomiting; mostly grade 1-2 in severity) and typically resolve within 2 weeks. A human ADME mass balance study demonstrated that pacritinib is predominantly cleared via hepatic metabolism and biliary excretion (>85% of administered dose). The major hepatic metabolite identified, M1, is not thought to materially contribute to the pharmacological activity of pacritinib. Hepatic diseases are known to impair hepatic blood flow, drug-metabolizing enzymes, and biliary transport systems and may affect drug absorption, disposition, efficacy, and toxicity. This phase 1 study evaluated the pharmacokinetics (PK) and safety of pacritinib and the M1 metabolite in study subjects with mild, moderate, or severe hepatic impairment (HI) and matched healthy subjects with normal liver function to determine if pacritinib dosage adjustments are necessary for patients with varying degrees of hepatic insufficiency. Study participants (aged 18-85 y) were enrolled into 4 groups based on their degree of HI as defined by Child-Pugh Clinical Assessment Score: mild (n=8), moderate (n=8), severe (n=4), and healthy volunteers (n=8) matched for age, BMI, and sex. Individuals with concomitant renal dysfunction or progressive liver disease were excluded. A single 400 mg dose of pacritinib was administered to all participants. Blood samples were obtained for PK evaluation predose and at multiple time points postdose through 168 h. Key PK parameters evaluated included maximum plasma concentration (Cmax), time to Cmax (Tmax), area under the plasma concentration time curve (AUC) from hour zero to last measurable concentration (AUC0-t), AUC extrapolated to infinity (AUC0-∞), and apparent terminal elimination half-life (t1/2). Following treatment, pacritinib was quantifiable for all study participants at 1 h through 168 h postdose. Systemic pacritinib exposure was similar between healthy volunteers and individuals with mild HI. However, there was a significant difference between those with moderate and severe HI and healthy volunteers with respect to peak concentration (Cmax) and plasma exposure (AUC0-t, AUC0-∞). Mean Cmax decreased by 47% and 57% respectively in participants with moderate and severe HI vs matched healthy volunteers. Similarly, mean AUC0-t decreased by 36% and 45% and mean AUC0-∞ decreased by 46% and 48%, respectively in individuals with moderate and severe HI vs healthy volunteers. Mean t1/2 ranged from 51.5 to 74.9 h across all groups. The variability on exposure ranged from 17.8% to 51.8% across all groups. Systemic exposure of M1 was also significantly decreased in study participants with moderate or severe HI vs. healthy participants and individuals with mild HI. These changes were not significantly dissimilar from the inter-patient variability in these parameters observed in healthy volunteers. All AEs were grade 1-2 in severity. Diarrhea and headache were the only AEs reported in >1 participant (n=4 each). Based on these observations, it is unlikely that dosage adjustments would be warranted in patients with mild, moderate, or severe HI treated with pacritinib.Keywords: pacritinib, myelofibrosis, hepatic impairment, pharmacokinetics
Procedia PDF Downloads 298133 Traditional Practices of Conserving Biodiversity: A Case Study around Jim Corbett National Park, Uttarakhand, India
Authors: Rana Parween, Rob Marchant
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With the continued loss of global biodiversity despite the application of modern conservation techniques, it has become crucial to investigate non-conventional methods. Accelerated destruction of ecosystems due to altered land use, climate change, cultural and social change, necessitates the exploration of society-biodiversity attitudes and links. While the loss of species and their extinction is a well-known and well-documented process that attracts much-needed attention from researchers, academics, government and non-governmental organizations, the loss of traditional ecological knowledge and practices is more insidious and goes unnoticed. The growing availability of 'indirect experiences' such as the internet and media are leading to a disaffection towards nature and the 'Extinction of Experience'. Exacerbated by the lack of documentation of traditional practices and skills, there is the possibility for the 'extinction' of traditional practices and skills before they are fully recognized and captured. India, as a mega-biodiverse country, is also known for its historical conservation strategies entwined in traditional beliefs. Indigenous communities hold skillsets, knowledge, and traditions that have accumulated over multiple generations and may play an important role in conserving biodiversity today. This study explores the differences in knowledge and attitudes towards conserving biodiversity, of three different stakeholder groups living around Jim Corbett National Park, based on their age, traditions, and association with the protected area. A triangulation designed multi-strategy investigation collected qualitative and quantitative data through a questionnaire survey of village elders, the general public, and forest officers. Following an inductive approach to analyzing qualitative data, the thematic content analysis was followed. All coding and analysis were completed using NVivo 11. Although the village elders and some general public had vast amounts of traditional knowledge, most of it was related to animal husbandry and the medicinal value of plants. Village elders were unfamiliar with the concept of the term ‘biodiversity’ albeit their way of life and attitudes ensured that they care for the ecosystem without having the scientific basis underpinning biodiversity conservation. Inherently, village elders were keen to conserve nature; the superimposition of governmental policies without any tangible benefit or consultation was seen as detrimental. Alienating villagers and consequently the village elders who are the reservoirs of traditional knowledge would not only be damaging to the social network of the area but would also disdain years of tried and tested techniques held by the elders. Forest officers advocated for biodiversity and conservation education for women and children. Women, across all groups, when questioned about nature conservation, showed more interest in learning and participation. Biodiversity not only has an ethical and cultural value, but also plays a role in ecosystem function and, thus, provides ecosystem services and supports livelihoods. Therefore, underpinning and using traditional knowledge and incorporating them into programs of biodiversity conservation should be explored with a sense of urgency.Keywords: biological diversity, mega-biodiverse countries, traditional ecological knowledge, society-biodiversity links
Procedia PDF Downloads 105132 Physiological Effects on Scientist Astronaut Candidates: Hypobaric Training Assessment
Authors: Pedro Llanos, Diego García
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This paper is addressed to expanding our understanding of the effects of hypoxia training on our bodies to better model its dynamics and leverage some of its implications and effects on human health. Hypoxia training is a recommended practice for military and civilian pilots that allow them to recognize their early hypoxia signs and symptoms, and Scientist Astronaut Candidates (SACs) who underwent hypobaric hypoxia (HH) exposure as part of a training activity for prospective suborbital flight applications. This observational-analytical study describes physiologic responses and symptoms experienced by a SAC group before, during and after HH exposure and proposes a model for assessing predicted versus observed physiological responses. A group of individuals with diverse Science Technology Engineering Mathematics (STEM) backgrounds conducted a hypobaric training session to an altitude up to 22,000 ft (FL220) or 6,705 meters, where heart rate (HR), breathing rate (BR) and core temperature (Tc) were monitored with the use of a chest strap sensor pre and post HH exposure. A pulse oximeter registered levels of saturation of oxygen (SpO2), number and duration of desaturations during the HH chamber flight. Hypoxia symptoms as described by the SACs during the HH training session were also registered. This data allowed to generate a preliminary predictive model of the oxygen desaturation and O2 pressure curve for each subject, which consists of a sixth-order polynomial fit during exposure, and a fifth or fourth-order polynomial fit during recovery. Data analysis showed that HR and BR showed no significant differences between pre and post HH exposure in most of the SACs, while Tc measures showed slight but consistent decrement changes. All subjects registered SpO2 greater than 94% for the majority of their individual HH exposures, but all of them presented at least one clinically significant desaturation (SpO2 < 85% for more than 5 seconds) and half of the individuals showed SpO2 below 87% for at least 30% of their HH exposure time. Finally, real time collection of HH symptoms presented temperature somatosensory perceptions (SP) for 65% of individuals, and task-focus issues for 52.5% of individuals as the most common HH indications. 95% of the subjects experienced HH onset symptoms below FL180; all participants achieved full recovery of HH symptoms within 1 minute of donning their O2 mask. The current HH study performed on this group of individuals suggests a rapid and fully reversible physiologic response after HH exposure as expected and obtained in previous studies. Our data showed consistent results between predicted versus observed SpO2 curves during HH suggesting a mathematical function that may be used to model HH performance deficiencies. During the HH study, real-time HH symptoms were registered providing evidenced SP and task focusing as the earliest and most common indicators. Finally, an assessment of HH signs of symptoms in a group of heterogeneous, non-pilot individuals showed similar results to previous studies in homogeneous populations of pilots.Keywords: slow onset hypoxia, hypobaric chamber training, altitude sickness, symptoms and altitude, pressure cabin
Procedia PDF Downloads 116131 The Contemporary Format of E-Learning in Teaching Foreign Languages
Authors: Nataliya G. Olkhovik
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Nowadays in the system of Russian higher medical education there have been undertaken initiatives that resulted in focusing on the resources of e-learning in teaching foreign languages. Obviously, the face-to-face communication in foreign languages bears much more advantages in terms of effectiveness in comparison with the potential of e-learning. Thus, we’ve faced the necessity of strengthening the capacity of e-learning via integration of active methods into the process of teaching foreign languages, such as project activity of students. Successful project activity of students should involve the following components: monitoring, control, methods of organizing the student’s activity in foreign languages, stimulating their interest in the chosen project, approaches to self-assessment and methods of raising their self-esteem. The contemporary methodology assumes the project as a specific method, which activates potential of a student’s cognitive function, emotional reaction, ability to work in the team, commitment, skills of cooperation and, consequently, their readiness to verbalize ideas, thoughts and attitudes. Verbal activity in the foreign language is a complex conception that consolidates both cognitive (involving speech) capacity and individual traits and attitudes such as initiative, empathy, devotion, responsibility etc. Once we organize the project activity by the means of e-learning within the ‘Foreign language’ discipline we have to take into consideration all mentioned above characteristics and work out an effective way to implement it into the teaching practice to boost its educational potential. We have integrated into the e-platform Moodle the module of project activity consisting of the following blocks of tasks that lead students to research, cooperate, strive to leadership, chase the goal and finally verbalize their intentions. Firstly, we introduce the project through activating self-activity of students by the tasks of the phase ‘Preparation of the project’: choose the topic and justify it; find out the problematic situation and its components; set the goals; create your team, choose the leader, distribute the roles in your team; make a written report on grounding the validity of your choices. Secondly, in the ‘Planning the project’ phase we ask students to represent the analysis of the problem in terms of reasons, ways and methods of solution and define the structure of their project (here students may choose oral or written presentation by drawing up the claim in the e-platform about their wish, whereas the teacher decides what form of presentation to prefer). Thirdly, the students have to design the visual aids, speech samples (functional phrases, introductory words, keywords, synonyms, opposites, attributive constructions) and then after checking, discussing and correcting with a teacher via the means of Moodle present it in front of the audience. And finally, we introduce the phase of self-reflection that aims to awake the inner desire of students to improve their verbal activity in a foreign language. As a result, by implementing the project activity into the e-platform and project activity, we try to widen the frameworks of a traditional lesson of foreign languages through tapping the potential of personal traits and attitudes of students.Keywords: active methods, e-learning, improving verbal activity in foreign languages, personal traits and attitudes
Procedia PDF Downloads 105130 Company's Orientation and Human Resource Management Evolution in Technological Startup Companies
Authors: Yael Livneh, Shay Tzafrir, Ilan Meshoulam
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Technological startup companies have been recognized as bearing tremendous potential for business and economic success. However, many entrepreneurs who produce promising innovative ideas fail to implement them as successful businesses. A key argument for such failure is the entrepreneurs' lack of competence in adaptation of the relevant level of formality of human resource management (HRM). The purpose of the present research was to examine multiple antecedents and consequences of HRM formality in growing startup companies. A review of the research literature identified two central components of HRM formality: HR control and professionalism. The effect of three contextual predictors was examined. The first was an intra-organizational factor: the development level of the organization. We based on a differentiation between knowledge exploration and knowledge exploitation. At a given time, the organization chooses to focus on a specific mix of these orientations, a choice which requires an appropriate level of HRM formality, in order to efficiently overcome the challenges. It was hypothesized that the mix of orientations of knowledge exploration and knowledge exploitation would predict HRM formality. The second predictor was the personal characteristics the organization's leader. According the idea of blueprint effect of CEO's on HRM, it was hypothesized that the CEO's cognitive style would predict HRM formality. The third contextual predictor was an external organizational factor: the level of investor involvement. By using the agency theory, and based on Transaction Cost Economy, it was hypothesized that the level of investor involvement in general management and HRM would be positively related to the HRM formality. The effect of formality on trust was examined directly and indirectly by the mediation role of procedural justice. The research method included a time-lagged field study. In the first study, data was obtained using three questionnaires, each directed to a different source: CEO, HR position-holder and employees. 43 companies participated in this study. The second study was conducted approximately a year later. Data was recollected using three questionnaires by reapplying the same sample. 41 companies participated in the second study. The organizations samples included technological startup companies. Both studies included 884 respondents. The results indicated consistency between the two studies. HRM formality was predicted by the intra-organizational factor as well as the personal characteristics of the CEO, but not at all by the external organizational context. Specifically, the organizational orientations was the greatest contributor to both components of HRM formality. The cognitive style predicted formality to a lesser extent. The investor's involvement was found not to have any predictive effect on the HRM formality. The results indicated a positive contribution to trust in HRM, mainly via the mediation of procedural justice. This study contributed a new concept for technological startup company development by a mixture of organizational orientation. Practical implications indicated that the level of HRM formality should be matched to that of the company's development. This match should be challenged and adjusted periodically by referring to the organization orientation, relevant HR practices, and HR function characteristics. A relevant matching could enhance further trust and business success.Keywords: control, formality, human resource management, organizational development, professionalism, technological startup company
Procedia PDF Downloads 264129 Permeable Asphalt Pavement as a Measure of Urban Green Infrastructure in the Extreme Events Mitigation
Authors: Márcia Afonso, Cristina Fael, Marisa Dinis-Almeida
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Population growth in cities has led to an increase in the infrastructures construction, including buildings and roadways. This aspect leads directly to the soils waterproofing. In turn, changes in precipitation patterns are developing into higher and more frequent intensities. Thus, these two conjugated aspects decrease the rainwater infiltration into soils and increase the volume of surface runoff. The practice of green and sustainable urban solutions has encouraged research in these areas. The porous asphalt pavement, as a green infrastructure, is part of practical solutions set to address urban challenges related to land use and adaptation to climate change. In this field, permeable pavements with porous asphalt mixtures (PA) have several advantages in terms of reducing the runoff generated by the floods. The porous structure of these pavements, compared to a conventional asphalt pavement, allows the rainwater infiltration in the subsoil, and consequently, the water quality improvement. This green infrastructure solution can be applied in cities, particularly in streets or parking lots to mitigate the floods effects. Over the years, the pores of these pavements can be filled by sediment, reducing their function in the rainwater infiltration. Thus, double layer porous asphalt (DLPA) was developed to mitigate the clogging effect and facilitate the water infiltration into the lower layers. This study intends to deepen the knowledge of the performance of DLPA when subjected to clogging. The experimental methodology consisted on four evaluation phases of the DLPA infiltration capacity submitted to three precipitation events (100, 200 and 300 mm/h) in each phase. The evaluation first phase determined the behavior after DLPA construction. In phases two and three, two 500 g/m2 clogging cycles were performed, totaling a 1000 g/m2 final simulation. Sand with gradation accented in fine particles was used as clogging material. In the last phase, the DLPA was subjected to simple sweeping and vacuuming maintenance. A precipitation simulator, type sprinkler, capable of simulating the real precipitation was developed for this purpose. The main conclusions show that the DLPA has the capacity to drain the water, even after two clogging cycles. The infiltration results of flows lead to an efficient performance of the DPLA in the surface runoff attenuation, since this was not observed in any of the evaluation phases, even at intensities of 200 and 300 mm/h, simulating intense precipitation events. The infiltration capacity under clogging conditions decreased about 7% on average in the three intensities relative to the initial performance that is after construction. However, this was restored when subjected to simple maintenance, recovering the DLPA hydraulic functionality. In summary, the study proved the efficacy of using a DLPA when it retains thicker surface sediments and limits the fine sediments entry to the remaining layers. At the same time, it is guaranteed the rainwater infiltration and the surface runoff reduction and is therefore a viable solution to put into practice in permeable pavements.Keywords: clogging, double layer porous asphalt, infiltration capacity, rainfall intensity
Procedia PDF Downloads 491128 The Analgesic Effect of Electroacupuncture in a Murine Fibromyalgia Model
Authors: Bernice Jeanne Lottering, Yi-Wen Lin
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Introduction: Chronic pain has a definitive lack of objective parameters in the measurement and treatment efficacy of diseases such as Fibromyalgia (FM). Persistent widespread pain and generalized tenderness are the characteristic symptoms affecting a large majority of the global population, particularly females. This disease has indicated a refractory tendency to conventional treatment ventures, largely resultant from a lack of etiological and pathogenic understanding of the disease development. Emerging evidence indicates that the central nervous system (CNS) plays a critical role in the amplification of pain signals and the neurotransmitters associated therewith. Various stimuli have been found to activate the channels existent on nociceptor terminals, thereby actuating nociceptive impulses along the pain pathways. The transient receptor potential vanalloid 1 (TRPV1) channel functions as a molecular integrator for numerous sensory inputs, such as nociception, and was explored in the current study. Current intervention approaches face a multitude challenges, ranging from effective therapeutic interventions to the limitation of pathognomonic criteria resultant from incomplete understanding and partial evidence on the mechanisms of action of FM. It remains unclear whether electroacupuncture (EA) plays an integral role in the functioning of the TRPV1 pathway, and whether or not it can reduce the chronic pain induced by FM. Aims: The aim of this study was to explore the mechanisms underlying the activation and modulation of the TRPV1 channel pathway in a cold stress model of FM applied to a murine model. Furthermore, the effect of EA in the treatment of mechanical and thermal pain, as expressed in FM was also to be investigated. Methods: 18 C57BL/6 wild type and 6 TRPV1 knockout (KO) mice, aged 8-12 weeks, were exposed to an intermittent cold stress-induced fibromyalgia-like pain model, with or without EA treatment at ZusanLi ST36 (2Hz/20min) on day 3 to 5. Von Frey and Hargreaves behaviour tests were implemented in order to analyze the mechanical and thermal pain thresholds on day 0, 3 and 5 in control group (C), FM group (FM), FM mice with EA treated group (FM + EA) and FM in KO group. Results: An increase in mechanical and thermal hyperalgesia was observed in the FM, EA and KO groups when compared to the control group. This initial increase was reduced in the EA group, which directs focus at the treatment efficacy of EA in nociceptive sensitization, and the analgesic effect EA has attenuating FM associated pain. Discussion: An increase in the nociceptive sensitization was observed through higher withdrawal thresholds in the von Frey mechanical test and the Hargreaves thermal test. TRPV1 function in mice has been scientifically associated with these nociceptive conduits, and the increased behaviour test results suggest that TRPV1 upregulation is central to the FM induced hyperalgesia. This data was supported by the decrease in sensitivity observed in results of the TRPV1 KO group. Moreover, the treatment of EA showed a decrease in this FM induced nociceptive sensitization, suggesting TRPV1 upregulation and overexpression can be attenuated by EA at bilateral ST36. This evidence compellingly implies that the analgesic effect of EA is associated with TRPV1 downregulation.Keywords: fibromyalgia, electroacupuncture, TRPV1, nociception
Procedia PDF Downloads 139127 Comparison of Nutritional Status of Asthmatic vs Non-asthmatic Adults
Authors: Ayesha Mushtaq
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Asthma is a pulmonary disease in which blockade of the airway takes place due to inflammation as a response to certain allergens. Breathing troubles, cough, and dyspnea are one of the few symptoms. Several studies have indicated a significant effect on asthma due to changes in dietary routines. Certain food items, such as oily foods and other materials, are known to cause an increase in the symptoms of asthma. Low dietary intake of fruits and vegetables may be important in relation to asthma prevalence. The objective of this study is to assess and compare the nutritional status of asthmatic and non-asthmatic patients. The significance of this study lies in the factor that it will help nutritionists to arrange a feasible dietary routine for asthmatic patients. This research was conducted at the Pulmonology Department of the Pakistan Institute of Medical Science Islamabad. About thirty hundred thirty-four million people are affected by asthma worldwide. Pakistan is on the verge of being an uplifted urban population and asthma cases are increasingly high these days. Several studies suggest an increase in the Asthmatic patient population due to improper diet. Other studies conducted at different institutions have conducted research on similar topics. These studies have suggested that there is a substantial alteration in the nutritional status of asthmatic and non-Asthmatic patients. This is a cross-sectional study aimed at assessing the nutritious standing of Asthmatic and non-asthmatic patients. This research took place at the Pakistan Institute of Medical Sciences (PIMS), Islamabad, Pakistan. The research included asthmatic and non-asthmatic patients coming to the pulmonology department clinic at the Pakistan Institute of Medical Sciences (PIMS). These patients were aged between 20-60 years. A questionnaire was developed for these patients to estimate their dietary plans in these patients. The methodology included four sections. The first section was the Socio-Demographic profile, which included age, gender, monthly income and occupation. The next section was anthropometric measurements which included the weight, height and body mass index (BMI) of the individual. The next section, section three, was about the biochemical attributes, such as for biochemical profiling, pulmonary function testing (PFT) was performed. In the next section, Dietary habits, which were assessed by using a food frequency questionnaire (FFQ) through food habits and consumption pattern, was assessed. The next section life style data, in which the person's level of physical activity, sleep and smoking habits were assessed. The next section was statistical analysis. All the data obtained from the study were statistically analyzed and assessed. Most of the asthma Patients were females, with weight more than normal or even obese. Body Mass Index (BMI) was higher in asthma Patients than those in non-Asthmatic ones. When the nutritional Values were assessed, we came to know that these patients were low on certain nutrients and their diet included more junk and oily food than healthy vegetables and fruits. Beverages intake was also included in the same assessment. It is evident from this study that nutritional status has a contributory effect on asthma. So, patients on the verge of developing asthma or those who have developed asthma should focus on their diet, maintain good eating habits and take healthy diets, including fruits and vegetables rather than oily foods. Proper sleep may also contribute to the control of asthma.Keywords: NUTRI, BMI, asthma, food
Procedia PDF Downloads 70126 A Long-Standing Methodology Quest Regarding Commentary of the Qur’an: Modern Debates on Function of Hermeneutics in the Quran Scholarship in Turkey
Authors: Merve Palanci
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This paper aims to reveal and analyze methodology debates on Qur’an Commentary in Turkish Scholarship and to make sound inductions on the current situation, with reference to the literature evolving around the credibility of Hermeneutics when the case is Qur’an commentary and methodological connotations related to it, together with the other modern approaches to the Qur’an. It is fair to say that Tafseer, constituting one of the main parts of basic Islamic sciences, has drawn great attention from both Muslim and non-Muslim scholars for a long time. And with the emplacement of an acute junction between natural sciences and social sciences in the post-enlightenment period, this interest seems to pave the way for methodology discussions that are conducted by theology spheres, occupying a noticeable slot in Tafseer literature, as well. A panoramic glance at the classical treatise in relation to the methodology of Tafseer, namely Usul al-Tafseer, leads the reader to the conclusion that these classics are intrinsically aimed at introducing the Qur’an and its early history of formation as a corpus and providing a better understanding of its content. To illustrate, the earliest methodology work extant for Qur’an commentary, al- Aql wa’l Fahm al- Qur’an by Harith al-Muhasibi covers content that deals with Qur’an’s rhetoric, its muhkam and mutashabih, and abrogation, etc. And most of the themes in question are evident to share a common ground: understanding the Scripture and producing an accurate commentary to be built on this preliminary phenomenon of understanding. The content of other renowned works in an overtone of Tafseer methodology, such as Funun al Afnan, al- Iqsir fi Ilm al- Tafseer, and other succeeding ones al- Itqan and al- Burhan is also rich in hints related to preliminary phenomena of understanding. However, these works are not eligible for being classified as full-fledged methodology manuals assuring a true understanding of the Qur’an. And Hermeneutics is believed to supply substantial data applicable to Qur’an commentary as it deals with the nature of understanding itself. Referring to the latest tendencies in Tafseer methodology, this paper envisages to centralize hermeneutical debates in modern scholarship of Qur’an commentary and the incentives that lead scholars to apply for Hermeneutics in Tafseer literature. Inspired from these incentives, the study involves three parts. In the introduction part, this paper introduces key features of classical methodology works in general terms and traces back the main methodological shifts of modern times in Qur’an commentary. To this end, revisionist Ecole, scientific Qur’an commentary ventures, and thematic Qur’an commentary are included and analysed briefly. However, historical-critical commentary on the Quran, as it bears a close relationship with hermeneutics, is handled predominantly. The second part is based on the hermeneutical nature of understanding the Scripture, revealing a timeline for the beginning of hermeneutics debates in Tafseer, and Fazlur Rahman’s(d.1988) influence will be manifested for establishing a theoretical bridge. In the following part, reactions against the application of Hermeneutics in Tafseer activity and pro-hermeneutics works will be revealed through cross-references to the prominent figures of both, and the literature in question in theology scholarship in Turkey will be explored critically.Keywords: hermeneutics, Tafseer, methodology, Ulum al- Qur’an, modernity
Procedia PDF Downloads 75125 Isolation and Transplantation of Hepatocytes in an Experimental Model
Authors: Inas Raafat, Azza El Bassiouny, Waldemar L. Olszewsky, Nagui E. Mikhail, Mona Nossier, Nora E. I. El-Bassiouni, Mona Zoheiry, Houda Abou Taleb, Noha Abd El-Aal, Ali Baioumy, Shimaa Attia
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Background: Orthotopic liver transplantation is an established treatment for patients with severe acute and end-stage chronic liver disease. The shortage of donor organs continues to be the rate-limiting factor for liver transplantation throughout the world. Hepatocyte transplantation is a promising treatment for several liver diseases and can, also, be used as a "bridge" to liver transplantation in cases of liver failure. Aim of the work: This study was designed to develop a highly efficient protocol for isolation and transplantation of hepatocytes in experimental Lewis rat model to provide satisfactory guidelines for future application on humans.Materials and Methods: Hepatocytes were isolated from the liver by double perfusion technique and bone marrow cells were isolated by centrifugation of shafts of tibia and femur of donor Lewis rats. Recipient rats were subjected to sub-lethal dose of irradiation 2 days before transplantation. In a laparotomy operation the spleen was injected by freshly isolated hepatocytes and bone marrow cells were injected intravenously. The animals were sacrificed 45 day latter and splenic sections were prepared and stained with H & E, PAS AFP and Prox1. Results: The data obtained from this study showed that the double perfusion technique is successful in separation of hepatocytes regarding cell number and viability. Also the method used for bone marrow cells separation gave excellent results regarding cell number and viability. Intrasplenic engraftment of hepatocytes and live tissue formation within the splenic tissue were found in 70% of cases. Hematoxylin and eosin stained splenic sections from 7 rats showed sheets and clusters of cells among the splenic tissues. Periodic Acid Schiff stained splenic sections from 7 rats showed clusters of hepatocytes with intensely stained pink cytoplasmic granules denoting the presence of glycogen. Splenic sections from 7 rats stained with anti-α-fetoprotein antibody showed brownish cytoplasmic staining of the hepatocytes denoting positive expression of AFP. Splenic sections from 7 rats stained with anti-Prox1 showed brownish nuclear staining of the hepatocytes denoting positive expression of Prox1 gene on these cells. Also, positive expression of Prox1 gene was detected on lymphocytes aggregations in the spleens. Conclusions: Isolation of liver cells by double perfusion technique using collagenase buffer is a reliable method that has a very satisfactory yield regarding cell number and viability. The intrasplenic route of transplantation of the freshly isolated liver cells in an immunocompromised model was found to give good results regarding cell engraftment and tissue formation. Further studies are needed to assess function of engrafted hepatocytes by measuring prothrombin time, serum albumin and bilirubin levels.Keywords: Lewis rats, hepatocytes, BMCs, transplantation, AFP, Prox1
Procedia PDF Downloads 317124 The Gender Criteria of Film Criticism: Creating the ‘Big’, Avoiding the Important
Authors: Eleni Karasavvidou
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Social and anthropological research, parallel to Gender Studies, highlighted the relationship between social structures and symbolic forms as an important field of interaction and recording of 'social trends.' Since the study of representations can contribute to the understanding of the social functions and power relations, they encompass. This ‘mirage,’ however, has not only to do with the representations themselves but also with the ways they are received and the film or critical narratives that are established as dominant or alternative. Cinema and the criticism of its cultural products are no exception. Even in the rapidly changing media landscape of the 21st century, movies remain an integral and widespread part of popular culture, making films an extremely powerful means of 'legitimizing' or 'delegitimizing' visions of domination and commonsensical gender stereotypes throughout society. And yet it is film criticism, the 'language per se,' that legitimizes, reinforces, rewards and reproduces (or at least ignores) the stereotypical depictions of female roles that remain common in the realm of film images. This creates the need for this issue to have emerged (also) in academic research questioning gender criteria in film reviews as part of the effort for an inclusive art and society. Qualitative content analysis is used to examine female roles in selected Oscar-nominated films against their reviews from leading websites and newspapers. This method was chosen because of the complex nature of the depictions in the films and the narratives they evoke. The films were divided into basic scenes depicting social functions, such as love and work relationships, positions of power and their function, which were analyzed by content analysis, with borrowings from structuralism (Gennette) and the local/universal images of intercultural philology (Wierlacher). In addition to the measurement of the general ‘representation-time’ by gender, other qualitative characteristics were also analyzed, such as: speaking time, sayings or key actions, overall quality of the character's action in relation to the development of the scenario and social representations in general, as well as quantitatively (insufficient number of female lead roles, fewer key supporting roles, relatively few female directors and people in the production chain and how they might affect screen representations. The quantitative analysis in this study was used to complement the qualitative content analysis. Then the focus shifted to the criteria of film criticism and to the rhetorical narratives that exclude or highlight in relation to gender identities and functions. In the criteria and language of film criticism, stereotypes are often reproduced or allegedly overturned within the framework of apolitical "identity politics," which mainly addresses the surface of a self-referential cultural-consumer product without connecting it more deeply with the material and cultural life. One of the prime examples of this failure is the Bechtel Test, which tracks whether female characters speak in a film regardless of whether women's stories are represented or not in the films analyzed. If perceived unbiased male filmmakers still fail to tell truly feminist stories, the same is the case with the criteria of criticism and the related interventions.Keywords: representations, context analysis, reviews, sexist stereotypes
Procedia PDF Downloads 83123 Harnessing Nature's Fury: Hyptis Suaveolens Loaded Bioactive Liposome for Photothermal Therapy of Lung Cancer
Authors: Sajmina Khatun, Monika Pebam, Aravind Kumar Rengan
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Photothermal therapy, a subset of nanomedicine, takes advantage of light-absorbing agents to generate localized heat, selectively eradicating cancer cells. This innovative approach minimizes damage to healthy tissues and offers a promising avenue for targeted cancer treatment. Unlike conventional therapies, photothermal therapy harnesses the power of light to combat malignancies precisely and effectively, showcasing its potential to revolutionize cancer treatment paradigms. The combined strengths of nanomedicine and photothermal therapy signify a transformative shift toward more effective, targeted, and tolerable cancer treatments in the medical landscape. Utilizing natural products becomes instrumental in formulating diverse bioactive medications owing to their various pharmacological properties attributed to the existence of phenolic structures, triterpenoids, and similar compounds. Hyptis suaveolens, commonly known as pignut, stands as an aromatic herb within the Lamiaceae family and represents a valuable therapeutic plant. Flourishing in swamps and alongside tropical and subtropical roadsides, these noxious weeds impede the development of adjacent plants. Hyptis suaveolens ranks among the most globally distributed alien invasive species. The present investigation revealed that a versatile, biodegradable liposome nanosystem (HIL NPs), incorporating bioactive molecules from Hyptis suaveolens, exhibits effective bioavailability to cancer cells, enabling tumor ablation upon near-infrared (NIR) laser exposure. The components within the nanosystem, specifically the bioactive molecules from Hyptis, function as anticancer agents, aiding in the photothermal ablation of highly metastatic lung cancer cells. Despite being a prolific weed impeding neighboring plant growth, Hyptis suaveolens showcases therapeutic benefits through its bioactive compounds. The obtained HIL NPs, characterized as a photothermally active liposome nanosystem, demonstrate a pronounced fluorescence absorption peak in the NIR range and achieve a high photothermal conversion efficiency under NIR laser irradiation. Transmission electron microscopy (TEM) and particle size analysis reveal that HIL NPs possess a spherical shape with a size of 141 ± 30 nm. Moreover, in vitro assessments of HIL NPs against lung cancer cell lines (A549) indicate effective anticancer activity through a combined cytotoxic effect and hyperthermia. Tumor ablation is facilitated by apoptosis induced by the overexpression of ɣ-H2AX, arresting cancer cell proliferation. Consequently, the multifunctional and biodegradable nanosystem (HIL NPs), incorporating bioactive compounds from Hyptis, provides valuable perspectives for developing an innovative therapeutic strategy originating from a challenging weed. This approach holds promise for potential applications in both bioimaging and the combined use of phyto-photothermal therapy for cancer treatment.Keywords: bioactive liposome, hyptis suaveolens, photothermal therapy, lung cancer
Procedia PDF Downloads 94122 COVID-19’s Impact on the Use of Media, Educational Performance, and Learning in Children and Adolescents with ADHD Who Engaged in Virtual Learning
Authors: Christina Largent, Tazley Hobbs
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Objective: A literature review was performed to examine the existing research on COVID-19 lockdown as it relates to ADHD child/adolescent individuals, media use, and impact on educational performance/learning. It was surmised that with the COVID-19 shut-down and transition to remote learning, a less structured learning environment, increased screen time, in addition to potential difficulty accessing school resources would impair ADHD individuals’ performance and learning. A resulting increase in the number of youths diagnosed and treated for ADHD would be expected. As of yet, there has been little to no published data on the incidence of ADHD as it relates to COVID-19 outside of reports from several nonprofit agencies such as CHADD (Children and Adults with Attention-Deficit/Hyperactivity Disorder ), who reported an increased number of calls to their helpline, The New York based Child Mind Institute, who reported an increased number of appointments to discuss medications, and research released from Athenahealth showing an increase in the number of patients receiving new diagnosis of ADHD and new prescriptions for ADHD medications. Methods: A literature search for articles published between 2020 and 2021 from Pubmed, Google Scholar, PsychInfo, was performed. Search phrases and keywords included “covid, adhd, child, impact, remote learning, media, screen”. Results: Studies primarily utilized parental reports, with very few from the perspective of the ADHD individuals themselves. Most findings thus far show that with the COVID-19 quarantine and transition to online learning, ADHD individuals’ experienced decreased ability to keep focused or adhere to the daily routine, as well as increased inattention-related problems, such as careless mistakes or lack of completion in homework, which in turn translated into overall more difficulty with remote learning. To add further injury, one study showed (just on evaluation of two different sites within the US) that school based services for these individuals decreased with the shift to online-learning. Increased screen time, television, social media, and gaming were noted amongst ADHD individuals. One study further differentiated the degree of digital media, identifying individuals with “problematic “ or “non-problematic” use. ADHD children with problematic digital media use suffered from more severe core symptoms of ADHD, negative emotions, executive function deficits, damage to family environment, pressure from life events, and a lower motivation to learn. Conclusions and Future Considerations: Studies found not only was online learning difficult for ADHD individuals but it, in addition to greater use of digital media, was associated with worsening ADHD symptoms impairing schoolwork, in addition to secondary findings of worsening mood and behavior. Currently, data on the number of new ADHD cases, in addition to data on the prescription and usage of stimulants during COVID-19, has not been well documented or studied; this would be well-warranted out of concern for over diagnosing or over-prescribing our youth. It would also be well-worth studying how reversible or long-lasting these negative impacts may be.Keywords: COVID-19, remote learning, media use, ADHD, child, adolescent
Procedia PDF Downloads 124121 Endometrial Ablation and Resection Versus Hysterectomy for Heavy Menstrual Bleeding: A Systematic Review and Meta-Analysis of Effectiveness and Complications
Authors: Iliana Georganta, Clare Deehan, Marysia Thomson, Miriam McDonald, Kerrie McNulty, Anna Strachan, Elizabeth Anderson, Alyaa Mostafa
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Context: A meta-analysis of randomized controlled trials (RCTs) comparing hysterectomy versus endometrial ablation and resection in the management of heavy menstrual bleeding. Objective: To evaluate the clinical efficacy, satisfaction rates and adverse events of hysterectomy compared to more minimally invasive techniques in the treatment of HMB. Evidence Acquisition: A literature search was performed for all RCTs and quasi-RCTs comparing hysterectomy with either endometrial ablation endometrial resection of both. The search had no language restrictions and was last updated in June 2020 using MEDLINE, EMBASE, Cochrane Central Register of Clinical Trials, PubMed, Google Scholar, PsycINFO, Clinicaltrials.gov and Clinical trials. EU. In addition, a manual search of the abstract databases of the European Haemophilia Conference on women's health was performed and further studies were identified from references of acquired papers. The primary outcomes were patient-reported and objective reduction in heavy menstrual bleeding up to 2 years and after 2 years. Secondary outcomes included satisfaction rates, pain, adverse events short and long term, quality of life and sexual function, further surgery, duration of surgery and hospital stay and time to return to work and normal activities. Data were analysed using RevMan software. Evidence synthesis: 12 studies and a total of 2028 women were included (hysterectomy: n = 977 women vs endometrial ablation or resection: n = 1051 women). Hysterectomy was compared with endometrial ablation only in five studies (Lin, Dickersin, Sesti, Jain, Cooper) and endometrial resection only in five studies (Gannon, Schulpher, O’Connor, Crosignani, Zupi) and a mixture of the Ablation and Resection in two studies (Elmantwe, Pinion). Of the 1² studies, 10 reported women’s perception of bleeding symptoms as improved. Meta-analysis showed that women in the hysterectomy group were more likely to show improvement in bleeding symptoms when compared with endometrial ablation or resection up to 2-year follow-up (RR 0.75, 95% CI 0.71 to 0.79, I² = 95%). Objective outcomes of improvement in bleeding also favored hysterectomy. Patient satisfaction was higher after hysterectomy within the 2 years follow-up (RR: 0.90, 95%CI: 0.86 to 0.94, I²:58%), however, there was no significant difference between the two groups at more than 2 years follow up. Sepsis (RR: 0.03, 95% CI 0.002 to 0.56; 1 study), wound infection (RR: 0.05, 95% CI: 0.01 to 0.28, I²: 0%, 3 studies) and Urinary tract infection (UTI) (RR: 0.20, 95% CI: 0.10 to 0.42, I²: 0%, 4 studies) all favoured hysteroscopic techniques. Fluid overload (RR: 7.80, 95% CI: 2.16 to 28.16, I² :0%, 4 studies) and perforation (RR: 5.42, 95% CI: 1.25 to 23.45, I²: 0%, 4 studies) however favoured hysterectomy in the short term. Conclusions: This meta-analysis has demonstrated that endometrial ablation and endometrial resection are both viable options when compared with hysterectomy for the treatment of heavy menstrual bleeding. Hysteroscopic procedures had better outcomes in the short term with fewer adverse events including wound infection, UTI and sepsis. The hysterectomy performed better when measuring more long-term impacts such as recurrence of symptoms, overall satisfaction at two years and the need for further treatment or surgery.Keywords: menorrhagia, hysterectomy, ablation, resection
Procedia PDF Downloads 155120 Formulation and Optimization of Self Nanoemulsifying Drug Delivery System of Rutin for Enhancement of Oral Bioavailability Using QbD Approach
Authors: Shrestha Sharma, Jasjeet K. Sahni, Javed Ali, Sanjula Baboota
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Introduction: Rutin is a naturally occurring strong antioxidant molecule belonging to bioflavonoid category. Due to its free radical scavenging properties, it has been found to be beneficial in the treatment of various diseases including inflammation, cancer, diabetes, allergy, cardiovascular disorders and various types of microbial infections. Despite its beneficial effects, it suffers from the problem of low aqueous solubility which is responsible for low oral bioavailability. The aim of our study was to optimize and characterize self-nanoemulsifying drug delivery system (SNEDDS) of rutin using Box-Behnken design (BBD) combined with a desirability function. Further various antioxidant, pharmacokinetic and pharmacodynamic studies were performed for the optimized rutin SNEDDS formulation. Methodologies: Selection of oil, surfactant and co-surfactant was done on the basis of solubility/miscibility studies. Sefsol+ Vitamin E, Solutol HS 15 and Transcutol P were selected as oil phase, surfactant and co-surfactant respectively. Optimization of SNEDDS formulations was done by a three-factor, three-level (33)BBD. The independent factors were Sefsol+ Vitamin E, Solutol HS15, and Transcutol P. The dependent variables were globule size, self emulsification time (SEF), % transmittance and cumulative percentage drug released. Various response surface graphs and contour plots were constructed to understand the effect of different factor, their levels and combinations on the responses. The optimized Rutin SNEDDS formulation was characterized for various parameters such as globule size, zeta potential, viscosity, refractive index , % Transmittance and in vitro drug release. Ex vivo permeation studies and pharmacokinetic studies were performed for optimized formulation. Antioxidant activity was determined by DPPH and reducing power assays. Anti-inflammatory activity was determined by using carrageenan induced rat paw oedema method. Permeation of rutin across small intestine was assessed using confocal laser scanning microscopy (CLSM). Major findings:The optimized SNEDDS formulation consisting of Sefsol+ Vitamin E - Solutol HS15 -Transcutol HP at proportions of 25:35:17.5 (w/w) was prepared and a comparison of the predicted values and experimental values were found to be in close agreement. The globule size and PDI of optimized SNEDDS formulation was found to be 16.08 ± 0.02 nm and 0.124±0.01 respectively. Significant (p˂0.05) increase in percentage drug release was achieved in the case of optimized SNEDDS formulation (98.8 %) as compared to rutin suspension. Furthermore, pharmacokinetic study showed a 2.3-fold increase in relative oral bioavailability compared with that of the suspension. Antioxidant assay results indicated better efficacy of the developed formulation than the pure drug and it was found to be comparable with ascorbic acid. The results of anti-inflammatory studies showed 72.93 % inhibition for the SNEDDS formulation which was significantly higher than the drug suspension 46.56%. The results of CLSM indicated that the absorption of SNEDDS formulation was considerably higher than that from rutin suspension. Conclusion: Rutin SNEDDS have been successfully prepared and they can serve as an effective tool in enhancing oral bioavailability and efficacy of Rutin.Keywords: rutin, oral bioavilability, pharamacokinetics, pharmacodynamics
Procedia PDF Downloads 500119 Anti-tuberculosis, Resistance Modulatory, Anti-pulmonary Fibrosis and Anti-silicosis Effects of Crinum Asiaticum Bulbs and Its Active Metabolite, Betulin
Authors: Theophilus Asante, Comfort Nyarko, Daniel Antwi
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Drug-resistant tuberculosis, together with the associated comorbidities like pulmonary fibrosis and silicosis, has been one of the most serious global public health threats that requires immediate action to curb or mitigate it. This prolongs hospital stays, increases the cost of medication, and increases the death toll recorded annually. Crinum asiaticum bulb (CAE) and betulin (BET) are known for their biological and pharmacological effects. Pharmacological effects reported on CAE include antimicrobial, anti-inflammatory, anti-pyretic, anti-analgesic, and anti-cancer effects. Betulin has exhibited a multitude of powerful pharmacological properties ranging from antitumor, anti-inflammatory, anti-parasitic, anti-microbial, and anti-viral activities. This work sought to investigate the anti-tuberculosis and resistant modulatory effects and also assess their effects on mitigating pulmonary fibrosis and silicosis. In the anti-tuberculosis and resistant modulatory effects, both CAE and BET showed strong antimicrobial activities (31.25 ≤ MIC ≤ 500) µg/ml against the studied microorganisms and also produced significant anti-efflux pump and biofilm inhibitory effects (ρ < 0.0001) as well as exhibiting resistance modulatory and synergistic effects when combined with standard antibiotics. Crinum asiaticum bulbs extract and betulin were shown to possess anti-pulmonary fibrosis effects. There was an increased survival rate in the CAE and BET treatment groups compared to the BLM-induced group. There was a marked decrease in the levels of hydroxyproline and collagen I and III in the CAE and BET treatment groups compared to the BLM-treated group. The treatment groups of CAE and BET significantly downregulated the levels of pro-fibrotic and pro-inflammatory cytokine concentrations such as TGF-β1, MMP9, IL-6, IL-1β and TNF-alpha compared to an increase in the BLM-treated groups. The histological findings of the lungs suggested the curative effects of CAE and BET following BLM-induced pulmonary fibrosis in mice. The study showed improved lung functions with a wide focal area of viable alveolar spaces and few collagen fibers deposition on the lungs of the treatment groups. In the anti-silicosis and pulmonoprotective effects of CAE and BET, the levels of NF-κB, TNF-α, IL-1β, IL-6 and hydroxyproline, collagen types I and III were significantly reduced by CAE and BET (ρ < 0.0001). Both CAE and BET significantly (ρ < 0.0001) inhibited the levels of hydroxyproline, collagen I and III when compared with the negative control group. On BALF biomarkers such as macrophages, lymphocytes, monocytes, and neutrophils, CAE and BET were able to reduce their levels significantly (ρ < 0.0001). The CAE and BET were examined for anti-oxidant activity and shown to raise the levels of catalase (CAT) and superoxide dismutase (SOD) while lowering the level of malondialdehyde (MDA). There was an improvement in lung function when lung tissues were examined histologically. Crinum asiaticum bulbs extract and betulin were discovered to exhibit anti-tubercular and resistance-modulatory properties, as well as the capacity to minimize TB comorbidities such as pulmonary fibrosis and silicosis. In addition, CAE and BET may act as protective mechanisms, facilitating the preservation of the lung's physiological integrity. The outcomes of this study might pave the way for the development of leads for producing single medications for the management of drug-resistant tuberculosis and its accompanying comorbidities.Keywords: fibrosis, crinum, tuberculosis, antiinflammation, drug resistant
Procedia PDF Downloads 83118 Impact of Urban Migration on Caste: Rohinton Mistry’s a Fine Balance and Rural-to-Urban Caste Migration in India
Authors: Mohua Dutta
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The primary aim of this research paper is to investigate the forced urban migration of Dalits in India who are fleeing caste persecution in rural areas. This paper examines the relationship between caste and rural-to-urban internal migration in India using a literary text, Rohinton Mistry’s A Fine Balance, highlighting the challenges faced by Dalits in rural areas that force them to migrate to urban areas. Despite the prevalence of such discussions in Dalit autobiographies written in vernacular languages, there is a lack of discussion regarding caste migration in Indian English Literature, including this present text, as evidenced by the existing critical interpretations of the novel, which this paper seeks to rectify. The primary research question is how urban migration affects caste system in India and why rural-to-urban caste migration occurs. The purpose of this paper is to better understand the reasons for Dalit migration, the challenges they face in rural and urban areas, and the lingering influence of caste in both rural and urban areas. The study reveals that the promise of mobility and emancipation provided by class operations drives rural-to-urban caste migration in India, but it also reveals that caste marginalization in rural areas is closely linked to class marginalization and other forms of subalternity in urban areas. Moreover, the caste system persists in urban areas as well, making Dalit migrants more vulnerable to social, political, and economic discrimination. The reason for this is that, despite changes in profession and urban migration, the trapped structure of caste capital and family networks exposes migrants to caste and class oppressions. To reach its conclusion, this study employs a variety of methodologies. Discourse analysis is used to investigate the current debates and narratives surrounding caste migration. Critical race theory, specifically intersectional theory and social constructivism, aids in comprehending the complexities of caste, class, and migration. Mistry's novel is subjected to textual analysis in order to identify and interpret references to caste migration. Secondary data, such as theoretical understanding of the caste system in operation and scholarly works on caste migration, are also used to support and strengthen the findings and arguments presented in the paper. The study concludes that rural-to-urban caste migration in India is primarily motivated by the promise of socioeconomic mobility and emancipation offered by urban spaces. However, the caste system persists in urban areas, resulting in the continued marginalisation and discrimination of Dalit migrants. The study also highlights the limitations of urban migration in providing true emancipation for Dalit migrants, as they remain trapped within caste and family network structures. Overall, the study raises awareness of the complexities surrounding caste migration and its impact on the lives of India's marginalised communities. This study contributes to the field of Migration Studies by shedding light on an often-overlooked issue: Dalit migration. It challenges existing literary critical interpretations by emphasising the significance of caste migration in Indian English Literature. The study also emphasises the interconnectedness of caste and class, broadening understanding of how these systems function in both rural and urban areas.Keywords: rural-to-urban caste migration in india, internal migration in india, caste system in india, dalit movement in india, rooster coop of caste and class, urban poor as subalterns
Procedia PDF Downloads 72117 Feasibility of Applying a Hydrodynamic Cavitation Generator as a Method for Intensification of Methane Fermentation Process of Virginia Fanpetals (Sida hermaphrodita) Biomass
Authors: Marcin Zieliński, Marcin Dębowski, Mirosław Krzemieniewski
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The anaerobic degradation of substrates is limited especially by the rate and effectiveness of the first (hydrolytic) stage of fermentation. This stage may be intensified through pre-treatment of substrate aimed at disintegration of the solid phase and destruction of substrate tissues and cells. The most frequently applied criterion of disintegration outcomes evaluation is the increase in biogas recovery owing to the possibility of its use for energetic purposes and, simultaneously, recovery of input energy consumed for the pre-treatment of substrate before fermentation. Hydrodynamic cavitation is one of the methods for organic substrate disintegration that has a high implementation potential. Cavitation is explained as the phenomenon of the formation of discontinuity cavities filled with vapor or gas in a liquid induced by pressure drop to the critical value. It is induced by a varying field of pressures. A void needs to occur in the flow in which the pressure first drops to the value close to the pressure of saturated vapor and then increases. The process of cavitation conducted under controlled conditions was found to significantly improve the effectiveness of anaerobic conversion of organic substrates having various characteristics. This phenomenon allows effective damage and disintegration of cellular and tissue structures. Disintegration of structures and release of organic compounds to the dissolved phase has a direct effect on the intensification of biogas production in the process of anaerobic fermentation, on reduced dry matter content in the post-fermentation sludge as well as a high degree of its hygienization and its increased susceptibility to dehydration. A device the efficiency of which was confirmed both in laboratory conditions and in systems operating in the technical scale is a hydrodynamic generator of cavitation. Cavitators, agitators and emulsifiers constructed and tested worldwide so far have been characterized by low efficiency and high energy demand. Many of them proved effective under laboratory conditions but failed under industrial ones. The only task successfully realized by these appliances and utilized on a wider scale is the heating of liquids. For this reason, their usability was limited to the function of heating installations. Design of the presented cavitation generator allows achieving satisfactory energy efficiency and enables its use under industrial conditions in depolymerization processes of biomass with various characteristics. Investigations conducted on the laboratory and industrial scale confirmed the effectiveness of applying cavitation in the process of biomass destruction. The use of the cavitation generator in laboratory studies for disintegration of sewage sludge allowed increasing biogas production by ca. 30% and shortening the treatment process by ca. 20 - 25%. The shortening of the technological process and increase of wastewater treatment plant effectiveness may delay investments aimed at increasing system output. The use of a mechanical cavitator and application of repeated cavitation process (4-6 times) enables significant acceleration of the biogassing process. In addition, mechanical cavitation accelerates increases in COD and VFA levels.Keywords: hydrodynamic cavitation, pretreatment, biomass, methane fermentation, Virginia fanpetals
Procedia PDF Downloads 435116 Effects on Inflammatory Biomarkers and Respiratory Mechanics in Laparoscopic Bariatric Surgery: Desflurane vs. Total Intravenous Anaesthesia with Propofol
Authors: L. Kashyap, S. Jha, D. Shende, V. K. Mohan, P. Khanna, A. Aravindan, S. Kashyap, L. Singh, S. Aggarwal
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Obesity is associated with a chronic inflammatory state. During surgery, there is an interplay between anaesthetic and surgical stress vis-a-vis the already present complex immune state. Moreover, the postoperative period is dictated by inflammation, which is crucial for wound healing and regeneration. An excess of inflammatory response might hamper recovery besides increasing the risk for infection and complications. There is definite evidence of the immunosuppressive role of inhaled anaesthetic agents. This immune modulation may be brought into effect directly by influencing the innate and adaptive immunity cells. The effects of propofol on immune mechanisms in has been widely elucidated because of its popularity. It reduces superoxide generation, elastase release, and chemotaxis. However, there is no unequivocal proof of one’s superiority over the other. Hence, an anaesthetic regimen with lesser inflammatory potential and specific to the obese patient is needed. OBESITA trial protocol (2019) by Sousa and co-workers in progress aims to test the hypothesis that anaesthesia with sevoflurane results in a weaker proinflammatory response compared to propofol, as evidenced by lower IL-6 and other biomarkers and an increased macrophage differentiation into M2 phenotype in adipose tissue. IL-6 was used as the objective parameter to evaluate inflammation as it is regulated by both surgery and anesthesia. It is the most sensitive marker of the inflammatory response to tissue damage since it is released within minutes by blood leukocytes. We hypothesized that maintenance of anaesthesia with propofol would lead to less inflammation than that with desflurane. Aims: The effect of two anaesthetic techniques, total intravenous anaesthesia (TIVA) with propofol and desflurane, on surgical stress response was evaluated. The primary objective was to compare serum interleukin-6 (IL-6) levels before and after surgery. Methods: In this prospective single-blinded randomized controlled trial undertaken, 30 obese patients (BMI>30 kg/m2) undergoing laparoscopic bariatric surgery under general anaesthesia were recruited. Patients were randomized to receive desflurane or TIVA using a target-controlled infusion for maintenance of anaesthesia. As a marker of inflammation, pre-and post-surgery IL-6 levels were compared. Results: After surgery, IL-6 levels increased significantly in both groups. The rise in IL-6 was less with TIVA than with desflurane; however, it did not reach significance. IL-6 rise post-surgery correlated positively with the complexity of procedure and duration of surgery and anaesthesia, rather than anaesthetic technique. Both groups did not differ in terms of intra-operative hemodynamic and respiratory variables, time to awakening, postoperative pulmonary complications, and duration of hospital stay. The incidence of nausea was significantly higher with desflurane than with TIVA. Conclusion: Inflammatory response did not differ as a function of anaesthetic technique when propofol and desflurane were compared. Also, patient and surgical variables dictated post-operative inflammation more than the anaesthetic factors. Further, larger sample size is needed to confirm or refute these findings.Keywords: bariatric, biomarkers, inflammation, laparoscopy
Procedia PDF Downloads 123115 Relationship Between Brain Entropy Patterns Estimated by Resting State fMRI and Child Behaviour
Authors: Sonia Boscenco, Zihan Wang, Euclides José de Mendoça Filho, João Paulo Hoppe, Irina Pokhvisneva, Geoffrey B.C. Hall, Michael J. Meaney, Patricia Pelufo Silveira
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Entropy can be described as a measure of the number of states of a system, and when used in the context of physiological time-based signals, it serves as a measure of complexity. In functional connectivity data, entropy can account for the moment-to-moment variability that is neglected in traditional functional magnetic resonance imaging (fMRI) analyses. While brain fMRI resting state entropy has been associated with some pathological conditions like schizophrenia, no investigations have explored the association between brain entropy measures and individual differences in child behavior in healthy children. We describe a novel exploratory approach to evaluate brain fMRI resting state data in two child cohorts, and MAVAN (N=54, 4.5 years, 48% males) and GUSTO (N = 206, 4.5 years, 48% males) and its associations to child behavior, that can be used in future research in the context of child exposures and long-term health. Following rs-fMRI data pre-processing and Shannon entropy calculation across 32 network regions of interest to acquire 496 unique functional connections, partial correlation coefficient analysis adjusted for sex was performed to identify associations between entropy data and Strengths and Difficulties questionnaire in MAVAN and Child Behavior Checklist domains in GUSTO. Significance was set at p < 0.01, and we found eight significant associations in GUSTO. Negative associations were found between two frontoparietal regions and cerebellar posterior and oppositional defiant problems, (r = -0.212, p = 0.006) and (r = -0.200, p = 0.009). Positive associations were identified between somatic complaints and four default mode connections: salience insula (r = 0.202, p < 0.01), dorsal attention intraparietal sulcus (r = 0.231, p = 0.003), language inferior frontal gyrus (r = 0.207, p = 0.008) and language posterior superior temporal gyrus (r = 0.210, p = 0.008). Positive associations were also found between insula and frontoparietal connection and attention deficit / hyperactivity problems (r = 0.200, p < 0.01), and insula – default mode connection and pervasive developmental problems (r = 0.210, p = 0.007). In MAVAN, ten significant associations were identified. Two positive associations were found = with prosocial scores: the salience prefrontal cortex and dorsal attention connection (r = 0.474, p = 0.005) and the salience supramarginal gyrus and dorsal attention intraparietal sulcus (r = 0.447, p = 0.008). The insula and prefrontal connection were negatively associated with peer problems (r = -0.437, p < 0.01). Conduct problems were negatively associated with six separate connections, the left salience insula and right salience insula (r = -0.449, p = 0.008), left salience insula and right salience supramarginal gyrus (r = -0.512, p = 0.002), the default mode and visual network (r = -0.444, p = 0.009), dorsal attention and language network (r = -0.490, p = 0.003), and default mode and posterior parietal cortex (r = -0.546, p = 0.001). Entropy measures of resting state functional connectivity can be used to identify individual differences in brain function that are correlated with variation in behavioral problems in healthy children. Further studies applying this marker into the context of environmental exposures are warranted.Keywords: child behaviour, functional connectivity, imaging, Shannon entropy
Procedia PDF Downloads 202114 Molecular Migration in Polyvinyl Acetate Matrix: Impact of Compatibility, Number of Migrants and Stress on Surface and Internal Microstructure
Authors: O. Squillace, R. L. Thompson
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Migration of small molecules to, and across the surface of polymer matrices is a little-studied problem with important industrial applications. Tackifiers in adhesives, flavors in foods and binding agents in paints all present situations where the function of a product depends on the ability of small molecules to migrate through a polymer matrix to achieve the desired properties such as softness, dispersion of fillers, and to deliver an effect that is felt (or tasted) on a surface. It’s been shown that the chemical and molecular structure, surface free energies, phase behavior, close environment and compatibility of the system, influence the migrants’ motion. When differences in behavior, such as occurrence of segregation to the surface or not, are observed it is then of crucial importance to identify and get a better understanding of the driving forces involved in the process of molecular migration. In this aim, experience is meant to be allied with theory in order to deliver a validated theoretical and computational toolkit to describe and predict these phenomena. The systems that have been chosen for this study aim to address the effect of polarity mismatch between the migrants and the polymer matrix and that of a second migrant over the first one. As a non-polar resin polymer, polyvinyl acetate is used as the material to which more or less polar migrants (sorbitol, carvone, octanoic acid (OA), triacetin) are to be added. Through contact angle measurement a surface excess is seen for sorbitol (polar) mixed with PVAc as the surface energy is lowered compare to the one of pure PVAc. This effect is increased upon the addition of carvon or triacetin (non-polars). Surface micro-structures are also evidenced by atomic force microscopy (AFM). Ion beam analysis (Nuclear Reaction Analysis), supplemented by neutron reflectometry can accurately characterize the self-organization of surfactants, oligomers, aromatic molecules in polymer films in order to relate the macroscopic behavior to the length scales that are amenable to simulation. The nuclear reaction analysis (NRA) data for deuterated OA 20% shows the evidence of a surface excess which is enhanced after annealing. The addition of 10% triacetin, as a second migrant, results in the formation of an underlying layer enriched in triacetin below the surface excess of OA. The results show that molecules in polarity mismatch with the matrix tend to segregate to the surface, and this is favored by the addition of a second migrant of the same polarity than the matrix. As studies have been restricted to materials that are model supported films under static conditions in a first step, it is also wished to address the more challenging conditions of materials under controlled stress or strain. To achieve this, a simple rig and PDMS cell have been designed to stretch the material to a defined strain and to probe these mechanical effects by ion beam analysis and atomic force microscopy. This will make a significant step towards exploring the influence of extensional strain on surface segregation, flavor release in cross-linked rubbers.Keywords: polymers, surface segregation, thin films, molecular migration
Procedia PDF Downloads 132113 Application of Harris Hawks Optimization Metaheuristic Algorithm and Random Forest Machine Learning Method for Long-Term Production Scheduling Problem under Uncertainty in Open-Pit Mines
Authors: Kamyar Tolouei, Ehsan Moosavi
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In open-pit mines, the long-term production scheduling optimization problem (LTPSOP) is a complicated problem that contains constraints, large datasets, and uncertainties. Uncertainty in the output is caused by several geological, economic, or technical factors. Due to its dimensions and NP-hard nature, it is usually difficult to find an ideal solution to the LTPSOP. The optimal schedule generally restricts the ore, metal, and waste tonnages, average grades, and cash flows of each period. Past decades have witnessed important measurements of long-term production scheduling and optimal algorithms since researchers have become highly cognizant of the issue. In fact, it is not possible to consider LTPSOP as a well-solved problem. Traditional production scheduling methods in open-pit mines apply an estimated orebody model to produce optimal schedules. The smoothing result of some geostatistical estimation procedures causes most of the mine schedules and production predictions to be unrealistic and imperfect. With the expansion of simulation procedures, the risks from grade uncertainty in ore reserves can be evaluated and organized through a set of equally probable orebody realizations. In this paper, to synthesize grade uncertainty into the strategic mine schedule, a stochastic integer programming framework is presented to LTPSOP. The objective function of the model is to maximize the net present value and minimize the risk of deviation from the production targets considering grade uncertainty simultaneously while satisfying all technical constraints and operational requirements. Instead of applying one estimated orebody model as input to optimize the production schedule, a set of equally probable orebody realizations are applied to synthesize grade uncertainty in the strategic mine schedule and to produce a more profitable and risk-based production schedule. A mixture of metaheuristic procedures and mathematical methods paves the way to achieve an appropriate solution. This paper introduced a hybrid model between the augmented Lagrangian relaxation (ALR) method and the metaheuristic algorithm, the Harris Hawks optimization (HHO), to solve the LTPSOP under grade uncertainty conditions. In this study, the HHO is experienced to update Lagrange coefficients. Besides, a machine learning method called Random Forest is applied to estimate gold grade in a mineral deposit. The Monte Carlo method is used as the simulation method with 20 realizations. The results specify that the progressive versions have been considerably developed in comparison with the traditional methods. The outcomes were also compared with the ALR-genetic algorithm and ALR-sub-gradient. To indicate the applicability of the model, a case study on an open-pit gold mining operation is implemented. The framework displays the capability to minimize risk and improvement in the expected net present value and financial profitability for LTPSOP. The framework could control geological risk more effectively than the traditional procedure considering grade uncertainty in the hybrid model framework.Keywords: grade uncertainty, metaheuristic algorithms, open-pit mine, production scheduling optimization
Procedia PDF Downloads 105112 Development of an Artificial Neural Network to Measure Science Literacy Leveraging Neuroscience
Authors: Amanda Kavner, Richard Lamb
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Faster growth in science and technology of other nations may make staying globally competitive more difficult without shifting focus on how science is taught in US classes. An integral part of learning science involves visual and spatial thinking since complex, and real-world phenomena are often expressed in visual, symbolic, and concrete modes. The primary barrier to spatial thinking and visual literacy in Science, Technology, Engineering, and Math (STEM) fields is representational competence, which includes the ability to generate, transform, analyze and explain representations, as opposed to generic spatial ability. Although the relationship is known between the foundational visual literacy and the domain-specific science literacy, science literacy as a function of science learning is still not well understood. Moreover, the need for a more reliable measure is necessary to design resources which enhance the fundamental visuospatial cognitive processes behind scientific literacy. To support the improvement of students’ representational competence, first visualization skills necessary to process these science representations needed to be identified, which necessitates the development of an instrument to quantitatively measure visual literacy. With such a measure, schools, teachers, and curriculum designers can target the individual skills necessary to improve students’ visual literacy, thereby increasing science achievement. This project details the development of an artificial neural network capable of measuring science literacy using functional Near-Infrared Spectroscopy (fNIR) data. This data was previously collected by Project LENS standing for Leveraging Expertise in Neurotechnologies, a Science of Learning Collaborative Network (SL-CN) of scholars of STEM Education from three US universities (NSF award 1540888), utilizing mental rotation tasks, to assess student visual literacy. Hemodynamic response data from fNIRsoft was exported as an Excel file, with 80 of both 2D Wedge and Dash models (dash) and 3D Stick and Ball models (BL). Complexity data were in an Excel workbook separated by the participant (ID), containing information for both types of tasks. After changing strings to numbers for analysis, spreadsheets with measurement data and complexity data were uploaded to RapidMiner’s TurboPrep and merged. Using RapidMiner Studio, a Gradient Boosted Trees artificial neural network (ANN) consisting of 140 trees with a maximum depth of 7 branches was developed, and 99.7% of the ANN predictions are accurate. The ANN determined the biggest predictors to a successful mental rotation are the individual problem number, the response time and fNIR optode #16, located along the right prefrontal cortex important in processing visuospatial working memory and episodic memory retrieval; both vital for science literacy. With an unbiased measurement of science literacy provided by psychophysiological measurements with an ANN for analysis, educators and curriculum designers will be able to create targeted classroom resources to help improve student visuospatial literacy, therefore improving science literacy.Keywords: artificial intelligence, artificial neural network, machine learning, science literacy, neuroscience
Procedia PDF Downloads 119111 Tales of Two Cities: 'Motor City' Detroit and 'King Cotton' Manchester: Transatlantic Transmissions and Transformations, Flows of Communications, Commercial and Cultural Connections
Authors: Dominic Sagar
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Manchester ‘King Cotton’, the first truly industrial city of the nineteenth century, passing on the baton to Detroit ‘Motor City’, is the first truly modern city. We are exploring the tales of the two cities, their rise and fall and subsequent post-industrial decline, their transitions and transformations, whilst alongside paralleling their corresponding, commercial, cultural, industrial and even agricultural, artistic and musical transactions and connections. The paper will briefly contextualize how technologies of the industrial age and modern age have been instrumental in the development of these cities and other similar cities including New York. However, the main focus of the study will be the present and more importantly the future, how globalisation and the advancements of digital technologies and industries have shaped the cities developments from AlanTuring and the making of the first programmable computer to the effect of digitalisation and digital initiatives. Manchester now has a thriving creative digital infrastructure of Digilabs, FabLabs, MadLabs and hubs, the study will reference the Smart Project and the Manchester Digital Development Association whilst paralleling similar digital and creative industrial initiatives now starting to happen in Detroit. The paper will explore other topics including the need to allow for zones of experimentation, areas to play, think and create in order develop and instigate new initiatives and ideas of production, carrying on the tradition of influential inventions throughout the history of these key cities. Other topics will be briefly touched on, such as urban farming, citing the Biospheric foundation in Manchester and other similar projects in Detroit. However, the main thread will focus on the music industries and how they are contributing to the regeneration of cities. Musically and artistically, Manchester and Detroit have been closely connected by the flow and transmission of information and transfer of ideas via ‘cars and trains and boats and planes’ through to the new ‘super highway’. From Detroit to Manchester often via New York and Liverpool and back again, these musical and artistic connections and flows have greatly affected and influenced both cities and the advancement of technology are still connecting the cities. In summary two hugely important industrial cities, subsequently both experienced massive decline in fortunes, having had their large industrial hearts ripped out, ravaged leaving dying industrial carcasses and car crashes of despair, dereliction, desolation and post-industrial wastelands vacated by a massive exodus of the cities’ inhabitants. To examine the affinity, similarity and differences between Manchester & Detroit, from their industrial importance to their post-industrial decline and their current transmutations, transformations, transient transgressions, cities in transition; contrasting how they have dealt with these problems and how they can learn from each other. With a view to framing these topics with regard to how various communities have shaped these cities and the creative industries and design [the new cotton/car manufacturing industries] are reinventing post-industrial cities, to speculate on future development of these themes in relation to Globalisation, digitalisation and how cities can function to develop solutions to communal living in cities of the future.Keywords: cultural capital, digital developments, musical initiatives, zones of experimentation
Procedia PDF Downloads 194110 Structural Molecular Dynamics Modelling of FH2 Domain of Formin DAAM
Authors: Rauan Sakenov, Peter Bukovics, Peter Gaszler, Veronika Tokacs-Kollar, Beata Bugyi
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FH2 (formin homology-2) domains of several proteins, collectively known as formins, including DAAM, DAAM1 and mDia1, promote G-actin nucleation and elongation. FH2 domains of these formins exist as oligomers. Chain dimerization by ring structure formation serves as a structural basis for actin polymerization function of FH2 domain. Proper single chain configuration and specific interactions between its various regions are necessary for individual chains to form a dimer functional in G-actin nucleation and elongation. FH1 and WH2 domain-containing formins were shown to behave as intrinsically disordered proteins. Thus, the aim of this research was to study structural dynamics of FH2 domain of DAAM. To investigate structural features of FH2 domain of DAAM, molecular dynamics simulation of chain A of FH2 domain of DAAM solvated in water box in 50 mM NaCl was conducted at temperatures from 293.15 to 353.15K, with VMD 1.9.2, NAMD 2.14 and Amber Tools 21 using 2z6e and 1v9d PDB structures of DAAM was obtained on I-TASSER webserver. Calcium and ATP bound G-actin 3hbt PDB structure was used as a reference protein with well-described structural dynamics of denaturation. Topology and parameter information of CHARMM 2012 additive all-atom force fields for proteins, carbohydrate derivatives, water and ions were used in NAMD 2.14 and ff19SB force field for proteins in Amber Tools 21. The systems were energy minimized for the first 1000 steps, equilibrated and produced in NPT ensemble for 1ns using stochastic Langevin dynamics and the particle mesh Ewald method. Our root-mean square deviation (RMSD) analysis of molecular dynamics of chain A of FH2 domains of DAAM revealed similar insignificant changes of total molecular average RMSD values of FH2 domain of these formins at temperatures from 293.15 to 353.15K. In contrast, total molecular average RMSD values of G-actin showed considerable increase at 328K, which corresponds to the denaturation of G-actin molecule at this temperature and its transition from native, ordered, to denatured, disordered, state which is well-described in the literature. RMSD values of lasso and tail regions of chain A of FH2 domain of DAAM exhibited higher than total molecular average RMSD at temperatures from 293.15 to 353.15K. These regions are functional in intra- and interchain interactions and contain highly conserved tryptophan residues of lasso region, highly conserved GNYMN sequence of post region and amino acids of the shell of hydrophobic pocket of the salt bridge between Arg171 and Asp321, which are important for structural stability and ordered state of FH2 domain of DAAM and its functions in FH2 domain dimerization. In conclusion, higher than total molecular average RMSD values of lasso and post regions of chain A of FH2 domain of DAAM may explain disordered state of FH2 domain of DAAM at temperatures from 293.15 to 353.15K. Finally, absence of marked transition, in terms of significant changes in average molecular RMSD values between native and denatured states of FH2 domain of DAAM at temperatures from 293.15 to 353.15K, can make it possible to attribute these formins to the group of intrinsically disordered proteins rather than to the group of intrinsically ordered proteins such as G-actin.Keywords: FH2 domain, DAAM, formins, molecular modelling, computational biophysics
Procedia PDF Downloads 136109 Benefits of High Power Impulse Magnetron Sputtering (HiPIMS) Method for Preparation of Transparent Indium Gallium Zinc Oxide (IGZO) Thin Films
Authors: Pavel Baroch, Jiri Rezek, Michal Prochazka, Tomas Kozak, Jiri Houska
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Transparent semiconducting amorphous IGZO films have attracted great attention due to their excellent electrical properties and possible utilization in thin film transistors or in photovoltaic applications as they show 20-50 times higher mobility than that of amorphous silicon. It is also known that the properties of IGZO films are highly sensitive to process parameters, especially to oxygen partial pressure. In this study we have focused on the comparison of properties of transparent semiconducting amorphous indium gallium zinc oxide (IGZO) thin films prepared by conventional sputtering methods and those prepared by high power impulse magnetron sputtering (HiPIMS) method. Furthermore we tried to optimize electrical and optical properties of the IGZO thin films and to investigate possibility to apply these coatings on thermally sensitive flexible substrates. We employed dc, pulsed dc, mid frequency sine wave and HiPIMS power supplies for magnetron deposition. Magnetrons were equipped with sintered ceramic InGaZnO targets. As oxygen vacancies are considered to be the main source of the carriers in IGZO films, it is expected that with the increase of oxygen partial pressure number of oxygen vacancies decreases which results in the increase of film resistivity. Therefore in all experiments we focused on the effect of oxygen partial pressure, discharge power and pulsed power mode on the electrical, optical and mechanical properties of IGZO thin films and also on the thermal load deposited to the substrate. As expected, we have observed a very fast transition between low- and high-resistivity films depending on oxygen partial pressure when deposition using conventional sputtering methods/power supplies have been utilized. Therefore we established and utilized HiPIMS sputtering system for enlargement of operation window for better control of IGZO thin film properties. It is shown that with this system we are able to effectively eliminate steep transition between low and high resistivity films exhibited by DC mode of sputtering and the electrical resistivity can be effectively controlled in the wide resistivity range of 10-² to 10⁵ Ω.cm. The highest mobility of charge carriers (up to 50 cm2/V.s) was obtained at very low oxygen partial pressures. Utilization of HiPIMS also led to significant decrease in thermal load deposited to the substrate which is beneficial for deposition on the thermally sensitive and flexible polymer substrates. Deposition rate as a function of discharge power and oxygen partial pressure was also systematically investigated and the results from optical, electrical and structure analysis will be discussed in detail. Most important result which we have obtained demonstrates almost linear control of IGZO thin films resistivity with increasing of oxygen partial pressure utilizing HiPIMS mode of sputtering and highly transparent films with low resistivity were prepared already at low pO2. It was also found that utilization of HiPIMS technique resulted in significant improvement of surface smoothness in reactive mode of sputtering (with increasing of oxygen partial pressure).Keywords: charge carrier mobility, HiPIMS, IGZO, resistivity
Procedia PDF Downloads 297108 An Engineer-Oriented Life Cycle Assessment Tool for Building Carbon Footprint: The Building Carbon Footprint Evaluation System in Taiwan
Authors: Hsien-Te Lin
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The purpose of this paper is to introduce the BCFES (building carbon footprint evaluation system), which is a LCA (life cycle assessment) tool developed by the Low Carbon Building Alliance (LCBA) in Taiwan. A qualified BCFES for the building industry should fulfill the function of evaluating carbon footprint throughout all stages in the life cycle of building projects, including the production, transportation and manufacturing of materials, construction, daily energy usage, renovation and demolition. However, many existing BCFESs are too complicated and not very designer-friendly, creating obstacles in the implementation of carbon reduction policies. One of the greatest obstacle is the misapplication of the carbon footprint inventory standards of PAS2050 or ISO14067, which are designed for mass-produced goods rather than building projects. When these product-oriented rules are applied to building projects, one must compute a tremendous amount of data for raw materials and the transportation of construction equipment throughout the construction period based on purchasing lists and construction logs. This verification method is very cumbersome by nature and unhelpful to the promotion of low carbon design. With a view to provide an engineer-oriented BCFE with pre-diagnosis functions, a component input/output (I/O) database system and a scenario simulation method for building energy are proposed herein. Most existing BCFESs base their calculations on a product-oriented carbon database for raw materials like cement, steel, glass, and wood. However, data on raw materials is meaningless for the purpose of encouraging carbon reduction design without a feedback mechanism, because an engineering project is not designed based on raw materials but rather on building components, such as flooring, walls, roofs, ceilings, roads or cabinets. The LCBA Database has been composited from existing carbon footprint databases for raw materials and architectural graphic standards. Project designers can now use the LCBA Database to conduct low carbon design in a much more simple and efficient way. Daily energy usage throughout a building's life cycle, including air conditioning, lighting, and electric equipment, is very difficult for the building designer to predict. A good BCFES should provide a simplified and designer-friendly method to overcome this obstacle in predicting energy consumption. In this paper, the author has developed a simplified tool, the dynamic Energy Use Intensity (EUI) method, to accurately predict energy usage with simple multiplications and additions using EUI data and the designed efficiency levels for the building envelope, AC, lighting and electrical equipment. Remarkably simple to use, it can help designers pre-diagnose hotspots in building carbon footprint and further enhance low carbon designs. The BCFES-LCBA offers the advantages of an engineer-friendly component I/O database, simplified energy prediction methods, pre-diagnosis of carbon hotspots and sensitivity to good low carbon designs, making it an increasingly popular carbon management tool in Taiwan. To date, about thirty projects have been awarded BCFES-LCBA certification and the assessment has become mandatory in some cities.Keywords: building carbon footprint, life cycle assessment, energy use intensity, building energy
Procedia PDF Downloads 139107 Creation of a Test Machine for the Scientific Investigation of Chain Shot
Authors: Mark McGuire, Eric Shannon, John Parmigiani
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Timber harvesting increasingly involves mechanized equipment. This has increased the efficiency of harvesting, but has also introduced worker-safety concerns. One such concern arises from the use of harvesters. During operation, harvesters subject saw chain to large dynamic mechanical stresses. These stresses can, under certain conditions, cause the saw chain to fracture. The high speed of harvester saw chain can cause the resulting open chain loop to fracture a second time due to the dynamic loads placed upon it as it travels through space. If a second fracture occurs, it can result in a projectile consisting of one-to-several chain links. This projectile is referred to as a chain shot. It has speeds similar to a bullet but typically has greater mass and is a significant safety concern. Numerous examples exist of chain shots penetrating bullet-proof barriers and causing severe injury and death. Improved harvester-cab barriers can help prevent injury however a comprehensive scientific understanding of chain shot is required to consistently reduce or prevent it. Obtaining this understanding requires a test machine with the capability to cause chain shot to occur under carefully controlled conditions and accurately measure the response. Worldwide few such test machine exist. Those that do focus on validating the ability of barriers to withstand a chain shot impact rather than obtaining a scientific understanding of the chain shot event itself. The purpose of this paper is to describe the design, fabrication, and use of a test machine capable of a comprehensive scientific investigation of chain shot. The capabilities of this machine are to test all commercially-available saw chains and bars at chain tensions and speeds meeting and exceeding those typically encountered in harvester use and accurately measure the corresponding key technical parameters. The test machine was constructed inside of a standard shipping container. This provides space for both an operator station and a test chamber. In order to contain the chain shot under any possible test conditions, the test chamber was lined with a base layer of AR500 steel followed by an overlay of HDPE. To accommodate varying bar orientations and fracture-initiation sites, the entire saw chain drive unit and bar mounting system is modular and capable of being located anywhere in the test chamber. The drive unit consists of a high-speed electric motor with a flywheel. Standard Ponsse harvester head components are used to bar mounting and chain tensioning. Chain lubrication is provided by a separate peristaltic pump. Chain fracture is initiated through ISO standard 11837. Measure parameters include shaft speed, motor vibration, bearing temperatures, motor temperature, motor current draw, hydraulic fluid pressure, chain force at fracture, and high-speed camera images. Results show that the machine is capable of consistently causing chain shot. Measurement output shows fracture location and the force associated with fracture as a function of saw chain speed and tension. Use of this machine will result in a scientific understanding of chain shot and consequently improved products and greater harvester operator safety.Keywords: chain shot, safety, testing, timber harvesters
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