Search results for: membrane integrity

Authors: Purva Khurana

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Traditional textile crafts are universally found to have been significantly impeded by the uprise of innovative technologies, but sustained human endeavor, in sync with dynamic market nuances, holds key to these otherwise getting fast-extinct marvels. The metamorphosis of such art-forms into niche markets pre-supposes sharp concentration on adaptability. The author has concentrated on the ancient handicraft of Ikat in Andhra Pradesh (India), a manifestation of their cultural heritage and esoteric cottage industry, so very intrinsic to the development and support of local economy and identity. Like any other traditional practice, ikat weaving has been subjected to the challenges of modernization. However, owing to its unique character, personalize production and adaptability, both of material and process, ikat weaving has stood the test of time by way of judiciously embellishing innovation with contemporary taste. To survive as a living craft as also to justify its role as a universal language of aesthetic sensibility, it is imperative that ikat tradition should lend itself continuous process of experiments, change and growth. Besides, the instant paper aims to examine the contours of ikat production process from its pure form, to more fashion and market oriented production, with upgraded process, material and tools. Over the time, it has adapted well to new style-paradigms, duly matching up with the latest fashion trends, in tandem with the market-sensitivities. Apart, it is an effort to investigate how this craft could respond constructively to the pressure of contemporary technical developments in order to be at cutting edge, while preserving its integrity. In order to approach these issues, the methodology adopted is, conceptual analysis of the craft practices, its unique strength and how they could be used to advance the craft in relation to the emergence of technical developments. The paper summarizes the result of the study carried out by the author on the peculiar advantages of suitably- calibrated vat dyes over natural dyes, in terms of its recycling ability and eco-friendly properties, thus holding definite edge, both in terms of socio-economic as well as environmental concerns.

Keywords: craft, eco-friendly dyes, ikat, metamorphosis

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Authors: Chen Wang, Jared Evans, Yan Asmann

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With the quick evolvement of next-generation sequencing techniques, whole-exome or exome-panel data have become a cost-effective way for detection of small exonic mutations, but there has been a growing desire to accurately detect copy number variations (CNVs) as well. In order to address this research and clinical needs, we developed a sequencing coverage pattern-based method not only for copy number detections, data integrity checks, CNV calling, and visualization reports. The developed methodologies include complete automation to increase usability, genome content-coverage bias correction, CNV segmentation, data quality reports, and publication quality images. Automatic identification and removal of poor quality outlier samples were made automatically. Multiple experimental batches were routinely detected and further reduced for a clean subset of samples before analysis. Algorithm improvements were also made to improve somatic CNV detection as well as germline CNV detection in trio family. Additionally, a set of utilities was included to facilitate users for producing CNV plots in focused genes of interest. We demonstrate the somatic CNV enhancements by accurately detecting CNVs in whole exome-wide data from the cancer genome atlas cancer samples and a lymphoma case study with paired tumor and normal samples. We also showed our efficient reuses of existing exome sequencing data, for improved germline CNV calling in a family of the trio from the phase-III study of 1000 Genome to detect CNVs with various modes of inheritance. The performance of the developed method is evaluated by comparing CNV calling results with results from other orthogonal copy number platforms. Through our case studies, reuses of exome sequencing data for calling CNVs have several noticeable functionalities, including a better quality control for exome sequencing data, improved joint analysis with single nucleotide variant calls, and novel genomic discovery of under-utilized existing whole exome and custom exome panel data.

Keywords: bioinformatics, computational genetics, copy number variations, data reuse, exome sequencing, next generation sequencing

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Authors: Kasun U. G. Palihakkara

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Although vaccine coverage in Sri Lanka is close to 100%, with the widely spreading vaccine rejection trend reaching South Asian regions, it is essential to catch on whether Sri Lankans are being misinformed from the common misconceptions regarding vaccines. As the rates of target diseases decrease, parents become less accepting of even minor common adverse events. It is essential to preserve the integrity of immunization programs and protect public health by finding out the prevalence of anti-immunization trends. The primary objective of this study was to assess the immunization practices and prevalence of trends related to anti-immunization among urban community in Sri Lanka. A descriptive cross-sectional quantitative study on 323 participants using convenient sampling with 213 self-administered questionnaires. Additionally, 110 online questionnaires were distributed. 31% of the study population does not maintain immunization records for their children. While majority seek information regarding immunization from reliable sources such as the family physician or specialist pediatricians, 30% also refer to unreliable sources such as online communities for their opinion. 31% of study population had not vaccinated for Japanese encephalitis. 73% of the study population had encountered with side effects of vaccination such as fever & 47% believed that such side effects are rare. 52% of the population had hostile attitude regarding the administration of several doses multiple vaccines within a child’s first year. Diseases like polio had been successfully eradicated from Sri Lanka with the help of vigorous vaccination programs. However, majority of the study population believe that there’s no need to keep vaccinating the children for those eradicated diseases and exposing the child for adverse effects of such vaccines. Majority of the population were aware of the existing misconceptions regarding immunization. The most popular misconceptions about vaccines popular among the study population were the MMR (Measles, Mumps, and Rubella) vaccine being a possible cause leading to autism and bowel disease and children getting infected with the disease even after they get vaccinated, may be due to the inactivated vaccine. Disturbingly 22% of the study population believed that vaccines are useless in preventing diseases nowadays. These data obtained from the urban study population reveals that even though statistically Sri Lankan immunization coverage is 100%, there is a possibility of anti-vaccination trend arising in Sri Lanka due to the prevalence of various misconceptions and rumors related to it. Therefore these data recommend the need for thorough awareness among the mothers.

Keywords: anti-vaccination, immunization, infectious diseases, pediatric health

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Authors: Emilio A. Berny-Brandt, Sonia E. Ruiz

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Steel tubular towers serving as support structures for large wind turbines are subject to several hundred million stress cycles arising from the turbulent nature of the wind. This causes high-cycle fatigue which can govern tower design. The practice of maintaining the support structure after wind turbines reach its typical 20-year design life have become common, but without quantifying the changes in the reliability on the tower. There are several studies on this topic, but most of them are based on the S-N curve approach using the Miner’s rule damage summation method, the de-facto standard in the wind industry. However, the qualitative nature of Miner’s method makes desirable the use of fracture mechanics to measure the effects of fatigue in the capacity curve of the structure, which is important in order to evaluate the integrity and reliability of these towers. Temporal and spatially varying wind speed time histories are simulated based on power spectral density and coherence functions. Simulations are then applied to a SAP2000 finite element model and step-by-step analysis is used to obtain the stress time histories for a range of representative wind speeds expected during service conditions of the wind turbine. Rainflow method is then used to obtain cycle and stress range information of each of these time histories and a statistical analysis is performed to obtain the distribution parameters of each variable. Monte Carlo simulation is used here to evaluate crack growth over time in the tower base using the Paris-Erdogan equation. A nonlinear static pushover analysis to assess the capacity curve of the structure after a number of years is performed. The capacity curves are then used to evaluate the changes in reliability of a steel tower located in Oaxaca, Mexico, where wind energy facilities are expected to grow in the near future. Results show that fatigue on the tower base can have significant effects on the structural capacity of the wind turbine, especially after the 20-year design life when the crack growth curve starts behaving exponentially.

Keywords: crack growth, fatigue, Monte Carlo simulation, structural reliability, wind turbines

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Authors: Venkateswara R. Naira, Debasish Das, Soumen K. Maiti

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Achieving high cell densities of microalgae under obligatory light-limiting and high light conditions of diurnal (low-high-low variations of daylight intensity) sunlight are further limited by CO₂ supply and dissolved oxygen (DO) accumulation in large-scale photobioreactors. High DO levels cause low growth due to photoinhibition and/or photorespiration. Hence, scalable elevated CO₂ levels (% in air) and their effect on DO accumulation in a 10 L cylindrical membrane photobioreactor (a vertical tubular type) are studied in the present study. The CO₂ elevation strategies; biomass-based, pH control based (types II & I) and diurnal light based, were explored to study the growth of Chlorella sp. FC2 IITG under single-sided LED lighting in the laboratory, mimicking diurnal sunlight. All the experiments were conducted in fed-batch mode by maintaining N and P sources at least 50% of initial concentrations of the optimized BG-11 medium. It was observed that biomass-based (2% - 1st day, 2.5% - 2nd day and 3% - thereafter) and well-known pH control based, type-I (5.8 pH throughout) strategies were found lethal for FC2 growth. In both strategies, the highest peak DO accumulation of 150% air saturation was resulted due to high photosynthetic activity caused by higher CO₂ levels. In the pH control based type-I strategy, automatically resulted CO₂ levels for pH control were recorded so high (beyond the inhibition range, 5%). However, pH control based type-II strategy (5.8 – 2 days, 6.3 – 3 days, 6.7 – thereafter) showed final biomass titer up to 4.45 ± 0.05 g L⁻¹ with peak DO of 122% air saturation; high CO₂ levels beyond 5% (in air) were recorded thereafter. Thus, it became sustainable for obtaining high biomass. Finally, a diurnal light based (2% - low light, 2.5 % - medium light and 3% - high light) strategy was applied on the basis of increasing/decreasing photosynthesis due to increase/decrease in diurnal light intensity. It has resulted in maximum final biomass titer of 5.33 ± 0.12 g L⁻¹, with total biomass productivity of 0.59 ± 0.01 g L⁻¹ day⁻¹. The values are remarkably higher than constant 2% CO₂ level (final biomass titer: 4.26 ± 0.09 g L⁻¹; biomass productivity: 0.27 ± 0.005 g L⁻¹ day⁻¹). However, 135% air saturation of peak DO was observed. Thus, the diurnal light based elevation should be further improved by using CO₂ enriched N₂ instead of air. To the best of knowledge, the light-based CO₂ elevation strategy is not reported elsewhere.

Keywords: Chlorella sp., CO₂ elevation strategy, dissolved oxygen accumulation, diurnal light based CO₂ elevation, high cell density, microalgae, scale-up

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Authors: Dina Siniora, Jasia Baig

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During the past few decades, the healthcare system has undergone profound changes in their healthcare decision-making competencies and moral aptitudes due to the vast advancement in technology, clinical skills, and scientific knowledge. Healthcare decision-making deals with morally contentious dilemmas ranging from illness, life and death judgments that require sensitivity and awareness towards the patient’s preferences while taking into consideration medicine’s abilities and boundaries. As the ever-evolving field of medicine continues to become more scientifically and morally multifarious; physicians and the hospital administrators increasingly rely on ethics committees to resolve problems that arise in everyday patient care. The role and latitude of responsibilities of ethics committees which includes being dispute intermediaries, moral analysts, policy educators, counselors, advocates, and reviewers; suggest the importance and effectiveness of a fully integrated committee. Despite achievements on Integrated Ethics and progress in standards and competencies, there is an imminent necessity for further improvement in quality within ethics consultation services in areas of credentialing, professionalism and standards of quality, as well as the quality of healthcare throughout the system. These concerns can be resolved first by collecting data about particular quality gaps and comprehend the level to which ethics committees are consistent with newly published ASBH quality standards. Policymakers should pursue improvement strategies that target both academic bioethics community and major stakeholders at hospitals, who directly influence ethics committees. This broader approach oriented towards education and intervention outcome in conjunction with preventive ethics to address disparities in quality on a systematic level. Adopting tools for improving competencies and processes within ethics consultation by implementing a credentialing process, upholding normative significance for the ASBH core competencies, advocating for professional Code of Ethics, and further clarifying the internal structures will improve productivity, patient satisfaction, and institutional integrity. This cannot be systemically achieved without a written certification exam for HCEC practitioners, credentialing and privileging HCEC practitioners at the hospital level, and accrediting HCEC services at the institutional level.

Keywords: ethics consultation, hospital, medical ethics, quality

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Authors: Endris Yibru Hanurry, Wei-Hsin Hsu, Hsieh-Chih Tsai

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In recent years, the discovery of small interfering RNAs (siRNAs) has got great attention for the treatment of cancer and other diseases. However, the therapeutic efficacy of siRNAs has been faced with many drawbacks because of short half-life in blood circulation, poor membrane penetration, weak endosomal escape and inadequate release into the cytosol. To overcome these drawbacks, we designed a non-viral vector by conjugating polyamidoamine generation 4.5 dendrimer (PDG4.5) with diethylenetriamine (DETA)- and tetraethylenepentamine (TEPA) followed by binding with siRNA to form polyplexes through electrostatic interaction. The result of 1H nuclear magnetic resonance (NMR), 13C NMR, correlation spectroscopy, heteronuclear single–quantum correlation spectroscopy, and Fourier transform infrared spectroscopy confirmed the successful conjugation of DETA and TEPA with PDG4.5. Then, the size, surface charge, morphology, binding ability, stability, release assay, toxicity and cellular internalization were analyzed to explore the physicochemical and biological properties of PDG4.5-DETA and PDG4.5-TEPA polyplexes at specific N/P ratios. The polyplexes (N/P = 8) exhibited spherical nanosized (125 and 85 nm) particles with optimum surface charge (13 and 26 mV), showed strong siRNA binding ability, protected the siRNA against enzyme digestion and accepted biocompatibility to the HeLa cells. Qualitatively, the fluorescence microscopy image revealed the delocalization (Manders’ coefficient 0.63 and 0.53 for PDG4.5-DETA and PDG4.5-TEPA, respectively) of polyplexes and the translocation of the siRNA throughout the cytosol to show a decent cellular internalization and intracellular biodistribution of polyplexes in HeLa cells. Quantitatively, the flow cytometry result indicated that a significant (P < 0.05) amount of siRNA was internalized by cells treated with PDG4.5-DETA (68.5%) and PDG4.5-TEPA (73%) polyplexes. Generally, PDG4.5-DETA and PDG4.5-TEPA were ideal nanocarriers of siRNA in vitro and might be used as promising candidates for in vivo study and future pharmaceutical applications.

Keywords: non-viral carrier, oligoalkylamine, poly(amidoamine) dendrimer, polyplexes, siRNA

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Authors: Faizul Azly Abd Dzubir, Muhammad F. Othman

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Conventional structural health monitoring approach for mechanical equipment uses inspection data from Non-Destructive Testing (NDT) during plant shut down window and fitness for service evaluation to estimate the integrity of the equipment that is prone to crack damage. Yet, this forecast is fraught with uncertainty because it is often based on assumptions of future operational parameters, and the prediction is not continuous or online. Advanced Diagnostic and Prognostic Technology (ADaPT) uses Acoustic Emission (AE) technology and a stochastic prognostic model to provide real-time monitoring and prediction of mechanical defects or cracks. The forecast can help the plant authority handle their cracked equipment before it ruptures, causing an unscheduled shutdown of the facility. The ADaPT employs process historical data trending, finite element analysis, fitness for service, and probabilistic statistical analysis to develop a prediction model for crack initiation and growth due to mechanical damage. The prediction model is combined with live equipment operating data for real-time prediction of the remaining life span owing to fracture. ADaPT was devised at a hot combined feed exchanger (HCFE) that had suffered creep crack damage. The ADaPT tool predicts the initiation of a crack at the top weldment area by April 2019. During the shutdown window in April 2019, a crack was discovered and repaired. Furthermore, ADaPT successfully advised the plant owner to run at full capacity and improve output by up to 7% by April 2019. ADaPT was also used on a coke drum that had extensive fatigue cracking. The initial cracks are declared safe with ADaPT, with remaining crack lifetimes extended another five (5) months, just in time for another planned facility downtime to execute repair. The prediction model, when combined with plant information data, allows plant operators to continuously monitor crack propagation caused by mechanical damage for improved maintenance planning and to avoid costly shutdowns to repair immediately.

Keywords: mechanical damage, cracks, continuous monitoring tool, remaining life, acoustic emission, prognostic model

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Authors: Jelena Radmanovic

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On 5 March 2020, the International Criminal Court has decided to authorize the investigation into the crimes allegedly committed on the territory of Afghanistan after 1 May 2003. The said determination has raised several controversies, including the recently imposed sanctions by the United States, furthering the United States' long-standing rejection of the authority of the International Criminal Court. The purpose of this research is to address the said investigation in light of its importance for the prevention of impunity in the cases where the perpetrators are nationals of Non-Party States to the Rome Statute. Difficulties that the International Criminal Court has been facing, concerning the establishment of its jurisdiction in those instances where an involved state is not a Party to the Rome Statute, have become the most significant stumbling block undermining the importance, integrity, and influence of the Court. The Situation in Afghanistan raises even further concern, bearing in mind that the Prosecutor’s Request for authorization of an investigation pursuant to article 15 from 20 November 2017 has initially been rejected with the ‘interests of justice’ as an applied rationale. The first method used for the present research is the description of the actual events regarding the aforementioned decisions and the following reactions in the international community, while with the second method – the method of conceptual analysis, the research will address the decisions pertaining to the International Criminal Court’s jurisdiction and will attempt to address the mentioned Decision of 5 March 2020 as an example of good practice and a precedent that should be followed in all similar situations. The research will attempt parsing the reasons used by the International Criminal Court, giving rather greater attention to the latter decision that has authorized the investigation and the points raised by the officials of the United States. It is a find of this research that the International Criminal Court, together with other similar judicial instances (Nuremberg and Tokyo Tribunals, The International Criminal Tribunal for the former Yugoslavia, The International Criminal Tribunal for Rwanda), has presented the world with the possibility of non-impunity, attempting to prosecute those responsible for the gravest of crimes known to the humanity and has shown that such persons should not enjoy the benefits of their immunities, with its focus primarily on the victims of such crimes. Whilst it is an issue that will most certainly be addressed further in the future, with the situations that will be brought before the International Criminal Court, the present research will make an attempt at pointing to the significance of the situation in Afghanistan, the International Criminal Court as such and the international criminal justice as a whole, for the purpose of putting an end to impunity.

Keywords: Afghanistan, impunity, international criminal court, sanctions, United States

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Authors: Nazedah Ain Ibrahim, Mohamed Mansor Manan

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Treatment of suspected early onset neonatal sepsis (EONS) in Neonatal Intensive Care Unit (NICU) is essential. However, information regarding EONS pathogens may vary between regions. Global perspectives showed Group B Streptococcal (GBS) as the most common causative pathogens, but the widespread use of intrapartum antibiotics has changed the pathogens pattern towards gram negative microorganisms, especially E. coli. Objective of this study is to describe the pathogens isolated, to assess current treatment and risk of EONS. Records of 899 neonates born in three General Hospitals between 2009 until 2012 were retrospectively reviewed. The inclusion criteria were neonates with blood culture taken prior to empiric antibiotics administration and within 72 hours of life. Of the study group, a total of 734 (82%) cases had documented blood culture that met the inclusion criteria. Proven EONS (as confirmed by positive blood culture) was found in 22 (3%) neonates. The majority was isolated with gram positive organisms, 17 (2.3%). In addition, other common gram positive organism isolated were Coagulase negative staphylococci (7) followed by Bacillus sp. (5) and Streptococcus pneumonia (2), and only one case isolated with GBS, Streptococcus spp. and Enterococcus sp. Meanwhile, only five cases of gram negative organisms [Stenotropomonas (xantho) maltophi (1), Haemophilus influenza (1), Spingomonas paucimobilis (1), Enterobacter gergoviae (1) and E. coli (1)] were isolated. A total of 286 (39%) cases were exposed to intrapartum antibiotics and of those, 157 (21.4%) were administered prior to delivery. All grams positive and most gram negative organisms showed sensitivity to the tested antibiotics. Only two rare gram negative organisms showed total resistant. Male, surfactant, caesarean delivery and prolonged rapture of membrane >18hours were a possible risk of proven EONS. Although proven EONS remains uncommon in Malaysia, nonetheless, the effect of intrapartum antibiotics still required continuous surveillance. However, by analyzing isolated pathogens it can be used as treatment guidance in managing suspected EONS.

Keywords: early onset neonatal sepsis, neonates, pathogens, gram positive, gram negative

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Authors: Menna Ewida, Dalal Abou El-Ella, Dina Lasheen, Huessin El-Subbagh

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Introduction: Vascular Endothelial Growth Factor receptor (VEGF) is a signal protein produced by cells that stimulates vasculogenesis to create new blood vessels. VEGF family binds to three trans-membrane tyrosine kinase receptors,Dihydrofolate reductase (DHFR) is an enzyme of crucial importance in medicinal chemistry. DHFR catalyzes the reduction 7,8 dihydro-folate to tetrahydrofolate and intimately couples with thymidylate synthase which is a pivotal enzyme that catalysis the reductive methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) utilizing N5,N10-methylene tetrahydrofolate as a cofactor which functions as the source of the methyl group. Purpose: Novel substituted Thiazole agents were designed as DHFR and VEGF-TK inhibitors with increased synergistic activity and decreased side effects. Methods: Five series of compounds were designed with a rational that mimic the pharmacophoric features present in the reported active compounds that target DHFR & VEGFR. These molecules were docked against Methotrexate & Sorafenib as controls. An in silico ADMET study was also performed to validate the bioavailability of the newly designed compounds. The in silico molecular docking & ADMET study were also applied to the non-classical antifolates for comparison. The interaction energy comparable to that of MTX for DHFRI and Sorafenib for VEGF-TKI activity were recorded. Results: Compound 5 exhibited the highest interaction energy when docked against Sorafenib, While Compound 9 showed the highest interaction energy when docked against MTX with the perfect binding mode. Comparable results were also obtained for the ADMET study. Most of the compounds showed absorption within (95-99) zone which varies according to the type of substituents. Conclusions: The Substituted Thiazole Analogues could be a suitable template for antitumor drugs that possess enhanced bioavailability and act as DHFR and VEGF-TK inhibitors.

Keywords: anti-tumor agents, DHFR, drug design, molecular modeling, VEGFR-TKIs

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Authors: Adhithy Menon E., Biju C. A.

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Heritage monuments were first introduced to the public in the 1960s when the concept of preserving them was introduced. As a result of the 1990s, the concept of cultural landscapes gained importance, emphasizing the importance of culture and heritage in the context of the landscape. It is important to note that this paper is primarily concerned with the second category of ecological landscapes, which is organically evolving landscapes, as they represent a complex network of tangible, intangible, and environment, and the connections they share with the communities in which they are situated. The United Nations Educational, Scientific, and Cultural Organization has identified 39 cultural sites as being in danger, including the Iranian city of Bam and the historic city of Zabid in Yemen. To ensure its protection in the future, it is necessary to conduct a detailed analysis of the factors contributing to this degradation. An analysis of selected cultural landscapes from around the world is conducted to determine which parameters cause their degradation. The paper follows the objectives of understanding cultural landscapes and their importance for development, followed by examining various criteria for identifying cultural landscapes, their various classifications, as well as agencies that focus on their protection. To identify and analyze the parameters contributing to the deterioration of cultural landscapes based on literature and case studies (cultural landscape of Sintra, Rio de Janeiro, and Varanasi). As a final step, strategies should be developed to enhance deteriorating cultural landscapes based on these parameters. The major findings of the study are the impact of community in the parameters derived - integrity (natural factors, natural disasters, demolition of structures, deterioration of materials), authenticity (living elements, sense of place, building techniques, religious context, artistic expression) public participation (revenue, dependence on locale), awareness (demolition of structures, resource management) disaster management, environmental impact, maintenance of cultural landscape (linkages with other sites, dependence on locale, revenue, resource management). The parameters of authenticity, public participation, awareness, and maintenance of the cultural landscape are directly related to the community in which the cultural landscape is located. Therefore, by focusing on the community and addressing the parameters identified, the deterioration curve of cultural landscapes can be altered.

Keywords: community, cultural landscapes, heritage, organically evolved, public participation

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Authors: Eman M. Sarhan, Doaa A. Ghareeb, Gabriella Ortore, Amr A. Amara, Mohamed M. El-Sayed

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Drug salting and nanoparticle-based drug delivery formulations are considered to be an effective means for rendering the hydrophobic drugs’ nano-scale dispersion in aqueous media, and thus circumventing the pitfalls of their poor solubility as well as enhancing their membrane permeability. The current study aims to increase the bioavailability of quaternary ammonium berberine through acid salting and biodegradable bovine serum albumin (BSA)-based nanoparticulate drug formulation. Berberine hydroxide (BBR-OH) that was chemically synthesized by alkalization of the commercially available berberine hydrochloride (BBR-HCl) was then acidified to get Di-berberine sulfate (BBR)₂SO₄. The purified crystals were spectrally characterized. The desolvation technique was optimized for the preparation of size-controlled BSA-BBR-HCl, BSA-BBR-OH, and BSA-(BBR)₂SO₄ nanoparticles. Particle size, zeta potential, drug release, encapsulation efficiency, Fourier transform infrared spectroscopy (FTIR), tandem MS-MS spectroscopy, energy-dispersive X-ray spectroscopy (EDX), scanning and transmitting electron microscopic examination (SEM, TEM), in vitro bioactivity, and in silico drug-polymer interaction were determined. BSA (PDB ID; 4OR0) protonation state at different pH values was predicted using Amber12 molecular dynamic simulation. Then blind docking was performed using Lamarkian genetic algorithm (LGA) through AutoDock4.2 software. Results proved the purity and the size-controlled synthesis of berberine-BSA-nanoparticles. The possible binding poses, hydrophobic and hydrophilic interactions of berberine on BSA at different pH values were predicted. Antioxidant, anti-hemolytic, and cell differentiated ability of tested drugs and their nano-formulations were evaluated. Thus, drug salting and the potentially effective albumin berberine nanoparticle formulations can be successfully developed using a well-optimized desolvation technique and exhibiting better in vitro cellular bioavailability.

Keywords: berberine, BSA, BBR-OH, BBR-HCl, BSA-BBR-HCl, BSA-BBR-OH, (BBR)₂SO₄, BSA-(BBR)₂SO₄, FTIR, AutoDock4.2 Software, Lamarkian genetic algorithm, SEM, TEM, EDX

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Authors: Les Moncrieff

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In a world awash with potent opioids flaming an international crisis, the need to explore safe alternatives has never been more urgent. Bio-electrode Therapy is a novel adjunctive treatment method for relieving acute opioid withdrawal symptoms and many types of complex acute and chronic pain (often the underlying cause of opioid dependence). By combining the science of developmental bioelectricity with Traditional Chinese Medicine’s theory of meridians, rapid relief from pain is routinely being achieved in the clinical setting. Human body functions are dependent on electrical factors, and acupuncture points on the body are known to have higher electrical conductivity than surrounding skin tissue. When tiny gold- and silver-plated electrodes are secured to the skin at specific acupuncture points using established Chinese Medicine principles and protocols, an enhanced microcurrent and electrical field are created between the electrodes, influencing the entire meridian and connecting meridians. No external power source or electrical devices are required. Endogenous DC electric fields are an essential fundamental component for development, regeneration, and wound healing. Disruptions in the normal ion-charge in the meridians and circulation of blood will manifest as pain and development of disease. With the application of these simple electrodes (gold acting as cathode and silver as anode) according to protocols, the resulting microcurrent is directed along the selected meridians to target injured or diseased organs and tissues. When injured or diseased cells have been stimulated by the microcurrent and electrical fields, the permeability of the cell membrane is affected, resulting in an immediate relief of pain, a rapid balancing of positive and negative ions (sodium, potassium, etc.) in the cells, the restoration of intracellular fluid levels, replenishment of electrolyte levels, pH balance, removal of toxins, and a re-establishment of homeostasis.

Keywords: bioelectricity, electrodes, electrical fields, acupuncture meridians, complex pain, opioid withdrawal management

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Authors: S. Gariani, I. Shyha

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Cutting titanium alloys are usually accompanied with low productivity, poor surface quality, short tool life and high machining costs. This is due to the excessive generation of heat at the cutting zone and difficulties in heat dissipation due to relatively low heat conductivity of this metal. The cooling applications in machining processes are crucial as many operations cannot be performed efficiently without cooling. Improving machinability, increasing productivity, enhancing surface integrity and part accuracy are the main advantages of cutting fluids. Conventional fluids such as mineral oil-based, synthetic and semi-synthetic are the most common cutting fluids in the machining industry. Although, these cutting fluids are beneficial in the industries, they pose a great threat to human health and ecosystem. Vegetable oils (VOs) are being investigated as a potential source of environmentally favourable lubricants, due to a combination of biodegradability, good lubricous properties, low toxicity, high flash points, low volatility, high viscosity indices and thermal stability. Fatty acids of vegetable oils are known to provide thick, strong, and durable lubricant films. These strong lubricating films give the vegetable oil base stock a greater capability to absorb pressure and high load carrying capacity. This paper details preliminary experimental results when turning Ti-6Al-4V. The impact of various VO-based cutting fluids, cutting tool materials, working conditions was investigated. The full factorial experimental design was employed involving 24 tests to evaluate the influence of process variables on average surface roughness (Ra), tool wear and chip formation. In general, Ra varied between 0.5 and 1.56 µm and Vasco1000 cutting fluid presented comparable performance with other fluids in terms of surface roughness while uncoated coarse grain WC carbide tool achieved lower flank wear at all cutting speeds. On the other hand, all tools tips were subjected to uniform flank wear during whole cutting trails. Additionally, formed chip thickness ranged between 0.1 and 0.14 mm with a noticeable decrease in chip size when higher cutting speed was used.

Keywords: cutting fluids, turning, Ti-6Al-4V, vegetable oils, working conditions

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Authors: Wujian Han

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In the process of human interaction and communication, speech act verbs are considered to be the most active component and the main means for information transmission, and are also taken as an indication of the structure of linguistic behavior. The theoretical value and practical significance of such everyday built-in metalanguage have long been recognized. This paper, which is part of a bigger study, is aimed to provide useful insights for a more precise and systematic application to speech act verbs translation between English and Chinese, especially with regard to the degree to which generic integrity is maintained in the practice of translation of legal documents. In this study, the corpus, i.e. Chinese legal texts and their English translations, English legal texts, ordinary Chinese texts, and ordinary English texts, serve as a testing ground for examining contrastively the usage of English and Chinese directive speech act verbs in legal genre. The scope of this paper is relatively wide and essentially covers all directive speech act verbs which are used in ordinary English and Chinese, such as order, command, request, prohibit, threat, advice, warn and permit. The researcher, by combining the corpus methodology with a contrastive perspective, explored a range of characteristics of English and Chinese directive speech act verbs including their semantic, syntactic and pragmatic features, and then contrasted them in a structured way. It has been found that there are similarities between English and Chinese directive speech act verbs in legal genre, such as similar semantic components between English speech act verbs and their translation equivalents in Chinese, formal and accurate usage of English and Chinese directive speech act verbs in legal contexts. But notable differences have been identified in areas of difference between their usage in the original Chinese and English legal texts such as valency patterns and frequency of occurrences. For example, the subjects of some directive speech act verbs are very frequently omitted in Chinese legal texts, but this is not the case in English legal texts. One of the practicable methods to achieve adequacy and conciseness in speech act verb translation from Chinese into English in legal genre is to repeat the subjects or the message with discrepancy, and vice versa. In addition, translation effects such as overuse and underuse of certain directive speech act verbs are also found in the translated English texts compared to the original English texts. Legal texts constitute a particularly valuable material for speech act verb study. Building up such a contrastive picture of the Chinese and English speech act verbs in legal language would yield results of value and interest to legal translators and students of language for legal purposes and have practical application to legal translation between English and Chinese.

Keywords: contrastive analysis, corpus-based, directive speech act verbs, legal texts, translation between English and Chinese

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Authors: Rhoda N. Kayongo

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As behavior analysts in education continue to debate on how higher institutions can continue to benefit from their social and academic related programs, higher education is facing challenges in the area of character development. This is manifested in the percentages of college completion rates, teen pregnancies, drug abuse, sexual abuse, suicide, plagiarism, lack of academic integrity, and violence among their students. Attending college is a perceived opportunity to positively influence the actions and behaviors of the next generation of society; thus colleges and universities have to provide opportunities to develop students’ values and behaviors. Prior studies were mainly conducted in private institutions and more so in developed countries. However, with the complexity of the nature of student body currently due to the changing world, a multidimensional approach combining multiple factors that enhance character development outcomes is needed to suit the changing trends. The main purpose of this study was to identify opportunities in colleges and develop a model for predicting character development outcomes. A survey questionnaire composed of 7 scales including in-classroom interaction, out-of-classroom interaction, school climate, personal lifestyle, home environment, and peer influence as independent variables and character development outcomes as the dependent variable was administered to a total of five hundred and one students of 3rd and 4th year level in selected public colleges and universities in the Philippines and Rwanda. Using structural equation modelling, a predictive model explained 57% of the variance in character development outcomes. Findings from the results of the analysis showed that in-classroom interactions have a substantial direct influence on character development outcomes of the students (r = .75, p < .05). In addition, out-of-classroom interaction, school climate, and home environment contributed to students’ character development outcomes but in an indirect way. The study concluded that in the classroom are many opportunities for teachers to teach, model and integrate character development among their students. Thus, suggestions are made to public colleges and universities to deliberately boost and implement experiences that cultivate character within the classroom. These may contribute tremendously to the students' character development outcomes and hence render effective models of behaviour analysis in higher education.

Keywords: character development, tertiary institutions, predictive model, behavior analysis

Procedia PDF Downloads 118

Authors: Solene Masloh, Anne Chevrel, Maxime Culot, Leonardo Scapozza, Magali Zeisser-Labouebe

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The limited stability of clinically proven therapeutic antibodies limits their administration by the parenteral route. However, oral administration remains the best alternative as it is the most convenient and less invasive one. Obtaining a targeted treatment based on biologics, which can be orally administered, would, therefore, be an ideal situation to improve patient adherence and compliance. Nevertheless, the delivery of macromolecules through the intestine remains challenging because of their sensitivity to the harsh conditions of the gastrointestinal tract and their low permeability across the intestinal mucosa. To address this challenge, this project aims to demonstrate that targeting receptor-mediated endocytosis followed by transcytosis could maximize the intestinal uptake and transport of large molecules, such as Nanofitins. These affinity proteins of 7 kDa with binding properties similar to antibodies have already demonstrated retained stability in the digestive tract and local efficiency. However, their size does not allow passive diffusion through the intestinal barrier. Nanofitins having a controlled affinity for membrane receptors involved in the transcytosis mechanism used naturally for the transport of large molecules in humans were generated. Proteins were expressed using ribosome display and selected based on affinity to the targeted receptor and other characteristics. Their uptake and transport ex vivo across viable porcine intestines were investigated using an Ussing chambers system. In this paper, we will report the results achieved while addressing the different challenges linked to this study. To validate the ex vivo model, first, we proved the presence of the receptors targeted in humans on the porcine intestine. Then, after the identification of an optimal way of detection of Nanofitins, transport experiments were performed on porcine intestines with viability followed during the time of the experiment. The results, showing that the physiological process of transcytosis is capable of being triggered by the binding of Nanofitins on their target, will be reported here. In conclusion, the results show that Nanofitins can be transported across the intestinal barrier by triggering the receptor-mediated transcytosis and that the ex vivo model is an interesting technique to assess biologics absorption through the intestine.

Keywords: ex-vivo, Nanofitins, oral administration, transcytosis

Procedia PDF Downloads 160

Authors: Narayan Moger, Divya B., Preethi Jambagi, Krishnaveni C. K., Apsana M. R., B. R. Patil, Basvaraj Bagewadi

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Salinity is one of the major threats to world food security. Considering the requirement for salt tolerant crop plants in the present study was undertaken to clone and transferred the salt tolerant ectA gene from marine ecosystem into agriculture crop system to impart salinity tolerance. Ectoine is the compatible solute which accumulates in the cell membrane, is known to be involved in salt tolerance activity in most of the Halophiles. The present situation is insisting to development of salt tolerant transgenic lines to combat abiotic stress. In this background, the investigation was conducted to develop transgenic tomato lines by cloning and transferring of ectA gene is an ectoine derivative capable of enzymatic action for the production of acetyl-diaminobutyric acid. The gene ectA is involved in maintaining the osmotic balance of plants. The PCR amplified ectA gene (579bp) was cloned into T/A cloning vector (pTZ57R/T). The construct pDBJ26 containing ectA gene was sequenced by using gene specific forward and reverse primers. Sequence was analyzed using BLAST algorithm to check similarity of ectA gene with other isolates. Highest homology of 99.66 per cent was found with ectA gene sequences of isolates Halomonas elongata with the available sequence information in NCBI database. The ectA gene was further sub cloned into pRI101-AN plant expression vector and transferred into E. coli DH5α for its maintenance. Further pDNM27 was mobilized into A. tumefaciens LBA4404 through tri-parental mating system. The recombinant Agrobacterium containing pDNM27 was transferred into tomato plants through In planta plant transformation method. Out of 300 seedlings, co-cultivated only twenty-seven plants were able to well establish under the greenhouse condition. Among twenty-seven transformants only twelve plants showed amplification with gene specific primers. Further work must be extended to evaluate the transformants at T1 and T2 generations for ectoine accumulation, salinity tolerance, plant growth and development and yield.

Keywords: salinity, computable solutes, ectA, transgenic, in planta transformation

Procedia PDF Downloads 61

Authors: Zahra Jandaghian, Mehdi Ghobadi, Michal Bartko, Alex Hayes, Marianne Armstrong, Alexandra Thompson, Michael Lacasse

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The Intergovernmental Panel on Climate Change (IPCC) report stated the urgent need to cut greenhouse gas emissions to avoid the adverse impacts of climatic changes. The United Nations has forecasted that nearly 70 percent of people will live in urban areas by 2050 resulting in a doubling of the global building stock. Given that buildings are currently recognised as emitting 40 percent of global carbon emissions, there is thus an urgent incentive to decarbonize existing buildings and to build net-zero carbon buildings. To attain net zero carbon emissions in communities in the future requires action in two directions: I) reduction of emissions; and II) removal of on-going emissions from the atmosphere once de-carbonization measures have been implemented. Nature-based solutions (NBS) have a significant role to play in achieving net zero carbon communities, spanning both emission reductions and removal of on-going emissions. NBS for the decarbonisation of buildings can be achieved by using green roofs and green walls – increasing vertical and horizontal vegetation on the building envelopes – and using nature-based materials that either emit less heat to the atmosphere thus decreasing photochemical reaction rates, or store substantial amount of carbon during the whole building service life within their structure. The NBS approach can also mitigate urban flooding and overheating, improve urban climate and air quality, and provide better living conditions for the urban population. For existing buildings, de-carbonization mostly requires retrofitting existing envelopes efficiently to use NBS techniques whereas for future construction, de-carbonization involves designing new buildings with low carbon materials as well as having the integrity and system capacity to effectively employ NBS. This paper presents the opportunities and challenges in respect to the de-carbonization of buildings using NBS for both building retrofits and new construction. This review documents the effectiveness of NBS to de-carbonize Canadian buildings, identifies the missing links to implement these techniques in cold climatic conditions, and determine a road map and immediate approaches to mitigate the adverse impacts of climate change such as urban heat islanding. Recommendations are drafted for possible inclusion in the Canadian building and energy codes.

Keywords: decarbonization, nature-based solutions, GHG emissions, greenery enhancement, buildings

Procedia PDF Downloads 73

Authors: Cathal Merz, Gareth O’Donnell

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Coil reinforced thin-walled (CRTW) tubes are used in medicine to treat problems affecting blood vessels within the body through minimally invasive procedures. The CRTW tube considered in this research makes up part of such a device and is inserted into the patient via their femoral or brachial arteries and manually navigated to the site in need of treatment. This procedure replaces the requirement to perform open surgery but is limited by reduction of blood vessel lumen diameter and increase in tortuosity of blood vessels deep in the brain. In order to maximize the capability of these procedures, CRTW tube devices are being manufactured with decreasing wall thicknesses in order to deliver treatment deeper into the body and to allow passage of other devices through its inner diameter. This introduces significant stresses to the device materials which have resulted in an observed increase in the breaking of the proximal segment of the device into two separate pieces after it has failed by buckling. As there is currently no international standard for measuring the mechanical properties of these CRTW tube devices, it is difficult to accurately analyze this problem. The aim of the current work is to address this discrepancy in the biomedical device industry by developing a measurement system that can be used to quantify the effect of process and design changes on CRTW tube performance, aiding in the development of better performing, next generation devices. Using materials testing frames, micro-computed tomography (micro-CT) imaging, experiment planning, analysis of variance (ANOVA), T-tests and regression analysis, test methods have been developed for assessing the impact of process and design changes on the device. The major findings of this study have been an insight into the suitability of buckle and three-point bend tests for the measurement of the effect of varying processing factors on the device’s performance, and guidelines for interpreting the output data from the test methods. The findings of this study are of significant interest with respect to verifying and validating key process and design changes associated with the device structure and material condition. Test method integrity evaluation is explored throughout.

Keywords: neurovascular catheter, coil reinforced tube, buckling, three-point bend, tensile

Procedia PDF Downloads 95

Authors: Oday A. Al-Juhaishi, Sa`ad M. Ismail, Hung-Hsun Yen, Christina M. Murray, Helen M. S. Davies

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The functional anatomy of the fascia in the greyhound is still poorly understood, and incompletely described. The basic knowledge of fascia stems mainly from anatomical, histological and ultrastructural analyses. In this study, twelve specimens of hindlimbs from six fresh greyhound cadavers (3 male, 3 female) were used to examine the topographical relationships of the superficial fascia with the skin and underlying tissue. The first incision was made along the dorsal midline from the level of the thoracolumbar junction caudally to the level of the mid sacrum. The second incision was begun at the level of the first incision and extended along the midline of the lateral aspect of the hindlimb distally, to just proximal to the tarsus, and, the skin margins carefully separated to observe connective tissue links between the skin and superficial fascia, attachment points of the fascia and the relationships of the fascia with blood vessels that supply the skin. A digital camera was used to record the anatomical features as they were revealed. The dissections identified fibrous septa connecting the skin with the superficial fascia and deep fascia in specific areas. The presence of the adipose tissue was found to be very rare within the superficial fascia in these specimens. On the extensor aspects of some joints, a fusion between the superficial fascia and deep fascia was observed. This fusion created a subcutaneous bursa in the following areas: a prepatellar bursa of the stifle, a tarsal bursa caudal to the calcaneus bone, and an ischiatic bursa caudal to the ischiatic tuberosity. The evaluation of blood vessels showed that the perforating vessels passed through fibrous septa in a perpendicular direction to supply the skin, with the largest branch noted in the gluteal area. The attachment points between the superficial fascia and skin were mainly found in the region of the flexor aspect of the joints, such as caudal to the stifle joint. The numerous fibrous septa between the superficial fascia and skin that have been identified in some areas, may create support for the blood vessels that penetrate fascia and into the skin, while allowing for movement between the tissue planes. The subcutaneous bursae between the skin and the superficial fascia where it is fused with the deep fascia may be useful to decrease friction between moving areas. The adhesion points may be related to the integrity and loading of the skin. The attachment points fix the skin and appear to divide the hindlimb into anatomical compartments.

Keywords: attachment points, fibrous septa, greyhound, subcutaneous bursa, superficial fascia

Procedia PDF Downloads 338

Authors: Michael P. Mannino, Gerald W. Hart

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The majority of glucose metabolism proceeds through glycolytic pathways such as glycolysis or pentose phosphate pathway, however, about 5% is shunted through the hexosamine biosynthetic pathway, producing uridine diphosphate N-acetyl glucosamine (UDP-GlcNAc). This precursor can then be incorporated into complex oligosaccharides decorating the cell surface or remain as an intracellular post-translational-modification (PTM) of serine/threonine residues (O-GlcNAcylation, OGN), which has been identified on over 4,000 cytosolic or nuclear proteins. Intracellular OGN has major implications on cellularprocesses, typically by modulating protein localization, protein-protein interactions, protein degradation, and gene expression. Additionally, OGN is known to have an extensive cross-talk with phosphorylation, be in a competitive or cooperative manner. Unlike other PTMs there are only two cycling enzymes that are capable of adding or removing the GlcNAc moiety, O-linked N-aceytl glucosamine Transferase (OGT) and O-linked N-acetyl glucoamidase (OGA), respectively. The activity of OGT has been shown to be sensitive to cellular UDP-GlcNAc levels, even changing substrate affinity. Owing to this and that the concentration of UDP-GlcNAc is related to the metabolisms of glucose, amino acid, fatty acid, and nucleotides, O-GlcNAc is often referred to as a nutrient sensing rheostat. Indeed OGN is known to regulate several signaling pathways as a result of nutrient levels, such as insulin signaling. Dysregulation of OGN is associated with several disease states such as cancer, diabetes, and neurodegeneration. Improvements in glycomics over the past 10-15 years has significantly increased the OGT substrate pool, suggesting O-GlcNAc’s involvement in a wide variety of signaling pathways. However, O-GlcNAc’s role at the receptor level has only been identified in a case-by-case basis of known pathways. Examining the OGN of the plasma membrane (PM) may better focus our understanding of O-GlcNAc-effected signaling pathways. In this current study, PM fractions were isolated from several cell types via ultracentrifugation, followed by purification and MS/MS analysis in several cell lines. This process was repeated with or without OGT/OGA inhibitors or with increased/decreased glucose levels in media to ascertain the importance of OGN. Various pathways are followed up on in more detailed studies employing methods to localize OGN at the PM specifically.

Keywords: GlcNAc, nutrient sensitive, post-translational-modification, receptor

Procedia PDF Downloads 89

Authors: Leandra Prempeh, Emily Malugen

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Prenatal drug exposure can have a molecular impact on the hypothalamic and reward genes that regulate feeding behavior. This can impact feeding regulation, resulting in feeding difficulties and growth failure. This was potentially seen in “McKayla,” a 19- month old girl with a history of in-utero drug exposure, patent ductus arteriosus, and gastroesophageal reflux disease who presented for intensive day treatment feeding therapy. She was diagnosed with Avoidant Restrictive Food Intake Disorder, described as total food refusal and meeting 100% of her caloric needs from a gastrostomy tube. The primary goals during intensive feeding therapy were to increase her oral intake and decrease her reliance on supplementation with formula. Several behavioral antecedent manipulations were implemented to establish consistent responding and make progress towards treatment goals. This included multiple modified bolus placements (using underloaded and Nuk brush), reinforcement contingencies, and variety fading before stability was finally achieved. Following, increasing retention of bites then increasing volume and variety were goals targeted. From treatment onset to the last 3 days of treatment, McKayla's rate of rapid acceptance of bite presentations increased significantly from 33.33% to 93.13%, rapid swallowing went from 0.00% to 92.32%, and her percentage of inappropriate mealtime behavior and expels decreased from 58.33% and 100% to 2.31% and 7.68%, respectively. Overall, the treatment team successfully introduced and increased the bite size of 7 pureed foods, generalize the treatment to caregivers with high integrity, and began facilitating tube weaning. She was receiving about 33.42% of her needs by mouth at the time of discharge. Other nutritional concerns addressed during treatment included drinking a nutritionally complete drink out of an open cup and age appropriate growth. McKayla continued to have emesis almost daily, as was her baseline before starting treatment; however, the frequency during mealtime decreased. Overall, McKayla responded well to treatment. She had a very slow response to treatment and required a lot of antecedent manipulations to establish consistent responding. As the literature suggests, [drug]-exposed neonates, like McKayla, may be at increased risk for nutritional and growth challenges that may persist throughout development. This supports the need for longterm follow-up of infant growth.

Keywords: behavioral intervention, feeding problems, in-utero drug exposure, intensive multidisciplinary intervention

Procedia PDF Downloads 47

Authors: Jihane Bouabid

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The urgency to transition towards sustainable energy sources has revealed itself imperative. Today, in the 21st Century, the intellectual society have imposed technological advancements and improvements, and anticipates expeditious outcomes as an integral component of its relentless pursuit of an elevated standard of living. As a part of empowering human development, driving economic growth and meeting social needs, the access to energy services has become a necessity. As a part of these improvements, we are introducing the project "Mywindturbine" - an interactive web user interface for design and analysis in the field of wind energy, with a particular adherence to the IEC (International Electrotechnical Commission) standard 61400-2 "Wind turbines – Part 2: Design requirements for small wind turbines". Wind turbines play a pivotal role in Morocco's renewable energy strategy, leveraging the nation's abundant wind resources. The IEC 61400-2 standard ensures the safety and design integrity of small wind turbines deployed in Morocco, providing guidelines for performance and safety protocols. The conformity with this standard ensures turbine reliability, facilitates standards alignment, and accelerates the integration of wind energy into Morocco's energy landscape. The aim of the GUI (Graphical User Interface) for engineers and professionals from the field of wind energy systems who would like to design a small wind turbine system following the safety requirements of the international standards IEC 61400-2. The interface provides an easy way to analyze the structure of the turbine machine under normal and extreme load conditions based on the specific inputs provided by the user. The platform introduces an overview to sustainability and renewable energy, with a focus on wind turbines. It features a cross-examination of the input parameters provided from the user for the SLM (Simple Load Model) of small wind turbines, and results in an analysis according to the IEC 61400-2 standard. The analysis of the simple load model encompasses calculations for fatigue loads on blades and rotor shaft, yaw error load on blades, etc. for the small wind turbine performance. Through its structured framework and adherence to the IEC standard, "Mywindturbine" aims to empower professionals, engineers, and intellectuals with the knowledge and tools necessary to contribute towards a sustainable energy future.

Keywords: small wind turbine, IEC 61400-2 standard, user interface., simple load model

Procedia PDF Downloads 34

Authors: Richa Dhingra, Monika, Manav Malhotra, Tilak Raj Bhardwaj, Neelima Dhingra

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5-Alpha-reductases (5AR), a membrane bound, NADPH dependent enzyme and convert male hormone testosterone (T) into more potent androgen dihydrotestosterone (DHT). DHT is the required for the development and function of male sex organs, but its overproduction has been found to be associated with physiological conditions like Benign Prostatic Hyperplasia (BPH). Thus the inhibition of 5ARs could be a key target for the treatment of BPH. In present study, 2D and 3D Quantitative Structure Activity Relationship (QSAR) pharmacophore models have been generated for 5AR based on known inhibitory concentration (IC₅₀) values with extensive validations. The four featured 2D pharmacophore based PLS model correlated the topological interactions (–OH group connected with one single bond) (SsOHE-index); semi-empirical (Quadrupole2) and physicochemical descriptors (Mol. wt, Bromines Count, Chlorines Count) with 5AR inhibitory activity, and has the highest correlation coefficient (r² = 0.98, q² =0.84; F = 57.87, pred r² = 0.88). Internal and external validation was carried out using test and proposed set of compounds. The contribution plot of electrostatic field effects and steric interactions generated by 3D-QSAR showed interesting results in terms of internal and external predictability. The well validated 2D Partial Least Squares (PLS) and 3D k-nearest neighbour (kNN) models were used to search novel 5AR inhibitors with different chemical scaffold. To gain more insights into the molecular mechanism of action of these steroidal derivatives, molecular docking and in silico absorption, distribution, metabolism, and excretion (ADME) studies were also performed. Studies have revealed the hydrophobic and hydrogen bonding of the ligand with residues Alanine (ALA) 63A, Threonine (THR) 60A, and Arginine (ARG) 456A of 4AT0 protein at the hinge region. The results of QSAR, molecular docking, in silico ADME studies provide guideline and mechanistic scope for the identification of more potent 5-Alpha-reductase inhibitors (5ARI).

Keywords: 5α-reductase inhibitor, benign prostatic hyperplasia, ligands, molecular docking, QSAR

Procedia PDF Downloads 139

Authors: Ádám Vass, István Bakos, Irina Borbáth, Zoltán Pászti, István Sajó, András Tompos

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Important requirements for the anode side electrocatalysts of polymer electrolyte membrane (PEM) fuel cells are CO-tolerance, stability and corrosion resistance. Carbon is still the most common material for electrocatalyst supports due to its low cost, high electrical conductivity and high surface area, which can ensure good dispersion of the Pt. However, carbon becomes degraded at higher potentials and it causes problem during application. Therefore it is important to explore alternative materials with improved stability. Molybdenum-oxide can improve the CO-tolerance of the Pt/C catalysts, but it is prone to leach in acidic electrolyte. The Mo was stabilized by isovalent substitution of molybdenum into the rutile phase titanium-dioxide lattice, achieved by a modified multistep sol-gel synthesis method optimized for preparation of Ti0.7Mo.3O2-C composite. High degree of Mo incorporation into the rutile lattice was developed. The conductivity and corrosion resistance across the anticipated potential/pH window was ensured by mixed oxide – activated carbon composite. Platinum loading was carried out using NaBH4 and ethylene glycol; platinum content was 40 wt%. The electrocatalyst was characterized by both material investigating methods (i.e. XRD, TEM, EDS, XPS techniques) and electrochemical methods (cyclic-voltammetry, COads stripping voltammetry, hydrogen oxidation reaction on rotating disc electrode). The electrochemical activity of the sample was compared to commercial 40 wt% Pt/C (Quintech) and PtRu/C (Quintech, Pt= 20 wt%, Ru= 10 wt%) references. Enhanced CO tolerance of the electrocatalyst prepared using the Ti0.7Mo.3O2-C composite material was evidenced by the appearance of a CO-oxidation related 'pre-peak' and by the pronounced shift of the maximum of the main CO oxidation peak towards less positive potential compared to Pt/C. Fuel cell polarization measurements were also carried out using Bio-Logic and Paxitech FCT-150S test device. All details on the design, preparation, characterization and testing by both electrochemical measurements and fuel cell test device of electrocatalyst supported on Ti0.7Mo.3O2-C composite material will be presented and discussed.

Keywords: anode electrocatalyst, composite material, CO-tolerance, TiMoOx

Procedia PDF Downloads 267

Authors: Amr Mohamadien, Ali Imanpour, Sylvester Agbo, Nader Yoosef-Ghodsi, Samer Adeeb

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The fracture toughness resistance curve (e.g., J-R curve and crack tip opening displacement (CTOD) or δ-R curve) is important in facilitating strain-based design and integrity assessment of oil and gas pipelines. This paper aims to present laboratory experimental data to characterize the fracture behavior of pipeline steel. The influential parameters associated with the fracture of API 5L X52 pipeline steel, including different initial crack sizes, were experimentally investigated for a single notch edge bend (SENB). A total of 9 small-scale specimens with different crack length to specimen depth ratios were conducted and tested using single edge notch bending (SENB). ASTM E1820 and BS7448 provide testing procedures to construct the fracture resistance curve (Load-CTOD, CTOD-R, or J-R) from test results. However, these procedures are limited by standard specimens’ dimensions, displacement gauges, and calibration curves. To overcome these limitations, this paper presents the use of small-scale specimens and a 3D-digital image correlation (DIC) system to extract the parameters required for fracture toughness estimation. Fracture resistance curve parameters in terms of crack mouth open displacement (CMOD), crack tip opening displacement (CTOD), and crack growth length (∆a) were carried out from test results by utilizing the DIC system, and an improved regression fitting resistance function (CTOD Vs. crack growth), or (J-integral Vs. crack growth) that is dependent on a variety of initial crack sizes was constructed and presented. The obtained results were compared to the available results of the classical physical measurement techniques, and acceptable matchings were observed. Moreover, a case study was implemented to estimate the maximum strain value that initiates the stable crack growth. This might be of interest to developing more accurate strain-based damage models. The results of laboratory testing in this study offer a valuable database to develop and validate damage models that are able to predict crack propagation of pipeline steel, accounting for the influential parameters associated with fracture toughness.

Keywords: fracture toughness, crack propagation in pipeline steels, CTOD-R, strain-based damage model

Procedia PDF Downloads 42

Authors: Svetlana Guryeva, Inna Kornienko, Andrey Usanov, Dmitry Usanov, Elena Petersen

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Every day cells in our organism are exposed to various factors: chemical agents, reactive oxygen species, ionizing radiation, and others. These factors can cause damage to DNA, cellular membrane, intracellular compartments, and proteins. The fate of cells depends on the exposure intensity and duration. The prolonged and intense exposure causes the irreversible damage accumulation, which triggers the permanent cell cycle arrest (cellular senescence) or cell death programs. In the case of low dose of impacts, it can lead to cell renovation and to cell functional state improvement. Therefore, it is a pivotal question to investigate the factors and doses that result in described positive effects. In order to estimate the influence of different agents, the proliferation index and levels of cell death markers (annexin V/propidium iodide), senescence-associated β-galactosidase, and lipofuscin were measured. The experiments were conducted on primary human fibroblasts of the 8th passage. According to the levels of mentioned markers, these cells were defined as senescent cells. The effect of low-frequency magnetic field was investigated. Different modes of magnetic field exposure were tested. The physical agents were compared with chemical agents: metformin (10 mM) and taurine (0.8 mM and 1.6 mM). Cells were incubating with chemicals for 5 days. The highest decrease in the level of senescence-associated β-galactosidase (21%) and lipofuscin (17%) was observed in the primary senescent fibroblasts after 5 days after double treatments with 48 h intervals with low-frequency magnetic field. There were no significant changes in the proliferation index after magnetic field application. The cytotoxic effect of magnetic field was not observed. The chemical agent taurine (1.6 mM) decreased the level of senescence-associated β-galactosidase (23%) and lipofuscin (22%). Metformin improved the activity of senescence-associated β-galactosidase on 15% and the level of lipofuscin on 19% in this experiment. According to these results, the effect of double treatment with 48 h interval with low-frequency magnetic field and the effect of taurine (1.6 mM) were comparable to the effect of metformin, for which anti-aging properties are proved. In conclusion, this study can become the first step towards creation of the standardized system for the investigation of different effects on senescent cells.

Keywords: biomarkers, magnetic field, metformin, primary fibroblasts, senescence, taurine

Procedia PDF Downloads 257

Authors: K. Karuppasamy

Abstract:

In this paper analysis of an infinite beam resting on multilayer tensionless extensible geosynthetic reinforced granular fill - poor soil system overlying soft soil strata under moving the load with constant velocity is presented. The beam is subjected to a concentrated load moving with constant velocity. The upper reinforced granular bed is modeled by a rough membrane embedded in Pasternak shear layer overlying a series of compressible nonlinear Winkler springs representing the underlying the very poor soil. The multilayer tensionless extensible geosynthetic layer has been assumed to deform such that at the interface the geosynthetic and the soil have some deformation. Nonlinear behavior of granular fill and the very poor soil has been considered in the analysis by means of hyperbolic constitutive relationships. Governing differential equations of the soil foundation system have been obtained and solved with the help of appropriate boundary conditions. The solution has been obtained by employing finite difference method by means of Gauss-Siedel iterative scheme. Detailed parametric study has been conducted to study the influence of various parameters on the response of soil – foundation system under consideration by means of deflection and bending moment in the beam and tension mobilized in the geosynthetic layer. These parameters include the magnitude of applied load, the velocity of the load, damping, the ultimate resistance of the poor soil and granular fill layer. The range of values of parameters has been considered as per Indian Railways conditions. This study clearly observed that the comparisons of multilayer tensionless extensible geosynthetic reinforcement with poor foundation soil and magnitude of applied load, relative compressibility of granular fill and ultimate resistance of poor soil has significant influence on the response of soil – foundation system. However, for the considered range of velocity, the response has been found to be insensitive towards velocity. The ultimate resistance of granular fill layer has also been found to have no significant influence on the response of the system.

Keywords: infinite beams, multilayer tensionless extensible geosynthetic, granular layer, moving load and nonlinear behavior of poor soil

Procedia PDF Downloads 414