Search results for: drug discovery

Authors: Anyimc, C. J. Aneke, J. O. Orji, O. Nworie, U. C. C. Egbule

Abstract:

The microbial examination and antimicrobial susceptibility profile of microorganism isolated from the salt mining site in Ebonyi state were evaluated in the present study using a standard microbiological technique. A total of 300 samples were randomly collected in three sample groups (A, B, and C) of 100 each. Isolation, Identification and characterization of organization present on the soil samples were determined by culturing, gram-staining and biochemical technique. The result showed the following organisms were isolated with their frequency as follow: Bacillus species (37.3%) and Staphylococcus species(23.5%) had the highest frequency in the whole Sample group A and B while Klebsiella specie (15.7%), Pseudomonas species(13.7%), and Erwinia species (9.8%) had the least. Rhizopus species (42.0%) and Aspergillus species (26.0%) were the highest fungi isolated, followed by Penicillum species (20.0%) while Mucor species (4.0%), and Fusarium species (8.0%) recorded the least. Sample group C showed high microbial population of all the microbial isolates when compared to sample group A and B. Disc diffusion method was used to determine the susceptibility of isolated bacteria to various antibiotics (oxfloxacin, pefloxacin, ciprorex, augumentin, gentamycin, ciproflox, septrin, ampicillin), while agar well diffusion method was used to determine the susceptibility of isolated fungi to some antifungal drugs (metronidazole, ketoconazole, itraconazole fluconazole). The antibacterial activity of the antibiotics used showed that ciproflux has the best inhibitory effect on all the test bacteria. Ketoconazole showed the highest inhibitory effect on the fungal isolates, followed by itraconazole, while metronidazole and fluconazole showed the least inhibitory effect on the entire test fungal isolates. Hence, the multiple drug resistance of most isolates to appropriate drugs of choice are of great public health concern and cells for periodic monitoring of antibiograms to detect possible changing patterns. Microbes isolated in the salt mining site can also be used as a source of gene(s) that can increase salt tolerance in different crop species through genetic engineering.

Keywords: microorganisms, antibacterial, antifungal, resistance, salt mining site, Ebonyi State

Procedia PDF Downloads 291

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

Abstract:

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

Procedia PDF Downloads 212

Authors: Meichen He, Xuan Yang

Abstract:

Background: In the field of psychotherapy, the role of the family of origin is of utmost importance. Over the past few decades, both individual-oriented and family-oriented approaches to child therapy have shown moderate success in reducing children's psychological and behavioral issues. Objective: However, in exploring how the family of origin influences individuals, it has been noted that there is a lack of comprehensive measurement indicators and an absence of an exact model to assess the impact of the family of origin on individual development. Therefore, this study aims to develop a model based on a literature review regarding the influence of the family of origin on children. Specifically, it will examine the effects of factors such as education level, economic status, maternal age, family integration, family violence, marital conflict, parental substance abuse, and alcohol consumption on children's self-confidence and life satisfaction. Through this research, we aim to further investigate the impact of the family of origin on children and provide directions for future research in positive psychology and psychotherapy. Methods: This study will employ a literature review methodology to gather and analyze relevant research articles on the influence of the family of origin on children. Subsequently, we will conduct quantitative analyses to establish a comprehensive model explaining how family of origin factors affect children's psychological and behavioral outcomes. Findings: the research has revealed that family of origin factors, including education level, economic status, maternal age, family integration, family violence, marital conflict, parental drug and alcohol consumption, have an impact on children's self-confidence and life satisfaction. These factors can affect children's psychological well-being and happiness through various pathways. Implications: The results of this study will contribute to a better understanding of the influence of the family of origin on children and provide valuable directions for future research in positive psychology and psychotherapy. This research will enhance awareness of children's psychological well-being and lay the foundation for improving psychotherapeutic methods.

Keywords: family of origion, positive psychology, developmental psychology, family education, social psychology, educational psychology

Procedia PDF Downloads 124

Authors: B. Shaw, K. Doherty

Abstract:

The Cultural Communication and Computing Research Institute (C3RI) is a diverse multidisciplinary research institute including art, design, media production, communication studies, computing and engineering. Across these disciplines it can seem like there are enormous differences of research practice and convention, including differing positions on objectivity and subjectivity, certainty and evidence, and different political and ethical parameters. These differences sit within, often unacknowledged, histories, codes, and communication styles of specific disciplines, and it is all these aspects that can make understanding of research practice across disciplines difficult. To explore this, a one day event was orchestrated, testing how a PhD community might communicate and share research in progress in a multi-disciplinary context. Instead of presenting results at a conference, research students were tasked to articulate their method of inquiry. A working party of students from across disciplines had to design a conference call, visual identity and an event framework that would work for students across all disciplines. The process of establishing the shape and identity of the conference was revealing. Even finding a linguistic frame that would meet the expectations of different disciplines for the conference call was challenging. The first abstracts submitted either resorted to reporting findings, or only described method briefly. It took several weeks of supported intervention for research students to get ‘inside’ their method and to understand their research practice as a process rich with philosophical and practical decisions and implications. In response to the abstracts the conference committee generated key methodological categories for conference sessions, including sampling, capturing ‘experience’, ‘making models’, researcher identities, and ‘constructing data’. Each session involved presentations by visual artists, communications students and computing researchers with inter-disciplinary dialogue, facilitated by alumni Chairs. The apparently simple focus on method illuminated research process as a site of creativity, innovation and discovery, and also built epistemological awareness, drawing attention to what is being researched and how it can be known. It was surprisingly difficult to limit students to discussing method, and it was apparent that the vocabulary available for method is sometimes limited. However, by focusing on method rather than results, the genuine process of research, rather than one constructed for approval, could be captured. In unlocking the twists and turns of planning and implementing research, and the impact of circumstance and contingency, students had to reflect frankly on successes and failures. This level of self – and public- critique emphasised the degree of critical thinking and rigour required in executing research and demonstrated that honest reportage of research, faults and all, is good valid research. The process also revealed the degree that disciplines can learn from each other- the computing students gained insights from the sensitive social contextualizing generated by communications and art and design students, and art and design students gained understanding from the greater ‘distance’ and emphasis on application that computing students applied to their subjects. Finding the means to develop dialogue across disciplines makes researchers better equipped to devise and tackle research problems across disciplines, potentially laying the ground for more effective collaboration.

Keywords: interdisciplinary, method, research student, training

Procedia PDF Downloads 187

Authors: Yutong Wan, John N. Wood

Abstract:

Introduction: SCN9A encoded Nav1.7 is an ideal therapeutic target with minimal side effects for the pharmaceutical industry because SCN9A variants can cause both human gains of function pain-related mutations and loss of function pain-free mutations. This study reviews the clinical effectiveness of existing Nav1.7 inhibitors, which theoretically should be powerful analgesics. Methods: A systematic review is conducted on the effectiveness of current Nav1.7 blockers undergoing clinical trials. Studies were mainly extracted from PubMed, U.S. National Library of Medicine Clinical Trials, World Health Organization International Clinical Trials Registry, ISRCTN registry platform, and Integrated Research Approval System by NHS. Only studies with full text available and those conducted using double-blinded, placebo controlled, and randomised designs and reporting at least one analgesic measurement were included. Results: Overall, 61 trials were screened, and eight studies covering PF 05089771 (Pfizer), TV 45070 (Teva & Xenon), and BIIB074 (Biogen) met the inclusion criteria. Most studies were excluded because results were not published. All three compounds demonstrated insignificant analgesic effects, and the comparison between PF 05089771 and pregabalin/ibuprofen showed that PF 05089771 was a much weaker analgesic. All three drug candidates only have mild side effects, indicating the potentials for further investigation of Nav1.7 antagonists. Discussion: The failure of current Nav1.7 small molecule inhibitors might attribute to ignorance of the key role of endogenous systems in Nav1.7 null mutants, the lack of selectivity and blocking potency, and central impermeability. The synergistic combination of analgesic drugs, a recent UCL patent, combining a small dose of Nav1.7 blockers and opioids or enkephalinase inhibitors dramatically enhanced the analgesic effects. Conclusion: The current clinical testing Nav1.7 blockers are generally disappointing. However, the newer generation of Nav1.7 targeting analgesics has overcome the major constraints of its predecessors.

Keywords: chronic pain, Nav1.7 blockers, SCN9A, systematic review

Procedia PDF Downloads 111

Authors: Nadia K. Thalji

Abstract:

In the timeless tapestry of human culture, theater, mythology, and psychology intersect to weave narratives that transcend temporal and spatial boundaries. For millennia, actors have stood as guardians of intuitive wisdom, their craft serving as a conduit for the collective unconscious. This paper embarks on a journey through the realms of creative expression, melding the insights of cross-cultural psychology with the mystical allure of serendipity and synchronicity. At the nexus of these disciplines lies the enigmatic process of active imagination, a gateway to the depths of the psyche elucidated by Jung. Within the hallowed confines of the black box theater at the Department of Performing Arts, UFRGS University in Brazil, this study unfolds. Over the span of four months, a cadre of artists embarked on a voyage of exploration, harnessing the powers of imagery, movement, sound, and dreams to birth a performance that resonated with the echoes of ancient wisdom. Drawing inspiration from the fabled Oracle of Delphi and the priestesses who once dwelled within its sacred precincts, the production delves into the liminal spaces where myth and history intertwine. Through the alchemy of storytelling, participants navigate the labyrinthine corridors of cultural memory, unraveling the threads that bind the past to the present. Central to this endeavor is the phenomenon of synchronicity, wherein seemingly disparate elements coalesce in a dance of cosmic resonance. Serendipity becomes a guiding force, leading actors and audience alike along unexpected pathways of discovery. As the boundaries between performer and spectator blur, the performance becomes a crucible wherein individual narratives merge to form a collective tapestry of shared experience. Yet, beneath the surface of spectacle lies a deeper truth: the exploration of the spiritual dimensions of artistic expression. Through intuitive inquiry and embodied practice, artists tap into reservoirs of insight that transcend rational comprehension. In the communion of minds and bodies, the stage becomes a sacred space wherein the numinous unfolds in all its ineffable glory. In essence, this paper serves as a testament to the transformative power of the creative act. Across cultures and epochs, the theater has served as a crucible wherein humanity grapples with the mysteries of existence. Through the lens of cross-cultural psychology, we glimpse the universal truths that underlie the myriad manifestations of human creativity. As we navigate the turbulent currents of modernity, the wisdom of the ancients beckons us to heed the call of the collective unconscious. In the synthesis of myth and meaning, we find solace amidst the chaos, forging connections that transcend the boundaries of time and space. And in the sacred precincts of the theater, we discover the eternal truth that art is, and always shall be, the soul's journey into the unknown.

Keywords: theater, mythology, cross-cultural, synchronicity, creativity, serendipity, spiritual

Procedia PDF Downloads 43

Authors: Lukasz Kaniuk, Mateusz M. Marzec, Andrzej Bernasik, Urszula Stachewicz

Abstract:

Electrospinning is one of the commonly used methods to produce micro- or nano-fibers. The properties of electrospun fibers allow them to be used to produce tissue scaffolds, biodegradable bandages, or purification membranes. The morphology of the obtained fibers depends on the composition of the polymer solution as well as the processing parameters. Interesting properties such as high fiber porosity can be achieved by changing humidity during electrospinning. Moreover, by changing voltage polarity in electrospinning, we are able to alternate functional groups at the surface of fibers. In this study, electrospun fibers were made of natural, thermoplastic polyester – PHBV (poly(3-hydroxybutyric acid-co-3-hydrovaleric acid). The fibrous mats were obtained using both positive and negative voltage polarities, and their surface was characterized using X-ray photoelectron spectroscopy (XPS, Ulvac-Phi, Chigasaki, Japan). Furthermore, the effect of the humidity on surface morphology was investigated using scanning electron microscopy (SEM, Merlin Gemini II, Zeiss, Germany). Electrospun PHBV fibers produced with positive and negative voltage polarity had similar morphology and the average fiber diameter, 2.47 ± 0.21 µm and 2.44 ± 0.15 µm, respectively. The change of the voltage polarity had a significant impact on the reorientation of the carbonyl groups what consequently changed the surface potential of the electrospun PHBV fibers. The increase of humidity during electrospinning causes porosity in the surface structure of the fibers. In conclusion, we showed within our studies that the process parameters such as humidity and voltage polarity have a great influence on fiber morphology and chemistry, changing their functionality. Surface properties of polymer fiber have a significant impact on cell integration and attachment, which is very important in tissue engineering. The possibility of changing surface porosity allows the use of fibers in various tissue engineering and drug delivery systems. Acknowledgment: This study was conducted within 'Nanofiber-based sponges for atopic skin treatment' project., carried out within the First TEAM programme of the Foundation for Polish Science co-financed by the European Union under the European Regional Development Fund, project no POIR.04.04.00-00- 4571/18-00.

Keywords: cells integration, electrospun fiber, PHBV, surface characterization

Procedia PDF Downloads 101

Authors: Rodrigo Arnaldo Scarpel

Abstract:

Trend following is a widely accepted investment strategy that adopts a rule-based trading mechanism that rather than striving to predict market direction or on information gathering to decide when to buy and when to sell a stock. Thus, in trend following one must respond to market’s movements that has recently happen and what is currently happening, rather than on what will happen. Optimally, in trend following strategy, is to catch a bull market at its early stage, ride the trend, and liquidate the position at the first evidence of the subsequent bear market. For applying the trend following strategy one needs to find the trend and identify trade signals. In order to avoid false signals, i.e., identify fluctuations of short, mid and long terms and to separate noise from real changes in the trend, most academic works rely on moving averages and other technical analysis indicators, such as the moving average convergence divergence (MACD) and the relative strength index (RSI) to uncover intelligible stock trading rules following trend following strategy philosophy. Recently, some works has applied machine learning techniques for trade rules discovery. In those works, the process of rule construction is based on evolutionary learning which aims to adapt the rules to the current environment and searches for the global optimum rules in the search space. In this work, instead of focusing on the usage of machine learning techniques for creating trading rules, a time series trend classification employing a semi-supervised approach was used to early identify both the beginning and the end of upward and downward trends. Such classification model can be employed to identify trade signals and the decision-making procedure is that if an up-trend (down-trend) is identified, a buy (sell) signal is generated. Semi-supervised learning is used for model training when only part of the data is labeled and Semi-supervised classification aims to train a classifier from both the labeled and unlabeled data, such that it is better than the supervised classifier trained only on the labeled data. For illustrating the proposed approach, it was employed daily trade information, including the open, high, low and closing values and volume from January 1, 2000 to December 31, 2022, of the São Paulo Exchange Composite index (IBOVESPA). Through this time period it was visually identified consistent changes in price, upwards or downwards, for assigning labels and leaving the rest of the days (when there is not a consistent change in price) unlabeled. For training the classification model, a pseudo-label semi-supervised learning strategy was used employing different technical analysis indicators. In this learning strategy, the core is to use unlabeled data to generate a pseudo-label for supervised training. For evaluating the achieved results, it was considered the annualized return and excess return, the Sortino and the Sharpe indicators. Through the evaluated time period, the obtained results were very consistent and can be considered promising for generating the intended trading signals.

Keywords: evolutionary learning, semi-supervised classification, time series data, trading signals generation

Procedia PDF Downloads 64

Authors: Dong-An Wang

Abstract:

All kinds of microspheres have been extensively employed as carriers for drug, gene and therapeutic cell delivery. Most therapeutic cell delivery microspheres rely on a two-step methodology: fabrication of microspheres and subsequent seeding of cells onto them. In this study, we have developed a novel one-step cell encapsulation technique using a convenient and instant water-in-oil single emulsion approach to form cell-encapsulated gelatin microspheres. This technology is adopted for hyaline cartilage tissue engineering, in which autologous chondrocytes are used as therapeutic cells. Cell viability was maintained throughout and after the microsphere formation (75-100 µm diameters) process that avoids involvement of any covalent bonding reactions or exposure to any further chemicals. Further encapsulation of cell-laden microspheres in alginate gels were performed under 4°C via a prompt process. Upon the formation of alginate constructs, they were immediately relocated into CO2 incubator where the temperature was maintained at 37°C; under this temperature, the cell-laden gelatin microspheres dissolved within hours to yield similarly sized cavities and the chondrocytes were therefore suspended within the cavities inside the alginate gel bulk. Hence, the gelatin cell-laden microspheres served two roles: as cell delivery vehicles which can be removable through temperature curing, and as porogens within an alginate hydrogel construct to provide living space for cell growth and tissue development as well as better permeability for mutual diffusions. These cell-laden microspheres, namely “temperature-cured dissolvable gelatin microsphere based cell carriers” (tDGMCs), were further encapsulated in a chondrocyte-laden alginate scaffold system and analyzed by WST-1, gene expression analyses, biochemical assays, histology and immunochemistry stains. The positive results consistently demonstrated the promise of tDGMC technology in delivering these non-anchorage dependent cells (chondrocytes). It can be further conveniently translated into delivery of other non-anchorage dependent cell species, including stem cells, progenitors or iPS cells, for regeneration of tissues in internal organs, such as engineered hepatogenesis or pancreatic regeneration.

Keywords: biomaterials, tissue engineering, microsphere, hydrogel, porogen, anchorage dependence

Procedia PDF Downloads 373

Authors: Yee-Seul So, Guiseppe Ianiri, Alex Idnurm, Yong-Sun Bahn

Abstract:

Tor1 is a serine/threonine protein kinase that is widely conserved across eukaryotic species. Tor1 was first identified in Saccharomyces cerevisiae as a target of rapamycin (TOR). The TOR pathway has been implicated in regulating cellular responses to nutrients, proliferation, translation, transcription, autophagy, and ribosome biogenesis. Here we identified two homologues of S. cerevisiae Tor proteins, CNAG_06642 (Tor1) and CNAG_05220 (Tlk1, TOR-like kinase 1), in Cryptococcus neoformans causing a life-threatening fungal meningoencephalitis. Both Tor1 and Tlk1 have rapamycin-binding (RB) domains but Tlk1 has truncated RB form. To study the TOR-signaling pathway in the fungal pathogen, we attempt to construct the tor1Δ and tlk1Δ mutants and phenotypically analyze them. Although we failed to construct the tor1Δ mutant, we successfully construct the tlk1Δ mutant. The tlk1Δ mutant does not exhibit any discernable phenotypes, suggesting that Tlk1 is dispensable in C. neoformans. The essentiality of TOR1 is independently confirmed by constructing the TOR1 promoter replacement strain by using a copper transporter 4 (CTR4) promoter and the TOR1/tor1 heterozygous mutant in diploid C. neoformans strain background followed by sporulation analysis. To further analyze the function of Tor1, we construct TOR1 overexpression mutant using a constitutively active histone H3 in C. neoformans. We find that the Tor1 overexpression mutant is resistant to rapamycin but the tlk1Δ mutant does not exhibit any altered resistance to rapamycin, further confirming that Tor1, but not Tlk1, is critical for TOR signaling. Furthermore, we found that Tor1 is involved in response to diverse stresses, including genotoxic stress, oxidative stress, thermo-stress, antifungal drug treatment, and production of melanin. To identify any TOR-related transcription factors, we screened C. neoformans transcription factor library that we constructed in our previous study and identified several potential downstream factors of Tor1, including Atf1, Crg1 and Bzp3. In conclusion, the current study provides insight into the role of the TOR signaling pathway in human fungal pathogens as well as C. neoformans.

Keywords: fungal pathogen, serine/threonine kinase, target of rapamycin, transcription factor

Procedia PDF Downloads 209

Authors: E. O. Okan, A. Kepic, P. Williams

Abstract:

Iron oxide copper gold (IOCG) deposits constitute important sources of copper and gold in Australia especially since the discovery of the supergiant Olympic Dam deposits in 1975. They are considered to be metasomatic expressions of large crustal-scale alteration events occasioned by intrusive actions and are associated with felsic igneous rocks in most cases, commonly potassic igneous magmatism, with the deposits ranging from ~2.2 –1.5 Ga in age. For the past two decades, geological, geochemical and potential methods have been used to identify the structures hosting these deposits follow up by drilling. Though these methods have largely been successful for shallow targets, at deeper depth due to low resolution they are limited to mapping only very large to gigantic deposits with sufficient contrast. As the search for ore-bodies under regolith cover continues due to depletion of the near surface deposits, there is a compelling need to develop new exploration technology to explore these deep seated ore-bodies within 1-4km which is the current mining depth range. Seismic reflection method represents this new technology as it offers a distinct advantage over all other geophysical techniques because of its great depth of penetration and superior spatial resolution maintained with depth. Further, in many different geological scenarios, it offers a greater ‘3D mapability’ of units within the stratigraphic boundary. Despite these superior attributes, no arguments for crustal scale seismic surveys have been proposed because there has not been a compelling argument of economic benefit to proceed with such work. For the seismic reflection method to be used at these scales (100’s to 1000’s of square km covered) the technical risks or the survey costs have to be reduced. In addition, as most IOCG deposits have large footprint due to its association with intrusions and large fault zones; we hypothesized that these deposits can be found by mainly looking for the seismic signatures of intrusions along prospective structures. In this study, we present two of such cases: - Olympic Dam and Vulcan iron-oxide copper-gold (IOCG) deposits all located in the Gawler craton, South Australia. Results from our 2D modelling experiments revealed that seismic reflection surveys using 20m geophones and 40m shot spacing as an exploration tool for locating IOCG deposit is possible even when hosted in very complex structures. The migrated sections were not only able to identify and trace various layers plus the complex structures but also show reflections around the edges of intrusive packages. The presences of such intrusions were clearly detected from 100m to 1000m depth range without losing its resolution. The modelled seismic images match the available real seismic data and have the hypothesized characteristics; thus, the seismic method seems to be a valid exploration tool to find IOCG deposits. We therefore propose that 2D seismic survey is viable for IOCG exploration as it can detect mineralised intrusive structures along known favourable corridors. This would help in reducing the exploration risk associated with locating undiscovered resources as well as conducting a life-of-mine study which will enable better development decisions at the very beginning.

Keywords: crustal scale, exploration, IOCG deposit, modelling, seismic surveys

Procedia PDF Downloads 310

Authors: Patarasuda Chaisupa, R. Clay Wright

Abstract:

The selection of appropriate biomolecular targets is a crucial aspect of biopharmaceutical development. The Auxin-Inducible Degron Degradation (AID) technology has demonstrated remarkable potential in efficiently and rapidly degrading target proteins, thereby enabling the identification and acquisition of drug targets. The AID system also offers a viable method to deplete specific proteins, particularly in cases where the degradation pathway has not been exploited or when the adaptation of proteins, including the cell environment, occurs to compensate for the mutation or gene knockout. In this study, we have engineered an improved AID system tailored to deplete proteins of interest. This AID construct combines the auxin-responsive E3 ubiquitin ligase binding domain, AFB2, and the substrate degron, IAA17, fused to the target genes. Essential genes of fungi with the lowest percent amino acid similarity to human and plant orthologs, according to the Basic Local Alignment Search Tool (BLAST), were cloned into the AID construct in S. cerevisiae (AID-tagged strains) using a modular yeast cloning toolkit for multipart assembly and direct genetic modification. Each E3 ubiquitin ligase and IAA17 degron was fused to a fluorescence protein, allowing for real-time monitoring of protein levels in response to different auxin doses via cytometry. Our AID system exhibited high sensitivity, with an EC50 value of 0.040 µM (SE = 0.016) for AFB2, enabling the specific promotion of IAA17::target protein degradation. Furthermore, we demonstrate how this improved AID system enhances quantitative functional studies of various proteins in fungi. The advancements made in auxin-inducible protein degradation in this study offer a powerful approach to investigating critical target protein viability in fungi, screening protein targets for drugs, and regulating intracellular protein abundance, thus revolutionizing the study of protein function underlying a diverse range of biological processes.

Keywords: synthetic biology, bioengineering, molecular biology, biotechnology

Procedia PDF Downloads 71

Authors: Avani Jain, Hasmukh Jain, S. Shelley, M. Indirani, Shilpa Kalal, Jayakanth Amalachandran

Abstract:

Aim of the Study: To assess the effect of orally administered Itopride on gall bladder ejection fraction by fatty meal cholescintigraphy in patients with diabetes. Materials and Methods: Thirty patients (20 males, 10 females, mean age 46+10 yrs) with history of diabetes mellitus (mean duration 4.8+4.1 yrs, fasting blood glucose level 130+35 mg/dl and 2-hours post-prandial blood glucose level 196+76 mg/dl) and found to have gall bladder dysfunction on fatty-meal stimulated cholescintigraphy were selected for this study. These patients underwent a repeat cholescintigraphy similar to baseline study, with 50 mg of Itopride orally along with fatty meal. Pre- and post-Itopride GBEF were then compared to assess the effect of Itopride on gall bladder contraction. Results: Out of these 30 patients, 2 had dyskinetic, 4 had akinetic, 22 had moderately hypokinetic and the remaining 2 had hypokinetic gall bladder function in the baseline study with > 60% GBEF being taken as the normal value. Mean percentage of GBEF in the baseline study was 32%+13% and the mean percentage of GBEF in the post-Itopride study was 57%+17% with change in mean percentage of GBEF being 24%+21%. GBEF of the “baseline study” was significantly lower as compared to GBEF in the “post-Itopride study” (p < 0.05). Conclusion: Diabetic patients with biliary-type pain often tend to have impaired gallbladder function. Cholescintigraphy with fatty meal-stimulation is a simple, cheap and useful investigation for assessment of gallbladder dysfunction in these patients, before any structural changes occur within the lumen or wall of the gall bladder. Improvement in gallbladder ejection fraction after oral administration of a single dose of Itopride, a newer prokinetic drug with fewer side effects, as assessed by cholescintigraphy, provides enough evidence of future therapeutic response. Administration of Itopride, in therapeutic dosage, therefore may be expected to cause significant improvement in gallbladder ejection fraction and hence prolong stone formation within the gall bladder and also prevent the associated long term complications. Hence, based on scintigraphic evidence, Itopride may be recommended, by clinicians, for management of symptomatic diabetic patients having gallbladder dysfunction.

Keywords: itopride, gall bladder ejection fraction, fatty meal, cholescintigraphy, diabetes

Procedia PDF Downloads 412

Authors: S. Alemayehu, F. A. Abera, K. M. Ayimut, R. Mahroof, J. Harvey, B. Subramanyam

Abstract:

The occurrence of mycotoxins in sesame seeds poses a significant threat to food safety and the economy in Ethiopia. This study aimed to determine the levels and occurrence of mycotoxins in on-farm stored sesame seeds in major-growing districts of Ethiopia. A total of 470 sesame seed samples were collected from randomly selected farmers' storage structures in five major-growing districts using purposive sampling techniques. An enzyme-linked immunosorbent assay (ELISA) was used to analyze the collected samples for the presence of four mycotoxins: total aflatoxins (AFT), ochratoxin A (OTA), total fumonisins (FUM), and deoxynivalenol (DON). The study found that all samples contained varying levels of mycotoxins, with AFT and DON being the most prevalent. AFT concentrations in detected samples ranged from 2.5 to 27.8 parts per billion (ppb), with a mean concentration of 13.8 ppb. OTA levels ranged from 5.0 ppb to 9.7 ppb, with a mean level of 7.1 ppb. Total fumonisin concentrations ranged from 300 to 1300 ppb in all samples, with a mean of 800 ppb. DON concentrations ranged from 560 to 700 ppb in the analyzed samples. The majority (96.8%) of the samples were safe from AFT, FUM, and DON mean levels when compared to the Federal Drug Administration maximum limit. AFT-OTA, DON-OTA, AFT-FUM, FUM-DON, and FUM-OTA, respectively, had co-occurrence rates of 44.0, 38.3, 33.8, 30.2, 29.8 and 26.0% for mycotoxins. On average, 37.2% of the sesame samples had fungal infection, and seed germination rates ranged from 66.8% to 91.1%. The Limmu district had higher levels of total aflatoxins, kernel infection, and lower germination rates than other districts. The Wollega variety of sesame had higher kernel infection, total aflatoxins concentration, and lower germination rates than other varieties. Grain age had a statistically significant (p<0.05) effect on both kernel infection and germination. The storage methods used for sesame in major-growing districts of Ethiopia favor mycotoxin-producing fungi. As the levels of mycotoxins in sesame are of public health significance, stakeholders should come together to identify secure and suitable storage technologies to maintain the quantity and quality of sesame at the level of smallholder farmers. This study suggests the need for suitable storage technologies to maintain the quality of sesame and reduce the risk of mycotoxin contamination.

Keywords: districts, seed germination, kernel infection, moisture content, relative humidity, temperature

Procedia PDF Downloads 101

Authors: Bhargavi G. Iyer, Ojaswi Bhagat

Abstract:

It is often noted that the value of a novel idea lies in its successful implementation. However, successful implementation requires the nurturing and encouragement of innovation. Nascent competitors are a true representation of innovation in any given industry. A nascent competitor is an entity whose prospective innovation poses a future threat to an incumbent dominant competitor. While a nascent competitor benefits in several ways, it is also exposed significantly and is at greater risk of facing the brunt of exclusionary practises and abusive conduct by dominant incumbent competitors in the industry. This research paper aims to explore the risks and threats faced by nascent competitors and analyse the benefits they accrue as well as the advantages they proffer to the economy; through an analytical, critical study. In such competitive market environments, a rise of the acquisitions of nascent competitors by the incumbent dominants is observed. Therefore, this paper will examine the dynamics of nascent acquisition. Further, this paper hopes to specifically delve into the role of antitrust bodies in regulating nascent acquisition. This paper also aspires to deal with the question how to distinguish harmful from harmless acquisitions in order to facilitate ideal enforcement practice. This paper proposes mechanisms of scrutiny in order to ensure healthy market practises and efficient merger control in the context of nascent acquisitions. Taking into account the scope and nature of the topic, as well as the resources available and accessible, a combination of the methods of doctrinal research and analytical research were employed, utilising secondary sources in order to assess and analyse the subject of research. While legally evaluating the Killer Acquisition theory and the Nascent Potential Acquisition theory, this paper seeks to critically survey the precedents and instances of nascent acquisitions. In addition to affording a compendious account of the legislative framework and regulatory mechanisms in the United States, the United Kingdom, and the European Union; it hopes to suggest an internationally practicable legal foundation for domestic legislation and enforcement to adopt. This paper hopes to appreciate the complexities and uncertainties with respect to nascent acquisitions and attempts to suggest viable and plausible policy measures in antitrust law. It additionally attempts to examine the effects of such nascent acquisitions upon the consumer and the market economy. This paper weighs the argument of shifting the evidentiary burden on to the merging parties in order to improve merger control and regulation and expounds on its discovery of the strengths and weaknesses of the approach. It is posited that an effective combination of factual, legal, and economic analysis of both the acquired and acquiring companies possesses the potential to improve ex post and ex ante merger review outcomes involving nascent companies; thus, preventing anti-competitive practises. This paper concludes with an analysis of the possibility and feasibility of industry-specific identification of anti-competitive nascent acquisitions and implementation of measures accordingly.

Keywords: acquisition, antitrust law, exclusionary practises merger control, nascent competitor

Procedia PDF Downloads 142

Authors: Gabriel Dolabella, Henrique Rangel, Stella Araújo, Carlos Bolonha, Igor de Lazari

Abstract:

Public security is a common subject on the Brazilian political agenda. The seventh largest economy in the world has high crime and insecurity rates. Specialists try to explain this social picture based on poverty, inequality or public policies addressed to drug trafficking. This excerpt approaches State measures to handle that picture. Therefore, the public security - law enforcement institutions - is at the core of this paper, particularly the relationship among federal and state law enforcement agencies, mainly ruled by a system of urgency. The problems are informal changes on law enforcement management and public opinion collaboration to these changes. Whenever there were huge international events, Brazilian armed forces occupied streets to assure law enforcement - ensuring the order. This logic, considered in the long time, could impact the federal structure of the country. The post-madisonian theorists verify that urgency is often associated to delegation of powers, which is true for Brazilian law enforcement, but here there is a different delegation: States continuously delegate law enforcement powers to the federal government throughout the use of Armed Forces. Therefore, the hypothesis is: Brazil is under a political process of federalization of public security. The political framework addressed here can be explained by the disrespect of legal constraints and the failure of rule of law theoretical models. The methodology of analysis is based on general criteria. Temporally, this study investigates events from 2003, when discussions about the disarmament statute begun. Geographically, this study is limited to Brazilian borders. Materially, the analysis result from the observation of legal resources and political resources (pronouncements of government officials). The main parameters are based on post-madisonianism and federalization of public security can be assessed through credibility and popularity that allow evaluation of this political process of constitutional change. The objective is to demonstrate how the Military Forces are used in public security, not as a random fact or an isolated political event, in order to understand the political motivations and effects that stem from that use from an institutional perspective.

Keywords: public security, governability, rule of law, federalism

Procedia PDF Downloads 656

Authors: Recep Kesli, Gulşah Asik, Cengiz Demir, Onur Turkyilmaz

Abstract:

Objective: Acinetobacter baumannii (A. baumannii) can cause health-care associated infections, such as bacteremia, urinary tract and wound infections, endocarditis, meningitis, and pneumonia, particularly in intensive care unit patients. In this study, we aimed to evaluate A. baumannii production in sputum and bronchoalveolar lavage and susceptibilities for antibiotics in a 24 months period. Methods: Between October 2013 and September 2015, Acinetobacter baumannii isolated from respiratory tract speciments were evaluated retrospectively. The strains were isolated from the different intensive care units patients. A. baumannii strains were identified by both the conventional methods and aoutomated identification system -VITEK 2 (bio-Merieux, Marcy l’etoile, France). Antibiotic resistance testing was performed by Kirby-Bauer disc diffusion method according to CLSI criteria. Results: All the ninety isolates included in the study were from respiratory tract specimens. While of all the isolated 90 Acinetobacter baumannii strains were found to be resistant (100%), against ceftriaxone, ceftazidime, ciprofloxacin and piperacillin/ tazobactam, resistance rates against other tested antibiotics found as follows; meropenem 77, 86%, imipenem 75, 83%, trimethoprim-sulfamethoxazole (TMP-STX) 69, 76,6%, gentamicin 51, 56,6% and amikacin 48, 53,3%. Colistin was found as the most effective antibiotic against Acinetobacter baumannii, and there were not found any resistant (0%) strain against colistin. Conclusion: This study demonstrated that the no resistance was found in Acinetobacter baumannii against to colistin. High rates of resistance to carbapenems (imipenem and meropenem) and other tested antibiotics (ceftiaxone, ceftazidime, ciprofloxacine, piperacilline-tazobactam, TMP-STX gentamicin and amikacin) also have remarkable resistance rates. There was a significant relationship between demographic features of patients such as age, undergoing mechanical ventilation, length of hospital stay with resistance rates. High resistance rates against antibiotics require implementation of the infection control program and rational use of antibiotics. In the present study, while there were not found colistin resistance, panresistance were found against to ceftriaxone, ceftazidime, ciprofloxacin and piperacillin/ tazobactam.

Keywords: acinetobacter baumannii, antibiotic resistance, multi drug resistance, intensive care unit

Procedia PDF Downloads 267

Authors: Živilė Jurgelėnė, Vitalijus Karabanovas, Augustas Morkvėnas, Reda Dzingelevičienė, Nerijus Dzingelevičius, Saulius Raugelė, Boguslaw Buszewski

Abstract:

The short- and long-term effects of COVID-19 antiviral drug molnupiravir and micro/nanoplastics on the early development of Salmo trutta were investigated using accumulation and exposure studies. Salmo trutta were used as standardized test organisms in toxicity studies of COVID-19 waste contaminants. The 2D/3D imaging was performed using confocal fluorescence spectral imaging microscopy to assess the uptake, bioaccumulation, and distribution of molnupiravir and micro/nanoplastics complex in live fish. Our study results demonstrated that molnupiravir may interact with a micro/nanoplastics and modify their spectroscopic parameters and toxicity to S. trutta embryos and larvae. The 0.2 µm size microplastics at a concentration of 10 mg/L were found to be stable in aqueous media than 0.02 µm, and 2 µm sizes polymeric particles. This study demonstrated that polymeric particles can adsorb molnupiravir that are present in mixtures and modify the accumulation of molnupiravir in Salmo trutta embryos and larvae. In addition, 2D/3D confocal fluorescence imaging showed that the single polymeric particle hardly accumulates and couldn't penetrate outer tissues of the tested organism. However, co-exposure micro/nanoplastics and molnupiravir could significantly enhance the polymeric particles capability of accumulating on surface tissues and penetrating surface tissue of fish in early development. Exposure to molnupiravir at 2 g/L concentration and co-exposure to micro/nanoplastics and molnupiravir did not bring about survival changes in in the early stages of Salmo trutta development, but we observed the reduction in heart rate and decrease in gill ventilation. The statistical analysis confirmed that micro/nanoplastics used in combination with molnupiravir enhance the toxicity of the latter micro/nanoplastics to embryos and larvae. This research has received funding from the European Regional Development Fund (project No 13.1.1-LMT-K-718-05-0014) under a grant agreement with the Research Council of Lithuania (LMTLT), and it was funded as part of the European Union’s measure in response to the COVID-19 pandemic.

Keywords: fish, micro/nanoplastics, molnupiravir, toxicity

Procedia PDF Downloads 73

Authors: Tasha L. Golden

Abstract:

Girls in the U.S. juvenile justice system are most often arrested for truancy, drug use, or running from home, all of which are symptoms of abuse. In fact, some have called this 'The Sexual Abuse to Prison Pipeline.' Such abuse has consequences for girls' health, education, employment, and parenting, often resulting in significant health disparities. Yet when arrested, girls rarely encounter services designed to meet their unique needs. Instead, they are expected to cope with a system that was historically designed for males. In fact, even literature advocating for increased gender equity frequently fails to include girls’ voices and firsthand accounts. In response to these combined injustices, public health researchers launched a trauma-informed creative writing intervention in a southern juvenile detention facility. The program was designed to improve the health of detained girls, while also establishing innovative methods of both data collection and social justice advocacy. Girls’ poems and letters were collected and coded, adding rich qualitative data to traditional survey responses. In addition, as part of the intervention, these poems are regularly published by international literary publisher Sarabande Books—and distributed to judges, city leaders, attorneys, state representatives, and more. By utilizing a creative medium, girls generated substantial civic engagement with their concerns—thus expanding their influence and improving policy advocacy efforts. Researchers hypothesized that having access to their communities and policy makers would provide its own health benefits for incarcerated girls: cultivating self-esteem, locus of control, and a sense of leadership. This paper discusses the establishment of this intervention, examines findings from its evaluation, and includes several girls’ poems as exemplars. Grounded in social science regarding expressive writing, stigma, muted group theory, and health promotion, the paper theorizes about the application of arts-based advocacy efforts to other social justice endeavors.

Keywords: advocacy, public health, social justice, women’s health

Procedia PDF Downloads 147

Authors: Serhat Tüzün, Tufan Demirel

Abstract:

Decision Support Systems (DSS) have been investigated by researchers and technologists for more than 35 years. This paper analyses the developments in the architecture and software of these systems, provides a systematic analysis for different Web-based DSS approaches and Intelligent Decision-making Technologies (IDT), with the suggestion for future studies. Decision Support Systems literature begins with building model-oriented DSS in the late 1960s, theory developments in the 1970s, and the implementation of financial planning systems and Group DSS in the early and mid-80s. Then it documents the origins of Executive Information Systems, online analytic processing (OLAP) and Business Intelligence. The implementation of Web-based DSS occurred in the mid-1990s. With the beginning of the new millennia, intelligence is the main focus on DSS studies. Web-based technologies are having a major impact on design, development and implementation processes for all types of DSS. Web technologies are being utilized for the development of DSS tools by leading developers of decision support technologies. Major companies are encouraging its customers to port their DSS applications, such as data mining, customer relationship management (CRM) and OLAP systems, to a web-based environment. Similarly, real-time data fed from manufacturing plants are now helping floor managers make decisions regarding production adjustment to ensure that high-quality products are produced and delivered. Web-based DSS are being employed by organizations as decision aids for employees as well as customers. A common usage of Web-based DSS has been to assist customers configure product and service according to their needs. These systems allow individual customers to design their own products by choosing from a menu of attributes, components, prices and delivery options. The Intelligent Decision-making Technologies (IDT) domain is a fast growing area of research that integrates various aspects of computer science and information systems. This includes intelligent systems, intelligent technology, intelligent agents, artificial intelligence, fuzzy logic, neural networks, machine learning, knowledge discovery, computational intelligence, data science, big data analytics, inference engines, recommender systems or engines, and a variety of related disciplines. Innovative applications that emerge using IDT often have a significant impact on decision-making processes in government, industry, business, and academia in general. This is particularly pronounced in finance, accounting, healthcare, computer networks, real-time safety monitoring and crisis response systems. Similarly, IDT is commonly used in military decision-making systems, security, marketing, stock market prediction, and robotics. Even though lots of research studies have been conducted on Decision Support Systems, a systematic analysis on the subject is still missing. Because of this necessity, this paper has been prepared to search recent articles about the DSS. The literature has been deeply reviewed and by classifying previous studies according to their preferences, taxonomy for DSS has been prepared. With the aid of the taxonomic review and the recent developments over the subject, this study aims to analyze the future trends in decision support systems.

Keywords: decision support systems, intelligent decision-making, systematic analysis, taxonomic review

Procedia PDF Downloads 261

Authors: Birgit A. A. Solem, Kristin Bentsen

Abstract:

Scholarly attention in entrepreneurship is currently directed towards understanding entrepreneurial venture creation as a process -the journey of new economic activities from nonexistence to existence often studied through flow- or network models. To complement existing research on entrepreneurial venture creation with more interactivity-based research of organized activities, this study examines two pop-up stores as anchor events involving on-site activities of fifteen participating entrepreneurs launching their new ventures. The pop-up stores were arranged in two middle-sized Norwegian cities and contained different brand stores that brought together actors of sub-networks and communities executing venture creation activities. The pop-up stores became on-site arenas for the entrepreneurs to create, maintain, and rejuvenate their networks, at the same time as becoming venues for temporal coordination of activities involving existing and potential customers in their venture creation. In this work, we apply a conceptual framework based on frequently addressed dilemmas within entrepreneurship theory (discovery/creation, causation/effectuation) to further shed light on the broad aspect of on-site anchor event activities and their venture creation outcomes. The dilemma-based concepts are applied as an analytic toolkit to pursue answers regarding the nature of anchor event activities typically found within entrepreneurial venture creation and how these anchor event activities affect entrepreneurial venture creation outcomes. Our study combines researcher participation with 200 hours of observation and twenty in-depth interviews. Data analysis followed established guidelines for hermeneutic analysis and was intimately intertwined with ongoing data collection. Data was coded and categorized in NVivo 12 software, and iterated several times as patterns were steadily developing. Our findings suggest that core anchor event activities typically found within entrepreneurial venture creation are; a concept- and product experimentation with visitors, arrangements to socialize (evening specials, auctions, and exhibitions), store-in-store concepts, arranged meeting places for peers and close connection with municipality and property owners. Further, this work points to four main entrepreneurial venture creation outcomes derived from the core anchor event activities; (1) venture attention, (2) venture idea-realization, (3) venture collaboration, and (4) venture extension. Our findings show that, depending on which anchor event activities are applied, the outcomes vary. Theoretically, this study offers two main implications. First, anchor event activities are both discovered and created, following the logic of causation, at the same time as being experimental, based on “learning by doing” principles of effectuation during the execution. Second, our research enriches prior studies on venture creation as a process. In this work, entrepreneurial venture creation activities and outcomes are understood through pop-up stores as on-site anchor event arenas, particularly suitable for interactivity-based research requested by the entrepreneurship field. This study also reveals important managerial implications, such as that entrepreneurs should allow themselves to find creative physical venture creation arenas (e.g., pop-up stores, showrooms), as well as collaborate with partners when discovering and creating concepts and activities based on new ideas. In this way, they allow themselves to both strategically plan for- and continually experiment with their venture.

Keywords: anchor event, interactivity-based research, pop-up store, entrepreneurial venture creation

Procedia PDF Downloads 73

Authors: Ziwei Song, Junjun Fan, Jeremy Teo, Yang Yu, Yukun Ma, Jie Yan, Shupei Mo, Lisa Tucker-Kellogg, Peter So, Hanry Yu

Abstract:

Liver is the center of detoxification and exposed to toxic metabolites all the time. It is highly regenerative after injury, with the ability to restore even after 70% partial hepatectomy. Most of the previous studies were using hepatectomy as injury models for liver regeneration study. There is limited understanding of small-scale liver injury, which can be caused by either low dose drug consumption or hepatocyte routine metabolism. Although these small in situ injuries do not cause immediate symptoms, repeated injuries will lead to aberrant wound healing in liver. Therefore, the cellular dynamics during liver regeneration is critical for our understanding of liver regeneration mechanism. We aim to study the liver regeneration of small-scale in situ liver injury in transgenic mice labeling actin (Lifeact-GFP). Previous studies have been using sample sections and biopsies of liver, which lack real-time information. In order to trace every individual hepatocyte during the regeneration process, we have developed and optimized an intravital imaging system that allows in vivo imaging of mouse liver for consecutive 5 days, allowing real-time cellular tracking and quantification of hepatocytes. We used femtosecond-laser ablation to make controlled and repeatable liver injury model, which mimics the real-life small in situ liver injury. This injury model is the first case of its kind for in vivo study on liver. We found that small-scale in situ liver injury is repaired by the coordination of hypertrophy and migration of hepatocytes. Hypertrophy is only transient at initial phase, while migration is the main driving force to complete the regeneration process. From cellular aspect, Akt/mTOR pathway is activated immediately after injury, which leads to transient hepatocyte hypertrophy. From mechano-sensing aspect, the actin cable, formed at apical surface of wound proximal hepatocytes, provides mechanical tension for hepatocyte migration. This study provides important information on both chemical and mechanical signals that promote liver regeneration of small in situ injury. We conclude that hypertrophy and migration play a dominant role at different stages of liver regeneration.

Keywords: hepatocyte, hypertrophy, intravital imaging, liver regeneration, migration

Procedia PDF Downloads 193

Authors: Anjana Aggarwal, Sheilja Walia

Abstract:

Prevalence of obesity and overweight is increasing due to sedentary lifestyles and busy schedules of people that spend less time on physical exercise. To reduce weight, people are finding easier and more convenient ways. The easiest solution is the use of dietary supplements and fat burners. These are products that decrease body weight by increasing the basal metabolic rate. Various reports have been published on the consumption of fat burners leading to heart palpitations, seizures, anxiety, depression, psychosis, bradycardia, insomnia, muscle contractions, hepatotoxicity, and even liver failure. Case reports and series are reporting that the ingredients present in the fat burners caused acute liver failure (ALF) and hepatic toxicity in many cases. Another contributing factor is the absence of regulations from the Food and Drug Administration on these products, leading to increased consumption and a higher risk of liver diseases among the population. This systematic review aims to attain a better understanding of the dietary supplements used globally to reduce weight and document the case reports/series of acute liver failure caused by the consumption of fat burners. Electronic databases like PubMed, Cochrane, Google Scholar, etc., will be systematically searched for relevant articles. Various websites of dietary products and brands that sell such supplements, Journals of Hepatology, National and international projects launched for ALF, and their reports, along with the review of grey literature, will also be done to get a better understanding of the topic. After discussing with the co-author, the selection and screening of the articles will be performed by the author. The studies will be selected based on the predefined inclusion and exclusion criteria. The case reports and case series that will be included in the final list of the studies will be assessed for methodological quality using the CARE guidelines. The results from this study will provide insights and a better understanding of fat burners. Since the supplements are easily available in the market without any restrictions on their sale, people are unaware of their adverse effects. The consumption of these supplements causes acute liver failure. Thus, this review will provide a platform for future larger studies to be conducted.

Keywords: acute liver failure, dietary supplements, fat burners, weight loss supplements

Procedia PDF Downloads 64

Authors: Holm Zerbe, Laura Macias, Hans-Joachim Schuberth, Wolfram Petzl

Abstract:

Mastitis is among the most important production diseases in cows. It accounts for large parts of antimicrobial drug use in the dairy industry worldwide. Due to the imminent normative to reduce the use of antimicrobial drugs in livestock, new ways for therapy and prophylaxis of mastitis are needed. Recently epigenetic regulation of inflammation by chromatin modifications has increasingly drawn attention. Currently, some epigenetic modifiers have already been approved for the use in humans, however little is known about their actions in the bovine system. The aim of our study was to investigate whether three selected epigenetic modifiers (Vitamin D3, SAHA and S2101) influence the initial immune response towards mastitis pathogens in bovine udder tissue in vitro. Tissue explants of the teat cistern and udder parenchyma were collected from 21 cows and were incubated for 36 hours in the absence and presence of epigenetic modifiers. Additionally, the tissue was stimulated with heat-inactivated particles of Escherichia coli and Staphylococcus aureus, which are regarded as two of the most important mastitis pathogens. After incubation, the explants were tested by RT-qPCR for transcript abundances of immune-related candidate genes. Gene expression was validated in culture supernatants by an AlphaLISA assay. Furthermore, the culture supernatants were analyzed for their chemotactic capacity through a chemotaxis assay. Statistical analysis of data was performed with the program ‘R’ version 3.2.3. Vitamin D3 had no effect on the immune response of udder tissue in vitro after stimulation with mastitis pathogens. The epigenetic modifiers SAHA and S2101 however significantly blocked the pathogen-induced upregulation of CXCL8, TNFα, S100A9 and LAP (P < 0.05). The regulation of IL10 was not affected by treatment with SAHA and S2101. Transcript abundances for CXCL8 were reflected by IL8 contents and chemotactic activity in culture supernatants. In conclusion, these data show the potential of epigenetic modifiers (SAHA and S2101) to block overshooting inflammation in the udder. Thus epigenetic modifiers may serve in future as immune modulators for the treatment and/or prophylaxis of clinical mastitis. (Funded by Deutsche Forschungsgemeinschaft PE 1495/2-1).

Keywords: mastitis, cattle, epigenetics, immunomodulation

Procedia PDF Downloads 215

Authors: Mohammad Khazaei, Reza Rostami, Hasan Gharayagh Zandi, Rouhollah Basatnia, Mahbubeh Ghayour Najafabadi

Abstract:

Objective: Methylphenidate has been demonstrated to enhance attention and cognitive processes, and placebo treatments have also been found to improve attention and cognitive processes. Additionally, methylphenidate may have positive effects on motion perception and sports performance. Nevertheless, additional research is needed to fully comprehend the neural mechanisms underlying the effects of methylphenidate and placebo on cognitive and motor functions. Methods: In this randomized controlled trial, 18 young semi-professional basketball players aged 18-23 years were randomly and equally assigned to either a Ritalin or Placebo group. The participants performed 20 consecutive free throws; their scores were recorded on a 0-3 scale. The participants’ brain activity was recorded using electroencephalography (EEG) for 5 minutes seated with their eyes closed. The Ritalin group received a 10 mg dose of methylphenidate, while the Placebo group received a 10mg dose of placebo. The EEG was obtained 90 minutes after the drug was administere Results: There was no significant difference in the absolute power of brain waves between the pre-test and post-tests in the Placebo group. However, in the Ritalin group, a significant difference in the absolute power of brain waves was observed in the Theta band (5-6 Hz) and Beta band (21-30 Hz) between pre- and post-tests in Fp2, F8, and Fp1. In these areas, the absolute power of Beta waves was higher during the post-test than during the pre-test. The Placebo group showed a more significant difference in free throw scores than the Ritalin group. Conclusions: In conclusion, these results suggest that Ritalin effect on brain activity in areas associated with attention and cognitive processes, as well as improve basketball free throws. However, there was no significant placebo effect on brain activity performance, but it significantly affected the improvement of free throws. Further research is needed to fully understand the effects of methylphenidate and placebo on cognitive and motor functions.

Keywords: methylphenidate, placebo effect, electroencephalography, basketball free throw

Procedia PDF Downloads 63

Authors: Rania F. Ahmed, Sally A. El Awdan, Gehad A. Abdel Jaleel, Dalia O. Saleh, Omar A. H. Ahmed-Farid

Abstract:

The metabolic syndrome is an important public health concern often related to obesity, improper diet, and sedentary lifestyles and can predispose individuals to the development of many dangerous health conditions, disability and early death. This research aimed to investigate the efficacy of resveratrol (RSV) to reverse the neuro-complications associated with metabolic syndrome experimentally-induced in rats using an eight weeks high fat, high fructose diet (HFHF) model. The corresponding drug treatments were administered orally during the last 10 days of the diet. Behavioural tests namely the open field test (OFT) and the forced swimming test (FST) were conducted. Brain levels of monoamines viz. serotonin, norepinephrine and dopamine as well as their metabolites were assessed. 8-hydroxyguanosine (8-OHDG) as an indicative of DNA-fragmentation, nitric oxide (NOx) and tumor necrosis factor-α (TNF- α) were estimated. Finally, brain antioxidant parameters namely malondialdehyde (MDA), reduced and oxidized glutathione (GSH, GSSG) were evaluated. HFHF-induced metabolic syndrome resulted in decreased activity in the OFT and increased immobility duration in the FST. Furthermore, HFHF-induced metabolic syndrome lead to a significant increase in brain monoamines turn over as well as elevation in 8-OHDG, NOx, TNF- α, MDA and GSSG; and reduction in GSH. Ten days daily treatment with RSV (20 and 40 mg/kg p.o) dose dependently increased activity in the OFT and decreased immobility duration in the FST. Moreover, RSV normalized brain monoamines contents, reduced 8-OHDG, NOx, TNF- α, MDA and GSSG; and elevated GSH. In conclusion, we can say that RSV showed neuro-protective properties against HFHF-induced metabolic syndrome represented by monoamines preservation, prevention of neurodegeneration, anti-inflammatory and antioxidant potentials and could be recommended as a beneficial daily dietary supplement to treat the neuronal side effects associated with HFHF-induced metabolic syndrome.

Keywords: antioxidants, DNA-fragmentation, forced swimming test, HFHF-induced metabolic syndrome, monoamines, nitric oxide (NOx), open field, resveratrol, tumor necrosis factor-α (TNF- α), 8-hydroxyguanosine (8-OHDG)

Procedia PDF Downloads 260

Authors: Xingyu Gao, Qiang Wu, Yuanyuan Liu, Yue Yang

Abstract:

In the era of the knowledge economy, the relationship between scientific knowledge and patents has garnered significant attention. Understanding the intricate interplay between the foundations of science and technological innovation has emerged as a pivotal challenge for both researchers and policymakers. This study establishes a coupled network of artificial intelligence patents based on co-cited scientific papers. Leveraging centrality metrics from network analysis offers a fresh perspective on understanding the influence of information flow and knowledge sharing within the network on patent impact. The study initially obtained patent numbers for 446,890 granted US AI patents from the United States Patent and Trademark Office’s artificial intelligence patent database for the years 2002-2020. Subsequently, specific information regarding these patents was acquired using the Lens patent retrieval platform. Additionally, a search and deduplication process was performed on scientific non-patent references (SNPRs) using the Web of Science database, resulting in the selection of 184,603 patents that cited 37,467 unique SNPRs. Finally, this study constructs a coupled network comprising 59,379 artificial intelligence patents by utilizing scientific papers co-cited in patent backward citations. In this network, nodes represent patents, and if patents reference the same scientific papers, connections are established between them, serving as edges within the network. Nodes and edges collectively constitute the patent coupling network. Structural characteristics such as node degree centrality, betweenness centrality, and closeness centrality are employed to assess the scientific connections between patents, while citation count is utilized as a quantitative metric for patent influence. Finally, a negative binomial model is employed to test the nonlinear relationship between these network structural features and patent influence. The research findings indicate that network structural features such as node degree centrality, betweenness centrality, and closeness centrality exhibit inverted U-shaped relationships with patent influence. Specifically, as these centrality metrics increase, patent influence initially shows an upward trend, but once these features reach a certain threshold, patent influence starts to decline. This discovery suggests that moderate network centrality is beneficial for enhancing patent influence, while excessively high centrality may have a detrimental effect on patent influence. This finding offers crucial insights for policymakers, emphasizing the importance of encouraging moderate knowledge flow and sharing to promote innovation when formulating technology policies. It suggests that in certain situations, data sharing and integration can contribute to innovation. Consequently, policymakers can take measures to promote data-sharing policies, such as open data initiatives, to facilitate the flow of knowledge and the generation of innovation. Additionally, governments and relevant agencies can achieve broader knowledge dissemination by supporting collaborative research projects, adjusting intellectual property policies to enhance flexibility, or nurturing technology entrepreneurship ecosystems.

Keywords: centrality, patent coupling network, patent influence, social network analysis

Procedia PDF Downloads 39

Authors: AliAkbar Hafezi, Jamshid Abedi, Jalal Taherian, Behnam Kadkhodaei, Mahsa Elahi

Abstract:

Background. Peripheral neuropathy is a common side effect of the administration of neurotoxic chemotherapy agents. This adverse effect is a major dose-limiting factor of many commonly used chemotherapy drugs. Currently, there are no Food and Drug Administration (FDA) approved medications for the prevention or treatment of chemotherapy-induced peripheral neuropathy. Therefore, this study was performed to investigate the efficacy and safety of metformin on paclitaxel-induced peripheral neuropathy (PIPN). Methods. In this randomized clinical trial, cancer patients who were candidates for chemotherapy with paclitaxel referred to the radiation oncology departments in Iran from 2022 to 2023 were studied. Patients were randomly divided into two groups; 1- Case group (n = 30) received metformin 500 mg orally twice a day after meals during chemotherapy with paclitaxel, and 2- Control group (30 people) received chemotherapy without metformin or any additional medication. Patients were visited in terms of numbness or other neurological symptoms two weeks before chemotherapy, 1-2 days before and weekly during chemotherapy, and at the end of the study. They were assessed by nerve conduction study (NCS) before intervention and one week after the end of chemotherapy. The primary outcome was the efficacy in reducing PIPN and the secondary outcome was adverse effects. Eventually, the outcomes were compared between the two groups of patients. Results. A total of 60 female cancer patients receiving chemotherapy with paclitaxel were evaluated in two groups. The groups were matched in terms of age, body mass index, fasting blood sugar, smoking, pathologic stage, and creatinine levels. The results showed that 18 patients (60.0 %) in the case group and 23 patients (76.6 %) in the control group had PIPN clinically (P = 0.267), and NCS showed 11 patients (36.6 %) in the case group and 15 patients (50.0 %) in the control group suffered from PIPN which no significant difference was observed between the two groups (P = 0.435). Diarrhea (n = 3; 10.0 %) and nausea (n = 3; 10.0 %) were the most common side effects of metformin in the case group and no serious side effects (lactic acidosis and anemia) were found in these patients. Conclusion. This study indicated that metformin did not significantly prevent PIPN in cancer patients receiving chemotherapy, although the frequency of peripheral neuropathy in the case group was lower than in the control group. The use of metformin in the patients had acceptable safety and no serious side effects were reported.

Keywords: peripheral neuropathy, chemotherapy, paclitaxel, metformin

Procedia PDF Downloads 22

Authors: Kathryn Nderitu, Atunga Nyachieo, Ezekiel Mecha

Abstract:

Introduction: Solanum nigrum , also known as black nightshade, biosynthesizes various phytochemical compounds with various pharmacological activities, including treating cardiovascular diseases and type 2 diabetes, among others. Materials and Methods: To assess the anti-obesity effects of Solanum nigrum using high-fat-fed diet rats, Sprague Dawley male rats (n = 35) of weights 160–180 g were assigned randomly into seven groups comprising n = 5 rats each. Each group was fed for 11 weeks as follows: normal group (normal chow rat feed); high-fat diet control (HFD); HFD and standard drug (Orlistat 30 mg/kg bw); HFD and methanolic extract 150 mg/kgbw; HFD and methanolic extract 300 mg/kgbw; HFD and dichloromethane extract 150 mg/kgbw; HFD and dichloromethane extract 300 mg/kgbw. Body mass index and food intake were monitored per week, and an oral glucose tolerance test was measured in weeks 5 and 10. Lipid profiles, liver function tests, adipose tissue, liver weights, and phytochemical analysis of Solanum nigrum were later carried out. Results: High-fat diet control group rats exhibited a significant increase in body mass index (BMI), while rats administered with leaf extracts of Solanum nigrum showed a reduction in BMI. Both low doses of dichloromethane (150 mg/kgbw) and high doses of methanol extracts (300 mg/kgbw) showed a better reduction in BMI than the other treatment groups. A significant decrease (p <0.05) in low-density lipoprotein-cholesterol, triglycerides, and cholesterol was observed among the rats administered with Solanum nigrum extracts compared to those of HFD control. Moreover, the HFD control group significantly increased liver and adipose tissue weights compared to other treatment groups (p<0.05). Solanum nigrum also decreased glycemic levels and normalized the hepatic enzymes of HFD control. However, food intake among the groups showed no significant difference (p>0.05). Qualitative analysis of Solanum nigrum leaf extracts indicated the presence of various bioactive compounds associated with anti-obesity. Conclusion: These results validate the use of Solanum nigrum in controlling obesity.

Keywords: solanum nigrum, High fat diet, phytocompounds, obesity

Procedia PDF Downloads 39

Authors: N. Gopal, K. Jaasminerjiit, L. Z. Xiang

Abstract:

Quinazoline-4(3H)-one ring system has been consistently regarded as promising privileged structural icon owing to its pharmacodynamic versatility in many of its synthetic derivatives as well as in several naturally occurring alkaloids. The literature reveals that 2nd & 3rd positions of the quinazolin-4(3H)-one pharmacophore are the target for substitution with other moieties. On the other hand, sulphanilamide derivatives and isatin moiety also displayed valuable biological activities. Hence, it was thought worthwhile to study the effects of three pharmacophoric moieties like quinazolinone, sulphanilamide and isatin in a single molecule for the better analgesic activity with lower toxicity. Series of novel 2,3-disubstituted quinazolin-4(3H)-one derivatives have been synthesised from the intermediate Schiff base of 2-(4’-substitutedphenyl)-3-[(N-2-oxoindolin-3-ylidene)-4”-sulphonamidophenyl]-quinazolin-4(3H)-one derivatives, which was prepared from reacting 2-(substituted phenyl)-4H-benzo[d][1,3]-oxazin-4-one with sulphanilamide. The required benzoxazinone derivatives were prepared by reacting anthranilic acid with benzoyl chloride. All the compounds structure was characterised by using H1 NMR, IR and Mass spectroscopy. The intermediate Schiff base and final Mannich base compounds were evaluated for their analgesic activity by acetic acid-induced writhing method at the dose of 25mg/kg, 50 mg/kg, and 100 mg/kg (bw) and Diclofenac (25mg/kg of body weight) will be used as the reference drugs. From the results of the study, it has been observed that final Mannich base showed a better analgesic activity when compared to the parent Schiff bases, it was found that compound substituted with N-methyl piperazine at 1st position of the indole nucleus of the final quinazolinone derivatives (GA4B1) i.e. 2-(4’-methoxy phenyl)-3-[4-(N-(1-N-methyl piperazine amine) methyl-2-oxo indoilin-3-ylidene] benzenesulfonyl quinazolin-4(3H)-one increases the analgesic activity and among the synthesised compounds, GA4B1 exhibited quite superior analgesic activity. The remaining Schiff bases and Mannich base derivatives exhibited moderate analgesic activity. All the compounds showed a dose dependent activity. None of the synthesised compound showed ulcer index whereas the standard drug, diclofenac [25 mg/kg (bw)] showed significantly higher gross ulcer index values.

Keywords: analgesic activity, isatin, mannich base, quinazolin-4(3H)-one

Procedia PDF Downloads 325