Search results for: molecular evolution
726 Curative Role of Bromoenol Lactone, an Inhibitor of Phospholipase A2 Enzyme, during Cigarette Smoke Condensate Induced Anomalies in Lung Epithelium
Authors: Subodh Kumar, Sanjeev Kumar Sharma, Gaurav Kaushik, Pramod Avti, Phulen Sarma, Bikash Medhi, Krishan Lal Khanduja
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Background: It is well known that cigarette smoke is one of the causative factors in various lung diseases especially cancer. Carcinogens and oxidant molecules present in cigarette smoke not only damage the cellular constituents (lipids, proteins, DNA) but may also regulate the molecular pathways involved in inflammation and cancer. Continuous oxidative stress caused by the constituents of cigarette smoke leads to higher PhospholipaseA₂ (PLA₂) activity, resulting in elevated levels of secondary metabolites whose role is well defined in cancer. To reduce the burden of chronic inflammation as well as oxidative stress, and higher levels of secondary metabolites, we checked the curative potential of PLA₂ inhibitor Bromoenol Lactone (BEL) during continuous exposure of cigarette smoke condensate (CSC). Aim: To check the therapeutic potential of Bromoenol Lactone (BEL), an inhibitor of PhospholipaseA₂s, in pathways of CSC-induced changes in type I and type II alveolar epithelial cells. Methods: Effect of BEL on CSC-induced PLA2 activity were checked using colorimetric assay, cellular toxicity using cell viability assay, membrane integrity using fluorescein di-acetate (FDA) uptake assay, reactive oxygen species (ROS) levels and apoptosis markers through flow cytometry, and cellular regulation using MAPKinases levels, in lung epithelium. Results: BEL significantly mimicked CSC-induced PLA₂ activity, ROS levels, apoptosis, and kinases level whereas improved cellular viability and membrane integrity. Conclusions: Current observations revealed that BEL may be a potential therapeutic agent during Cigarette smoke-induced anomalies in lung epithelium.Keywords: cigarette smoke condensate, phospholipase A₂, oxidative stress, alveolar epithelium, bromoenol lactone
Procedia PDF Downloads 189725 Exploring Barriers to Social Innovation: Swedish Experiences from Nine Research Circles
Authors: Claes Gunnarsson, Karin Fröding, Nina Hasche
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Innovation is a necessity for the evolution of societies and it is also a driving force in human life that leverages value creation among cross-sector participants in various network arrangements. Social innovations can be characterized as the creation and implementation of a new solution to a social problem, which is more effective and sustainable than existing solutions in terms of improvement of society’s conditions and in particular social inclusion processes. However, barriers exist which may restrict the potential of social innovations to live up to its promise as a societal welfare promoting driving force. The literature points at difficulties in tackling social problems primarily related to problem complexity, access to networks, and lack of financial muscles. Further research is warranted at detailed at detail clarification of these barriers, also connected to recognition of the interplay between institutional logics on the development of cross-sector collaborations in networks and the organizing processes to achieve innovation barrier break-through. There is also a need to further elaborate how obstacles that spur a difference between the actual and desired state of innovative value creating service systems can be overcome. The purpose of this paper is to illustrate barriers to social innovations, based on qualitative content analysis of 36 dialogue-based seminars (i.e. research circles) with nine Swedish focus groups including more than 90 individuals representing civil society organizations, private business, municipal offices, and politicians; and analyze patterns that reveal constituents of barriers to social innovations. The paper draws on central aspects of innovation barriers as discussed in the literature and analyze barriers basically related to internal/external and tangible/intangible characteristics. The findings of this study are that existing institutional structures highly influence the transformative potential of social innovations, as well as networking conditions in terms of building a competence-propelled strategy, which serves as an offspring for overcoming barriers of competence extension. Both theoretical and practical knowledge will contribute to how policy-makers and SI-practitioners can facilitate and support social innovation processes to be contextually adapted and implemented across areas and sectors.Keywords: barriers, research circles, social innovation, service systems
Procedia PDF Downloads 257724 The Pathology of Bovine Rotavirus Infection in Calves That Confirmed by Enzyme Linked Immunosorbant Assay, Reverse Transcription Polymerase Chain Reaction and Real-Time RT-PCR
Authors: Shama Ranjan Barua, Tofazzal M. Rakib, Mohammad Alamgir Hossain, Tania Ferdushy, Sharmin Chowdhury
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Rotavirus is one of the main etiologies of neonatal diarrhea in bovine calves that causes significant economic loss in Bangladesh. The present study was carried out to investigate the pathology of neonatal enteritis in calves due to bovine rotavirus infection in south-eastern part of Bangladesh. Rotavirus was identified by using ELISA, RT-PCR (Reverse Transcription Polymerase Chain Reaction), real-time RT-PCR. We examined 12 dead calves with history of diarrhea during necropsy. Among 12 dead calves, in gross examination, 6 were found with pathological changes in intestine, 5 calves had congestion of small intestine and rest one had no distinct pathological changes. Intestinal contents and/or faecal samples of all dead calves were collected and examined to confirm the presence of bovine rotavirus A using Enzyme linked immunosorbant assay (ELISA), RT-PCR and real-time RT-PCR. Out 12 samples, 5 (42%) samples revealed presence of bovine rotavirus A in three diagnostic tests. The histopathological changes were found almost exclusively limited in the small intestine. The lesions of rotaviral enteritis ranged from slight to moderate shortening (atrophy) of villi in the jejunum and ileum with necrotic crypts. The villi were blunt and covered by immature epithelial cells. Infected cells, stained with Haematoxylin and Eosin staining method, showed characteristic syncytia and eosinophilc intracytoplasmic inclusion body. The presence of intracytoplasmic inclusion bodies in enterocytes is the indication of viral etiology. The presence of rotavirus in the affected tissues and/or lesions was confirmed by three different immunological and molecular tests. The findings of histopathological changes will be helpful in future diagnosis of rotaviral infection in dead calves.Keywords: calves, diarrhea, pathology, rotavirus
Procedia PDF Downloads 252723 Gene Expressions in Left Ventricle Heart Tissue of Rat after 150 Mev Proton Irradiation
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Introduction: In mediastinal radiotherapy and to a lesser extend also in total-body irradiation (TBI) radiation exposure may lead to development of cardiac diseases. Radiation-induced heart disease is dose-dependent and it is characterized by a loss of cardiac function, associated with progressive heart cells degeneration. We aimed to determine the in-vivo radiation effects on fibronectin, ColaA1, ColaA2, galectin and TGFb1 gene expression levels in left ventricle heart tissues of rats after irradiation. Material and method: Four non-treatment adult Wistar rats as control group (group A) were selected. In group B, 4 adult Wistar rats irradiated to 20 Gy single dose of 150 Mev proton beam locally in heart only. In heart plus lung irradiate group (group C) 4 adult rats was irradiated by 50% of lung laterally plus heart radiation that mentioned in before group. At 8 weeks after radiation animals sacrificed and left ventricle heart dropped in liquid nitrogen for RNA extraction by Absolutely RNA® Miniprep Kit (Stratagen, Cat no. 400800). cDNA was synthesized using M-MLV reverse transcriptase (Life Technologies, Cat no. 28025-013). We used Bio-Rad machine (Bio Rad iQ5 Real Time PCR) for QPCR testing by relative standard curve method. Results: We found that gene expression of fibronectin in group C significantly increased compared to control group, but it was not showed significant change in group B compared to group A. The levels of gene expressions of Cola1 and Cola2 in mRNA did not show any significant changes between normal and radiation groups. Changes of expression of galectin target significantly increased only in group C compared to group A. TGFb1 expressions in group C more than group B showed significant enhancement compared to group A. Conclusion: In summary we can say that 20 Gy of proton exposure of heart tissue may lead to detectable damages in heart cells and may distribute function of them as a component of heart tissue structure in molecular level.Keywords: gene expression, heart damage, proton irradiation, radiotherapy
Procedia PDF Downloads 489722 Molecular Dissection of Late Flowering under a Photoperiod-Insensitive Genetic Background in Soybean
Authors: Fei Sun, Meilan Xu, Jianghui Zhu, Maria Stefanie Dwiyanti, Cheolwoo Park, Fanjiang Kong, Baohui Liu, Tetsuya Yamada, Jun Abe
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Reduced or lack of sensitivity to long daylengths is a key character for soybean, a short-day crop, to adapt to higher latitudinal environments. However, the photoperiod-insensitivity often results in a reduction of the duration of vegetative growth and final yield. To overcome this limitation, a photoperiod insensitive line (RIL16) was developed in this study that delayed flowering from the recombinant inbred population derived from a cross between a photoperiod-insensitive cultivar AGS292 and a late-flowering Thai cultivar K3. Expression analyses under SD and LD conditions revealed that the expression levels of FLOWERING LOCUS T (FT) orthologues, FT2a and FT5a, were lowered in RIL16 relative to AGS292, although the expression of E1, a soybean-specific suppressor for FTs, was inhibited in both conditions. A soybean orthologue of TARGET OF EAT1 (TOE1), another suppressor of FT, showed an upregulated expression in RIL16, which appeared to reflect a lower expression of miR172a. Our data suggest that the delayed flowering of RIL16 most likely is controlled by genes involved in an age-dependent pathway in flowering. The QTL analysis based on 1,125 SNPs obtained from Restriction Site Associated DNA Sequencing revealed two major QTLs for flowering dates in Chromosome 16 and two minor QTLs in Chromosome 4, all of which accounted for 55% and 48% of the whole variations observed in natural day length and artificially-induced long day length conditions, respectively. The intervals of the major QTLs harbored FT2a and FT5a, respectively, on the basis of annotated genes in the Williams 82 reference genome. Sequencing analysis further revealed a nonsynonymous mutation in FT2a and an SNP in the 3′ UTR region of FT5a. A further study may elucidate a detailed mechanism underlying the QTL for late flowering. The alleles from K3 at the two QTLs can be used singly or in combination to retain an appropriate duration of vegetative growth to maximize the final yield of photoperiod-insensitive soybeans.Keywords: FT genes, miR72a, photoperiod-insensitive, soybean flowering
Procedia PDF Downloads 221721 Cytotoxicity of 13 South African Macrofungal Species and Mechanism/s of Action against Cancer Cell Lines
Authors: Gerhardt Boukes, Maryna Van De Venter, Sharlene Govender
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Macrofungi have been used for the past two thousand years in Asian countries, and more recently in Western countries, for their medicinal properties. Biological activities include antimicrobial, antioxidant, anti-inflammatory, antidiabetic, anticancer and immunomodulatory to name a few. Several biologically active compounds have been identified and isolated. Macrofungal research in Africa is poorly documented and to the best of our knowledge non-existent. South Africa has a rich macrofungal biodiversity, which includes endemic and exotic macrofungal species. Ethanolic extracts of 13 macrofungal species, including mushrooms, bracket fungi and puffballs, were prepared and screened for cytotoxicity against a panel of seven cell lines, including A549 (human lung adenocarcinoma), HeLa (human cervical adenocarcinoma), HT-29 (human colorectal adenocarcinoma), MCF7 (human breast adenocarcinoma), MIA PaCa-2 (human pancreatic ductal adenocarcinoma), PC-3 (human prostate adenocarcinoma) and Vero (African green monkey kidney epithelial) cells using MTT. Cell lines were chosen according to the most prevalent cancer types affecting males and females in South Africa and globally, and the mutations they contain. Preliminary results have shown that three of the macrofungal genera, i.e. Fomitopsis, Gymnopilus and Pycnoporus, have shown cytotoxic activity, ranging between IC50 ~20 and 200 µg/mL. The molecular mechanism of action contributing to cell death investigated and being investigated include apoptosis (i.e. DNA cell cycle arrest, caspase-3 activation and mitochondrial membrane potential), autophagy (i.e. acridine orange and LC3B staining) and ER stress (i.e. thioflavin T staining and caspase-12) in the presence of melphalan, chloroquine and thapsigargin/tuncamycin as positive controls, respectively. The genus, Pycnoporus, has shown the best cytotoxicity of the three macrofungal genera. Future work will focus on the identification and isolation of novel active compounds and elucidating the mechanism/s of action.Keywords: cancer, cytotoxicity, macrofungi, mechanism/s of action
Procedia PDF Downloads 246720 Dual Thermoresponsive Polyzwitterionic Core-Shell Microgels and Study of Their Anti-Fouling Effect
Authors: P. Saha, R. Ganguly, N. K .Singha, A. Pich
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Microgel, a smart class of material, has drawn attention in the past few years due to its response to external stimuli like temperature, pH, and ionic strength of the solution. Among them, one type of polymer becomes soluble, and the other becomes insoluble in water upon heating displaying upper critical solution temperature (UCST) (e.g., polysulfobetaine, PSB) and lower critical solution temperature (LCST) (e.g., poly(N-vinylcaprolactam, PVCL)) respectively. Polyzwitterions, electrically neutral polymers are biocompatible, biodegradable, and non-cytotoxic in nature, and presence of zwitterionic pendant group in the main backbone makes them stable against temperature and pH variations and strong hydration capability in salt solution promotes them to be used as interfacial bio-adhesion resistance material. Majority of zwitterionic microgels have been synthesized in mini- emulsion technique using free radical polymerization approach. Here, a new route to synthesize dual thermo-responsive PVCL microgels decorated with appreciable amount of zwitterionic PSB chains was developed by a purely water-based surfactant-free reversible addition–fragmentation chain transfer (RAFT) precipitation polymerization. PSB macro-RAFTs having different molecular weights were synthesized and utilized for surface-grafting with PVCL microgels varying the macro-RAFT concentration using N,N′-methylenebis(acrylamide) (BIS) as cross-linker. Increasing the PSB concentration in the PVCL microgels resulted in a linear increase in UCST but decrease in hydrodynamic radius due to strong intrachain coulombic attraction forces acting between the opposite charges present in the zwitterionic groups. Anti- fouling effect was observed on addition of BSA protein solution on the microgel-coated membrane surfaces as studied by fluorescence spectrophotoscopy.Keywords: microgels, polyzwitterions, upper critical solution temperature-lower critical solution temperature, UCST-LCST, ionic crosslinking
Procedia PDF Downloads 116719 Proposed Design of an Optimized Transient Cavity Picosecond Ultraviolet Laser
Authors: Marilou Cadatal-Raduban, Minh Hong Pham, Duong Van Pham, Tu Nguyen Xuan, Mui Viet Luong, Kohei Yamanoi, Toshihiko Shimizu, Nobuhiko Sarukura, Hung Dai Nguyen
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There is a great deal of interest in developing all-solid-state tunable ultrashort pulsed lasers emitting in the ultraviolet (UV) region for applications such as micromachining, investigation of charge carrier relaxation in conductors, and probing of ultrafast chemical processes. However, direct short-pulse generation is not as straight forward in solid-state gain media as it is for near-IR tunable solid-state lasers such as Ti:sapphire due to the difficulty of obtaining continuous wave laser operation, which is required for Kerr lens mode-locking schemes utilizing spatial or temporal Kerr type nonlinearity. In this work, the transient cavity method, which was reported to generate ultrashort laser pulses in dye lasers, is extended to a solid-state gain medium. Ce:LiCAF was chosen among the rare-earth-doped fluoride laser crystals emitting in the UV region because of its broad tunability (from 280 to 325 nm) and enough bandwidth to generate 3-fs pulses, sufficiently large effective gain cross section (6.0 x10⁻¹⁸ cm²) favorable for oscillators, and a high saturation fluence (115 mJ/cm²). Numerical simulations are performed to investigate the spectro-temporal evolution of the broadband UV laser emission from Ce:LiCAF, represented as a system of two homogeneous broadened singlet states, by solving the rate equations extended to multiple wavelengths. The goal is to find the appropriate cavity length and Q-factor to achieve the optimal photon cavity decay time and pumping energy for resonator transients that will lead to ps UV laser emission from a Ce:LiCAF crystal pumped by the fourth harmonics (266nm) of a Nd:YAG laser. Results show that a single ps pulse can be generated from a 1-mm, 1 mol% Ce³⁺-doped LiCAF crystal using an output coupler with 10% reflectivity (low-Q) and an oscillator cavity that is 2-mm long (short cavity). This technique can be extended to other fluoride-based solid-state laser gain media.Keywords: rare-earth-doped fluoride gain medium, transient cavity, ultrashort laser, ultraviolet laser
Procedia PDF Downloads 357718 Peptide-Gold Nanocluster as an Optical Biosensor for Glycoconjugate Secreted from Leishmania
Authors: Y. A. Prada, Fanny Guzman, Rafael Cabanzo, John J. Castillo, Enrique Mejia-Ospino
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In this work, we show the important results about of synthesis of photoluminiscents gold nanoclusters using a small peptide as template for biosensing applications. Interestingly, we design one peptide (NBC2854) homologue to conservative domain from 215 250 residue of a galactolectin protein which can recognize the proteophosphoglycans (PPG) from Leishmania. Peptide was synthetized by multiple solid phase synthesis using FMoc group methodology in acid medium. Finally, the peptide was purified by High-Performance Liquid Chromatography using a Vydac C-18 preparative column and the detection was at 215 nm using a Photo Diode Array detector. Molecular mass of this peptide was confirmed by MALDI-TOF and to verify the α-helix structure we use Circular Dichroism. By means of the methodology used we obtained a novel fluorescents gold nanoclusters (AuNC) using NBC2854 as a template. In this work, we described an easy and fast microsonic method for the synthesis of AuNC with ≈ 3.0 nm of hydrodynamic size and photoemission at 630 nm. The presence of cysteine residue in the C-terminal of the peptide allows the formation of Au-S bond which confers stability to Peptide-based gold nanoclusters. Interactions between the peptide and gold nanoclusters were confirmed by X-ray Photoemission and Raman Spectroscopy. Notably, from the ultrafine spectra shown in the MALDI-TOF analysis which containing only 3-7 KDa species was assigned to Au₈-₁₈[NBC2854]₂ clusters. Finally, we evaluated the Peptide-gold nanocluster as an optical biosensor based on fluorescence spectroscopy and the fluorescence signal of PPG (0.1 µg-mL⁻¹ to 1000 µg-mL⁻¹) was amplified at the same wavelength emission (≈ 630 nm). This can suggest that there is a strong interaction between PPG and Pep@AuNC, therefore, the increase of the fluorescence intensity can be related to the association mechanism that take place when the target molecule is sensing by the Pep@AuNC conjugate. Further spectroscopic studies are necessary to evaluate the fluorescence mechanism involve in the sensing of the PPG by the Pep@AuNC. To our best knowledge the fabrication of an optical biosensor based on Pep@AuNC for sensing biomolecules such as Proteophosphoglycans which are secreted in abundance by parasites Leishmania.Keywords: biosensing, fluorescence, Leishmania, peptide-gold nanoclusters, proteophosphoglycans
Procedia PDF Downloads 169717 Understanding the Information in Principal Component Analysis of Raman Spectroscopic Data during Healing of Subcritical Calvarial Defects
Authors: Rafay Ahmed, Condon Lau
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Bone healing is a complex and sequential process involving changes at the molecular level. Raman spectroscopy is a promising technique to study bone mineral and matrix environments simultaneously. In this study, subcritical calvarial defects are used to study bone composition during healing without discomposing the fracture. The model allowed to monitor the natural healing of bone avoiding mechanical harm to the callus. Calvarial defects were created using 1mm burr drill in the parietal bones of Sprague-Dawley rats (n=8) that served in vivo defects. After 7 days, their skulls were harvested after euthanizing. One additional defect per sample was created on the opposite parietal bone using same calvarial defect procedure to serve as control defect. Raman spectroscopy (785 nm) was established to investigate bone parameters of three different skull surfaces; in vivo defects, control defects and normal surface. Principal component analysis (PCA) was utilized for the data analysis and interpretation of Raman spectra and helped in the classification of groups. PCA was able to distinguish in vivo defects from normal surface and control defects. PC1 shows that the major variation at 958 cm⁻¹, which corresponds to ʋ1 phosphate mineral band. PC2 shows the major variation at 1448 cm⁻¹ which is the characteristic band of CH2 deformation and corresponds to collagens. Raman parameters, namely, mineral to matrix ratio and crystallinity was found significantly decreased in the in vivo defects compared to surface and controls. Scanning electron microscope and optical microscope images show the formation of newly generated matrix by means of bony bridges of collagens. Optical profiler shows that surface roughness increased by 30% from controls to in vivo defects after 7 days. These results agree with Raman assessment parameters and confirm the new collagen formation during healing.Keywords: Raman spectroscopy, principal component analysis, calvarial defects, tissue characterization
Procedia PDF Downloads 223716 Characterization of Transcription Factors Involved in Early Defense Response during Interaction of Oil Palm Elaeis guineensis Jacq. with Ganoderma boninense
Authors: Sakeh N. Mohd, Bahari M. N. Abdul, Abdullah S. N. Akmar
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Oil palm production generates high export earnings to many countries especially in Southeast Asian region. Infection by necrotrophic fungus, Ganoderma boninense on oil palm results in basal stem rot which compromises oil palm production leading to significant economic loss. There are no reliable disease treatments nor promising resistant oil palm variety has been cultivated to eradicate the disease up to date. Thus, understanding molecular mechanisms underlying early interactions of oil palm with Ganoderma boninense may be vital to promote preventive or control measure of the disease. In the present study, four months old oil palm seedlings were infected via artificial inoculation of Ganoderma boninense on rubber wood blocks. Roots of six biological replicates of treated and untreated oil palm seedlings were harvested at 0, 3, 7 and 11 days post inoculation. Next-generation sequencing was performed to generate high-throughput RNA-Seq data and identify differentially expressed genes (DEGs) during early oil palm-Ganoderma boninense interaction. Based on de novo transcriptome assembly, a total of 427,122,605 paired-end clean reads were assembled into 30,654 unigenes. DEGs analysis revealed upregulation of 173 transcription factors on Ganoderma boninense-treated oil palm seedlings. Sixty-one transcription factors were categorized as DEGs according to stringent cut-off values of genes with log2 ratio [Number of treated oil palm seedlings/ Number of untreated oil palm seedlings] ≥ |1.0| (corresponding to 2-fold or more upregulation) and P-value ≤ 0.01. Transcription factors in response to biotic stress will be screened out from abiotic stress using reverse transcriptase polymerase chain reaction. Transcription factors unique to biotic stress will be verified using real-time polymerase chain reaction. The findings will help researchers to pinpoint defense response mechanism specific against Ganoderma boninense.Keywords: Ganoderma boninense, necrotrophic, next-generation sequencing, transcription factors
Procedia PDF Downloads 266715 Ho-Doped Lithium Niobate Thin Films: Raman Spectroscopy, Structure and Luminescence
Authors: Edvard Kokanyan, Narine Babajanyan, Ninel Kokanyan, Marco Bazzan
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Lithium niobate (LN) crystals, renowned for their exceptional nonlinear optical, electro-optical, piezoelectric, and photorefractive properties, stand as foundational materials in diverse fields of study and application. While they have long been utilized in frequency converters of laser radiation, electro-optical modulators, and holographic information recording media, LN crystals doped with rare earth ions represent a compelling frontier for modern compact devices. These materials exhibit immense potential as key components in infrared lasers, optical sensors, self-cooling systems, and radiation balanced laser setups. In this study, we present the successful synthesis of Ho-doped lithium niobate (LN:Ho) thin films on sapphire substrates employing the Sol-Gel technique. The films exhibit a strong crystallographic orientation along the perpendicular direction to the substrate surface, with X-ray diffraction analysis confirming the predominant alignment of the film's "c" axis, notably evidenced by the intense (006) reflection peak. Further characterization through Raman spectroscopy, employing a confocal Raman microscope (LabRAM HR Evolution) with exciting wavelengths of 532 nm and 785 nm, unraveled intriguing insights. Under excitation with a 785 nm laser, Raman scattering obeyed selection rules, while employing a 532 nm laser unveiled additional forbidden lines reminiscent of behaviors observed in bulk LN:Ho crystals. These supplementary lines were attributed to luminescence induced by excitation at 532 nm. Leveraging data from anti-Stokes Raman lines facilitated the disentanglement of luminescence spectra from the investigated samples. Surface scanning affirmed the uniformity of both structure and luminescence across the thin films. Notably, despite the robust orientation of the "c" axis perpendicular to the substrate surface, Raman signals indicated a stochastic distribution of "a" and "b" axes, validating the mosaic structure of the films along the mentioned axis. This study offers valuable insights into the structural properties of Ho-doped lithium niobate thin films, with the observed luminescence behavior holding significant promise for potential applications in optoelectronic devices.Keywords: lithium niobate, Sol-Gel, luminescence, Raman spectroscopy
Procedia PDF Downloads 60714 Georgian Churches in the Eastern Provinces of Turkey
Authors: Mustafa Tahir Ocak, Gülsün Tanyeli
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Georgia became Christian in the 4th century. During the 7th and 8th centuries, Georgia, with its capital at Tiflis, was devastated by Arab invasions from the south and east. Tiflis was abandoned and a new Georgia, with its capital at present-day Ardanuç; in Turkey, was established, based on the provinces of Tao, Klarjeti and Shavsheti. Georgian power revived during the 9th century and the new kings embarked on a notable period of church building, each prince intent on raising memorials to his reign. Georgia was weakened again in the 11th century. First, by Byzantium which now feared the Georgians’ growing power and, second, by the advance of the Seljuk Turks. But defeat did not last long and under David II, ‘the Builder’, Georgian armies recaptured Tiflis in 1122, heralding a second political and cultural renascence. There has been a remarkable increase in the number of monuments in 9th-11th centuries. Kingdom of Georgia’s boundaries have changed lots of times over the centuries, and consequently a considerable number of churches are to be found in other countries, especially in north-eastern provinces of Turkey. Georgian monuments spread to valleys of the Çoruh, Oltu and Tortum rivers in north-east Turkey. These churches have significant role in architectural history. The medieval Georgians and the Armenians had known contacts with Byzantium. Their churches influenced mid-Byzantine architecture and were a factor in the evolution of the Romanesque style in Europe. In the centuries following the inclusion of Tao and Klarjeti within the expanding Ottoman Empire, the monasteries and churches were gradually abandoned with migration of Christian population. Although some of those monuments are in good condition through the conversion of churches to use as mosques, the rest of those monuments are under threat from neglect and lack of maintenance. Many fell into ruin or were plundered for their stone; others were damaged by earthquakes, by treasure hunters. The only hope for the Georgian churches is for them to be recognised as a touristic value in a beautiful region of deep valleys and magnificent mountain scenery. As coeval churches in modern Georgian boundaries, these churches in north-eastern provinces of Turkey have to evaluated by UNESCO. This study aims to create awereness about the conservation of Georgian churches in north-eastern provinces of Turkey as world heritage taking advantages of tourism. Georgian churches as a heritage should be evaluated not only a monument but also cultural landscape. The cultural route is created visiting both churches and the other medieval structures in these regions.Keywords: Georgian churches, medieval monuments, Tao-Klarjeti, Turkey
Procedia PDF Downloads 286713 Optimizing Residential Housing Renovation Strategies at Territorial Scale: A Data Driven Approach and Insights from the French Context
Authors: Rit M., Girard R., Villot J., Thorel M.
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In a scenario of extensive residential housing renovation, stakeholders need models that support decision-making through a deep understanding of the existing building stock and accurate energy demand simulations. To address this need, we have modified an optimization model using open data that enables the study of renovation strategies at both territorial and national scales. This approach provides (1) a definition of a strategy to simplify decision trees from theoretical combinations, (2) input to decision makers on real-world renovation constraints, (3) more reliable identification of energy-saving measures (changes in technology or behaviour), and (4) discrepancies between currently planned and actually achieved strategies. The main contribution of the studies described in this document is the geographic scale: all residential buildings in the areas of interest were modeled and simulated using national data (geometries and attributes). These buildings were then renovated, when necessary, in accordance with the environmental objectives, taking into account the constraints applicable to each territory (number of renovations per year) or at the national level (renovation of thermal deficiencies (Energy Performance Certificates F&G)). This differs from traditional approaches that focus only on a few buildings or archetypes. This model can also be used to analyze the evolution of a building stock as a whole, as it can take into account both the construction of new buildings and their demolition or sale. Using specific case studies of French territories, this paper highlights a significant discrepancy between the strategies currently advocated by decision-makers and those proposed by our optimization model. This discrepancy is particularly evident in critical metrics such as the relationship between the number of renovations per year and achievable climate targets or the financial support currently available to households and the remaining costs. In addition, users are free to seek optimizations for their building stock across a range of different metrics (e.g., financial, energy, environmental, or life cycle analysis). These results are a clear call to re-evaluate existing renovation strategies and take a more nuanced and customized approach. As the climate crisis moves inexorably forward, harnessing the potential of advanced technologies and data-driven methodologies is imperative.Keywords: residential housing renovation, MILP, energy demand simulations, data-driven methodology
Procedia PDF Downloads 68712 Series Connected GaN Resonant Tunneling Diodes for Multiple-Valued Logic
Authors: Fang Liu, JunShuai Xue, JiaJia Yao, XueYan Yang, ZuMao Li, GuanLin Wu, HePeng Zhang, ZhiPeng Sun
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III-Nitride resonant tunneling diode (RTD) is one of the most promising candidates for multiple-valued logic (MVL) elements. Here, we report a monolithic integration of GaN resonant tunneling diodes to realize multiple negative differential resistance (NDR) regions for MVL application. GaN RTDs, composed of a 2 nm quantum well embedded in two 1 nm quantum barriers, are grown by plasma-assisted molecular beam epitaxy on free-standing c-plane GaN substrates. Negative differential resistance characteristic with a peak current density of 178 kA/cm² in conjunction with a peak-to-valley current ratio (PVCR) of 2.07 is observed. Statistical properties exhibit high consistency showing a peak current density standard deviation of almost 1%, laying the foundation for the monolithic integration. After complete electrical isolation, two diodes of the designed same area are connected in series. By solving the Poisson equation and Schrodinger equation in one dimension, the energy band structure is calculated to explain the transport mechanism of the differential negative resistance phenomenon. Resonant tunneling events in a sequence of the series-connected RTD pair (SCRTD) form multiple NDR regions with nearly equal peak current, obtaining three stable operating states corresponding to ternary logic. A frequency multiplier circuit achieved using this integration is demonstrated, attesting to the robustness of this multiple peaks feature. This article presents a monolithic integration of SCRTD with multiple NDR regions driven by the resonant tunneling mechanism, which can be applied to a multiple-valued logic field, promising a fast operation speed and a great reduction of circuit complexity and demonstrating a new solution for nitride devices to break through the limitations of binary logic.Keywords: GaN resonant tunneling diode, multiple-valued logic system, frequency multiplier, negative differential resistance, peak-to-valley current ratio
Procedia PDF Downloads 81711 Multilingualism in Medieval Romance: A French Case Study
Authors: Brindusa Grigoriu
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Inscribing itself in the field of the history of multilingual communities with a focus on the evolution of language didactics, our paper aims at providing a pragmatic-interactional approach on a corpus proposing to scholars of the international scientific community a relevant text of early modern European literature: the first romance in French, The Conte of Flore and Blanchefleur by Robert d’Orbigny (1150). The multicultural context described by the romance is one in which an Arab-speaking prince, Floire, and his Francophone protégée, Blanchefleur, learn Latin together at the court of Spain and become fluent enough to turn it into the language of their love. This learning process is made up of interactional patterns of affective relevance, in which the proficiency of the protagonists in the domain of emotive acts becomes a matter of linguistic and pragmatic emulation. From five to ten years old, the pupils are efficiently stimulated by their teacher of Latin, Gaidon – a Moorish scholar of the royal entourage – to cultivate their competencies of oral expression and reading comprehension (of Antiquity classics), while enjoying an ever greater freedom of written expression, including the composition of love poems in this second language of culture and emotional education. Another relevant parameter of the educational process at court is that Latin shares its prominent role as a language of culture with French, whose exemplary learner is the (Moorish) queen herself. Indeed, the adult 'First lady' strives to become a pupil benefitting from lifelong learning provided by a fortuitous slave-teacher with little training, her anonymous chambermaid and Blanchefleur’s mother, who, despite her status of a war trophy, enjoys her Majesty’s confidence as a cultural agent of change in linguistic and theological fields. Thus, the two foreign languages taught at Spains’s court, Latin and French – as opposed to Arabic -, suggest a spiritual authority allowing the mutual enrichment of intercultural pioneers of cross-linguistic communication, in the aftermath of religious wars. Durably, and significantly – if not everlastingly – the language of physical violence rooted in intra-cultural solipsism is replaced by two Romance languages which seem to embody, together and yet distinctly, the parlance of peace-making.Keywords: multilingualism, history of European language learning, French and Latin learners, multicultural context of medieval romance
Procedia PDF Downloads 139710 Clinical Applications of Amide Proton Transfer Magnetic Resonance Imaging: Detection of Brain Tumor Proliferative Activity
Authors: Fumihiro Ima, Shinichi Watanabe, Shingo Maeda, Haruna Imai, Hiroki Niimi
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It is important to know growth rate of brain tumors before surgery because it influences treatment planning including not only surgical resection strategy but also adjuvant therapy after surgery. Amide proton transfer (APT) imaging is an emerging molecular magnetic resonance imaging (MRI) technique based on chemical exchange saturation transfer without administration of contrast medium. The underlying assumption in APT imaging of tumors is that there is a close relationship between the proliferative activity of the tumor and mobile protein synthesis. We aimed to evaluate the diagnostic performance of APT imaging of pre-and post-treatment brain tumors. Ten patients with brain tumor underwent conventional and APT-weighted sequences on a 3.0 Tesla MRI before clinical intervention. The maximum and the minimum APT-weighted signals (APTWmax and APTWmin) in each solid tumor region were obtained and compared before and after clinical intervention. All surgical specimens were examined for histopathological diagnosis. Eight of ten patients underwent adjuvant therapy after surgery. Histopathological diagnosis was glioma in 7 patients (WHO grade 2 in 2 patients, WHO grade 3 in 3 patients and WHO grade 4 in 2 patients), meningioma WHO grade1 in 2 patients and primary lymphoma of the brain in 1 patient. High-grade gliomas showed significantly higher APTW-signals than that in low-grade gliomas. APTWmax in one huge parasagittal meningioma infiltrating into the skull bone was higher than that in glioma WHO grade 4. On the other hand, APTWmax in another convexity meningioma was the same as that in glioma WHO grade 3. Diagnosis of primary lymphoma of the brain was possible with APT imaging before pathological confirmation. APTW-signals in residual tumors decreased dramatically within one year after adjuvant therapy in all patients. APT imaging demonstrated excellent diagnostic performance for the planning of surgery and adjuvant therapy of brain tumors.Keywords: amides, magnetic resonance imaging, brain tumors, cell proliferation
Procedia PDF Downloads 139709 Methylglyoxal Induced Glycoxidation of Human Low Density Lipoprotein: A Biophysical Perspective and Its Role in Diabetes and Periodontitis
Authors: Minhal Abidi, Moinuddin
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Diabetes mellitus (DM) induced metabolic abnormalities causes oxidative stress which leads to the pathogenesis of complications associated with diabetes like retinopathy, nephropathy periodontitis etc. Combination of glycation and oxidation 'glycoxidation' occurs when oxidative reactions affect the early state of glycation products. Low density lipoprotein (LDL) is prone to glycoxidative attack by sugars and methylglyoxal (MGO) being a strong glycating agent may have severe impact on its structure and consequent role in diabetes. Pro-inflammatory cytokines like IL1β and TNFα produced by the action of gram negative bacteria in periodontits (PD) can in turn lead to insulin resistance. This work discusses modifications to LDL as a result of glycoxidation. The changes in the protein molecule have been characterized by various physicochemical techniques and the immunogenicity of the modified molecules was also evaluated as they presented neo-epitopes. Binding of antibodies present in diabetes patients to the native and glycated LDL has been evaluated. Role of modified epitopes in the generation of antibodies in diabetes and periodontitis has been discussed. The structural perturbations induced in LDL were analyzed by UV–Vis, fluorescence, circular dichroism and FTIR spectroscopy, molecular docking studies, thermal denaturation studies, Thioflavin T assay, isothermal titration calorimetry, comet assay. MALDI-TOF, ketoamine moieties, carbonyl content and HMF content were also quantitated in native and glycated LDL. IL1β and TNFα levels were also measured in the type 2 DM and PD patients. We report increased carbonyl content, ketoamine moieties and HMF content in glycated LDL as compared to native analogue. The results substantiate that in hyperglycemic state MGO modification of LDL causes structural perturbations making the protein antigenic which could obstruct normal physiological functions and might contribute in the development of secondary complications in diabetic patients like periodontitis.Keywords: advanced glycation end products, diabetes mellitus, glycation, glycoxidation, low density lipoprotein, periodontitis
Procedia PDF Downloads 191708 Rooibos Extract Antioxidants: In vitro Models to Assess Their Bioavailability
Authors: Ntokozo Dambuza, Maryna Van De Venter, Trevor Koekemoer
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Oxidative stress contributes to the pathogenesis of many diseases and consequently antioxidant therapy has attracted much attention as a potential therapeutic strategy. Regardless of the quantities ingested, antioxidants need to reach the diseased tissues at concentrations sufficient to combat oxidative stress. Bioavailability is thus a defining criterion for the therapeutic efficacy of antioxidants. In addition, therapeutic antioxidants must possess biologically relevant characteristics which can target the specific molecular mechanisms responsible for disease related oxidative stress. While many chemical antioxidant assays are available to quantify antioxidant capacity, they relate poorly to the biological environment and provide no information as to the bioavailability. The present comparative study thus aims to characterise green and fermented rooibos extracts, well recognized for their exceptional antioxidant capacity, in terms of antioxidant bioavailability and efficacy in a disease relevant cellular setting. Chinese green tea antioxidant activity was also evaluated. Chemical antioxidant assays (FRAP, DPPH and ORAC) confirmed the potent antioxidant capacity of both green and fermented rooibos, with green rooibos possessing antioxidant activity superior to that of fermented rooibos and Chinese green tea. Bioavailability was assessed using the PAMPA assay and the results indicate that green and fermented rooibos have a permeation coefficient of 5.7 x 10-6 and 6.9 x 10-6 cm/s, respectively. Chinese green tea permeability coefficient was 8.5 x 10-6 cm/s. These values were comparable to those of rifampicin, which is known to have a high permeability across intestinal epithelium with a permeability coefficient of 5 x 10 -6 cm/s. To assess the antioxidant efficacy in a cellular context, U937 and red blood cells were pre-treated with rooibos and Chinese green tea extracts in the presence of a dye DCFH-DA and then exposed to oxidative stress. Green rooibos exhibited highest activity with an IC50 value of 29 μg/ml and 70 μg/ml, when U937 and red blood cells were exposed oxidative stress, respectively. Fermented rooibos and Chinese green tea had IC50 values of 61 μg/ml and 57 μg/ml for U937, respectively, and 221 μg/ml and 405 μg/ml for red blood cells, respectively. These results indicate that fermented and green rooibos extracts were able to permeate the U937 cells and red blood cell membrane and inhibited oxidation of DCFH-DA to a fluorescent DCF within the cells.Keywords: rooibos, antioxidants, permeability, bioavailability
Procedia PDF Downloads 317707 Modulating Photoelectrochemical Water-Splitting Activity by Charge-Storage Capacity of Electrocatalysts
Authors: Yawen Dai, Ping Cheng, Jian Ru Gong
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Photoelctrochemical (PEC) water splitting using semiconductors (SCs) provides a convenient way to convert sustainable but intermittent solar energy into clean hydrogen energy, and it has been regarded as one of most promising technology to solve the energy crisis and environmental pollution in modern society. However, the record energy conversion efficiency of a PEC cell (~3%) is still far lower than the commercialization requirement (~10%). The sluggish kinetics of oxygen evolution reaction (OER) half reaction on photoanodes is a significant limiting factor of the PEC device efficiency, and electrocatalysts (ECs) are always deposited on SCs to accelerate the hole injection for OER. However, an active EC cannot guarantee enhanced PEC performance, since the newly emerged SC-EC interface complicates the interfacial charge behavior. Herein, α-Fe2O3 photoanodes coated with Co3O4 and CoO ECs are taken as the model system to glean fundamental understanding on the EC-dependent interfacial charge behavior. Intensity modulated photocurrent spectroscopy and electrochemical impedance spectroscopy were used to investigate the competition between interfacial charge transfer and recombination, which was found to be dominated by the charge storage capacities of ECs. The combined results indicate that both ECs can store holes and increase the hole density on photoanode surface. It is like a double-edged sword that benefit the multi-hole participated OER, as well as aggravate the SC-EC interfacial charge recombination due to the Coulomb attraction, thus leading to a nonmonotonic PEC performance variation trend with the increasing surface hole density. Co3O4 has low hole storage capacity which brings limited interfacial charge recombination, and thus the increased surface holes can be efficiently utilized for OER to generate enhanced photocurrent. In contrast, CoO has overlarge hole storage capacity that causes severe interfacial charge recombination, which hinders hole transfer to electrolyte for OER. Therefore, the PEC performance of α-Fe2O3 is improved by Co3O4 but decreased by CoO despite the similar electrocatalytic activity of the two ECs. First-principle calculation was conducted to further reveal how the charge storage capacity depends on the EC’s intrinsic property, demonstrating that the larger hole storage capacity of CoO than that of Co3O4 is determined by their Co valence states and original Fermi levels. This study raises up a new strategy to manipulate interfacial charge behavior and the resultant PEC performance by the charge storage capacity of ECs, providing insightful guidance for the interface design in PEC devices.Keywords: charge storage capacity, electrocatalyst, interfacial charge behavior, photoelectrochemistry, water-splitting
Procedia PDF Downloads 141706 Discrimination of Bio-Analytes by Using Two-Dimensional Nano Sensor Array
Authors: P. Behera, K. K. Singh, D. K. Saini, M. De
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Implementation of 2D materials in the detection of bio analytes is highly advantageous in the field of sensing because of its high surface to volume ratio. We have designed our sensor array with different cationic two-dimensional MoS₂, where surface modification was achieved by cationic thiol ligands with different functionality. Green fluorescent protein (GFP) was chosen as signal transducers for its biocompatibility and anionic nature, which can bind to the cationic MoS₂ surface easily, followed by fluorescence quenching. The addition of bio-analyte to the sensor can decomplex the cationic MoS₂ and GFP conjugates, followed by the regeneration of GFP fluorescence. The fluorescence response pattern belongs to various analytes collected and transformed to linear discriminant analysis (LDA) for classification. At first, 15 different proteins having wide range of molecular weight and isoelectric points were successfully discriminated at 50 nM with detection limit of 1 nM. The sensor system was also executed in biofluids such as serum, where 10 different proteins at 2.5 μM were well separated. After successful discrimination of protein analytes, the sensor array was implemented for bacteria sensing. Six different bacteria were successfully classified at OD = 0.05 with a detection limit corresponding to OD = 0.005. The optimized sensor array was able to classify uropathogens from non-uropathogens in urine medium. Further, the technique was applied for discrimination of bacteria possessing resistance to different types and amounts of drugs. We found out the mechanism of sensing through optical and electrodynamic studies, which indicates the interaction between bacteria with the sensor system was mainly due to electrostatic force of interactions, but the separation of native bacteria from their drug resistant variant was due to Van der Waals forces. There are two ways bacteria can be detected, i.e., through bacterial cells and lysates. The bacterial lysates contain intracellular information and also safe to analysis as it does not contain live cells. Lysates of different drug resistant bacteria were patterned effectively from the native strain. From unknown sample analysis, we found that discrimination of bacterial cells is more sensitive than that of lysates. But the analyst can prefer bacterial lysates over live cells for safer analysis.Keywords: array-based sensing, drug resistant bacteria, linear discriminant analysis, two-dimensional MoS₂
Procedia PDF Downloads 143705 Surface Modification of Co-Based Nanostructures to Develop Intrinsic Fluorescence and Catalytic Activity
Authors: Monalisa Pal, Kalyan Mandal
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Herein we report the molecular functionalization of promising transition metal oxide nanostructures, such as Co3O4 nanocubes, using nontoxic and biocompati-ble organic ligand sodium tartrate. The electronic structural modification of the nanocubes imparted through functionalization and subsequent water solubilization reveals multiple absorption bands in the UV-vis region. Further surface modification of the solubilized nanocubes, leads to the emergence of intrinsic multi-color fluorescence (from blue, cyan, green to red region of the spectrum), upon excitation at proper wavelengths, where the respective excitation wavelengths have a direct correlation with the observed UV-vis absorption bands. Using a multitude of spectroscopic tools we have investigated the mechanistic insight behind the origin of different UV-vis absorption bands and emergence of multicolor photoluminescence from the functionalized nanocubes. Our detailed study shows that ligand to metal charge transfer (LMCT) from tartrate ligand to Co2+/Co3+ ions and d-d transitions involving Co2+/Co3+ ions are responsible for generation of this novel optical properties. Magnetic study reveals that, antiferromagnetic nature of Co3O4 nanocubes changes to ferromagnetic behavior upon functionalization, however, the overall magnetic response was very weak. To combine strong magnetism with this novel optical property, we followed the same surface modification strategy in case of CoFe2O4 nanoparticles, which reveals that irrespective of size and shape, all Co-based oxides can develop intrinsic multi-color fluorescence upon facile functionalization with sodium tartrate ligands and the magnetic response was significantly higher. Surface modified Co-based oxide nanostructures also show excellent catalytic activity in degradation of biologically and environmentally harmful dyes. We hope that, our developed facile functionalization strategy of Co-based oxides will open up new opportunities in the field of biomedical applications such as bio-imaging and targeted drug delivery.Keywords: co-based oxide nanostructures, functionalization, multi-color fluorescence, catalysis
Procedia PDF Downloads 387704 Flipping the Script: Opportunities, Challenges, and Threats of a Digital Revolution in Higher Education
Authors: James P. Takona
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In a world that is experiencing sharp digital transformations guided by digital technologies, the potential of technology to drive transformation and evolution in the higher is apparent. Higher education is facing a paradigm shift that exposes susceptibilities and threats to fully online programs in the face of post-Covid-19 trends of commodification. This historical moment is likely to be remembered as a critical turning point from analog to digital degree-focused learning modalities, where the default became the pivot point of competition between higher education institutions. Fall 2020 marks a significant inflection point in higher education as students, educators, and government leaders scrutinize higher education's price and value propositions through the new lens of traditional lecture halls versus multiple digitized delivery modes. Online education has since tiled the way for a pedagogical shift in how teachers teach and students learn. The incremental growth of online education in the west can now be attributed to the increasing patronage among students, faculty, and institution administrators. More often than not, college instructors assume paraclete roles in this learning mode, while students become active collaborators and no longer passive learners. This paper offers valuable discernments into the threats, challenges, and opportunities of a massive digital revolution in servicing degree programs. To view digital instruction and learning demands for instructional practices that revolve around collaborative work, engaging students in learning activities, and an engagement that promotes active efforts to solicit strong connections between course activities and expected learning pace for all students. Appropriate digital technologies demand instructors and students need prior solid skills. Need for the use of digital technology to support instruction and learning, intelligent tutoring offers great promise, and failures at implementing digital learning may not improve outcomes for specific student populations. Digital learning benefits students differently depending on their circumstances and background and those of the institution and/or program. Students have alternative options, access to the convenience of learning anytime and anywhere, and the possibility of acquiring and developing new skills leading to lifelong learning.Keywords: digi̇tized learning, digital education, collaborative work, high education, online education, digitize delivery
Procedia PDF Downloads 91703 Phenotypic Characterization of Desi Naked Neck Chicken and Its Association with Insulin-Like Growth Factor-I (IGF-I) Gene Polymorphism in Pakistan
Authors: Akbar Nawaz Khan, Abdul Ghaffar, Muhammad Naeem Riaz
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The study was conducted to investigate the phenotypic features, morphometry and production potentialities of indigenous naked neck chicken (NN) of Pakistan under intensive management condition. A total of 35 NN chicks were randomly selected, and the experiment was performed at Poultry and wildlife research section NARC Islamabad for a period of 22 weeks. The predominant plumage color was black and golden while skin color was observed white. The average shank length, leg length, thigh length, keel length, chest breadth, head width, wing space, wing length, body length, body girth, body height and pubic bone width in adult males and females were 69.19 ± 3.34mm, 117.93 ± 4.42mm, 117.93 ± 4.42mm, 90.87 ± 6.53mm, 95.03 ± 4.56mm, 49.77 ± 2.53mm, 30.63 ± 1.50cm, 27.24 ± 2.71cm, 18.88 ± 0.65cm, 17.77 ± 1.01cm, 25.96 ± 0.56cm, 47.81 ± 1.41cm and 35.69 ± 4.09mm respectively. The average age and live body weight of NN chicken at sexual maturity were recorded as 165.85 days and 1269.38 g. While hen-day egg production of NN was recorded as 45%. The present study was aimed to investigate the existence of polymorphism at IGF-I gene in indigenous naked neck chicken through PCR based Restriction Fragment Length Polymorphism. Based on restriction analysis using Hinf I restriction enzyme, three genotypes were detected designated as AA, AC, and CC. Restriction analysis of PCR amplified product showed the presence of DNA fragments of 622, 378, 244 and 191, (genotypes). The PCR-RFLP analysis is easy, cost effective method which permits the easy characterization of IGF-I gene. This showed the investigated IGF-I genes can serve as good molecular markers for marker assisted selection (MAS) concerning growth related traits in chicken.Keywords: Desi chicken, naked neck, morphology, morphometry, production potential, egg traits, egg geometry, IGF-I, growth, PCR- RFLP, chicken
Procedia PDF Downloads 389702 Abridging Pharmaceutical Analysis and Drug Discovery via LC-MS-TOF, NMR, in-silico Toxicity-Bioactivity Profiling for Therapeutic Purposing Zileuton Impurities: Need of Hour
Authors: Saurabh B. Ganorkar, Atul A. Shirkhedkar
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The need for investigations protecting against toxic impurities though seems to be a primary requirement; the impurities which may prove non - toxic can be explored for their therapeutic potential if any to assist advanced drug discovery. The essential role of pharmaceutical analysis can thus be extended effectively to achieve it. The present study successfully achieved these objectives with characterization of major degradation products as impurities for Zileuton which has been used for to treat asthma since years. The forced degradation studies were performed to identify the potential degradation products using Ultra-fine Liquid-chromatography. Liquid-chromatography-Mass spectrometry (Time of Flight) and Proton Nuclear Magnetic Resonance Studies were utilized effectively to characterize the drug along with five major oxidative and hydrolytic degradation products (DP’s). The mass fragments were identified for Zileuton and path for the degradation was investigated. The characterized DP’s were subjected to In-Silico studies as XP Molecular Docking to compare the gain or loss in binding affinity with 5-Lipooxygenase enzyme. One of the impurity of was found to have the binding affinity more than the drug itself indicating for its potential to be more bioactive as better Antiasthmatic. The close structural resemblance has the ability to potentiate or reduce bioactivity and or toxicity. The chances of being active biologically at other sites cannot be denied and the same is achieved to some extent by predictions for probability of being active with Prediction of Activity Spectrum for Substances (PASS) The impurities found to be bio-active as Antineoplastic, Antiallergic, and inhibitors of Complement Factor D. The toxicological abilities as Ames-Mutagenicity, Carcinogenicity, Developmental Toxicity and Skin Irritancy were evaluated using Toxicity Prediction by Komputer Assisted Technology (TOPKAT). Two of the impurities were found to be non-toxic as compared to original drug Zileuton. As the drugs are purposed and repurposed effectively the impurities can also be; as they can have more binding affinity; less toxicity and better ability to be bio-active at other biological targets.Keywords: UFLC, LC-MS-TOF, NMR, Zileuton, impurities, toxicity, bio-activity
Procedia PDF Downloads 195701 Everolimus Loaded Polyvinyl Alcohol Microspheres for Sustained Drug Delivery in the Treatment of Subependymal Giant Cell Astrocytoma
Authors: Lynn Louis, Bor Shin Chee, Marion McAfee, Michael Nugent
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This article aims to develop a sustained release formulation of microspheres containing the mTOR inhibitor Everolimus (EVR) using Polyvinyl alcohol (PVA) to enhance the bioavailability of the drug and to overcome poor solubility characteristics of Everolimus. This paper builds on recent work in the manufacture of microspheres using the sessile droplet technique by freezing the polymer-drug solution by suspending the droplets into pre-cooled ethanol vials immersed in liquid nitrogen. The spheres were subjected to 6 freezing cycles and 3 freezing cycles with thawing to obtain proper geometry, prevent aggregation, and achieve physical cross-linking. The prepared microspheres were characterised for surface morphology by SEM, where a 3-D porous structure was observed. The in vitro release studies showed a 62.17% release over 12.5 days, indicating a sustained release due to good encapsulation. This result is comparatively much more than the 49.06% release achieved within 4 hours from the solvent cast Everolimus film as a control with no freeze-thaw cycles performed. The solvent cast films were made in this work for comparison. A prolonged release of Everolimus using a polymer-based drug delivery system is essential to reach optimal therapeutic concentrations in treating SEGA tumours without systemic exposure. These results suggest that the combination of PVA and Everolimus via a rheological synergism enhanced the bioavailability of the hydrophobic drug Everolimus. Physical-chemical characterisation using DSC and FTIR analysis showed compatibility of the drug with the polymer, and the stability of the drug was maintained owing to the high molecular weight of the PVA. The obtained results indicate that the developed PVA/EVR microsphere is highly suitable as a potential drug delivery system with improved bioavailability in treating Subependymal Giant cell astrocytoma (SEGA).Keywords: drug delivery system, everolimus, freeze-thaw cycles, polyvinyl alcohol
Procedia PDF Downloads 127700 Clinical Applications of Amide Proton Transfer Magnetic Resonance Imaging: Detection of Brain Tumor Proliferative Activity
Authors: Fumihiro Imai, Shinichi Watanabe, Shingo Maeda, Haruna Imai, Hiroki Niimi
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It is important to know the growth rate of brain tumors before surgery because it influences treatment planning, including not only surgical resection strategy but also adjuvant therapy after surgery. Amide proton transfer (APT) imaging is an emerging molecular magnetic resonance imaging (MRI) technique based on chemical exchange saturation transfer without the administration of a contrast medium. The underlying assumption in APT imaging of tumors is that there is a close relationship between the proliferative activity of the tumor and mobile protein synthesis. We aimed to evaluate the diagnostic performance of APT imaging of pre-and post-treatment brain tumors. Ten patients with brain tumor underwent conventional and APT-weighted sequences on a 3.0 Tesla MRI before clinical intervention. The maximum and the minimum APT-weighted signals (APTWmax and APTWmin) in each solid tumor region were obtained and compared before and after a clinical intervention. All surgical specimens were examined for histopathological diagnosis. Eight of ten patients underwent adjuvant therapy after surgery. Histopathological diagnosis was glioma in 7 patients (WHO grade 2 in 2 patients, WHO grade 3 in 3 patients, and WHO grade 4 in 2 patients), meningioma WHO grade 1 in 2 patients, and primary lymphoma of the brain in 1 patient. High-grade gliomas showed significantly higher APTW signals than that low-grade gliomas. APTWmax in one huge parasagittal meningioma infiltrating into the skull bone was higher than that in glioma WHO grade 4. On the other hand, APTWmax in another convexity meningioma was the same as that in glioma WHO grade 3. Diagnosis of primary lymphoma of the brain was possible with APT imaging before pathological confirmation. APTW signals in residual tumors decreased dramatically within one year after adjuvant therapy in all patients. APT imaging demonstrated excellent diagnostic performance for the planning of surgery and adjuvant therapy of brain tumors.Keywords: amides, magnetic resonance imaging, brain tumors, cell proliferation
Procedia PDF Downloads 86699 Exploration of the Nonlinear Viscoelastic Behavior of Yogurt Using Lissajous Curves
Authors: Hugo Espinosa-Andrews
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Introduction: Yogurt is widely accepted worldwide due to its high nutritional value, consistency, and texture. Their rheological properties play a significant role in consumer acceptance and are related to the manufacturing process and formulation. Typically, the viscoelastic characteristics of yogurts are studied using the small amplitude oscillatory shear test; however, the initial stages of flow and oral processing are described in the nonlinear zone, in which a large amplitude oscillatory stress test is applied. The objective of this work was to analyze the nonlinear viscoelastic behavior of commercial yogurts using Lissajous curves. Methods: Two commercial yogurts were purchased in a local store in Guadalajara Jalisco Mexico: a natural Greek-style yogurt and a low-fat traditional yogurt. Viscoelastic properties were evaluated using a large amplitude oscillatory stress procedure (LAOS). A crosshatch geometry of 40 mm and a truncation of 1000 µm were used. Stress sweeps were performed at 6.28 rad/s from 1 to 250 Pa at 5°C. The nonlinear viscoelastic properties were analyzed using the Lissajous curves. Results: The yogurts showed strain-viscoelastic behavior related to deformation-dependent materials. In the low-strain region, the elastic modulus predominated over the viscous modulus, showing gel-elastic properties. The sol-gel transitions were observed at approximately 66.5 Pa for the Greek yogurt, double that detected for traditional yogurt. The viscoelastic behavior of the yogurts was characteristic of weak excess deformation: behavior indicating a stable molecular structure at rest, and moderate structure at medium shear-forces. The normalized Lissajous curves characterized viscoelastic transitions of the yogurt as the stress increased. Greater viscoelasticity deformation was observed in Greek yogurt than in traditional yogurt, which is related to the presence of a protein network with a greater degree of crosslinking. Conclusions: The yogurt composition influences the viscoelastic properties of the material. Yogurt with the higher percentage of protein has greater viscoelastic and viscous properties, which describe a product of greater consistency and creaminess.Keywords: yogurt, viscoelastic properties, LAOS, elastic modulus
Procedia PDF Downloads 21698 The Effect of Organic Matter Maturation and Porosity Evolution on Methane Storage Potential in Shale-Gas Reservoirs
Authors: T. Topór, A. Derkowski, P. Ziemiański
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Formation of organic matter (OM)-hosted nanopores upon thermal maturation are one of the key factor controlling methane storage potential in unconventional shale-gas reservoirs. In this study, the subcritical CO₂ and N₂ gas adsorption measurements combined with scanning electron microscopy and supercritical methane adsorption have been used to characterize pore system and methane storage potential in black shales from the Baltic Basin (Poland). The samples were collected from a virtually equivalent Llandovery strata across the basin and represent a complete digenetic sequence, from thermally immature to overmature. The results demonstrate that the thermal maturation is a dominant mechanism controlling the formation of OM micro- and mesopores in the Baltic Basin shales. The formation of micro- and mesopores occurs in the oil window (vitrinite reflectance; leavedVR; ~0.5-0.9%) as a result of oil expulsion from kerogenleft OM highly porous. The generated hydrocarbons then turn into solid bitumen causing pore blocking and substantial decrease in micro- and mesopore volume in late-mature shales (VR ~0.9-1.2%). Both micro- and mesopores are regenerated in a middle of the catagenesis range (VR 1.4-1.9%) due to secondary cracking of OM and gas formation. The micropore volume in investigated shales is almost exclusively controlled by the OM content. The contribution of clay minerals to micropore volume is insignificant and masked by a strong contribution from OM. Methane adsorption capacity in the Baltic Basin shales is predominantly controlled by microporous OM with pores < 1.5 nm. The mesopore volume (2-50 nm) and mesopore surface area have no effect on methane sorption behavior. The adsorbed methane density equivalent, calculated as absolute methane adsorption divided by micropore volume, reviled a decrease of the methane loading potential in micropores with increasing maturity. The highest methane loading potential in micropores is observed for OM before metagenesis (VR < 2%), where the adsorbed methane density equivalent is greater than the density of liquid methane. This implies that, in addition to physical adsorption, absorption of methane in OM may occur before metagenesis. After OM content reduction using NaOCl solution methane adoption capacity substantially decreases, suggesting significantly greater adsorption potential for OM microstructure than for the clay minerals matrix.Keywords: maturation, methane sorption, organic matter, porosity, shales
Procedia PDF Downloads 236697 One Pot Synthesis of Ultrasmall NiMo Catalysts Supported on Amorphous Alumina with Enhanced type 2 Sites for Hydrodesulfurization Reaction: A Combined Experimental and Theoretical Study
Authors: Shalini Arora, Sri Sivakumar
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The deep removal of high molecular weight sulphur compounds (e.g., 4,6, dimethyl dibenzothiophene) is challenging due to their steric hindrance. Hydrogenation desulfurization (HYD) pathway is the main pathway to remove these sulfur compounds, and it is mainly governed by the number of type 2 sites. The formation of type 2 sites can be enhanced by modulating the pore structure and the interaction between the active metal and support. To this end, we report the enhanced HDS catalytic activity of ultrasmall NiMo supported on amorphous alumina (A-Al₂O₃) catalysts by one pot colloidal synthesis method followed by calcination and sulfidation. The amorphous alumina (A-Al₂O₃) was chosen as the support due to its lower surface energy, better physicochemical properties, and enhanced acidic sites (due to the dominance of tetra and penta coordinated [Al] sites) than crystalline alumina phase. At 20% metal oxide composition, NiMo supported on A-Al₂O₃ catalyst showed 1.4 and 1.2 times more reaction rate constant and turn over frequency (TOF) respectively than the conventional catalyst (wet impregnated NiMo catalysts) for HDS reaction of dibenzothiophene reactant molecule. A-Al₂O₃ supported catalysts represented enhanced type 2 sites formation (because this catalystpossesses higher sulfidation degree (80%) and NiMoS sites (19.3 x 10¹⁷ sites/mg) with desired optimum stacking degree (2.5) than wet impregnated catalyst at same metal oxide composition 20%) along with higher active metal dispersion, Mo edge site fraction. The experimental observations were also supported by DFT simulations. Lower heat of adsorption (< 4.2 ev for MoS2 interaction and < 3.15 ev for Ni doped MoS2 interaction) values for A-Al₂O₃ confirmed the presence of weaker metal-support interaction in A-Al₂O₃ in contrast to crystalline ℽ-Al₂O3. The weak metal-support interaction for prepared catalysts clearly suggests the higher formation of type 2 sites which leads to higher catalytic activity for HDS reaction.Keywords: amorphous alumina, colloidal, desulfurization, metal-support interaction
Procedia PDF Downloads 267