Search results for: therapeutic response

Authors: Ranjeeta Kumari, Makesh M, Gayatri Tripathi, K V Rajendran, Megha Bedekar

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A comparative study on DNA immunization with recombinant glyceraldehyde-3-phosphate dehydrogenase (GAPDH) construct of Edwardsiella tarda (pGPD group) and a bicistronic construct expressing GAPDH plus IFN-γ of Labeo rohita as adjuvant (pGPD+IFN group) was undertaken in Labeo rohita along with the control animals. Successful co-expression of two genes that is GAPDH and IFN-γ was confirmed in SSN-1 cells line by RT-qPCR and western blot. The protective immune response of host to DNA vaccine construct was determined by RPS and specific antibody production. Fishes immunized with plasmids via intramuscular injection (I/M) exhibited a considerable relative percentage survivability of 66.66% in pGPD+IFN immunized group and 53.34% in pGPD immunized group after challenge with E. tarda. Antibody response was also significantly high in pGPD+IFN group at all time points under study. This was analysed by competitive ELISA, using anti GAPDH monoclonal antibodies. The experiment revealed that the GAPDH gene of E. tarda is one of the ideal candidates for generating protective immune response in L. rohita. Further addition of Interferon gamma to DNA vaccine construct can enhance the immune response in host.

Keywords: DNA vaccine, Edwardsiella tarda, Labeo rohita, zoonosis, immune response

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

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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

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Authors: I Made Ginarsa, Agung Budi Muljono, I Made Ari Nrartha

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Transient voltage response appears in power system operation when an additional loading is forced to load bus of power systems. In this research, improvement of transient voltage response is done by using power system stabilizer-static var compensator (PSS-SVC) based on adaptive neuro-fuzzy inference system (ANFIS)-algorithm. The main function of the PSS is to add damping component to damp rotor oscillation through automatic voltage regulator (AVR) and excitation system. Learning process of the ANFIS is done by using off-line method where data learning that is used to train the ANFIS model are obtained by simulating the PSS-SVC conventional. The ANFIS model uses 7 Gaussian membership functions at two inputs and 49 rules at an output. Then, the ANFIS-PSS and ANFIS-SVC models are applied to power systems. Simulation result shows that the response of transient voltage is improved with settling time at the time of 4.25 s.

Keywords: improvement, transient voltage, PSS-SVC, ANFIS, settling time

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Authors: Nishank Raisinghani

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Efficiently predicting drug response remains a challenge in the realm of drug discovery. To address this issue, we propose four model architectures that combine graphical representation with varying positions of multiheaded self-attention mechanisms. By leveraging two types of multi-omics data, transcriptomics and genomics, we create a comprehensive representation of target cells and enable drug response prediction in precision medicine. A majority of our architectures utilize multiple transformer models, one with a graph attention mechanism and the other with a multiheaded self-attention mechanism, to generate latent representations of both drug and omics data, respectively. Our model architectures apply an attention mechanism to both drug and multiomics data, with the goal of procuring more comprehensive latent representations. The latent representations are then concatenated and input into a fully connected network to predict the IC-50 score, a measure of cell drug response. We experiment with all four of these architectures and extract results from all of them. Our study greatly contributes to the future of drug discovery and precision medicine by looking to optimize the time and accuracy of drug response prediction.

Keywords: drug discovery, transformers, graph neural networks, multiomics

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Authors: Vijaya Madhuri Devraj, Swarnalatha Guditi, Kiran Kumar Bokara, Gangadhar Taduri

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Cell-based strategies may open therapeutic approaches that promote tolerance through manipulation of macrophages to increase long-term transplant survival rates and minimize side effects of the current immune suppressive regimens. The aim of the present study was, therefore, to test and compare the therapeutic potential of MSC and Tregs on macrophage polarization to develop an alternate cell-based treatment option in kidney transplantation. In the current protocol, macrophages from kidney transplant recipients with graft dysfunction were co-cultured with MSCs and Treg cells with and without cell-cell contact on transwell plates, further to quantitatively assess macrophage polarization in response to MSC and Treg treatment over time, M1 and M2 cell surface markers were used. Additionally, multiple soluble analytes were analyzed in cell supernatant by using bead-based immunoassays. Furthermore, to confirm our findings, gene expression analysis was done. MSCs induced the formation of M2 macrophages more than Tregs when macrophages M0 were cultured in transwell without cell contact. From this, we deduced the mechanism that soluble factors present in the MSCs condition media are involved in skewing of macrophages towards type 2 macrophages; similarly, in co-culture with cell-cell contact, MSCs resulted in more M2 type macrophages than Tregs. And an important finding of this study is the combination of both MSC-Treg showed significantly effective and consistent results in both with and without cell contact setups. Hence, it is suggestive to prefer MSCs over Tregs for secretome-based therapy and a combination of both for either therapy for effective transplantation outcomes. Our findings underline a key role of Tregs and MSCs in promoting macrophage polarization towards anti-inflammatory type. The study has great importance in prolongation of allograft and patient survival without any rejection by cell-based therapy, which induce self-tolerance and controlling infection.

Keywords: graft rejection, graft tolerance, macrophage polarization, mesenchymal stem cells, regulatory T cells, transplant immunology

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Authors: Mark Berry

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A number of studies have identified several factors involved in the malignant progression of cancer cells. The Primary modulator in driving inflammation to these transformed cells has been identified as the transcription factor known as nuclear factor-κB. This essential regulator of inflammation and the development of cancer, combined with a microenvironment of inflammation and signaling molecules, plays a major role in the malignant progression of cancer, and this progression is the result of the mutagenic predisposition of persistent substances that combat infection at tumor sites and other areas of chronic inflammation. Inflammation-induced tumors, and their inflammatory cells and regulators may be the primary source of metastasis of tumor cells through angiogenesis. Previous research on cytokines and chemokines, including their downstream targets, has been the focus of the cancer/inflammation connection. The identification of the biological mechanisms of other proteins vital to the inflammation cascade and their interactions are crucial to novel and effective therapeutic protocols for the treatment of inflammation-induced cancers. The Ancelim HSRP Protocol is just such a therapeutic intervention.

Keywords: ancelim, cancer, inflammation, tumor

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Authors: Bal Chandra Yadav, Rakesh K. Sonker, Anjali Sharma, Punit Tyagi, Vinay Gupta, Monika Tomar

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In the present study, ZnO doped SnO2 thin films of various compositions were deposited on the surface of a corning substrate by dropping the two sols containing the precursors for composite (ZSO) with subsequent heat treatment. The sensor materials used for selective detection of nitrogen dioxide (NO2) were designed from the correlation between the sensor composition and gas response. The available NO2 sensors are operative at very high temperature (150-800 °C) with low sensing response (2-100) even in higher concentrations. Efforts are continuing towards the development of NO2 gas sensor aiming with an enhanced response along with a reduction in operating temperature by incorporating some catalysts or dopants. Thus in this work, a novel sensor structure based on ZSO nanocomposite has been fabricated using chemical route for the detection of NO2 gas. The structural, surface morphological and optical properties of prepared films have been studied by using X-ray diffraction (XRD), Atomic force microscopy (AFM), Transmission electron microscope (TEM) and UV-visible spectroscopy respectively. The effect of thickness variation from 230 nm to 644 nm of ZSO composite thin film has been studied and the ZSO thin film of thickness ~ 460 nm was found to exhibit the maximum gas sensing response ~ 2.1×103 towards 20 ppm NO2 gas at an operating temperature of 90 °C. The average response and recovery times of the sensor were observed to be 3.51 and 6.91 min respectively. Selectivity of the sensor was checked with the cross-exposure of vapour CO, acetone, IPA, CH4, NH3 and CO2 gases. It was found that besides the higher sensing response towards NO2 gas, the prepared ZSO thin film was also highly selective towards NO2 gas.

Keywords: ZSO nanocomposite thin film, ZnO tetrapod structure, NO2 gas sensor, sol-gel method

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Authors: Abigail Tan, Heng Liang Tan, Vanessa Ding, James Hui, Eng Hin Lee, Andre Choo

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Introduction: Comparative oncology investigates the similarities in spontaneous carcinogenesis between humans and animals, in order to identify treatments that can benefit these patients. Companion animals (CA), like canines and felines, are of special interest when it comes to studying human cancers due to their exposure to the same environmental factors and develop tumours with similar features. The purpose of this study is to explore the cross-reactivity of monoclonal antibodies (mAbs) across cancers in humans and CA. Material and Methods: A panel of CA mAbs generated in the lab was screened on multiple human cancer cell lines through flow cytometry to identify for positive binders. Shortlisted candidates were then characterised by biochemical and functional assays e.g., antibody-drug conjugate (ADC) and western blot assays, including glycan studies. Results: Candidate mAb KP52 was generated from whole-cell immunisation using feline mammary carcinoma. KP52 showed strong positive binding to human cancer cells, such as breast cancer and ovarian cancer. Furthermore, KP52 demonstrated strong killing ( > 50%) as an ADC with Saporin as the payload. Western blot results revealed the molecular weight of the antigen targets to be approximately 45kD and 50kD under reduced conditions. Glycan studies suggest that the epitope is glycan in nature, specifically an O-linked glycan. Conclusion: Candidate mAb KP52 has a therapeutic potential as an ADC against feline mammary cancer, human ovarian cancer, human mammary cancer, human pancreatic cancer, and human gastric cancer.

Keywords: ADC, comparative oncology, mAb, therapeutic

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Authors: Rahaba Marima, Clement Penny

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The Health-related quality of life (HRQoL) for HIV positive patients has improved since the introduction of the highly active antiretroviral treatment (HAART). However, in the present HAART era, HIV co-morbidities such as lung cancer, a non-AIDS (NAIDS) defining cancer have been documented to be on the rise. Under normal physiological conditions, cells grow, repair and proliferate through the cell-cycle as cellular homeostasis is important in the maintenance and proper regulation of tissues and organs. Contrarily, the deregulation of the cell-cycle is a hallmark of cancer, including lung cancer. The association between lung cancer and the use of HAART components such as Efavirenz (EFV) is poorly understood. This study aimed at elucidating the effects of EFV on the cell-cycle genes’ expression in lung cancer. For this purpose, the human cell-cycle gene array composed of 84 genes was evaluated on both normal lung fibroblasts (MRC-5) cells and adenocarcinoma (A549) lung cells, in response to 13µM EFV or 0.01% vehicle. The ±2 up or down fold change was used as a basis of target selection, with p < 0.05. Additionally, RT-qPCR was done to validate the gene array results. Next, In-silico bio-informatics tools, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Reactome, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Ingenuity Pathway Analysis (IPA) were used for gene/gene interaction studies as well as to map the molecular and biological pathways influenced by the identified targets. Interestingly, the DNA damage response (DDR) pathway genes such as p53, Ataxia telangiectasia mutated and Rad3 related (ATR), Growth arrest and DNA damage inducible alpha (GADD45A), HUS1 checkpoint homolog (HUS1) and Role of radiation (RAD) genes were shown to be upregulated following EFV treatment, as revealed by STRING analysis. Additionally, functional enrichment analysis by the KEGG pathway revealed that most of the differentially expressed gene targets function at the cell-cycle checkpoint such as p21, Aurora kinase B (AURKB) and Mitotic Arrest Deficient-Like 2 (MAD2L2). Core analysis by IPA revealed that p53 downstream targets such as survivin, Bcl2, and cyclin/cyclin dependent kinases (CDKs) complexes are down-regulated, following exposure to EFV. Furthermore, Reactome analysis showed a significant increase in cellular response to stress genes, DNA repair genes, and apoptosis genes, as observed in both normal and cancerous cells. These findings implicate the genotoxic effects of EFV on lung cells, provoking the DDR pathway. Notably, the constitutive expression of this pathway (DDR) often leads to uncontrolled cell proliferation and eventually tumourigenesis, which could be the attribute of HAART components’ (such as EFV) effect on human cancers. Targeting the cell-cycle and its regulation holds a promising therapeutic intervention to the potential HAART associated carcinogenesis, particularly lung cancer.

Keywords: cell-cycle, DNA damage response, Efavirenz, lung cancer

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Authors: Joshua Chew, Vesa Cheng, David Thomson

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Background: Hereditary angioedema (HAE) or C1 esterase deficiency is a relatively rare entity that has a potential for significant anesthetic complications. Methods: A literature review was performed of published cases of surgery in patients with HAE. Results were limited to English language only and cases were examined for management strategies and successful prevention of acute attacks. Results: The literature revealed the successful use of C1 esterase inhibitors as the most common agent in surgical prophylaxis therapy. Other therapeutic targets described included kallikrein inhibitors and bradykinin B2 receptor antagonists. Conclusions: Therapeutic targets that exist for the management of acute attacks in HAE have been successfully employed in the setting of surgery. The data is currently limited and could not be used as a firm evidence base, but the limited outcomes seen are positive and reassuring for the prospective anesthetic management of this potentially fatal condition.

Keywords: anesthesia, C1 esterase deficiency, hereditary angioedema, surgical prophylaxis

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Authors: Y. Bhatt, N. Ghosh, N. Tiwari

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Acreage response function are modeled taking account of expected harvest prices, weather related variables and other non-price variables allowing for partial adjustment possibility. At the outset, based on the literature on price expectation formation, we explored suitable formulations for estimating the farmer’s expected prices. Assuming that farmers form expectations rationally, the prices of food and biofuel crops are modeled using time-series methods for possible ARCH/GARCH effects to account for volatility. The prices projected on the basis of the models are then inserted to proxy for the expected prices in the acreage response functions. Food crop acreages in different growing states are found sensitive to their prices relative to those of one or more of the biofuel crops considered. The required percentage improvement in food crop yields is worked to offset the acreage loss.

Keywords: acreage response function, biofuel, food security, sustainable development

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Authors: Agnieszka Stempniewicz, Piotr Ceranowicz, Wojciech Macyk, Jakub Cieszkowski, Beata Kuśnierz-Cabała, Katarzyna Gałązka, Zygmunt Warzecha

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Objectives: There are numerous strategies for the prevention or treatment of oral mucositis. However, their effectiveness is limited and does not correspond to expectations. Recent studies have shown that obestatin exhibits a protective effect and accelerates the healing of gastrointestinal mucosa. The aim of the present study was to examine the influence of obestatin administration on oral ulcers in rats. Methods: lingual ulcers were induced by the use of acetic acid. Rats were treated twice a day intraperitoneally with saline or obestatin(4, 8, or 16 nmol/kg/dose) for five days. The study determined: lingual mucosa morphology, cell proliferation, mucosal blood flow, and mucosal pro-inflammatory interleukin-1β level(IL-1β). Results: In animals without induction of oral ulcers, treatment with obestatin was without any effect. Obestatin administration in rats with lingual ulcers increased the healing rate of these ulcers. Obestatin given at the dose of 8 or 16 nmol/kg/dose caused the strongest and similar therapeutic effect. This result was associated with a significant increase in blood flow and cell proliferation in gingival mucosa, as well as a significant decrease in IL-1β level. Conclusions: Obestatin accelerates the healing of lingual ulcers in rats. This therapeutic effect is well-correlated with an increase in blood flow and cell proliferation in oral mucosa, as well as a decrease in pro-inflammatory IL-1β levels. Obestatin is a potentially useful candidate for the prevention and treatment of oral mucositis. Acknowledgment: Agnieszka Stempniewicz acknowledges the support of InterDokMed project no. POWR.03.02.00- 00-I013/16.

Keywords: oral mucositis, ulcers, obestatin, lingual mucosa

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Authors: Tianjiao Chu, Carla Rios Luci, Christy Maksoudian, Ara Sargsian, Bella B. Manshian, Stefaan J. Soenen

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Nanomaterials have gained high interest in their use as potent anticancer agents. Apart from delivering chemotherapeutic agents in order to reduce off-target effects, molecular agents have also been widely explored. The advances in our understanding of cell biology and cell death mechanisms1 has generated a broad library of potential therapeutic targets by siRNA, mRNA, or pDNA complexes. In the present study, we explore the ability of pDNA-polyplexes to induce tumor-specific necroptosis. This results in a cascade of effects, where immunogenic cell death potentiates anti-tumor immune responses and results in an influx of dendritic cells and cytotoxic T cells, rendering the tumor more amenable to immune checkpoint inhibition. This study aims to explore whether the induction of necroptosis in a subpopulation of tumor cells can be used to potentiate immune checkpoint inhibition studies.

Keywords: nanoparticle, MLKL, necroptosis, immunotherapy

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Authors: M. Naderi, N. Iyyer, K. Goel, N. Phan

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A micromechanical analysis of the influence of fiber-matrix interface fracture properties on the transverse tensile response of fiber-reinforced composite is investigated. Augmented finite element method (AFEM) is used to provide high-fidelity damage initiation and propagation along the micromechanical analysis. Effects of fiber volume fraction and fiber shapes are also studies in representative volume elements (RVE) to capture the stochastic behavior of the composite under loading. In addition, defects and voids influence on the composite response are investigated in micromechanical analysis. The results reveal that the response of RVE with constant interface properties overestimates the composite transverse strength. It is also seen that the damage initiation and propagation locations are controlled by the distributions of fracture properties, fibers’ shapes, and defects.

Keywords: cohesive model, fracture, computational mechanics, micromechanics

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Authors: Timur Zhukov, Yuko Yamashita

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Music as a product of hedonic consumption has been researched at least since the early 20th century, but little light has been shed on how language affects its consumption process. At the intersection of music consumption, language impact, and consumer behavior, this research explores the influence of language on music consumption in Japan. Its aim is to clarify how listening to music in different languages affects the listener’s purchase intention and sharing intention by conducting a survey where respondents listen to three versions of the same song in different languages in random order. It uses an existing framework that views the flow of music consumption as a combination of responses (emotional response, sensory response, imaginal response, analytical responses) affecting the experiential response, which then affects the overall affective response, followed by the need to reexperience and lastly the purchase intention. In this research, the sharing intention has been added to the model to better fit the modern consumption model (e.g., AISAS). This research shows how positive and negative emotions and imaginal and analytical responses change depending on the language and what impact it has on consumer behavior. It concludes by proposing how modern music businesses can learn from the language differences and cater to the needs of the audiences who speak different languages.

Keywords: AISAS, consumer behavior, first language, music consumption, second language

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Authors: Nahid H. Hajrah, Jamal S. M. Sabir, Neil Hall

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The jasmonic pathway is ubiquitous in plants and is crucial to plant development. It Is involved in fertility, ripening, and sex determination as well as in response to environmental stresses such as herbivory, pathogen drought or temperature shock. Essentially the jasmonic pathway acts to shut down growth in order to induce defence pathways. These pathways include the production of secondary metabolites which have evolved to defend against herbivores and pathogens but are of increasing interest due to their roll in medicine and biotechnology. Here we describe the transcriptional response of Rhazia stricta (a poisonous shrub widely used in traditional medicine) to jasmonic acid, in order to better characterize the genes involved in secondary metabolite production and its response to stress. We observe coordinated upregulation of flavonoid biosynthesis pathway leading to flavonols, flavones and anthocyanins but no similar coordination of the monoterpene indole alkaloid pathway.

Keywords: medicinal plants, Rhazia stricta, jasmonic acid, transcriptional analysis

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Authors: F. D. Konstandakopoulou, G. A. Papagiannopoulos, N. G. Pnevmatikos, G. D. Hatzigeorgiou

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This paper examines the effects of pile-soil-structure interaction on the dynamic response of offshore platforms under the action of near-fault earthquakes. Two offshore platforms models are investigated, one with completely fixed supports and one with piles which are clamped into deformable layered soil. The soil deformability for the second model is simulated using non-linear springs. These platform models are subjected to near-fault seismic ground motions. The role of fault mechanism on platforms’ response is additionally investigated, while the study also examines the effects of different angles of incidence of seismic records on the maximum response of each platform.

Keywords: hazard analysis, offshore platforms, earthquakes, safety

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Authors: Alisher Agzamov, Hanan Al Harbi

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BACKGROUND: The timely assessment and treatment of ICU Surgical and Medical Oncology patients is important for Oncology surgeons and Medical Oncologists and Intensivists. We hypothesized that the use of Robot Physician’s (RP - 7) ICU management and care in ICU can improve ICU physician rapid response to unstable ICU Oncology patients. METHODS: This is a prospective study using a before-after, cohort-control design to test the effectiveness of RP. We have used RP to make multidisciplinary ICU rounds in the ICU and for Emergency cases. Data concerning several aspects of the RP interaction including the latency of the response, the problem being treated, the intervention that was ordered, and the type of information gathered using the RP were documented. The effect of RP on ICU length of stay and cost was assessed. RESULTS: The use of RP was associated with a reduction in latency of attending physician face-to-face response for routine and urgent pages compared to conventional care (RP: 10.2 +/- 3.3 minutes vs conventional: 220 +/- 80 minutes). The response latencies to Oncology Emergency (8.0 +/- 2.8 vs 150 +/- 55 minutes) and for Respiratory Failure (12 +/- 04 vs 110 +/- 45 minutes) were reduced (P < .001), as was the LOS for patients with AML (5 days) and ARDS (10 day). There was an increase in ICU occupancy by 20 % compared with the prerobot era, and there was an ICU cost savings of KD2.5 million attributable to the use of RP. CONCLUSION: The use of RP enabled rapid face-to-face ICU Intensivist - physician response to unstable ICU Oncology patients and resulted in decreased ICU cost and LOS.

Keywords: robot physician, oncology patients, rp - 7 in icu management, cost and icu occupancy

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Authors: Krishna Mohan Bathula, Fatou Bintou Loucoubar, FNU Kaleemunnisa, Christelle Scharff, Mark Anthony De Castro

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Voice recognition algorithms such as automatic speech recognition and text-to-speech systems with African languages can play an important role in bridging the digital divide of Artificial Intelligence in Africa, contributing to the establishment of a fully inclusive information society. This paper proposes a Deep Learning model that can classify the user responses as inputs for an interactive voice response system. A dataset with Wolof language words ‘yes’ and ‘no’ is collected as audio recordings. A two stage Data Augmentation approach is adopted for enhancing the dataset size required by the deep neural network. Data preprocessing and feature engineering with Mel-Frequency Cepstral Coefficients are implemented. Convolutional Neural Networks (CNNs) have proven to be very powerful in image classification and are promising for audio processing when sounds are transformed into spectra. For performing voice response classification, the recordings are transformed into sound frequency feature spectra and then applied image classification methodology using a deep CNN model. The inference model of this trained and reusable Wolof voice response recognition system can be integrated with many applications associated with both web and mobile platforms.

Keywords: automatic speech recognition, interactive voice response, voice response recognition, wolof word classification

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Authors: Anna Cameron, Chunxia Zhao, Haofei Wang, Yun Liu, Guang Ze Yang

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Since the first publication in 1775, cancer research has built a comprehensive understanding of how cellular components of the tumor niche promote disease development. However, only within the last decade has research begun to establish the impact of non-cellular components of the niche, particularly the extracellular matrix (ECM). The ECM, a three-dimensional scaffold that sustains the tumor microenvironment, plays a crucial role in disease progression. Cancer cells actively deregulate and remodel the ECM to establish a tumor-promoting environment. Recent work has highlighted the need to further our understanding of the complexity of this cancer-ECM relationship. In vitro models use hydrogels to mimic the ECM, as hydrogel matrices offer biological compatibility and stability needed for long term cell culture. However, natural hydrogels are being used in these models verbatim, without tuning their biophysical characteristics to achieve pathophysiological relevance, thus limiting their broad use within cancer research. The biophysical attributes of these gels dictate cancer cell proliferation, invasion, metastasis, and therapeutic response. Evaluating the three most widely used natural hydrogels, Matrigel, collagen, and agarose gel, the permeability, stiffness, and pore-size of each gel were measured and compared to the in vivo environment. The pore size of all three gels fell between 0.5-6 µm, which coincides with the 0.1-5 µm in vivo pore size found in the literature. However, the stiffness for hydrogels able to support cell culture ranged between 0.05 and 0.3 kPa, which falls outside the range of 0.3-20,000 kPa reported in the literature for an in vivo ECM. Permeability was ~100x greater than in vivo measurements, due in large part to the lack of cellular components which impede permeation. Though, these measurements prove important when assessing therapeutic particle delivery, as the ECM permeability decreased with increasing particle size, with 100 nm particles exhibiting a fifth of the permeability of 10 nm particles. This work explores ways of adjusting the biophysical characteristics of hydrogels by changing protein concentration and the trade-off, which occurs due to the interdependence of these factors. The global aim of this work is to produce a more pathophysiologically relevant model for each tumor type.

Keywords: cancer, extracellular matrix, hydrogel, microfluidic

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Authors: N. Hoosain, S. Nene, B. Pearce, C. Jacobs, M. Du Plessis, M. Benjeddou

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Organic Cation Transporters play a vital role in the absorption, tissue distribution and elimination of various substrates. Numerous studies have suggested that variations in non-synonymous single nucleotide polymorphisms (SNPs) of SLC22A2 could influence an individual’s response to various treatments, including clinically important drugs. This study is the first to determine the baseline frequency distribution for twenty SNPs of SLC22A2in the Zulu population. DNA was collected from 101 unrelated “healthy” Zulu participants. Genotypes of all samples were determined using a multiplex PCR and SNaPshot assay followed by the generation of the haplotype structure. This is the first time that the baseline frequency distribution of SNPs is reported for the Zulu population. Data from this study could be used in in vitro and in vivo pharmacogenetic and pharmacokinetic studies to evaluate the potential role the studied SNPs play in the therapeutic efficacy of clinically important drugs.

Keywords: SLC22A2 gene, SNaPshot assay, PCR, Zulu population

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Authors: Razi Khalafi

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Brain is the information processing center of the human body. Stimuli in form of information are transferred to the brain and then brain makes the decision on how to respond to them. In this research we propose a new partial differential equation which analyses the EEG signals and make a relationship between the incoming stimuli and the brain response to them. In order to test the proposed model, a set of external stimuli applied to the model and the model’s outputs were checked versus the real EEG data. The results show that this model can model the EEG signal well. The proposed model is useful not only for modeling of the EEG signal in case external stimuli but it can be used for the modeling of brain response in case of internal stimuli.

Keywords: Brain, stimuli, partial differential equation, response, eeg signal

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Authors: Wissam Aljundi, Loay Daas, Yaser Abu Dail, Barbara Käsmann-Kellner, Berthold Seitz, Alaa Din Abdin

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Purpose: To investigate the effectiveness of nonsteroidal anti-inflammatory eye drops (NSAIDs) combined with oral acetazolamide for postoperative macular edema (PME) after uncomplicated phacoemulsification (PE) and to identify predictors of non-response. Methods: We analyzed data of uncomplicated PE and identified eyes with PME. First-line therapy included topical NSAIDs combined with oral acetazolamide. In case of non-response, triamcinolone was administered subtenonally. Outcome measures included best-corrected visual acuity (BCVA) and central macular thickness (CMT). Results: 94 eyes out of 9750 uncomplicated PE developed PME, of which 60 eyes were included. Follow-ups occurred 6.4±1.8, 12.5±3.7, and 18.6±6.0 weeks after diagnosis. BCVA and CMT improved significantly in all follow-ups. 40 eyes showed response to first-line therapy at first follow-up (G1). The remaining 20 eyes showed no response and required subtenon triamcinolone (G2), of which 11 eyes showed complete regression at the second follow-up and 4 eyes at the third follow-up. 5 eyes showed no response and required intravitreal injection. Multivariate linear regression model showed that diabetes mellitus (DM) and increased cumulative dissipated energy (CDE) are predictors of non-response. Conclusion: Topical NSAIDs with acetazolamide resulted in complete regression of PME in 67% of all cases. DM and increased CDE might be considered as predictors of nonresponse to this treatment.

Keywords: postoperative macular edema, intravitreal injection, cumulative energy, irvine gass syndrome, pseudophakie

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Authors: Song Ni, Junxiang Xu

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This paper concerns quasi-periodic perturbations with parameters of 2-dimensional degenerate systems. If the equilibrium point of the unperturbed system is elliptic-type degenerate. Assume that the perturbation is real analytic quasi-periodic with diophantine frequency. Without imposing any assumption on the perturbation, we can use a path of equilibrium points to tackle with the Melnikov non-resonance condition, then by the Leray-Schauder Continuation Theorem and the Kolmogorov-Arnold-Moser technique, it is proved that the equation has a small response solution for many sufficiently small parameters.

Keywords: quasi-periodic systems, KAM-iteration, degenerate equilibrium point, response solution

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Authors: Sukant Mehra, Parth Gupta, Varun Arora, Sarvoday Singh, Amit Kohli

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The study was emphasised on dry sliding wear behavior of AISI 1042 steel. Dry sliding wear tests were performed using pin-on-disk apparatus under normal loads of 5, 7.5 and 10 kgf and at speeds 600, 750 and 900 rpm. Response surface methodology (RSM) was utilized for finding optimal values of process parameter and experiment was based on rotatable, central composite design (CCD). It was found that the wear followed linear pattern with the load and rpm. The obtained optimal process parameters have been predicted and verified by confirmation experiments.

Keywords: central composite design (CCD), optimization, response surface methodology (RSM), wear

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Authors: Jyoti Jaiswal, Satyendra Mourya, Gaurav Malik, Ramesh Chandra

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In the present work, we have fabricated and studied a resistive H₂ gas sensor based on Pd-Pt decorated room temperature sputter grown nanocrystalline porous titanium dioxide (p-TiO₂) thin film on porous silicon (p-Si) substrate for fast H₂ detection. The gas sensing performance of Pd-Pt/p-TiO₂/p-Si sensing electrode towards H₂ gas under low (10-500 ppm) detection limit and operating temperature regime (25-200 °C) was discussed. The sensor is highly sensitive even at room temperature, with response (Ra/Rg) reaching ~102 for 500 ppm H₂ in dry air and its capability of sensing H₂ concentrations as low as ~10 ppm was demonstrated. At elevated temperature of 200 ℃, the response reached more than ~103 for 500 ppm H₂. Overall the fabricated resistive gas sensor exhibited high selectivity, good sensing response, and fast response/recovery time with good stability towards H₂.

Keywords: sputtering, porous silicon (p-Si), TiO₂ thin film, hydrogen gas sensor

Procedia PDF Downloads 258

Authors: Syed Ali Taqi, Muhammad Ismail

Abstract:

A comparative study of estimators of population means in two phase sampling in the presence of non-response when Unknown population means of the auxiliary variable(s) and incomplete information of study variable y as well as of auxiliary variable(s) is made. Three real data sets of University students, hospital and unemployment are used for comparison of all the available techniques in two phase sampling in the presence of non-response with the newly generalized ratio estimators.

Keywords: two-phase sampling, ratio estimator, product estimator, generalized estimators

Procedia PDF Downloads 233

Authors: M. Eskandarighadi, C. R. McGann

Abstract:

It is observed from past experiences of earthquakes that local site conditions can significantly affect the strong ground motion characteristicssuch as frequency content, amplitude, and duration of seismic waves. The most common method for investigating site response is one-dimensional seismic site response analysis. The infinite horizontal length of the model and the homogeneous characteristic of the soil are crucial assumptions of this method. One boundary condition that can be used in the sides is tying the sides horizontally for vertical 1D wave propagation. However, 1D analysis cannot account for the 2D nature of wave propagation in the condition where the soil profile is not fully horizontal or has heterogeneity within layers. Therefore, 2D seismic site response analysis can be used to take all of these limitations into account for a better understanding of local site conditions. Different types of boundary conditions can be appliedin 2D site response models, such as tied boundary condition, massive columns, and free-field boundary condition. The tied boundary condition has been used in 1D analysis, which is useful for 1D wave propagation. Employing two massive columns at the sides is another approach for capturing the 2D nature of wave propagation. Free-field boundary condition can simulate the free-field motion that would exist far from the domain of interest. The goal for free-field boundary condition is to minimize the unwanted reflection from sides. This research focuses on the comparison between these methods with examples and discusses the details and limitations of each of these boundary conditions.

Keywords: boundary condition, free-field, massive columns, opensees, site response analysis, wave propagation

Procedia PDF Downloads 183

Authors: J. R. Wang, J. H. Yang, Y. Chiang, H. C. Chen, C. Shih, S. W. Chen, S. C. Chiang, T. Y. Yu

Abstract:

In this study of ultimate response guideline (URG), Kuosheng BWR/6 nuclear power plant (NPP) TRACE model was established. The reactor depressurization, low pressure water injection, and containment venting are the main actions of URG. This research focuses to evaluate the efficiency of URG under Fukushima-like conditions. Additionally, the sensitivity study of URG was also performed in this research. The analysis results of TRACE present that URG can keep the peak cladding temperature (PCT) below 1088.7 K (the failure criteria) under Fukushima-like conditions. It implied that Kuosheng NPP was at the safe situation.

Keywords: BWR, TRACE, safety analysis, ultimate response guideline (URG)

Procedia PDF Downloads 562

Authors: Fatemeh Torabi, Jamal El-Den, Narumon Sriratanviriyakul

Abstract:

Perpetual changes in the workplace and daily business activities bring a need for imbedding organizational knowledge sharing within the organizations’ culture, routines and processes. Organizations should adapt to the changing in the environment in order to survive. Accordingly, the management should promote a knowledge sharing culture which might result in knowledge accumulation, hence better response to these changing environmental conditions. Researchers in the field of strategy and marketing stressed that employees’, as well as the overall performance of the organization, would improve as a result of implementing a knowledge-oriented culture. The research investigated the significant impact of knowledge sharing on market response and the competitiveness of organizations. A knowledge sharing framework was developed based on current literary frameworks with additional constructs such as employees’ learning commitments, experiences and prior knowledge. Linear regression was used to analyze the relationships among dependent and independent variables. The research’s results indicated strong positive correlation between the dependent and independent variables, especially in organizational market sharing. We anticipate that this correlation would improve organizational knowledge sharing related practices and the associated knowledge entities. The research posits the introduced framework could be a solid ground for further investigations on how some organizational factors would influence the organization’s response to the market as well as on competitiveness. Final results support all hypotheses. Finding of this research show that knowledge sharing intention had the significant and positive effect on market response and competitiveness of organizations.

Keywords: knowledge management, knowledge sharing, market response, organizational competitiveness

Procedia PDF Downloads 206