Search results for: expression

Authors: Daniel Osorio, Janneth Gonzalez, Andres Pinzon

Abstract:

In this work, proteins and metabolic pathways associated with the neuroprotective response mediated by the synthetic neurosteroid tibolone under a palmitate-induced inflammatory model were identified by flux balance analysis (FBA). Three different metabolic scenarios (‘healthy’, ‘inflamed’ and ‘medicated’) were modeled over a gene expression data-driven constructed tissue-specific metabolic reconstruction of mature astrocytes. Astrocyte reconstruction was built, validated and constrained using three open source software packages (‘minval’, ‘g2f’ and ‘exp2flux’) released through the Comprehensive R Archive Network repositories during the development of this work. From our analysis, we predict that tibolone executes their neuroprotective effects through a reduction of neurotoxicity mediated by L-glutamate in astrocytes, inducing the activation several metabolic pathways with neuroprotective actions associated such as taurine metabolism, gluconeogenesis, calcium and the Peroxisome Proliferator Activated Receptor signaling pathways. Also, we found a tibolone associated increase in growth rate probably in concordance with previously reported side effects of steroid compounds in other human cell types.

Keywords: astrocytes, flux balance analysis, genome scale metabolic reconstruction, inflammation, neuroprotection, tibolone

Procedia PDF Downloads 223

Authors: Ahmed M. Hjazi, Bader M. Hjazi

Abstract:

Protein 4.1 is a crucial component of complex interactions between the cytoskeleton and other junctional complex proteins. When the gene encoding this protein is altered, resulting in reduced expression, or when the protein is absent, the red cell undergoes a significant structural change. This research aims to achieve a deeper comprehension of the biochemical effects of red cell protein deficiency. A Tandem Mass Spectrometry Analysis (TMT-MS/MS) of patient cells lacking protein 4.1 compared to three healthy controls was achieved by the Proteomics Institute of the University of Bristol. The SDS-PAGE and Western blotting were utilized on the original patient sample and controls to partially confirm TMT MS/MS data analysis of the protein-4.1-deficient cells. Compared to healthy controls, protein levels in samples lacking protein 4.1 had a significantly higher concentration of proteins that probably originated from reticulocytes. This could occur if the patient has an elevated reticulocyte count. The increase in chaperone and reticulocyte-associated proteins was most notable in this study. This may result from elevated quantities of reticulocytes in patients with hereditary elliptocytosis.

Keywords: hereditary elliptocytosis, protein 4.1, red cells, tandem mass spectrometry data.

Procedia PDF Downloads 79

Authors: Billel Kenidra, Mohamed Benmohammed

Abstract:

Data mining technique used in the field of clustering is a subject of active research and assists in biological pattern recognition and extraction of new knowledge from raw data. Clustering means the act of partitioning an unlabeled dataset into groups of similar objects. Each group, called a cluster, consists of objects that are similar between themselves and dissimilar to objects of other groups. Several clustering methods are based on partitional clustering. This category attempts to directly decompose the dataset into a set of disjoint clusters leading to an integer number of clusters that optimizes a given criterion function. The criterion function may emphasize a local or a global structure of the data, and its optimization is an iterative relocation procedure. The K-Means algorithm is one of the most widely used partitional clustering techniques. Since K-Means is extremely sensitive to the initial choice of centers and a poor choice of centers may lead to a local optimum that is quite inferior to the global optimum, we propose a strategy to initiate K-Means centers. The improved K-Means algorithm is compared with the original K-Means, and the results prove how the efficiency has been significantly improved.

Keywords: microarray data mining, biological pattern recognition, partitional clustering, k-means algorithm, centroid initialization

Procedia PDF Downloads 190

Authors: Libo Jiang, Huan Li, Rongling Wu

Abstract:

Ordinary differentiation equations (ODE) have proven to be powerful for reconstructing precise and informative gene regulatory networks (GRNs) from dynamic gene expression data. However, joint modeling and analysis of all genes, essential for the systematical characterization of genetic interactions, are challenging due to high dimensionality and a complex pattern of genetic regulation including activation, repression, and antitermination. Here, we address these challenges by unifying variable selection and game theory through ODE. Each gene within a GRN is co-expressed with its partner genes in a way like a game of multiple players, each of which tends to choose an optimal strategy to maximize its “fitness” across the whole network. Based on this unifying theory, we designed and conducted a real experiment to infer salt tolerance-related GRNs for Euphrates poplar, a hero tree that can grow in the saline desert. The pattern and magnitude of interactions between several hub genes within these GRNs were found to determine the capacity of Euphrates poplar to resist to saline stress.

Keywords: gene regulatory network, ordinary differential equation, game theory, LASSO, saline resistance

Procedia PDF Downloads 639

Authors: Gaby Fahmy

Abstract:

The last decades have seen a rise in metabolic disorders like diabetes, obesity, and fatty liver disease around the world. Environmental factors, especially nutrition, have contributed to this increase. Additionally, pre-conceptional parental nutritional choices have been shown to result in epigenetic modifications affecting gene expression during the developmental process in-utero. These epigenetic modifications have also been seen to extend to the following offspring in a trans-generational effect. This further highlights the significance and relevance of epigenetics and epigenetic tags, which were previously thought to be stripped in newly formed embryos. Suitable prenatal nutrition may partially counteract adverse outcomes caused by exposures to environmental contaminants, ultimately resulting in improved metabolic profiles like body weight and glucose homeostasis. This was seen in patients who were given dietary interventions like restrictive caloric intake, intermittent fasting, and time-restricted feeding. Changes in nutrition are pivotal in the regulation of epigenetic modifications that are transgenerational. For example, dietary choices such as fatty foods vs. vegetables and nuts in fathers were shown to significantly affect sperm motility and volume. This was pivotal in understanding the importance of paternal inheritance. Further research in the field is needed as it remains unclear how many generations are affected by these changes.

Keywords: epigenetics, transgenerational, diet, fasting

Procedia PDF Downloads 96

Authors: Ravinder Singh, C Rajesh, Saroj Badhan, Shailendra Mishra, Ranjit Singh Kataria

Abstract:

Heat shock protein 60 and 70 are crucial chaperones that guide appropriate folding of denatured proteins under heat stress conditions. HSP60 and HSP70 provide assistance in correct folding of a multitude of denatured proteins. The heat shock factors are the family of some transcription factors which controls the regulation of gene expression of proteins involved in folding of damaged or improper folded proteins during stress conditions. Under normal condition heat shock proteins bind with HSF-1 and act as its repressor as well as aids in maintaining the HSF-1’s nonactive and monomeric confirmation. The experimental protein structure for all these proteins in Bubalus bubalis is not known till date. Therefore computational approach was explored to identify three-dimensional structure analysis of all these proteins. In this study, an extensive in silico analysis has been performed including sequence comparison among species to comparative modeling of Bubalus bubalis HSP60, HSP70 and HSF-1 protein. The stereochemical properties of proteins were assessed by utilizing several scrutiny bioinformatics tools to ensure model accuracy. Further docking approach was used to study interactions between Heat shock proteins and HSF-1.

Keywords: Bubalus bubalis, comparative modelling, docking, heat shock protein

Procedia PDF Downloads 322

Authors: Khries Sawsan

Abstract:

the phenomenon of urbanization is considered as one of the most important tourism resources that differ from one country to another and from one region to another in the same country. Our concern in tourism accommodation is explained by the fact that their location is directly related to the movement to tourist sites .Besides, these constructions comport security considered as the most important motivation for tourists in their choice of any destination. Hotels are the most representative expression of tourism. This is due to their physical prominence in the landscape and being the sole urban component totally unique to tourism. This study sheds light on the impact of tourism development on the spatial pattern in Jordan. It describes the linkages between existing tourism development policies and the spatial development patterns that have occurred as a result throughout Jordan, particularly looking at the impact that tourism has had on the physical environment of major tourism destinations. It puts an illustrative plan of the impact of the augmentation of tourism accommodations in Jordan in the past 40 years ago. The findings of this study help us to understand better the operation of Jordan’ dynamic changes in the location An intensive analysis is then applied on a representative case study in three regions: Amman, Petra and Aqaba. The study proceeds from an historical perspective to, show the evolution of the current development patterns an increase of tourism’s impact on spatial, in the presence of factors as political and economic stability, is expected.

Keywords: spatial patterns, urbanisation, spatial transformations, tourism planning, Jordan

Procedia PDF Downloads 548

Authors: Prativa Das, Lay Poh Tan

Abstract:

Three-dimensional microenvironment is a need to study the event cascades of liver fibrosis in vitro. Electrospun nanofibers modified with essential extracellular matrix proteins can closely mimic the random fibrous structure of native liver extracellular matrix (ECM). In this study, we fabricate a series of 3D electrospun scaffolds by wet electrospinning process modified with different ratios of collagen-I to fibronectin to achieve optimized distribution of these two ECM proteins on the fiber surface. A ratio of 3:1 of collagen-I to fibronectin was found to be optimum for surface modification of electrospun poly(lactic-co-glycolic acid) (PLGA) fibers by chemisorption process. In 3:1 collagen-I to fibronectin modified scaffolds the total protein content increased by ~2 fold compared to collagen-I modified and ~1.5 fold compared to 1:1/9:1 collagen-I to fibronectin modified scaffolds. We have cultured LX-2 cells on this scaffold over 14 days and found that LX-2 cells acquired more quiescent phenotype throughout the culture period and shown significantly lower expression of alpha smooth muscle actin and collagen-I. Thus, this system can be used as a model to study liver fibrosis by using different fibrogenic mediators in vitro.

Keywords: electrospinning, collagen-I and fibronectin, surface modification of fiber, LX-2 cells, liver fibrosis

Procedia PDF Downloads 126

Authors: Sebastian Leal-Arenas

Abstract:

English uses in-situ Nuclear Stress (NS) to express the meanings of theticity and focus. The NS is phonetically represented by an increase in duration, intensity, and pitch range. On the other hand, Spanish conveys the same meanings by aligning the constituent that carries the NS to the end of the sentence via word-order movement. However, little is known about heritage speakers’ production of theticity and focus in English or Spanish. The present study investigates heritage speakers’ production of thetic and subject focus statements. Participants (n = 11) were heritage speakers of Spanish with varying proficiency enrolled in a writing course at a university in the United States. In the production task, participants observed contextualized images and uttered a sentence to answer a provided question. Duration, intensity, and F0 peak were the correlates to stress considered in this investigation. Results indicated that participants tended to present an intonation closer to what is expected in English monolinguals in subject-focus statements than in thetic sentences. However, participants with lower Spanish proficiency used in-situ NS placement in thetic statements more often than those with higher proficiency. Results are discussed in terms of the production patterns observed in heritage speakers with emphasis on the role of language dominance.

Keywords: focus, heritage speakers, prosody, theticity

Procedia PDF Downloads 71

Authors: Forhana Rahman Noor, Shafia Jannat Khanam

Abstract:

The image of old age in Bangladesh is associated with graying of hair, wrinkling of skin, with poor physical health, and decreased ability to work. The common expression “bura hoechi”, to be aged, means to be limited in terms of performing economically productive activities, known as ‘work’. For ‘old-old’ age, there is a saying, “uthan akhon onek dure”, which literally means “even the courtyard is like a very distant place (for an old person).” Traditionally, Bengali society had a structure caring the life of older people. It was common in the joint families of Bangladeshi culture. The situation has been changing. Complexities of the societies with growing rapid urbanization are influencing the traditional respects and caring structure of the elderly persons and facing social challenges. Bangladesh is projected to have 10 percent of its population of age 60 years and above in the year 2025. The ageing process is expected to accelerate in the next century, mainly because the large cohorts born in 1950s and 1960s respectively will be joining the ranks of 60 years and over during this period. The decline in mortality, particularly at young ages, also means that a higher proportion of the large cohorts will survive to old age. The country does not have enough policy or strategy to face this upcoming challenge for the aged persons which needs immediate attention.

Keywords: ageing, gender, dimension, elderly population, Bangladesh

Procedia PDF Downloads 237

Authors: Chao Wu

Abstract:

Thioredoxin reductase 2 is a mitochondrial enzyme that belongs to the cellular defense against oxidative stress. We deleted mitochondrial Txnrd2 in a KrasG12D-driven pancreatic tumor model. Despite an initial increase in precursor lesions, tumor incidence decreased significantly. We isolated cancer cell lines from these genetically engineered mice and observed an impaired proliferation and colony formation. Reactive Oxygen Species, as determined by DCF fluorescence, were increased. We detected a higher mitochondrial copy number in Txnrd2-deficient cells (KTP). However, measurement of mitochondrial bioenergetics showed no impairment of mitochondrial function and comparable O₂-consumption and extracellular acidification rates. In addition, the mitochondrial complex composition was affected in Txnrd2 deleted cell lines. To gain better insight into the role of Txnrd2, we deleted Txnrd2 in clones from parental KrasG12D cell lines using Crispr/Cas9 technology. The deletion was confirmed by western blot and activity assay. Interestingly, and in line with previous RNA expression analysis, we saw changes in EMT markers in Txnrd2 deleted cell lines and control cell lines. This might help us explain the reduced tumor incidence in KrasG12D; Txnrd2∆panc mice.

Keywords: PDAC, TXNRD2, epithelial-to-mesenchymal-transition, ROS

Procedia PDF Downloads 122

Authors: Ali Oztuna, Meral Sarper, Deniz Torun, Fatma Bayrakdar, Selcuk Kilic, Mehmet Baysallar

Abstract:

Bacillus anthracis is one of the biological agents most likely to be used in case of bioterrorist attack as well as being the cause of anthrax. The bacterium's major virulence factors are the anthrax toxins and an antiphagocytic polyglutamic capsule. TEM8 (ANTXR1) and CMG2 (ANTXR2) are ubiquitously expressed type I transmembrane proteins, and ANTXR2 is the major receptor for anthrax toxins. MicroRNAs are 21-24 bp small noncoding RNAs that regulate gene expression by base pairing with the 3' UTR (untranslated regions) of their target mRNAs resulting in mRNA degradation and/or translational repression. MicroRNAs contribute to regulation of most biological processes and influence numerous pathological states like infectious disease. In this study, post-exposure (toxins) protective effect of the hsa-miR-124-3p against Bacillus anthracis was examined. In this context, i) THP-1 and U937 cells were differentiated to MΦ macrophage, ii) miRNA transfection efficiencies were evaluated by flow cytometry and qPCR, iii) protection against Bacillus anthracis toxins were investigated by XTT, cAMP ELISA and MEK2 cleavage assays. Acknowledgements: This work was supported by the Scientific and Technological Research Council of Turkey (TUBITAK) under Grant SBAG-218S467.

Keywords: ANTXR2, hsa-miR-124-3p, MΦ macrophage, THP-1, U937

Procedia PDF Downloads 153

Authors: Hsin-Yang Wang, K. M. A. Salam, Ying-Jia Lin, Daniel Tan, Tzu-Hsuan Chou, Hung-Yu Kao

Abstract:

Detecting user intent from natural language expression has a wide variety of use cases in different natural language processing applications. Recently few-shot training has a spike of usage on commercial domains. Due to the lack of significant sample features, the downstream task performance has been limited or leads to an unstable result across different domains. As a state-of-the-art method, the pre-trained BERT model gathering the sentence-level information from a large text corpus shows improvement on several NLP benchmarks. In this research, we are proposing a method to change multi-class classification tasks into binary classification tasks, then use the confidence score to rank the results. As a language model, BERT performs well on sequence data. In our experiment, we change the objective from predicting labels into finding the relations between words in sequence data. Our proposed method achieved 71.0% accuracy in the internal intent detection dataset and 63.9% accuracy in the HuffPost dataset. Acknowledgment: This work was supported by NCKU-B109-K003, which is the collaboration between National Cheng Kung University, Taiwan, and SoftBank Corp., Tokyo.

Keywords: OSML, BERT, text classification, one shot

Procedia PDF Downloads 101

Authors: Narges Nemati, Mohammadreza Fallahpour, Hossein Bozorgian

Abstract:

Reading is one of the receptive skills which has an important role in improving other skills like writing and speaking. Furthermore, language learners can acquire plenty of vocabularies and become more acquainted with written expression through reading. Also, negative attitudes toward reading can cause negligible reading comprehension, which could prompt poor performance in the English language. Considering the fact that reading instruction was discussed as a low priority skill in the field of EFL teacher education, this study attempted to investigate EFL teachers’ attitudes toward reading instruction. Therefore, to serve the purpose of this study, a mixed-method approach was utilized by inviting 100 Iranian EFL teachers who taught at English language institutes of Iran to fill out a validated questionnaire on teachers’ attitude toward reading. Subsequently, 10 participants were randomly selected for further observations and interview sessions to evaluate the differences between their stated attitude and their actual practices. The findings from analyzing questionnaires, observations, and interviews revealed that EFL teachers’ stated attitude toward reading instruction was positive; whereas, due to some reasons like lack of time, scarcity of interesting passages, and lack of interest in reading long passages, teachers did not show positive actual attitude toward teaching reading skill.

Keywords: English as foreign language classroom, English language, reading skill, teachers' attitude

Procedia PDF Downloads 154

Authors: Lavinia Ruta, Ileana Farcasanu

Abstract:

The yeast surface display (YSD) technique enables the expression of proteins on yeast cell surfaces, facilitating the identification and isolation of proteins with targeted binding properties, such as nanobodies. Nanobodies, derived from camelid species, are single-domain antibody fragments renowned for their high affinity and specificity towards target proteins, making them valuable in research and potentially in therapeutics. Their advantages include a compact size (~15 kDa), robust stability, and the ability to target challenging epitopes. The project endeavors to establish and validate a platform for producing Green Fluorescent Protein (GFP) and mCherry nanobodies using the yeast surface display method. mCherry, a prevalent red fluorescent protein sourced from coral species, is commonly utilized as a genetic marker in biological studies due to its vibrant red fluorescence. The GFP-nanobody, a single variable domain of heavy-chain antibodies (VHH), exhibits specific binding to GFP, offering a potent means for isolating and engineering fluorescent protein fusions across various biological research domains. Both GFP and mCherry nanobodies find specific utility in cellular imaging and protein analysis applications.

Keywords: YSD, nanobodies, GFP, Saccharomyces cerevisiae

Procedia PDF Downloads 61

Authors: Loo Fung Ying, Loo Fung Chiat

Abstract:

The formation of a musical identity that shapes the nation in this multiracial country reveals many complexities, conundrums, and contingencies. Creativity and identity formation at the level of an individual or a collective group further diversified musical expression, representation, and style, which has led to an absence of regularities. In addition, ‘contemporizing accretion,’ borrowing a term used by Schnelle in theology (2009), further complicates musical identity, authenticity, conception, and realization. Thus, in this paper, we attempt to define the issues surrounding the teaching and learning of the multiracial Malaysian national music identity. We also discuss unnecessary power hierarchies, interracial conflicts, and sentiments in the construct of a multiracial national music identity by referring to genetic origins, the evolution of music, and the neglected issues of representation and reception at a global level from a diachronic perspective. Lastly, by synthesizing Ladson-Billings, Gay, Kruger, and West-Burns’s culturally relevant/responsive pedagogical theories, we discuss possible analytic tools for consideration that are more multiculturally relevant and responsive for the teaching, learning, and construction of a multiracial Malaysian national music identity.

Keywords: Malaysia, music, multiracial, national music identity, culturally relevant/responsive pedagogy

Procedia PDF Downloads 201

Authors: Olutola Funmilayo Adekeye

Abstract:

Tradition African practice of architecture can be said to be deeply rooted in Green Architecture in concept, design and execution. A study into the ancient building techniques in Ilorin Emirate depicts prominent (eco-centric approach of) Green Architecture principles. In the Pre-colonial era before the introduction of modern architecture and Western building materials, the Nigeria traditional communities built their houses to meet their cultural, religious and social needs using mainly indigenous building materials such as mud (Amo), cowdung (Boto), straws (koriko), palm fronts (Imo-Ope) to mention a few. This research attempts to identify the various techniques of applying the traditional African principles of Green Architecture to Ilorin traditional buildings. It will examine and assess some case studies to understand the extent to which Green architecture principles have been applied to traditional building designs that are still preserved today in Ilorin, Nigeria. Furthermore, this study intends to answer many questions, which can be summarized into two basic questions which are: (1) What aspects of what today are recognized as important green architecture principles have been applied to Ilorin traditional buildings? (2) To what extent have the principles of green architecture applied to Ilorin traditional buildings been ways of demonstrating a cultural attachment to the earth as an expression of the African sense of human being as one with nature?

Keywords: green architecture, Ilorin, traditional buildings, design principles, ecocentric, application

Procedia PDF Downloads 549

Authors: Zaia Derrar Kaddour

Abstract:

The study of a beam throughout an optical path is generally achieved by means of diffraction integral. Unfortunately, in some problems, this tool turns out to be not very friendly and hard to implement. Instead, the beam expansion method for computing field profiles appears to be an interesting alternative. The beam expansion method consists of expanding the field pattern as a series expansion in a set of orthogonal functions. Propagating each individual component through a circuit and adding up the derived elements leads easily to the result. The problem is then reduced to finding how the expansion coefficients change in a circuit. The beam expansion method requires a systematic study of each type of optical element that can be met in the considered optical path. In this work, we analyze the following fundamental elements: first order optical systems, hard apertures and waveguides. We show that the former element type is completely defined thanks to the Gouy phase shift expression we provide and the latters require a suitable mode conversion. For endorsing the usefulness and relevance of the beam expansion approach, we show here some of its applications such as the treatment of the thermal lens effect and the study of unstable resonators.

Keywords: gouy phase shift, modes, optical resonators, unstable resonators

Procedia PDF Downloads 62

Authors: Zoe Lynch, Kirsty Zieschank

Abstract:

There are several factors that compromise the utility and wide-spread use of existing emotional and behavioural distress screening instruments. Some of these factors include lengthy administration times, high costs, feasibility issues, and a lack of self-report options for children under 12 years of age. This animation-based resource was developed to overcome as many of these factors as possible. Developed for educators and medical and mental health professionals, this resource offers children a self-guided mechanism for reporting any current emotional and behavioural distress. An avatar assistant, selected by the child, accompanies them through each stage of the screening process, offering further instruction if prompted. Children enter their age and gender before viewing comparative animations conveying common childhood emotional and behavioural difficulties. The child then selects the most relatable animations, along with the frequency with which they experience the depicted emotions. From a perspective of intellectual development, an engaging, animated format means that outcomes will not be constrained by children’s reading, writing, cognitive, or verbal expression abilities. Having been user-tested with children aged 6 to 12, this resource shows promising results as a self-guided screening instrument.

Keywords: animation-based screening instrument, mental health, primary-aged children, self-guided

Procedia PDF Downloads 158

Authors: Rachel-Kate Bowdler

Abstract:

Wartime efforts, news, and heroic stories are important to the public in understanding the political climate, yet hard to digest. However, graphic novels are able to portray intense sociopolitical themes and reinvent the account for the public. Modern comics centered around war introduces the historical context to new audiences, thus keeping history relevant and remembered. This is a trend in graphic novels that is popular for expressing wartime and political stories. Graphic novels make historical accounts and stories easier to understand and more enjoyable to read through creative expression and stylistic choices like color, design, and personified depictions of characters. This results in the need to analyze intense wartime themes in terms of artistic style and elements contributing to the portrayal of the story. Whether directly or indirectly, comics became an outlet for discussing and portraying wars, especially following World War II. It may also be relevant that comics are influential in attitudes towards war efforts. in conducting in analysis on comic books relating to war time stories and a literature review, this paper will seek to analyze the role that comics play in the dissemination of information and feelings surrounding war efforts and attitudes.

Keywords: artistic style, comics, historical, war, art and culture, journalism and media

Procedia PDF Downloads 111

Authors: Amandeep Thakur, Yi-Hsuan Chu, Chun-Hsu Pan, Kunal Nepali

Abstract:

The transfer of ADP-ribose residues onto target substrates from nicotinamide adenine dinucleotide (NAD) (PARylation) is catalyzed by Poly (ADP-ribose) polymerases (PARPs). Amongst the PARP family members, the DNA damage response in cancer is majorly regulated by PARP1 and PARP2. The blockade of DNA repair by PARP inhibitors leads to the progression of DNA single-strand breaks (induced by some triggering factors) to double-strand breaks. Notably, PARP inhibitors are remarkably effective in cancers with defective homologous recombination repair (HRR). In particular, cancer cells with BRCA mutations are responsive to therapy with PARP inhibitors. The aforementioned requirement for PARP inhibitors to be effective confers a narrow activity spectrum to PARP inhibitors, which hinders their clinical applicability. Thus, the quest to expand the application horizons of PARP inhibitors beyond BRCA mutations is the need of the hour. Literature precedents reveal that HDAC inhibition induces BRCAness in cancer cells and can broaden the therapeutic scope of PARP inhibitors. Driven by such disclosures, dual inhibitors targeting both PARP and HDAC enzymes were designed by our research group to extend the efficacy of PARP inhibitors beyond BRCA-mutated cancers to cancers with induced BRCAness. The design strategy involved the installation of Veliparib, an investigational PARP inhibitor, as a surface recognition part in the HDAC inhibitor pharmacophore model. The chemical architecture of veliparib was deemed appropriate as a starting point for the generation of dual inhibitors by virtue of its size and structural flexibility. A validatory docking study was conducted at the outset to predict the binding mode of the designed dual modulatory chemical architectures. Subsequently, the designed chemical architectures were synthesized via a multistep synthetic route and evaluated for antitumor efficacy. Delightfully, one compound manifested impressive anti-leukemic effects (HL-60 cell lines) mediated via dual inhibition of PARP and class I HDACs. The outcome of the western blot analysis revealed that the compound could downregulate the expression levels of PARP1 and PARP2 and the HDAC isoforms (HDAC1, 2, and 3). Also, the dual PARP-HDAC inhibitor upregulated the protein expression of the acetyl histone H3, confirming its abrogation potential for class I HDACs. In addition, the dual modulator could arrest the cell cycle at the G0/G1 phase and induce autophagy. Further, polymer-based nanoformulation of the dual inhibitor was furnished to afford targeted delivery of the dual inhibitor at the cancer site. Transmission electron microscopy (TEM) results indicate that the nanoparticles were monodispersed and spherical. Moreover, the polymeric nanoformulation exhibited an appropriate particle size. Delightfully, pH-sensitive behavior was manifested by the polymeric nanoformulation that led to selective antitumor effects towards the HL-60 cell lines. In light of the magnificent anti-leukemic profile of the identified dual PARP-HDAC inhibitor, in-vivo studies (pharmacokinetics and pharmacodynamics) are currently being conducted. Notably, the optimistic findings of the aforementioned study have spurred our research group to initiate several medicinal chemistry campaigns to create bifunctional small molecule inhibitors addressing PARP as the primary target.

Keywords: PARP inhibitors, HDAC inhibitors, BRCA mutations, leukemia

Procedia PDF Downloads 23

Authors: Serap Keskin Tunç, Cennet Neslihan Eroğlu, Sevinç Şahin, Selda Seçkin

Abstract:

It has been suggested that various viruses may play a role in the pathogenesis of cancerous oral lesions in the literature. The aim of this study was to investigate the presence of both possible precancerous viral markers (HPV, HHV8, HSV1, HSV2, and EBV), and p53 and Ki-67 in the dental follicles of asymptomatic impacted teeth. A hundred healthy volunteers, older than 18 years old, included in the study. Dental follicles of extracted impacted teeth were excised and fixated in 10% formaldehyde. Histopathological and immunohistochemical examinations using HPV (containing HPV 8 and HPV 11), p16 (containing HPV 16), HHV8, HSV1, HSV2, EBV, p53 and Ki-67 antibodies were carried out. Also, the immunohistochemical results were correlated with the clinicopathological feature by Chi-square test statistically No dysplasia or neoplasm was observed. 62% of the cases were positive for p16, 32% were positive for EBV, 26% were positive for HSV1, immunohistochemically. All cases were immunonegative for HPV, HSV2, and HHV8. There was statistically significant correlation between overexpression of p53 with both EBV and p16 positivity (p<0.05). Direct correlation between higher expression of Ki-67 between EBV immunopositivity was detected (p<0.05). Thus, these viruses may be suggested to show trophism to the dental follicles acting as a reservoir. In conclusion, all dental follicles of extracted impacted teeth should be examined histopathologically in order to detect and prevent possible viral oncogenesis.

Keywords: dental follicles, Ki67, p53, precancerous markers viral markers

Procedia PDF Downloads 290

Authors: Renu Yadav, Sanjeev Kumar

Abstract:

In northern India, chickpea (Cicer arietinum L.) come across with terminal high-temperature stress during reproductive stage which leads to reduced yield. Hence, stable production of chickpea will depend on the development of new methods like ‘priming’ which allow improved adaptation to the drought and heat stress. In the present experiment, 11-day chickpea seedling was primed with mild drought stress and put on recovery stage by irrigating and finally 30-day seedlings were exposed to heat stress 38°C (4 hours), 35°C (8 hours) and 32°C (12 hours). To study the effect of combinatorial stress, heat and drought stress was applied simultaneously. Analyses of various physiological parameters like membrane damage assay, photosynthetic pigments, antioxidative enzyme, total sugars were estimated at all stages. To study the effect of heat stress on the metabolites of the plants, GC-MS and HPLC were performed, while at transcriptional level Real-Time PCR of predicted heat stress-related genes was done. It was concluded that the heat stress significantly affected the chickpea plant at physiological and molecular level in all the five varieties. Results also show less damaging effect in primed plants by increasing the activity of antioxidative enzymes and increased expression of heat shock proteins and heat shock factors.

Keywords: chickpea, combinatorial stress, heat stress, oxidative stress, priming, RT-PCR

Procedia PDF Downloads 161

Authors: Yong Wook Kim

Abstract:

The diversity of students in regular classrooms is increasing due to expand inclusive education and increase multicultural students in South Korea. In this diverse classroom environment, the universal design for learning (UDL) has been proposed as a way to meet both the educational need and social expectation of student achievement. UDL offers a variety of practical teaching methods, one of which is a differentiating instruction. The differentiating instruction has been pointed out resource limitation, organizational resistance, and lacks easy-to-implement framework. However, through the framework provided by the UDL, differentiating instruction is able to be flexible in their implementation. In practice, the UDL and differentiating instruction are complementary, but there is still a lack of research that suggests specific implementation methods that apply both concepts at the same time. This study was conducted to investigate the effects of differentiating instruction strategies according to learner characteristics (readiness, interest, learning profile), components of differentiating instruction (content, process, performance, learning environment), especially UDL principles (representation, behavior and expression, participation) existed in differentiating instruction, and implementation of UDL-based differentiating instruction through the Planning for All Learner (PAL) and UDL Lesson Plan Cycle. It is meaningful that such a series of studies can enhance the possibility of more concrete and realistic UDL-based teaching and learning strategies in the classroom, especially in inclusive settings.

Keywords: universal design for learning, differentiating instruction, UDL lesson plan, PAL

Procedia PDF Downloads 194

Authors: Slim Amami

Abstract:

A model is developed to prevent the risks related to climate conditions in the agricultural sector. It will determine the yearly optimum premium to be paid by a farmer in order to reach his required turnover. The model is mainly based on both climatic stability and 'soft' responses of usually grown species to average climate variations at the same place and inside a safety ball which can be determined from past meteorological data. This allows the use of linear regression expression for dependence of production result in terms of driving meteorological parameters, main ones of which are daily average sunlight, rainfall and temperature. By a simple best parameter fit from the expert table drawn with professionals, optimal representation of yearly production is deduced from records of previous years, and yearly payback is evaluated from minimum yearly produced turnover. Optimal premium is then deduced, and gives the producer a useful bound for negotiating an offer by insurance companies to effectively protect their harvest. The application to wheat production in the French Oise department illustrates the reliability of the present model with as low as 6% difference between predicted and real data. The model can be adapted to almost every agricultural field by changing state parameters and calibrating their associated coefficients.

Keywords: agriculture, database, meteorological factors, production model, optimal price

Procedia PDF Downloads 222

Authors: Abdelbary Prince, Said Moussa, Hyungkyu Kim, Eman Gouda, Jin Han

Abstract:

We compared the dynamic alterations of mitochondrial proteome of control, ischemia-reperfusion (IR) and ischemic preconditioned (IPC) rabbit hearts. Using 2-DE, we identified 29 mitochondrial proteins that were differentially expressed in the IR heart compared with the control and IPC hearts. For two of the spots, the expression patterns were confirmed by Western blotting analysis. These proteins included succinate dehydrogenase complex, Acyl-CoA dehydrogenase, carnitine acetyltransferase, dihydrolipoamide dehydrogenase, Atpase, ATP synthase, dihydrolipoamide succinyltransferase, ubiquinol-cytochrome c reductase, translation elongation factor, acyl-CoA dehydrogenase, actin alpha, succinyl-CoA Ligase, dihydrolipoamide S-succinyltransferase, citrate synthase, acetyl-Coenzyme A dehydrogenase, creatine kinase, isocitrate dehydrogenase, pyruvate dehydrogenase, prohibitin, NADH dehydrogenase (ubiquinone) Fe-S protein, enoyl Coenzyme A hydratase, superoxide dismutase [Mn], and 24-kDa subunit of complex I. Interestingly, most of these proteins are associated with the mitochondrial respiratory chain, antioxidant enzyme system, and energy metabolism. The results provide clues as to the cardioprotective mechanism of ischemic preconditioning at the protein level and may serve as potential biomarkers for detection of ischemia-induced cardiac injury.

Keywords: ischemic preconditioning, mitochondria, proteome, cardioprotection

Procedia PDF Downloads 349

Authors: Maria Vinca Novenia

Abstract:

The number of school-aged children with autism in Indonesia has been increasing each year. Autism is a developmental disorder which can be diagnosed in childhood. One of the symptoms is the lack of communication skills. Music therapy is known as an effective treatment for children with autism. Music elements and structures create a good space for children with autism to express their feelings and communicate their thoughts. School-aged children are expected to be able to communicate non-verbally very well, but children with autism experience the difficulties of communicating non-verbally. The aim of this research is to analyze the significance of music therapy treatment to improve non-verbal communication tools for children with autism. This research informs teachers and parents on how music can be used as a media to communicate with children with autism. The qualitative method is used to analyze this research, while the result is described with the microanalysis technique. The result is measured specifically from the whole experiment, hours of every week, minutes of every session, and second of every moment. The samples taken are four school-aged children with autism in the age range of six to 11 years old. This research is conducted within four months started with observation, interview, literature research, and direct experiment. The result demonstrates that music therapy could be effectively used as a non-verbal communication tool for children with autism, such as changes of body gesture, eye contact, and facial expression.

Keywords: autism, improvisation, microanalysis, music therapy, nonverbal communication, school-aged

Procedia PDF Downloads 222

Authors: Reza Salehi, Peter L. Dold, Yves Comeau

Abstract:

The aim of the present study was to investigate the effect of a total of 6 operating parameters including pH (X1), temperature (X2), stirring speed (X3), chemical oxygen demand (COD) (X4), volatile suspended solids (VSS) (X5) and time (X6) on anaerobic orthophosphate release from enhanced biological phosphorus removal (EBPR) sludge. An 8-run Plackett Burman design was applied and the statistical analysis of the experimental data was performed using Minitab16.2.4 software package. The Analysis of variance (ANOVA) results revealed that temperature, COD, VSS and time had a significant effect with p-values of less than 0.05 whereas pH and stirring speed were identified as non-significant parameters, but influenced orthophosphate release from the EBPR sludge. The mathematic expression obtained by the first-order multiple linear regression model between orthophosphate release from the EBPR sludge (Y) and the operating parameters (X1-X6) was Y=18.59+1.16X1-3.11X2-0.81X3+3.79X4+9.89X5+4.01X6. The model p-value and coefficient of determination (R2) value were 0.026 and of 99.87%, respectively, which indicates the model is significant and the predicted values of orthophosphate release from the EBPR sludge have been excellently correlated with the observed values.

Keywords: anaerobic, operating parameters, orthophosphate release, Plackett-Burman design

Procedia PDF Downloads 279

Authors: Hamidreza Jabal Ameli, Anahita Movahedi

Abstract:

Purpose: In radionuclide therapy, radioactive atoms are coupled to monoclonal antibodies (mAbs) for treating cancer tumor while limiting radiation to healthy tissues. We know that tumoral and normal tissues are not equally sensitive to radiation. In fact, biological effects such as cellular repair processes or the presence of less radiosensitive cells such as hypoxic cells should be taken account. For this reason, in this paper, we want to calculate biological effect dose (BED) inside tumoral area and healthy cells around tumors. Methods: In this study, deposited doses of a radionuclide, gold-198, inside cells lattice and surrounding healthy tissues were calculated with Monte Carlo method. The elemental compositions and density of malignant and healthy tissues were obtained from ICRU Report 44. For reaching to real condition of oxygen effects, the necrosis and hypoxia area inside tumors has been assessed. Results: With regard to linear-quadratic expression which was defined in Monte Carlo, results showed that a large amount of BED is deposited in the well-oxygenated part of the hypoxia area compared to necrosis area. Moreover, there is a significant difference between the curves of absorbed dose with BED and without BED.

Keywords: biological dose, monte carlo, hypoxia, radionuclide therapy

Procedia PDF Downloads 487

Authors: Abir Touati, Syed Jawad Hussain, Farid Touati, Ammar Bouallegue

Abstract:

Although there has been a growing interest in the hybrid free-space optical link and radio frequency FSO/RF communication system, the current literature is limited to results obtained in moderate or cold environment. In this paper, using a soft switching approach, we investigate the effect of weather inhomogeneities on the strength of turbulence hence the channel refractive index under Qatar harsh environment and their influence on the hybrid FSO/RF availability. In this approach, either FSO/RF or simultaneous or none of them can be active. Based on soft switching approach and a finite state Markov Chain (FSMC) process, we model the channel fading for the two links and derive a mathematical expression for the outage probability of the hybrid system. Then, we evaluate the behavior of the hybrid FSO/RF under hazy and harsh weather. Results show that the FSO/RF soft switching renders the system outage probability less than that of each link individually. A soft switching algorithm is being implemented on FPGAs using Raptor code interfaced to the two terminals of a 1Gbps/100 Mbps FSO/RF hybrid system, the first being implemented in the region. Experimental results are compared to the above simulation results.

Keywords: atmospheric turbulence, haze, hybrid FSO/RF, outage probability, refractive index

Procedia PDF Downloads 419