Search results for: somatic sequence mutations

Authors: Samia A. El-Fiky, F. A. Abou-Zaid, Ibrahim M. Farag, Naira M. Efiky

Abstract:

Clomipramine hydrochloride is one of the most used tricyclic antidepressant drug in Egypt. This drug contains in its chemical structure on two benzene rings. Benzene is considered to be toxic and clastogenic agent. So, the present study was designed to assess the genotoxic effect of Clomipramine hydrochloride on somatic and germ cells in mice. Three dose levels 0.195 (Low), 0.26 (Medium), and 0.65 (High) mg/kg.b.wt. were used. Seven groups of male mice were utilized in this work. The first group was employed as a control. In the remaining six groups, each of the above doses was orally administrated for two groups, one of them was treated for 5 days and the other group was given the same dose for 30 days. At the end of experiments, the animals were sacrificed for cytogenetic and sperm examination as well as histopathological investigations by using hematoxylin and eosin stains (H and E stains) and electron microscope. Concerning the sperm studies, these studies were confined to 5 days treatment with different dose levels. Moreover, the ultrastructural investigation by electron microscope was restricted to 30 days treatment with drug doses. The results of the dose dependent effect of Clomipramine showed that the treatment with three different doses induced increases of frequencies of chromosome aberrations in bone marrow and spermatocyte cells as compared to control. In addition, mitotic and meiotic activities of somatic and germ cells were declined. The treatments with medium or high doses were more effective for inducing significant increases of chromosome aberrations and significant decreases of cell divisions than treatment with low dose. The effect of high dose was more pronounced for causing such genetic deleterious in respect to effect of medium dose. Moreover, the results of the time dependent effect of Clomipramine observed that the treatment with different dose levels for 30 days led to significant increases of genetic aberrations than treatment for 5 days. Sperm examinations revealed that the treatment with Clomipramine at different dose levels caused significant increase of sperm shape abnormalities and significant decrease in sperm count as compared to control. The adverse effects on sperm shape and count were more obviousness by using the treatments with medium or high doses than those found in treatment with low dose. The group of mice treated with high dose had the highest rate of sperm shape abnormalities and the lowest proportion of sperm count as compared to mice received medium dose. In histopathological investigation, hematoxylin and eosin stains showed that, the using of low dose of Clomipramine for 5 or 30 days caused a little pathological changes in liver tissue. However, using medium and high doses for 5 or 30 days induced severe damages than that observed in mice treated with low dose. The treatment with high dose for 30 days gave the worst results of pathological changes in hepatic cells. Moreover, ultrastructure examination revealed, the mice treated with low dose of Clomipramine had little differences in liver histological architecture as compared to control group. These differences were confined to cytoplasmic inclusions. Whereas, prominent pathological changes in nuclei as well as dilated of rough Endoplasmic Reticulum (rER) were observed in mice treated with medium or high doses of Clomipramine drug. In conclusion, the present study adds evidence that treatments with medium or high doses of Clomipramine have genotoxic effects on somatic and germ cells of mice, as unwanted side effects. However, the using of low dose (especially for short time, 5 days) can be utilized as a therapeutic dose, where it caused relatively similar proportions of genetic, sperm, and histopathological changes as those found in normal control.

Keywords: clomipramine, mice, chromosome aberrations, sperm abnormalities, histopathology

Procedia PDF Downloads 396

Authors: Keaghan Brown

Abstract:

The prioritization of drug resistance mutations impacting protein folding or protein-drug and protein-DNA interactions within macromolecular systems is critical to the success of treatment regimens. With a continual increase in computational tools to assess these impacts, the need for scalability and reproducibility became an essential component of computational analysis and experimental research. Here it introduce a bioinformatics pipeline that combines several structural analysis tools in a simplified workflow, by optimizing the present computational hardware and software to automatically ease the flow of data transformations. Utilizing preestablished software tools, it was possible to develop a pipeline with a set of pre-defined functions that will automate mutation introduction into the HIV-1 Integrase protein structure, calculate the gain and loss of polar interactions and calculate the change in energy of protein fold. Additionally, an automated molecular dynamics analysis was implemented which reduces the constant need for user input and output management. The resulting pipeline, Automated Mutation Introduction and Analysis (AMIA) is an open source set of scripts designed to introduce and analyse the effects of mutations on the static protein structure as well as the results of the multi-conformational states from molecular dynamic simulations. The workflow allows the user to visualize all outputs in a user friendly manner thereby successfully enabling the prioritization of variant systems for experimental validation.

Keywords: automated workflow, variant prioritization, drug resistance, HIV Integrase

Procedia PDF Downloads 36

Authors: Yudi Zhao, Ziyun Zhou, Yueting Yao, Shuying Dai, Zhiling Yan, Longyu Yang, Chuanyin Li, Li Shi, Yufeng Yao

Abstract:

HPV16 E4 gene plays an important role in viral genome amplification and release. Therefore, a variation of the E4 gene nucleic acid sequence may affect the carcinogenicity of HPV16. In order to understand the relationship between the variation of HPV16 E4 gene and cervical cancer, this study was to amplify and sequence the DNA sequences of E4 genes in 118 HPV16-positive cervical cancer patients and 151 HPV16-positive asymptomatic individuals. After obtaining E4 gene sequences, the phylogenetic trees were constructed by the Neighbor-joining method for gene variation analysis. The results showed that: 1) The distribution of HPV16 variants between the case group and the control group differed greatly (P = 0.015)，and the Asian-American（AA）variant was likely to relate to the occurrence of cervical cancer. 2) DNA sequence analysis showed that there were significant differences in the distribution of 8 variants between the case group and the control group (P < 0.05). And 3) In European (EUR) variant, two variations, C3384T (L18L) and A3449G (P39P), were associated with the initiation and development of cervical cancer. The results suggested that the variation of HPV16 E4 gene may be a contributor affecting the occurrence as well as the development of cervical cancer, and different HPV16 variants may have different carcinogenic capability.

Keywords: cervical cancer, HPV16, E4 gene, variations

Procedia PDF Downloads 141

Authors: Reza Hedayati, Meysam Jahanbakhshi

Abstract:

Fracture Mechanics is used to predict debonding propagation in adhesive joint between aluminum and composite plates. Three types of loadings and two types of glass-epoxy composite sequences: [0/90]2s and [0/45/-45/90]s are considered for the composite plate and their results are compared. It was seen that generally the cases with stacking sequence of [0/45/-45/90]s have much shorter lives than cases with [0/90]2s. It was also seen that in cases with λ=0 the ends of the debonding front propagates forward more than its middle, while in cases with λ=0.5 or λ=1 it is vice versa. Moreover, regardless of value of λ, the difference between the debonding propagations of the ends and the middle of the debonding front is very close in cases λ=0.5 and λ=1. Another main conclusion was the non-dimensionalized debonding front profile is almost independent of sequence type or the applied load value.

Keywords: fatigue, debonding, Paris law, APDL, adhesive

Procedia PDF Downloads 334

Authors: Mike Wei, Nebu Koshy, Koen van Besien, Giorgio Inghirami, Steven M. Horwitz

Abstract:

T-cell prolymphocytic leukemia (T-PLL) is a rare hematologic disease characterized by a T-cell phenotype, rapid progression, and poor prognosis with median survival of less than a year. Alemtuzumab-based chemotherapy has increased the rate of complete remissions but these are often short-lived, and allogeneic transplant is considered the only curative therapy. In recent studies, JAK3 activating mutations have been identified in T-cell cancers, with T-PLL having the highest rate of JAK3 mutations (30 – 42%). As such, T-PLL is a model disease for evaluating the utility of JAK3 inhibitors. We present a case of a 64-year-old man with relapsed-refractory T-PLL. He was initially treated with alemtuzumab and obtained complete response and was consolidated with matched unrelated donor stem cell transplant. His disease stayed in remission for approximately 1.5 years before relapse, which was then treated with a clinical trial of romidepsin-lenalidomide (partial responses then progression at 6 months) and later alemtuzumab. Due to complications of myelosuppression and CMV reactivation, his treatment was interrupted leading to disease progression. The doubling time of lymphocyte count was approximately 20 days and over a span of 60 days the lymphocyte count rose from 8 x 109/L to 68 x 109/L. Exon sequencing showed a JAK3 mutation. The patient consented to and was treated with FDA-approved tofacitinib (initially 5 mg BID, increased to 10 mg BID after 15 days of treatment). An initial decrease in lymphocyte count was followed by progression. In vitro treatment of the patient’s cells showed modest effects of tofacitinib and ruxolitinib as single agents, in the range of doxorubicin, but synergy between the agents. After 40 days of treatment with tofacitinib and with a lymphocyte count of 150 x 109/L, ruxolitinib (5mg BID) was added. Over the 60 days since dual inhibition was started, the lymphocyte count has stabilized. The patient has remained completely asymptomatic during treatment with tofacitinib and ruxolitinib. Neutrophil count has remained normal. Platelet count and hemoglobin have however declined from ~50 x109/L to ~30 x109/L and from 11 g/dL to 8.1 g/dL respectively, since the introduction of ruxolitinib. The stabilization in lymphocyte count confirms the clinical activity of JAK inhibitors in T-PLL as suggested by the presence of JAK3 mutations and by in-vitro assays. It also suggests clinical synergy between ruxolitinib and tofacitinib in this setting. Prospective studies of JAK inhibitors in PLL patients with formal dose-finding studies are needed.

Keywords: tofacitinib, ruxolitinib, T-cell prolymphocytic leukemia, JAK3

Procedia PDF Downloads 289

Authors: Samia A. El-Fiky, Fouad A. Abou-Zaid, Ibrahim M. Farag, Naira M. El-Fiky

Abstract:

Clomipramine hydrochloride is one of the most used tricyclic antidepressant drug in Egypt. This drug contains in its chemical structure on two benzene rings. Benzene is considered to be toxic and clastogenic agent. So, the present study was designed to assess the genotoxic effect of Clomipramine hydrochloride on somatic and germ cells in mice. Three dose levels 0.195 (Low), 0.26 (Medium), and 0.65 (High) mg/kg.b.wt. were used. Seven groups of male mice were utilized in this work. The first group was employed as a control. In the remaining six groups, each of the above doses was orally administrated for two groups, one of them was treated for 5 days and the other group was given the same dose for 30 days. At the end of experiments, the animals were sacrificed for cytogenetic and sperm examination as well as histopathological investigations by using hematoxylin and eosin stains (H and E stains) and electron microscope. Concerning the sperm studies, these studies were confined to 5 days treatment with different dose levels. Moreover, the ultrastructural investigation by electron microscope was restricted to 30 days treatment with drug doses. The results of the dose dependent effect of Clomipramine showed that the treatment with three different doses induced increases of frequencies of chromosome aberrations in bone marrow and spermatocyte cells as compared to control. In addition, mitotic and meiotic activities of somatic and germ cells were declined. The treatments with medium or high doses were more effective for inducing significant increases of chromosome aberrations and significant decreases of cell divisions than treatment with low dose. The effect of high dose was more pronounced for causing such genetic deleterious in respect to effect of medium dose. Moreover, the results of the time dependent effect of Clomipramine observed that the treatment with different dose levels for 30 days led to significant increases of genetic aberrations than treatment for 5 days. Sperm examinations revealed that the treatment with Clomipramine at different dose levels caused significant increase of sperm shape abnormalities and significant decrease in sperm count as compared to control. The adverse effects on sperm shape and count were more obviousness by using the treatments with medium or high doses than those found in treatment with low dose. The group of mice treated with high dose had the highest rate of sperm shape abnormalities and the lowest proportion of sperm count as compared to mice received medium dose. In histopathological investigation, hematoxylin and eosin stains showed that, the using of low dose of Clomipramine for 5 or 30 days caused a little pathological changes in liver tissue. However, using medium and high doses for 5 or 30 days induced severe damages than that observed in mice treated with low dose. The treatment with high dose for 30 days gave the worst results of pathological changes in hepatic cells. Moreover, ultrastructure examination revealed, the mice treated with low dose of Clomipramine had little differences in liver histological architecture as compared to control group. These differences were confined to cytoplasmic inclusions. Whereas, prominent pathological changes in nuclei as well as dilated of rough Endoplasmic Reticulum (rER) were observed in mice treated with medium or high doses of Clomipramine drug. In conclusion, the present study adds evidence that treatments with medium or high doses of Clomipramine have genotoxic effects on somatic and germ cells of mice, as unwanted side effects. However, the using of low dose (especially for short time, 5 days) can be utilized as a therapeutic dose, where it caused relatively similar proportions of genetic, sperm, and histopathological changes as those found in normal control.

Keywords: chromosome aberrations, clomipramine, mice, histopathology, sperm abnormalities

Procedia PDF Downloads 496

Authors: M. I. Tyletc, O. I. Podgornya, T. G. Shaposhnikova, S. V. Shabelnikov, A. G. Mittenberg, M. A. Daugavet

Abstract:

Ascidiacea is the most numerous class of the Tunicata subtype. These chordates' distinctive feature of the anatomical structure is a tunic consisting of cellulose fibrils, protein molecules, and single cells. The mechanisms of the tunic formation are not known in detail; tunic formation could be used as the model system for studying the interaction of cells with the extracellular matrix. Our model species is the ascidian Styela rustica, which is prevalent in benthic communities of the White Sea. As previously shown, the tunic formation involves morula blood cells, which contain the major 48 kDa protein p48. P48 participation in the tunic formation was proved using antibodies against the protein. The nature of the protein and its function remains unknown. The current research aims to determine the amino acid sequence of p48, as well as to clarify its role in the tunic formation. The peptides that make up the p48 amino acid sequence were determined by mass spectrometry. A search for peptides in protein sequence databases identified sequences homologous to p48 in Styela clava, Styela plicata, and Styela canopus. Based on sequence alignment, their level of similarity was determined as 81-87%. The correspondent sequence of ascidian Styela canopus was used for further analysis. The Styela rustica p48 sequence begins with a signal peptide, which could indicate that the protein is secretory. This is consistent with experimentally obtained data: the contents of morula cells secreted in the tunic matrix. The isoelectric point of p48 is 9.77, which is consistent with the experimental results of acid electrophoresis of morula cell proteins. However, the molecular weight of the amino acid sequence of ascidian Styela canopus is 103 kDa, so p48 of Styela rustica is a shorter homolog. The search for conservative functional domains revealed the presence of two Ca-binding EGF-like domains, thrombospondin (TSP1) and tyrosinase domains. The p48 peptides determined by mass spectrometry fall into the region of the sequence corresponding to the last two domains and have amino acid substitutions as compared to Styela canopus homolog. The tyrosinase domain (pfam00264) is known to be part of the phenoloxidase enzyme, which participates in melanization processes and the immune response. The thrombospondin domain (smart00209) interacts with a wide range of proteins, and is involved in several biological processes, including coagulation, cell adhesion, modulation of intercellular and cell-matrix interactions, angiogenesis, wound healing and tissue remodeling. It can be assumed that the tyrosinase domain in p48 plays the role of the phenoloxidase enzyme, and TSP1 provides a link between the extracellular matrix and cell surface receptors, and may also be responsible for the repair of the tunic. The results obtained are consistent with experimental data on p48. The domain organization of protein suggests that p48 is an enzyme involved in the tunic tunning and is an important regulator of the organization of the extracellular matrix.

Keywords: ascidian, p48, thrombospondin, tyrosinase, tunic, tunning

Procedia PDF Downloads 79

Authors: Marilei Amadeu Sabino

Abstract:

Before the advent of Cognitive Linguistics, metaphor was considered a stylistic issue, but now it is viewed as a critical component of everyday language and a fundamental mechanism of human conceptualizations of the world. It means that human beings' conceptual system (the way we think and act) is metaphorical in nature. Another interesting hypothesis in Cognitive Linguistics is that cognition is embodied, that is, our cognition is influenced by our experiences in the physical world: the mind is connected to the body and the body influences the mind. In this sense, it is believed that many conceptual metaphors appear to be potentially universal or near-universal, because people across the world share certain bodily experiences. In these terms, many metaphors may be identical or very similar in several languages. Thus, in this study, we analyzed some somatic (also called body) idioms of Italian and Portuguese languages, in order to investigate the proportion in which their metaphors are the same, similar or different in both languages. It was selected hundreds of Italian idioms in dictionaries and indicated their corresponding idioms in Portuguese. The analysis allowed to conclude that much of the studied expressions are really structurally, semantically and metaphorically identical or similar in both languages. We also contrasted some Portuguese and Italian somatic expressions to their corresponding English idioms to have a multilingual perspective of the issue, and it also led to the conclusion that the most common idioms based on metaphors are probably those that have to do with the human body. Although this is mere speculation and needs more study, the results found incite relevant discussions on issues that matter Foreign and Second Language Teaching and Learning, including the retention of vocabulary. The teaching of the metaphorically different body idioms also plays an important role in language learning and teaching as it will be shown in this paper. Acknowledgments: FAPESP – São Paulo State Research Support Foundation –the financial support offered (proc. n° 2017/02064-7).

Keywords: body idioms, cognitive linguistics, metaphor, vocabulary teaching and learning

Procedia PDF Downloads 301

Authors: Irena Maus, Katharina Gabriella Cibis, Andreas Bremges, Yvonne Stolze, Geizecler Tomazetto, Daniel Wibberg, Helmut König, Alfred Pühler, Andreas Schlüter

Abstract:

Within the agricultural sector, the production of biogas from organic substrates represents an economically attractive technology to generate bioenergy. Complex consortia of microorganisms are responsible for biomass decomposition and biogas production. Recently, species belonging to the phylum Thermotogae were detected in thermophilic biogas-production plants utilizing renewable primary products for biomethanation. To analyze adaptive genome features of representative Thermotogae strains, Defluviitoga tunisiensis L3 was isolated from a rural thermophilic biogas plant (54°C) and completely sequenced on an Illumina MiSeq system. Sequencing and assembly of the D. tunisiensis L3 genome yielded a circular chromosome with a size of 2,053,097 bp and a mean GC content of 31.38%. Functional annotation of the complete genome sequence revealed that the thermophilic strain L3 encodes several genes predicted to facilitate growth of this microorganism on arabinose, galactose, maltose, mannose, fructose, raffinose, ribose, cellobiose, lactose, xylose, xylan, lactate and mannitol. Acetate, hydrogen (H2) and carbon dioxide (CO2) are supposed to be end products of the fermentation process. The latter gene products are metabolites for methanogenic archaea, the key players in the final step of the anaerobic digestion process. To determine the degree of relatedness of dominant biogas community members within selected digester systems to D. tunisiensis L3, metagenome sequences from corresponding communities were mapped on the L3 genome. These fragment recruitments revealed that metagenome reads originating from a thermophilic biogas plant covered 95% of D. tunisiensis L3 genome sequence. In conclusion, availability of the D. tunisiensis L3 genome sequence and insights into its metabolic capabilities provide the basis for biotechnological exploitation of genome features involved in thermophilic fermentation processes utilizing renewable primary products.

Keywords: genome sequence, thermophilic biogas plant, Thermotogae, Defluviitoga tunisiensis

Procedia PDF Downloads 468

Authors: Seyed Davar Siadat, Samira Tarashi, Abolfazl Fateh, Arfa Moshiri

Abstract:

Background: The global health issue of tuberculosis (TB) still affects patients in every country. TB control may not be as effective as it should be, especially when resistant strains are involved. In this regard, mycobacterial MTases play a major role in tuberculosis, but the mechanisms underlying their function have yet to be fully deciphered. Methods: Five resistant isolates of M.tb were accumulated. As a reference strain, M.tb H37Rv (ATCC 27249) was used. For this analysis, seven putative mycobacterial MTase genes (Rv0645c, Rv1694, Rv2966c, Rv3919c, Rv2756c, Rv1988, and Rv3263), as well as Rv1392 as SAM synthase, were selected. Comparing mutations and expression levels of MTases in different strains was accomplished by PCR-sequencing and qRT-PCR. The relative expression levels of these genes were calculated using the 2 -ΔΔCt method. Results: The Rv3919c gene (T to G in codon 341) and Rv1392 gene (G to A in codon 97) were the only mutations found in the INHR strain. In all sensitive and resistant isolates, Rv0645c, Rv3263, Rv2756c, and Rv2966c were overexpressed. However, the expression of Rv1988 and Rv3919c decreased in the sensitive strains, whereas the expression of Rv1694 increased. There was also a decreased expression of Rv1392 in the INHR isolate. Conclusion: The presence of mycobacterial MTases as well as resistance to antibiotics were found to be correlated in M.tb strains. Undoubtedly, there are some MTases that are associated with the virulence process. It is necessary to conduct additional studies to fully explore the impact of mycobacterial MTases within specific strains of M.tb to develop novel diagnostic and treatment strategies.

Keywords: mycobacterium tuberculosis, drug resistance, methyltransferases, s-adenosylmethionine

Procedia PDF Downloads 72

Authors: Shin-Shin Kao, Hsiu-Chunj Pan

Abstract:

Given a graph G. A cycle of G is a sequence of vertices of G such that the first and the last vertices are the same. A hamiltonian cycle of G is a cycle containing all vertices of G. The graph G is k-ordered (resp. k-ordered hamiltonian) if for any sequence of k distinct vertices of G, there exists a cycle (resp. hamiltonian cycle) in G containing these k vertices in the specified order. Obviously, any cycle in a graph is 1-ordered, 2-ordered and 3-ordered. Thus the study of any graph being k-ordered (resp. k-ordered hamiltonian) always starts with k = 4. Most studies about this topic work on graphs with no real applications. To our knowledge, the chordal ring families were the first one utilized as the underlying topology in interconnection networks and shown to be 4-ordered [1]. Furthermore, based on computer experimental results in [1], it was conjectured that some of them are 4-ordered hamiltonian. In this paper, we intend to give some possible directions in proving the conjecture.

Keywords: Hamiltonian cycle, 4-ordered, Chordal rings, 3-regular

Procedia PDF Downloads 407

Authors: Mohammed Althobiti, Patrick Booms, Dorota Fiszer, Philip Hopkins

Abstract:

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle. MH results from anaesthetics induced breakdown of calcium homeostasis. RYR1 and CACN1AS mutations represent the aetiology in ~70% of the MH population. Previous studies indicate that up to 25% of MH patients carry no variants in these genes. Therefore, the aim of this study is to investigate the relationships between MH susceptibility and genes encoding skeletal muscle Ca2+ channels as well as accessory proteins. The JSRP, encoding JP-45, was previously sequenced and novel genetic variants were identified. The variant p.P108L (c.323C > T) was identified in exon 4 and encodes a change from a proline at amino acid 108 to leucine residue. The variant P108L was detected in two patients out of 50 with 4% frequency in the sample population. The alignment of DNA sequences in different species indicates highly conserved proline sequences involved in the substitution of the P108L variant. In this study, the variant P108L co-segregates with the SNP p.V92A (c.275T > C) at the same exon, both variants being inherited in the same two patients only. This indicates that the two variants may represent a haplotype. Therefore, a set of single nucleotide polymorphisms and statistical analysis will be used to investigate the effects of haplotypes on MH susceptibility. Furthermore, investigating the effect of the P108L variant in combination with RYR1 mutations or other genetic variants in other genes as a combination of two or more genetic variants, haplotypes may then provide stronger genetic evidence indicating that JSRP1 is associated with MH susceptibility. In conclusion, these preliminary results lend a potential modifier role of the variant P108L in JSRP1 in MH susceptibility and further investigations are suggested to confirm these results.

Keywords: JSRP1, malignant hyperthermia, RyR1, skeletal muscle

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Authors: Umar Yusuf Batsari

Abstract:

Let E be a uniformly smooth and uniformly convex real Banach space and C be a nonempty, closed and convex subset of E. Let $V= \{S_i : C\to C, ~i=1, 2, 3\cdots N\}$ be a convex set of relatively nonexpansive mappings containing identity. In this paper, an iterative sequence obtained from CQ algorithm was shown to have strongly converge to a point $\hat{x}$ which is a common fixed point of relatively nonexpansive mappings in V and also solve the system of equilibrium problems in E. The result improve some existing results in the literature.

Keywords: relatively nonexpansive mappings, strong convergence, equilibrium problems, uniformly smooth space, uniformly convex space, convex set, kadec klee property

Procedia PDF Downloads 393

Authors: Mayank, Navneet Kaur, Narinder Singh

Abstract:

The V599 mutations in the BRAF protein are extremely oncogenic, responsible for countless of malignant conditions. Along with wild type, V599E, V599D, and V599R are the important mutated variants of the BRAF proteins. The BRAF inhibitory anticancer agents are continuously developing, and sorafenib is a BRAF inhibitor that is under clinical use. The crystal structure of sorafenib bounded to wild type, and V599 is known, showing a similar interaction pattern in both the case. The mutated 599th residue, in both the case, is also found not interacting directly with the co-crystallized sorafenib molecule. However, the IC50 value of sorafenib was found extremely different in both the case, i.e., 22 nmol/L for wild and 38 nmol/L for V599E protein. Molecular docking study and MMGBSA binding energy results also revealed a significant difference in the binding pattern of sorafenib in both the case. Therefore, to explore the role of distinctively situated 599th residue, we have further conducted comprehensive computational studies. The molecular dynamics simulation, residue interaction network (RIN) analysis, and residue correlation study results revealed the importance of the 599th residue on the therapeutic outcome and overall dynamic of the BRAF protein. Therefore, although the position of 599th residue is very much distinctive from the ligand-binding cavity of BRAF, still it has exceptional control over the overall functional outcome of the protein. The insight obtained here may seem extremely important and guide us while designing ideal BRAF inhibitory anticancer molecules.

Keywords: BRAF, oncogenic, sorafenib, computational studies

Procedia PDF Downloads 93

Authors: Perdana Rakhmana Putra, Hansen Wijaya, Sri Budiyani, Muhamad Natsir, Alexis badai Samudra

Abstract:

The Palembang Sub-Basin (PSB) located in southern part of South Sumatera basin (SSB) consist of half-graben complex trending N-S to NW-SE. These geometries are believe as an impact of strike-slip regime developed in Eocene-Oligocene. Generally, most of the wells in this area produced hydrocarbon from late stage of syn-rift sequences called Lower Talang Akar (LTAF) and post-rift sequences called Batu Raja Formation (BRF) and drilled to proved hydrocarbon on structural trap; three-way dip anticline, four-way dip anticline, dissected anticline, and stratigraphy trap; carbonate build-up and stratigraphic pinch out. Only a few wells reached the deeper syn-rift sequences called Lahat Formation (LAF) and Lemat Formation (LEF). The new interpretation of subsurface data was done by the tectonostratigraphy concept and focusing on syn-rift sequence. Base on seismic characteristic on basin centre, it divided into four sequences: pre-rift sequence, rift initiation, maximum rift and late rift. These sequences believed as a new exploration target on PSB mature basin. This paper will demonstrate the paleo depositional setting during Paleogene and exploration play concept of syn-rift sequence in PSB. The main play for this area consists of stratigraphic and structure play, where the stratigraphic play is Eocene-Oligocene sediment consist of LAF sandstone, LEF-Benakat formation, and LAF with pinch-out geometry. The pinch-out, lenses geometry and on-lap features can be seen on the seismic reflector and formed at the time of the syn-rift sequence. The structural play is dominated by a 3 Way Dip play related to reverse fault trap.

Keywords: syn-rift, tectono-stratigraphy, exploration play, basin center play, south sumatera basin

Procedia PDF Downloads 163

Authors: Okike Benjamin, E. J. D. Garba

Abstract:

The protection of sensitive information against unauthorized access or fraudulent changes has been of prime concern throughout the centuries. Modern communication techniques, using computers connected through networks, make all data even more vulnerable to these threats. The researchers in this work propose a new encryption technique to be known as Merged Irregular Transposition Cipher. In this proposed encryption technique, a message to be encrypted will first of all be split into multiple parts depending on the length of the message. After the split, different keywords are chosen to encrypt different parts of the message. After encrypting all parts of the message, the positions of the encrypted message could be swapped to other position thereby making it very difficult to decrypt by any unauthorized user.

Keywords: information security, message splitting, pattern, sequence

Procedia PDF Downloads 257

Authors: Yujie Zhou, Hee-Seong Byun, Sang-In Bak, Eui-Joon Kil, Kyung Joo Min, Vivek Chavan, Won Kyong Cho, Sukchan Lee, Seung-Woo Hong, Tae-Sun Park

Abstract:

Fast neutron irradiation (FNI) can cause mutations on plant genome but, in the most of cases, these irradiated plants have not shown significant characteristics phenotypically. In this study, we utilized RNA-Seq to generate a high-resolution transcriptome map of the tomato (Solanum lycopersicum) genome effected by FNI. To quantify the different transcription levels in tomato irradiated by FNI, tomato seeds were irradiated by using MC-50 cyclotron (KIRAMS, Korea) for 0, 30 and 90 minutes, respectively. To investigate the effects on the pre-soaking condition, experimental groups were divided into dry and soaked seeds, which were soaked for 8 hours before irradiation. There was no noticeable difference in the percentage germination (PG) among dry seeds, while irradiated soaked seeds have about 10 % lower PG compared to the unirradiated control group. Using whole transcriptome sequencing by HiSeq 2000, we analyzed the differential gene expression in response to different time of FNI in dry and soaked seeds. More than 1.4 million base pair reads were mapped onto the tomato reference genome and the expression pattern differences between irradiated and unirradiated seeds were assessed. In 0, 30 and 90 minutes irradiation, 12,135, 28,495 and 28,675 transcripts were generated, respectively. Gene ontology analysis suggested the different enrichment of transcripts involved in response to different FNI. The present study showed that FNI effects on plant gene expression, which can become a new parameters for evaluating the responses against FNI on plants. In addition, the comparative analysis of differentially expressed genes in D and S seeds by FNI will also give us a chance to deep explore novel candidate genes for FNI, which could be a good model system to understand the mechanisms behind the adaption of plant to space biology research.

Keywords: tomato (solanum lycopersicum), fast neutron irradiation, RNA-sequence, transcriptome expression

Procedia PDF Downloads 281

Authors: YingWei Tan, XueFeng Ding

Abstract:

Attention-based voice activity detection models have gained significant attention in recent years due to their fast training speed and ability to capture a wide contextual range. The inclusion of multi-head style and position embedding in the attention architecture are crucial. Having multiple attention heads allows for differential focus on different parts of the sequence, while position embedding provides guidance for modeling dependencies between elements at various positions in the input sequence. In this work, we propose an approach by considering each head as a node, enabling the application of graph neural networks (GNN) to identify correlations among the different nodes. In addition, we adopt an implementation named rotary position embedding (RoPE), which encodes absolute positional information into the input sequence by a rotation matrix, and naturally incorporates explicit relative position information into a self-attention module. We evaluate the effectiveness of our method on a synthetic dataset, and the results demonstrate its superiority over the baseline CRNN in scenarios with low signal-to-noise ratio and noise, while also exhibiting robustness across different noise types. In summary, our proposed framework effectively combines the strengths of CNN and RNN (LSTM), and further enhances detection performance through the integration of graph neural networks and rotary position embedding.

Keywords: voice activity detection, CRNN, graph neural networks, rotary position embedding

Procedia PDF Downloads 31

Authors: Nitish Sharma, G. G. Karady

Abstract:

This paper presents a scheme for the protection of loop system from all type of faults using the direction of fault current. The presence of distributed generation in today’s system increases the complexity of fault detection as the power flow is bidirectional. Hence, protection scheme specific to this purpose needs to be developed. This paper shows a fast protection scheme using communication which can be fiber optic or wireless. In this paper, the possibility of wireless communication for protection is studied to exchange the information between the relays. The negative sequence and positive sequence directional elements are used to determine the direction of fault current. A PSCAD simulation is presented and validated using commercial SEL relays.

Keywords: smart grid protection, pilot protection, power system simulation, wireless communication

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Authors: Mustafa Yorgancılar, Emine Atalay, Necdet Akgün, Ali Topal

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In this study, polymerase chain reaction based Inter-simple sequence repeat (ISSR) from DNA fingerprinting techniques were used to investigate the genetic relationships among barley crossbreed genotypes in Turkey. It is important that selection based on the genetic base in breeding programs via ISSR, in terms of breeding time. 14 ISSR primers generated a total of 97 bands, of which 81 (83.35%) were polymorphic. The highest total resolution power (RP) value was obtained from the F2 (0.53) and M16 (0.51) primers. According to the ISSR result, the genetic similarity index changed between 0.64–095; Lane 3 with Line 6 genotypes were the closest, while Line 36 were the most distant ones. The ISSR markers were found to be promising for assessing genetic diversity in barley crossbreed genotypes.

Keywords: barley, crossbreed, genetic similarity, ISSR

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Authors: Weizhi Zhong, Xiaoyi Lu, Lei Xu

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In order to solve the problem of inaccurate synchronization for distributed multiple-input multiple-output (MIMO) system in multipath environment, a golay pair aided timing synchronization method is proposed in this paper. A new synchronous training sequence based on golay pair is designed. By utilizing the aperiodic auto-correlation complementary property of the new training sequence, the fine timing point is obtained at the receiver. Simulation results show that, compared with the tradition timing synchronization approaches, the proposed algorithm can provide high accuracy in synchronization, especially under multipath condition.

Keywords: distributed MIMO system, golay pair, multipath, synchronization

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Authors: Dalia G. Aseel

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The potato (Solanum tubersum, L.) has become one of the major vegetable crops in Egypt and all over the world. Potato leafroll virus(PLRV) was observed on potato plants collected from different governorates in Egypt. Three cultivars, Spunta, Diamont, and Cara, infected with PLRV were collected; RNA was extracted and subjected to Real-Time PCR using the coat protein gene primers. The results showed that the expression of the coat protein was 39.6-fold, 12.45-fold, and 47.43-fold, respectively, for Spunta, Diamont, and Cara cultivars. Differential Display Polymerase Chain Reaction (DD-PCR) using pathogenesis-related protein 1 (PR-1), β-1,3-glucanases (PR-2), chitinase (PR-3), peroxidase (POD), and polyphenol oxidase (PPO) forward primers for pathogenesis-related proteins (PR). The obtained data revealed different banding patterns depending on the viral type and the region of infection. Regarding PLRV, 58 up-regulated and 19 down-regulated genes were detected. Sequence analysis of the up-and down-regulated genes revealed that infected plants were observed in comparison with the healthy control. Sequence analysis of the up-regulated gene was performed, and the encoding sequence analysis showed that the obtained genes include: induced stolen tip protein. On the other hand, two down-regulated genes were identified: disease resistance RPP-like protein and non-specific lipid-transfer protein. In this study, the expressions of PR-1, PR-2, PR-3, POD, and PPO genes in the infected leaves of three potato cultivars were estimated by quantitative real-time PCR. We can conclude that the PLRV-infection of potato plants inhibited the expression of the five PR genes. On the contrary, infected leaves by PLRV elevated the expression of some defense genes. This interaction may also induce and/or suppress the expression of some genes responsible for the plant's defense mechanisms.

Keywords: PLRV, pathogenesis-related proteins (PRs), DD-PCR, sequence, real-time PCR

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Authors: Farzad Hosseini Hossein Abadi, Cristina Prieto Sierra, Cesar Álvarez Díaz

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Predicting streamflow accurately in flashy catchments prone to floods is a major research and operational challenge in hydrological modeling. Recent advancements in deep learning, particularly Long Short-Term Memory (LSTM) networks, have shown to be promising in achieving accurate hydrological predictions at daily and hourly time scales. In this work, a multi-timescale LSTM (MTS-LSTM) network was applied to the context of regional hydrological predictions at an hourly time scale in flashy catchments. The case study includes 40 catchments allocated in the Basque Country, north of Spain. We explore the impact of hyperparameters on the performance of streamflow predictions given by regional deep learning models through systematic hyperparameter tuning - where optimal regional values for different catchments are identified. The results show that predictions are highly accurate, with Nash-Sutcliffe (NSE) and Kling-Gupta (KGE) metrics values as high as 0.98 and 0.97, respectively. A principal component analysis reveals that a hyperparameter related to the length of the input sequence contributes most significantly to the prediction performance. The findings suggest that input sequence lengths have a crucial impact on the model prediction performance. Moreover, employing catchment-scale analysis reveals distinct sequence lengths for individual basins, highlighting the necessity of customizing this hyperparameter based on each catchment’s characteristics. This aligns with well known “uniqueness of the place” paradigm. In prior research, tuning the length of the input sequence of LSTMs has received limited focus in the field of streamflow prediction. Initially it was set to 365 days to capture a full annual water cycle. Later, performing limited systematic hyper-tuning using grid search, revealed a modification to 270 days. However, despite the significance of this hyperparameter in hydrological predictions, usually studies have overlooked its tuning and fixed it to 365 days. This study, employing a simultaneous systematic hyperparameter tuning approach, emphasizes the critical role of input sequence length as an influential hyperparameter in configuring LSTMs for regional streamflow prediction. Proper tuning of this hyperparameter is essential for achieving accurate hourly predictions using deep learning models.

Keywords: LSTMs, streamflow, hyperparameters, hydrology

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Authors: Agampodi Promoda Perera, Yong Shin, Mi Kyoung Park

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The successful detection of pathogenic bacteria in blood provides important information for early detection, diagnosis and the prevention and treatment of infectious diseases. Silicon microring resonators are refractive-index-based optical biosensors that provide highly sensitive, label-free, real-time multiplexed detection of biomolecules. We demonstrate the technique of using GO (graphene oxide) to enhance the signal output of the silicon microring optical sensor. The activated carboxylic groups in GO molecules bind directly to single stranded DNA with an amino modified 5’ end. This conjugation amplifies the shift in resonant wavelength in a real-time manner. We designed a capture probe for strain Staphylococcus aureus of 21 bp and a longer complementary target sequence of 70 bp. The mismatched target sequence we used was of Streptococcus agalactiae of 70 bp. GO is added after the complementary binding of the probe and target. GO conjugates to the unbound single stranded segment of the target and increase the wavelength shift on the silicon microring resonator. Furthermore, our results show that GO could successfully differentiate between the mismatched DNA sequences from the complementary DNA sequence. Therefore, the proposed concept could effectively enhance sensitivity of pathogen detection sensors.

Keywords: label free biosensor, pathogenic bacteria, graphene oxide, diagnosis

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Authors: Cristina Lavilla, Andreas Heise

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The synthesis of sequence-controlled polymers has received increasing attention in the last years. Well-defined polyacrylates, polyacrylamides and styrene-maleimide copolymers have been synthesized by sequential or kinetic addition of comonomers. However this approach has not yet been introduced to the synthesis of polypeptides, which are in fact polymers developed by nature in a sequence-controlled way. Polypeptides are natural materials that possess the ability to self-assemble into complex and highly ordered structures. Their folding and properties arise from precisely controlled sequences and compositions in their constituent amino acid monomers. So far, solid-phase peptide synthesis is the only technique that allows preparing short peptide sequences with excellent sequence control, but also requires extensive protection/deprotection steps and it is a difficult technique to scale-up. A new strategy towards sequence control in the synthesis of polypeptides is introduced, based on the sequential addition of α-amino acid-N-carboxyanhydrides (NCAs). The living ring-opening process is conducted to full conversion and no purification or deprotection is needed before addition of a new amino acid. The length of every block is predefined by the NCA:initiator ratio in every step. This method yields polypeptides with a specific sequence and controlled molecular weights. A series of polypeptides with varying block sequences have been synthesized with the aim to identify structure-property relationships. All of them are able to adopt secondary structures similar to natural polypeptides, and display properties in the solid state and in solution that are characteristic of the primary structure. By design the prepared polypeptides allow selective modification of individual block sequences, which has been exploited to introduce functionalities in defined positions along the polypeptide chain. Poly(ethylene glycol)(PEG) was the functionality chosen, as it is known to favor hydrophilicity and also yield thermoresponsive materials. After PEGylation, hydrophilicity of the polypeptides is enhanced, and their thermal response in H2O has been studied. Noteworthy differences in the behavior of the polypeptides having different sequences have been found. Circular dichroism measurements confirmed that the α-helical conformation is stable over the examined temperature range (5-90 °C). It is concluded that PEG units are the main responsible of the changes in H-bonding interactions with H2O upon variation of temperature, and the position of these functional units along the backbone is a factor of utmost importance in the resulting properties of the α-helical polypeptides.

Keywords: α-amino acid N-carboxyanhydrides, multiblock copolymers, poly(ethylene glycol), polypeptides, ring-opening polymerization, sequence control

Procedia PDF Downloads 172

Authors: Xu LiYun, Briand Florent, Fan GuoLiang

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The loop-layout design problem (LLDP) aims at optimizing the sequence of positioning of the machines around the cyclic production line. Traffic congestion is the usual criteria to minimize in this type of problem, i.e. the number of additional cycles spent by each part in the network until the completion of its required routing sequence of machines. This paper aims at applying several improvements mechanisms such as a positioned-based crossover operator for the Genetic Algorithm (GA) called a Two Points Crossover (TPC) and an offspring selection process. The performance of the improved GA is measured using well-known examples from literature and compared to other evolutionary algorithms. Good results show that GA can still be competitive for this type of problem against more recent evolutionary algorithms.

Keywords: crossover, genetic algorithm, layout design problem, loop-layout, manufacturing optimization

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Authors: Ahmed Sameer, Braj Bhushan

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The objective of our study was to compare two techniques (no landmark vs imaginary landmark) of remembering route while traversing in an unfamiliar homogenous environment. We used two videos each having nine identical turns with no landmarks. In the first video participant was required to remember the sequence of turns. In the second video participant was required to imagine a landmark at each turn and associate the turn with it. In both the task the participant was asked to recall the sequence of turns as it appeared in the video. Results showed that performance in the first condition i.e. without use of landmarks was better than imaginary landmark condition. The difference, however, became significant when the participant were tested again about 30 minutes later though performance was still better in no-landmark condition. The finding is surprising given the past research in memory and is explained in terms of cognitive factors such as mental workload.

Keywords: wayfinding, landmarks, unfamiliar environment, cognitive psychology

Procedia PDF Downloads 445

Authors: Salam M. H. Kareem

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Instructional or teaching procedures and their proper sequence are essential for high-quality learning outcomes. These actions are the path that the teacher takes during the learning process after setting the learning objectives. Teachers and specialists in the education field should include teaching procedures with putting in place an effective mechanism for the procedure’s implementation to achieve a logical sequence with the desired output of overall education process. Determining the sequence of these actions may be a strategic process outlined by a strategic educational plan or drawn by teachers with a high level of experience, enabling them to determine those logical procedures. While specific actions may be necessary for a specific form, many Physical Education (PE) teachers can work out on various sports disciplines. This study was conducted to investigate the impact of using the teaching sequence of the teaching pyramid in raising the level of enjoyment in swimming classes. Four months later of teaching swimming skills to the control and experimental groups of the study, we figured that using the tools shown in the teaching pyramid with the experimental group led to statistically significant differences in the positive tendencies of students to participate in the swimming classes by using the traditional procedures of teaching and using of successive procedures in the teaching pyramid, and in favor of the teaching pyramid, The students are influenced by enhancing their tendency to participate in swimming classes when the teaching procedures followed are sensitive to individual differences and are based on the element of pleasure in learning, and less positive levels of the tendency of students when using traditional teaching procedures, by getting the level of skills' requirements higher and more difficult to perform. The level of positive tendencies of students when using successive procedures in the teaching pyramid was increased, by getting the level of skills' requirements higher and more difficult to perform, because of the high level of motivation and the desire to challenge the self-provided by the teaching pyramid.

Keywords: physical education, swimming classes, teaching process, teaching pyramid

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Authors: Ganesh Nandakumaran, Mehmet Karaata

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A wave is a distributed execution, often made up of a broadcast phase followed by a feedback phase, requiring the participation of all the system processes before a particular event called decision is taken. Wave algorithms with one initiator such as the 1-wave algorithm have been shown to be very efficient for broadcasting messages in tree networks. Extensions of this algorithm broadcasting a sequence of waves using a single initiator have been implemented in algorithms such as the m-wave algorithm. However as the network size increases, having a single initiator adversely affects the message delivery times to nodes further away from the initiator. As a remedy, broadcast waves can be allowed to be initiated by multiple initiator nodes distributed across the network to reduce the completion time of broadcasts. These waves initiated by one or more initiator processes form a collection of waves covering the entire network. Solutions to global-snapshots, distributed broadcast and various synchronization problems can be solved efficiently using waves with multiple concurrent initiators. In this paper, we propose the first stabilizing multi-wave sequence algorithm implementing waves started by multiple initiator processes such that every process in the network receives at least one sequence of broadcasts. Due to being stabilizing, the proposed algorithm can withstand transient faults and do not require initialization. We view a fault as a transient fault if it perturbs the configuration of the system but not its program.

Keywords: distributed computing, multi-node broadcast, propagation of information with feedback and cleaning (PFC), stabilization, wave algorithms

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Authors: Navkiran Kaur, Apoorva Mathur, Abhishree Agarwal, Sakshi Gupta, Tuhin Rashmi

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Aim: Breast cancer is the most common cancer in women worldwide, and resistance to the current therapeutics, often concurrently, is an increasing clinical challenge. Glycosylation of proteins is one of the most important post-translational modifications. It is widely known that aberrant glycosylation has been implicated in many different diseases due to changes associated with biological function and protein folding. Alterations in cell surface glycosylation, can promote invasive behavior of tumor cells that ultimately lead to the progression of cancer. In breast cancer, there is an increasing evidence pertaining to the role of glycosylation in tumor formation and metastasis. In the present study, an attempt has been made to study the disease associated sialoglycoproteins in breast cancer by using bioinformatics tools. The sequence will be retrieved from UniProt database. A database in the form of a word document was made by a collection of FASTA sequences of breast cancer gene sequence. Glycosylation was studied using yinOyang tool on ExPASy and Differential genes expression and protein analysis was done in context of breast cancer metastasis. The number of residues predicted O-glc NAc threshold containing 50 aberrant glycosylation sites or more was detected and recorded for individual sequence. We found that the there is a significant change in the expression profiling of glycosylation patterns of various proteins associated with breast cancer. Differential aberrant glycosylated proteins in breast cancer cells with respect to non-neoplastic cells are an important factor for the overall progression and development of cancer.

Keywords: breast cancer, bioinformatics, cancer, metastasis, glycosylation

Procedia PDF Downloads 267