Search results for: molecular identification

Authors: Vrushali Guhe, Shailza Singh

Abstract:

Cutaneous leishmaniasis is neglected tropical disease present worldwide caused by the protozoan parasite Leishmania major, the therapeutic armamentarium for leishmaniasis are showing several limitations as drugs are showing toxic effects with increasing resistance by a parasite. Thus identification of novel therapeutic targets is of paramount importance. Previous studies have shown that autophagy, a cellular process, can either facilitate infection or aid in the elimination of the parasite, depending on the specific parasite species and host background in leishmaniasis. In the present study, our objective was to target the essential autophagy protein ATG8, which plays a crucial role in the survival, infection dynamics, and differentiation of the Leishmania parasite. ATG8 in Leishmania major and its homologue, LC3, in Homo sapiens, act as autophagic markers. Present study manifested the crucial role of ATG8 protein as a potential target for combating Leishmania major infection. Through bioinformatics analysis, we identified non-conserved motifs within the ATG8 protein of Leishmania major, which are not present in LC3 of Homo sapiens. Against these two non-conserved motifs, we generated a peptide library of 60 peptides on the basis of physicochemical properties. These peptides underwent a filtering process based on various parameters, including feasibility of synthesis and purification, compatibility with Selective Reaction Monitoring (SRM)/Multiple reaction monitoring (MRM), hydrophobicity, hydropathy index, average molecular weight (Mw average), monoisotopic molecular weight (Mw monoisotopic), theoretical isoelectric point (pI), and half-life. Further filtering criterion shortlisted three peptides by using molecular docking and molecular dynamics simulations. The direct interaction between ATG8 and the shortlisted peptides was confirmed through Surface Plasmon Resonance (SPR) experiments. Notably, these peptides exhibited the remarkable ability to penetrate the parasite membrane and exert profound effects on Leishmania major. The treatment with these peptides significantly impacted parasite survival, leading to alterations in the cell cycle and morphology. Furthermore, the peptides were found to modulate autophagosome formation, particularly under starved conditions, suggesting their involvement in disrupting the regulation of autophagy within Leishmania major. In vitro, studies demonstrated that the selected peptides effectively reduced the parasite load within infected host cells. Encouragingly, these findings were corroborated by in vivo experiments, which showed a reduction in parasite burden upon peptide administration. Additionally, the peptides were observed to affect the levels of LC3II within host cells. In conclusion, our findings highlight the efficacy of these novel peptides in targeting Leishmania major’s ATG8 and disrupting parasite survival. These results provide valuable insights into the development of innovative therapeutic strategies against leishmaniasis via targeting autophagy protein ATG8 of Leishmania major.

Keywords: ATG8, leishmaniasis, surface plasmon resonance, MD simulation, molecular docking, peptide designing, therapeutics

Procedia PDF Downloads 50

Authors: Mehdi Moradi Sarmeidani, Peyman Keyhani, Hasan Momtaz

Abstract:

Chlamydophila psittaci is a avian pathogen that may cause respiratory disorders in humans. Conjunctival and cloacal swabs from 54 captive psittacine birds presented at veterinary clinics were collected to determine the prevalence of C. psittaci in domestic birds in Isfahan. Samples were collected during 2014 from a total of 10 different species of parrots, with African gray(33), Cockatiel lutino(3), Cockatiel gray(2), Cockatiel cinnamon(1), Pearl cockatiel(6), Timneh African grey(1), Ringneck parakeet(2), Melopsittacus undulatus(1), Alexander parakeet(2), Green Parakeet(3) being the most representative species sampled. C. psittaci was detected in 27 (50%) birds using molecular detection (PCR) method. The detection of this bacterium in captive psittacine birds shows that there is a potential risk for human whom has a direct contact and there is a possibility of infecting other birds.

Keywords: chlamydophila psittaci, psittacine birds, PCR, Isfahan

Procedia PDF Downloads 339

Authors: Amir Doustgani

Abstract:

Melt electrospinning is a safe and simple technique for the production of micro and nanofibers which can be an alternative to conventional solvent electrospinning. The effects of various melt-electrospinning parameters, including molecular weight, electric field strength, flow rate and temperature on the morphology and fiber diameter of polylactic acid were studied. It was shown that molecular weight was the predominant factor in determining the obtainable fiber diameter of the collected fibers. An orthogonal design was used to examine process parameters. Results showed that molecular weight is the most effective parameter on the average fiber diameter of melt electrospun PLA nanofibers and the flow rate has the less important impact. Mean fiber diameter increased by increasing MW and flow rate, but decreased by increasing electric field strength and temperature. MFD of optimized fibers was below 100 nm and the result of software was in good agreement with the experimental condition.

Keywords: fiber formation, processing, spinning, melt blowing

Procedia PDF Downloads 411

Authors: Mouna Baassi, Mohamed Moussaoui, Sanchaita Rajkhowa, Hatim Soufi, Said Belaaouad

Abstract:

The objective of this paper is to address the challenging task of targeting Human Immunodeficiency Virus type 1 Reverse Transcriptase (HIV-1 RT) in the treatment of AIDS. Reverse Transcriptase inhibitors (RTIs) have limitations due to the development of Reverse Transcriptase mutations that lead to treatment resistance. In this study, a combination of statistical analysis and bioinformatics tools was adopted to develop a mathematical model that relates the structure of compounds to their inhibitory activities against HIV-1 Reverse Transcriptase. Our approach was based on a series of compounds recognized for their HIV-1 RT enzymatic inhibitory activities. These compounds were designed via software, with their descriptors computed using multiple tools. The most statistically promising model was chosen, and its domain of application was ascertained. Furthermore, compounds exhibiting comparable biological activity to existing drugs were identified as potential inhibitors of HIV-1 RT. The compounds underwent evaluation based on their chemical absorption, distribution, metabolism, excretion, toxicity properties, and adherence to Lipinski's rule. Molecular docking techniques were employed to examine the interaction between the Reverse Transcriptase (Wild Type and Mutant Type) and the ligands, including a known drug available in the market. Molecular dynamics simulations were also conducted to assess the stability of the RT-ligand complexes. Our results reveal some of the new compounds as promising candidates for effectively inhibiting HIV-1 Reverse Transcriptase, matching the potency of the established drug. This necessitates further experimental validation. This study, beyond its immediate results, provides a methodological foundation for future endeavors aiming to discover and design new inhibitors targeting HIV-1 Reverse Transcriptase.

Keywords: QSAR, ADMET properties, molecular docking, molecular dynamics simulation, reverse transcriptase inhibitors, HIV type 1

Procedia PDF Downloads 53

Authors: O. O. Fola-Matthews, O. O. Soyinka, D. N. Bitalo

Abstract:

Nigeria is one of the major shark fishing nations in Africa, but its fisheries managers still record catch data in aggregates ‘sharks’ with no species-specific details. This is because most of the shark specimens look identical in morphology, and field identification of some closely related species is tricky. This study uses DNA barcoding as a method to identify shark species from five different landing areas off the Nigerian Coast. 100 dorsal fins were sampled in order to provide a Chondrichthyan sequence that would be matched to reference specimens in a DNA barcode database

Keywords: BOLD, DNA barcoding, nigeria, sharks

Procedia PDF Downloads 134

Authors: Mohammad Hossein Modarressi, Mozhgan Mondeali, Khabat Barkhordari, Ali Etemadi

Abstract:

The COVID-19 pandemic, caused by SARS-CoV-2, has led to significant concerns worldwide due to its catastrophic effects on public health. The SARS-CoV-2 infection is initiated with the binding of the receptor-binding domain (RBD) in its spike protein to the ACE2 receptor in the host cell membrane. Due to the error-prone entity of the viral RNA-dependent polymerase complex, the virus genome, including the coding region for the RBD, acquires new mutations, leading to the appearance of multiple variants. These variants can potentially impact transmission, virulence, antigenicity and evasive immune properties. S477N mutation located in the RBD has been observed in the SARS-CoV-2 omicron (B.1.1. 529) variant. In this study, we investigated the consequences of S477N mutation at the molecular level using computational approaches such as molecular dynamics simulation, protein-protein interaction analysis, immunoinformatics and free energy computation. We showed that displacement of Ser with Asn increases the stability of the spike protein and its affinity to ACE2 and thus increases the transmission potential of the virus. This mutation changes the folding and secondary structure of the spike protein. Also, it reduces antibody neutralization, raising concern about re-infection, vaccine breakthrough and therapeutic values.

Keywords: S477N, COVID-19, molecular dynamic, SARS-COV2 mutations

Procedia PDF Downloads 141

Authors: Mallikarjun Warad, C. M. Kalleshwaraswamy, P. R. Shashank

Abstract:

Studies were conducted to record the occurrence of different species of hairy caterpillar on different host plants in and around Shivamogga, Karnataka, India. Twelve genera of hairy caterpillars belonging to Arctiinae and Lymantriinae were recorded on different host plants and reared to adults in laboratory on their respective hosts. The Porthesia sp. feed on castor, Creatonotus gangis on cocoa, Perina nuda on fig, Pericalia ricini on pigeon pea, Utetheisa pulchella on sunhemp and Euproctis sp. on paddy and banana. Illustrations of immature and adults were made to associate them. Along with this, light traps were also set during the rainy season, to capture adults of hairy caterpillars. An illustrated identification key was provided for easy and accurate identification of adult of hairy caterpillars based on their morphological (male genitalial) characters. The study through a light on the existence of sexual dimorphism, polyphagous nature and diapause are the major hindrance in taxonomic identification. Hence, attempts were made to address these issues in the study.

Keywords: Erebidae, hairy caterpillars, male genitalia, taxonomy

Procedia PDF Downloads 165

Authors: Devinder Kaur Sugga, Ekamdeep Kaur, Jaspreet Kaur, C. Rajesh, Preeti Rajesh, Harsimran Kaur

Abstract:

Withanolides are steroidal lactones and are highly oxygenated phytoconstituents that can be developed as potential anti-carcinogenic agents. The two main withanolides, namely Withaferin A and Withanolides D, have been extensively studied for their pharmacological activities. Both these withanolides are present in the Withania somnifera (WS) leaves belonging to the family Solanaceae, also known as “Indian ginseng .”In this study effects of WS leaf extract on the MCF7 breast cancer cell line were investigated by performing a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay to evaluate the cytotoxic effects and in vitro wound-healing assay to study the effect on cancer cell migration. Our data suggest WS extracts have cytotoxic effects and are effective anti-migrating agents and thus can be a source of potential candidates for the development of potential agents against metastasis. Thus, it can be a source of potential candidates for the development of potential agents against metastasis. Insight into these results, the in-silico approach to identify the possible protein targets interacting with withanolides was taken. Protein kinase C alpha (PKCα) was among the selected 5 top-ranked target proteins identified by the Swiss Target Prediction tool. PKCα is known to promote the growth and invasion of cancer cells and is being evaluated as a prognostic biomarker and therapeutic target in clinically aggressive tumors. Molecular docking of Withaferin A and Withanolides D was performed using AutoDock Vina. Both the bioactive compounds interacted with PKCα. The targets predicted using this approach will serve as leads for the possible therapeutic potential of withanolides, the bioactive ingredients of WS extracts, as anti-cancer drugs.

Keywords: withania somnifera, withaferin A, withanolides D, PKCα

Procedia PDF Downloads 103

Authors: Ben Soltane Cheima, Ittansa Yonas Kelbesa

Abstract:

Speaker Identification (SI) is the task of establishing identity of an individual based on his/her voice characteristics. The SI task is typically achieved by two-stage signal processing: training and testing. The training process calculates speaker specific feature parameters from the speech and generates speaker models accordingly. In the testing phase, speech samples from unknown speakers are compared with the models and classified. Even though performance of speaker identification systems has improved due to recent advances in speech processing techniques, there is still need of improvement. In this paper, a Closed-Set Tex-Independent Speaker Identification System (CISI) based on a Multiple Classifier System (MCS) is proposed, using Mel Frequency Cepstrum Coefficient (MFCC) as feature extraction and suitable combination of vector quantization (VQ) and Gaussian Mixture Model (GMM) together with Expectation Maximization algorithm (EM) for speaker modeling. The use of Voice Activity Detector (VAD) with a hybrid approach based on Short Time Energy (STE) and Statistical Modeling of Background Noise in the pre-processing step of the feature extraction yields a better and more robust automatic speaker identification system. Also investigation of Linde-Buzo-Gray (LBG) clustering algorithm for initialization of GMM, for estimating the underlying parameters, in the EM step improved the convergence rate and systems performance. It also uses relative index as confidence measures in case of contradiction in identification process by GMM and VQ as well. Simulation results carried out on voxforge.org speech database using MATLAB highlight the efficacy of the proposed method compared to earlier work.

Keywords: feature extraction, speaker modeling, feature matching, Mel frequency cepstrum coefficient (MFCC), Gaussian mixture model (GMM), vector quantization (VQ), Linde-Buzo-Gray (LBG), expectation maximization (EM), pre-processing, voice activity detection (VAD), short time energy (STE), background noise statistical modeling, closed-set tex-independent speaker identification system (CISI)

Procedia PDF Downloads 279

Authors: Camilla Elphick, Graham Hole, Samuel Hutton, Graham Pike

Abstract:

Pupil size has been found to change irrespective of luminosity, suggesting that it can be used to make inferences about cognitive processes, such as cognitive load. To see whether identifying a target requires a different cognitive load to rejecting distractors, the effect of viewing a target (compared with viewing distractors) on pupil size was investigated using a sequential video lineup procedure with two lineup sessions. Forty one participants were chosen randomly via the university. Pupil sizes were recorded when viewing pre target distractors and post target distractors and compared to pupil size when viewing the target. Overall, pupil size was significantly larger when viewing the target compared with viewing distractors. In the first session, pupil size changes were significantly different between participants who identified the target (Hits) and those who did not. Specifically, the pupil size of Hits reduced significantly after viewing the target (by 26%), suggesting that cognitive load reduced following identification. The pupil sizes of Misses (who made no identification) and False Alarms (who misidentified a distractor) did not reduce, suggesting that the cognitive load remained high in participants who failed to make the correct identification. In the second session, pupil sizes were smaller overall, suggesting that cognitive load was smaller in this session, and there was no significant difference between Hits, Misses and False Alarms. Furthermore, while the frequency of Hits increased, so did False Alarms. These two findings suggest that the benefits of including a second session remain uncertain, as the second session neither provided greater accuracy nor a reliable way to measure it. It is concluded that pupil size is a measure of face recognition strength in the first session of a target present lineup procedure. However, it is still not known whether cognitive load is an adequate explanation for this, or whether cognitive engagement might describe the effect more appropriately. If cognitive load and cognitive engagement can be teased apart with further investigation, this would have positive implications for understanding eyewitness identification. Nevertheless, this research has the potential to provide a tool for improving the reliability of lineup procedures.

Keywords: cognitive load, eyewitness identification, face recognition, pupillometry

Procedia PDF Downloads 370

Authors: Jonghoon Chun, Insung Kim, Jonghyun Lim, Gun Ro

Abstract:

We believe that it is possible to provide a solution to reduce patient safety accidents by displaying correct medical records and prescription information through interactive patient identification. Our system is based on the use of smart bands worn by patients and these bands communicate with the hybrid gateways which understand both BLE and Wifi communication protocols. Through the convergence of low-power Bluetooth (BLE) and hybrid gateway technology, which is one of short-range wireless communication technologies, we implement ‘Intelligent Patient Identification and Location Tracking System’ to prevent medical malfunction frequently occurring in medical institutions. Based on big data and IOT technology using MongoDB, smart band (BLE, NFC function) and hybrid gateway, we develop a system to enable two-way communication between medical staff and hospitalized patients as well as to store locational information of the patients in minutes. Based on the precise information provided using big data systems, such as location tracking and movement of in-hospital patients wearing smart bands, our findings include the fact that a patient-specific location tracking algorithm can more efficiently operate HIS (Hospital Information System) and other related systems. Through the system, we can always correctly identify patients using identification tags. In addition, the system automatically determines whether the patient is a scheduled for medical service by the system in use at the medical institution, and displays the appropriateness of the medical treatment and the medical information (medical record and prescription information) on the screen and voice. This work was supported in part by the Korea Technology and Information Promotion Agency for SMEs (TIPA) grant funded by the Korean Small and Medium Business Administration (No. S2410390).

Keywords: BLE, hybrid gateway, patient identification, IoT, safety management, smart band

Procedia PDF Downloads 281

Authors: Neha Kanodia, M. Kamil

Abstract:

Properties of mono layers of Pluronic F127 at air/water interface have been investigated by using Langmuir trough method. Pluronic F127 is a triblock copolymer of poly (ethyleneoxide) (PEO groups)– poly (propylene oxide) (PO groups)–poly(ethylene oxide) (PEO groups). Surface pressure versus mean molecular area isotherms is studied. The isotherm of the mono layer showed the characteristics of a pancake-to-brush transition upon compression of the mono layer. The effect of adding surfactant (SDS) to polymer and the effect of increasing loading on polymer was also studied. The effect of repeated compression and expansion cycle (or hysteresis curve) is investigated to know about stability of the film formed. Static elasticity of mono layer gives information about molecular arrangement, phase structure and phase transition.

Keywords: surface-pressure, mean molecular area isotherms, hysteresis, static elasticity

Procedia PDF Downloads 416

Authors: Isaac Quiros-Fernandez, Angel Cid-Arregui

Abstract:

Tumor-reactive T cell receptors (TCRs) are being subject of intense investigation since they offer great potential in adoptive cell therapies against cancer. However, the identification of tumor-specific TCRs has proven challenging, for instance, due to the limited expansion capacity of tumor-infiltrating T cells (TILs) and the extremely low frequencies of tumor-reactive T cells in the repertoire of patients and healthy donors. We have developed an approach for rapid identification and characterization of neoepitope-reactive TCRs from the T cell repertoire of healthy donors. CD8 T cells isolated from multiple donors are subjected to a first sorting step after staining with HLA multimers carrying the peptide of interest. The isolated cells are expanded for two weeks, after which a second sorting is performed using the same peptide-HLA multimers. The cells isolated in this way are then processed for single-cell sequencing of their TCR alpha and beta chains. Newly identified TCRs are cloned in appropriate expression vectors for functional analysis on Jurkat, NK92, and primary CD8 T cells and tumor cells expressing the appropriate antigen. We have identified TCRs specifically binding HLA-A2 presenting epitopes of tumor antigens, which are capable of inducing TCR-mediated cell activation and cytotoxicity in target cancer cell lines. This method allows the identification of tumor-reactive TCRs in about two to three weeks, starting from peripheral blood samples of readily available healthy donors.

Keywords: cancer, TCR, tumor antigens, immunotherapy

Procedia PDF Downloads 34

Authors: Dharmendra Pratap

Abstract:

Large Cardamom (Amomum subulatum), family Zingiberaceae is an aromatic spice crop and has rich medicinal value. Large Cardamom is as synonymous to Sikkim as Tea is to Darjeeling. Since Sikkim alone contributes up to 88% of India's large cardamom production which is the world leader by producing over 50% of the global yield. However, the production of large cardamom has declined almost to half since last two decade. The economic losses have been attributed to two viral diseases namely, chirke and Foorkey. Chirke disease is characterized by light and dark green streaks on leaves. The affected leaves exhibit streak mosaic, which gradually coalesce, turn brown and eventually dry up. Excessive sprouting and formation of bushy dwarf clumps at the base of mother plants that gradually die characterize the foorkey disease. In our surveys in Sikkim–Darjeeling hill area during 2012-14, 40-45% of plants were found to be affected with foorkey disease and 10-15% with chirke. Mechanical and aphid transmission study showed banana as an alternate host for both the disease. For molecular identification, total genomic DNA and RNA was isolated from the infected leaf tissues and subjected to Rolling circle amplification (RCA) and RT-PCR respectively. The DNA concatamers produced in the RCA reaction were monomerized by different restriction enzymes and the bands corresponding to ~1 kb genomes were purified and cloned in the respective sites. The nucleotide sequencing results revealed the association of Nanovirus with the foorkey disease of large cardamom. DNA1 showed 74% identity with Replicase gene of FBNYV, DNA2 showed 77% identity with the NSP gene of BBTV and DNA3 showed 74% identity with CP gene of BBTV. The finding suggests the presence of a new species of nanovirus associated with foorkey disease of large cardamom in Sikkim and Darjeeling hills. The details of their epidemiology and other factors would be discussed.

Keywords: RCA, nanovirus, large cardamom, molecular virology and microbiology

Procedia PDF Downloads 473

Authors: Hassan Nour, Nouh Mounadi, Oussama Abchir, Belaidi Salah, Samir Chtita

Abstract:

Cholinesterase enzymes are biological catalysts essential for the transformation of acetylcholine, which is a neurotransmitter implicated in memory and learning, into acetic acid and choline, altering the neurotransmission process in Alzheimer’s disease patients. Therefore, inhibition of cholinesterase enzymes is a relevant strategy for the symptomatic treatment of Alzheimer’s disease. The current investigation aims to explore potential cholinesterase (ChE) inhibitors through a comprehensive computational approach. Forty-nine phytoconstituents extracted from Cannabis sativa L. were in-silico screened using molecular docking and pharmacokinetic and toxicological analysis to evaluate their possible inhibitory effect on the cholinesterase enzymes. Two phytoconstituents belonging to cannabinoid derivatives were revealed to be promising candidates for Alzheimer's therapy by acting as cholinesterase inhibitors. They have exhibited high binding affinities towards the cholinesterase enzymes and showed their ability to interact with key residues involved in cholinesterase enzymatic activity. In addition, they presented good ADMET profiles allowing them to be promising oral drug candidates. Furthermore, molecular dynamics (MD) simulations were executed to explore their interaction stability under mimetic biological conditions and thus support our findings. To corroborate the docking results, the binding free energy corresponding to the more stable ligand-ChE complexes was re-estimated by applying the MM-PBSA method. MD and MM-PBSA studies affirmed that the ligand-ChE recognition is a spontaneous reaction leading to stable complexes. The conducted investigations have led to great findings that would strongly guide the pharmaceutical industries toward the rational development of potent anti-Alzheimer agents.

Keywords: Alzheimer’s disease, molecular docking, Cannabis sativa L., cholinesterase inhibitors, molecular dynamics, ADMET, MM-PBSA

Procedia PDF Downloads 50

Authors: Mostafa ‘Neo’ Mohsenvand, Mohammad Rasool Izadi, Pattie Maes

Abstract:

EEG-based biometrics (user identification) has been explored on small datasets of no more than 157 subjects. Here we show that the accuracy of modern supervised methods falls rapidly as the number of users increases to a few thousand. Moreover, supervised methods require a large amount of labeled data for training which limits their applications in real-world scenarios where acquiring data for training should not take more than a few minutes. We show that using contrastive learning for pre-training, it is possible to maintain high accuracy on a dataset of 2130 subjects while only using a fraction of labels. We compare 5 different self-supervised tasks for pre-training of the encoder where our proposed method achieves the accuracy of 96.4%, improving the baseline supervised models by 22.75% and the competing self-supervised model by 3.93%. We also study the effects of the length of the signal and the number of channels on the accuracy of the user-identification models. Our results reveal that signals from temporal and frontal channels contain more identifying features compared to other channels.

Keywords: brainprint, contrastive learning, electroencephalo-gram, self-supervised learning, user identification

Procedia PDF Downloads 130

Authors: W. P. Hu, J. V. Kumar, Jeffrey J. P. Tsai

Abstract:

The inhibition of SH2 domain regulated protein-protein interactions is an attractive target for developing an effective chemotherapeutic approach in the treatment of disease. Molecular simulation is a useful tool for developing new drugs and for studying molecular recognition. In this study, we searched potential drug compounds for the inhibition of SH2 domain by performing structural similarity search in PubChem Compound Database. A total of 37 compounds were screened from the database, and then we used the LibDock docking program to evaluate the inhibition effect. The best three compounds (AP22408, CID 71463546 and CID 9917321) were chosen for MD simulations after the LibDock docking. Our results show that the compound CID 9917321 can produce a more stable protein-ligand complex compared to other two currently known inhibitors of Src SH2 domain. The compound CID 9917321 may be useful for the inhibition of SH2 domain based on these computational results. Subsequently experiments are needed to verify the effect of compound CID 9917321 on the SH2 domain in the future studies.

Keywords: nonpeptide inhibitor, Src SH2 domain, LibDock, molecular dynamics simulation

Procedia PDF Downloads 238

Authors: András Farkas, István Molnár, Jan Vrána, Veronika Burešová, Petr Cápal, András Cseh, Márta Molnár-Láng, Jaroslav Doležel

Abstract:

Species of Aegilops played a central role in the evolution of wheat and are sources of traits related to yield quality and tolerance against biotic and abiotic stresses. These wild genes and alleles are desirable to use in crop improvement programs via introgressive hybridization. However, the success of chromosome mediated gene transfer to wheat are hampered by the pour knowledge on the genome structure of Aegilops relative to wheat and by the low number of cost-effective molecular markers specific for Aegilops chromosomes. The COS markers specific for genes conserved throughout evolution in both sequence and copy number between Triticeae/Aegilops taxa and define orthologous regions, thus enabling the comparison of regions on the chromosomes of related species. The present study compared individual chromosomes of Aegilops umbellulata (UU), Ae. comosa (MM), Ae. speltoides (SS) and Ae. caudata (CC) purified by flourescent labelling with oligonucleotid SSR repeats and biparametric flow cytometry with wheat by identifying orthologous chromosomal regions by COS markers. The linear order of bin-mapped COS markers along the wheat D chromosomes was identified by the use of chromosome-specific sequence data and virtual gene order. Syntenic regions of wheat identifying genome rearrangements differentiating the U, M, S or C genomes from the D genome of wheat were detected. The conserved orthologous set markers assigned to Aegilops chromosomes promise to accelerate gene introgression by facilitating the identification of alien chromatin. The syntenic relationships between the Aegilops species and wheat will facilitate the targeted development of new markers specific for U, M, S and C genomic regions and will contribute to the understanding of molecular processes related to the evolution of Aegilops.

Keywords: Aegilops, cos-markers, flow-sorting, wheat

Procedia PDF Downloads 467

Authors: Rozhgar A. Khailany, Mehri Igci, Emine Bayraktar, Sakip Erturhan, Metin Karakok, Ahmet Arslan

Abstract:

Kidney cancer is the most lethal urological cancer accounting for 3% of adult malignancies. VHL, a tumor-suppressor gene, is best known to be associated with renal cell carcinoma (RCC). The VHL functions as negative regulator of hypoxia inducible factors. Recent sequencing efforts have identified several novel frequent mutations of histone modifying and chromatin remodeling genes in ccRCC (clear cell RCC) including PBRM1 and SETD2. The PBRM1 gene encodes the BAF180 protein, which involved in transcriptional activation and repression of selected genes. SETD2 encodes a histone methyltransferase, which may play a role in suppressing tumor development. In this study, RNAs of 30 paired tumor and normal samples that were grouped according to the types of kidney cancer and clinical characteristics of patients, including gender and average age were examined by RT-PCR, SSCP and sequencing techniques. VHL, PBRM1 and SETD2 expressions were relatively down-regulated. However, statistically no significance was found (Wilcoxon signed rank test, p > 0.05). Interestingly, no mutation was observed on the contrary of previous studies. Understanding the molecular mechanisms involved in the pathogenesis of RCC has aided the development of molecular-targeted drugs for kidney cancer. Further analysis is required to identify the responsible genes rather than VHL, PBRM1 and SETD2 in kidney cancer.

Keywords: kidney cancer, molecular biomarker, expression analysis, mutation screening

Procedia PDF Downloads 423

Authors: Lotfi O. Gargab, Ruichong R. Zhang

Abstract:

A wave-based framework is presented for modeling seismic motion in multistory buildings and using measured response for system identification which can be utilized to extract important information regarding structure integrity. With one pair of building response at two locations, a generalized model response is formulated based on wave propagation features and expressed as frequency and time response functions denoted, respectively, as GFRF and GIRF. In particular, GIRF is fundamental in tracking arrival times of impulsive wave motion initiated at response level which is dependent on local model properties. Matching model and measured-structure responses can help in identifying model parameters and infer building properties. To show the effectiveness of this approach, the Millikan Library in Pasadena, California is identified with recordings of the Yorba Linda earthquake of September 3, 2002.

Keywords: system identification, continuous-discrete mass modeling, damage detection, post-earthquake

Procedia PDF Downloads 344

Authors: Alok Shiomurti Tripathi, Ajay Kumar Timiri, Papiya Mitra Mazumder, Anil Chandewar

Abstract:

The present study evaluates the possible drug interaction between glimepiride (GLIM) and sildenafil citrate (SIL) in streptozotocin (STZ) induced in diabetic nephropathic (DN) animals and also postulates the possible mechanism of interaction by molecular modeling studies. Diabetic nephropathy was induced by single dose of STZ (60 mg/kg, ip) and confirms it by assessing the blood and urine biochemical parameters on 28th day of its induction. Selected DN animals were used for the drug interaction between GLIM (0.5mg/kg, p.o.) and SIL (2.5 mg/kg, p.o.) after 29th and 70th day of protocol. Drug interaction were assessed by evaluating the plasma drug concentration using HPLC-UV and also determine the change in the biochemical parameter in blood and urine. Mechanism of the interaction was postulated by molecular modeling study using Maestro module of Schrodinger software. DN was confirmed as there was significant alteration in the blood and urine biochemical parameter in STZ treated groups. The concentration of SIL increased significantly (p<0.001) in rat plasma when co administered with GLIM after 70th day of protocol. Molecular modelling study revealed few important interactions with rat serum albumin and CYP2C9.GLIM has strong hydrophobic interaction with binding site residues of rat serum albumin compared to SIL. Whereas, for CYP2C9, GLIM has strong hydrogen bond with polar contacts and hydrophobic interactions than SIL. Present study concludes that bioavailability of SIL increases when co-administered chronically with GLIM in the management of DN animals and mechanism has been supported by molecular modeling studies.

Keywords: diabetic nephropathy, glimepiride, sildenafil citrate, pharmacokinetics, homology modeling, schrodinger

Procedia PDF Downloads 339

Authors: Nahush Modak, Meena Pangarkar, Anand Pathak, Ankita Tamhane

Abstract:

Background: Breast cancer is the prominent cause of cancer and mortality among women. This study was done to show the statistical analysis of a cohort of over 250 patients detected with breast cancer diagnosed by oncologists using Immunohistochemistry (IHC). IHC was performed by using ER; PR; HER2; Ki-67 antibodies. Materials and methods: Formalin fixed Paraffin embedded tissue samples were obtained by surgical manner and standard protocol was followed for fixation, grossing, tissue processing, embedding, cutting and IHC. The Ventana Benchmark XT machine was used for automated IHC of the samples. Antibodies used were supplied by F. Hoffmann-La Roche Ltd. Statistical analysis was performed by using SPSS for windows. Statistical tests performed were chi-squared test and Correlation tests with p<.01. The raw data was collected and provided by National Cancer Insitute, Jamtha, India. Result: Luminal B was the most prevailing molecular subtype of Breast cancer at our institute. Chi squared test of homogeneity was performed to find equality in distribution and Luminal B was the most prevalent molecular subtype. The worse prognostic indicator for breast cancer depends upon expression of Ki-67 and her2 protein in cancerous cells. Our study was done at p <.01 and significant dependence was observed. There exists no dependence of age on molecular subtype of breast cancer. Similarly, age is an independent variable while considering Ki-67 expression. Chi square test performed on Human epidermal growth factor receptor 2 (HER2) statuses of patients and strong dependence was observed in percentage of Ki-67 expression and Her2 (+/-) character which shows that, value of Ki depends upon Her2 expression in cancerous cells (p<.01). Surprisingly, dependence was observed in case of Ki-67 and Pr, at p <.01. This shows that Progesterone receptor proteins (PR) are over-expressed when there is an elevation in expression of Ki-67 protein. Conclusion: We conclude from that Luminal B is the most prevalent molecular subtype at National Cancer Institute, Jamtha, India. There was found no significant correlation between age and Ki-67 expression in any molecular subtype. And no dependence or correlation exists between patients’ age and molecular subtype. We also found that, when the diagnosis is Luminal A, out of the cohort of 257 patients, no patient shows >14% Ki-67 value. Statistically, extremely significant values were observed for dependence of PR+Her2- and PR-Her2+ scores on Ki-67 expression. (p<.01). Her2 is an important prognostic factor in breast cancer. Chi squared test for Her2 and Ki-67 shows that the expression of Ki depends upon Her2 statuses. Moreover, Ki-67 cannot be used as a standalone prognostic factor for determining breast cancer.

Keywords: breast cancer molecular subtypes , correlation, immunohistochemistry, Ki-67 and HR, statistical analysis

Procedia PDF Downloads 97

Authors: Martin Cermak, Tomas Karasek, Jaroslav Rojicek

Abstract:

The key role in phenomenological modelling of cyclic plasticity is good understanding of stress-strain behaviour of given material. There are many models describing behaviour of materials using numerous parameters and constants. Combination of individual parameters in those material models significantly determines whether observed and predicted results are in compliance. Parameter identification techniques such as random gradient, genetic algorithm, and sensitivity analysis are used for identification of parameters using numerical modelling and simulation. In this paper genetic algorithm and sensitivity analysis are used to study effect of 4 parameters of modified AbdelKarim-Ohno cyclic plasticity model. Results predicted by Finite Element (FE) simulation are compared with experimental data from biaxial ratcheting test with semi-elliptical loading path.

Keywords: genetic algorithm, sensitivity analysis, inverse approach, finite element method, cyclic plasticity, ratcheting

Procedia PDF Downloads 417

Authors: Rizwan H. Khan, Saima Nusrat

Abstract:

Despite the fact that amyloid associated neurodegenerative diseases and non-neuropathic systemic amyloidosis have allured the research endeavors, as no curative drugs have been proclaimed up till now except for symptomatic cure. Therapeutic compounds which can diminish or disaggregate such toxic oligomers and fibrillar species have been examined and more are on its way. In the present study, we had reported an extensive biophysical, microscopic and computational study, revealing that L-3, 4-dihydroxyphenylalanine (L-Dopa) possess undeniable potency to inhibit heat induced human lysozyme (HL) amyloid fibrillation and also retain the fibril disaggregating potential. L-Dopa interferes in the amyloid fibrillogenesis process by interacting hydrophobically and also by forming hydrogen bonds with the amino acid residues found in amyloid fibril forming prone region of HL as elucidated by molecular docking results. L-Dopa also disaggregates the mature amyloid fibrils into some unorganised species. Thus, L-Dopa and related compounds can work as a promising inhibitor for the therapeutic advancement prospective against systemic amyloidosis.

Keywords: amyloids, disaggregation, human lysozyme, molecular docking

Procedia PDF Downloads 297

Authors: Murali Aarthy, Sanjeev Kumar Singh

Abstract:

High risk human papillomaviruses are highly associated with the carcinoma of the cervix and the other genital tumors. Cervical cancer develops through the multistep process in which increasingly severe premalignant dysplastic lesions called cervical intraepithelial neoplastic progress to invasive cancer. The oncoprotein E7 of human papillomavirus expressed in the lower epithelial layers drives the cells into S-phase creating an environment conducive for viral genome replication and cell proliferation. The replication of the virus occurs in the terminally differentiating epithelium and requires the activation of cellular DNA replication proteins. To date, no suitable drug molecule is available to treat HPV infection whereas identification of potential drug targets and development of novel anti-HPV chemotherapies with unique mode of actions are expected. Hence, our present study aimed to identify the potential inhibitors analogous to EGCG, a green tea molecule which is considered to be safe to use for mammalian systems. A 3D similarity search on the natural small molecule library from natural product database using EGCG identified 11 potential hits based on their similarity score. The structure based docking strategies were implemented in the potential hits and the key interacting residues of protein with compounds were identified through simulation studies and binding free energy calculations. The conformational changes between the apoprotein and the complex were analyzed with the simulation and the results demonstrated that the dynamical and structural effects observed in the protein were induced by the compounds and indicated the dominance to the oncoprotein. Overall, our study provides the basis for the structural insights of the identified potential hits and EGCG and hence, the analogous compounds identified can be potent inhibitors against the HPV 16 E7 oncoprotein.

Keywords: EGCG, oncoprotein, molecular dynamics simulation, analogues

Procedia PDF Downloads 98

Authors: Huixia Shi, Can Hu, Jun Zhu, Hongling Guo, Haiyan Li, Hongyan Du

Abstract:

The identification of human body fluids during forensic investigations is a critical step to determine key details, and present strong evidence to testify criminal in a case. With the popularity of DNA and improved detection technology, the potential question must be revolved that whether the suspect’s DNA derived from saliva or semen, menstrual or peripheral blood, how to identify the red substance or aged blood traces on the spot is blood; How to determine who contribute the right one in mixed stains. In recent years, molecular approaches have been developing increasingly on mRNA, miRNA, DNA methylation and microbial markers, but appear expensive, time-consuming, and destructive disadvantages. Physicochemical methods are utilized frequently such us scanning electron microscopy/energy spectroscopy and X-ray fluorescence and so on, but results only showing one or two characteristics of body fluid itself and that out of working in unknown or mixed body fluid stains. This paper focuses on using chemistry methods Raman spectroscopy and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to discriminate species of peripheral blood, menstrual blood, semen, saliva, vaginal secretions, urine or sweat. Firstly, non-destructive, confirmatory, convenient and fast Raman spectroscopy method combined with more accurate matrix-assisted laser desorption/ionization time-of-flight mass spectrometry method can totally distinguish one from other body fluids. Secondly, 11 spectral signatures and specific metabolic molecules have been obtained by analysis results after 70 samples detected. Thirdly, Raman results showed peripheral and menstrual blood, saliva and vaginal have highly similar spectroscopic features. Advanced statistical analysis of the multiple Raman spectra must be requested to classify one to another. On the other hand, it seems that the lactic acid can differentiate peripheral and menstrual blood detected by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, but that is not a specific metabolic molecule, more sensitivity ones will be analyzed in a forward study. These results demonstrate the great potential of the developed chemistry methods for forensic applications, although more work is needed for method validation.

Keywords: body fluids, identification, Raman spectroscopy, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

Procedia PDF Downloads 99

Authors: Aadhya Kaul, Gautam Manocha, Preeti Nagrath

Abstract:

Our environment comprises of a wide variety of plants that are similar to each other and sometimes the similarity between the plants makes the identification process tedious thus increasing the workload of the botanist all over the world. Now all the botanists cannot be accessible all the time for such laborious plant identification; therefore, there is an urge for a quick classification model. Also, along with the identification of the plants, it is also necessary to classify the plant as healthy or not as for a good lifestyle, humans require good food and this food comes from healthy plants. A large number of techniques have been applied to classify the plants as healthy or diseased in order to provide the solution. This paper proposes one such method known as anomaly detection using autoencoders using a set of collections of leaves. In this method, an autoencoder model is built using Keras and then the reconstruction of the original images of the leaves is done and the threshold loss is found in order to classify the plant leaves as healthy or diseased. A dataset of plant leaves is considered to judge the reconstructed performance by convolutional autoencoders and the average accuracy obtained is 71.55% for the purpose.

Keywords: convolutional autoencoder, anomaly detection, web application, FLASK

Procedia PDF Downloads 130

Authors: Ali Al-Ghalib, Fouad Mohammad

Abstract:

The identification of damage in reinforced concrete structures subjected to incremental cracking performance exploiting vibration data is recognized as a challenging topic in the published and heavily cited literature. Therefore, this paper attempts to shine light on the extent of dynamic methods when applied to reinforced concrete beams simulated with various scenarios of defects. For this purpose, three different reinforced concrete beams are tested through the course of the study. The three beams are loaded statically to failure in incremental successive load cycles and later rehabilitated. After each static load stage, the beams are tested under free-free support condition using experimental modal analysis. The beams were all of the same length and cross-sectional area (2.0x0.14x0.09)m, but they were different in concrete compressive strength and the type of damage presented. The experimental modal parameters as damage identification parameters were showed computationally expensive, time consuming and require substantial inputs and considerable expertise. Nonetheless, they were proved plausible for the condition monitoring of the current case study as well as structural changes in the course of progressive loads. It was accentuated that a satisfactory localization and quantification for structural changes (Level 2 and Level 3 of damage identification problem) can only be achieved reasonably through considering frequencies and mode shapes of a system in a proper analytical model. A convenient post analysis process for various datasets of vibration measurements for the three beams is conducted in order to extract, check and correlate the basic modal parameters; namely, natural frequency, modal damping and mode shapes. The results of the extracted modal parameters and their combination are utilized and discussed in this research as quantification parameters.

Keywords: experimental modal analysis, damage identification, structural health monitoring, reinforced concrete beam

Procedia PDF Downloads 235

Authors: Uraib Sharaha, Ahmad Salman, Eladio Rodriguez-Diaz, Elad Shufan, Klaris Riesenberg, Irving J. Bigio, Mahmoud Huleihel

Abstract:

Antimicrobial drugs have played an indispensable role in controlling illness and death associated with infectious diseases in animals and humans. However, the increasing resistance of bacteria to a broad spectrum of commonly used antibiotics has become a global healthcare problem. Many antibiotics had lost their effectiveness since the beginning of the antibiotic era because many bacteria have adapted defenses against these antibiotics. Rapid determination of antimicrobial susceptibility of a clinical isolate is often crucial for the optimal antimicrobial therapy of infected patients and in many cases can save lives. The conventional methods for susceptibility testing require the isolation of the pathogen from a clinical specimen by culturing on the appropriate media (this culturing stage lasts 24 h-first culturing). Then, chosen colonies are grown on media containing antibiotic(s), using micro-diffusion discs (second culturing time is also 24 h) in order to determine its bacterial susceptibility. Other methods, genotyping methods, E-test and automated methods were also developed for testing antimicrobial susceptibility. Most of these methods are expensive and time-consuming. Fourier transform infrared (FTIR) microscopy is rapid, safe, effective and low cost method that was widely and successfully used in different studies for the identification of various biological samples including bacteria; nonetheless, its true potential in routine clinical diagnosis has not yet been established. The new modern infrared (IR) spectrometers with high spectral resolution enable measuring unprecedented biochemical information from cells at the molecular level. Moreover, the development of new bioinformatics analyses combined with IR spectroscopy becomes a powerful technique, which enables the detection of structural changes associated with resistivity. The main goal of this study is to evaluate the potential of the FTIR microscopy in tandem with machine learning algorithms for rapid and reliable identification of bacterial susceptibility to antibiotics in time span of few minutes. The UTI E.coli bacterial samples, which were identified at the species level by MALDI-TOF and examined for their susceptibility by the routine assay (micro-diffusion discs), are obtained from the bacteriology laboratories in Soroka University Medical Center (SUMC). These samples were examined by FTIR microscopy and analyzed by advanced statistical methods. Our results, based on 700 E.coli samples, were promising and showed that by using infrared spectroscopic technique together with multivariate analysis, it is possible to classify the tested bacteria into sensitive and resistant with success rate higher than 90% for eight different antibiotics. Based on these preliminary results, it is worthwhile to continue developing the FTIR microscopy technique as a rapid and reliable method for identification antibiotic susceptibility.

Keywords: antibiotics, E.coli, FTIR, multivariate analysis, susceptibility, UTI

Procedia PDF Downloads 150

Authors: Shokofeh Ebrtahimi

Abstract:

Let G be the chemical graph of a molecule. The matrix D = [dij ] is called the detour matrix of G, if dij is the length of longest path between atoms i and j. The sum of all entries above the main diagonal of D is called the detour index of G.Chemical graph theory is the topology branch of mathematical chemistry which applies graph theory to mathematical modelling of chemical phenomena.[1] The pioneers of the chemical graph theory are Alexandru Balaban, Ante Graovac, Ivan Gutman, Haruo Hosoya, Milan Randić and Nenad TrinajstićLet G be the chemical graph of a molecule. The matrix D = [dij ] is called the detour matrix of G, if dij is the length of longest path between atoms i and j. The sum of all entries above the main diagonal of D is called the detour index of G. In this paper, a new program for computing the detour index of molecular graphs of nanotubes by heptagons is determineded. Some Conjectures about detour index of Molecular graphs of nanotubes is included.

Keywords: chemical graph, detour matrix, Detour index, carbon nanotube

Procedia PDF Downloads 256