Search results for: molecular karyotyping
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2064

Search results for: molecular karyotyping

2064 Microarrays: Wide Clinical Utilities and Advances in Healthcare

Authors: Salma M. Wakil

Abstract:

Advances in the field of genetics overwhelmed detecting large number of inherited disorders at the molecular level and directed to the development of innovative technologies. These innovations have led to gene sequencing, prenatal mutation detection, pre-implantation genetic diagnosis; population based carrier screening and genome wide analyses using microarrays. Microarrays are widely used in establishing clinical and diagnostic setup for genetic anomalies at a massive level, with the advent of cytoscan molecular karyotyping as a clinical utility card for detecting chromosomal aberrations with high coverage across the entire human genome. Unlike a regular karyotype that relies on the microscopic inspection of chromosomes, molecular karyotyping with cytoscan constructs virtual chromosomes based on the copy number analysis of DNA which improves its resolution by 100-fold. We have been investigating a large number of patients with Developmental Delay and Intellectual disability with this platform for establishing micro syndrome deletions and have detected number of novel CNV’s in the Arabian population with the clinical relevance.

Keywords: microarrays, molecular karyotyping, developmental delay, genetics

Procedia PDF Downloads 432
2063 Detection, Analysis and Determination of the Origin of Copy Number Variants (CNVs) in Intellectual Disability/Developmental Delay (ID/DD) Patients and Autistic Spectrum Disorders (ASD) Patients by Molecular and Cytogenetic Methods

Authors: Pavlina Capkova, Josef Srovnal, Vera Becvarova, Marie Trkova, Zuzana Capkova, Andrea Stefekova, Vaclava Curtisova, Alena Santava, Sarka Vejvalkova, Katerina Adamova, Radek Vodicka

Abstract:

ASDs are heterogeneous and complex developmental diseases with a significant genetic background. Recurrent CNVs are known to be a frequent cause of ASD. These CNVs can have, however, a variable expressivity which results in a spectrum of phenotypes from asymptomatic to ID/DD/ASD. ASD is associated with ID in ~75% individuals. Various platforms are used to detect pathogenic mutations in the genome of these patients. The performed study is focused on a determination of the frequency of pathogenic mutations in a group of ASD patients and a group of ID/DD patients using various strategies along with a comparison of their detection rate. The possible role of the origin of these mutations in aetiology of ASD was assessed. The study included 35 individuals with ASD and 68 individuals with ID/DD (64 males and 39 females in total), who underwent rigorous genetic, neurological and psychological examinations. Screening for pathogenic mutations involved karyotyping, screening for FMR1 mutations and for metabolic disorders, a targeted MLPA test with probe mixes Telomeres 3 and 5, Microdeletion 1 and 2, Autism 1, MRX and a chromosomal microarray analysis (CMA) (Illumina or Affymetrix). Chromosomal aberrations were revealed in 7 (1 in the ASD group) individuals by karyotyping. FMR1 mutations were discovered in 3 (1 in the ASD group) individuals. The detection rate of pathogenic mutations in ASD patients with a normal karyotype was 15.15% by MLPA and CMA. The frequencies of the pathogenic mutations were 25.0% by MLPA and 35.0% by CMA in ID/DD patients with a normal karyotype. CNVs inherited from asymptomatic parents were more abundant than de novo changes in ASD patients (11.43% vs. 5.71%) in contrast to the ID/DD group where de novo mutations prevailed over inherited ones (26.47% vs. 16.18%). ASD patients shared more frequently their mutations with their fathers than patients from ID/DD group (8.57% vs. 1.47%). Maternally inherited mutations predominated in the ID/DD group in comparison with the ASD group (14.7% vs. 2.86 %). CNVs of an unknown significance were found in 10 patients by CMA and in 3 patients by MLPA. Although the detection rate is the highest when using CMA, recurrent CNVs can be easily detected by MLPA. CMA proved to be more efficient in the ID/DD group where a larger spectrum of rare pathogenic CNVs was revealed. This study determined that maternally inherited highly penetrant mutations and de novo mutations more often resulted in ID/DD without ASD in patients. The paternally inherited mutations could be, however, a source of the greater variability in the genome of the ASD patients and contribute to the polygenic character of the inheritance of ASD. As the number of the subjects in the group is limited, a larger cohort is needed to confirm this conclusion. Inherited CNVs have a role in aetiology of ASD possibly in combination with additional genetic factors - the mutations elsewhere in the genome. The identification of these interactions constitutes a challenge for the future. Supported by MH CZ – DRO (FNOl, 00098892), IGA UP LF_2016_010, TACR TE02000058 and NPU LO1304.

Keywords: autistic spectrum disorders, copy number variant, chromosomal microarray, intellectual disability, karyotyping, MLPA, multiplex ligation-dependent probe amplification

Procedia PDF Downloads 333
2062 Thick Disc Molecular Gas Fraction in NGC 6946

Authors: Narendra Nath Patra

Abstract:

Several recent studies reinforce the existence of a thick molecular disc in galaxies along with the dynamically cold thin disc. Assuming a two-component molecular disc, we model the disc of NGC 6946 as a four-component system consists of stars, HI, thin disc molecular gas, and thick disc molecular gas in vertical hydrostatic equilibrium. Following, we set up the joint Poisson-Boltzmann equation of hydrostatic equilibrium and solve it numerically to obtain a three-dimensional density distribution of different baryonic components. Using the density solutions and the observed rotation curve, we further build a three-dimensional dynamical model of the molecular disc and consecutively produce simulated CO spectral cube and spectral width profile. We find that the simulated spectral width profiles distinguishably differs for different assumed thick disc molecular gas fraction. Several CO spectral width profiles are then produced for different assumed thick disc molecular gas fractions and compared with the observed one to obtain the best fit thick disc molecular gas fraction profile. We find that the thick disc molecular gas fraction in NGC 6946 largely remains constant across its molecular disc with a mean value of 0.70 +/- 0.09. We also estimate the amount of extra-planar molecular gas in NGC 6946. We find 60% of the total molecular gas is extra-planar at the central region, whereas this fraction reduces to ~ 35% at the edge of the molecular disc. With our method, for the first time, we estimate the thick disc molecular gas fraction as a function of radius in an external galaxy with sub-kpc resolution.

Keywords: galaxies: kinematics and dynamic, galaxies: spiral, galaxies: structure , ISM: molecules, molecular data

Procedia PDF Downloads 121
2061 Molecular Clustering and Velocity Increase in Converging-Diverging Nozzle in Molecular Dynamics Simulation

Authors: Jeoungsu Na, Jaehawn Lee, Changil Hong, Suhee Kim

Abstract:

A molecular dynamics simulation in a converging-diverging nozzle was performed to study molecular collisions and their influence to average flow velocity according to a variety of vacuum levels. The static pressures and the dynamic pressure exerted by the molecule collision on the selected walls were compared to figure out the intensity variances of the directional flows. With pressure differences constant between the entrance and the exit of the nozzle, the numerical experiment was performed for molecular velocities and directional flows. The result shows that the velocities increased at the nozzle exit as the vacuum level gets higher in that area because less molecular collisions.

Keywords: cavitation, molecular collision, nozzle, vacuum, velocity increase

Procedia PDF Downloads 418
2060 Molecular Junctions between Graphene Strips: Electronic and Transport Properties

Authors: Adel Belayadi, Ahmed Mougari, Boualem Bourahla

Abstract:

Molecular junctions are currently considered a promising style in the miniaturization of electronic devices. In this contribution, we provide a tight-binding model to investigate the quantum transport properties across-molecular junctions sandwiched between 2D-graphene nanoribbons in the zigzag direction. We investigate, in particular, the effect of embedded atoms such as Gold and Silicon across the molecular junction. The results exhibit a resonance behavior in terms of incident Fermi levels, depending on the molecular junction type. Additionally, the transport properties under a perpendicular magnetic field exhibit an oscillation for the transmittance versus the magnetic field strength.

Keywords: molecular junction, 2D-graphene nanoribbons, quantum transport properties, magnetic field

Procedia PDF Downloads 81
2059 Molecular Docking Assessment of Pesticides Binding to Bacterial Chitinases

Authors: Diana Larisa Vladoiu, Vasile Ostafe, Adriana Isvoran

Abstract:

Molecular docking calculations reveal that pesticides provide favorable interactions with the bacterial chitinases. Pesticides interact with both hydrophilic and aromatic residues involved in the active site of the enzymes, their positions partially overlapping the substrate and the inhibitors locations. Molecular docking outcomes, in correlation with experimental literature data, suggest that the pesticides may be degraded or having an inhibitor effect on the activity of these enzymes, depending of the application dose and rate.

Keywords: chitinases, inhibition, molecular docking, pesticides

Procedia PDF Downloads 530
2058 Effect of Plasticizer Additives on the Mechanical Properties of Cement Composite: A Molecular Dynamics Analysis

Authors: R. Mohan, V. Jadhav, A. Ahmed, J. Rivas, A. Kelkar

Abstract:

Cementitious materials are an excellent example of a composite material with complex hierarchical features and random features that range from nanometer (nm) to millimeter (mm) scale. Multi-scale modeling of complex material systems requires starting from fundamental building blocks to capture the scale relevant features through associated computational models. In this paper, molecular dynamics (MD) modeling is employed to predict the effect of plasticizer additive on the mechanical properties of key hydrated cement constituent calcium-silicate-hydrate (CSH) at the molecular, nanometer scale level. Due to complexity, still unknown molecular configuration of CSH, a representative configuration widely accepted in the field of mineral Jennite is employed. The effectiveness of the Molecular Dynamics modeling to understand the predictive influence of material chemistry changes based on molecular/nanoscale models is demonstrated.

Keywords: cement composite, mechanical properties, molecular dynamics, plasticizer additives

Procedia PDF Downloads 432
2057 Application of Molecular Markers for Crop Improvement

Authors: Monisha Isaac

Abstract:

Use of molecular markers for selecting plants with desired traits has been started long back. Due to their heritable characteristics, they are useful for identification and characterization of specific genotypes. The study involves various types of molecular markers used to select multiple desired characters in plants, their properties, and advantages to improve crop productivity in adverse climatological conditions for the purpose of providing food security to fast-growing global population. The study shows that genetic similarities obtained from molecular markers provide more accurate information and the genetic diversity can be better estimated from the genetic relationship obtained from the dendrogram. The information obtained from markers assisted characterization is more suitable for the crops of economic importance like sugarcane.

Keywords: molecular markers, crop productivity, genetic diversity, genotype

Procedia PDF Downloads 490
2056 Environmental /Occupational Factors and Seasonality of Birth- Male Infertility

Authors: C. Lalitha, R. Sayee, D. Apoorva

Abstract:

Reproductive failure or infertility may be due to several factors that are not limited to one sex. It remains a common problem causing significant psychological distress to those affected individuals and who are increasingly seeking medical advice. Male infertility means inability to induce conception in normal woman within a year. The etiological factors associated with male infertility are anatomical, developmental, seminal, hormonal, immunological and environmental factors. The paper was aimed to highlight the environmental factors and its association to male infertility and seasonality of birth and its influence. The data was collected from the 75 male patients referred with infertility for karyotyping and counseling. Their age ranged from 21 to 45 years. It is opined that certain occupations are preferentially associated with male infertility.

Keywords: environmental, occupational, seasonal, male infertility

Procedia PDF Downloads 251
2055 Topological Analysis of Hydrogen Bonds in Pyruvic Acid-Water Mixtures

Authors: Ferid Hammami

Abstract:

The molecular geometries of the possible conformations of pyruvic acid-water complexes (PA-(H₂O)ₙ = 1- 4) have been fully optimized at DFT/B3LYP/6-311G ++ (d, p) levels of calculation. Among several optimized molecular clusters, the most stable molecular arrangements obtained when one, two, three, and four water molecules are hydrogen-bonded to a central pyruvic acid molecule are presented in this paper. Apposite topological and geometrical parameters are considered as primary indicators of H-bond strength. Atoms in molecules (AIM) analysis shows that pyruvic acid can form a ring structure with water, and the molecular structures are stabilized by both strong O-H...O and C-H...O hydrogen bonds. In large clusters, classical O-H...O hydrogen bonds still exist between water molecules, and a cage-like structure is built around some parts of the central molecule of pyruvic acid. The electrostatic potential energy map (MEP) and the HOMO-LUMO molecular orbital (highest occupied molecular orbital-lowest unoccupied molecular orbital) analysis has been performed for all considered complexes.

Keywords: pyruvic acid, PA-water complex, hydrogen bonding, DFT, AIM, MEP, HOMO-LUMO

Procedia PDF Downloads 194
2054 Characterization on Molecular Weight of Polyamic Acids Using GPC Coupled with Multiple Detectors

Authors: Mei Hong, Wei Liu, Xuemin Dai, Yanxiong Pan, Xiangling Ji

Abstract:

Polyamic acid (PAA) is the precursor of polyimide (PI) prepared by a two-step method, its molecular weight and molecular weight distribution not only play an important role during the preparation and processing, but also influence the final performance of PI. However, precise characterization on molecular weight of PAA is still a challenge because of the existence of very complicated interactions in the solution system, including the electrostatic interaction, hydrogen bond interaction, dipole-dipole interaction, etc. Thus, it is necessary to establisha suitable strategy which can completely suppress these complex effects and get reasonable data on molecular weight. Herein, the gel permeation chromatography (GPC) coupled with differential refractive index (RI) and multi-angle laser light scattering (MALLS) detectors were applied to measure the molecular weight of (6FDA-DMB) PAA using different mobile phases, LiBr/DMF, LiBr/H3PO4/THF/DMF, LiBr/HAc/THF/DMF, and LiBr/HAc/DMF, respectively. It was found that combination of LiBr with HAc can shield the above-mentioned complex interactions and is more conducive to the separation of PAA than only addition of LiBr in DMF. LiBr/HAc/DMF was employed for the first time as a mild mobile phase to effectively separate PAA and determine its molecular weight. After a series of conditional experiments, 0.02M LiBr/0.2M HAc/DMF was fixed as an optimized mobile phase to measure the relative and absolute molecular weights of (6FDA-DMB) PAA prepared, and the obtained Mw from GPC-MALLS and GPC-RI were 35,300 g/mol and 125,000 g/mol, respectively. Particularly, such a mobile phase is also applicable to other PAA samples with different structures, and the final results on molecular weight are also reproducible.

Keywords: Polyamic acids, Polyelectrolyte effects, Gel permeation chromatography, Mobile phase, Molecular weight

Procedia PDF Downloads 35
2053 Molecular Modeling of 17-Picolyl and 17-Picolinylidene Androstane Derivatives with Anticancer Activity

Authors: Sanja Podunavac-Kuzmanović, Strahinja Kovačević, Lidija Jevrić, Evgenija Djurendić, Jovana Ajduković

Abstract:

In the present study, the molecular modeling of a series of 24 17-picolyl and 17-picolinylidene androstane derivatives whit significant anticancer activity was carried out. Modelling of studied compounds was performed by CS ChemBioDraw Ultra v12.0 program for drawing 2D molecular structures and CS ChemBio3D Ultra v12.0 for 3D molecular modelling. The obtained 3D structures were subjected to energy minimization using molecular mechanics force field method (MM2). The cutoff for structure optimization was set at a gradient of 0.1 kcal/Åmol. Full geometry optimization was done by the Austin Model 1 (AM1) until the root mean square (RMS) gradient reached a value smaller than 0.0001 kcal/Åmol using Molecular Orbital Package (MOPAC) program. The obtained physicochemical, lipophilicity and topological descriptors were used for analysis of molecular similarities and dissimilarities applying suitable chemometric methods (principal component analysis and cluster analysis). These results are the part of the project No. 114-451-347/2015-02, financially supported by the Provincial Secretariat for Science and Technological Development of Vojvodina and CMST COST Action CM1306.

Keywords: androstane derivatives, anticancer activity, chemometrics, molecular descriptors

Procedia PDF Downloads 338
2052 An Insight into the Conformational Dynamics of Glycan through Molecular Dynamics Simulation

Authors: K. Veluraja

Abstract:

Glycan of glycolipids and glycoproteins is playing a significant role in living systems particularly in molecular recognition processes. Molecular recognition processes are attributed to their occurrence on the surface of the cell, sequential arrangement and type of sugar molecules present in the oligosaccharide structure and glyosidic linkage diversity (glycoinformatics) and conformational diversity (glycoconformatics). Molecular Dynamics Simulation study is a theoretical-cum-computational tool successfully utilized to establish glycoconformatics of glycan. The study on various oligosaccharides of glycan clearly indicates that oligosaccharides do exist in multiple conformational states and these conformational states arise due to the flexibility associated with a glycosidic torsional angle (φ,ψ) . As an example: a single disaccharide structure NeuNacα(2-3) Gal exists in three different conformational states due to the differences in the preferential value of glycosidic torsional angles (φ,ψ). Hence establishing three dimensional structural and conformational models for glycan (cartesian coordinates of every individual atoms of an oligosaccharide structure in a preferred conformation) is quite crucial to understand various molecular recognition processes such as glycan-toxin interaction and glycan-virus interaction. The gycoconformatics models obtained for various glycan through Molecular Dynamics Simulation stored in our 3DSDSCAR (3DSDSCAR.ORG) a public domain database and its utility value in understanding the molecular recognition processes and in drug design venture will be discussed.

Keywords: glycan, glycoconformatics, molecular dynamics simulation, oligosaccharide

Procedia PDF Downloads 118
2051 Computing Some Topological Descriptors of Single-Walled Carbon Nanotubes

Authors: Amir Bahrami

Abstract:

In the fields of chemical graph theory, molecular topology, and mathematical chemistry, a topological index or a descriptor index also known as a connectivity index is a type of a molecular descriptor that is calculated based on the molecular graph of a chemical compound. Topological indices are numerical parameters of a graph which characterize its topology and are usually graph invariant. Topological indices are used for example in the development of quantitative structure-activity relationships (QSARs) in which the biological activity or other properties of molecules are correlated with their chemical structure. In this paper some descriptor index (descriptor index) of single-walled carbon nanotubes, is determined.

Keywords: chemical graph theory, molecular topology, molecular descriptor, single-walled carbon nanotubes

Procedia PDF Downloads 312
2050 A Report of 5-Months-Old Baby with Balanced Chromosomal Rearrangements along with Phenotypic Abnormalities

Authors: Mohit Kumar, Beklashwar Salona, Shiv Murti, Mukesh Singh

Abstract:

We report here a case of five-months old male baby, born as second child of non-consanguineous parents with no considerable history of genetic abnormality which was referred to our cytogenetic laboratory for chromosomal analysis. Physical dysmorphic facial features including mongoloid face, cleft palate, simian crease, and developmental delay were observed. We present this case with unique balanced autosomal translocation of t(3;10)(p21;p13). The risk of phenotypic abnormalities based on de novo balanced translocation was estimated to be 7%. The association of balanced chromosomal rearrangement with Down syndrome features such as multiple congenital anomalies, facial dysmorphism and congenital heart anomalies are very rare in a 5-months old male child. Trisomy-21 is not uncommon in chromosomal abnormality with the birth defect and balanced translocations are frequently observed in patients with secondary infertility or recurrent spontaneous abortion (RSA). Two ml heparinized peripheral blood cells cultured in RPMI-1640 for 72 hours supplemented with 20% fetal bovine serum, phytohemagglutinin (PHA), and antibiotics were used for chromosomal analysis. A total 30 metaphases images were captured using Olympus-BX51 microscope and analyzed using Bio-view karyotyping software through GTG-banding (G bands by trypsin and Giemsa) according to International System for Human Cytogenetic Nomenclature 2016. The results showed balanced translocation between short arm of chromosome # 3 and short arm of chromosome # 10. The karyotype of the child was found to be 46,XY,t(3;10)(p21; p13). Chromosomal abnormalities are one of the major causes of birth defect in new born babies. Also, balanced translocations are frequently observed in patients with secondary infertility or recurrent spontaneous abortion. The index case presented with dysmorphic facial features and had a balanced translocation 46,XY,t(3;10)(p21;p13). This translocation with break points at (p21; p13) has not been reported in the literature in a child with facial dysmorphism. To the best of our knowledge, this is the first report of novel balanced translocation t(3;10) with break points in a child with dysmorphic features. We found balanced chromosomal translocation instead of any trisomy or unbalanced aberrations along with some phenotypic abnormalities. Therefore, we suggest that such novel balanced translocation with abnormal phenotype should be reported in order to enable the pathologist, pediatrician, and gynecologist to have a better insight into the intricacies of chromosomal abnormalities and their associated phenotypic features. We hypothesized that dysmorphic features as seen in this case may be the result of change in the pattern of genes located at the breakpoint area in balanced translocations or may be due to deletion or mutation of genes located on the p-arm of chromosome # 3 and p-arm of chromosome # 10.

Keywords: balanced translocation, karyotyping, phenotypic abnormalities, facial dimorphisms

Procedia PDF Downloads 193
2049 Efficacy of Preimplantation Genetic Screening in Women with a Spontaneous Abortion History with Eukaryotic or Aneuploidy Abortus

Authors: Jayeon Kim, Eunjung Yu, Taeki Yoon

Abstract:

Most spontaneous miscarriage is believed to be a consequence of embryo aneuploidies. Transferring eukaryotic embryos selected by PGS is expected to decrease the miscarriage rate. Current PGS indications include advanced maternal age, recurrent pregnancy loss, repeated implantation failure. Recently, use of PGS for healthy women without above indications for the purpose of improving in vitro fertilization (IVF) outcomes is on the rise. However, it is still controversy about the beneficial effect of PGS in this population, especially, in women with a history of no more than 2 miscarriages or miscarriage of eukaryotic abortus. This study aimed to investigate if karyotyping result of abortus is a good indicator of preimplantation genetic screening (PGS) in subsequent IVF cycle in women with a history of spontaneous abortion. A single-center retrospective cohort study was performed. Women who had spontaneous abortion(s) (less than 3) and dilatation and evacuation, and subsequent IVF from January 2016 to November 2016 were included. Their medical information was extracted from the charts. Clinical pregnancy was defined as presence of a gestational sac with fetal heart beat detected on ultrasound in week 7. Statistical analysis was performed using SPSS software. Total 234 women were included. 121 out of 234 (51.7%) underwent karyotyping of the abortus, and 113 did not have the abortus karyotyped. Embryo biopsy was performed on 3 or 5 days after oocyte retrieval, followed by embryo transfer (ET) on a fresh or frozen cycle. The biopsied materials were subjected to microarray comparative genomic hybridization. Clinical pregnancy rate per ET was compared between PGS and non-PGS group in each study group. Patients were grouped by two criteria: karyotype of the abortus from previous miscarriage (unknown fetal karyotype (n=89, Group 1), eukaryotic abortus (n=36, Group 2) or aneuploidy abortus (n=67, Group 3)), and pursuing PGS in subsequent IVF cycle (pursuing PGS (PGS group, n=105) or not pursuing PGS (non-PGS group, n=87)). The PGS group was significantly older and had higher number of retrieved oocytes and prior miscarriages compared to non-PGS group. There were no differences in BMI and AMH level between those two groups. In PGS group, the mean number of transferable embryos (eukaryotic embryo) was 1.3 ± 0.7, 1.5 ± 0.5 and 1.4 ± 0.5, respectively (p = 0.049). In 42 cases, ET was cancelled because all embryos biopsied turned out to be abnormal. In all three groups (group 1, 2, and 3), clinical pregnancy rates were not statistically different between PGS and non-PGS group (Group 1: 48.8% vs. 52.2% (p=0.858), Group 2: 70% vs. 73.1% (p=0.730), Group 3: 42.3% vs. 46.7% (p=0.640), in PGS and non-PGS group, respectively). In both groups who had miscarriage with eukaryotic and aneuploidy abortus, the clinical pregnancy rate between IVF cycles with and without PGS was not different. When we compare miscarriage and ongoing pregnancy rate, there were no significant differences between PGS and non-PGS group in all three groups. Our results show that the routine application of PGS in women who had less than 3 miscarriages would not be beneficial, even in cases that previous miscarriage had been caused by fetal aneuploidy.

Keywords: preimplantation genetic diagnosis, miscarriage, kpryotyping, in vitro fertilization

Procedia PDF Downloads 161
2048 Rheological and Self-Healing Properties of Poly (Vinyl Butyral)

Authors: Sunatda Arayachukiat, Shogo Nobukawa, Masayuki Yamaguchi

Abstract:

A new self-healing material was developed utilizing molecular entanglements for poly(vinyl butyral) (PVB) containing plasticizers. It was found that PVB shows autonomic self-healing behavior even below the glass transition temperature Tg because of marked molecular motion at surface. Moreover, the plasticizer addition enhances the chain mobility, leading to good healing behavior.

Keywords: Poly(vinyl butyral) (PVB), rheological properties, self-healing behaviour, molecular diffusion

Procedia PDF Downloads 412
2047 Study of Demographic, Hematological Profile and Risk Stratification in Chronic Myeloid Leukemia Patients

Authors: Rajandeep Kaur, Rajeev Gupta

Abstract:

Background: Chronic myeloid leukemia (CML) is the most common leukaemia in India. The annual incidence of chronic myeloid leukemia in India was originally reported to be 0.8 to 2.2 per 1,00,000 population. CML is a clonal disorder that is usually easily diagnosed because the leukemic cells of more than 95% of patients have a distinctive cytogenetic abnormality, the Philadelphia chromosome (Ph1). The approval of tyrosine kinase inhibitors (TKIs), which target BCR-ABL1 kinase activity, has significantly reduced the mortality rate associated with chronic myeloid leukemia (CML) and revolutionized treatment. Material and Methods: 80 diagnosed cases of CML were taken. Investigations were done. Bone marrow and molecular studies were also done and with EUTOS, patients were stratified into low and high-risk groups and then treatment with Imatinib was given to all patients and the molecular response was evaluated at 6 months and 12 months follow up with BCR-ABL by RT-PCR quantitative assay. Results: In the study population, out of 80 patients in the study population, 40 were females and 40 were males, with M: F is 1:1. Out of total 80 patients’ maximum patients (54) were in 31-60 years age group. Our study showed a most common symptom of presentation is abdominal discomfort followed by fever. Out of the total 80 patients, 25 (31.3%) patients had high EUTOS scores and 55 (68.8%) patients had low EUTOS scores. On 6 months follow up 36.3% of patients had Complete Molecular Response, 16.3% of patients had Major Molecular Response and 47.5% of patients had No Molecular Response but on 12 months follow up 71.3% of patients had Complete Molecular Response, 16.25% of patients had Major Molecular Response and 12.5% patients had No Molecular Response. Conclusion: In this study, we found a significant correlation between EUTOS score and Molecular response at 6 months and 12 months follow up after Imatinib therapy.

Keywords: chronic myeloid leukemia, European treatment and outcome study score, hematological response, molecular response, tyrosine kinase inhibitor

Procedia PDF Downloads 86
2046 Utilizing Quantum Chemistry for Nanotechnology: Electron and Spin Movement in Molecular Devices

Authors: Mahsa Fathollahzadeh

Abstract:

The quick advancement of nanotechnology necessitates the creation of innovative theoretical approaches to elucidate complex experimental findings and forecast novel capabilities of nanodevices. Therefore, over the past ten years, a difficult task in quantum chemistry has been comprehending electron and spin transport in molecular devices. This thorough evaluation presents a comprehensive overview of current research and its status in the field of molecular electronics, emphasizing the theoretical applications to various device types and including a brief introduction to theoretical methods and their practical implementation plan. The subject matter includes a variety of molecular mechanisms like molecular cables, diodes, transistors, electrical and visual switches, nano detectors, magnetic valve gadgets, inverse electrical resistance gadgets, and electron tunneling exploration. The text discusses both the constraints of the method presented and the potential strategies to address them, with a total of 183 references.

Keywords: chemistry, nanotechnology, quantum, molecule, spin

Procedia PDF Downloads 22
2045 Quantitative Structure-Property Relationship Study of Base Dissociation Constants of Some Benzimidazoles

Authors: Sanja O. Podunavac-Kuzmanović, Lidija R. Jevrić, Strahinja Z. Kovačević

Abstract:

Benzimidazoles are a group of compounds with significant antibacterial, antifungal and anticancer activity. The studied compounds consist of the main benzimidazole structure with different combinations of substituens. This study is based on the two-dimensional and three-dimensional molecular modeling and calculation of molecular descriptors (physicochemical and lipophilicity descriptors) of structurally diverse benzimidazoles. Molecular modeling was carried out by using ChemBio3D Ultra version 14.0 software. The obtained 3D models were subjected to energy minimization using molecular mechanics force field method (MM2). The cutoff for structure optimization was set at a gradient of 0.1 kcal/Åmol. The obtained set of molecular descriptors was used in principal component analysis (PCA) of possible similarities and dissimilarities among the studied derivatives. After the molecular modeling, the quantitative structure-property relationship (QSPR) analysis was applied in order to get the mathematical models which can be used in prediction of pKb values of structurally similar benzimidazoles. The obtained models are based on statistically valid multiple linear regression (MLR) equations. The calculated cross-validation parameters indicate the high prediction ability of the established QSPR models. This study is financially supported by COST action CM1306 and the project No. 114-451-347/2015-02, financially supported by the Provincial Secretariat for Science and Technological Development of Vojvodina.

Keywords: benzimidazoles, chemometrics, molecular modeling, molecular descriptors, QSPR

Procedia PDF Downloads 268
2044 Accelerated Molecular Simulation: A Convolution Approach

Authors: Jannes Quer, Amir Niknejad, Marcus Weber

Abstract:

Computational Drug Design is often based on Molecular Dynamics simulations of molecular systems. Molecular Dynamics can be used to simulate, e.g., the binding and unbinding event of a small drug-like molecule with regard to the active site of an enzyme or a receptor. However, the time-scale of the overall binding event is many orders of magnitude longer than the time-scale of simulation. Thus, there is a need to speed-up molecular simulations. In order to speed up simulations, the molecular dynamics trajectories have to be ”steared” out of local minimizers of the potential energy surface – the so-called metastabilities – of the molecular system. Increasing the kinetic energy (temperature) is one possibility to accelerate simulated processes. However, with temperature the entropy of the molecular system increases, too. But this kind ”stearing” is not directed enough to stear the molecule out of the minimum toward the saddle point. In this article, we give a new mathematical idea, how a potential energy surface can be changed in such a way, that entropy is kept under control while the trajectories are still steared out of the metastabilities. In order to compute the unsteared transition behaviour based on a steared simulation, we propose to use extrapolation methods. In the end we mathematically show, that our method accelerates the simulations along the direction, in which the curvature of the potential energy surface changes the most, i.e., from local minimizers towards saddle points.

Keywords: extrapolation, Eyring-Kramers, metastability, multilevel sampling

Procedia PDF Downloads 309
2043 Molecular Communication Noise Effect Analysis of Diffusion-Based Channel for Considering Minimum-Shift Keying and Molecular Shift Keying Modulations

Authors: A. Azari, S. S. K. Seyyedi

Abstract:

One of the unaddressed and open challenges in the nano-networking is the characteristics of noise. The previous analysis, however, has concentrated on end-to-end communication model with no separate modelings for propagation channel and noise. By considering a separate signal propagation and noise model, the design and implementation of an optimum receiver will be much easier. In this paper, we justify consideration of a separate additive Gaussian noise model of a nano-communication system based on the molecular communication channel for which are applicable for MSK and MOSK modulation schemes. The presented noise analysis is based on the Brownian motion process, and advection molecular statistics, where the received random signal has a probability density function whose mean is equal to the mean number of the received molecules. Finally, the justification of received signal magnitude being uncorrelated with additive non-stationary white noise is provided.

Keywords: molecular, noise, diffusion, channel

Procedia PDF Downloads 260
2042 Biological Evaluation and Molecular Modeling Study of Thiosemicarbazide Derivatives as Bacterial Type IIA Topoisomerases Inhibitors

Authors: Paweł Stączek, Tomasz Plech, Aleksandra Strzelczyk, Katarzyna Dzitko, Monika Wujec, Edyta Kuśmierz, Piotr Paneth, Agata Paneth

Abstract:

In this contribution, we will describe the inhibitory potency of nine thiosemicarbazide derivatives against bacterial type IIA topoisomerases, their antibacterial profile, and molecular modeling evaluation. We have found that one of the tested compounds, 4-benzoyl-1-(2-methyl-furan-3-ylcarbonyl) thiosemicarbazide, remarkably inhibits the activity of S. aureus DNA gyrase with the IC50 below 5 μM. Besides, this compound displays antibacterial activity on Staphylococcus spp. and E. faecalis at non-cytotoxic concentrations in mammalian cells, with minimal inhibitory concentrations (MICs) values at 25 μg/mL. Based on the enzymatic and molecular modeling studies we propose two factors, i.e. geometry of molecule and hydrophobic/hydrophilic balance as important molecular properties for developing thiosemicarbazide derivatives as potent Staphylococcus aureus DNA gyrase inhibitors.

Keywords: bioactivity, drug design, topoisomerase, molecular modeling

Procedia PDF Downloads 545
2041 Coarse-Grained Molecular Simulations to Estimate Thermophysical Properties of Phase Equilibria

Authors: Hai Hoang, Thanh Xuan Nguyen Thi, Guillaume Galliero

Abstract:

Coarse-Grained (CG) molecular simulations have shown to be an efficient way to estimate thermophysical (static and dynamic) properties of fluids. Several strategies have been developed and reported in the literature for defining CG molecular models. Among them, those based on a top-down strategy (i.e. CG molecular models related to macroscopic observables), despite being heuristic, have increasingly gained attention. This is probably due to its simplicity in implementation and its ability to provide reasonable results for not only simple but also complex systems. Regarding simple Force-Fields associated with these CG molecular models, it has been found that the four parameters Mie chain model is one of the best compromises to describe thermophysical static properties (e.g. phase diagram, saturation pressure). However, parameterization procedures of these Mie-chain GC molecular models given in literature are generally insufficient to simultaneously provide static and dynamic (e.g. viscosity) properties. To deal with such situations, we have extended the corresponding states by using a quantity associated with the liquid viscosity. Results obtained from molecular simulations have shown that our approach is able to yield good estimates for both static and dynamic thermophysical properties for various real non-associating fluids. In addition, we will show that on simple (e.g. phase diagram, saturation pressure) and complex (e.g. thermodynamic response functions, thermodynamic energy potentials) static properties, results of our scheme generally provides improved results compared to existing approaches.

Keywords: coarse-grained model, mie potential, molecular simulations, thermophysical properties, phase equilibria

Procedia PDF Downloads 320
2040 Molecular Electrostatic Potential in Z-3N(2-Ethoxyphenyl), 2-N'(2-Ethoxyphenyl) Imino Thiazolidin-4-one Molecule by Ab Initio and DFT Methods

Authors: Manel Boulakoud, Abdelkader Chouaih, Fodil Hamzaoui

Abstract:

In the present work we are interested in the determination of the Molecular electrostatic potential (MEP) in Z-3N(2-Ethoxyphenyl), 2-N’(2-Ethoxyphenyl) imino thiazolidin-4-one molecule by ab initio and Density Functional Theory (DFT) in the ground state. The MEP is related to the electronic density and is a very useful descriptor in understanding sites for electrophilic attack and nucleophilic reactions as well as hydrogen bonding interactions. First, geometry optimization was carried out using Hartree–Fock (HF) and DFT methods with 6-311G(d,p) basis set. In order to get more information on the molecule, its stability has been analyzed by natural bond orbital (NBO) analysis. Mulliken population analyses have been calculated. Finally, the molecular electrostatic potential (MEP) and HOMO-LUMO energy levels have been performed. The calculated HOMO and LUMO energies show also the charge transfer within the molecule. The energy gap obtained is about 4 eV which explain the stability of the studied compound. The obtained molecular electrostatic potential from the two methods confirms the nature of the electron charge transfer at the molecular shell and locate the electropositive part and the electronegative part in molecular scale of the title compound.

Keywords: DFT, ab initio, HOMO-LUMO, organic compounds

Procedia PDF Downloads 516
2039 Identifying Network Subgraph-Associated Essential Genes in Molecular Networks

Authors: Efendi Zaenudin, Chien-Hung Huang, Ka-Lok Ng

Abstract:

Essential genes play an important role in the survival of an organism. It has been shown that cancer-associated essential genes are genes necessary for cancer cell proliferation, where these genes are potential therapeutic targets. Also, it was demonstrated that mutations of the cancer-associated essential genes give rise to the resistance of immunotherapy for patients with tumors. In the present study, we focus on studying the biological effects of the essential genes from a network perspective. We hypothesize that one can analyze a biological molecular network by decomposing it into both three-node and four-node digraphs (subgraphs). These network subgraphs encode the regulatory interaction information among the network’s genetic elements. In this study, the frequency of occurrence of the subgraph-associated essential genes in a molecular network was quantified by using the statistical parameter, odds ratio. Biological effects of subgraph-associated essential genes are discussed. In summary, the subgraph approach provides a systematic method for analyzing molecular networks and it can capture useful biological information for biomedical research.

Keywords: biological molecular networks, essential genes, graph theory, network subgraphs

Procedia PDF Downloads 136
2038 X-Ray and DFT Electrostatics Parameters Determination of a Coumarin Derivative Compound C17H13NO3

Authors: Y. Megrous, A. Chouaih, F. Hamzaoui

Abstract:

The crystal structure of 4-Methyl-7-(salicylideneamino)coumarin C17H13NO3has been determined using X-ray diffraction to establish the configuration and stereochemistry of the molecule. This crystal is characterized by its nolinear activity. The molecular electron charge density distribution of the title compound is described accurately using the multipolar model of Hansen and Coppens. The net atomic charge and the molecular dipole moment in-crystal have been determined in order to understand the nature of inter-and intramolecular charge transfer. The study present the thermal motion and the structural analysis obtained from the least-square refinement on F2,this study has also allowed us to determine the electrostatic potential and therefore locate the electropositive part and the electronegative part in molecular scale of the title compound.

Keywords: electron charge density, net atomic charge, molecular dipole moment, X-ray diffraction

Procedia PDF Downloads 440
2037 The Study on Mechanical Properties of Graphene Using Molecular Mechanics

Authors: I-Ling Chang, Jer-An Chen

Abstract:

The elastic properties and fracture of two-dimensional graphene were calculated purely from the atomic bonding (stretching and bending) based on molecular mechanics method. Considering the representative unit cell of graphene under various loading conditions, the deformations of carbon bonds and the variations of the interlayer distance could be realized numerically under the geometry constraints and minimum energy assumption. In elastic region, it was found that graphene was in-plane isotropic. Meanwhile, the in-plane deformation of the representative unit cell is not uniform along armchair direction due to the discrete and non-uniform distributions of the atoms. The fracture of graphene could be predicted using fracture criteria based on the critical bond length, over which the bond would break. It was noticed that the fracture behavior were directional dependent, which was consistent with molecular dynamics simulation results.

Keywords: energy minimization, fracture, graphene, molecular mechanics

Procedia PDF Downloads 383
2036 The Extension of Monomeric Computational Results to Polymeric Measurable Properties: An Introductory Computational Chemistry Experiment

Authors: Jing Zhao, Yongqing Bai, Qiaofang Shi, Huaihao Zhang

Abstract:

Advances in software technology enable computational chemistry to be commonly applied in various research fields, especially in pedagogy. Thus, in order to expand and improve experimental instructions of computational chemistry for undergraduates, we designed an introductory experiment—research on acrylamide molecular structure and physicochemical properties. Initially, students construct molecular models of acrylamide and polyacrylamide in Gaussian and Materials Studio software respectively. Then, the infrared spectral data, atomic charge and molecular orbitals of acrylamide as well as solvation effect of polyacrylamide are calculated to predict their physicochemical performance. At last, rheological experiments are used to validate these predictions. Through the combination of molecular simulation (performed on Gaussian, Materials Studio) with experimental verification (rheology experiment), learners have deeply comprehended the chemical nature of acrylamide and polyacrylamide, achieving good learning outcomes.

Keywords: upper-division undergraduate, computer-based learning, laboratory instruction, molecular modeling

Procedia PDF Downloads 123
2035 Molecular Interactions Driving RNA Binding to hnRNPA1 Implicated in Neurodegeneration

Authors: Sakina Fatima, Joseph-Patrick W. E. Clarke, Patricia A. Thibault, Subha Kalyaanamoorthy, Michael Levin, Aravindhan Ganesan

Abstract:

Heteronuclear ribonucleoprotein (hnRNPA1 or A1) is associated with the pathology of different diseases, including neurological disorders and cancers. In particular, the aggregation and dysfunction of A1 have been identified as a critical driver for neurodegeneration (NDG) in Multiple Sclerosis (MS). Structurally, A1 includes a low-complexity domain (LCD) and two RNA-recognition motifs (RRMs), and their interdomain coordination may play a crucial role in A1 aggregation. Previous studies propose that RNA-inhibitors or nucleoside analogs that bind to RRMs can potentially prevent A1 self-association. Therefore, molecular-level understanding of the structures, dynamics, and nucleotide interactions with A1 RRMs can be useful for developing therapeutics for NDG in MS. In this work, a combination of computational modelling and biochemical experiments were employed to analyze a set of RNA-A1 RRM complexes. Initially, the atomistic models of RNA-RRM complexes were constructed by modifying known crystal structures (e.g., PDBs: 4YOE and 5MPG), and through molecular docking calculations. The complexes were optimized using molecular dynamics simulations (200-400 ns), and their binding free energies were computed. The binding affinities of the selected complexes were validated using a thermal shift assay. Further, the most important molecular interactions that contributed to the overall stability of the RNA-A1 RRM complexes were deduced. The results highlight that adenine and guanine are the most suitable nucleotides for high-affinity binding with A1. These insights will be useful in the rational design of nucleotide-analogs for targeting A1 RRMs.

Keywords: hnRNPA1, molecular docking, molecular dynamics, RNA-binding proteins

Procedia PDF Downloads 98