In this study, we model avascular tumour growth in epithelial tissue. This can help us to understand that how an avascular tumour interacts with its microenvironment and what type of physical changes ...can be observed within the tumour spheroid before angiogenesis. This understanding is likely to assist in the development of better diagnostics, improved therapies, and prognostics. In biological systems, most of the diffusive processes are through cellular membranes which are porous in nature. Due to its porous nature, diffusion in biological systems are heterogeneous. The fractional diffusion equation is well suited to model heterogeneous biological systems, though most of the early studies did not use this fact. They described tumour growth with simple diffusion-based model. We have developed a spherical model based on simple diffusion initially, and then the model is upgraded with fractional diffusion equations to express the anomalous nature of biological system. In this study, two types of fractional models are developed: one of fixed order and the other of variable order. The memory formalism technique is also included in these anomalous diffusion models. These three models are investigated from phenomenological point view by measuring some parameters for characterizing avascular tumour growth over time. Tumour microenvironment is very complex in nature due to several concurrent molecular mechanisms. Diffusion with memory (fixed as well as variable) formation may be an oversimplified technique, and does not reflect the detailed view of the tumour microenvironment. However, it is found that all the models offer realistic and insightful information of the tumour microenvironment at the macroscopic level, and approximate well the physical phenomena. Also, it is observed that the anomalous diffusion based models offer a closer description to clinical facts than the simple model. As the simulation parameters get modified due to different biochemical and biophysical processes, the robustness of the model is determined. It is found that the anomalous diffusion models are moderately sensitive to the parameters.
The EXAFS technique, which deals with fine structure oscillations observed in the X-ray absorption spectrum of an element from 50 eV to ~700 eV above its absorption edge, gives precise information ...regarding the short range order and local structure around the particular atomic species in the material. With the advent of modern bright synchrotron radiation sources, EXAFS has emerged to be the most powerful local structure determination technique, which can be applied to any type of material viz. amorphous, polycrystalline, polymers, surfaces and solutions etc. Over the last few years a comprehensive facility for carrying out EXAFS measurements with synchrotron radiation over variety of samples has been developed at the 2.5 GeV, Synchrotron Radiation Source (INDUS-2) at RRCAT, Indore, India. The facility consists of two operational beamlines viz., the energy dispersive EXAFS beamline (BL-08) and the Energy Scanning EXAFS beamline (BL-09).
Undoped nanocrystalline n-ZnO thin films were deposited on SiO
2-coated p-Si substrates by sol–gel technique to fabricate ZnO-based resistive sensors for methane detection. The resistance change was ...studied at different temperatures (50, 150, 200, 250, 300 and 350
°C) with two different metallic contacts to ZnO, e.g. gold and palladium-silver, in air and in the presence of three different concentrations (0.1, 0.5 and 1%) of methane in N
2 carrier gas. The response, response time and recovery time were studied in detail. A significant improvement of the sensor performance was observed with a Pd-Ag (26%) contact. The maximum response of 74.3% and the lowest response time of 16.3
s were obtained at 250
°C using the Pd-Ag (26%) catalytic metal contact to ZnO. The mechanism of sensing by ZnO was suggested similar to that of the SnO
2 sensors reported by Yamazoe.
We use asteroseismic data obtained by the NASA Kepler mission to estimate the fundamental properties of more than 500 main-sequence and sub-giant stars. Data obtained during the first 10 months of ...Kepler science operations were used for this work, when these solar-type targets were observed for one month each in survey mode. Stellar properties have been estimated using two global asteroseismic parameters and complementary photometric and spectroscopic data. Homogeneous sets of effective temperatures, Tsubeff , were available for the entire ensemble from complementary photometry; spectroscopic estimates of Tsubeff and Fe/H were available from a homogeneous analysis of ground-based data on a subset of 87 stars. We adopt a grid-based analysis, coupling six pipeline codes to 11 stellar evolutionary grids. Future analyses using individual oscillation frequencies will offer significant improvements on up to 150 stars, in particular for estimates of the ages, where having the individual frequency data is most important.
Ammonia borane (AB) is a candidate material for on-board hydrogen storage, and hydrolysis is one of the potential processes by which the hydrogen may be released. This paper presents hydrogen ...generation measurements from the hydrolysis of dilute AB aqueous solutions catalyzed by ruthenium supported on carbon. Reaction kinetics necessary for the design of hydrolysis reactors were derived from the measurements. The hydrolysis had reaction orders greater than zero but less than unity in the temperature range from 16
°C to 55
°C. A Langmuir–Hinshelwood kinetic model was adopted to interpret the data with parameters determined by a non-linear conjugate-gradient minimization algorithm. The ruthenium-catalyzed AB hydrolysis was found to have activation energy of 76
±
0.1
kJ
mol
−1 and adsorption energy of −42.3
±
0.33
kJ
mol
−1. The observed hydrogen release rates were 843
ml
H
2
min
−1 (g
catalyst)
−1 and 8327
ml
H
2
min
−1 (g
catalyst)
−1 at 25
°C and 55
°C, respectively. The hydrogen release from AB catalyzed by ruthenium supported on carbon is significantly faster than that catalyzed by cobalt supported on alumina. Finally, the kinetic rate of hydrogen release by AB hydrolysis is much faster than that of hydrogen release by base-stabilized sodium borohydride hydrolysis.
Yes-associated protein (YAP) has been shown to positively regulate p53 family members and to be negatively regulated by the AKT proto-oncogene product in promoting apoptosis. On the basis of this ...function and its location at 11q22.2, a site of frequent loss of heterozygosity (LOH) in breast cancer, we investigated whether YAP is a tumor suppressor in breast. Examination of tumors by immunohistochemistry demonstrated significant loss of YAP protein. LOH analysis revealed that protein loss correlates with specific deletion of the YAP gene locus. Functionally, short hairpin RNA knockdown of YAP in breast cell lines suppressed anoikis, increased migration and invasiveness, inhibited the response to taxol and enhanced tumor growth in nude mice. This is the first report indicating YAP as a tumor suppressor, revealing its decreased expression in breast cancer as well as demonstrating the functional implications of YAP loss in several aspects of cancer signaling.
The Pd sensitized porous silicon (PS) hydrogen sensor with a thin zinc oxide (ZnO) over layer demonstrated the improved gas response behaviour at the higher temperature. Porous silicon was produced ...by the electrochemical anodization of the p-type monocrystalline silicon substrate of the resistivity, 2–5
Ω
cm and (1
0
0) orientation, using a mixture of HF and ethanol as the electrolyte. The ZnO thin film was coated on the unmodified and on the Pd modified PS surfaces by the sol–gel dip coating method. The catalytic electrode to ZnO was the Pd–Ag (26
wt%) alloy and the contact electrode to the p-silicon substrate was Al. The effect of the Pd modified ZnO on the hydrogen sensing was also studied. The detail gas sensor study with the Pd–Ag/Pd:ZnO/Pd:PS/Si/Al structure indicates that the Pd sensitized ZnO on the Pd modified PS exhibits the minimum fluctuations in the current and the consistent hydrogen sensing performance including an improved gas response (86%), the response time (28
s) and the long-term stability. However, the long recovery time (∼290
s) is due to the slower desorption kinetics after the hydrogen cut off, for using nitrogen carrier gas instead of air that helps in avoiding the cross-sensitivity from the oxygen in air.
Targeted resequencing has become the most used and cost-effective approach for identifying causative mutations of Mendelian diseases both for diagnostics and research purposes. Due to very rapid ...technological progress, NGS laboratories are expanding their capabilities to address the increasing number of analyses. Several open source tools are available to build a generic variant calling pipeline, but a tool able to simultaneously execute multiple analyses, organize, and categorize the samples is still missing.
Here we describe VarGenius, a Linux based command line software able to execute customizable pipelines for the analysis of multiple targeted resequencing data using parallel computing. VarGenius provides a database to store the output of the analysis (calling quality statistics, variant annotations, internal allelic variant frequencies) and sample information (personal data, genotypes, phenotypes). VarGenius can also perform the "joint analysis" of hundreds of samples with a single command, drastically reducing the time for the configuration and execution of the analysis. VarGenius executes the standard pipeline of the Genome Analysis Tool-Kit (GATK) best practices (GBP) for germinal variant calling, annotates the variants using Annovar, and generates a user-friendly output displaying the results through a web page. VarGenius has been tested on a parallel computing cluster with 52 machines with 120GB of RAM each. Under this configuration, a 50 M whole exome sequencing (WES) analysis for a family was executed in about 7 h (trio or quartet); a joint analysis of 30 WES in about 24 h and the parallel analysis of 34 single samples from a 1 M panel in about 2 h.
We developed VarGenius, a "master" tool that faces the increasing demand of heterogeneous NGS analyses and allows maximum flexibility for downstream analyses. It paves the way to a different kind of analysis, centered on cohorts rather than on singleton. Patient and variant information are stored into the database and any output file can be accessed programmatically. VarGenius can be used for routine analyses by biomedical researchers with basic Linux skills providing additional flexibility for computational biologists to develop their own algorithms for the comparison and analysis of data. The software is freely available at: https://github.com/frankMusacchia/VarGenius.
The study was undertaken to establish the role of novel mutations within AdeRS (regulator of efflux pump AdeABC) associated with overexpression of AdeABC, hence cause carbapenem resistance among ...Acinetobacter baumannii. In addition, the study was designed to understand the possible atomic level interactions between carbapenems with AdeABC and molecular mechanism of efflux pump inhibition by PAβN (Efflux pump Inhibitor).
MIC of carbapenems was checked with and without PAβN among A. baumannii (n=56) causing neonatal septicaemia. Overexpression of AdeABC was determined by q-RT PCR. Mutations within AdeRS was determined by sequencing and their role was established using predictive modelling based 3D structure analysis. Protein-substrate interaction studies were performed using molecular docking to understand the binding pattern of FDA approved carbapenems and PAβN in three binding sites (periplasmic, proximal, distal) of AdeB.
Exposure of the carbapenem-resistant A. baumannii (CRABs) to PAβN resulted in a decrease in the MICs of carbapnems among 39% of isolates (15/38). Overall, 29% (11/38) of CRAB showed overexpression of AdeB. Mutations within AdeS (GLY186VAL, SER188PHE, GLU121LYS, VAL255ILE) and AdeR (VAL120ILE, ALA136VAL) were detected among which three novel mutations (GLY186VAL, SER188PHE, GLU121LYS) were found to be associated with overexpression of AdeABC established by homology modelling. Our study mechanistically shows how these mutations prevent the phospho-transfer to AdeR which inhibit the binding of AdeR to the Inter Cistronic Space and hence, cause overexpression of efflux pump. Moreover, molecular docking indicates less binding of carbapenems and PAβN at distal site as compared to other sites. However, PAβN was found to block the carbapenem interacting residues in AdeB which indicates its role as a competitive inhibitor of AdeB substrates.
Novel mutations within AdeRS are reported for the first time along with their role in AdeB overexpression using predictive 3D modelling. In addition, the study is first time reporting the illustrative demonstration of molecular interaction between AdeB, carbapenems and PAβN. This study revealed the key residues of AdeB that interact with carbapenems as well as PAβN that helping us to understand the molecular reasoning of inhibition as well as creating a future platform for designing novel inhibitors.
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