Abstract: In the Fe-3%Si sheets, grade Hi-B, with AlN and MnS
as inhibitors, the Goss grains which abnormally grow do not have a
size greater than the average size of the primary matrix. In this
heterogeneous microstructure, the size factor is not a required
condition for the secondary recrystallization. The onset of the small
Goss grain abnormal growth appears to be related to a particular
behavior of their grain boundaries, to the local texture and to the
distribution of the inhibitors. The presence and the evolution of
oriented clusters ensure to the small Goss grains a favorable
neighborhood to grow. The modified Monte-Carlo approach, which
is applied, considers the local environment of each grain. The grain
growth is dependent of its real spatial position; the matrix
heterogeneity is then taken into account. The grain growth conditions
are considered in the global matrix and in different matrixes
corresponding to A component clusters. The grain growth behaviour
is considered with introduction of energy only, energy and mobility,
energy and mobility and precipitates.
Abstract: Glutathione S-transferase was purified from human
erythrocytes and effects of some polyphenols were investigated on
the enzyme activity. The purification procedure was performed on
Glutathione-Agarose affinity chromatography after preparation of
erythrocytes hemolysate with a yield of 81%. The purified enzyme
showed a single band on the SDS-PAGE. The effects of some
poliphenolic compounds such as catechin, dopa, dopamine, progallol
and catechol were examined on the in vitro GST activity. Catechin
was determined to be inhibitor for the enzyme, but others were not
effective on the enzyme as inhibitors or activators. IC50 value -the
concentration of inhibitor which reduces enzyme activity by 50%-
was estimated to be 10 mM. Ki constants were also calculated as 6.38
± 0,70 mM with GSH substrate, and 3.86 ± 0,78 mM with CDNB
substrate using the equations of graphs for the inhibitor, and its
inhibition type was determined as non-competitive.
Abstract: The aim of this paper is to compare the effectiveness and electrochemical behavior of typical oilfield corrosion inhibitors with previous oilfield corrosion inhibitors under the same electrochemical techniques to control preferential weld corrosion of X65 pipeline steel in artificial seawater saturated with carbon dioxide at a pressure of one bar. A secondary aim is to investigate the conditions under which current reversal takes place. A flow channel apparatus was used in the laboratory to simulate the actual condition that occurs in marine pipelines. Different samples from the parent metal, the weld metal and the heat affected zone in the pipeline steel were galvanically coupled. The galvanic currents flowing between the weld regions were recorded using zero-resistance ammeters and tested under static and flowing conditions in both inhibited and uninhibited media. The results show that a current reversal took place when 30ppm of both green oilfield inhibitors were present, resulting in accelerated weld corrosion.
Abstract: Hypertension is characterized with stress on the heart and blood vessels thus increasing the risk of heart attack and renal diseases. The Renin angiotensin system (RAS) plays a major role in blood pressure control. Renin is the enzyme that controls the RAS at the rate-limiting step. Our aim is to develop new drug-like leads which can inhibit renin and thereby emerge as therapeutics for hypertension. To achieve this, molecular dynamics (MD) simulation and receptor-based pharmacophore modeling were implemented, and three rennin-inhibitor complex structures were selected based on IC50 value and scaffolds of inhibitors. Three pharmacophore models were generated considering conformations induced by inhibitor. The compounds mapped to these models were selected and subjected to drug-like screening. The identified hits were docked into the active site of renin. Finally, hit1 satisfying the binding mode and interaction energy was selected as possible lead candidate to be used in novel renin inhibitors.
Abstract: Matrix metalloproteinases (MMP) are a class of
structural and functional related enzymes involved in altering the
natural elements of the extracellular matrix. Most of the MMP
structures are cristalographycally determined and published in
WorldWide ProteinDataBank, isolated, in full structure or bound to
natural or synthetic inhibitors. This study proposes an algorithm to
replace missing crystallographic structures in PDB database. We
have compared the results of a chosen docking algorithm with a
known crystallographic structure in order to validate enzyme sites
reconstruction there where crystallographic data are missing.
Abstract: Australia, while being a large and eager consumer of
innovative and cutting edge Information and Communication
Technologies (ICT), continues to struggle to remain a leader in
Technological Innovation. This paper has two main contributions to
address certain aspects of this complex issue. The first being the
current findings of an ongoing research project on Information and
Innovation Management in the Australian Information and
Communication Technologies (ICT) sector. The major issues being
considered by the project include: investigation of the possible
inherent entrepreneurial nature of ICT; how to foster ICT innovation;
and examination of the inherent difficulties currently found within
the ICT industry of Australia in regards to supporting the
development of innovative and creative ideas. The second major
contribution is details of the I.-C.A.N. (Innovation by Collaborative
Anonymous Networking) software application information
management tool created and evolving in our research group. I-CAN,
besides having a positive reinforcement acronym, is aimed at
facilitating productive collaborative innovation in an Australian
workplace. Such a work environment is frequently subjected to
cultural influences such as the 'tall poppy syndrome' and 'negative'
or 'unconstructive' peer-pressure. There influences are frequently
seen as inhibitors to employee participation, entrepreneurship and
innovation.
Abstract: The effects of coatings based on sodium alginate (S.A) and carboxyl methyl cellulose (CMC) on the color and moisture characteristics of potato round slices were investigated. It is the first time that this combination of polysaccharides is used as edible coating which alone had the best performance as inhibitor of potato color discoloration during the storage of 15 days at 4oC. When ascorbic acid (AA) and green tea (GT) were added in the above edible coating its effects on potato round slices changed. The mixtures of sodium alginate and carboxyl methyl cellulose with ascorbic acid or with green tea behave as a potential moisture barrier, resulting to the extent of potato samples self–life. These data suggests that both GT and AA are potential inhibitors of dehydration in potatoes and not only natural antioxidants.
Abstract: The mathematical modeling of different biological
processes is usually used to predict or assess behavior of systems in
which these processes take place. This study deals with mathematical
and computer modeling of bi-substrate enzymatic reactions with
ping-pong mechanism, which play an important role in different
biochemical pathways. Besides that, three models of competitive
inhibition were designed using different software packages. The main
objective of this study is to represent the results from in silico
investigation of bi-substrate enzymatic reactions with ordered pingpong
mechanism in the presence of competitive inhibitors, as well as
to describe in details the inhibition effects. The simulation of the
models with certain kinetic parameters allowed investigating the
behavior of reactions as well as determined some interesting aspects
concerning influence of different cases of competitive inhibition.
Simultaneous presence of two inhibitors, competitive to the S1 and S2
substrates have been studied. Moreover, we have found the pattern of
simultaneous influence of both inhibitors.
Abstract: A gene network gives the knowledge of the regulatory
relationships among the genes. Each gene has its activators and
inhibitors that regulate its expression positively and negatively
respectively. Genes themselves are believed to act as activators and
inhibitors of other genes. They can even activate one set of genes and
inhibit another set. Identifying gene networks is one of the most
crucial and challenging problems in Bioinformatics. Most work done
so far either assumes that there is no time delay in gene regulation or
there is a constant time delay. We here propose a Dynamic Time-
Lagged Correlation Based Method (DTCBM) to learn the gene
networks, which uses time-lagged correlation to find the potential
gene interactions, and then uses a post-processing stage to remove
false gene interactions to common parents, and finally uses dynamic
correlation thresholds for each gene to construct the gene network.
DTCBM finds correlation between gene expression signals shifted in
time, and therefore takes into consideration the multi time delay
relationships among the genes. The implementation of our method is
done in MATLAB and experimental results on Saccharomyces
cerevisiae gene expression data and comparison with other methods
indicate that it has a better performance.
Abstract: 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) catalyzes the conversion of HMG-CoA to mevalonate using NADPH and the enzyme is involved in rate-controlling step of mevalonate. Inhibition of HMGR is considered as effective way to lower cholesterol levels so it is drug target to treat hypercholesterolemia, major risk factor of cardiovascular disease. To discover novel HMGR inhibitor, we performed structure-based pharmacophore modeling combined with molecular dynamics (MD) simulation. Four HMGR inhibitors were used for MD simulation and representative structure of each simulation were selected by clustering analysis. Four structure-based pharmacophore models were generated using the representative structure. The generated models were validated used in virtual screening to find novel scaffolds for inhibiting HMGR. The screened compounds were filtered by applying drug-like properties and used in molecular docking. Finally, four hit compounds were obtained and these complexes were refined using energy minimization. These compounds might be potential leads to design novel HMGR inhibitor.
Abstract: EcoDam is an adenine-N6 DNA methyltransferase
that methylates the GATC sites in the Escherichia coli genome.
DNA-adenine methylation is not present in higher eukaryotes
including humans. These observations raise the possibility that dam
inhibitors may be used as anti-microbial agents. Polyphosphate
(Poly(P)) is an important metabolite and signaling molecule in
prokaryotes and eukaryotes. Here, by using gel retardation
experiments to investigate the competition of DNA binding by
EcoDam in the presence of polyphosphate, we found that Poly (P)
strongly interferes with DNA binding by EcoDam, while same
concentration of monophosphate does not. In addition, we
demonstrated that Poly (P) binding inhibits the activity of EcoDam
and our results suggest that Poly (P) led to strong inhibition of the
EcoDam catalytic activity, while monophosphate had only moderate
effect.
Abstract: Our results showed that treatment with both
cyclooxygenase (COX1 or COX2) inhibitors impair reproduction
parameters of the medaka. Resveratrol (COX1 inhibitor) caused an
decrease in the number of spawning females at the first week of
feeding fish with experimental diets. In the group treated with NS-
398 (COX2 inhibitor) we found the lowest sperm velocity parameters
and decreased linearity of movement. The ovaries of the medaka fed
feed supplemented with Resveratrol or NS-398 were confirmed to
have a lower share of matured oocytes however during the
experiment (four weeks) the number of eggs spawned by females was
similar. Both inhibitors in fish diet (20 mg/kg body weight/day)
caused a decrease in the embryo survival. Our results revealed that
for the medaka female reproduction, activity of both COX enzymes
might be necessary whereas males reproduction competence, as
expressed by sperm motility parameters, might be related to COX2
activity.
Abstract: Gas hydrates form when a number of factors co-exist:
free water, hydrocarbon gas, cold temperatures and high pressures are typical of the near mud-line conditions in a deepwater drilling
operation. Subsequently, when drilling with water based muds, particularly on exploration wells, the risk of hydrate formation
associated with a gas influx is high. The consequences of gas hydrate
formation while drilling are severe, and as such, every effort should be made to ensure the risk of hydrate formation is either eliminated
or significantly reduced. Thermodynamic inhibitors are used to reduce the free water content of a drilling mud, and thus suppress the
hydrate formation temperature. Very little experimental work has
been performed by oil and gas research companies on the evaluation
of gas hydrate formation in a water-based drilling mud. The main
objective of this paper is to investigate the experimental gas hydrate
formation for a mixture of methane, carbon dioxide & nitrogen in a
water-based drilling mud with or without presence of different
concentrations of thermodynamic inhibitors including pure salt and a
combination of salt with methanol or ethylene glycol at different
concentrations in a static loop apparatus. The experiments were
performed using a static loop apparatus consisting of a 2.4307 cm
inside diameter and 800 cm long pipe. All experiments were conducted at 2200 psia. The temperature in the loop was decreased at
a rate of 3.33 °F/h from initial temperature of 80 °F.
Abstract: In this paper, a mathematical model of human immunodeficiency
virus (HIV) is utilized and an optimization problem is
proposed, with the final goal of implementing an optimal 900-day
structured treatment interruption (STI) protocol. Two type of commonly
used drugs in highly active antiretroviral therapy (HAART),
reverse transcriptase inhibitors (RTI) and protease inhibitors (PI), are
considered. In order to solving the proposed optimization problem an
adaptive memetic algorithm with population management (AMAPM)
is proposed. The AMAPM uses a distance measure to control the
diversity of population in genotype space and thus preventing the
stagnation and premature convergence. Moreover, the AMAPM uses
diversity parameter in phenotype space to dynamically set the population
size and the number of crossovers during the search process.
Three crossover operators diversify the population, simultaneously.
The progresses of crossover operators are utilized to set the number
of each crossover per generation. In order to escaping the local optima
and introducing the new search directions toward the global optima,
two local searchers assist the evolutionary process. In contrast to
traditional memetic algorithms, the activation of these local searchers
is not random and depends on both the diversity parameters in
genotype space and phenotype space. The capability of AMAPM in
finding optimal solutions compared with three popular metaheurestics
is introduced.
Abstract: Chitosan is a biopolymer composed of glucosamine
and N-acetyl glucosamine. Solubility and viscosity pose problems in
some applications. These problems can be overcome with unique
modifications. In this study, firstly, chitosan was modified by caffeic
acid and thioglycolic acid, separately. Then, growing effects of these
modified polymers was observed in U937 cell line. Caffeic acid is a
phenolic compound and its modifications act carcinogenic inhibitors
in drugs. Thiolated chitosans are commonly being used for drugdelivery
systems in various routes, because of enhancing
mucoadhesiveness property. U937 cell line was used model cell for
leukaemia. Modifications were achieved by 1 – 15 % binding range.
Increasing binding ratios showed higher radical-scavenging activity
and reducing cell growth, in compared to native chitosan. Caffeic
acid modifications showed higher radical-scavenging activity than
thiolated chitosans at the same concentrations. Caffeic acid and
thioglycolic acid modifications inhibited growth of U937, effectively.
Abstract: There is an urgent need to develop novel
Mycobacterium tuberculosis (Mtb) drugs that are active against drug
resistant bacteria but, more importantly, kill persistent bacteria. Our
study structured based on integrated analysis of metabolic pathways,
small molecule screening and similarity Search in PubChem
Database. Metabolic analysis approaches based on Unified weighted
used for potent target selection. Our results suggest that pantothenate
synthetase (panC) and and 3-methyl-2-oxobutanoate hydroxymethyl
transferase (panB) as a appropriate drug targets. In our study, we
used pantothenate synthetase because of existence inhibitors. We
have reported the discovery of new antitubercular compounds
through ligand based approaches using computational tools.
Abstract: An alarming emergence of multidrug-resistant strains
of the tuberculosis pathogen Mycobacterium tuberculosis and
continuing high worldwide incidence of tuberculosis has invigorated
the search for novel drug targets. The enzyme glutamate racemase
(MurI) in bacteria catalyzes the stereoconversion of L-glutamate to
D-glutamate which is a component of the peptidoglycan cell wall of
the bacterium. The inhibitors targeted against MurI from several
bacterial species have been patented and are advocated as promising
antibacterial agents. However there are none available against MurI
from Mycobacterium tuberculosis, due to the lack of its threedimensional
structure. This work accomplished two major objectives.
First, the tertiary structure of MtMurI was deduced computationally
through homology modeling using the templates from bacterial
homologues. It is speculated that like in other Gram-positive bacteria,
MtMurI exists as a dimer and many of the protein interactions at the
dimer interface are also conserved. Second, potent candidate
inhibitors against MtMurI were identified through docking against
already known inhibitors in other organisms.