2,201 research outputs found
Enhancement the performance of wire cutting process by additives nanopowder alumina (Al2O3)
Wire Electrical Discharge Machining (WEDM) is a non-traditional thermal machining
process used to manufacture irregularly profiled parts. WEDM includes high rates of
cutting and superior quality in improving machining performance onto hard materials.
Today the electric wire machine plays an important role in manufacturing a solar cell,
which is the main goal in the clean world; the improvement of the performance of this
machine required a new idea for that. So this problem can be solved by following the
unique approach of machining wire electro discharge process through the additives of
nanopowder to the dielectric solution so that the computers controlled wire-electrical
discharge machining processes performance be directly dependent upon spark energy
(spark gap voltage and peak current). This research mainly focuses on WEDM (Ti�6242) titanium alloys using two different dielectrics, a regular dielectric and a
Nanopowder dielectric (Al2O3) up to (2g/l) was selected as the main parameter.In
contrast, coat brass wire was used as an electrode. Three response variables, such as
material removal rate (MRR), recast layer (RL), and surface roughness (SR), was
modeled using the response surface methodology in the WEDM process. The
experimental design is based on the design of Box-Behnken. Six parameters were used
in this study, namely, peak current, Ip 10A to 12A, pulse on time of 120 to 130μs,
pulse off time of 50 to 60μs, the voltage at 20 to 50 V, wire feed 1 to 5 m/min and
tensions 1 to 5 kg. The optimization of multi-response through desirability has
optimized these reactions. ANOVA was used to identify the importance of the model
developed. The testing results confirm the validity and appropriateness of the existing
RSM model developed. In the case of machinability, the optimal parametric setting for
the optimization process has been designed. A micro model was also developed to
predict the recast layer, the substance removal rate, and surface roughness. The current
research's primary focus is on studying the working surface's integrity after machining
using dielectric Nanopowder WEDM. Nano (AL2O3) is the best option in the WEDM
machining of Ti-6242. Experimental findings show that the lowest SR value is 1.39µm
at the Ip=10A, Pon= 130µm, and Spv=20v with nanopowder in a dielectric
improvement. Due to deionized water decomposition, machined samples and wire
material were formed in free or compound form. Simultaneously, there was an
improvement on the surface in Nanopowder used in dielectric by (2g/l) under the same
operating conditions of the machine.
Extraction, Validation, And Evaluation Of Motivational Tactics Rules In A Web-Based Intelligent Tutoring System (WITS)
Kajian ini memberi tumpuan terhadap cara menlestarikan serta meningkatkan motivasi pelajar semasa proses pembelajaran dalam persekitaran Sistem Pentutoran Cerdas Berasaskan Web (Web-Based Intelligent Tutoring System, WITS)
The current study focuses on finding a way to sustain or enhance the learners’ motivation during the learning process within a Web-Based Intelligent Tutoring System (WITS) environmen
Performance of Ti-6242 production using nano powder mixed with different dielectrics
The recent scenario of modern manufacturing is tremendously improved in the sense of precision
machining and abstaining from environmental pollution and hazard issues. In the present work, Ti�6242 is machined through wire EDM (WEDM) process with powder mixed dielectric and analyzed the
influence of input parameters and inherent hazard issues. WEDM has different parameters such as peak
current, pulse on time, pulse off time, gap voltage, wire-speed, wire tension, and so on, as well as dielec�trics with powder mixed. These are playing an essential role in WEDM performances to improve the pro�cess efficiency by developing the metal removal rate. Even though the parameter’s influencing, the study
of the nano dielectric effect in the WEDM process is very essential during the machining process due to
the high discharge energy. In the present study, two different dielectric fluids were used, including deio�nised water, and nanopowder dielectrically, and analyzed the data by taking the response surface method
to use program design expert 10. From this study, it is established that dielectric types and powder sig�nificantly improve performances with a proper set of machining parameters and find out the risk factor
associated with the WEDM process
Enhancement of the performance surface roughness of wire cutting process by additives nano [AL2o3]
Experimental investigation and optimization of machining parameters in Wire EDM in terms adding particles
Nano-reinforced titanium alloy composite abstracts among the various mechanical processes, the process of
manufacturing in wire electrical discharge machines WIRE EDM is one of the most effective and cost�efficient manufacturing processes in the manufacture of titanium alloys Ti-6242. Ti has been dealt with in
this article investigate each of operating parameters such as pulse on time, pulse off time, voltage and current
insulating liquid with Nano powder [AL2O3] in WIRE EDM compounds titanium alloy. Experiments on
titanium alloy carried out with powder mixture with particles size average of [5 nm]. Operating parameters
such as voltage, pulse on time and pulse off time are taking into consideration four factors based on the
response surface methodology. The performance of thesis evaluated WIRE EDM for ti-6242 using the
surface roughness factor SURFACE ROUGHNESS. Quadratic models were developed between parameters
and WIRE EDM responses by regression analysis is. The derived mathematical models are then optimized
using Box-Behnken optimization based on desire analysis. The search indicates that the expected values of
the model obtained to match the experimental values. Improvement in surface roughness is observed in terms
of the values obtained from the Box-Behnken analysis
Propositional calculus for adjointness lattices
Recently, Morsi has developed a complete syntax for the class of all
adjointness algebras . There, is a partially ordered set with top element , is a
conjunction on for which is a left identity
element, and the two implication-like binary operations and on
are adjoints of .
In this paper, we extend that formal system to one for the class of
all 9-tuples , called \emph{%
adjointness lattices}; in each of which is a bounded lattice, and is an
adjointness algebra. We call it \emph{Propositional Calculus for Adjointness
Lattices}, abbreviated . Our axiom scheme for features four
inference rules and thirteen axioms. We deduce enough theorems and
inferences in to establish its completeness for ; by means of
a quotient-algebra structure (a Lindenbaum type of algebra). We study two
negation-like unary operations in an adjointness lattice, defined by means
of together with and . We end by developing complete syntax for
all adjointness lattices whose implications are -type implications
CDH1 and IL1-beta expression dictates FAK and MAPKK-dependent cross-talk between cancer cells and human mesenchymal stem cells
Is Figure S1 showing transfer of cellular components between hMSCs and cancer cells. (DOCX 214 kb
Pleiotropic effects of cancer cells' secreted factors on human stromal (mesenchymal) stem cells
INTRODUCTION: Studying cancer tumors’ microenvironment may reveal a novel role in driving cancer progression and metastasis. The biological interaction between stromal (mesenchymal) stem cells (MSCs) and cancer cells remains incompletely understood. Herein, we investigated the effects of tumor cells’ secreted factors as represented by a panel of human cancer cell lines (breast (MCF7 and MDA-MB-231); prostate (PC-3); lung (NCI-H522); colon (HT-29) and head & neck (FaDu)) on the biological characteristics of MSCs. METHODS: Morphological changes were assessed using fluorescence microscopy. Changes in gene expression were assessed using Agilent microarray and qRT-PCR. GeneSpring 12.1 and DAVID tools were used for bioinformatic and signaling pathway analyses. Cell migration was assessed using a transwell migration system. SB-431542, PF-573228 and PD98059 were used to inhibit transforming growth factor β (TGFβ), focal adhesion kinase (FAK), and mitogen activated protein kinase kinase (MAPKK) pathways, respectively. Interleukin-1β (IL1β) was measured using ELISA. RESULTS: MSCs exposed to secreted factors present in conditioned media (CM) from FaDu, MDA-MB-231, PC-3 and NCI-H522, but not from MCF7 and HT-29, developed an elongated, spindle-shaped morphology with bipolar processes. In association with phenotypic changes, genome-wide gene expression and bioinformatics analysis revealed an enhanced pro-inflammatory response of those MSCs. Pharmacological inhibitions of FAK and MAPKK severely impaired the pro-inflammatory response of MSCs to tumor CM (approximately 80% to 99%, and 55% to 88% inhibition, respectively), while inhibition of the TGFβ pathway was found to promote the pro-inflammatory response (approximately 3-fold increase). In addition, bioinformatics and pathway analysis of gene expression data from tumor cell lines combined with experimental validation revealed tumor-derived IL1β as one mediator of the pro-inflammatory phenotype observed in MSCs exposed to tumor CM. MSCs exhibited significant tropism toward secreted factors from the aforementioned tumor cell lines, while both normal and MSCs exposed to tumor CM were capable of attracting human peripheral blood mononuclear cells (PBMCs). CONCLUSIONS: Our data revealed tumor-derived IL1β as one mediator of the pro-inflammatory response in MSCs exposed to tumor CM, which was found to be positively regulated by FAK and MAPK signaling and negatively regulated by TGFβ signaling. Thus, our data support a model where MSCs could promote cancer progression through becoming pro-inflammatory cells within the cancer stroma
Genome-wide mRNA and miRNA expression profiling reveal multiple regulatory networks in colorectal cancer
Despite recent advances in cancer management, colorectal cancer (CRC) remains the third most common cancer and a major health-care problem worldwide. MicroRNAs have recently emerged as key regulators of cancer development and progression by targeting multiple cancer-related genes; however, such regulatory networks are not well characterized in CRC. Thus, the aim of this study was to perform global messenger RNA (mRNA) and microRNA expression profiling in the same CRC samples and adjacent normal tissues and to identify potential miRNA-mRNA regulatory networks. Our data revealed 1273 significantly upregulated and 1902 downregulated genes in CRC. Pathway analysis revealed significant enrichment in cell cycle, integrated cancer, Wnt (wingless-type MMTV integration site family member), matrix metalloproteinase, and TGF-β pathways in CRC. Pharmacological inhibition of Wnt (using XAV939 or IWP-2) or TGF-β (using SB-431542) pathways led to dose- and time-dependent inhibition of CRC cell growth. Similarly, our data revealed up- (42) and downregulated (61) microRNAs in the same matched samples. Using target prediction and bioinformatics, ~77% of the upregulated genes were predicted to be targeted by microRNAs found to be downregulated in CRC. We subsequently focused on EZH2 (enhancer of zeste homolog 2 ), which was found to be regulated by hsa-miR-26a-5p and several members of the let-7 (lethal-7) family in CRC. Significant inverse correlation between EZH2 and hsa-miR-26a-5p (R(2)=0.56, P=0.0001) and hsa-let-7b-5p (R(2)=0.19, P=0.02) expression was observed in the same samples, corroborating the belief of EZH2 being a bona fide target for these two miRNAs in CRC. Pharmacological inhibition of EZH2 led to significant reduction in trimethylated histone H3 on lysine 27 (H3K27) methylation, marked reduction in cell proliferation, and migration in vitro. Concordantly, small interfering RNA-mediated knockdown of EZH2 led to similar effects on CRC cell growth in vitro. Therefore, our data have revealed several hundred potential miRNA-mRNA regulatory networks in CRC and suggest targeting relevant networks as potential therapeutic strategy for CRC
Epigenetic Library Screen Identifies Abexinostat as Novel Regulator of Adipocytic and Osteoblastic Differentiation of Human Skeletal (Mesenchymal) Stem Cells
Abstract
The epigenetic mechanisms promoting lineage-specific commitment of human skeletal (mesenchymal or stromal) stem cells (hMSCs) into adipocytes or osteoblasts are still not fully understood. Herein, we performed an epigenetic library functional screen and identified several novel compounds, including abexinostat, which promoted adipocytic and osteoblastic differentiation of hMSCs. Using gene expression microarrays, chromatin immunoprecipitation for H3K9Ac combined with high-throughput DNA sequencing (ChIP-seq), and bioinformatics, we identified several key genes involved in regulating stem cell proliferation and differentiation that were targeted by abexinostat. Concordantly, ChIP-quantitative polymerase chain reaction revealed marked increase in H3K9Ac epigenetic mark on the promoter region of AdipoQ, FABP4, PPARγ, KLF15, CEBPA, SP7, and ALPL in abexinostat-treated hMSCs. Pharmacological inhibition of focal adhesion kinase (PF-573228) or insulin-like growth factor-1R/insulin receptor (NVP-AEW51) signaling exhibited significant inhibition of abexinostat-mediated adipocytic differentiation, whereas inhibition of WNT (XAV939) or transforming growth factor-β (SB505124) signaling abrogated abexinostat-mediated osteogenic differentiation of hMSCs. Our findings provide insight into the understanding of the relationship between the epigenetic effect of histone deacetylase inhibitors, transcription factors, and differentiation pathways governing adipocyte and osteoblast differentiation. Manipulating such pathways allows a novel use for epigenetic compounds in hMSC-based therapies and tissue engineering.
Significance
This unbiased epigenetic library functional screen identified several novel compounds, including abexinostat, that promoted adipocytic and osteoblastic differentiation of human skeletal (mesenchymal or stromal) stem cells (hMSCs). These data provide new insight into the understanding of the relationship between the epigenetic effect of histone deacetylase inhibitors, transcription factors, and differentiation pathways controlling adipocyte and osteoblast differentiation of hMSCs. Manipulating such pathways allows a novel use for epigenetic compounds in hMSC-based therapies for tissue engineering, bone disease, obesity, and metabolic-disorders.
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