In controlling biological diseases, it is often more potent to use a combination of agents than using individual ones. However, the number of possible combinations increases exponentially with the ...number of agents and their concentrations. It is prohibitive to search for effective agent combinations by trial and error as biological systems are complex and their responses to agents are often a slow process. This motivates to build a suitable model to describe the biological systems and help reduce the number of experiments. In this paper, we consider the use of fungicides to inhibit Bipolaris maydis and construct models that describe the responses to fungicide combinations. Three data-driven modeling methods, the polynomial regression, the artificial neural network and the support vector regression, are compared based on the experimental data of the inhibition rates of the southern corn leaf blight with different fungicide combinations. The analysis of the results demonstrates that the support vector regression is best suited to the construction of the response model in terms of achieving better prediction with fewer experiments.
The existing low gain feedback, which is a parameterized family of stabilizing state feedback gains whose magnitudes approach zero as the parameter decreases to zero, has been designed in very ...specific ways. In this paper, by recognizing the l ∞ and l 2 slow peaking phenomenon that exists in discrete-time systems under low gain feedback, more general notions of l ∞ and l 2 norm vanishment are considered so as to provide a full characterization of the nonexistence of slow peaking phenomenon in some measured signals. Low gain feedback that does not lead to l ∞ and l 2 slow peaking in the control input are respectively referred to as l ∞ and l 2 low gain feedback. Based on the notions of l ∞ and l 2 vanishment, not only can the existing low gain feedback been recognized as an l ∞ low gain feedback, but also a new design approach referred to as the l 2 low gain feedback approach is developed for discrete-time linear systems. Parallel to the effectiveness of l ∞ low gain feedback in magnitude constrained control, the l 2 low gain feedback is instrumental in the control of discrete-time systems with control energy constraints. The notions of l ∞ and l 2 -vanishment also result in a systematic approach to the design of l ∞ and l 2 low gain feedback by providing a family of solutions including those resulting from the existing design methods.
Transforming growth factor (TGF)-β1 is a profibrotic cytokine that plays a critical role in the progression of diabetic nephropathy (DN). Previous studies have demonstrated that the Smad ...transcriptional co-repressor, Ski-related novel protein N (SnoN), an antagonizer of TGF-β1/Smad signaling, is downregulated in the kidneys of diabetic rats; however, the underlying molecular mechanisms remain elusive. In the present study, we demonstrated that the upregulation of Smad ubiquitination regulatory factor-2 (Smurf2), through TGF-β1/Smad signaling, contributes to the downregulation of SnoN under high-glucose conditions in primary human renal proximal tubule epithelial cells (hRPTECs). The hRPTECs were cultured in high-glucose (30 mmol/l D-glucose) medium in the presence or absence of either the proteasome inhibitor, MG132, or the TGF-β type I receptor kinase inhibitor, SB-431542. Small interfering RNA (siRNA) was used to silence Smurf2. The expression levels of SnoN, Smurf2, Smad2 and phosphorylated (p-)Smad2 were measured by western blot analysis and RT-qPCR. The protein levels of SnoN were markedly downregulated, while its mRNA levels were increased in the hRPTECs cultured under high-glucose conditions. The protein and mRNA levels of Smurf2 were significantly increased under high-glucose conditions. The knockdown of Smurf2 increased SnoN expression in the hRPTECs cultured in high-glucose medium. Moreover, MG132 partially inhibited SnoN degradation in the hRPTECs under high-glucose conditions and SB-431542 decreased the phosphorylation of Smad2 and the expression of Smurf2 induced under high-glucose conditions. Taken together, the findings of this study demonstrate that the downregulation of SnoN expression in hRPTECs under high-glucose conditions is mediated by the increased expression of Smurf2 through the TGF-β1/Smad signaling pathway.
To examine the effect of angiotensin II (Ang II) on nuclear factor-kappa B (NF-kappaB) activation in human endothelial cell line ECV304 and the molecular mechanism by which Ang II activates ...NF-kappaB.
ECV304 cells were transiently cotransfected with an NF-kappaB/luciferase reporter gene and inactive NF-kappaB-inducing kinase (NIK), IkappaB kinase alpha (IKK(alpha)), IkappaB kinase beta (IKK(beta)) mutants or vectors, respectively. The effect on NF-kappaB was detected by using an electrophoretic mobility shift assay (EMSA) and overexpression of the mutants enabled blocking of reporter gene activation induced by Ang II. With immunofluorescence and immuno-electronic microscope techniques, including confocal microscopy and gold particle labeled electronic microscopy, definite cytoplasmic-to-nuclear translocations of NF-kappaB activation were detected using subunits p50 and p65 induced by Ang II.
The translocation of p50 in nuclei was highly remarkable 2 hours after Ang II stimulation, and the activity was somewhat reduced 6 hours after stimulation to the 18th hour. Northern blot also showed PDGF-B mRNA increased by stimulation of Ang II for 18 hours.
Ang II is effective in stimulating NF-kappaB activation through a pathway dependent on NIK, IKK(alpha) and IKK(beta), and induces PDGF-B transcription in the endothelial cell line, ECV304.v
To evaluate the possibility and efficiency of nanoparticle as a new vector in specific gene transference.
Nanoparticle-DNA complex was prepared with PLGA bearing antisense monocyte chemotactic ...protein-1 (A-MCP-1), a specific expression gene, and the package efficiency, release progress in vitro, and size of the complex were determined. The nanoparticl-DNA was trasnsfected into the cultured smooth muscle cells. PCR was used to evaluate the transfection of A-MCP-1. Cationic lipid (lipofectamine) was used to transfect A-MCP-1 as control. Forty-eight hours later, DNA in the SMCs was extracted and examined by PCR. Twenty New Zealand White rabbits underwent jugular vein-to-artery bypass grafting procedure, of which 6 received grafts transfected with nanopaticle-A-MCP-1 (200 microgram), 6 received grafts with cationic liposome (DOTAP)-A-MCP-1 (200 microgram), 4 received grafts with LNCX plasmid, and 4 received grafts without transfection as control. Fourteen days after surgery grafts were harvested. The expression o
Based on the principle of piecewise compensation, a modified high-order compensation technique with adaptive feedback control scheme for bandgap reference is proposed. This method focuses on forming ...multiple local extrema of the curve of reference voltage instead of single valley or peak in the entire operating temperature range, which significantly improves the temperature independence. The circuitry is simulated in CSMC 0.6 mum CMOS process, and it has a temperature coefficient in the -55degC to 105degC range of 0.46ppm/degC (average) with power supply current lower than 0.2 muA.
To study the mechanism of restenosis after angioplasty and to clarify the effect of thrombin and its receptor on restenosis development.
Balloon catheter-induced injury was adopted to induce intimal ...hyperplasia of the carotid arteries in rats. Antisense thrombin receptor (ATR) cDNA was transfected by perfusing recombinant LXSN ATR plasmid/nanoparticle complex into the segment of the injured carotid artery.
PCR result showed integration of the recombined gene. Dot blot showed the expression of antisense TR mediated by recombinant LXSN ATR plasmid/nanoparticle complex in the wall of common carotid arteries of the experimental group rats, which enabled to inhibit TR gene expression and intimal hyperplasia of the injured arteries.
Thrombin and its receptor play an important role in the formation of neointima after the injury, which provides a potential clue in developing a new approach for prevention and treatment of restenosis after angioplasty.
SUMMARY
1. Southern blot confirmed the emergence of the human apolipoprotein A1 (h‐apoAl) gene (four to 15 copies) in newborn transgenic mice. The inheritance pattern of h‐apoAl transgene in three ...generations of progeny was compatible with a single autosomal integration site.
2. Northern blot showed h‐apoA1 mRNA expressed mainly in liver, kidney and aorta. The total plasma apoA1 (murine plus human) level was significantly increased to 58 and 118 in transgenic mice without or under zinc induction, respectively. The majority was h‐apoA1. Plasma lecithin:cholesterol acyltransferase activity was positively correlated with h‐apoA1 levels in transgenic mice (r = 0.43; P < 0.01).
3. After a high cholesterol intake for 14 weeks, the incidence of fatty streak at the aortic sinus was 40% in transgenic mice and 80% in controls. Expression of platelet‐derived growth factor‐B, c‐myc and c‐fos proteins was much weaker in smooth muscle cells at the aortic sinus in transgenic mice.
To investigate the inhibitory effect of expressed human apolipoprotein AI (h-apo AI) and high density lipoprotein (HDL) on atherosclerosis development in transgenic mice, and cultivation of smooth ...muscle cells isolated from the aortic wall of transgenic mice that are able to produce human apo AI in vitro.
Both h-apo AI transgenic mice and normal C57 mice were fed with either a regular chow or a high-fat diet containing 5% pork lard, 1.25% cholesterol and 0.25% sodium cholate for 14 or 24 weeks respectively. Human apo AI mRNA were detected by Northern blot. Plasma apo AI levels were measured using a radio-immuno-diffusion assay, and plasma lipid levels were measured using a colorimetric assay. Image analysis was performed in order to quantify the fatty streak areas stained with oil red O. In addition, smooth muscle cells isolated from the media layer of the aortic wall of h-apo AI transgenic mice were cultured for the detection of human apo AI produced.
Higher levels of h-apo AI mRNA were found in liver, small intestine, kidneys and aortae in transgenic mice than in the controls all on a high-fat diet. The transgenic mice had an increased level of serum apo AI and HDL-cholesterol and the fatty streak area counted at the aortic sinus was approximately 5-fold less in the transgenic mice after feeding with a high fat ration, particularly after 24 weeks. SMC isolated from the transgenic mice aortae were cultivated and able to express h-apo AI mRNA and its related protein.
Elevation of h-apo AI and HDL in serum and aortic wall of the transgenic mice has a remarkably inhibitory effect on the development of experimental atherosclerosis.
