Highlights • Sulfuretin protects against Aβ25–35 -induced neurotoxicity. • Sulfuretin activates Nrf2 and induces HO-1 via PI3K/Akt. • Knockdown of Nrf2 reverses the neuroprotective effects of ...sulfuretin.
We propose an optimization algorithm to generate a robust magnetic force against position error to achieve good controllability of the magnetic robot in the region of interest of a magnetic ...navigation system comprising electromagnets. We formulate an optimization problem that minimizes the norm of the spatial derivatives of the magnetic force subject to the constraints of the magnetic flux density and magnetic force. The robust magnetic force generated by the proposed algorithm was compared with conventional pseudo-inverse matrix method and verified through an experiment in which a magnetic robot was successfully steered along a bifurcated glass tube to reach a target position.
Multidrug and toxin extrusion 2 (MATE2‐K (SLC47A2)), a polyspecific organic cation exporter, facilitates the renal elimination of the antidiabetes drug metformin. In this study, we characterized ...genetic variants of MATE2‐K, determined their association with metformin response, and elucidated their impact by means of a comparative protein structure model. Four nonsynonymous variants and four variants in the MATE2‐K basal promoter region were identified from ethnically diverse populations. Two nonsynonymous variants—c.485C>T and c.1177G>A—were shown to be associated with significantly lower metformin uptake and reduction in protein expression levels. MATE2‐K basal promoter haplotypes containing the most common variant, g.−130G>A (>26% allele frequency), were associated with a significant increase in luciferase activities and reduced binding to the transcriptional repressor myeloid zinc finger 1 (MZF‐1). Patients with diabetes who were homozygous for g.−130A had a significantly poorer response to metformin treatment, assessed as relative change in glycated hemoglobin (HbA1c) (−0.027 (−0.076, 0.033)), as compared with carriers of the reference allele, g.−130G (−0.15 (−0.17, −0.13)) (P = 0.002). Our study showed that MATE2‐K plays a role in the antidiabetes response to metformin.
Clinical Pharmacology & Therapeutics (2011); 90 5, 674–684. doi:10.1038/clpt.2011.165
The purpose of this paper is to exploit umbral calculus in order to derive some properties, recurrence relations, and identities related to the degenerate
r
-Stirling numbers of the second kind and ...the degenerate
r
-Bell polynomials. Especially, we will express the degenerate
r
-Bell polynomials as linear combinations of many well-known families of special polynomials.
This paper proposes a novel configuration of a unified power quality conditioner (UPQC) which can be connected to the distribution system without series injection transformers. The operation of the ...proposed system was analyzed through simulations with PSCAD/EMTDC and experimental works with a scaled hardware model, assuming that the UPQC is connected with the 22.9-kV distribution line. The proposed UPQC has the ultimate capability of improving power quality at the point of installation on power distribution systems. It has flexibility in expanding the operation voltage by increasing the number of H-bridge modules.
The expression of hypoxia-inducible factor-1 (HIF-1) correlates with poor clinical outcomes and confers resistance to the apoptosis of the tumor cells that are exposed to hypoxia. Presently, the ...mechanism underlying this phenomenon is poorly understood. In this study we provide evidence that transglutaminase 2 (TG2), an enzyme that catalyses protein crosslinking reactions, is a transcriptional target of HIF-1 to enhance the survival of hypoxic cells. We found that hypoxia induces TG2 expression through an HIF-1 dependent pathway and concurrently activates intracellular TG2. The hypoxic cells overexpressing TG2 showed resistance to apoptosis. Conversely, the hypoxic cells treated with either TG2 inhibitor or small interfering RNA (siRNA) became sensitive to apoptosis. Activation of TG2 in response to hypoxic stress inhibited caspase-3 activity by forming crosslinked multimer, resulting in insoluble aggregates. TG2 also activates nuclear factor (NF)-κB pathway after hypoxic stress, and thereby induces the expression of cellular inhibitor of apoptosis 2. The anti-apoptotic role of TG2 was further confirmed in vivo using xenografts in athymic mice. Our results indicate that TG2 is an antiapoptotic mediator of HIF-1 through modulating both apoptosis and survival pathways and may confer a selective growth advantage to tumor cells. These findings suggest that the inhibition of TG2 may offer a novel strategy for anticancer therapy. Oncogene (2010) 29, 356-367; doi: 10.1038/onc.2009.342; published online 19 October 2009 Keywords: apoptosis; caspase 3; hypoxia-inducible factor-1; NF-κB; transglutaminase 2
We developed a resonance control method to generate a high-speed rotating magnetic field in a three-phase magnetic navigation system composed of three electromagnets. The proposed resonance control ...method calculates the amplitudes and phases of voltages, while the capacitances suppressing the self and mutual inductances of the electromagnets to keep the currents and the magnitude of the rotating magnetic field constant, even if the frequency of the rotating magnetic field increases. Finally, we prototyped the three-phase magnetic navigation system and the variable capacitor module to validate the effectiveness of the proposed resonance control method experimentally.
We propose a novel position control method (PCM) for the Robotically Assisted MAgnetic Navigation (RAMAN) system to improve the pushability of the magnetic catheter (MC) by maximizing the magnetic ...force. We expressed the magnetic force acting on the magnetic catheter as the position and the current flowing through each of the electromagnets of the RAMAN system. Next, we formulated a PCM as an optimization problem to maximize the MF. From the proposed PCM, we can determine the position that generates the maximum MF in the desired direction within the region of interest of the RAMAN as well as the required applied current of each electromagnet. Finally, we performed a navigation experiment for the MC along the aorta to the right coronary artery in a cardiac vascular phantom model, and we showed that the proposed PCM can navigate through the vascular phantom effectively without buckling of the MC.
The behavior of CrCoFeMnNi high-entropy alloy (Cantor) during cyclic deformation at room temperature was compared with those of a twinning-induced plasticity (TWIP) steel and 304 stainless steel ...(SS304). The three materials with similar grain sizes (~65 μm) were made by controlled heat treatment and tested to evaluate tensile and low-cycle fatigue (LCF) properties. The tensile strength and ductility of Cantor were much lower than those of TWIP steel and SS304. Cantor and TWIP steel revealed cyclic hardening and then softening; SS304 showed secondary hardening at the latest stage of cyclic deformation due to formation of α′-martensite, which led to a significant decrease in its LCF life. At high total strain amplitudes >0.4% LCF life was longer in Cantor than in SS304, but shorter than in TWIP steel. However, at total strain amplitudes ≤0.4%, Cantor showed the shortest LCF life. It was found that the Coffin-Manson plot of Cantor followed the trend of TWIP steel rather than that of SS304. Microstructural analysis of the Cantor with increasing cycles revealed the formation of twins and well-defined cell structures, the latter of which is the evidence of wavy slip.
•The LCF life of Cantor alloy was higher than that of SS304 at high strain amplitude, but lower than that of TWIP at all strain amplitudes.•In Cantor alloy, mechanical twinning formation was evidenced by TEM images.•The most active mechanism during cyclic loading of Cantor alloy was the rearrangement of dislocations in cell structures.
Mutations of the isocitrate dehydrogenase 1 and 2 genes (
IDH1
and
IDH2
) are commonly found in primary brain cancers. We previously reported that a novel enzymatic activity of these mutations ...results in the production of the putative oncometabolite, R(−)-2-hydroxyglutarate (2-HG). Here we investigated the ability of magnetic resonance spectroscopy (MRS) to detect 2-HG production in order to non-invasively identify patients with
IDH1
mutant brain tumors. Patients with intrinsic glial brain tumors (
n
= 27) underwent structural and spectroscopic magnetic resonance imaging prior to surgery. 2-HG levels from MRS data were quantified using LC-Model software, based upon a simulated spectrum obtained from a GAMMA library added to the existing prior knowledge database. The resected tumors were then analyzed for
IDH1
mutational status by genomic DNA sequencing, Ki-67 proliferation index by immunohistochemistry, and concentrations of 2-HG and other metabolites by liquid chromatography–mass spectrometry (LC–MS). MRS detected elevated 2-HG levels in gliomas with
IDH1
mutations compared to those with wild-type
IDH1
(
P
= 0.003). The 2-HG levels measured in vivo with MRS were significantly correlated with those measured ex vivo from the corresponding tumor samples using LC–MS (
r
2
= 0.56;
P
= 0.0001). Compared with wild-type tumors, those with
IDH1
mutations had elevated choline (
P
= 0.01) and decreased glutathione (
P
= 0.03) on MRS. Among the
IDH1
mutated gliomas, quantitative 2-HG values were correlated with the Ki-67 proliferation index of the tumors (
r
2
= 0.59;
P
= 0.026). In conclusion, water-suppressed proton (
1
H) MRS provides a non-invasive measure of 2-HG in gliomas, and may serve as a potential biomarker for patients with
IDH1
mutant brain tumors. In addition to 2-HG, alterations in several other metabolites measured by MRS correlate with
IDH1
mutation status.
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