Full Length Research Paper Curcumin induces cleavage of -catenin by activation of capases and downregulates the &#946-catenin/Tcf signaling pathway in HT-29 cells

β-Catenin/Tcf-4 signaling pathway plays important roles in colorectal tumorigenesis. RT-PCR, western blotting and immunoprecipitation were used to study the effects of curcumin on β-catenin/Tcf-4 signaling pathway in HT-29 cells. Treatment of curcumin could induce cleavage of β-catenin and the cleavage could be inhibited by caspase inhibitors. The association of β-catenin with Tcf-4 in nucleus could be inhibited by curcumin. The expression of c-myc and cyclinD1 was downregulated by curcumin, which could not be blocked by Z-DEVD-FMK. The results showed curcumin could induce thecleavage of β-catenin by activition of caspases and downregulate the activity of β-catenin/Tcf signaling pathway independent of the caspases in HT-29 cells

Modeling, Oscillation Analysis and Distributed Stabilization Control of Autonomous PV-based Microgrids

Driven by rising energy demand and the goal of carbon neutrality, renewable energy generations (REGs), especially photovoltaic (PV) generations, are widely used in the urban power energy systems. While the intelligent control of microgrids (MG) brings economic and efficient operation, its potential stability problem cannot be ignored. To date, most of the research on modeling, analyzing and enhancing the stability of MG usually assume the DC-link as an ideal voltage source. However, this practice of ignoring the dynamics of DC-link may omit the latent oscillation phenomena of autonomous PV-based MG. First, this paper establishes a complete dynamic model of autonomous PV-based MG including PV panels and DC-link. Different from previous conclusions of idealizing DC-link dynamics, participation factor analysis finds the potential impact of DC-link dynamics on system dynamic performance, and different influence factors including critical control parameters and non-linear V-I output characteristic of PV array are considered to further reveal oscillation mechanisms. Second, based on the average consensus algorithm, a distributed stabilization controller with strong robustness is proposed to enhance stability of the PV-based MG, which does not affect the steady-state performance of the system. Finally, the correctness of all theoretical analysis and the effectiveness of the proposed controller are verified by time domain simulation and hardware-in-loop tests.10.13039/501100001809-National Natural Science Foundation of China (Grant Number: 51907031

A randomized, double-blind, placebo-controlled trial to assess safety and tolerability during treatment of type 2 diabetes with usual diabetes therapy and either Cycloset™ or placebo

Background: Cycloset™ is a quick-release formulation of bromocriptine mesylate, a dopamine agonist, which in animal models of insulin resistance and type 2 diabetes acts centrally to reduce resistance to insulin- mediated suppression of hepatic glucose output and tissue glucose disposal. In such animals, bromocriptine also reduces hepatic triglyceride synthesis and free fatty acid mobilization, manifesting decreases in both plasma triglycerides and free fatty acids. In clinical trials, morning administration of Cycloset™ either as monotherapy or adjunctive therapy to sulfonylurea or insulin reduces HbA1c levels relative to placebo by 0.55–1.2. Cycloset™ therapy also reduces plasma triglycerides and free fatty acid by approximately 25% and 20%, respectively, among those also receiving sulfonylurea therapies. The effects of once-daily morning Cycloset™ therapy on glycemic control and plasma lipids are demonstrable throughout the diurnal portion of the day (7 a.m. to 7 p.m.) across postprandial time points. Methods/Design: 3,095 individuals were randomized in a 2:1 ratio into a one year trial aimed to assess the safety and efficacy of Cycloset™ compared to placebo among individuals receiving a variety of treatments for type 2 diabetes. Eligibility criteria for this randomized placebo controlled trial included: age 30–80, HbA1c ≤ 10%, diabetes therapeutic regimen consisting of diet or no more than two hypoglycemic agents or insulin with or without one additional oral agent (usual diabetes therapy; UDT). The primary safety endpoint will test the hypothesis that the rate of all-cause serious adverse events after one year of usual diabetes therapy (UDT) plus Cycloset™ is not greater than that for UDT plus placebo by more than an acceptable margin defined as a hazard ratio of 1.5 with a secondary endpoint analysis of the difference in the rate of serious cardiovascular events, (myocardial infarction, stroke, coronary revascularization or hospitalization for or angina or congestive heart failure). Efficacy analyses will evaluate effects of Cycloset™ versus placebo on change from baseline in HbA1c, fasting glucose, body weight, waist circumference, blood pressure and plasma lipids. Discussion: This study will extend the current data on Cycloset™ safety, tolerability and efficacy in individuals with type 2 diabetes to include its effects in combination with thiazolodinediones, insulin secretagogues, metformin, alpha-glucosidase inhibitors and exogenous insulin regimens. Trial registration: clinical trials.gov NCT0037767

Non-monotonic field-dependence of the ZFC magnetization peak in some systems of magnetic nanoparticles

We have performed magnetic measurements on a diluted system of gamma-Fe2O3 nanoparticles (~7nm), and on a ferritin sample. In both cases, the ZFC-peak presents a non-monotonic field dependence, as has already been reported in some experiments,and discussed as a possible evidence of resonant tunneling. Within simple assumptions, we derive expressions for the magnetization obtained in the usual ZFC, FC, TRM procedures. We point out that the ZFC-peak position is extremely sensitive to the width of the particle size distribution, and give some numerical estimates of this effect. We propose to combine the FC magnetization with a modified TRM measurement, a procedure which allows a more direct access to the barrier distribution in a field. The typical barrier values which are obtained with this method show a monotonic decrease for increasing fields, as expected from the simple effect of anisotropy barrier lowering, in contrast with the ZFC results. From our measurements on gamma-Fe2O3 particles, we show that the width of the effective barrier distribution is slightly increasing with the field, an effect which is sufficient for causing the observed initial increase of the ZFC-peak temperatures.Comment: LaTeX file 19 pages, 9 postscript figures. To appear in Phys. Rev. B (tentative schedule: Dec.97

Normalization factors for magnetic relaxation of small particle systems in non-zero magnetic field

We critically discuss relaxation experiments in magnetic systems that can be characterized in terms of an energy barrier distribution, showing that proper normalization of the relaxation data is needed whenever curves corresponding to different temperatures are to be compared. We show how these normalization factors can be obtained from experimental data by using the $T \ln(t/\tau_0)$ scaling method without making any assumptions about the nature of the energy barrier distribution. The validity of the procedure is tested using a ferrofluid of Fe_3O_4 particles.Comment: 5 pages, 6 eps figures added in April 22, to be published in Phys. Rev. B 55 (1 April 1997

Differential adherence and expression of virulence traits by Candida albicans and Candida parapsilosis in mono- and dual-species cultures in artificial saliva

AIMS: To evaluate specific virulence factors of Candida albicans and Candida parapsilosis clinical oral isolates in mono- and dual-species culture in the presence of artificial saliva. METHODS AND RESULTS: Two of the strains used in this study were isolated from co-infection (C. albicans AM and C. parapsilosis AM2), and the other two were isolated from single infection (C. albicans AC and C. parapsilosis AD). The number of adhered yeast cells was measured and their enzymatic activity was determined simultaneously. In mono-species culture, C. parapsilosis strains adhered to a higher extent to the surface in comparison with the C. albicans strains. In dual-species culture, the C. parapsilosis strains adhered more in the presence of C. albicans AM. Interestingly, C. albicans AM and C. parapsilosis AD adhered to a higher extent when compared with all other co-cultures. In dual-species culture, the enzymatic activity of C. parapsilosis strains in the presence of C. albicans AC was higher than in the presence of C. albicans AM. CONCLUSIONS: The virulence factors of C. albicans and C. parapsilosis differ from strain to strain and are influenced by the presence of other species in culture. SIGNIFICANCE AND IMPACT OF THE STUDY: To understand the expression of virulence factors in Candida dual-species systems.This work was supported by Portuguese Foundation for Science and Technology (FCT) through the grant SFRH/BPD/20987/2004 attributed to Claudia Botelho

A novel approach using potable diagnostic ultrasound to inform treatment choices for hemiplegic shoulder pain – A case study

Introduction: Hemiplegic shoulder pain (HSP) has a reported incidence of up to 84% of patients. The purpose of this case study is to report findings from a patient with HSP who received problem specific treatment and underwent real-time scanning of shoulder region with a portable diagnostic ultrasound. Treatment was modified to address the problems. Methods/Case Description:The patient was a 45 year-old woman with right sided-hemiparesis resulting from a clot. Patient was undergoing rehabilitation in a private clinic and reported shoulder pain. Patient was undergoing rehabilitation (over-arm exercises, electrical stimulation, stretches, Saebo exercises) however, continued to complain of shoulder pain (VAS-7). Ultrasound scanning was undertaken and following observations were made on both affected (AF) and unaffected (UAF) shoulders. Acromion-greater tuberosity (AGT) distance (AF-3.35 cm, UAF-2.04 cm), diameter of supraspinatus in resting state (AF -1.16 cm, UAF-1.42cm) and contracted state (AF-1.14cm, UAF-1.63cm). Modified treatment included: 1) Isometric exercises to supraspinatus muscle 2) Trigger point release for trapezius 3) Electrical stimulation to lateral deltoid and supraspinatus 4) avoid over-arm activitiesResults: Ultrasound measurement suggested reduction in AGT immediately following treatment. 8 weeks later, VAS score was 3 and patient reported using her arm more for various functional tasks. Diameter of supraspinatus in resting state (AF -1.30 cm, UAF-1.45cm) and contracted state (AF-1.42cm, UAF-1.70cm) suggested some improvement.Conclusions: Real-time ultrasound has potential benefits as an assessment tool to inform treatment choices for HSP. Further studies are required in this area

Synthetic Lethality of Chk1 Inhibition Combined with p53 and/or p21 Loss During a DNA Damage Response in Normal and Tumor Cells

Cell cycle checkpoints ensure genome integrity and are frequently compromised in human cancers. A therapeutic strategy being explored takes advantage of checkpoint defects in p53-deficient tumors in order to sensitize them to DNA-damaging agents by eliminating Chk1-mediated checkpoint responses. Using mouse models, we demonstrated that p21 is a key determinant of how cells respond to the combination of DNA damage and Chk1 inhibition (combination therapy) in normal cells as well as in tumors. Loss of p21 sensitized normal cells to the combination therapy much more than did p53 loss and the enhanced lethality was partially blocked by CDK inhibition. In addition, basal pools of p21 (p53 independent) provided p53 null cells with protection from the combination therapy. Our results uncover a novel p53-independent function for p21 in protecting cells from the lethal effects of DNA damage followed by Chk1 inhibition. As p21 levels are low in a significant fraction of colorectal tumors, they are predicted to be particularly sensitive to the combination therapy. Results reported in this study support this prediction

Physical mapping integrated with syntenic analysis to characterize the gene space of the long arm of wheat chromosome 1A

Background: Bread wheat (Triticum aestivum L.) is one of the most important crops worldwide and its production faces pressing challenges, the solution of which demands genome information. However, the large, highly repetitive hexaploid wheat genome has been considered intractable to standard sequencing approaches. Therefore the International Wheat Genome Sequencing Consortium (IWGSC) proposes to map and sequence the genome on a chromosome-by-chromosome basis. Methodology/Principal Findings: We have constructed a physical map of the long arm of bread wheat chromosome 1A using chromosome-specific BAC libraries by High Information Content Fingerprinting (HICF). Two alternative methods (FPC and LTC) were used to assemble the fingerprints into a high-resolution physical map of the chromosome arm. A total of 365 molecular markers were added to the map, in addition to 1122 putative unique transcripts that were identified by microarray hybridization. The final map consists of 1180 FPC based or 583 LTC based contigs. Conclusions/Significance: The physical map presented here marks an important step forward in mapping of hexaploid bread wheat. The map is orders of magnitude more detailed than previously available maps of this chromosome, and the assignment of over a thousand putative expressed gene sequences to specific map locations will greatly assist future functional studies. This map will be an essential tool for future sequencing of and positional cloning within chromosome 1A

Model Reduction for Grid-Forming Hybrid Renewable Energy Microgrid Clusters Based on Multi-Timescale Characterization

10.13039/501100001809-National Natural Science Foundation of China (Grant Number: 51907031 and 62273104); 10.13039/501100021171-Basic and Applied Basic Research Foundation of Guangdong Province (Grant Number: 2022A1515011163); Science and Technology Program of Guangzhou, China (Grant Number: 2023A04J0273)