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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ejor.2006.12.024 Byline: Chang-Chun Lin (a), Yi-Ting Liu (b) Keywords: Portfolio selection; Markowitz model; Minimum transaction lots; Genetic algorithm; Fuzzy multi-objective decision making Abstract: Conventionally, portfolio selection problems are solved with quadratic or linear programming models. However, the solutions obtained by these methods are in real numbers and difficult to implement because each asset usually has its minimum transaction lot. Methods considering minimum transaction lots were developed based on some linear portfolio optimization models. However, no study has ever investigated the minimum transaction lot problem in portfolio optimization based on Markowitz' model, which is probably the most well-known and widely used. Based on Markowitz' model, this study presents three possible models for portfolio selection problems with minimum transaction lots, and devises corresponding genetic algorithms to obtain the solutions. The results of the empirical study show that the portfolios obtained using the proposed algorithms are very close to the efficient frontier, indicating that the proposed method can obtain near optimal and also practically feasible solutions to the portfolio selection problem in an acceptable short time. One model that is based on a fuzzy multi-objective decision-making approach is highly recommended because of its adaptability and simplicity. Author Affiliation: (a) Department of Information Management, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan 333, Taiwan, ROC (b) Institute of Information Management, National Chiao Tung University, 1001 Ta Hsueh Road, Hsinchu 300, Taiwan, ROC Article History: Received 12 March 2006; Accepted 11 December 2006

Pristimerin (Pris), a bioactive triterpenoid compound extracted from the Celastraceae and Hippocrateaceae families, has been reported to exhibit an anti-cancer property on various cancers. However, the effects of Pris on esophageal cancer are poorly investigated. This current study sought to explore the activity and underlying mechanism of Pris against human esophageal squamous cell carcinoma (ESCC) cells. We demonstrated that Pris showed cytotoxicity in TE-1 and TE-10 ESCC cell lines, and significantly inhibited cell viability in a concentration dependent manner. Pris induced G0/G1 phase arrest and triggered apoptosis. It was also observed that the intracellular ROS level was remarkedly increased by Pris treatment. Besides, the function of Pris mediating the activation of ER stress and the inhibition of AKT/GSK3β signaling pathway in TE-1 and TE-10 cells was further confirmed, which resulted in cell growth inhibition. And moreover, we revealed that all of the above pathways were regulated through ROS generation. In conclusion, our findings suggested that Pris might be considered as a novel natural compound for the developing anti-cancer drug candidate for human esophageal cancer. • Pristimerin exhibited notable anti-esophageal cancer activity. • Pristimerin induced cell cycle arrest, promoted apoptosis, and increased ROS level. • Pristimerin regulated AKT/GSK3β pathway via ROS production to inhibit cell growth. • Pristimerin suppressed cell growth through ROS-mediated ER stress. [ABSTRACT FROM AUTHOR]

To explore whether a climate services approach can enable both energy saving and indoor comfort. After analysis of the local weather forecast, the air conditioning temperature of a government building was set to be adjusted at 7:30, 11:00, and 17:00. The indoor temperature and humidity were measured by using a MAPS6.0 sensor, and thermal comfort was calculated using ISO 7730 standards. Multiple regression analysis was used to examine the correlation between the weather forecast and chiller energy consumption. After a three-stage air conditioning temperature control process was implemented, predicted mean vote values between 0 and 0.5 were achieved for 79.1% of the working hours in the experimental period. Outdoor and air conditioning temperatures were the most critical factors affecting the hourly energy consumption of the air conditioner and water-cooled chiller. With every 1 °C increase in the outdoor temperature, the hourly energy consumption increased by 6.57. Moreover, with every 1 °C increase in the air conditioner temperature, the hourly energy consumption decreased by 8.63. A predicted mean vote value of >0.5 was recorded for 15.9% of the working hours; this may be related to high indoor humidity, weather forecast inaccuracies, and the air conditioner being turned on too late in the day. From July to October 2021, 8749 kW h of electricity were saved, and carbon emissions were reduced by 1405 kg. Regulating air conditioning temperatures through weather forecasts can achieve energy savings. • Three-stage air conditioning control process reduces carbon emissions. • Three-stage air conditioning control process saves electricity. • Air conditioning temperature controlling using weather forecasts saves energy. [ABSTRACT FROM AUTHOR]

Abstract: This paper presents the development of a high-frequency power supply for surface quality improvement of wire electrical discharge machining (wire-EDM). A novel fixed pulse-width modulation pulse control method is proposed to generate high-frequency and short-duration pulse control signals. A spark gap model using a resistance–capacitance (RC) circuit and a Zener diode is proposed for circuit design and simulation analysis. Tests revealed that the developed power supply using anti-electrolysis circuitry and digital signal processor-based pulse control circuit can provide very low discharge energy pulses with a frequency of 4.4MHz, discharge duration of 90ns and a peak current of 1.2A. Experimental results demonstrate that a pulse duration ratio (defined as a ratio between pulse duration of positive polarity and that of negative polarity) of three can reduce the electrolytic effect of tungsten carbide for the machining conditions of high discharge frequency more than 500kHz. [Copyright &y& Elsevier]

Fluorescein silica core–shell nanoparticles, gold@silica@fluorescein were synthesized to study the effects of metal-enhanced fluorescence (MEF) on fluorescein in neutral and basic ethanol solutions. The interaction between gold nanoparticles and fluorescein with silica shells of different thicknesses as spacers was investigated by time-resolved fluorescence spectroscopy. Only the emission spectra of fluorescein overlapped with the surface plasmon resonance of gold nanoparticles, which is regarded as an example for the study of the emission-enhancement of MEF. The fluorescence spectra of GNP@silica@FiTC were red-shifted from those of silica@FiTC and FiTC in solution. And, the emission curves had biexponential decay, indicating multiple pathways for relaxation of the excited fluorophore. The values of fluorescence enhancement factor (EF) were slightly greater in neutral ethanol solution than in basic solution. The lowest silica shell thickness synthesized, ≈12 nm, had the largest fluorescence EF ≈ 2; this enhancement decreased as the shell thickness increased. At thickness 12 nm, the lifetime of the short component in the emission decay was 60–70 ps and its amplitude close to 90%. Based on the obtained lifetimes, ratios of component amplitudes, and proposed kinetic model, the rate constants for the process of the energy transfer between fluorophores and gold nanoparticles were attained. These rate constants for energy transfer displayed a dependence on the thickness of the silica shell, d-n, where n = 1.3–2.6. • Fluorescein binding on silica core-shell gold nanoparticle has an enhancement factor near 2 better in neutral than in basic solution. • Biexponential decay emission of GNP@slica@fluorescein indicates reversible reaction between fluorescein and GNP. • Fluorescein enclosed in silica spacer existed mostly dianion form. [ABSTRACT FROM AUTHOR]

• Recent understanding of ClpX had been summarized in this review. • A single molecular system had been designed to study the mechanical changes of ClpX. • ClpX mutants could be constructed to mimick their state of ATP-binding and ATP-free. • Experimental results would elucidate the mechanism of power stroke of ClpX. ClpXP in Escherichia coli is a proteasome degrading protein substrates. It consists of one hexamer of ATPase (ClpX) and two heptamers of peptidase (ClpP). The ClpX binds ATP and translocates the substrate protein into the ClpP chamber by binding and hydrolysis of ATP. At single molecular level, ClpX harnesses cycles of power stroke (dwell and burst) to unfold the substrates, then releases the ADP and Pi. Based on the construction and function of ClpXP, especially the recent progress on how ClpX unfold protein substrates, in this mini-review, a currently proposed single ClpX molecular model system detected by optical tweezers, and its prospective for the elucidation of the mechanism of force generation of ClpX in its power stroke and the subunit interaction with each other, were discussed in detail. [ABSTRACT FROM AUTHOR]

In this study, a 1.0 mm thick (Zr 48 Cu 32 Al 8 Ag 8 ,Ta 4 )Si 0.75 alloy composite (AC) plate was laser remelted (LR) by employing the Nd:YAG laser technique. To fully remelt the plate, a two-sided welding process with preselected parameters was employed. The microstructure, mechanical (microhardness), thermal properties, and corrosion resistance (potentiodynamic polarization) of the laser remelted alloy composite (LR-AC), the Zr-Cu AC (with the crystalline structure), and the Zr-Cu based bulk metallic glass composite (BMGC, the same composition as the AC. The amorphous matrix is produced by a rapid cooling rate) were then investigated and compared. The test results show that after the laser remelting processes, the LR-AC consisted of an amorphous matrix and reinforced phase, Ta, in the remelted areas, which is similar to the BMGC; however, the volume fractions and grain size of the micro-sized reinforced phase, Ta, in the LR-AC were reduced. When compared to those of the BMGC, the GFA indices of LR-AC were slightly improved. For the hardness tests, LR-AC showed a similar hardness to that of the BMGC; however, a higher value was obtained when compared to that of the AC. Furthermore, the LR-AC exhibits a lower I corr (a slower corrosion rate), which is attributed to the amorphous matrix and less micro-sized Ta content, eliminating corrosion occurring between the Ta and the matrix of the alloy. [ABSTRACT FROM AUTHOR]

To investigate the effect of the volume fraction of the ex-situ reinforced Ta additions on the weldability of Zr–Cu–Ag–Al bulk metallic glass composites (BMGCs), in this study, different Ta contents (0–6 vol%) of BMGCs are welded using the Nd:YAG pulsed laser technique with preselected welding parameters. After welding, the microstructure (including the parent material (PM), weld fusion zone (WFZ) and heat-affected zone (HAZ)), mechanical and thermal properties of the test samples are investigated. The test results show, for all BMGC welds, the micro-sized Ta particles in the PM, WFZ and HAZ to be covered by a crystallized interfacial layer (IL), ZrCu. For both un-welded and laser-welded BMGCs, as the Ta contents increase, the glass transformation temperature (T g ) increases, which in turn reduces the glass formation ability (GFA) indices, ΔT x , γ and γ m . However, when compared to that of un-welded BMGC, the GFA index, ΔT x , of the laser-welded BMGCs is slightly improved. However, the γ, and γ m of the BMGC welds seem not to be affected. In addition, due to the characteristics of the rapid thermal cycle of the laser welding process, two smaller sizes of Ta, nano-sized (mainly on the surface of WFZ) and sub micro-sized Ta, are found in the WFZ. These sub-micro-sized Ta particles normally locate near the micro-sized Ta, which tends to slightly reduce the hardness in this area. Furthermore, an increase in the volume fraction of Ta (0–6 vol%) in the BMGCs does not encourage the formation of the harmful crystalline phase in the amorphous matrix after the laser welding process. It is observed that, other than the IL (ZrCu) on the micro-sized Ta particles, no other type of crystalline is observed in the amorphous matrix of the laser-welded BMGCs. [ABSTRACT FROM AUTHOR]

Brain cancer is a deadly disease with low survival rates for over 70 % of patients. Therefore, there is a critical need to develop better treatment methods and strategies to improve patient outcomes. In this study, we explored the tumor microenvironment and discovered unique characteristics of microglia to interact with astrocytoma cells and promote proliferation and migration of collisions. The conditioned medium from the collisions expressed cell chemoattraction and anti-inflammatory responses. To further understand the interactions between microglia and astrocytoma cells, we used flow sorting and protein analysis found that the protein alterations were related to biogenesis in the astrocytoma cells and metabolic processes in the microglia. Both types of cells were involved in binding and activity in cell-cell interactions. Using STRING to demonstrate the protein cross-interaction between the cells. Furthermore, PHB and RDX interact with oncogenic proteins, which were significantly expressed in patients with Glioblastoma Multiforme (GBM) and low-grade glioma (LGG) according to GEPIA. To study the role of RDX in chemoattraction, the inhibitor-NSC668394 suppressed collision formation and migration in BV2 cells in vitro by down-regulating F-actin. Additionally, it suppressed macrophage infiltration in infiltrating islands in vivo of intracranial tumor-bearing mice. These findings provide evidence for the role of resident cells in mediating tumor development and invasiveness and suggest that potential interacting molecules may be a strategy for controlling tumor growth by regulating the infiltration of tumor-associated microglia in the brain tumor microenvironment. [ABSTRACT FROM AUTHOR]

Developing non-statin small molecules for the treatment of hypercholesterolemia remains challenging. The proprotein convertase subtilisin/kexin type 9 (PCSK9)-targeted therapies have attracted considerable attentions. Forty-five 7030B-C5 derivatives were synthesized and evaluated for the PCSK9 repression activity, taking the PCSK9 transcriptional inhibitor 7030B-C5 as the lead. Structure-activity relationship (SAR) analysis at C8 and N7-position was carried out, and compound 3s and 5r exhibited comparable PCSK9 transcriptional inhibitory activity but much lower cytotoxicity with the therapeutic index (TI) values doubled of that of 7030B-C5. In the in vitro assay, both compounds significantly reduced the level of PCSK9 protein and increased LDL receptor (LDLR) protein level. What's more, both compounds promoted LDL cholesterol (LDL-C) clearance more efficiently than 7030B-C5 in HepG2 cells. Most importantly, compound 3s reduced the atherosclerotic plaque areas with promising lipid-lowing effects in ApoE KO mice with a higher in vivo activity and lower toxicity. The regulatory mechanism of 3s was explored that it might target the transcription factor HNF1α and/or HINFP upstream of PCSK9 transcription, similar to that of 7030B-C5. Thus, 3s was considered as a potential anti-atherosclerosis drug candidate as a novel PCSK9 down-regulatory agent, worthy of further investigations. [Display omitted] • Novel PCSK9 modulators were synthesized and evaluated in vitro and in vivo. • Compound 3s promoted more LDL-C clearance than 7030B-C5 via PCSK9 in vitro. • Compound 3s exhibited much lower cytotoxicity than 7030B-C5. • Compound 3s reduced TC and plaque with higher in vivo activity and lower toxicity. • Compound 3s could be a potential candidate for the treatment of hyperlipidemia. [ABSTRACT FROM AUTHOR]

[Display omitted] • A series of phenylurea hydroxamic acids have been synthesized. • These synthetics were evaluated for antiproliferative, HDAC isoform activity, VEGFR-2 activity, and circulating endothelial progenitor cells activity. • Compound 14 not only inhibits HDAC but also has slight VEGFR-2 inhibitory activity. A series of phenylurea hydroxamic acids incorporating pharmacophores of inhibitors of HDAC inhibitors and VEGFR-2 has been designed. Most of the compounds show antiproliferative activity comparable to that of Vorinostat and Sorafenib, and better EPC inhibitory activity. Enzymatic assays and Western blotting results indicated that compound 14 not only inhibits HDAC but also has slight VEGFR-2 inhibitory activity. A docking study revealed that the polar hydroxamic acid retains the interaction with HDAC through a zinc ion and also interacts with some residues of the active site of VEGFR-2. Despite 14 displaying a weaker VEGFR-2 activity, a possible route to develop potent HDAC/VEGFR-2 inhibitors is suggested. [ABSTRACT FROM AUTHOR]

A series of C6-substituted N -hydroxy-2-quinolineacrylamides (3 – 15), with four types of bridging groups have been synthesized. Most of these compounds exhibit antiproliferative activity against A549 and HCT116 cells and Western blot analysis revealed that they are able to inhibit HDAC. Measurement of the HDAC isoform activity of ether-containing compounds showed that compound 9 has distinct HDAC6 selectivity, more than 300-fold over other isoforms. This paper describes the development of 6-aryloxy- N -hydroxy-2-quinolineacrylamides as potential HDAC6 inhibitors. [ABSTRACT FROM AUTHOR]