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Shikonin, the predominant naphthoquinone pigment isolated from the Chinese plant Lithospermum erythrorhizon, is anti-inflammatory, antiviral and exerts anticancer effects, amongst other biological activities. However, it is unknown whether shikonin affects bone formation. In the present study, the role of shikonin on cell proliferation was assessed via MTT assay, and shikonin was identified to markedly promote cell growth in a time- and dose-dependent manner in the MC3T3-E1 cell line. In addition, flow cytometric analysis was performed to evaluate the effect of shikonin on the cell cycle, and it was observed that shikonin markedly increased the percentage of S-phase MC3T3-E1 cells to accelerate the G1/S transition. To investigate the potential molecular mechanism by which shikonin enhances bone formation, the changes in bone morphogenic protein-2 (BMP-2), SMAD family member 5 (Smad5), runt related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and osteocalcin (OC) expression levels induced by shikonin were investigated using western blot analysis and quantitative polymerase chain reaction. The results indicated that shikonin increased the BMP-2 and Smad5 mRNA levels, and upregulated Smad5 and Runx2 protein expression levels to promote osteoblast differentiation. Furthermore, ALP staining was performed, and revealed that shikonin enhanced ALP activity. These results indicate that shikonin promotes cell proliferation and differentiation of MC3T3-E1 cells via the BMP-2/Smad5 signaling pathway. [ABSTRACT FROM AUTHOR]

Purpose - In today's electronic package development cycle, activities are managed by multiple participants in the supply chain, which might have different quality and reliability impacts to the end product. As a result, the reliability risk is much higher for companies who do not have insight into and/or control over the products received. The purpose of this paper is to show how design-for-reliability (DFR) approaches will come into play to manage the risk. Design/methodology/approach - In this paper, DFR approaches for package development will be discussed from the perspective of the original equipment manufacturers (OEMs). DFR practices through the package development cycle will be described based on key development modules. A case study for flip chip ball gris array package development using an advanced Cu/Low-k silicon technology will be presented. Key measures to help control the quality and improve the reliability will be presented. Findings - The proposed methodology significantly improves component and package reliability through the engagement in design, manufacturing, assessment and system evaluation. Originality/value - The paper discusses the research results and the proposed DFR methodology will be helpful for fabless design houses, electronics manufacturing service (EMS) partners in the supply chain, and OEMs to manage the reliability of the products. [ABSTRACT FROM AUTHOR]

The reliability of high-density enhanced ball grid array, (EBGA) packages using the eight-layer Cu metallization silicon was discussed. The key failure mechanisms included the die cracking (in the vicinity of the edge) and thin film delamination. It was noticed that the failure was unique to the Cu metallization silicon. The large package body size (45 mm²) and the die size (approximately 15 mm²) provided additional manufacturing and reliability challenges. The die-edge defects induced during the wafer sawing process were exhibited to be the culprits of the die cracking and the thin film delamination failures. Additionally, the height of die attach fillets significantly influenced the stresses on the die edge, and the excessive fillet height was found to help extend initial cracks at the edge of the silicon. The results demonstrated the adoption of a dual-step wafer sawing scheme and resin blades would control the defects and reduce the failure rate dramatically. A mixture of low-stress encapsulation and die attach materials would help improve the overall reliability of the packages as well. The solder joint reliability of the package was very robust based on the board-level reliability testing results. The statistical analysis of the test results confirmed that most of the die cracking and thin film delamination failures were early-life failures and random. A good sample screening scheme and the process improvement procedure would help improve the reliability and insure the customer a low failure rate for the lifetime of the product. The predicted reliability of the package met the application life needs for the products with process improvement plans in place. [ABSTRACT FROM AUTHOR]

A measurement-based method for extracting the parasitic parameters of active power electronics modules (IPEMs) is proposed. Parasitic inductances and capacitances inside the IPEM can all be extracted using this method without destroying the structure. The linearized model is derived from impedance measurement and it is valid from low frequency to frequencies as high as 100 MHz. Extracted parameters are compared to those from commercial software and the results are in good agreement. A parallel resonance method is proposed for the characterization of common-mode capacitances. [ABSTRACT FROM AUTHOR]

Liquid encapsulation techniques have been used extensively in advanced semiconductor packaging, including applications of underfilling, cavity-filling, and glob top encapsulation. Because of the advanced encapsulation materials and the automatic liquid dispensing equipment involved, it is very important to understand the encapsulation material characteristics, equipment characteristics, encapsulation process development techniques in order to achieve the encapsulation quality and reliability. In this paper, the authors will examine the various considerations in liquid encapsulation applications and address the concerns on material characterization, automatic liquid dispensing equipment/process characterization and the encapsulation quality and reliability. The discussions will be helpful for future material and process development of semiconductor packages. [ABSTRACT FROM AUTHOR]

Evaluates the four-channel multiplexed electrospray triple quadrupole mass spectrometer for validation of liquid chromatography, mobility spectrometry and mass spectrometry methods. Use of four differential preclinical matrixes.

Demonstrates the use of capillary isoelectic focusing (CIEF) with electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry, in the analysis of model proteins, human hemoglobin variants and Escherichia coli proteins. Description of experiments conducted; Identification of model proteins; Characterization of protein mixtures.

Organophosphate pesticide poisoning has become a global concern in recent decades. This study aimed to explore the protective effects of resveratrol, a well-known bioactive natural product, on human normal skin fibroblasts after paraoxon treatment and its specific mechanisms. The methyl thiazolyl tetrazolium assay was used to study the effect of resveratrol on the viability of normal skin fibroblasts after paraoxon treatment. Delta alpha pi staining was performed to observe apoptosis in the normal skin fibroblasts. JC-1 staining and 2’,7’-dichlorofluorescein staining were used to investigate mitochondrial damage. The expressions of p38-mitogen-activated protein kinase and c-Jun N-terminal kinase signaling pathwayrelated proteins were determined using western blotting. Resveratrol enhanced the viability of normal skin fibroblasts in a dose-dependent manner after paraoxon treatment. It significantly reduced the number of cells showing nuclear concentration/fragmentation and the apoptotic level after paraoxon treatment. Moreover, resveratrol significantly lowered the 2’,7’-dichlorofluorescein fluorescence intensity in normal skin fibroblasts, decreased the JC-1 green fluorescence level, and increased the red fluorescence level in normal skin fibroblasts with increasing concentrations. Finally, resveratrol considerably reduced the expressions of phosphorylated extracellular signal-regulated protein kinases, c-Jun N-terminal kinase, and p38-mitogen-activated protein kinase. Resveratrol can alleviate paraoxon toxicity in normal skin fibroblasts by reducing apoptosis, mitigating mitochondrial damage, and inhibiting the mitogen-activated protein kinase pathway. Therefore, resveratrol may be a novel therapeutic option for organophosphate pesticide poisoning. [ABSTRACT FROM AUTHOR]