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Background: Pyrotinib is a novel irreversible pan-ErbB receptor tyrosine kinase inhibitor. Evidence of the efficacy of pyrotinib-based treatments for HER2-positive metastatic breast cancer (MBC) in patients exposed to lapatinib is limited.Methods: Ninety-four patients who received pyrotinib as a third- or higher-line treatment for HER2-positive MBC were included in this retrospective study. The primary and secondary endpoints were overall survival (OS) and progression‐free survival (PFS). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analysis were implemented to balance important patient characteristics between groups.Results: Thirty (31.9%) patients were pretreated with lapatinib and subsequently received pyrotinib as an anti-HER2 treatment, and 64 (68.1%) patients did not receive this treatment. The OS and PFS indicated a beneficial trend in lapatinib-naive group compared to lapatinib-treated group in either the original cohort (PFS: 9.02 vs 6.36 months, p = 0.05; OS: 20.73 vs 14.35 months, p = 0.08) or the PSM (PFS: 9.02 vs 6.08 months, p = 0.07; OS: 19.07 vs 18.00 months, p = 0.61) or IPTW (PFS: 9.90 vs 6.17 months, p = 0.05; OS: 19.53 vs 15.10 months, p = 0.08) cohorts. Subgroup analyses demonstrated lapatinib treatment-related differences in PFS in the premenopausal subgroup and the no prior trastuzumab treatment subgroup, but no significant differences were observed in OS.Conclusion: Pyrotinib-based therapy demonstrated promising effects in HER2-positive MBC patients in a real-world study, especially in lapatinib-naive patients, and also some activity in lapatinib-treated patients.

Conopomorpha sinensis Bradley (Lepidoptera: Gracilariidae) is one of the major fruit borer pests of litchi and longan in Southern China. Although chemical control is effective, alternative, biorational strategies are preferable, and should be developed. Predators play an important role in the biological control of agricultural pests, but an accurate method for the evaluation of predation in agriculture has not yet been developed. Here, we report a new, specific primer pair to amplify a C. sinensis cytochrome c oxidase subunit I (COI) sequence fragment that can be used to detect consumption of C. sinensis by its predators. C. sinensis DNA was found in several arthropods collected in the field, including the important C. sinensis predators Menochilus sexmaculata (Coccinellidae), Leucauge magnifica (Tetragnathidae), Propylea japonica (Coccinellidae), and Oxyopes sertatus (Oxyopidae). The detection rates of C. sinensis COI DNA in these predators were 39.3, 36.4, 27.3, and 27.2%, respectively. Laboratory consumption and hunting capacity analysis of M. sexmaculata and P. japonica adults indicated that they exhibit a Holling type II functional response on C. sinensis eggs under field temperatures. A polymerase chain reaction digestion analysis of M. sexmaculata and P. japonica adults after consumption of a single C. sinensis egg indicated that positive detection decreased with the extension of digestion time, and estimated prey DNA half-lives were 16.3 h in M. sexmaculata and 6.0 h in P. japonica. These data serve to characterize two major predators of C. sinensis with potential for biological control of C. sinensis in litchi orchards.

To evaluate the effect of thiazovivin, a novel ROCK inhibitor, on the morphology and function of human corneal endothelial cells(HCECs).The primary HCECs were identified by light microscopy and immunofluorescence staining of neuron-specific enolase. To screen the optimal concentration and action time of thiazovivin for maintaining the morphology and function of primary HCECs, Na (+)/K (+)-ATPase and N-cadherin were chosen as indicators, and the morphology and function of HCECs in various concentrations(0 μmol/L, 2 μmol/L, 4 μmol/L, and 6 μmol/L)for different durations(24 h and 48 h)were examined by immunofluorescence experiments. The effect of thiazovivin on the expression of ROCK was investigated by immunofluorescence and Western blot.The primary HCECs cultured were hexagonal, closely packed, homogeneously and obviously stained by neuron-specific enolase. The immunofluorescence staining of Na(+)/K(+)-ATPase showed that when the primary HCECs cultured with various concentrations of thiazovivin(0, 2, 4, 6 μmol/L)for 24 h, the fluorescence were obvious, and the average absorbance values(A)were 1.27±0.08, 3.72±0.17, 21.07±4.67, 3.69±0.34, respectively. And the immunofluorescence staining of N-cadherin revealed that when the primary HCECs treated with 4 μmol/L thiazovivin for 24 h, the cell boundary was clear and the structure of the cells was intact. While the treating time of thiazovivin(4 μmol/L)on HCECs extended to 48 h, the immunofluorescence staining of Na(+)/K(+)-ATPase and N-cadherin showed that compared to HCECs treated with thiazovivin(4 μmol/L)for 24 h, the fluorescence intensity did not change significantly, but the cells arranged slightly untidy. In addition, the immunofluorescence staining of ROCK was weakened and the expression of ROCK was reduced by thiazovivin. Thiazovivin was effective for protecting the morphology and function of HCECs. An optimal improvement in the morphology, connection and function of HCECs was found when the primary HCECs were cultured with 4 μmol/L thiazovivin for 24 h. Moreover, the expression of ROCK protein could be significantly inhibited by thiazovivin. (Chin J Ophthalmol, 2016, 52: 686-692).

We present a study of the effects of substrate orientation and longitudinal channel stress on the performance of extremely thin silicon-on-insulator (ETSOI) MOSFETs with gate lengths down to 25 nm. We find that short-channel electron and hole mobilities follow the long-channel mobility trends versus substrate orientation and longitudinal channel stress. We show that with respect to (100) silicon-on-insulator (SOI) substrates, short-channel ETSOI MOSFETs on (110) SOI substrates lead to 25% enhancement of the p-channel FET drive current at the expense of 12% degradation of the n-channel FET drive current at a fixed off-current of 100 nA/μm and a supply voltage of 1 V. Finally, we estimate that an ETSOI complementary metal-oxide-semiconductor (CMOS) on (110) SOI substrates should lead to 10% faster ring oscillators compared with those on (100) SOI wafers, which also implies that (100)-oriented wafers with (110) sidewalls are a better choice for fabricating nonplanar FinFETs and trigate CMOS circuits.

Ruey-Jian Chen, MD1 Abstract The study subjects included 26 normal young women with regular menstruation cycles and 30 postmenopausal women. The blood and fasting morning urine samples of premenopausal women were taken between the 4th to 11th day of menstrual cycle. In postmenopausal women the blood and urine specimens were taken at least one year after natural menopause, two months after surgical castration, and two months after completion of radiation therapy for cervical cancer. Serum total estrogen level was measured by radioimmunoassay. The urine hydroxyproline concentration was determined by Kivirikko's method. The mean concentrations of serum total estrogens levels were 185.5 pg/ml and 71.7 pg/ml in premenopausal and postmenopausal women respectively. The mean values of urinary calcium/creatinine (Ca/Cr) molar ratio in premenopausal and postmenopausal women were 0.139 and 0.249 respectively. The mean value of hydroxyproline/creatinine (HOPr/Cr) molar ratio was 0.012 in premenopausal women and 0.028 in postmenopausal women. The parameters of bone loss, such as Ca/Cr ratio and HOPr/Cr ratio, are inversely related with the circulating total estrogen concentration. Therefore, decreased endogenous estrogen production seems to be the major pathophysiologic basis for the enhanced rate of urinary calcium and hydroxyproline excretion in Chinese postmenopausal women.

Single-point or limited-point wall fluid entry in a wellbore has been observed in different oil and gas wells all over the world through downhole video logging. The wall fluid entry is expected to affect both the fluid flow characteristics in a wellbore and the pressure drop along the wellbore. In order to investigate the impacts of the single-point wall fluid entry, a numerical simulation model has been set up and a series of numerical simulations have been conducted by using a commercial computational fluid dynamics (CFD) software package. Flow velocity profiles, streaklines, pressure distribution along the wellbore, and so on have been thoroughly investigated. The simulation results clearly demonstrate the influence of the wall fluid entry on the fluid flow as well as the pressure drop along the wellbore. The impacts on the pressure drop along the wellbore have further been quantified.

It is common that prices of raw materials, parts or products decrease significantly after they come onto the market. High technology products are good examples, such as PCs, CPUs, DRAM, and mobile phones. Consequently, the traditional economic production quantity (EPQ) model assuming a constant unit production cost is no longer suitable for today's time-based competition. This study incorporates linearly and exponentially decreasing unit production costs during the mature stage of a product life cycle and presents a mathematical inventory model for production policy. A recursive algorithm is developed to obtain the optimal production schedule and a one-dimension search method is applied to find the optimal number of production cycles. In addition, numerical examples to illustrate the proposed model and its significance with or without considering a continuous reduction in unit production costs for the production policy are discussed as well.

本研究主要在探討兩套新興的文件格式標準ODF和OOX；並且透過支援ODF和OOX的辦公室套裝軟體實際對文字檔、試算表和簡報檔進行實驗觀察及比較分析。發現其間有所差異並存在著相容性的問題。This research investigates two standards of office e-Documents—Open Document Format (ODF) and the Office OpenXML (OOX). Researchers also apply two office applications that one supports ODF and the other supports OOX to open and compare e-Documents of word-processing, spreadsheet and presentation. The result shows that there are some differences between ODF and OOX.

This study proposes a simple algorithm for obtaining an optimal solution on the classical inventory replenishment problem which represents with a linear function in demand for both increasing and decreasing cases. A general procedure is proposed and examples are given to illustrate that our simple approach is also as good as the approaches shown in the literature.

本研究透過維基平台收錄圖書資訊學期刊20種共1,746篇文章，以及9所圖書資訊學系、所共311篇博、碩士論文。然後，根據圖書資訊學研究領域分類表之分類體系分成8大類，再利用Excel及SPSS進行統計分析。結果顯示期刊在8大類的分佈很平均，但文章數量卻有逐漸下滑的趨勢；博、碩士論文的研究則偏重在使用者群服務、資訊系統與檢索及資訊組織的部分。藉由群集分析可將20種期刊分成5個各有其特性的群組。從期刊及博、碩士論文的主題分佈，可看出圖書資訊學研究的狀況。This research uses wiki platform to collect 1,746 articles from 20 Library and Information Science-related journals and 311 theses and/or dissertations from 9 universities. According to Library Information Science Research Areas Classification Scheme, these articles can be divided into eight areas and analyzed statistically by applying Excel and SPSS. The result shows that the collected articles are distributed evenly in these eight research areas. However, the total amount of articles is decreasing. The research focus of theses and dissertations have mainly been on “Services to user populations”, “information systems and retrieval”, and “Organization of information”. By using cluster analysis, 20 journals can be separated into five groups and the similarities of the journals within the same group are very high. From the distribution of topics of the journals, theses and dissertations, the status quo of Library and Information Science research can be understood.

學術出版不但促進了學術傳播，也增進了人類的文明。走過這幾百年，學術出版雖歷經各種變革，然而仍以紙本印刷方式出版為主。近年來由於資訊科技、數位化的快速演進及高速、無遠弗屆的網際網路出現，促使學術出版產生了巨變。本文即從電子出版及電子商務的角度來探討學術出版，同時指出以加值出版為理念，並在價值鏈上進行各種核心加值與服務作業，以為學術出版未來之發展方向。Scholarly publishing is not only to promote scholarly communication but also to enable the human being s civilization. Scholarly publishing had changed many times for several hundred years. But still published in paper form. However, in recent years information technology shifts and Internet grows so quickly that dramatically makes a great impact on the scholarly publishing. This paper dresses these changing and discusses scholarly publishing through electronic publishing and electronic commerce point of view. The paper also talks about value added publishing and core activities in a value chain of the scholar publishing.

Immune tolerance of human cells without generalized immunosuppression was created in groups of normal fetal rats at 17 days of gestation by inoculation ip with primary human hepatocytes in utero. One day after birth, suspensions of human hepatocytes were transplanted via intrasplenic injection and one week later groups of rats were inoculated with hepatitis B virus (HBV). Tolerized rats that were transplanted with human hepatocytes and subsequently infected with HBV produced hepatitis B surface antigen (HBsAg) in serum beginning on day 3. Levels rose fivefold and remained stable at 0.75 pg/ml through at least 60 days. Of cells that stained positive for human serum albumin, approximately 30% were found to be also positive for HBsAg by immunohistochemistry. Serum HBV DNA was detectable from 1 to 15 weeks postinfection. Finally, covalently closed circular DNA, reflecting HBV replication, was found in liver and serum. Controls that were tolerized and not transplanted, but inoculated with HBV, as well as untreated controls, had no evidence of HBV gene expression or replication under identical conditions. The data support the conclusion that primary human hepatocytes transplanted into genetically immunocompetent rodent hosts, survive and maintain sufficient differentiation to produce human serum albumin and be infected by HBV.

As a reslut of the rapid growth of information technology development, libraries deploy automation systems to improve their services. In the past few years, the grovernment spent 360 million NT dollars on public library automation systems. How did it work? Was it worth while? In what directions are library automation system heading? This paper will discuss the above questions and issues. First, it reviews the automation systems of the public libraries. Then, through data analysis, the authors propose suggestions for the public library automation systems in the near future. (Article content in Chinese with English abstract)

In this paper, an analytical model for chemical mechanical polishing (CMP) is described. This model relates the physical parameters of the CMP process to the in-die variation of interlayer dielectric (ILD) in multilevel metal processes. The physical parameters considered in this model include the deposited ILD profile, deformation of the polishing pad and the hydrodynamic pressure of slurry flow. Model parameters are adjusted based on the first ILD layer and then applied to the upper ILD layers. Comparison of simulated results with sample data is performed at the die level of a state-of-the-art microprocessor.

In this letter, we show that undoped-body extremely thin SOI (ETSOI) MOSFETs with SOI thickness in the 4-6-nm range have excellent short-channel control down to 20-25-nm gate lengths, suitable for the 22-nm technology node and beyond. We demonstrate that 6-nm-thin ETSOI devices can deliver high drive currents required for logic applications. Finally, we bring to fore the need for improvements in etch and doping processes to reduce series resistance of 4-nm-thin ETSOI devices in order to make them a viable option for the 15-nm technology node.

Variation in channel length degrades circuit reliability and yield. A common way to compensate for this problem is to increase the mean channel length, which, unfortunately, degrades circuit performance for digital circuits. One source of channel length variation is lithography, during which the line width is influenced by local layout patterns. It is possible to compensate for this effect by resizing transistor gates appropriately on the mask. However, the effectiveness of the correction is limited by constraints such as the mask correction resolution. To determine how to design a good correction scheme with limited resources, we have developed a method to compare different correction algorithms in terms of their impact on the performance of one of the main functional blocks in a state-of-the-art microprocessor. In particular, to evaluate correction algorithms while avoiding the high cost associated with generating multiple mask sets and fabricating product wafers with each of these mask sets, we present a method for predicting the correction results using simulation. Our methodology involves a DRC-based approach for gate resizing, along with critical path simulation for evaluating circuit performance. In-line CD measurement data were used to measure the impact of the proximity effect on transistor channel length. Electrical test results were used to calibrate the device models for circuit simulation.

The advantages and disadvantages of viral and non-viral vectors for gene delivery are reviewed. Advances in systems for introduction of new gene expression are described, including self-deleting retroviral transfer vectors, chimeric viruses and chimeric oligonucleotides. Systems for inhibition of gene expression are also discussed including antisense oligonucleotides, ribozymes and dominant-negative genes. Examples of the use of these systems in animal models and clinical trials for gastrointestinal disorders are discussed.

Due to the advances in in-line inspection technology it is now possible to obtain an early in-line prediction of yield. This paper introduces and compares two new in-line yield prediction methodologies: (1) multilayer critical area method and (2) defect-type-size kill-ratio method. These methods are more accurate than the past and other current approaches used in the semiconductor industry. The first method uses the design layout information along with the in-line defect data, whereas the second method uses the defect and yield data to empirically derive the kill-ratios. We demonstrate our methodologies using data collected in a real wafer fabrication facility at the polysilicon gate (Poly), and the first and second interconnect (Metal 1 and Metal 2) post etch inspection layers. We compare our in-line predictions with the actual yield.

Mitoxantrone can be efficiently loaded into large unilamellar vesicles using a transmembrane pH gradient. Release studies indicate that these drug-loaded carriers are highly stable and even after dissipation of the residual pH gradient retain more than 85% of encapsulated mitoxantrone following dialysis at 37 degrees C for 5 days. In murine studies we have compared the plasma clearance and biodistribution of both mitoxantrone and liposomal lipid following intravenous administration of free drug or mitoxantrone encapsulated in either conventional or sterically stabilized liposomes. In contrast to the rapid blood clearance observed for free mitoxantrone, both liposomal systems provided extended circulation lifetimes, with over 90% of the drug present 1 h after administration and 15-30% remaining at 24 h. In agreement with previous reports, longer plasma half-lives were observed for sterically stabilized liposomes than for conventional systems. In addition, a strong correlation between drug and carrier biodistribution was seen, with uptake occurring mainly in the liver and spleen and paralleling plasma clearance. This would suggest that tissue disposition reflects that of drug-loaded liposomes rather than the individual components. Liposomal encapsulation also significantly reduced mitoxantrone toxicity, allowing administration of higher, more efficacious drug doses. In a murine L1210 tumour model, for example, no long-term survivors were seen in animal groups treated with free drug, whereas at the maximum therapeutic dose of liposomal mitoxantrone survival rates of 40% were observed.

A study on behavior of cement based matrices reinforced by randomly distributed microfibers is summarized. Effects of volume fraction, length and type of fiber, and type of cement based matrix were experimentally examined using uniaxial tensile specimens and three-point bend beams. The matrix fracture properties were measured by a RILEM recommended test procedure. A confocal microscopy technique was used to measure fracture surface roughness, a parameter that was shown to correlate with fracture properties. By incorporating the obtained matrix fracture properties, fiber aspect ratio, and fiber-matrix interface bond into a fracture mechanical R-curve approach, mechanical responses of cement based matrices reinforced by fibers can be predicted.

The tensile properties of mortal reinforced with polyvinyl alcohol (PVA) fibers were studied in this article. Specimens reinforced with varying volume fractions of different-sized fibers were tested in direct tension. Pull-out tests were also conducted to evaluate the interfacial properties between the PVA fiber and mortar matrix. In addition, scanning electron microscopy was used to study the failure mechanism of the fibers in the direct tension test specimens. To study fiber distribution, images of the specimen cross-sections obtained with an optical microscope were analyzed. It was found that if the influence of fiber length is taken into account, the first peak stress can be expressed as a unique function of the measured fiber distance, regardless of fiber volume fraction and diameter.

Fracture processes in cement-based materials are characterized by a large-scale fracture process zone, localization of deformation, and strain softening. Many studies have been conducted to understand the toughening mechanisms of such quasi-brittle materials and to theoretically model their nonlinear response. This paper summarizes two innovative experimental techniques which are being developed at the ACBM Center to better define the fracture process zone in cement-based materials. A brief summary is also given of two types of theoretical approaches which attempt to simulate some of the observed nonlinear fracture response of these materials.

The characterization of fracture behavior is a continuing challenge to the cement and concrete community. The performance of a material can be evaluated by its stress-strain response. For an ideally brittle material, elastic response is terminated when stress suddenly drops to zero, as shown in Figure 1a. However, cement-based materials are considered quasi-brittle because they respond nonlinearly prior to peak stress, and their stress gradually decreases after reaching a peak, as indicated in Figure 1b.To make cement-based materials stronger and tougher, one needs to understand the fracture mechanisms associated with nonlinear stress-strain behavior and to characterize material fracture properties based on these fracture mechanisms. Three novel techniques are being used at the Center for Advanced Cement-Based Materials (ACBM) to detect the quasi-brittle nature of cement-based materials. These three techniques are laser holographic interferometry, acoustic emission, and microscopic surface analysis. This article summarizes both the fracture mechanisms in cement-based materials and the application of the three techniques to characterize and measure fracture properties.

We report the first genome-wide association study in 1000 bipolar I patients and 1000 controls, with a replication of the top hits in another 409 cases and 1000 controls in the Han Chinese population. Four regions with most strongly associated single-nucleotide polymorphisms (SNPs) were detected, of which three were not found in previous GWA studies in the Caucasian populations. Among them, SNPs close to specificity protein 8 (SP8) and ST8 α-N-acetyl- neuraminide α-2,8-sialyltransferase (ST8SIA2) are associated with Bipolar I, with P-values of 4.87 × 10(-7) (rs2709736) and 6.05 × 10(-6) (rs8040009), respectively. We have also identified SNPs in potassium channel tetramerization domain containing 12 gene (KCTD12) (rs2073831, P=9.74 × 10(-6)) and in CACNB2 (Calcium channel, voltage-dependent, β-2 subunit) gene (rs11013860, P=5.15 × 10(-5)), One SNP nearby the rs1938526 SNP of ANK3 gene and another SNP nearby the SNP rs11720452 in chromosome 3 reported in previous GWA studies also showed suggestive association in this study (P=6.55 × 10(-5) and P=1.48 × 10(-5), respectively). This may suggest that there are common and population-specific susceptibility genes for bipolar I disorder.

The intrinsic FinFET device structure can provide an estimated 10–20% reduction in delay relative to planar FETs at the 22nm technology node due to superior electrostatics. However, FinFETs are more prone to parasitic resistance and capacitance due to the thin body channel and 3-dimensional device architecture. Here we present strategies for minimizing FinFET parasitic resistance, and discuss overall device design optimization. Using FinFETs built at 45nm node dimensions, we have demonstrated FinFETs with an NFET/PFET external resistance of 230/350 Ω-um.