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Parkinson's disease (PD) and Spinocerebellar ataxia (SCA) are two age-related neurodegenerative disease that affect the movement of patients. A curative treatment does not exist for both diseases as the molecular mechanisms remain unclear. For a subset of PD cases and all SCA cases, the disease is caused by pathogenic variants in certain genes. Therefore, studying these variants provides molecular insights in the disease mechanisms. Specifically, using a toolbox of molecular techniques, including CRISPR-Cas9 gene-editing, we investigated genetic variants that are linked to SCA and PD to increase our understanding of these variants and the associated defective cellular pathways. We showed that the variants linked to PD cause defects in different pathways involving the removal of cellular waste products, such as the endolysosomal system and mitophagy. Furthermore, we made observations that hint to developmental defects in SCA. Together, we made some meaning of the molecular mechanisms underlying two monogenic movement disorders.

HMM based synthesis has attracted great interest due to its compact and flexible modelling of spectral and prosodic parameters. In this approach, short term spectra, fundamental frequency (F0) and duration are simultaneously modelled by multi-stream HMMs. However, since F0 values in unvoiced regions are normally considered as undefined, it is difficult to use standard HMMs for F0 modelling. The currently preferred solution to this is to use a multi-space distribution HMM (MSDHMM) in which discrete distributions are used for modelling the voiced/unvoiced decision and continuous Gaussian distributions are used for modelling the F0 values within the voiced regions. However, the assumption of undefined unvoiced F0 regions and the special structure of the MSDHMM lead to limitations in the accurate modelling of F0 patterns. In this paper an alternative is explored whereby unvoiced F0 values are assumed to exist and are modelled within the standard HMM framework using a globally tied distribution (GTD). Subjective evaluations show that these regular HMMs with GTD can produce significant improvements in the naturalness of the synthesised speech compared to the MSDHMM, and furthermore, the method is insensitive to the exact method used for unvoiced F0 generation., ICASSP2009: IEEE International Conference on Acoustics, Speech, and Signal Processing, April 19-24, 2009, Taipei, Taiwan.

Kai-Yu Wang,1 Yi-Chuan Chen,1,2 Jau-Yuan Chen,1,2 Song-Seng Loke,3 Wei-Chung Yeh,4 Wen-Cheng Li1,2,5 1Department of Family Medicine, Chang-Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Family Medicine, Chang-Gung Memorial Hospital at Kaohsiung, Kaohsiung, Taiwan; 4Department of Family Medicine, Chang-Gung Memorial Hospital at Keelung, Keelung, Taiwan; 5Department of Health Management, Xiamen Chang-Gung Hospital, Xiamen, People’s Republic of ChinaCorrespondence: Wen-Cheng Li, Email win3135@hotmail.comBackground: Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been recognized as a valuable biomarker for identifying the risk of cardiovascular diseases and inflammation. Furthermore, there is strong evidence to suggest that metabolic syndrome is closely associated with chronic inflammation. Accordingly, the present study endeavors to examine the potential correlation between metabolic syndrome and the levels of Lp-PLA2.Methods: To explore the relationship between Lp-PLA2 levels and metabolic syndrome, and to establish the predictive cut-off value of Lp-PLA2, a retrospective analysis was conducted using medical data from a sample of 3549 Chinese adults (comprising 2182 men and 1367 women) aged between 18 and 50 years, who had undergone health check-ups. In addition, the study also sought to investigate any potential differences in Lp-PLA2 levels based on sex and age.Results: The analysis of the data indicated that participants had a mean age of 44.2 years, a mean Lp-PLA2 level of 589 IU/L, and a metabolic syndrome prevalence of 22%. Lp-PLA2 levels were significantly different between males and females, and a significant correlation was observed between Lp-PLA2 levels and clinical and metabolic characteristics, including BMI, cholesterol, and triglycerides. Interestingly, Lp-PLA2 demonstrated potential as an indicator of metabolic syndrome, particularly in females, despite other bioma

A prominent theoretical framework spanning philosophy, psychology, and neuroscience holds that selective attention penetrates early stages of perceptual processing to alter the subjective visual experience of behaviorally relevant stimuli. For example, searching for a red apple at the grocery store might make the relevant color appear brighter and more saturated compared with seeing the exact same red apple while searching for a yellow banana. In contrast, recent proposals argue that data supporting attention-related changes in appearance reflect decision- and motor-level response biases without concurrent changes in perceptual experience. Here, we tested these accounts by evaluating attentional modulations of EEG responses recorded from male and female human subjects while they compared the perceived contrast of attended and unattended visual stimuli rendered at different levels of physical contrast. We found that attention enhanced the amplitude of the P1 component, an early evoked potential measured over visual cortex. A linking model based on signal detection theory suggests that response gain modulations of the P1 component track attention-induced changes in perceived contrast as measured with behavior. In contrast, attentional cues induced changes in the baseline amplitude of posterior alpha band oscillations (∼9-12 Hz), an effect that best accounts for cue-induced response biases, particularly when no stimuli are presented or when competing stimuli are similar and decisional uncertainty is high. The observation of dissociable neural markers that are linked to changes in subjective appearance and response bias supports a more unified theoretical account and demonstrates an approach to isolate subjective aspects of selective information processing.SIGNIFICANCE STATEMENT Does attention alter visual appearance, or does it simply induce response bias? In the present study, we examined these competing accounts using EEG and linking models based on signal detection

Semi-supervised semantic segmentation aims to utilize limited labeled images and abundant unlabeled images to achieve label-efficient learning, wherein the weak-to-strong consistency regularization framework, popularized by FixMatch, is widely used as a benchmark scheme. Despite its effectiveness, we observe that such scheme struggles with satisfactory segmentation for the local regions. This can be because it originally stems from the image classification task and lacks specialized mechanisms to capture fine-grained local semantics that prioritizes in dense prediction. To address this issue, we propose a novel framework called \texttt{MaskMatch}, which enables fine-grained locality learning to achieve better dense segmentation. On top of the original teacher-student framework, we design a masked modeling proxy task that encourages the student model to predict the segmentation given the unmasked image patches (even with 30\% only) and enforces the predictions to be consistent with pseudo-labels generated by the teacher model using the complete image. Such design is motivated by the intuition that if the predictions are more consistent given insufficient neighboring information, stronger fine-grained locality perception is achieved. Besides, recognizing the importance of reliable pseudo-labels in the above locality learning and the original consistency learning scheme, we design a multi-scale ensembling strategy that considers context at different levels of abstraction for pseudo-label generation. Extensive experiments on benchmark datasets demonstrate the superiority of our method against previous approaches and its plug-and-play flexibility.

The $W$ boson mass recently reported by the CDF collaboration shows a deviation from the standard model prediction with an excess at $7\sigma$ level. We investigate two simple extensions of the standard model with an extra $U(1)$ dark sector. One is the $U(1)_x$ extension, where the $U(1)_x$ gauge field mixes with the standard model through gauge kinetic terms. The other is a general $U(1)_{\alpha Y+\beta q}$ extension of the standard model. Fitting various experimental constraints we find the $U(1)_x$ extension with only kinetic mixing can enhance the $W$ boson mass for at most 10 MeV. While the $U(1)_{\alpha Y+\beta q}$ extension can easily generate 77 MeV enhancement of the $W$ boson mass and also offer a viable dark matter candidate with mass ranging from several hundred GeV to TeV, which may be detected by future dark matter direct detection experiments with improved sensitivities., Comment: 16 pages, 4 figures

Counterfeit-related studies have revealed motivational drives for counterfeit consumption. Little is known concerning the implications of consumers’ enduring and normative beliefs about proper standards of conduct as the determinants of counterfeit patronage. Drawing on the Schwartz theory of human values, experience literature and construal level theory, this research investigates counterfeits patronage by addressing three crucially important questions: 1) what personal values determine counterfeit patronage; 2) how do these relationships vary as a function of counterfeit experience; and 3) how do values have power in eliminating counterfeit consumption? Two studies provide robust evidence that self-transcendence values mitigate counterfeit patronage when consumers’ counterfeit experience is low. We also demonstrate that consumers who endorse self-transcendence values more exhibit higher levels of construal, which results in reduced counterfeit patronage.

The novel coronavirus disease (COVID-19) pandemic has made a huge impact on people's physical and mental health, and it remains a cause of death for many all over the world. To prevent the spread of coronavirus infection, different types of public health measures (social isolation, quarantine, lockdowns, and curfews) have been imposed by governments. However, mental health experts warn that the prolonged lockdown, quarantine, or isolation will create a “second pandemic” with severe mental health issues and suicides. The quarantined or isolated people may suffer from various issues such as physical inactivity, mental health, economic and social problems. As with the SARS outbreak in 2003, many suicide cases have been reported in connection with this current COVID-19 pandemic lockdown due to various factors such as social stigma, alcohol withdrawal syndrome, fear of COVID infection, loneliness, and other mental health issues. This paper provides an overview of risk factors that can cause suicide and outlines possible solutions to prevent suicide in this current COVID-19 pandemic.

Contains fulltext : 231334.pdf (Publisher’s version ) (Open Access)

Semi-supervised learning has substantially advanced medical image segmentation since it alleviates the heavy burden of acquiring the costly expert-examined annotations. Especially, the consistency-based approaches have attracted more attention for their superior performance, wherein the real labels are only utilized to supervise their paired images via supervised loss while the unlabeled images are exploited by enforcing the perturbation-based \textit{"unsupervised"} consistency without explicit guidance from those real labels. However, intuitively, the expert-examined real labels contain more reliable supervision signals. Observing this, we ask an unexplored but interesting question: can we exploit the unlabeled data via explicit real label supervision for semi-supervised training? To this end, we discard the previous perturbation-based consistency but absorb the essence of non-parametric prototype learning. Based on the prototypical network, we then propose a novel cyclic prototype consistency learning (CPCL) framework, which is constructed by a labeled-to-unlabeled (L2U) prototypical forward process and an unlabeled-to-labeled (U2L) backward process. Such two processes synergistically enhance the segmentation network by encouraging more discriminative and compact features. In this way, our framework turns previous \textit{"unsupervised"} consistency into new \textit{"supervised"} consistency, obtaining the \textit{"all-around real label supervision"} property of our method. Extensive experiments on brain tumor segmentation from MRI and kidney segmentation from CT images show that our CPCL can effectively exploit the unlabeled data and outperform other state-of-the-art semi-supervised medical image segmentation methods., Comment: 11 pages

Purpose: To investigate the activity of niraparib in patients with germline-mutated BRCA1/2 (gBRCAm) advanced breast cancer. Patients and Methods: BRAVO was a randomized, open-label phase III trial. Eligible patients had gBRCAm and HER2-negative advanced breast cancer previously treated with ≤2 prior lines of chemotherapy for advanced breast cancer or had relapsed within 12 months of adjuvant chemotherapy, and were randomized 2:1 between niraparib and physician’s choice chemotherapy (PC; monotherapy with eribulin, capecitabine, vinorelbine, or gemcitabine). Patients with hormone receptor–positive tumors had to have received ≥1 line of endocrine therapy and progressed during this treatment in the metastatic setting or relapsed within 1 year of (neo)adjuvant treatment. The primary endpoint was centrally assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), PFS by local assessment (local-PFS), objective response rate (ORR), and safety. Results: After the pre-planned interim analysis, recruitment was halted on the basis of futility, noting a high degree of discordance between local and central PFS assessment in the PC arm that resulted in informative censoring. At the final analysis (median follow-up, 19.9 months), median centrally assessed PFS was 4.1 months in the niraparib arm (n ¼ 141) versus 3.1 months in the PC arm [n ¼ 74; hazard ratio (HR), 0.96; 95% confidence interval (CI), 0.65–1.44; P ¼ 0.86]. HRs for OS and local-PFS were 0.95 (95% CI, 0.63–1.42) and 0.65 (95% CI, 0.46–0.93), respectively. ORR was 35% (95% CI, 26–45) with niraparib and 31% (95% CI, 19–46) in the PC arm. Conclusions: Informative censoring in the control arm prevented accurate assessment of the trial hypothesis, although there was clear evidence of niraparib’s activity in this patient population., SCOPUS: ar.j, info:eu-repo/semantics/published

Yong-Wei Yu,1,* Yang-Jing Xue,1,* La-La Qian,2 Zhi Chen,2 Jia-Qun Que,1 Kai-Yu Huang,1 Shuai Liu,1 Ying-Bei Weng,1 Fang-Ning Rong,1 Kang-Ting Ji,1 Jing-Ni Zeng1 1Department of Cardiology, The Second Affiliated and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 312500, People’s Republic of China; 2Department of Cardiology, Pingyang County Hospital of Traditional Chinese Medicine, Wenzhou 312500, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kang-Ting Ji; Jing-Ni ZengDepartment of Cardiology, The Second Affiliated and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 312500, People’s Republic of ChinaEmail jikt@wmu.edu.cn; zengjn6015@163.comBackground: Myocardial infarction (MI) is a common cause of death worldwide. It is characterized by coronary artery occlusion that causes ischemia and hypoxia of myocardial cells, leading to irreversible myocardial damage.Materials and Methods: To explore potential targets for treatment of MI, we reorganized and analyzed two microarray datasets (GSE4648 and GSE775). The GEO2R tool was used to screen for differentially expressed genes (DEGs) between infarcted and normal myocardium. We used the Database for Annotation, Visualization and Integrated Discovery (DAVID) to perform Gene Ontology functional annotation analysis (GO analysis) and the Kyoto Encyclopedia of Genes and Genomes for pathway enrichment analysis (KEGG analysis). We examined protein–protein interactions to characterize the relationship between differentially expressed genes, and we screened potential hub genes according to the degree of connection. PCR and Western blotting were used to identify the core genes.Results: At different times of infarction, a total of 35 genes showed upregulation at all times; however, none of the genes showed downregulation at all 3 times. Similarly, 10 hub genes with high degrees of connectivity were id

Yi-ming Li, 1,* Li-cheng Jiang, 2,* Jing-jing He, 1 Kai-yu Jia, 1 Yong Peng, 1 Mao Chen 1 1Department of Cardiology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Cardiology, The First Affiliated Hospital, Chengdu Medical College, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yong Peng; Mao ChenDepartment of Cardiology, West China Hospital, Sichuan University, 37 Guoxue Street, Chengdu 610041, People’s Republic of ChinaEmail pengyongcd@126.com; hmaochen@vip.sina.comAbstract: A formal risk assessment for identifying high-risk patients is essential in clinical practice and promoted in guidelines for the management of anterior acute myocardial infarction. In this study, we sought to evaluate the performance of different machine learning models in predicting the 1-year mortality rate of anterior ST-segment elevation myocardial infarction (STEMI) patients and to compare the utility of these models to the conventional Global Registry of Acute Coronary Events (GRACE) risk scores. We enrolled all of the patients aged > 18 years with discharge diagnoses of anterior STEMI in the Western China Hospital, Sichuan University, from January 2011 to January 2017. A total of 1244 patients were included in this study. The mean patient age was 63.8± 12.9 years, and the proportion of males was 78.4%. The majority (75.18%) received revascularization therapy. In the prediction of the 1-year mortality rate, the areas under the curve (AUCs) of the receiver operating characteristic curves (ROCs) of the six models ranged from 0.709 to 0.942. Among all models, XGBoost achieved the highest accuracy (92%), specificity (99%) and f1 score (0.72) for predictions with the full variable model. After feature selection, XGBoost still obtained the highest accuracy (93%), specificity (99%) and f1 score (0.73). In conclusion, machine learning algorithms can acc

Yi-ming Li, 1,* Li-cheng Jiang, 1, 2,* Jing-jing He, 1 Kai-yu Jia, 1 Yong Peng, 1 Mao Chen 1 1Department of Cardiology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Cardiology, The First Affiliated Hospital, Chengdu Medical College, Chengdu, People’s Republic of China*These authors contributed equally to this workThe authors have advised that the affiliation for author Li-cheng Jiang was presented incorrectly. Read the original article

The development of technology has ignited many innovations in business management, especially in the electronic commerce area. The essential example, that is, online stores and online shopping, is a critical evolution and innovation from traditional brick-and-mortar stores to clicks and mortar. Following previous research (Van Oorschot et al.), this present study adopted bibliometric and keyword analysis to review the main characteristics of electronic commerce innovations. Focused on the academic sources, the research data used in this study were searched for and collected from the Web of Science (WoS), a renowned academic database which covers the most influential research journals in electronic commerce. Based on a combination of several keywords related to “innovation” and “electronic commerce,” the keyword search in the WoS was conducted in May 2019. As a result, a total of 334 research articles related to electronic commerce innovations were collected. Derived from the bibliometric analysis, some keywords that were seldom used in the earlier decade (2000-2009), but which rapidly grew in use in the recent decade (2010-2018) were found, including m-commerce, platforms, social commerce, online review, and co-creation. In addition, the top 10 influential articles listed in each of the two decades were identified. The results show some of the research trajectories in EC innovations. In the first decade (2000-2009), the top 10 papers focused on traditional IT adoption, such as self-service technology, enterprise resource planning systems, and the adoption of general attitude-intention theories such as the technology acceptance model. In the recent decade (2010-2018), researchers have shown more diverse interest in innovative EC applications, such as RFID applications, cloud computing, crowdsourcing, etc. Accompanying these EC innovation contexts, in addition to general attitude-intention theories, more theories such as signaling theory, have been adopted.

Many image processing tasks involve image-to-image mapping, which can be addressed well by fully convolutional networks (FCN) without any heavy preprocessing. Although empirically designing and training FCNs can achieve satisfactory results, reasons for the improvement in performance are slightly ambiguous. Our study is to make progress in understanding their generalization abilities through visualizing the optimization landscapes. The visualization of objective functions is obtained by choosing a solution and projecting its vicinity onto a 3D space. We compare three FCN-based networks (two existing models and a new proposed in this paper for comparison) on multiple datasets. It has been observed in practice that the connections from the pre-pooled feature maps to the post-upsampled can achieve better results. We investigate the cause and provide experiments to shows that the skip-layer connections in FCN can promote flat optimization landscape, which is well known to generalize better. Additionally, we explore the relationship between the models generalization ability and loss surface under different batch sizes. Results show that large-batch training makes the model converge to sharp minimizers with chaotic vicinities while small-batch method leads the model to flat minimizers with smooth and nearly convex regions. Our work may contribute to insights and analysis for designing and training FCNs., Comment: In AAAI-19 Workshop on Network Interpretability for Deep Learning

Combinatorial drugs have been used for decades to improve therapeutic efficacy in cancer treatments through drug synergistic mediation. Although they are believed to have good efficiency in killing cancer cells by simultaneously suppress multi-drug resistance through targeting different cellular mechanisms, its remedial effects is still limited when considering heterogeneity of cancer cells. Recently, nanosystem-based agents have become new drug delivery systems to improve therapeutic efficiency as well as safeness. However, it is still difficult in optimizing desired effects combinations and fails to enhance drug efficacy efficiently. Thus, feedback system control (FSC) platform has been introduced to circumvent limitations in optimizing drug combinations for either unmodified or nanotechnology driven therapeutics. The FSC platform provides an algorithm that integrally and swiftly produces an ideal combination consisting of three nanodiamond-modified anticancer drugs: doxorubicin, mitoxantrone, bleomycin and one unmodified anticancer drug- paclitaxel. Particularly, the therapeutic windows obtained from the FSC-based nanodiamond-drug combinations were significantly higher than the ones in optimized unmodified drug combinations, single nanodiamond and unmodified drug administration, and randomly sampled nanodiamond-drug combination treatment. Moreover, the FSC methodology intrinsically considers cancer cell heterogeneity and sophisticated intracellular mechanisms. This approach can be potentially applied in optimizing multi-therapeutic systems clinically, expressing a favorable candidate in personalized medication development in the future.

The earliest recorded Chinese literature that has survived consists of folk songs mixed with verses and rhymes. Two factors determined the general pattern of subsequent development in Chinese literature: the nature of the written Chinese language and the establishment of the Confucian school as the orthodoxy in literary criticism. By 1800 there were more books printed in Chinese than there were printed in all other languages combined. The main body of the massive collection of Chinese books included histories and commentaries on Confucian classics, but even manuals on herb medicine were written in the same stilted classical language, and were treated as proper literature. The ideological trend in Chinese literature from the 1920's on has been one that shifted from a literary revolution that stressed a drastic change in the linguistic style to a social and political revolution. The most noticeable difference between the concrete Chinese and the abstract Western literature reveals the Western mind's preoccupations with the search for what is; a relentless search in nature that spurred the development of psychology, as contrasted with the Chinese concentration on what works. (Author/AM)

We analyzed the Suzaku data of M86 and its adjacent regions to study the extended emission around it. The M86 core, the plume, and the tail extending toward the northwest were clearly detected, as well as the extended halo around them. From the position angle $\sim45\deg$ to $\sim275\deg$, the surface brightness distribution of the core and the extended halo was represented relatively well with a single $\beta$-model of $\beta\sim0.5$ up to 15'-20'. The X-ray spectra of the core was represented with a two-temperature model of $kT\sim 0.9$ keV and $\sim0.6$ keV. The temperatures of the core and the halo have a positive gradient in the center, and reach the maximum of $kT\sim1.0$ keV at $r\sim7'$, indicating that the halo gas is located in a larger scale potential structure than that of the galaxy. The temperatures of the plume and the tail were $0.86\pm0.01$ keV and $1.00\pm0.01$ keV. We succeeded in determining the abundances of $\alpha$-element separately, for the core, the plume, the tail, and the halo for the first time. Abundance ratios with respect to Fe were consistent with the solar ratios everywhere, except for Ne. The abundance of Fe was $\sim0.7$ in the core and in the plume, while that in the tail was $\sim1.0$, but the difference was not significant considering the uncertainties of the ICM. The abundance of the halo was almost the same up to $r\sim10'$, and then it becomes significantly smaller (0.2-0.3) at $r\gtrsim10'$, indicating the gas with low metal abundance still remains in the outer halo. From the surface brightness distribution, we estimated the gas mass ($\sim3\times10^{10}M_\odot$) and the dynamical mass ($\sim3\times10^{12}M_\odot$) in $r<100$~kpc. The gas mass to the dynamical mass ratio was $10^{-3}$-$10^{-2}$, suggesting a significant fraction of the halo gas has been stripped., Comment: 17 pages, 14 figures, 7 tables

We investigate mesoscale turbulence (10–1000 km) in the ocean winds over the Kuroshio Extension ( math formulaN– math formulaN, math formulaE– math formulaE) using the QuikSCAT data set (November 1999 to October 2009). We calculate the second (Djj) and third-order structure functions (Djjj) and the spatial variance (Vj) as a function of scale r ( math formula denotes, respectively, the longitudinal (divergent) and transverse (vortical) component). The most interesting results of the analysis follow. Although both math formula and math formula measure the turbulent kinetic energy (TKE), we find that math formula is the more robust measure. The spatial variance density (dVj/dr) has a broad peak near 450 km (close to the midlatitude Rossby radius of deformation). On interannual time scales, TKE correlates well with the El Niño 3.4 index. According to turbulence theory, the kinetic energy cascades downscale (upscale) if math formula (also skewness math formula) is negative (positive). Our results for the Kuroshio Extension are consistent with a downscale cascade (indicating convergence dominates). Furthermore, classical turbulence theory predicts that math formula and independent of r; however, we find SL varies strongly with r, from −4 at small scales to −0.3 at large scales. This nonclassical behavior implies strong-scale interaction, which we attribute to the rapid, and sometimes explosive, growth of storms in the region through baroclinic instability. Finally, we find that ST (a measure of cyclonic/anticyclonic asymmetry) is positive (cyclonic) and also varies strongly with r, from 4 at small scales to 0.5 at large scales. New turbulence models are needed to explain these results, and that will benefit Weather Prediction and climate modeling

Background Cimicifuga racemosa is one of the herbs used for the treatment of climacteric syndrome, and it has been cited as an alternative therapy to estrogen. Apart from hectic fevers, dyspareunia and so on, dry mouth also increase significantly after menopause. It has not yet been reported whether C. racemosa has any impact on the sublingual gland, which may relate to dry mouth. In an attempt to determine this, we have compared the effects of estrogen and C. racemosa on the sublingual gland of ovariectomized rats. Results HE staining showed that the acinar cell area had contracted and that the intercellular spaces were broadened in the OVX (ovariectomized rats) group, while treatment with estradiol (E2) and iCR (isopropanolic extract of C. racemosa) improved these lesions. Transmission electron microscopy showed that rough endoplasmic reticulum expansion in mucous and serous acinar epithelial cells and apoptotic cells was more commonly seen in the OVX group than in the SHAM (sham-operated rats) group. Mitochondria and plasma membrane infolding lesions in the striated ducts were also observed. These lesions were alleviated by both treatments. It is of note that, in the OVX + iCR group, the volume of mitochondria in the striated duct was larger than in other groups. Immunohistochemical staining showed that the ratio of caspase-3 positive cells was significantly increased in the acinar cells of the OVX group compared with the SHAM group (p < 0.05); and the MA (mean absorbance) of caspase-3 in the striated ducts also increased (p < 0.05). Estradiol decreased the ratio of caspase-3 positive cells and the MA of caspase-3 in striated ducts significantly (p < 0.05). ICR also reduced the ratio of caspase-3 positive cells and the MA in the striated ducts (p < 0.05), but the reduction of the MA in striated ducts was inferior to that of the OVX + E2 group (p < 0.05). Conclusion Both estradiol and iCR can inhibit subcellular structural damage, and down-regulate the ex

Combination chemotherapy can mediate drug synergy to improve treatment efficacy against a broad spectrum of cancers. However, conventional multidrug regimens are often additively determined, which have long been believed to enable good cancer-killing efficiency but are insufficient to address the nonlinearity in dosing. Despite improved clinical outcomes by combination treatment, multi-objective combination optimization, which takes into account tumor heterogeneity and balance of efficacy and toxicity, remains challenging given the sheer magnitude of the combinatorial dosing space. To enhance the properties of the therapeutic agents, the field of nanomedicine has realized novel drug delivery platforms that can enhance therapeutic efficacy and safety. However, optimal combination design that incorporates nanomedicine agents still faces the same hurdles as unmodified drug administration. The work reported here applied a powerful phenotypically driven platform, termed feedback system control (FSC), that systematically and rapidly converges upon a combination consisting of three nanodiamond-modified drugs and one unmodified drug that is simultaneously optimized for efficacy against multiple breast cancer cell lines and safety against multiple control cell lines. Specifically, the therapeutic window achieved from an optimally efficacious and safe nanomedicine combination was markedly higher compared to that of an optimized unmodified drug combination and nanodiamond monotherapy or unmodified drug administration. The phenotypically driven foundation of FSC implementation does not require any cellular signaling pathway data and innately accounts for population heterogeneity and nonlinear biological processes. Therefore, FSC is a broadly applicable platform for both nanotechnology-modified and unmodified therapeutic optimizations that represent a promising path toward phenotypic personalized medicine.

With the increasing sales of counterfeits worldwide today, a more comprehensive understanding of the psychological processes concerning counterfeits consumption, combined with the illegality and/or socially undesirable nature of counterfeits, the important but largely overlooked underlying mechanisms of counterfeit consumption propensities, will significantly contribute to the literature and may help marketers set up more refined and more effective marketing strategies. To achieve this end, this research addresses the following research questions which are yet to be fully addressed by extant research: Are there any other motivational factors (for example intrinsic motivations) not comprehensively described by previous research?; Are there any psychological concerns (negative outcomes) associated with consuming luxury (high involvement) brand counterfeits?; and How do consumers rationalize or justify their behavior? For the purposes of this study, we chose the Chinese marketplace as our context, because China is both the largest producer (International Anti-Counterfeiting Coalition, 2010) and consumer of counterfeit products (Cheung and Prendergast, 2006), while it is estimated that 20% of domestic sales in China are counterfeits (Swike et al., 2008). We conducted sixteen one-to-one in depth interviews with Chinese consumers, aged 18 to 30 years old, and of varied socio-economic backgrounds who had experience with counterfeits. The analysis led to the generation of three primary themes relating to the psychological aspects of counterfeit consumption and purchase: 1. Cognitive elements, namely the interplay between motivation and rationalization/neutralization of the behavior; 2. Consumer expertise and confusion; and 3. Risks avoidance, pursuing rewards and self-conscious emotions. This research advances of our theoretical understanding of consumer motivations underpinning counterfeit consumption. Building on previous research, for example Wilcox et al. (2009), this r

Healthcare data mining and business intelligence are attracting huge industry interest in recent years. Engineers encounter a bottleneck when applying data mining tools to textual healthcare records. Many medical terms in the healthcare records are different from the standard form, which are referred to as informal medical terms in this work. Study indicates that in Chinese healthcare records, a majority of the informal terms are abbreviations or typos. In this work, a multi-field indexing approach is proposed, which accomplishes the term normalization task with information retrieval algorithm with four level indices: word, character, pinyin and its initial. Experimental results show that the proposed approach is advantageous over the state-of-the-art approaches. © Springer-Verlag Berlin Heidelberg 2014.

Total body center of mass (TBCM) is a useful kinematic measurement of body sway. However, expensive equipment and high technical requirement limit the use of motion capture systems in large-scale clinical settings. Center of pressure (CP) measurement obtained from force plates cannot accurately represent TBCM during large body sway movement. Microsoft Kinect is a rapidly developing, inexpensive, and portable posturographic device, which provides objective and quantitative measurement of TBCM sway. The purpose of this study was to evaluate Kinect as a clinical assessment tool for TBCM sway measurement. The performance of the Kinect system was compared with a Vicon motion capture system and a force plate. Ten healthy male subjects performed four upright quiet standing tasks: (1) eyes open (EOn), (2) eyes closed (ECn), (3) eyes open standing on foam (EOf), and (4) eyes closed standing on foam (ECf). Our results revealed that the Kinect system produced highly correlated measurement of TBCM sway (mean RMSE = 4.38 mm; mean CORR = 0.94 in Kinect-Vicon comparison), as well as comparable intra-session reliability to Vicon. However, the Kinect device consistently overestimated the 95% CL of sway by about 3 mm. This offset could be due to the limited accuracy, resolution, and sensitivity of the Kinect sensors. The Kinect device was more accurate in the medial-lateral than in the anterior-posterior direction, and performed better than the force plate in more challenging balance tasks, such as (ECf) with larger TBCM sway. Overall, Kinect is a cost-effective alternative to a motion capture and force plate system for clinical assessment of TBCM sway.

Background and Purpose: Hyper-nociceptive PGE2 EP4 receptors and prostacyclin (IP) receptors are present in adult rat dorsal root ganglion (DRG) neurones and glial cells in culture. The present study has investigated the cell-specific expression of two other Gs-protein coupled hyper-nociceptive receptor systems: β-adrenoceptors and calcitonin gene-related peptide (CGRP) receptors in isolated DRG cells and has examined the influence of neurone-glial cell interactions in regulating adenylyl cyclase (AC) activity. Experimental Approach: Agonist-stimulated AC activity was determined in mixed DRG cell cultures from adult rats and compared with activity in DRG neurone-enriched cell cultures and pure DRG glial cell cultures. Key Results: Pharmacological analysis showed the presence of Gs-coupled β2-adrenoceptors and CGRP receptors, but not β1-adrenoceptors, in all three DRG cell preparations. Agonist-stimulated AC activity was weakest in DRG neurone-enriched cell cultures. DRG neurones inhibited IP receptor-stimulated glial cell AC activity by a process dependent on both cell-cell contact and neurone-derived soluble factors, but this is unlikely to involve purine or glutamine receptor activation. Conclusions and Implications Gs-coupled hyper-nociceptive receptors are readily expressed on DRG glial cells in isolated cell cultures and the activity of CGRP, EP4 and IP receptors, but not β2-adrenoceptors, in glial cells is inhibited by DRG neurones. Studies using isolated DRG cells should be aware that hyper-nociceptive ligands may stimulate receptors on glial cells in addition to neurones, and that variable numbers of neurones and glial cells will influence absolute measures of AC activity and affect downstream functional responses. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Isolated cells from adult rat dorsal root ganglia (DRG) are frequently used as a model system to study responses of primary sensory neurons to nociceptor sensitizing agents such as prostaglandin E2 and prostacyclin, which are presumed to act only on the neurons in typical mixed cell cultures. In the present study, we evaluated the expression of prostaglandin E2 (EP4) and prostacyclin (IP) receptors in cultures of mixed DRG cells and in purified DRG glia. We show here that EP4 and IP receptor agonists stimulated adenylyl cyclase activity in both mixed DRG cells and in purified DRG glia, and that these responses were specifically inhibited by EP4 and IP receptor antagonists, respectively. The presence of EP4 and IP receptors in DRG glia was further confirmed by the expression of EP4 and IP receptor immunoreactivity and mRNA. With the increasing awareness of neuron-glial interactions within intact DRG and the use of isolated DRG cells in the study of mechanisms underlying nociception, it will be essential to consider the role played by EP4 and IP receptor-expressing glial cells when evaluating prostanoid-induced sensitization of DRG neurons. © 2011 Elsevier B.V. All rights reserved.

Dorsal root ganglia (DRG) cell preparations are commonly used to study the properties of sensory neurons in relation to nociception. A typical DRG cell preparation contains both neurons and glial cells, and in addition to a conventional supportive role of glial cells, an increasing volume of literature has reported interactions between neurons and accompanying glial cells. A typical mixed DRG cell preparation can be separated into a neuron-enriched cell fraction and a preparation of purified glial cells. Using these purified cell fractions, we can study the relative contributions and interactions between neurons and glial cells in regulating neurite outgrowth and adenylyl cyclase-dependent cell signalling activity in vitro., From our previous studies, pretreating DRG cell cultures with pertussis toxin (PTx) caused neurite retraction over a period of 2 h following the initial stimulus of removal from incubator. The purpose of the current study was to investigate whether this PIx-dependent response was specific to anyone of the three subpopulations of DRG neurons. Interestingly, no neurite retraction response was observed in enriched DRG cultures, including cultures enriched with isolectin B4 (IB4)-positive neurons or IB4-negative neurons. Addition of glial cells or conditioned medium from glial cells to IB4-negative cultures was necessary to restore the PTx-dependent neurite retraction response, which was then only observed in large diameter proprioceptive neurons. To conclude, glial cells constitutively release factor/s that stimulate neurite retraction in larger diameter neurons, and is counterbalanced by neuroprotective Gilo protein signalling pathway., From our studies, we have provided evidence of bidirectional interactions between neurons and glial cells, with glial cells regulating neurite outgrowth and neurons regulating adenylyl cyclase activity in glial cells. These findings reveal the properties of glial cells in regulating neurite outgrowth and in producing prostanoid-stimulated responses. Moreover, our fmdings provide foundation to understand complex neuron-glia interactions in vivo which will eventually help to overcome obstacles in promoting neurite regeneration and in controlling pain., In a parallel study, we proved that hyperalgesic agents such as prostaglandin E2 (PGE2) and the prostacyclin (PGI2) mimetic (cicaprost) stimulate cAMP production in DRG cell culture via EP4 and IP receptors, respectively. These prostanoids were presumed to act only on the neurons in typical mixed cell cultures, but since we had acquired purified glial cell preparation, we tested for involvement of glial cells in measurement of agonist-stimulated cAMP production. Interestingly, a purified glial cell cultures also produced EP4 and IP-dependent responses. The expression of EP4 and IP receptors by DRG glia was further confirmed by the detection of EP4 and IP-like immunoreactivity and mRNA. Moreover, these agonist-stimulated responses were greatest in the glial cell preparation, and surprisingly weakest in the neuron-enriched cell cultures. Furthermore, the presence of neurons significantly inhibited both EP4 and IP receptor-dependent signalling in glial cells, but was without effect on forskolin (agonist-independent) stimulation of adenylyl cyclase. In order to characterize this neuron-glia interaction, we tested the adenylyl cyclase activities in glial cell cultures which were treated with conditioned medium derived from neurons or were separated from physical contact with neurons plated on transwell membrane. These studies further suggest that the neuron-glia interactions were dependent on both soluble factors and cell-cell contact., Ng, Kai Yu., Adviser: Helen Wise., Source: Dissertation Abstracts International, Volume: 73-04, Section: B, page: ., Thesis (Ph.D.)--Chinese University of Hong Kong, 2011., Includes bibliographical references (leaves 152-172)., Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web., Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web., also in Chinese., isbn: 9781267099709, Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/)

When pretreated with pertussis toxin (PTX), the neurites of adult rat dorsal root ganglion (DRG) cells in mixed cell cultures retract over a period of 2 h following the initial stimulus of removal from the cell culture incubator for brief periods of observation. The purpose of this investigation was to determine whether this PTX-dependent response was specific to any one of the three subpopulations of DRG neurons. However, no neurite retraction response was observed in neuron-enriched populations of cells, or in cultures enriched in isolectin B4 (IB4)-positive neurons or in IB4-negative neurons. But, the addition of non-neuronal cells, and/or medium conditioned by non-neuronal cells, was sufficient to restore the PTX-dependent neurite retraction response, but only in large diameter IB4-negative neurons. In conclusion, we have identified a regulatory response, mediated by Gi/o-proteins, which prevents retraction of neurites in large diameter IB4-negative cells of adult rat DRG. The non-neuronal cells of adult rat DRG constitutively release factor/s that can stimulate neurite retraction of a subset of isolated DRG neurons, but this property of non-neuronal cells is only observed when the Gi/o-proteins of large diameter IB4-negative cells are inhibited.

Recently, common variants on human chromosome 8q24 were found to be associated with prostate cancer risk. While conducting a genome-wide association study in the Cancer Genetic Markers of Susceptibility project with 550,000 SNPs in a nested case-control study (1,172 cases and 1,157 controls of European origin), we identified a new association at 8q24 with an independent effect on prostate cancer susceptibility. The most significant signal is 70 kb centromeric to the previously reported SNP, rs1447295, but shows little evidence of linkage disequilibrium with it. A combined analysis with four additional studies (total: 4,296 cases and 4,299 controls) confirms association with prostate cancer for rs6983267 in the centromeric locus (P = 9.42 times 10-13; heterozygote odds ratio (OR): 1.26, 95% confidence interval (c.i.): 1.13–1.41; homozygote OR: 1.58, 95% c.i.: 1.40–1.78). Each SNP remained significant in a joint analysis after adjusting for the other (rs1447295 P = 1.41 times 10-11; rs6983267 P = 6.62 times 10-10). These observations, combined with compelling evidence for a recombination hotspot between the two markers, indicate the presence of at least two independent loci within 8q24 that contribute to prostate cancer in men of European ancestry. We estimate that the population attributable risk of the new locus, marked by rs6983267, is higher than the locus marked by rs1447295 (21% versus 9%).

by Leung Sui Wai, Tam Kai Yu Margaret., Thesis (M.B.A.)--Chinese University of Hong Kong, 1998., Includes bibliographical references (leaf 73)., p.II, TABLE OF CONTENTS --- p.IV, LIST OF ILLUSTRATIONS --- p.VII, LIST OF TABLES --- p.VIII, PREFACE --- p.XI, Chapter 1. --- INTRODUCTION --- p.1, Chapter 1.1 --- Objectives --- p.2, Chapter 2 --- HO USING SUPPLIES IN HONG KONG --- p.4, Chapter 2.1 --- Public Housing --- p.5, Chapter 2.1.1 --- Public rental flats --- p.5, Chapter 2.1.2 --- Owning flats under public housing schemes --- p.8, Chapter 2.1.3 --- Home Ownership Scheme --- p.9, Chapter 2.1.4 --- Middle Income Housing --- p.11, Chapter 2.1.5 --- New Home Starter Loan Scheme --- p.12, Chapter 2.1.6 --- Sandwich Class Housing Scheme --- p.12, Chapter 2. 2 --- Private property --- p.14, Chapter 3. --- PROPERTY IN MAINLAND CHINA --- p.17, Chapter 3.1 --- Pricing of property in Mainland China --- p.17, Chapter 3.2 --- Buyers of properties in Mainland China --- p.18, Chapter 3.3 --- Threat of incomplete commodity housing (lanmeilou) --- p.18, Chapter 3.4 --- Hong Kong property agents --- p.19, Chapter 4. --- ENVIRONMENTAL CHANGE WITHIN RESEARCH PERIOD --- p.20, Chapter 4.1 --- Residential Property Market --- p.20, Chapter 4.2 --- The Real Estate Chill --- p.20, Chapter 4.3 --- The SAR Property Policy --- p.21, Chapter 4.4 --- "Long-teRm Housing Strategy, 1997" --- p.22, Chapter 4.5 --- Land release --- p.24, Chapter 4.6 --- loan for First-time Home Buyers and Sandwich-Class Buyers --- p.25, Chapter 4.7 --- Privatizing Public Housing --- p.26, Chapter 5. --- METHODOLOGY --- p.29, Chapter 5.1 --- Surveys --- p.29, Chapter 5.2 --- Questionnaire Design --- p.29, Chapter 5.3 --- Selection of Respondents --- p.33, Chapter 5.4 --- Data Analysis --- p.33, Chapter 6. --- SURVEY RESULTS AND ANALYSIS --- p.35, Chapter 6.1 --- Results and Analysis - Section 1 --- p.35, Chapter 6.2 --- Results and Analysis - Section 2 --- p.37, Chapter 6.3 --- Results and Analysis - Potential Buyers --- p.42, Chapter 6.3.1 --- Age --- p.42, Chapter 6.3.2 --- Marital Status --- p.43, Chapter 6.3.3 --- Relatives in China --- p.44, Chapter 6.3.4 --- Currently Living With --- p.45, Chapter 6.3.5 --- Currently Living In --- p.46, Chapter 6.3.6 --- Education Level --- p.48, Chapter 6.3.7 --- Number of Property Currently Owned --- p.50, Chapter 6.3.8 --- Income --- p.51, Chapter 6.3.9 --- Summary of Characteristics of Potential Buyers --- p.52, Chapter 7. --- RECOMMENDATION --- p.54, Chapter 7.1 --- Product --- p.54, Chapter 7.2 --- Price --- p.56, Chapter 7.3 --- Promotion --- p.57, Chapter 7.3.1 --- Advertising --- p.57, Chapter 7.3.2 --- Publicity --- p.58, Chapter 7.3.3 --- Sales promotion --- p.58, Chapter 7.3.4 --- Personal selling --- p.58, Chapter 7.4 --- Distribution --- p.59, Chapter 8. --- CONCLUSION --- p.60, Chapter 8.1 --- Feasibility of residing in China but working in Hong Kong --- p.60, Chapter 8.2 --- Demographic profiles of potential buyers --- p.62, Chapter 8.3 --- Implications of the current situation --- p.62, Chapter 9. --- LIMITATIONS --- p.64, APPENDIX --- p.66, Appendix A The Importance of Each Consideration when Buying Property in Mainland China --- p.66, Appendix B Copy and results of the survey used in this project --- p.70, BIBLIOGRAPHY --- p.73, http://library.cuhk.edu.hk/record=b5889404, Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Consumer demand for counterfeit luxury brands is unethical, but it is also robust and growing. The aim of this exploratory research, which employs in-depth interviews, is two-fold: 1) to identify the psychological and emotional insights that drive and result from the consumption of higher involvement counterfeit goods; and 2) to uncover the coping strategies related to unethical counterfeit consumption. This research reveals new psychological motivations (e.g., “thrill of the hunt”, being part of a “secret society” and genuine interest) underlying counterfeit consumption and the associated emotional outcomes (e.g., embarrassment, shame and positive hedonic gains). This research is also one of the few studies to identify cognitive moral logics by disclosing the neutralization techniques (specifically denial of responsibility and appealing to higher loyalties) that consumers adopt to cope with the cognitive dissonance associated with debatable counterfeit consumption. The paper contributes to scholarly, managerial and policy conversations.

Consumer demand for counterfeit luxury brands is unethical, but it is also robust and growing. The aim of this exploratory research, which employs in-depth interviews, is two-fold: 1) to identify the psychological and emotional insights that drive and result from the consumption of higher involvement counterfeit goods; and 2) to uncover the coping strategies related to unethical counterfeit consumption. This research reveals new psychological motivations (e.g., “thrill of the hunt”, being part of a “secret society” and genuine interest) underlying counterfeit consumption and the associated emotional outcomes (e.g., embarrassment, shame and positive hedonic gains). This research is also one of the few studies to identify cognitive moral logics by disclosing the neutralization techniques (specifically denial of responsibility and appealing to higher loyalties) that consumers adopt to cope with the cognitive dissonance associated with debatable counterfeit consumption. The paper contributes to scholarly, managerial and policy conversations.

Consumer demand for counterfeit luxury brands is unethical, but it is also robust and growing. The aim of this exploratory research, which employs in-depth interviews, is two-fold: 1) to identify the psychological and emotional insights that drive and result from the consumption of higher involvement counterfeit goods; and 2) to uncover the coping strategies related to unethical counterfeit consumption. This research reveals new psychological motivations (e.g., “thrill of the hunt”, being part of a “secret society” and genuine interest) underlying counterfeit consumption and the associated emotional outcomes (e.g., embarrassment, shame and positive hedonic gains). This research is also one of the few studies to identify cognitive moral logics by disclosing the neutralization techniques (specifically denial of responsibility and appealing to higher loyalties) that consumers adopt to cope with the cognitive dissonance associated with debatable counterfeit consumption. The paper contributes to scholarly, managerial and policy conversations.

Consumer demand for counterfeit luxury brands is unethical, but it is also robust and growing. The aim of this exploratory research, which employs in-depth interviews, is two-fold: 1) to identify the psychological and emotional insights that drive and result from the consumption of higher involvement counterfeit goods; and 2) to uncover the coping strategies related to unethical counterfeit consumption. This research reveals new psychological motivations (e.g., “thrill of the hunt”, being part of a “secret society” and genuine interest) underlying counterfeit consumption and the associated emotional outcomes (e.g., embarrassment, shame and positive hedonic gains). This research is also one of the few studies to identify cognitive moral logics by disclosing the neutralization techniques (specifically denial of responsibility and appealing to higher loyalties) that consumers adopt to cope with the cognitive dissonance associated with debatable counterfeit consumption. The paper contributes to scholarly, managerial and policy conversations.

Consumer demand for counterfeit luxury brands is unethical, but it is also robust and growing. The aim of this exploratory research, which employs in-depth interviews, is two-fold: 1) to identify the psychological and emotional insights that drive and result from the consumption of higher involvement counterfeit goods; and 2) to uncover the coping strategies related to unethical counterfeit consumption. This research reveals new psychological motivations (e.g., “thrill of the hunt”, being part of a “secret society” and genuine interest) underlying counterfeit consumption and the associated emotional outcomes (e.g., embarrassment, shame and positive hedonic gains). This research is also one of the few studies to identify cognitive moral logics by disclosing the neutralization techniques (specifically denial of responsibility and appealing to higher loyalties) that consumers adopt to cope with the cognitive dissonance associated with debatable counterfeit consumption. The paper contributes to scholarly, managerial and policy conversations.