This paper uses two methodologies to explore the extent to which greater labor force participation among older Malaysians can expand Malaysia’s labor supply. The Milligan–Wise method estimates the ...potential to increase the labor force participation rate of older Malaysians by estimating how much they would work if they were to work as much as those with the same mortality rate in the past. The Cutler, Meara, and Richards-Shubik ( 2013 ) method estimates the same potential by estimating how much older Malaysians would work if they worked as much as their younger counterparts in similar health. We made further simulations to quantify the capacity of older Malaysians to work after they are 60 years old. The results show significant additional work capacity among older people in Malaysia, particularly males, urban dwellers, and those with low educational attainment.
Many important gram-negative bacterial pathogens use highly sophisticated type III protein secretion systems (T3SSs) to establish complex host-pathogen interactions. Bacterial-host cell contact ...triggers the activation of the T3SS and the subsequent insertion of a translocon pore into the target cell membrane, which serves as a conduit for the passage of effector proteins. Therefore the initial interaction between T3SS-bearing bacteria and host cells is the critical step in the deployment of the protein secretion machine, yet this process remains poorly understood. Here, we use high-throughput cryo-electron tomography (cryo-ET) to visualize the T3SS-mediated
-host cell interface. Our analysis reveals the intact translocon at an unprecedented level of resolution, its deployment in the host cell membrane, and the establishment of an intimate association between the bacteria and the target cells, which is essential for effector translocation. Our studies provide critical data supporting the long postulated direct injection model for effector translocation.
We investigate the relationship between economic growth and lagged international capital flows, disaggregated into FDI, portfolio investment, equity investment, and short-term debt. We follow about ...100 countries during 1990–2010 when emerging markets became more integrated into the international financial system. We look at the relationship both before and after the global crisis. Our study reveals a complex and mixed picture. The relationship between growth and lagged capital flows depends on the type of flows, economic structure, and global growth patterns. We find a large and robust relationship between FDI – both inflows and outflows – and growth. The relationship between growth and equity flows is smaller and less stable. Finally, the relationship between growth and short-term debt is nil before the crisis, and negative during the crisis.
A major goal for HIV-1 vaccine development is the production of an immunogen to mimic native, functional HIV-1 envelope trimeric spikes (Env) on the virion surface. We lack a reliable description of ...a native, functional trimer, however, because of inherent instability and heterogeneity in most preparations. We describe here two conformationally homogeneous Envs derived from difficult-to-neutralize primary isolates. All their non-neutralizing epitopes are fully concealed and independent of their proteolytic processing. Most broadly neutralizing antibodies (bnAbs) recognize these native trimers. Truncation of their cytoplasmic tail has little effect on membrane fusion, but it diminishes binding to trimer-specific bnAbs while exposing non-neutralizing epitopes. These results yield a more accurate antigenic picture than hitherto possible of a genuinely untriggered and functional HIV-1 Env; they can guide effective vaccine development.
Hormone receptor-positive and HER2-negative breast cancer (HR+/HER2-BC) is the most common type with a favorable prognosis under endocrine therapy. However, it still demonstrates unpredictable ...progression and recurrences influenced by high tumoral diversity and microenvironmental status. To address these heterogeneous molecular characteristics of HR+/HER2-BC, we aimed to simultaneously characterize its transcriptomic landscape and genetic architecture at the same resolution. Using advanced single-cell RNA and DNA sequencing techniques together, we defined four distinct tumor subtypes. Notably, the migratory tumor subtype was closely linked to genomic alterations of EGFR, related to the tumor-promoting behavior of IL6-positive inflammatory tumor-associated fibroblast, and contributing to poor prognosis. Our study comprehensively utilizes integrated analysis to uncover the complex dynamics of this breast cancer subtype, highlighting the pivotal role of the migratory tumor subtype in influencing surrounding cells. This sheds light on potential therapeutic targets by offering enhanced insights for HR+/HER2-BC treatment.
Recently, convolutional neural network (CNN)-based classification models have shown good performance for motor imagery (MI) brain-computer interfaces (BCI) using electroencephalogram (EEG) in ...end-to-end learning. Although a few explainable artificial intelligence (XAI) techniques have been developed, it is still challenging to interpret the CNN models for EEG-based BCI classification effectively. In this research, we propose 3D-EEGNet as a 3D CNN model to improve both the explainability and performance of MI EEG classification. The proposed approach exhibited better performances on two MI EEG datasets than the existing EEGNet, which uses a 2D input shape. The MI classification accuracies are improved around 1.8% and 6.1% point in average on the datasets, respectively. The permutation-based XAI method is first applied for the reliable explanation of the 3D-EEGNet. Next, to find a faster XAI method for spatio-temporal explanation, we design a novel technique based on the normalized discounted cumulative gain (NDCG) for selecting the best among a few saliency-based methods due to their higher time complexity than the permutation-based method. Among the saliency-based methods, DeepLIFT was selected because the NDCG scores indicated its results are the most similar to the permutation-based results. Finally, the fast spatio-temporal explanation using DeepLIFT provides deeper understanding for the classification results of the 3D-EEGNet and the important properties in the MI EEG experiments.
In this study, we analyse the effect of financial uncertainty on corporate investment using firm-level panel data from the Republic of Korea. We find that financial uncertainty has a significant ...negative effect on corporate investment, and that the effect is heterogeneous across firms of different sizes. Small firms and large firms are more exposed to the negative effect of uncertainty than medium-sized firms. The negative effect of uncertainty on large firms slightly declined after the global financial crisis (GFC), but it increased for small and medium-sized enterprises (SMEs). Financial constraints and investment irreversibility amplify the negative effect of uncertainty. The inverted U-shaped curve of the uncertainty effect along the firm-size spectrum can be understood as follows: Small firms are more financially constrained and large firms’ investments are more irreversible in nature. Lastly, contrary to widespread belief, uncertainty has waned since 1990, dampening the trend of declining investment ratios. To counter the negative effect of uncertainty on SMEs, policies need to be directed toward the development of capital markets and bond markets for SMEs. Furthermore, SME policies should be redirected to target competitiveness, not protection.
The intermediate filament protein, nestin, is a widely employed marker of multipotent neural stem cells (NSCs). Recent in vitro studies have implicated nestin in a number of cellular processes, but ...there is no data yet on its in vivo function. Here, we report the construction and functional characterization of Nestin knockout mice. We found that these mice show embryonic lethality, with neuroepithelium of the developing neural tube exhibiting significantly fewer NSCs and much higher levels of apoptosis. Consistent with this in vivo observation, NSC cultures derived from knockout embryos show dramatically reduced self‐renewal ability that is associated with elevated apoptosis but no overt defects in cell proliferation or differentiation. Unexpectedly, nestin deficiency has no detectable effect on the integrity of the cytoskeleton. Furthermore, the knockout of Vimentin, which abolishes nestin's ability to polymerize into intermediate filaments in NSCs, does not lead to any apoptotic phenotype. These data demonstrate that nestin is important for the proper survival and self‐renewal of NSCs, and that this function is surprisingly uncoupled from nestin's structural involvement in the cytoskeleton. STEM CELLS 2010;28:2162–2171
Asia is aging, although there is significant heterogeneity across subregions and economies. Population aging poses two strategic challenges for the region: sustaining economic growth and delivering ...old-age economic security. In this paper, we leverage the lifecycle perspective—that individuals’ consumption and labor income differ at each age—and the National Transfer Accounts database to construct and analyze key economic indicators. Our analysis confirms that demographic change will challenge the region’s future growth and increase the cost of funding the consumption of the elderly. We also find that it will have a substantial impact on the public finances of some Asian economies.
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