To acquire wisdom : the "way" of Wang Yang-Ming (1472-1529)

This is a study of Wang Yang-ming's philosophy, considered as a "Way" of acquiring wisdom and sage­ hood, based on his central insight into the nature of (mind-and-heart), the fundamental principle of all human activity which is capable of determining and of perfecting itself through its intuitive knowledge of the good, at once inborn and acquired. The "Introduction" indicates the broad problem of the quest for wisdom, and of the question of "correctness" of approach and "orthodoxy" of thought which arises, in the context of traditional Chinese philosophy. The first chapter defines the so-called "Confucian Way" as a quest for wisdom, with the latter consisting of the attainment of consciousness of the unity of man with all. things, and of the realisation of a high moral character. It speaks of Han Yu’s effort to "restore" Confucian learning, and especially of the Neo-Confucian synthesis accomplished by Chu His. A brief description of Wang Yang-ming as man and philosopher follows, with special emphasis on his interior evolution. His philosophy is then presented in its gradual development, through an analysis of his teachings of hsin, leading up, after exchanges with certain of his contemporary thinkers, to the discovery of his method of acquiring wisdom through the "extension of liang-chih (knowledge of the good)". The deeper implications of his thought and method are then discussed, expecialy his teaching of the "unity of all things". His expressed attitudes concerning Taoism and Buddhism are also studied, revealing his readiness to accept truth and goodness or "orthodoxy". The concluding chapter offers a critique of his philosophy, evaluating his attempt to solve the basic problem of the acquisition of wisdom, and indicating certain unresolved ambiguities which he has left behind

Targeting Membrane Trafficking as a Strategy for Cancer Treatment

Membrane trafficking is emerging as an attractive therapeutic strategy for cancer. Recent reports have found a connection between Wnt signaling, receptor-mediated endocytosis, V-ATPase, lysosomal activity, and macropinocytosis through the canonical Wnt pathway. In macropinocytic cells, a massive internalization of the plasma membrane can lead to the loss of cell-surface cadherins, integrins, and other antigens that mediate cell–cell adhesion, favoring an invasive phenotype. V-ATPase is a key regulator in maintaining proper membrane trafficking, homeostasis, and the earliest developmental decisions in the Xenopus vertebrate development model system. Here, we review how the interference of membrane trafficking with membrane trafficking inhibitors might be clinically relevant in humans

Closely-related Borrelia burgdorferi (sensu stricto) strains exhibit similar fitness in single infections and asymmetric competition in multiple infections

Wild hosts are commonly co-infected with complex, genetically diverse, pathogen communities. Competition is expected between genetically or ecologically similar pathogen strains which may influence patterns of coexistence. However, there is little data on how specific strains of these diverse pathogen species interact within the host and how this impacts pathogen persistence in nature. Ticks are the most common disease vector in temperate regions with Borrelia burgdorferi, the causative agent of Lyme disease, being the most common vector-borne pathogen in North America. Borrelia burgdorferi is a pathogen of high public health concern and there is significant variation in infection phenotype between strains, which influences predictions of pathogen dynamics and spread.In a laboratory experiment, we investigated whether two closely-related strains of B. burgdorferi (sensu stricto) showed similar transmission phenotypes, how the transmission of these strains changed when a host was infected with one strain, re-infected with the same strain, or co-infected with two strains. Ixodes scapularis, the black-legged tick, nymphs were used to sequentially infect laboratory-bred Peromyscus leucopus, white-footed mice, with one strain only, homologous infection with the same stain, or heterologous infection with both strains. We used the results of this laboratory experiment to simulate long-term persistence and maintenance of each strain in a simple simulation model.Strain LG734 was more competitive than BL206, showing no difference in transmission between the heterologous infection groups and single-infection controls, while strain BL206 transmission was significantly reduced when strain LG734 infected first. The results of the model show that this asymmetry in competition could lead to extinction of strain BL206 unless there was a tick-to-host transmission advantage to this less competitive strain.This asymmetric competitive interaction suggests that strain identity and the biotic context of co-infection is important to predict strain dynamics and persistence

The GMRT EoR Experiment: Limits on Polarized Sky Brightness at 150 MHz

The GMRT reionization effort aims to map out the large scale structure of the Universe during the epoch of reionization (EoR). Removal of polarized Galactic emission is a difficult part of any 21 cm EoR program, and we present new upper limits to diffuse polarized foregrounds at 150 MHz. We find no high significance evidence of polarized emission in our observed field at mid galactic latitude (J2000 08h26m+26). We find an upper limit on the 2-dimensional angular power spectrum of diffuse polarized foregrounds of [l^2 C_l/(2 PI)]^{1/2}< 3K in frequency bins of width 1 MHz at 300<l<1000. The 3-dimensional power spectrum of polarized emission, which is most directly relevant to EoR observations, is [k^3 P_p(k)/(2 PI^2)]^{1/2} 0.03 h/Mpc, k < 0.1 h/Mpc. This can be compared to the expected EoR signal in total intensity of [k^3 P(k)/ (2 PI^2) ]^{1/2} ~ 10 mK. We find polarized structure is substantially weaker than suggested by extrapolation from higher frequency observations, so the new low upper limits reported here reduce the anticipated impact of these foregrounds on EoR experiments. We discuss Faraday beam and depth depolarization models and compare predictions of these models to our data. We report on a new technique for polarization calibration using pulsars, as well as a new technique to remove broadband radio frequency interference. Our data indicate that, on the edges of the main beam at GMRT, polarization squint creates ~ 3% leakage of unpolarized power into polarized maps at zero rotation measure. Ionospheric rotation was largely stable during these solar minimum night time observations.Comment: 17 pages, 6 figures, 2 tables; changed figures, added appendices. To appear in MNRA

Gene Expression Profiling of Biological Pathway Alterations by Radiation Exposure

[[abstract]]Though damage caused by radiation has been the focus of rigorous research, the mechanisms through which radiation exerts harmful effects on cells are complex and not well-understood. In particular, the influence of low dose radiation exposure on the regulation of genes and pathways remains unclear. In an attempt to investigate the molecular alterations induced by varying doses of radiation, a genome-wide expression analysis was conducted. Peripheral blood mononuclear cells were collected from five participants and each sample was subjected to 0.5 Gy, 1 Gy, 2.5 Gy, and 5 Gy of cobalt 60 radiation, followed by array-based expression profiling. Gene set enrichment analysis indicated that the immune system and cancer development pathways appeared to be the major affected targets by radiation exposure. Therefore, 1 Gy radioactive exposure seemed to be a critical threshold dosage. In fact, after 1 Gy radiation exposure, expression levels of several genes including FADD, TNFRSF10B, TNFRSF8, TNFRSF10A, TNFSF10, TNFSF8, CASP1, and CASP4 that are associated with carcinogenesis and metabolic disorders showed significant alterations. Our results suggest that exposure to low-dose radiation may elicit changes in metabolic and immune pathways, potentially increasing the risk of immune dysfunctions and metabolic disorders.[[notice]]補正完畢[[incitationindex]]SCI[[incitationindex]]EI[[booktype]]電子

Genome-wide analysis of the RpoN regulon in Geobacter sulfurreducens

Background The role of the RNA polymerase sigma factor RpoN in regulation of gene expression in Geobacter sulfurreducens was investigated to better understand transcriptional regulatory networks as part of an effort to develop regulatory modules for genome-scale in silico models, which can predict the physiological responses of Geobacter species during groundwater bioremediation or electricity production. Results An rpoN deletion mutant could not be obtained under all conditions tested. In order to investigate the regulon of the G. sulfurreducens RpoN, an RpoN over-expression strain was made in which an extra copy of the rpoN gene was under the control of a taclac promoter. Combining both the microarray transcriptome analysis and the computational prediction revealed that the G. sulfurreducens RpoN controls genes involved in a wide range of cellular functions. Most importantly, RpoN controls the expression of the dcuB gene encoding the fumarate/succinate exchanger, which is essential for cell growth with fumarate as the terminal electron acceptor in G. sulfurreducens. RpoN also controls genes, which encode enzymes for both pathways of ammonia assimilation that is predicted to be essential under all growth conditions in G. sulfurreducens. Other genes that were identified as part of the RpoN regulon using either the computational prediction or the microarray transcriptome analysis included genes involved in flagella biosynthesis, pili biosynthesis and genes involved in central metabolism enzymes and cytochromes involved in extracellular electron transfer to Fe(III), which are known to be important for growth in subsurface environment or electricity production in microbial fuel cells. The consensus sequence for the predicted RpoN-regulated promoter elements is TTGGCACGGTTTTTGCT. Conclusion The G. sulfurreducens RpoN is an essential sigma factor and a global regulator involved in a complex transcriptional network controlling a variety of cellular processes

Bioinformatic analysis of gene regulation in Geobacter sulfurreducens

Background Geobacteraceae are a family of microorganisms from the delta subdivision of Proteobacteria. They have potential for environmental bioremediation and electricity generation. In this presentation, we describe our recent bioinformatic analyses of gene regulation in Geobacter sulfurreducens, a model representative of this family. Results and conclusion We have developed an online database, GSEL (Geobacter Sequence Elements), which compiles regulatory information for G. sulfurreducens. We have recently completed the development of a new, significantly expanded and updated, relational version 2 of the GSEL database and its accompanying online query system, which compiles manually curated information on operon organization and transcription regulatory elements in the genome of G. sulfurreducens. GSEL v. 2 incorporates a graphical browser and provides significantly expanded search capabilities. It also includes new information on predicted and/or experimentally validated genome regulatory sites and provides links to information from microarray experiments stored in public gene expression databases, and to original publications describing how particular regulatory interactions were identified. Using sequence and gene expression analyses, we investigated target genes and promoters regulated by RpoN, an alternative RNA polymerase sigma factor, which regulates a variety of important cellular processes in G. sulfurreducens. Our current studies are focusing on an investigation of several transcription regulatory systems involved in RpoN-dependent regulatory pathways. We have investigated target regulatory sites for an enhancer binding protein, PilR, which participates in RpoN-dependent transcriptional regulation of the pilA gene encoding structural pilin. We predicted multiple PilR-regulated sites upstream of operons related to biosynthesis, assembly, and function of pili and flagella, type II secretory pathways, and cell wall biogenesis. We also investigated sequence changes and molecular classification of the TetR family of transcriptional regulators. In G. sulfurreducens, we identified RpoN-regulated promoters upstream of several operons containing tetR family genes. The genome of G. sulfurreducens contains nine tetR family genes. Some of them are located upstream of operons encoding functionally important c-type cytochromes. In order to better understand the roles of TetR family members in the ability of Geobacteraceae to participate in electron transfer, we investigated phylogenetic relationships among TetR proteins in Geobacteraceae and in other microbial species. We identified their conserved and variable domains, which may be important for the diversity of their functional roles, and classified them into subgroups based on sequence similarities

A simulation-calibrated limit on the H i power spectrum from the GMRT Epoch of Reionization experiment

The Giant Metrewave Radio Telescope Epoch of Reionization experiment is an ongoing effort to measure the power spectrum from neutral hydrogen at high redshift. We have previously reported an upper limit of (70 mK)^2 at wavenumbers of k ≈ 0.65 h Mpc^(−1) using a basic piecewise-linear foreground subtraction. In this paper, we explore the use of a singular value decomposition to remove foregrounds with fewer assumptions about the foreground structure. Using this method, we also quantify, for the first time, the signal loss due to the foreground filter and present new power spectra adjusted for this loss, providing a revised measurement of a 2σ upper limit at (248 mK)^2 for k = 0.50 h Mpc^(−1). While this revised limit is larger than previously reported, we believe it to be more robust and still represents the best current constraint on reionization at z ≈ 8.6