Locally concentrated nuclear factors ensure efficient binding to DNA templates, facilitating RNA polymerase II recruitment and frequent reutilization of stable preinitiation complexes. We have ...uncovered a mechanism for effective viral transcription by focal assembly of RNA polymerase II around Kaposi's sarcoma-associated herpesvirus (KSHV) genomes in the host cell nucleus. Using immunofluorescence labeling of latent nuclear antigen (LANA) protein, together with fluorescence
RNA hybridization (RNA-FISH) of the intron region of immediate early transcripts, we visualized active transcription of viral genomes in naturally infected cells. At the single-cell level, we found that not all episomes were uniformly transcribed following reactivation stimuli. However, those episomes that were being transcribed would spontaneously aggregate to form transcriptional "factories," which recruited a significant fraction of cellular RNA polymerase II. Focal assembly of "viral transcriptional factories" decreased the pool of cellular RNA polymerase II available for cellular gene transcription, which consequently impaired cellular gene expression globally, with the exception of selected ones. The viral transcriptional factories localized with replicating viral genomic DNAs. The observed colocalization of viral transcriptional factories with replicating viral genomic DNA suggests that KSHV assembles an "all-in-one" factory for both gene transcription and DNA replication. We propose that the assembly of RNA polymerase II around viral episomes in the nucleus may be a previously unexplored aspect of KSHV gene regulation by confiscation of a limited supply of RNA polymerase II in infected cells.
B cells infected with Kaposi's sarcoma-associated herpesvirus (KSHV) harbor multiple copies of the KSHV genome in the form of episomes. Three-dimensional imaging of viral gene expression in the nucleus allows us to study interactions and changes in the physical distribution of these episomes following stimulation. The results showed heterogeneity in the responses of individual KSHV episomes to stimuli within a single reactivating cell; those episomes that did respond to stimulation, aggregated within large domains that appear to function as viral transcription factories. A significant portion of cellular RNA polymerase II was trapped in these factories and served to transcribe viral genomes, which coincided with an overall decrease in cellular gene expression. Our findings uncover a strategy of KSHV gene regulation through focal assembly of KSHV episomes and a molecular mechanism of late gene expression.
The three-dimensional structure of chromatin organized by genomic loops facilitates RNA polymerase II access to distal promoters. The Kaposi's sarcoma-associated herpesvirus (KSHV) lytic ...transcriptional program is initiated by a single viral transactivator, K-Rta. Here we report the KSHV genomic structure and its relationship with K-Rta recruitment sites using Capture Hi-C analyses. High-resolution 3D viral genomic maps identify a number of direct physical, long-range, and dynamic genomic interactions. Mutant KSHV chromosomes harboring point mutations in the K-Rta responsive elements (RE) significantly attenuate not only the directly proximate downstream gene, but also distal gene expression in a domain-specific manner. Genomic loops increase in the presence of K-Rta, while abrogation of K-Rta binding impairs the formation of inducible genomic loops, decreases the expression of genes networked through the looping, and diminishes KSHV replication. Our study demonstrates that genomic architectural dynamics plays an essential role in herpesvirus gene expression.
One primary concern about receiving care at home is that survival might be shortened because the quality and quantity of treatment provided at home will be inferior to that given in the hospital. ...Although our previous study demonstrated a longer survival of those with home-based palliative care (PC), it lacked adjustment for some potential confounders including symptoms and treatments during the stay. We aimed to compare the survival times among advanced cancer patients receiving home-based and hospital-based PC with adjusting for symptoms and treatments.
We compared survival time of participants who enrolled two multicenter, prospective cohort studies of advanced cancer patients at 45-home-based PC services between July 2017 and December 2017, and at 23-hospital-based PC services between January 2017 and December 2017. We analyzed with stratification by the estimated survival of Days, Weeks, and Months, which were defined by modified Prognosis in Palliative care Study predictor models-A. We conducted a Cox regression analysis with adjusting for potential confounders including symptoms and treatments during the stay.
A total of 2,998 patients were enrolled in both studies and 2,878 patients were analyzed; 988 patients receiving home-based PC and 1,890 receiving hospital-based PC. The survival time of patients receiving home-based PC was significantly longer than that of patients receiving hospital-based PC for the Days Prognosis (estimated median survival time: 10 days 95% CI 8.1-11.8 vs. 9 days 95% CI 8.3-10.4, p = 0.157), the Weeks prognosis (32 days 95% CI 28.9-35.4 vs. 22 days 95% CI 20.3-22.9, p < 0.001), and the Months Prognosis, (65 days 95% CI 58.2-73.2 vs. 32 days 95% CI 28.9-35.4, p < 0.001).
In this cohort of advanced cancer patients with a Weeks or Months prognosis, those receiving home-based PC survived longer than those receiving hospital-based PC after adjusting for symptoms and treatments.
abstFig src='/00280005/13.jpg' width='300' text='VRFT model matching problem with prefilter
F(z)
' Prefilters for Virtual Reference Feedback Tuning (VRFT) in the time domain are realized by the ...least-squares method with step reference response data acquired from the closed-loop system to be tuned and are used to obtain controller parameters for making closed-loop systems as close as possible to the desired reference model. The usefulness of this proposal is shown in numerical examples in which fifth-order and PID controllers for a flexible transmission system are tuned by VRFT with prefilters.
This paper presents a new recognition system for shockable arrhythmias for patients suffering from sudden cardiac arrest. In order to develop the recognition system, lots of electrocardiogram (ECGs) ...have been analyzed by using gabor wavelet transform (GWT). Although, there is a huge number of spectrum feature parameters, recognition performance for all combinations for spectrum feature parameters are evaluated, and on the basis of the evaluation results, useful and effective spectrum features for ECGs are extracted. As a result, the proposed recognition system based on the selected effective spectrum feature parameters can achieved good performance comparing with the existing results.
The downsampling of a discrete wavelet transform (DWT) has a side effect of the lack of shiftinvariance. There are two main solutions for this effect: one is the stationary wavelet transform (SWT), ...which does not apply downsampling. The other is the complex DWT (CDWT), which uses dual multiresolution analysis(MRA). We choose the CDWT as a target of research. It is well known that wavelet functions become Hilbert transform pairs if the low-pass filters (LPFs) on the reconstruction side have half-sample shifts. In this paper, we propose a quasi-shift-invariant (QSI) CDWT for bi-/orthogonal wavelets as a new CDWT. We report three new works (W1-W3) on it: (W1) we generalized the condition of Hilbert transform pairs and employed a complex wavelet function as a conjugate analytical signal. (W2) We defined a structure that achieves shift-invariance. The structure requires half-sample delays between the inputs of real and imaginary parts. (W3) We proposed an implementation of the QSI-CDWT and confirmed that our method has higher shift-invariance than the conventional CDWT. However, two problems (P1, P2) remain unsolved: (P1) our method requires more resources, such as memory and calculation time, than the conventional CDWT. (P2) Our theory cannot make all packets shift-invariant in a classical wavelet packet transform tree.
This paper addresses a path tracking problem with obstacle avoidance for Lagrange systems. The proposed method is based on field potential methods in combination with navigation functions for ...obstacle avoidance. First, it is shown that a simple combination of the navigation function with the conventional path tracking controller does not work. Therefore, in order to cope with this problem, a new feedback law is proposed for a path parameter which characterizes the reference path. It is proved that the proposed controller achieves both path following and collision avoidance. Moreover, since the method adopts bounded navigation functions, the proposed controllers generate bounded input signals even when target systems approach obstacles. Finally, an experimental evaluation is performed with a two-link manipulator to illustrate the effectiveness of the proposed method.
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