An Efficient Method to Identify Conditionally Activated Transcription Factors and their Corresponding Signal Transduction Pathway Segments

A signal transduction pathway (STP) is a cascade composed of a series of signal transferring steps, which often activate one or more transcription factors (TFs) to control the transcription of target genes. Understanding signaling pathways is important to our understanding of the molecular mechanisms of disease. Many condition-annotated pathways have been deposited in public databases. However, condition-annotated pathways are far from complete, considering the large number of possible conditions. Computational methods to assist in the identification of conditionally activated pathways are greatly needed. In this paper, we propose an efficient method to identify conditionally activated pathway segments starting from the identification of conditionally activated TFs, by incorporating protein-DNA binding data, gene expression data and protein interaction data. Applying our methods on several microarray datasets, we have discovered many significantly activated TFs and their corresponding pathway segments, which are supported by evidence in the literature

Transcriptional regulation in eukaryotic ribosomal protein genes

AbstractUnderstanding ribosomal protein gene regulation provides a good avenue for understanding gene regulatory networks. Even after 5 decades of research on ribosomal protein gene regulation, little is known about how higher eukaryotic ribosomal protein genes are coordinately regulated at the transcriptional level. However, a few recent papers shed some light on this complicated problem

Donor Natural Killer Cells and Their Therapeutic Potential in Allogeneic Hematopoietic Stem Cell Transplantation

Natural killer (NK) cells were first identified and named for their “natural” cytotoxicity to reject bone-marrow allografts in lethally irradiated mice. Different from T cells, NK cells require no prior sensitization or immunization to lyse transformed or virally infected target cells and are non-major histocompatibility complex (MHC)–restricted. However, recent progress in understanding of NK cells biology has proved that NK cells share some similar characteristics with T cells. During development, NK cells also undergo “education” according to “missing self” principle, thereby become mature and acquire effector function. The discovery that NK cells are able to “remember” prior certain stimulations indicates they may also contribute to adaptive immunity. After hematopoietic stem cell transplantation (HSCT), NK cells are the first donor-derived lymphogenous cells to reconstitute and alloreactivitiy of donor-derived NK cells have been shown to mediate graft-versus-leukemia (GvL) effect rather than to induce graft-versus-host disease (GvHD). These properties make donor-derived NK cells appealing for applications to benefit the outcome of HSCT. Here, we will review the improved understanding of NK cell biology, discuss characteristics of donor-derived NK cells which are associated with beneficial outcome of HSCT and explore novel methodologies that enhance the therapeutic effect of donor NK cells

A new measurement of sequence conservation

<p>Abstract</p> <p>Background</p> <p>Understanding sequence conservation is important for the study of sequence evolution and for the identification of functional regions of the genome. Current studies often measure sequence conservation based on every position in contiguous regions. Therefore, a large number of functional regions that contain conserved segments separated by relatively long divergent segments are ignored. Our goal in this paper is to define a new measurement of sequence conservation such that both contiguously conserved regions and discontiguously conserved regions can be detected based on this new measurement. Here and in the following, conserved regions are those regions that share similarity higher than a pre-specified similarity threshold with their homologous regions in other species. That is, conserved regions are good candidates of functional regions and may not be always functional. Moreover, conserved regions may contain long and divergent segments.</p> <p>Results</p> <p>To identify both discontiguously and contiguously conserved regions, we proposed a new measurement of sequence conservation, which measures sequence similarity based only on the conserved segments within the regions. By defining conserved segments using the local alignment tool CHAOS, under the new measurement, we analyzed the conservation of 1642 experimentally verified human functional non-coding regions in the mouse genome. We found that the conservation in at least 11% of these functional regions could be missed by the current conservation analysis methods. We also found that 72% of the mouse homologous regions identified based on the new measurement are more similar to the human functional sequences than the aligned mouse sequences from the UCSC genome browser. We further compared BLAST and discontiguous MegaBLAST with our method. We found that our method picks up many more conserved segments than BLAST and discontiguous MegaBLAST in these regions.</p> <p>Conclusions</p> <p>It is critical to have a new measurement of sequence conservation that is based only on the conserved segments in one region. Such a new measurement can aid the identification of better local "orthologous" regions. It will also shed light on the identification of new types of conserved functional regions in vertebrate genomes <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>.</p

Comparison and experiment of pressure drop of radial and annular type magnetorheological valves

The magnetorheological (MR) valve is a smart control mechanism using the magnetorheologcial fluid as the working fluid. The advantages of regulating pressure drop and fast response time make the valve have a promising application prospects in the hydraulic servo system, and the MR valve can also be used as a bypass valve to control the MR damper, which can be applied to the different types of vibration attenuating system. The change of pressure drop of MR valve considering radial and annular fluid flow paths was outlined through theory analysis, numerical simulation and experimental verification. The magnetized resistance gaps of both MR valves were constrained within a width of 2.5 mm and a length of 80 mm. The mathematical models of pressure drop of both MR valves were derived separately. The finite element modelling was carried out using ANSYS/Emag software to investigate the distribution of magnetic flux density and dynamic yield stress, and the analytical pressure drop was also obtained, the maximum theoretical pressure drops for the radial and annular type MR valves are 1930 kPa and 982 kPa respectively. Furthermore, a test rig was set up to test the pressure drop under different applied direct currents and different load cases, the maximum experimental pressure dropts for the radial and annular type MR valves are 950 kPa and 660 kPa, respectively. The simulation and experimental results showed that the pressure drop of the radial type MR valve was superior to that of annular type MR valve under the same geometry conditions and the same electromagnetic parameters. The results can provide a new guideline for design of other types MR valve

A CLT for the LSS of large dimensional sample covariance matrices with diverging spikes

In this paper, we establish the central limit theorem (CLT) for linear spectral statistics (LSS) of large-dimensional sample covariance matrix when the population covariance matrices are not uniformly bounded, which is a nontrivial extension of the Bai-Silverstein theorem (BST) (2004). The latter has strongly influenced the development of high-dimensional statistics, especially in applications of random matrix theory to statistics. However, the assumption of uniform boundedness of the population covariance matrices has seriously limited the applications of the BST. The aim of this paper is to remove the barriers for the applications of the BST. The new CLT, allows spiked eigenvalues to exist, which may be bounded or tend to infinity. An important feature of our result is that the roles of either spiked eigenvalues or the bulk eigenvalues predominate in the CLT, depending on which variance is nonnegligible in the summation of the variances. The CLT for LSS is then applied to compare four linear hypothesis tests: The Wilk's likelihood ratio test, the Lawly-Hotelling trace test, the Bartlett-Nanda-Pillai trace test, and Roy's largest root test. We also derive and analyze their power function under particular alternatives.Comment: Comparing with the old manuscript, we modified the title of the paper. arXiv admin note: text overlap with arXiv:2205.07280. arXiv admin note: text overlap with arXiv:2205.0728