Defining the chromatin signature of inducible genes in T cells

BACKGROUND Specific chromatin characteristics, especially the modification status of the core histone proteins, are associated with active and inactive genes. There is growing evidence that genes that respond to environmental or developmental signals may possess distinct chromatin marks. Using a T cell model and both genome-wide and gene-focused approaches, we examined the chromatin characteristics of genes that respond to T cell activation. RESULTS To facilitate comparison of genes with similar basal expression levels, we used expression-profiling data to bin genes according to their basal expression levels. We found that inducible genes in the lower basal expression bins, especially rapidly induced primary response genes, were more likely than their non-responsive counterparts to display the histone modifications of active genes, have RNA polymerase II (Pol II) at their promoters and show evidence of ongoing basal elongation. There was little or no evidence for the presence of active chromatin marks in the absence of promoter Pol II on these inducible genes. In addition, we identified a subgroup of genes with active promoter chromatin marks and promoter Pol II but no evidence of elongation. Following T cell activation, we find little evidence for a major shift in the active chromatin signature around inducible gene promoters but many genes recruit more Pol II and show increased evidence of elongation. CONCLUSIONS These results suggest that the majority of inducible genes are primed for activation by having an active chromatin signature and promoter Pol II with or without ongoing elongation

On q-Gaussians and Exchangeability

The q-Gaussians are discussed from the point of view of variance mixtures of normals and exchangeability. For each q< 3, there is a q-Gaussian distribution that maximizes the Tsallis entropy under suitable constraints. This paper shows that q-Gaussian random variables can be represented as variance mixtures of normals. These variance mixtures of normals are the attractors in central limit theorems for sequences of exchangeable random variables; thereby, providing a possible model that has been extensively studied in probability theory. The formulation provided has the additional advantage of yielding process versions which are naturally q-Brownian motions. Explicit mixing distributions for q-Gaussians should facilitate applications to areas such as option pricing. The model might provide insight into the study of superstatistics.Comment: 14 page

Evidence for Two Modes of Synergistic Induction of Apoptosis by Mapatumumab and Oxaliplatin in Combination with Hyperthermia in Human Colon Cancer Cells

Colorectal cancer is the third leading cause of cancer-related mortality in the world-- the main cause of death from colorectal cancer is hepatic metastases, which can be treated with isolated hepatic perfusion (IHP). Searching for the most clinically relevant approaches for treating colorectal metastatic disease by isolated hepatic perfusion (IHP), we developed the application of oxaliplatin concomitantly with hyperthermia and humanized death receptor 4 (DR4) antibody mapatumumab (Mapa), and investigated the molecular mechanisms of this multimodality treatment in human colon cancer cell lines CX-1 and HCT116 as well as human colon cancer stem cells Tu-12, Tu-21 and Tu-22. We showed here, in this study, that the synergistic effect of the multimodality treatment-induced apoptosis was caspase dependent and activated death signaling via both the extrinsic apoptotic pathway and the intrinsic pathway. Death signaling was activated by c-Jun N-terminal kinase (JNK) signaling which led to Bcl-xL phosphorylation at serine 62, decreasing the anti-apoptotic activity of Bcl-xL, which contributed to the intrinsic pathway. The downregulation of cellular FLICE inhibitory protein long isoform (c-FLIPL) in the extrinsic pathway was accomplished through ubiquitination at lysine residue (K) 195 and protein synthesis inhibition. Overexpression of c-FLIPL mutant (K195R) and Bcl-xL mutant (S62A) completely abrogated the synergistic effect. The successful outcome of this study supports the application of multimodality strategy to patients with colorectal hepatic metastases who fail to respond to standard chemoradiotherapy that predominantly targets the mitochondrial apoptotic pathway. © 2013 Song et al

The Analysis and the Performance of the Parallel-Partial Reset Control System

Reset controllers have demonstrated their effectiveness in enhancing performance in precision motion systems. To further exploiting the potential of reset controllers, this study introduces a parallel-partial reset control structure. Frequency response analysis is effective for the design and fine-tuning of controllers in industries. However, conducting frequency response analysis for reset control systems poses challenges due to their nonlinearities. We develop frequency response analysis methods for both the open-loop and closed-loop parallel-partial reset systems. Simulation results validate the accuracy of the analysis methods, showcasing precision enhancements exceeding 100% compared to the traditional describing function method. Furthermore, we design a parallel-partial reset controller within the Proportional-Integral-Derivative (PID) control structure for a mass-spring-damper system. The frequency response analysis of the designed system indicates that, while maintaining the same bandwidth and phase margin of the first-order harmonics, the new system exhibits lower magnitudes of higher-order harmonics, compared to the traditional reset system. Moreover, simulation results demonstrate that the new system achieves lower overshoot and quicker settling time compared to both the traditional reset and linear systems.Comment: Submitted to The European Control Conference 202

The embedment of social media in small business supply network management

In recent years, research trends have focused on analyzing supply chain management from the perspective of social networks in small- and medium-size enterprises (SMEs) (Borgatti & Li, 2009). In supply chain management, social networks are helpful to build relationships among members and to identify risks in supply chain activities (Cruz & Liu, 2011). Since social media may have its greatest and most natural application on the soft side (i.e., people) of supply chain management, the surge of social media could spur communication and information-sharing among supply-chain participants and, therefore, contribute to firms’ supply chain relationship development (O’Leary, 2011)

Defining the chromatin signature of inducible genes in T cells

Inducible genes in T cells show the chromatin characteristics of active genes, suggesting they are primed for transcription

Analytical solution to heat transfer in compressible laminar flow in a flat minichannel

This work was supported by the Beijing Science and Technology Project [grant number Z181100004518004] and the Fundamental Research Funds for the Central Universities [grant number FRF-GF-17-B31]. CB thanks for the China Scholarship Council (CSC) fellowship support.Heat transfer in compressible laminar flow in mini-/micro-channels, a classical and general topic in fields of fuel cells, electronics, micro heat exchanger, etc., is revisited. Based on a two-dimensional continuum flow model, analytical solutions of the dimensionless model are achieved in closed-form symbolic algebras of Whittaker eigenfunctions, corresponding to two kinds of boundary conditions with arbitrarily prescribed wall temperature or wall heat flux. As the eigenvalues and eigenfunctions are independent on the dimensionless quantities, which influence the along-the-channel behaviors, the algorithm reveals the common features of compressible laminar thermal flows. The algorithms do not require the assumption of a linear pressure distribution, which is proved to be untenable in some cases (e.g. constant wall heat flux). The algorithms are validated well by the exact (numerical) computations in exemplary cases of both small and moderate Reynolds number, Mach number and Eckert number of air. Although expressed in a series of eigenfunctions, only several terms (sometimes one or two terms) of solutions are required for a practical computation.PostprintPeer reviewe

Mathematical Model of Movement of a Mobile Robot with Omnidirectional Wheels

The article discusses the issue of controlling a four-wheeled mobile robot with omnidirectional wheelsof the mecanum type. An analysis of the rotational motion of the omnidirectional mecanum wheel was carriedout, based on its kinematics. For a specific robot with certain overall parameters, a graph of changes in the radiusof the mecanum wheel depending on the angle of its rotation was constructed. Kinematic and dynamic modelsof a mobile four-wheeled robot have been compiled, taking into account its geometric characteristics. The presented expressions are a mathematical description of the behavior of a mobile robot in statics and dynamics. Basedon the obtained models, the principles of operation of the motion control system for a four-wheeled mobile roboton omnidirectional wheels of the mecanum type are formed

Genome-wide imaging screen uncovers molecular determinants of arsenite-induced protein aggregation and toxicity

The toxic metalloid arsenic causes widespread misfolding and aggregation of cellular proteins. How these protein aggregates are formed in vivo, the mechanisms by which they affect cells and how cells prevent their accumulation is not fully understood. To find components involved in these processes, we performed a genome-wide imaging screen and identified Saccharomyces cerevisiae deletion mutants with either enhanced or reduced protein aggregation levels during arsenite exposure. We show that many of the identified factors are crucial to safeguard protein homeostasis (proteostasis) and to protect cells against arsenite toxicity. The hits were enriched for various functions including protein biosynthesis and transcription, and dedicated follow-up experiments highlight the importance of accurate transcriptional and translational control for mitigating protein aggregation and toxicity during arsenite stress. Some of the hits are associated with pathological conditions, suggesting that arsenite-induced protein aggregation may affect disease processes. The broad network of cellular systems that impinge on proteostasis during arsenic stress identified in this current study provides a valuable resource and a framework for further elucidation of the mechanistic details of metalloid toxicity and pathogenesis. This article has an associated First Person interview with the first authors of the paper