Increased ATP generation in the host cell is required for efficient vaccinia virus production

To search for cellular genes up-regulated by vaccinia virus (VV) infection, differential display-reverse transcription-polymerase chain reaction (ddRT-PCR) assays were used to examine the expression of mRNAs from mock-infected and VV-infected HeLa cells. Two mitochondrial genes for proteins that are part of the electron transport chain that generates ATP, ND4 and CO II, were up-regulated after VV infection. Up-regulation of ND4 level by VV infection was confirmed by Western blotting analysis. Up-regulation of ND4 was reduced by the MAPK inhibitor, apigenin, which has been demonstrated elsewhere to inhibit VV replication. The induction of ND4 expression occurred after viral DNA replication since ara C, an inhibitor of poxviral DNA replication, could block this induction. ATP production was increased in the host cells after VV infection. Moreover, 4.5 μM oligomycin, an inhibitor of ATP production, reduced the ATP level 13 hr after virus infection to that of mock-infected cells and inhibited viral protein expression and virus production, suggesting that increased ATP production is required for efficient VV production. Our results further suggest that induction of ND4 expression is through a Bcl-2 independent pathway

A genetic algorithm-based boolean delay model of intracellular signal transduction in inflammation

Abstract Background Signal transduction is the major mechanism through which cells transmit external stimuli to evoke intracellular biochemical responses. Understanding relationship between external stimuli and corresponding cellular responses, as well as the subsequent effects on downstream genes, is a major challenge in systems biology. Thus, a systematic approach to integrate experimental data and qualitative knowledge to identify the physiological consequences of environmental stimuli is needed. Results In present study, we employed a genetic algorithm-based Boolean model to represent NF-κB signaling pathway. We were able to capture feedback and crosstalk characteristics to enhance our understanding on the acute and chronic inflammatory response. Key network components affecting the response dynamics were identified. Conclusions We designed an effective algorithm to elucidate the process of immune response using comprehensive knowledge about network structure and limited experimental data on dynamic responses. This approach can potentially be implemented for large-scale analysis on cellular processes and organism behaviors. </jats:sec

Quantum correlation generation capability of experimental processes

Einstein-Podolsky-Rosen (EPR) steering and Bell nonlocality illustrate two different kinds of correlations predicted by quantum mechanics. They not only motivate the exploration of the foundation of quantum mechanics, but also serve as important resources for quantum-information processing in the presence of untrusted measurement apparatuses. Herein, we introduce a method for characterizing the creation of EPR steering and Bell nonlocality for dynamical processes in experiments. We show that the capability of an experimental process to create quantum correlations can be quantified and identified simply by preparing separable states as test inputs of the process and then performing local measurements on single qubits of the corresponding outputs. This finding enables the construction of objective benchmarks for the two-qubit controlled operations used to perform universal quantum computation. We demonstrate this utility by examining the experimental capability of creating quantum correlations with the controlled-phase operations on the IBM Quantum Experience and Amazon Braket Rigetti superconducting quantum computers. The results show that our method provides a useful diagnostic tool for evaluating the primitive operations of nonclassical correlation creation in noisy intermediate scale quantum devices.Comment: 5 figures, 3 appendice

Computational modeling with forward and reverse engineering links signaling network and genomic regulatory responses: NF-κB signaling-induced gene expression responses in inflammation

<p>Abstract</p> <p>Background</p> <p>Signal transduction is the major mechanism through which cells transmit external stimuli to evoke intracellular biochemical responses. Diverse cellular stimuli create a wide variety of transcription factor activities through signal transduction pathways, resulting in different gene expression patterns. Understanding the relationship between external stimuli and the corresponding cellular responses, as well as the subsequent effects on downstream genes, is a major challenge in systems biology. Thus, a systematic approach is needed to integrate experimental data and theoretical hypotheses to identify the physiological consequences of environmental stimuli.</p> <p>Results</p> <p>We proposed a systematic approach that combines forward and reverse engineering to link the signal transduction cascade with the gene responses. To demonstrate the feasibility of our strategy, we focused on linking the NF-κB signaling pathway with the inflammatory gene regulatory responses because NF-κB has long been recognized to play a crucial role in inflammation. We first utilized forward engineering (Hybrid Functional Petri Nets) to construct the NF-κB signaling pathway and reverse engineering (Network Components Analysis) to build a gene regulatory network (GRN). Then, we demonstrated that the corresponding IKK profiles can be identified in the GRN and are consistent with the experimental validation of the IKK kinase assay. We found that the time-lapse gene expression of several cytokines and chemokines (TNF-α, IL-1, IL-6, CXCL1, CXCL2 and CCL3) is concordant with the NF-κB activity profile, and these genes have stronger influence strength within the GRN. Such regulatory effects have highlighted the crucial roles of NF-κB signaling in the acute inflammatory response and enhance our understanding of the systemic inflammatory response syndrome.</p> <p>Conclusion</p> <p>We successfully identified and distinguished the corresponding signaling profiles among three microarray datasets with different stimuli strengths. In our model, the crucial genes of the NF-κB regulatory network were also identified to reflect the biological consequences of inflammation. With the experimental validation, our strategy is thus an effective solution to decipher cross-talk effects when attempting to integrate new kinetic parameters from other signal transduction pathways. The strategy also provides new insight for systems biology modeling to link any signal transduction pathways with the responses of downstream genes of interest.</p

Enterovirus type 71 2A protease functions as a transcriptional activator in yeast

Enterovirus type 71 (EV71) 2A protease exhibited strong transcriptional activity in yeast cells. The transcriptional activity of 2A protease was independent of its protease activity. EV71 2A protease retained its transcriptional activity after truncation of 40 amino acids at the N-terminus but lost this activity after truncation of 60 amino acids at the N-terminus or deletion of 20 amino acids at the C-terminus. Thus, the acidic domain at the C-terminus of this protein is essential for its transcriptional activity. Indeed, deletion of amino acids from 146 to 149 (EAME) in this acidic domain lost the transcriptional activity of EV71 2A protein though still retained its protease activity. EV71 2A protease was detected both in the cytoplasm and nucleus using confocal microscopy analysis. Coxsackie virus B3 2A protease also exhibited transcriptional activity in yeast cells. As expected, an acidic domain in the C-terminus of Coxsackie virus B3 2A protease was also identified. Truncation of this acidic domain resulted in the loss of transcriptional activity. Interestingly, this acidic region of poliovirus 2A protease is critical for viral RNA replication. The transcriptional activity of the EV71 or Coxsackie virus B3 2A protease should play a role in viral replication and/or pathogenesis

Biosensor for human IgE detection using shear-mode FBAR devices

Abstract Film bulk acoustic resonators (FBARs) have been evaluated for use as biosensors because of their high sensitivity and small size. This study fabricated a novel human IgE biosensor using shear-mode FBAR devices with c-axis 23°-tilted AlN thin films. Off-axis radio frequency (RF) magnetron sputtering method was used for deposition of c-axis 23°-tilted AlN thin films. The deposition parameters were adopted as working pressure of 5 mTorr, substrate temperature of 300°C, sputtering power of 250 W, and 50 mm distance between off-axis and on-axis. The characteristics of the AlN thin films were investigated by X-ray diffraction and scanning electron microscopy. The frequency response was measured with an HP8720 network analyzer with a CASCADE probe station. The X-ray diffraction revealed (002) preferred wurtzite structure, and the cross-sectional image showed columnar structure with 23°-tilted AlN thin films. In the biosensor, an Au/Cr layer in the FBAR backside cavity was used as the detection layer and the Au surface was modified using self-assembly monolayers (SAMs) method. Then, the antigen and antibody were coated on biosensor through their high specificity property. Finally, the shear-mode FBAR device with k t 2 of 3.18% was obtained, and the average sensitivity for human IgE detection of about 1.425 × 105 cm2/g was achieved.</jats:p

A Low Power Fully Integrated Analog Baseband Circuit with Variable Bandwidth for 802.11 a/b/g WLAN

Abstract: This paper presents experimental results of an analog baseband circuit with variable bandwidth for WLAN direct conversion receiver in UMC 0.18um CMOS process. A seventh order chebyshev lowpass filter with triple bandwidth is used in the analog baseband circuit. The bandwidth is selectable from 7.56MHz, 19.5MHz, or 26.5MHz. The circuit adopts the servo loop for dc offset cancellation. It also has a gain range from 20dB to 60 dB with 10 dB steps while only dissipating 22.248mW. In addition, an automatic frequency tuning loop (ATL) is reported to achieve the bandwidth accuracy of the filter

Atomic layer deposition-based functionalization of materials for medical and environmental health applications

Nanoporous alumina membranes exhibit high pore densities, well-controlled and uniform pore sizes, as well as straight pores. Owing to these unusual properties, nanoporous alumina membranes are currently being considered for use in implantable sensor membranes and water purification membranes. Atomic layer deposition is a thin-film growth process that may be used to modify the pore size in a nanoporous alumina membrane while retaining a narrow pore distribution. In addition, films deposited by means of atomic layer deposition may impart improved biological functionality to nanoporous alumina membranes. In this study, zinc oxide coatings and platinum coatings were deposited on nanoporous alumina membranes by means of atomic layer deposition. PEGylated nanoporous alumina membranes were prepared by self-assembly of 1-mercaptoundec-11-yl hexa(ethylene glycol) on platinum-coated nanoporous alumina membranes. The pores of the PEGylated nanoporous alumina membranes remained free of fouling after exposure to human platelet-rich plasma; protein adsorption, fibrin networks and platelet aggregation were not observed on the coated membrane surface. Zinc oxide-coated nanoporous alumina membranes demonstrated activity against two waterborne pathogens, Escherichia coli and Staphylococcus aureus. The results of this work indicate that nanoporous alumina membranes may be modified using atomic layer deposition for use in a variety of medical and environmental health applications