Potential Role of Early-life Rhinovirus Infection in the Development of Asthma.

Early-life human rhinovirus (RV) infection has been linked to asthma development in high risk infants and children. Nevertheless, the role of RV infection in the initiation of asthma remains unclear. Because the airway epithelium is the primary target of respiratory viral infection, thymic stromal lymphopoietin (TSLP) and IL-25 and their downstream cellular targets are uniquely positioned to play a role in viral-induced chronic airways disease. We hypothesized that neonatal RV infection induces TSLP and IL-25, enhancing type 2 cytokine production from innate immune cells, thereby leading to mucous metaplasia and airways hyperresponsiveness. To resolve this issue, six day-old BALB/c mice and TSLP receptor (TSLPR) KO mice as well as eight week-old BALB/c mice were inoculated with sham HeLa cell lysate or RV. Airway responses from 1 to 28 days after infection were assessed by qPCR, ELISA, histology, immunofluorescence microscopy, flow cytometry and methacholine responsiveness. Selected mice were treated with a neutralizing antibody to IL-25. Compared to mature mice, RV infection in neonatal mice increased lung IL-13, IL-25 and TSLP production whereas IFN-gamma, IL-12p40 and TNF-alpha expression were suppressed. Induction of IL-25 and TSLP was regulated in an age-dependent manner. In addition, the population of IL-13-secreting type 2 innate lymphoid cells (ILC2s) was expanded with RV infection in neonatal but not in mature mice. ILC2 cells were the major cell type secreting IL-13 in neonates. Compared to control mice, TSLPR KO neonatal mice, or neonates treated with anti-IL-25 neutralizing antibody showed attenuated ILC2 expansion, mucous hypersecretion and airways responsiveness. When combined with IL-25 and IL-33, TSLP had a direct synergistic effect on ILC2 maturation and function. We conclude that TSLP and IL-25 is required for persistent mucus metaplasia and airway hyperresponsiveness as well as ILC2 expansion in RV-infected neonatal mice. These findings may suggest, with an appropriate genetic background, early-life RV infection may modulate and induce type 2 immune response, thereby leading to the development of persistent mucus metaplasia and airway hyperresponsiveness.PhDMolecular and Integrative PhysiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/111373/1/hongjy_1.pd

A Practical Cooperative Multicell MIMO-OFDMA Network Based on Rank Coordination

An important challenge of wireless networks is to boost the cell edge performance and enable multi-stream transmissions to cell edge users. Interference mitigation techniques relying on multiple antennas and coordination among cells are nowadays heavily studied in the literature. Typical strategies in OFDMA networks include coordinated scheduling, beamforming and power control. In this paper, we propose a novel and practical type of coordination for OFDMA downlink networks relying on multiple antennas at the transmitter and the receiver. The transmission ranks, i.e.\ the number of transmitted streams, and the user scheduling in all cells are jointly optimized in order to maximize a network utility function accounting for fairness among users. A distributed coordinated scheduler motivated by an interference pricing mechanism and relying on a master-slave architecture is introduced. The proposed scheme is operated based on the user report of a recommended rank for the interfering cells accounting for the receiver interference suppression capability. It incurs a very low feedback and backhaul overhead and enables efficient link adaptation. It is moreover robust to channel measurement errors and applicable to both open-loop and closed-loop MIMO operations. A 20% cell edge performance gain over uncoordinated LTE-A system is shown through system level simulations.Comment: IEEE Transactions or Wireless Communications, Accepted for Publicatio

Prediction for Irregular Ocean Wave and Floating Body Motion by Regularization: Part 1. Irregular Wave Prediction

Ocean waves can be explained in terms of many factors, including wave spectrum, which has the characteristics of wave height and periodicity, directional spreading function, which has a directional property, and random phase, which randomly represents a certain property. Under the assumption of a linear system, ocean waves show irregular behaviours, which can be observed in the forms of wave spectrum, directional spreading function, and complex phase calculations using the method of linear superposition. Ocean waves, which include a variety of periodic elements, exhibit direct proportionality between their period and propagation velocity. The purpose of this study was to understand the phase components of the period and to make exact calculations on the deterministic phase in order to make predictions on ocean waves. However, measurements of actual ocean waves exist only in the form of information on wave elevation, so we faced an inverse problem of having to analyse this information and calculate the deterministic phase. Regularization was used as part of the solution, and various methods were used to obtain stable values

Wave Run-Up Phenomenon on Offshore Platforms: Part 1. Tension Leg Platform

This study reports on an extensive experimental campaign carried out to evaluate non-linear waves applied to offshore structures in extreme marine environments. An offshore tension leg platform (TLP) model was used to observe the waves around a fixed-type offshore structure. The wave amplitude measured in the experiments of this study was indicated as a wave run-up ratio. Both the first-order analysis and the analysis of the entire wave amplitude were described. The experimental results were compared with the calculations from a potential-based code in order to verify the effectiveness of the developed technology

Prediction for Irregular Ocean Wave and Floating Body Motion by Regularization: Part 2. Motion Prediction

In the analysis of the motion of a floating body, the domains can broadly be divided into the frequency domain and the time domain. The essence of the frequency domain analysis lies in calculating the hydrodynamic coefficient from the equation of motion, which has six degrees of freedom, by applying several methods. In this research, Bureau Veritas’s “HydroStar” software was used, and the comparison and the verification were carried out by experiments. For the time domain analysis, we used an existing method proposed by Cummins and made motion predictions by using deterministic random phases calculated in the time domain calculations of the excitation force. Lastly, the potential of wave and motion predictions was verified through the data obtained from a motion analysis experiment using a tension leg platform in the context of irregular waves

The Effect of Exercise on Endoplasmic Reticulum Stress-Associated Vascular Dysfunction

Atherosclerosis and Alzheimer’s disease (AD) constitute a high health threat worldwide. Endothelial dysfunction is generally known as an early pathogenic response in atherosclerosis and a major culprit for the development of AD. Chronic endoplasmic reticulum (ER) stress in endothelial cells contributes to endothelial dysfunction with an increase in oxidative stress, inflammation, and apoptosis, which leads to cell death. Alleviation of ER stress in the vascular system can be an important therapeutic strategy for retardation and treatment of pathophysiology response in atherosclerosis and AD. Exercise training is considered to be frontline therapy for prevention and treatment of vascular dysfunction through the mitigation of oxidative stress and the inflammatory and apoptotic response in cardiovascular and neurodegenerative diseases. However, the role of exercise training in ER stress-associated vascular dysfunction in different vascular beds and its underlying mechanism in atherosclerosis and AD is still largely unknown. Therefore, the central aim of the dissertation study was to identify the underlying mechanisms by which exercise training mitigates ER stress-associated vascular dysfunction in different vascular beds and pathologies. To achieve the central aim of study, we investigated a comprehensive understanding of exercise effects on ER stress-associated endothelial dysfunction in different vascular beds (mesenteric artery and coronary arterioles) in atherosclerosis and on its molecular mechanisms. In addition, we explored the in-depth knowledge of the exercise effect on ER stress and purinergic receptor-associated cerebrovascular dysfunction using isolated intact posterior cerebral artery (PCA) from the transgenic mice model of AD and cultured human brain microvascular endothelial cells (HBMECs). To measure vascular function, we isolated the mesenteric arteries and coronary arterioles from ApoE knock-out mice for atherosclerosis and PCA from APP/PS1 double transgenic mice for AD. Also, we utilized programmed treadmill running as an exercise training intervention. To find an in-depth understanding of the exercise-induced effects at the cellular level, HBMECs were exposed to laminar shear stress (LSS). Our study demonstrates that ER stress impaired ACh-induced endothelial function in both mesenteric arteries and coronary arterioles of atherosclerosis through the reduction of eNOS expression and abnormal expression of ER stress markers, TXNIP/NLRP3 inflammasome, apoptosis, and oxidative stress. However, exercise training ameliorated ER stress-associated endothelial dysfunction in both vascular beds by reversing these abnormal molecular signaling pathways. In AD, ER stress impairs cerebrovascular function via the diminished eNOS expression, and increased ER stress markers and apoptosis expressions in AD mice brain, but exercise training improved cerebrovascular dysfunction by dampening these negative signaling cascades. Furthermore, ATP induced vasoconstriction in PCA from AD mice through the attenuation of eNOS and P2Y2 receptor expressions in AD mice brain. However, exercise training reversed ATP-induced vasoconstriction to vasodilation in PCA from AD mice with an increase in P2Y2 receptor-mediated eNOS signaling pathway in AD mice brain. Likewise, LSS upregulated the eNOS signaling and P2Y2 receptor expression in HBMECs, but inhibition of P2Y2 receptor blunted eNOS expression in LSS-induced HBMECs. The findings of this study will provide novel insight into the protective and therapeutic effect of exercise on ER stress- and purinergic receptor-associated vascular disease in atherosclerosis and AD.Health and Human Performance, Department o

Serial Magnetic Resonance Imagings of Multiple Brain Abscesses in a Patient with Pneumococcal Meningoencephalitis

We report a 43-yr-old man manifesting bacterial meningoencephalitis and multiple abscesses by Streptococcus pneumoniae. Serial magnetic resonance (MR) imagings and MR spectroscopy showed the evolution of multiple brain abscesses over 4 weeks: the enhanced rings became thicker and the dimension of whole lesions larger despite shrinkage of the ring-enhanced regions. These findings may be evidence of active inflammation working to sequestrate the lesion and protect the surrounding normal brain parenchyma from additional damage, even in the final stage of the brain abscess

REMOTE SENSING OF WAVE DIRECTIONALITY BY TWO-DIMENSIONAL DIRECTIONAL WAVELETS: PART 1. THE DETECTION TOOLS OF DIRECTIONALITY IN SIGNALS

This paper presents the results of a study investigating methods of wave directionality based on wavelet transform. In part 1 of this paper, the theoretical background and characteristics of directional wavelet were discussed. Morlet wavelet and Cauchy wavelet were examined to test their efficiency in detection of directionality in signals. These wavelets were tested on numerical images which were considered to describe the basic characteristics of directionality of ocean waves