Microbial Interactions in Biofilms: Impacts on Homeostasis and Pathogenesis

Microbes in nature or in the human body are predominantly associated with surfaces and living in biofilms. Species diversity, high cell density and close proximity of cells are typical of life in biofilms, where organisms interact with each other and develop complex interactions that can be either competitive or cooperative. Competition between species is a well-recognized ecological force to drive microbial metabolism, diversity and evolution. However, it was not until recently that microbial cooperative activities are also recognized to play important roles in microbial physiology and ecology. Importantly, these microbial interactions in biofilms profoundly affect their overall function, biomass, diversity and pathogenesis. It is now known that every human body contains a personalized microbiome that is essential to maintain host health. Remarkably, the indigenous species in most microbial communities often maintain a relatively stable and harmless relationship with the hosts despite regular exposure to minor environmental perturbations and host defence factors. Such stability or homeostasis results from a dynamic balance of microbial–microbial and microbial–host interactions. Under some circumstances, however, the homeostasis may breakdown, predisposing a site to diseases. The evidence has accumulated that such biofilm or community-based diseases can be prevented or treated not only by targeting putative pathogens, but also by interfering with the processes that drive breakdown of the homeostasis in biofilms

Structural and functional insights into a quorum-sensing signal peptide receptor, the ComD histidine protein kinase of streptococcus mutans

Quorum sensing activation by signal peptide pheromones (SP) in Gram-positive bacteria depends on a membrane-associated histidine kinase receptor, which senses the signal and triggers the signaling cascade for various cell density-dependent activities. However, relatively little is known of peptide pheromone-receptor interactions in these bacteria, largely because of technical challenges in working with membrane-associated proteins in these bacteria. Recently, we have described a genetic approach and several analysis methods to studying membrane topology and structure-function interaction of a quorum sensing pheromone receptor ComD in a Gram-positive bacterium Streptococcus mutans. Using these methods, we confirm that the membrane-spanning domain of the ComD protein forms six transmembrane segments and three extracellular loops, loopA, loopB and loopC. By mutational analyses of these three extracellular loops, we demonstrate that both loopC and loopB are required for signal recognition and quorum sensing activation, while loopA plays little role in signal detection. In particular, a deletion or substitution mutation of four residues NVIP within loopC abolishes signal recognition for quorum sensing activation. Consistent with these findings, the loopC and loopB mutants are completely or partially defective in bacteriocin production. We conclude that both loopC and loopB are required to form the signal peptide receptor and the residues NVIP of loopC are essential for signal recognition and quorum sensing activation in S. mutans

Identity Laws and Privacy Protection in a Modern State: The Legal History Concerning Personal Information in Taiwan (1895-2015)

This article investigates the continuity and transformation of the personal identity and identification legal systems in Taiwan. From 1895 to 2015, Japan and subsequently the Republic of China (ROC) ruled Taiwan and transplanted different legal systems of personal information to Taiwan. This article analyzes how these systems were applied to and impacted Taiwanese society in three periods: the Japanese rule period (1895–1945), the period of strict control by the ROC government (1945–1992), and the rise and evolution of the privacy period (1993–2015). When Taiwan was ruled by the Qing Empire (1683–1895), there was no precise personal information database in Taiwan. After the Sino-Japanese War, in 1895 the Qing Dynasty ceded Taiwan to Japan, which spent a ten years using its police to conduct surveys to collect person information of all residents in Taiwan. Based on the survey results, Japan established a modern household registration system to govern legal identity and identification affairs in Taiwan. While this personal database facilitated the enforcement of public policies, the main purpose of the Japanese household registration system was to allow the police to closely monitor the residents in Taiwan. After World War II, the ROC government ruled Taiwan since 1945. Using the Japanese household registration records as a foundation, the ROC government was able to quickly construct its own household registration system. Moreover, in order to counter the threats of the Communist Party in Mainland China, the ROC government combined the household registration system with the police system and issued National Identification Cards (National ID Cards) for every Taiwanese adult citizen for mobilization and surveillance. The combination of the police and the household registration systems was in effect until 1992. However, advanced computer technology made fingerprint databases feasible, which posed new threats to privacy rights. In 1997, the ROC Legislative Yuan amended the Household Registration Act to establish a fingerprint database for strengthening social order. Article 8 of the amended act required all Taiwanese adults to provide their fingerprints when they renewed their National ID Cards. This requirement raised heated debates on the issue of whether the government’s collection of fingerprints intruded on right of privacy. Responding to such dispute, in 2005 the Constitutional Court struck down Article 8 of the Household Registration Act for violating individual privacy rights. The repeal of the Household Registration Act signified a landmark event for privacy protection in Taiwan. After about one hundred years of suppression and surveillance, the Taiwanese people ultimately become aware of the value of privacy rights. Yet, due to the threats of terrorism and advanced technology, Taiwan and other countries are facing concerns about the collection of information, improvement of national security, and protection of privacy rights. The Taiwanese people, as well as people around the world, must carefully seek to balance these competing interests

Pricing Web Advertisement: Display Ads V.S. Contextual Ads

Most web sites provide display advertising and contextual advertising services simultaneously, which are the main ad formats in Internet. With multimedia format, the pricing of display ads is generally based on the occurrence of ad impressions. However, targeting their customers more accurately, contextual ads are performance based advertisements and are charged only if one visitor clicks a client’s appointed ad. In this paper, we develop an economic model to examine the pricing strategy, profitability, and social efficiency of these two heterogeneous web advertising channels, with respect to different market structures

Integration of WiMAX and WiFi Services: Bandwidth Sharing and Channel Collaboration

and WiMAX networks; however, most of them either concentrate on the design of collaborated protocols or figure out the issue without the overall consideration of customer preference and contract design. In the present study, we consider a wireless service market in which there are two wireless service providers operating WiFi and WiMAX, respectively. One of the research dimensions given in the study is whether wireless operators implement bandwidth sharing, while the other is whether wireless operators make decisions independently or jointly. By involving customer preference and wholesale price contract in the present model, we find that bandwidth sharing would benefit a WiMAX service provider, yet a WiFi service provider has no significant saving under a wholesale price contract. In addition, the profit of a WiMAX service may increase with WiFi coverage when bandwidth sharing is implemented but decease with WiFi coverage when both wireless services operate without bandwidth sharing. Besides, the WiMAX service provider would allocate more capacity when average usage rate increases, but decrease the amount of capacity when average usage rate is too large

Regulation of substance P and Neurokinin-1 receptor expression in a mouse model of acute pancreatitis

Ph.DDOCTOR OF PHILOSOPH

Medicare beneficiary panel characteristics associated with high Part D biologic disease-modifying anti-rheumatic drug prescribing for older adults among rheumatologists.

ABSTRACT: The aim of this study was to investigate beneficiary panel characteristics associated with rheumatologists' prescribing of biologic DMARDs (bDMARDs) for older adults.In this retrospective observational study, we used Medicare Public Use Files (PUFs) to identify rheumatologists who met criteria for high-prescribing, defined as bDMARD prescription constituting ≥20% of their DMARD claims for beneficiaries ≥65 years of age. We first used descriptive analysis then multivariable regression model to test the association of high prescribing of bDMARDs with rheumatologists' panel size and beneficiary characteristics. In particular, we quantified the proportion of panel beneficiaries ≥75 years of age to assess how caring for an older panel correlate with prescribing of bDMARDs.We identified 3197 unique rheumatologists, of whom 405 (13%) met criteria for high prescribing of bDMARDs for Medicare beneficiaries ≥65 years of age. The high-prescribers provided care to 12% of study older adults, and yet accounted for 21% of bDMARD prescriptions for them. High prescribing of bDMARDs was associated with smaller panel size, and their beneficiaries were more likely to be non-black, ≥75 years of age, non-dual eligible, have diagnosis of CHF, however, less likely to have CKD.Rheumatologists differ in their prescribing of bDMARDs for older adults, and those caring for more beneficiaries ≥75 years of age are more likely to be high-prescribers. Older adults are more prone to the side-effects of bDMARDs and further investigation is warranted to understand drivers of differential prescribing behaviors to optimize use of these high-risk and high-cost medications.http://deepblue.lib.umich.edu/bitstream/2027.42/170715/2/Medicare beneficiary panel characteristics associated with high Part D biologic disease-modifying anti-rheumatic drug prescr.pdfPublished versio

Building Cooperation in VoIP Network through a Reward Mechanism

In this paper, for solving the moral hazard problem of super nodes in VOIP network and achieving better communication quality, we establish a reward mechanism based on classical efficiency-wage models. In the reward mechanism, the function of reward is to encourage super nodes to contribute their bandwidth and cover their effort costs, whereas the function of fine is to prevent opportunistic super nodes from shirking. We consider that network quality and idle bandwidth are the essential criterions for selecting qualified super nodes. Once all super nodes can satisfy specific conditions, the required reward can be derived so as to improve the VoIP platform\u27s revenue. Moreover, we also suggest several targets both in technical and economic view that the platform provider can strive in order to boost his/her market share. In addition, the case of Skype is discussed in this study and we also examine its current pricing strategy

Neurokinin-1 Receptor Antagonist Treatment in Polymicrobial Sepsis: Molecular Insights

Neurokinin-1 receptor blocking has been shown to be beneficial against lung injury in polymicrobial sepsis. In this paper, we evaluated the possible mediators and the mechanism involved. Mice were subjected to cecal ligation and puncture (CLP-) induced sepsis or sham surgery. Vehicle or SR140333 [1 mg/kg; subcutaneous (s.c.)] was administered to septic mice either 30 min before or 1 h after the surgery. Lung tissue was collected 8 h after surgery and further analyzed. CLP alone caused a significant increase in the activation of the transcription factors, protein kinase C-α, extracellular signal regulated kinases, neurokinin receptors, and substance P levels in lung when compared to sham-operated mice. SR140333 injected pre- and post surgery significantly attenuated the activation of transcription factors and protein kinase C-α and the plasma levels of substance P compared to CLP-operated mice injected with the vehicle. In addition, GR159897 (0.12 mg/kg; s.c.), a neurokinin-2 receptor antagonist, failed to show beneficial effects. We conclude that substance P acting via neurokinin-1 receptor in sepsis initiated signaling cascade mediated mainly by protein kinase C-α, led to NF-κB and activator protein-1 activation, and further modulated proinflammatory mediators