Transcriptional down-regulation of suppressor of cytokine signaling (SOCS)-3 in chronic obstructive pulmonary disease

Background: Tobacco is a leading environmental factor in the initiation of respiratory diseases and causes chronic obstructive pulmonary disease (COPD). Suppressor of cytokine signaling (SOCS) family members are involved in the pathogenesis of many inflammatory diseases and SOCS-3 has been shown to play an important role in the regulation, onset and maintenance of airway allergic inflammation indicating that SOCS-3 displays a potential therapeutic target for anti-inflammatory respiratory drugs development. Since chronic obstructive pulmonary disease (COPD) is also characterized by inflammatory changes and airflow limitation, the present study assessed the transcriptional expression of SOCS-3 in COPD. Methods: Real-time PCR was performed to assess quantitative changes in bronchial biopsies of COPD patients in comparison to unaffected controls. Results: SOCS-3 was significantly down-regulated in COPD at the transcriptional level while SOCS-4 and SOCS-5 displayed no change. Conclusions: It can be concluded that the presently observed inhibition of SOCS-3 mRNA expression may be related to the dysbalance of cytokine signaling observed in COPD

Polystyrene-grafted Carbon Fibers: Surface Properties and Adhesion to Polystyrene

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.It is highly desirable to improve attractive interactions between carbon fibers and unreactive thermoplastic matrices to the possible maximum. This could be achieved by a simple grafting process to create a covalently bonded interface or interlayer, which should result in cohesive interactions between the polymer-grafted fibers and the same matrix material, leading to a better adhesion strength in the obtained composite material. Here, we are describing the grafting of styrene onto unmodified and unsized carbon fibers via free-radical bulk polymerization in the presence of fibers. After grafting, the surface properties of the carbon fiber approach those of pure polystyrene which was proven by contact angle and zeta (ζ) potential measurements. As indicated by the water contact angle, the carbon fiber surface becomes more hydrophobic. Scanning electron microscopy (SEM) provides evidence of grafted polymer. This simple procedure results in a continuous polystyrene coating. The fiber diameter increases significantly after polymer grafting. The adhesion and fracture behavior between the original and polystyrene-grafted carbon fibers to a polystyrene (VESTYRON®) matrix was characterized using the single-fiber pull-out test. There is a considerable increase in the measurable adhesion, i.e., the interfacial shear strength IFSS, by almost 300% between the grafted fibers and polystyrene as compared to untreated original fibers. Two planes of interfacial failure could be distinguished; first in the fiber coating interface leading to lower interfacial shear strength and second in the PS-matrix-PS-coating interphase resulting in a higher interfacial shear strength. In addition to the improved adhesion, there are also clear differences in the pull-out behavior between the nongrafted and grafted fibers. After the initial debonding process corresponding to the maximal pull-out force is completed, the pull-out force is increasing again

A Rollback Mechanism to Recover from Software Failures in Role-based Adaptive Software Systems

Context-dependent applications are relatively complex due to their multiple variations caused by context activation, especially in the presence of unanticipated adaptation. Testing these systems is challenging, as it is hard to reproduce the same execution environments. Therefore, a software failure caused by bugs is no exception. This paper presents a rollback mechanism to recover from software failures as part of a role-based runtime with support for unanticipated adaptation. The mechanism performs checkpoints before each adaptation and employs specialized sensors to detect bugs resulting from recent configuration changes. When the runtime detects a bug, it assumes that the bug belongs to the latest configuration. The runtime rolls back to the recent checkpoint to recover and subsequently notifes the developer to fix the bug and re-applying the adaptation through unanticipated adaptation. We prototype the concept as part of our role-based runtime engine LyRT and demonstrate the applicability of the rollback recovery mechanism for unanticipated adaptation in erroneous situations

A Dynamic Instance Binding Mechanism Supporting Run-Time Variability of Role-Based Software Systems

Role-based approaches gain more and more interest for modeling and implementing variable software systems. Role models clearly separate static behavior represented by players and dynamic behavior modeled as roles which can be dynamically bound and unbound to players at run time. To support the execution of role-based systems, a dynamic binding mechanism is required. Especially, since instances of the same player type can play different roles in a single context, the binding mechanism is required to operate at instance level. In this paper, we introduce a mechanism called dynamic instance binding for implementing a runtime for role-based systems. It maintains a look-up table that allows the run-time system to determine and invoke the currently active role binding at instance level. We explain dynamic instance binding mechanism in detail and demonstrate that it is flexible enough to support both adaptation and evolution of software systems at run time

Consistent Unanticipated Adaptation for Context-Dependent Applications

Unanticipated adaptation allows context-dependent applications to overcome the limitation of foreseen adaptation by incorporating previously unknown behavior. Introducing this concept in language-based approaches leads to inconsistencies as an object can have different views in different contexts. Existing language-based approaches do not address unanticipated adaptation and its associated run-time inconsistencies. We propose an architecture for unanticipated adaptation at run time based on dynamic instance binding crafted in a loosely manner to asynchronously replace adaptable entities that allow for behavioral changes of objects. To solve inconsistencies, we introduce the notion of transactions at the object level. Transactions guard the changing objects during their execution, ensuring consistent views. This allows for disruption-free, safe updates of adaptable entities by means of consistent unanticipated adaptation

Experimenting with Cigarettes and Physical Activity Among Mexican Origin Youth: A Cross Sectional Analysis of the Interdependent Associations Among Sensation Seeking, Acculturation, and Gender

Sensation seeking tendencies tend to manifest during adolescence and are associated with both health-compromising behaviors and health-enhancing behaviors. The purpose of this study is to evaluate the relationship between sensation seeking and physical activity, a health-enhancing behavior, and between sensation seeking and experimenting with cigarettes, a health compromising-behavior, among a cohort of Mexican origin adolescents residing in the United States with different levels of acculturation. Methods: In 2009, 1,154 Mexican origin youth (50.5% girls, mean age 14.3 years (SD = 1.04)) provided data on smoking behavior, physical activity, linguistic acculturation, and sensation seeking. We conducted Pearson's chi(2) tests to examine the associations between categorical demographic characteristics (i.e. gender, age, country of birth and parental educational attainment) and both cigarette experimentation and physical activity and Student's t-tests to examine mean differences on the continuous variables (i.e. sensation seeking subscale) by the behaviors. We examined mean differences in the demographic characteristics, acculturation, and both behaviors for each of the sensation seeking subscales using analysis of variance (ANOVA). To examine relationships between the sensation seeking subscales, gender, and both behaviors, at different levels of acculturation we completed unconditional logistic regression analyses stratified by level of acculturation. Results: Overall, 23.3% had experimented with cigarettes and 29.0% reported being physically active for at least 60 minutes/day on at least 5 days/week. Experimenting with cigarettes and being physically active were more prevalent among boys than girls. Among girls, higher levels of sensation seeking tendencies were associated with higher levels of acculturation and experimentation with cigarettes, but not with physical activity. Among boys, higher levels of sensation seeking tendencies were associated with higher levels of acculturation, experimenting with cigarettes and being physically active. Conclusions: Our results suggest that interventions designed to prevent smoking among Mexican origin youth may need to address social aspects associated with acculturation, paying close attention to gendered manifestations of sensation seeking.National Cancer Institute CA105203, CA126988Caroline W. Law Fund for Cancer PreventionDan Duncan Family Institute for Cancer Prevention and Risk AssessmentCenter for Health Promotion and Disease Prevention Research in Underserved Population

Decentralized Coordination of Dynamic Software Updates in the Internet of Things

Large scale IoT service deployments run on a high number of distributed, interconnected computing nodes comprising sensors, actuators, gateways and cloud infrastructure. Since IoT is a fast growing, dynamic domain, the implementation of software components are subject to frequent changes addressing bug fixes, quality insurance or changed requirements. To ensure the continuous monitoring and control of processes, software updates have to be conducted while the nodes are operating without losing any sensed data or actuator instructions. Current IoT solutions usually support the centralized management and automated deployment of updates but are restricted to broadcasting the updates and local update processes at all nodes. In this paper we propose an update mechanism for IoT deployments that considers dependencies between services across multiple nodes involved in a common service and supports a coordinated update of component instances on distributed nodes. We rely on LyRT on all IoT nodes as the runtime supporting local disruption-minimal software updates. Our proposed middleware layer coordinates updates on a set of distributed nodes. We evaluated our approach using a demand response scenario from the smart grid domain

Achieving global perfect homeostasis through transporter regulation

Nutrient homeostasis—the maintenance of relatively constant internal nutrient concentrations in fluctuating external environments—is essential to the survival of most organisms. Transcriptional regulation of plasma membrane transporters by internal nutrient concentrations is typically assumed to be the main mechanism by which homeostasis is achieved. While this mechanism is homeostatic we show that it does not achieve global perfect homeostasis—a condition where internal nutrient concentrations are completely independent of external nutrient concentrations for all external nutrient concentrations. We show that the criterion for global perfect homeostasis is that transporter levels must be inversely proportional to net nutrient flux into the cell and that downregulation of active transporters (activity-dependent regulation) is a simple and biologically plausible mechanism that meets this criterion. Activity-dependent transporter regulation creates a trade-off between robustness and efficiency, i.e., the system's ability to withstand perturbation in external nutrients and the transporter production rate needed to maintain homeostasis. Additionally, we show that a system that utilizes both activity-dependent transporter downregulation and regulation of transporter synthesis by internal nutrient levels can create a system that mitigates the shortcomings of each of the individual mechanisms. This analysis highlights the utility of activity-dependent regulation in achieving homeostasis and calls for a re-examination of the mechanisms of regulation of other homeostatic systems

The Signal Sequence Coding Region Promotes Nuclear Export of mRNA

In eukaryotic cells, most mRNAs are exported from the nucleus by the transcription export (TREX) complex, which is loaded onto mRNAs after their splicing and capping. We have studied in mammalian cells the nuclear export of mRNAs that code for secretory proteins, which are targeted to the endoplasmic reticulum membrane by hydrophobic signal sequences. The mRNAs were injected into the nucleus or synthesized from injected or transfected DNA, and their export was followed by fluorescent in situ hybridization. We made the surprising observation that the signal sequence coding region (SSCR) can serve as a nuclear export signal of an mRNA that lacks an intron or functional cap. Even the export of an intron-containing natural mRNA was enhanced by its SSCR. Like conventional export, the SSCR-dependent pathway required the factor TAP, but depletion of the TREX components had only moderate effects. The SSCR export signal appears to be characterized in vertebrates by a low content of adenines, as demonstrated by genome-wide sequence analysis and by the inhibitory effect of silent adenine mutations in SSCRs. The discovery of an SSCR-mediated pathway explains the previously noted amino acid bias in signal sequences and suggests a link between nuclear export and membrane targeting of mRNAs