Prototype of Fault Adaptive Embedded Software for Large-Scale Real-Time Systems

This paper describes a comprehensive prototype of large-scale fault adaptive embedded software developed for the proposed Fermilab BTeV high energy physics experiment. Lightweight self-optimizing agents embedded within Level 1 of the prototype are responsible for proactive and reactive monitoring and mitigation based on specified layers of competence. The agents are self-protecting, detecting cascading failures using a distributed approach. Adaptive, reconfigurable, and mobile objects for reliablility are designed to be self-configuring to adapt automatically to dynamically changing environments. These objects provide a self-healing layer with the ability to discover, diagnose, and react to discontinuities in real-time processing. A generic modeling environment was developed to facilitate design and implementation of hardware resource specifications, application data flow, and failure mitigation strategies. Level 1 of the planned BTeV trigger system alone will consist of 2500 DSPs, so the number of components and intractable fault scenarios involved make it impossible to design an `expert system' that applies traditional centralized mitigative strategies based on rules capturing every possible system state. Instead, a distributed reactive approach is implemented using the tools and methodologies developed by the Real-Time Embedded Systems group.Comment: 2nd Workshop on Engineering of Autonomic Systems (EASe), in the 12th Annual IEEE International Conference and Workshop on the Engineering of Computer Based Systems (ECBS), Washington, DC, April, 200

Prototype of Fault Adaptive Embedded Software for Large-Scale Real-Time Systems

This paper describes a comprehensive prototype of large-scale fault adaptive embedded software developed for the proposed Fermilab BTeV high energy physics experiment. Lightweight self-optimizing agents embedded within Level 1 of the prototype are responsible for proactive and reactive monitoring and mitigation based on specified layers of competence. The agents are self-protecting, detecting cascading failures using a distributed approach. Adaptive, reconfigurable, and mobile objects for reliability are designed to be self-configuring to adapt automatically to dynamically changing environments. These objects provide a self-healing layer with the ability to discover, diagnose, and react to discontinuities in real-time processing. A generic modeling environment was developed to facilitate design and implementation of hardware resource specifications, application data flow, and failure mitigation strategies. Level 1 of the planned BTeV trigger system alone will consist of 2500 DSPs, so the number of components and intractable fault scenarios involved make it impossible to design an “expert system” that applies traditional centralized mitigative strategies based on rules capturing every possible system state. Instead, a distributed reactive approach is implemented using the tools and methodologies developed by the RealTime Embedded Systems group

Haul-Out Behavior of Harbor Seals (Phoca vitulina) in Hood Canal, Washington

The goal of this study was to model haul-out behavior of harbor seals (Phoca vitulina) in the Hood Canal region of Washington State with respect to changes in physiological, environmental, and temporal covariates. Previous research has provided a solid understanding of seal haul-out behavior. Here, we expand on that work using a generalized linear mixed model (GLMM) with temporal autocorrelation and a large dataset. Our dataset included behavioral haul-out records from archival and VHF radio tag deployments on 25 individual seals representing 61,430 seal hours. A novel application for increased computational efficiency allowed us to examine this large dataset with a GLMM that appropriately accounts for temporal autocorellation. We found significant relationships with the covariates hour of day, day of year, minutes from high tide and year. Additionally, there was a significant effect of the interaction term hour of day : day of year. This interaction term demonstrated that seals are more likely to haul out during nighttime hours in August and September, but then switch to predominantly daylight haul-out patterns in October and November. We attribute this change in behavior to an effect of human disturbance levels. This study also examined a unique ecological event to determine the role of increased killer whale (Orcinus orca) predation on haul-out behavior. In 2003 and 2005 these harbor seals were exposed to unprecedented levels of killer whale predation and results show an overall increase in haul-out probability after exposure to killer whales. The outcome of this study will be integral to understanding any changes in population abundance as a result of increased killer whale predation

Vacuolar ATPase Regulates Surfactant Secretion in Rat Alveolar Type II Cells by Modulating Lamellar Body Calcium

Lung surfactant reduces surface tension and maintains the stability of alveoli. How surfactant is released from alveolar epithelial type II cells is not fully understood. Vacuolar ATPase (V-ATPase) is the enzyme responsible for pumping H+ into lamellar bodies and is required for the processing of surfactant proteins and the packaging of surfactant lipids. However, its role in lung surfactant secretion is unknown. Proteomic analysis revealed that vacuolar ATPase (V-ATPase) dominated the alveolar type II cell lipid raft proteome. Western blotting confirmed the association of V-ATPase a1 and B1/2 subunits with lipid rafts and their enrichment in lamellar bodies. The dissipation of lamellar body pH gradient by Bafilomycin A1 (Baf A1), an inhibitor of V-ATPase, increased surfactant secretion. Baf A1-stimulated secretion was blocked by the intracellular Ca2+ chelator, BAPTA-AM, the protein kinase C (PKC) inhibitor, staurosporine, and the Ca2+/calmodulin-dependent protein kinase II (CaMKII), KN-62. Baf A1 induced Ca2+ release from isolated lamellar bodies. Thapsigargin reduced the Baf A1-induced secretion, indicating cross-talk between lamellar body and endoplasmic reticulum Ca2+ pools. Stimulation of type II cells with surfactant secretagogues dissipated the pH gradient across lamellar bodies and disassembled the V-ATPase complex, indicating the physiological relevance of the V-ATPase-mediated surfactant secretion. Finally, silencing of V-ATPase a1 and B2 subunits decreased stimulated surfactant secretion, indicating that these subunits were crucial for surfactant secretion. We conclude that V-ATPase regulates surfactant secretion via an increased Ca2+ mobilization from lamellar bodies and endoplasmic reticulum, and the activation of PKC and CaMKII. Our finding revealed a previously unrealized role of V-ATPase in surfactant secretion

Severe Asthma Standard-of-Care Background Medication Reduction With Benralizumab: ANDHI in Practice Substudy

Background: The phase IIIb, randomized, parallel-group, placebo-controlled ANDHI double-blind (DB) study extended understanding of the efficacy of benralizumab for patients with severe eosinophilic asthma. Patients from ANDHI DB could join the 56-week ANDHI in Practice (IP) single-arm, open-label extension substudy. Objective: Assess potential for standard-of-care background medication reductions while maintaining asthma control with benralizumab. Methods: Following ANDHI DB completion, eligible adults were enrolled in ANDHI IP. After an 8-week run-in with benralizumab, there were 5 visits to potentially reduce background asthma medications for patients achieving and maintaining protocol-defined asthma control with benralizumab. Main outcome measures for non-oral corticosteroid (OCS)-dependent patients were the proportions with at least 1 background medication reduction (ie, lower inhaled corticosteroid dose, background medication discontinuation) and the number of adapted Global Initiative for Asthma (GINA) step reductions at end of treatment (EOT). Main outcomes for OCS-dependent patients were reductions in daily OCS dosage and proportion achieving OCS dosage of 5 mg or lower at EOT. Results: For non-OCS-dependent patients, 53.3% (n = 208 of 390) achieved at least 1 background medication reduction, increasing to 72.6% (n = 130 of 179) for patients who maintained protocol-defined asthma control at EOT. A total of 41.9% (n = 163 of 389) achieved at least 1 adapted GINA step reduction, increasing to 61.8% (n = 110 of 178) for patients with protocol-defined EOT asthma control. At ANDHI IP baseline, OCS dosages were 5 mg or lower for 40.4% (n = 40 of 99) of OCS-dependent patients. Of OCS-dependent patients, 50.5% (n = 50 of 99) eliminated OCS and 74.7% (n = 74 of 99) achieved dosages of 5 mg or lower at EOT. Conclusions: These findings demonstrate benralizumab's ability to improve asthma control, thereby allowing background medication reduction

Severe Asthma Standard-of-Care Background Medication Reduction With Benralizumab: ANDHI in Practice Substudy

peer reviewedBackground: The phase IIIb, randomized, parallel-group, placebo-controlled ANDHI double-blind (DB) study extended understanding of the efficacy of benralizumab for patients with severe eosinophilic asthma. Patients from ANDHI DB could join the 56-week ANDHI in Practice (IP) single-arm, open-label extension substudy. Objective: Assess potential for standard-of-care background medication reductions while maintaining asthma control with benralizumab. Methods: Following ANDHI DB completion, eligible adults were enrolled in ANDHI IP. After an 8-week run-in with benralizumab, there were 5 visits to potentially reduce background asthma medications for patients achieving and maintaining protocol-defined asthma control with benralizumab. Main outcome measures for non–oral corticosteroid (OCS)-dependent patients were the proportions with at least 1 background medication reduction (ie, lower inhaled corticosteroid dose, background medication discontinuation) and the number of adapted Global Initiative for Asthma (GINA) step reductions at end of treatment (EOT). Main outcomes for OCS-dependent patients were reductions in daily OCS dosage and proportion achieving OCS dosage of 5 mg or lower at EOT. Results: For non–OCS-dependent patients, 53.3% (n = 208 of 390) achieved at least 1 background medication reduction, increasing to 72.6% (n = 130 of 179) for patients who maintained protocol-defined asthma control at EOT. A total of 41.9% (n = 163 of 389) achieved at least 1 adapted GINA step reduction, increasing to 61.8% (n = 110 of 178) for patients with protocol-defined EOT asthma control. At ANDHI IP baseline, OCS dosages were 5 mg or lower for 40.4% (n = 40 of 99) of OCS-dependent patients. Of OCS-dependent patients, 50.5% (n = 50 of 99) eliminated OCS and 74.7% (n = 74 of 99) achieved dosages of 5 mg or lower at EOT. Conclusions: These findings demonstrate benralizumab's ability to improve asthma control, thereby allowing background medication reduction. © 202

Identification of a Protein Biomarker Unique to the Pandemic O3:K6 Clone of Vibrio parahaemolyticus

The present method of characterizing Vibrio parahaemolyticus strains involves serotyping or detection methods based on assessment of the presence or absence of genes thought to be markers of an organism's pathogenicity. It is unclear whether these assays detect all pathogenic V. parahaemolyticus strains since a clear correlation between the presence of a particular gene and the organism's pathogenicity has not yet been observed. We have described a proteomics-based method to distinguish individual V. parahaemolyticus strains on the basis of their protein profiles and identified a specific protein that is characteristic of the pandemic O3:K6 strain and its clonal derivatives. In the pandemic clone of V. parahaemolyticus, a histone-like DNA-binding protein, HU-α, has a C-terminal amino acid sequence different from those of other strains of V. parahaemolyticus. Upon further study, it was discovered that the gene encoding this protein has a 16-kbp insert at the 3′ terminus of the open reading frame for this protein. By using the protein sequence of the unique biomarker for the pandemic clone of V. parahaemolyticus, it was possible to rationally design specific PCR-based probes and assays that permit the rapid and precise identification of pandemic strains of V. parahaemolyticus

The Association Between Caregiver Substance Abuse and Self-Reported Violence Exposure Among Young Urban Children

This study examined the relative importance of caregiver substance abuse as a correlate of child-reported exposure to violence. A total of 407 female African-American primary caregivers and their children age 6 to 7 were evaluated. The association between child report of violence and exposure to substance abuse by others (both within and outside the home) was considered after controlling for variance accounted for by child characteristics, caregiver characteristics, home environment, and neighborhood environment (including neighborhood crime). Caregiver alcohol abuse, children\u27s witnessing of drug use in the home, and children\u27s witnessing of drug deals all explained significant additional variance in violence exposure. These findings suggest that for early elementary-age children, meaningful prevention of violence exposure may be possible via addressing their exposure to substance abuse in their home and community