Framework For Improving Complex System Performance

This paper introduces a framework for improvement of complex system performance. Complex systems are besieged with conditions marked by increasing uncertainty, emergence, and ambiguity. Additionally, demands for increased productivity, resource efficiencies, and performance improvement make new approaches paramount for modern systems engineers. In response, a framework to improve complex system performance is developed. Following an introduction, the paper pursues four objectives: (1) introduction of Complex System Governance (CSG) as a foundation to describe essential system functions, (2) suggest system `pathologies\u27 as an explanation for deep system performance issues, (3) exploration of system performance improvement as a function of `requisite variety\u27 to compensate for deep system issues, and (4) introduce a framework for complex system performance improvement using system pathologies as `unab-sorbed variety\u27. The paper closes with some challenges for further development of the framework for deployment and application guidance for practitioners

Paper Session III-C - Earth Dividends From the Development of Space Vehicle Robotics: Technologies and Techniques

This paper identifies and describes advanced robotics technologies and novel applications of state-of-the-art techniques which presently focus on space-related missions but which could result in other dividends on Earth. The paper has three sections. The first section focuses on the development of technology to help NASA automate the reprocessing of low-Earth-orbit vehicles. These advanced technologies include vibration isolation for robot arms and end-effectors, automated handling of fuels and other hazardous materials, and automated safety systems for process control. The second section describes the use of state-of-the-art solid modeling techniques to assist in the design of a robot arm, camera systems, sensors, and platforms for characterizing and exploring a planetary terrain. The third section discusses the use of these advanced technologies and novel applications to provide dividends on Earth in both space- and nonspacerelated applications. Vibration isolation could improve the performance of long manipulator arms used for vehicle processing and cleaning Department of Energy waste tanks. Automated handling of hazardous fluids could help automate the fueling of commercial and passenger vehicles. The advanced safety circuit could enhance many chemical process control operations. Modeling techniques for designing terrain exploration systems could assist the design of vehicles for exploring the many sites on Earth where human entry may be unsafe or inefficient, such as nuclear waste sites, military sites with unexploded ordnance, and widespread geological and agricultural surveys

Functional Status After Operation for Ebstein Anomaly The Mayo Clinic Experience

ObjectivesThe objective of this study was to review the long-term functional outcome of patients with Ebstein anomaly who had cardiac operation at our institution.BackgroundEbstein anomaly is a spectrum of tricuspid valvular and right ventricular dysplasia. Many patients will require operation in an attempt to improve quality of life.MethodsFrom April 1, 1972, to January 1, 2006, 539 patients with Ebstein anomaly underwent 604 cardiac operations at the Mayo Clinic in Rochester, Minnesota. Patient records were reviewed, and all patients known to still be alive were mailed a medical questionnaire or contacted by telephone.ResultsAt the initial operation at our institution, the mean age of the patients was 24 years (range 8 days to 79 years) and 53% were female patients. Survival at 5, 10, 15, and 20 years was 94%, 90%, 86%, and 76%, respectively. Survival free of late reoperation was 86%, 74%, 62%, and 46% at 5, 10, 15, and 20 years, respectively. Surveys were returned by 285 of 448 (64%) patients known to be alive at the time of this study. Two hundred thirty-seven (83%) patients were in New York Heart Association functional class I or II, and 34% were taking no cardiac medication. One hundred three patients (36%) reported an incident of atrial fibrillation or flutter, 5 patients (2%) reported having had endocarditis, and 1 patient (<1%) reported having a stroke. There were 275 pregnancies among 82 women. The recurrence of congenital heart disease was reported in 9 of 232 (3.9%) liveborn children.ConclusionsPatients have good long-term survival and functional outcomes after undergoing surgery for Ebstein anomaly. Atrial arrhythmias are common both before and after surgery. Many patients have had one or more successful pregnancies with a low-recurrence risk of congenital heart disease

Functional Status After Operation for Ebstein Anomaly The Mayo Clinic Experience

ObjectivesThe objective of this study was to review the long-term functional outcome of patients with Ebstein anomaly who had cardiac operation at our institution.BackgroundEbstein anomaly is a spectrum of tricuspid valvular and right ventricular dysplasia. Many patients will require operation in an attempt to improve quality of life.MethodsFrom April 1, 1972, to January 1, 2006, 539 patients with Ebstein anomaly underwent 604 cardiac operations at the Mayo Clinic in Rochester, Minnesota. Patient records were reviewed, and all patients known to still be alive were mailed a medical questionnaire or contacted by telephone.ResultsAt the initial operation at our institution, the mean age of the patients was 24 years (range 8 days to 79 years) and 53% were female patients. Survival at 5, 10, 15, and 20 years was 94%, 90%, 86%, and 76%, respectively. Survival free of late reoperation was 86%, 74%, 62%, and 46% at 5, 10, 15, and 20 years, respectively. Surveys were returned by 285 of 448 (64%) patients known to be alive at the time of this study. Two hundred thirty-seven (83%) patients were in New York Heart Association functional class I or II, and 34% were taking no cardiac medication. One hundred three patients (36%) reported an incident of atrial fibrillation or flutter, 5 patients (2%) reported having had endocarditis, and 1 patient (<1%) reported having a stroke. There were 275 pregnancies among 82 women. The recurrence of congenital heart disease was reported in 9 of 232 (3.9%) liveborn children.ConclusionsPatients have good long-term survival and functional outcomes after undergoing surgery for Ebstein anomaly. Atrial arrhythmias are common both before and after surgery. Many patients have had one or more successful pregnancies with a low-recurrence risk of congenital heart disease

Descriptive Drinking Norms: For Whom Does Reference Group Matter?

Objective: Perceived descriptive drinking norms often differ from actual norms and are positively related to personal consumption. However, it is not clear how normative perceptions vary with specificity of the reference group. Are drinking norms more accurate and more closely related to drinking behavior as reference group specificity increases? Do these relationships vary as a function of participant demographics? The present study examined the relationship between perceived descriptive norms and drinking behavior by ethnicity (Asian or White), sex, and fraternity/sorority status. Method: Participants were 2,699 (58% female) White (75%) or Asian (25%) undergraduates from two universities who reported their own alcohol use and perceived descriptive norms for eight reference groups: typical student ; same sex, ethnicity, or fraternity/sorority status; and all combinations of these three factors. Results: Participants generally reported the highest perceived norms for the most distal reference group (typical student), with perceptions becoming more accurate as individuals\u27 similarity to the reference group increased. Despite increased accuracy, participants perceived that all reference groups drank more than was actually the case. Across specific subgroups (fraternity/sorority members and men) different patterns emerged. Fraternity/sorority members reliably reported higher estimates of drinking for reference groups that included fraternity/ sorority status, and, to a lesser extent, men reported higher estimates for reference groups that included men. Conclusions: The results suggest that interventions targeting normative misperceptions may need to provide feedback based on participant demography or group membership. Although reference group-specific feedback may be important for some subgroups, typical student feedback provides the largest normative discrepancy for the majority of students

LAB/NTAL Facilitates Fungal/PAMP-induced IL-12 and IFN-γ Production by Repressing β-Catenin Activation in Dendritic Cells.

Fungal pathogens elicit cytokine responses downstream of immunoreceptor tyrosine-based activation motif (ITAM)-coupled or hemiITAM-containing receptors and TLRs. The Linker for Activation of B cells/Non-T cell Activating Linker (LAB/NTAL) encoded by Lat2, is a known regulator of ITAM-coupled receptors and TLR-associated cytokine responses. Here we demonstrate that LAB is involved in anti-fungal immunity. We show that Lat2−/− mice are more susceptible to C. albicans infection than wild type (WT) mice. Dendritic cells (DCs) express LAB and we show that it is basally phosphorylated by the growth factor M-CSF or following engagement of Dectin-2, but not Dectin-1. Our data revealed a unique mechanism whereby LAB controls basal and fungal/pathogen-associated molecular patterns (PAMP)-induced nuclear β-catenin levels. This in turn is important for controlling fungal/PAMP-induced cytokine production in DCs. C. albicans- and LPS-induced IL-12 and IL-23 production was blunted inLat2−/− DCs. Accordingly, Lat2−/− DCs directed reduced Th1 polarization in vitro and Lat2−/−mice displayed reduced Natural Killer (NK) and T cell-mediated IFN-γ production in vivo/ex vivo. Thus our data define a novel link between LAB and β-catenin nuclear accumulation in DCs that facilitates IFN-γ responses during anti-fungal immunity. In addition, these findings are likely to be relevant to other infectious diseases that require IL-12 family cytokines and an IFN-γ response for pathogen clearance

Propofol induces MAPK/ERK cascade dependant expression of cFos and Egr-1 in rat hippocampal slices

Background: Propofol is a commonly used intravenous anesthetic agent, which produce rapid induction of and recovery from general anesthesia. Numerous clinical studies reported that propofol can potentially cause amnesia and memory loss in human subjects. The underlying mechanism for this memory loss is unclear but may potentially be related to the induction of memory-associated genes such as c-Fos and Egr-1 by propofol. This study explored the effects of propofol on c-Fos and Egr-1 expression in rat hippocampal slices. Findings: Hippocampal brain slices were exposed to varying concentrations of propofol at multiple time intervals. The transcription of the immediate early genes, c-Fos and Egr-1, was quantified using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). MAPK/ERK inhibitors were used to investigate the mechanism of action. We demonstrate that propofol induced the expression of c-Fos and Egr-1 within 30 and 60 min of exposure time. At 16.8 μM concentration, propofol induced a 110% increase in c-Fos transcription and 90% decrease in the transcription of Egr-1. However, at concentrations above 100 μM, propofol failed to induce expression of c-Fos but did completely inhibit the transcription of Egr-1. Propofol-induced c-Fos and Egr-1 transcription was abolished by inhibitors of RAS, RAF, MEK, ERK and p38-MAPK in the MAPK/ERK cascade. Conclusions: Our study shows that clinically relevant concentrations of propofol induce c-Fos and down regulated Egr-1 expression via an MAPK/ERK mediated pathway. We demonstrated that propofol induces a time and dose dependant transcription of IEGs c-Fos and Egr-1 in rat hippocampal slices. We further demonstrate for the first time that propofol induced IEG expression was mediated via a MAPK/ERK dependant pathway. These novel findings provide a new avenue to investigate transcription-dependant mechanisms and suggest a parallel pathway of action with an unclear role in the activity of general anesthetics

eIF4A1-dependent mRNAs employ purine-rich 5’UTR sequences to activate localised eIF4A1-unwinding through eIF4A1-multimerisation to facilitate translation

Altered eIF4A1 activity promotes translation of highly structured, eIF4A1-dependent oncogene mRNAs at root of oncogenic translational programmes. It remains unclear how these mRNAs recruit and activate eIF4A1 unwinding specifically to facilitate their preferential translation. Here, we show that single-stranded RNA sequence motifs specifically activate eIF4A1 unwinding allowing local RNA structural rearrangement and translation of eIF4A1-dependent mRNAs in cells. Our data demonstrate that eIF4A1-dependent mRNAs contain AG-rich motifs within their 5’UTR which specifically activate eIF4A1 unwinding of local RNA structure to facilitate translation. This mode of eIF4A1 regulation is used by mRNAs encoding components of mTORC-signalling and cell cycle progression, and renders these mRNAs particularly sensitive to eIF4A1-inhibition. Mechanistically, we show that binding of eIF4A1 to AG-rich sequences leads to multimerization of eIF4A1 with eIF4A1 subunits performing distinct enzymatic activities. Our structural data suggest that RNA-binding of multimeric eIF4A1 induces conformational changes in the RNA resulting in an optimal positioning of eIF4A1 proximal to the RNA duplex enabling efficient unwinding. Our data proposes a model in which AG-motifs in the 5’UTR of eIF4A1-dependent mRNAs specifically activate eIF4A1, enabling assembly of the helicase-competent multimeric eIF4A1 complex, and positioning these complexes proximal to stable localised RNA structure allowing ribosomal subunit scanning

CXCL12-Mediated Guidance of Migrating Embryonic Stem Cell-Derived Neural Progenitors Transplanted into the Hippocampus

Stem cell therapies for neurodegenerative disorders require accurate delivery of the transplanted cells to the sites of damage. Numerous studies have established that fluid injections to the hippocampus can induce lesions in the dentate gyrus (DG) that lead to cell death within the upper blade. Using a mouse model of temporal lobe epilepsy, we previously observed that embryonic stem cell-derived neural progenitors (ESNPs) survive and differentiate within the granule cell layer after stereotaxic delivery to the DG, replacing the endogenous cells of the upper blade. To investigate the mechanisms for ESNP migration and repair in the DG, we examined the role of the chemokine CXCL12 in mice subjected to kainic acid-induced seizures. We now show that ESNPs transplanted into the DG show extensive migration through the upper blade, along the septotemporal axis of the hippocampus. Seizures upregulate CXCL12 and infusion of the CXCR4 antagonist AMD3100 by osmotic minipump attenuated ESNP migration. We also demonstrate that seizures promote the differentiation of transplanted ESNPs toward neuronal rather than astrocyte fates. These findings suggest that ESNPs transplanted into the adult rodent hippocampus migrate in response to cytokine-mediated signals

Effects of African dust deposition on phytoplankton in the western tropical Atlantic Ocean off Barbados

Bioassay incubation experiments conducted with nutrients and local atmospheric aerosol amendments indicate that phosphorus (P) availability limited phytoplankton growth in the low-nutrient low-chlorophyll (LNLC) ocean off Barbados. Atmospheric deposition provides a relatively large influx of new nutrients and trace metals to the surface ocean in this region in comparison to other nutrient sources. However, the impact on native phytoplankton is muted due to the high ratio of nitrogen (N) to P (NO3:SRP > 40) and the low P solubility of these aerosols. Atmospheric deposition induces P limitation in this LNLC region by adding more N and iron (Fe) relative to P. This favors the growth of Prochlorococcus, a genus characterized by low P requirements and highly efficient P acquisition mechanisms. A global three-dimensional marine ecosystem model that includes species-specific phytoplankton elemental quotas/stoichiometry and the atmospheric deposition of N, P, and Fe supports this conclusion. Future increases in aerosol N loading may therefore influence phytoplankton community structure in other LNLC areas, thereby affecting the biological pump and associated carbon sequestration