Analysis of Control Strategies for Aircraft Flight Upset Recovery

This paper proposes a framework for studying the ability of a control strategy, consisting of a control law and a command law, to recover an aircraft from ight conditions that may extend beyond the normal ight envelope. This study was carried out (i) by evaluating time responses of particular ight upsets, (ii) by evaluating local stability over an equilibrium manifold that included stall, and (iii) by bounding the set in the state space from where the vehicle can be safely own to wings-level ight. These states comprise what will be called the safely recoverable ight envelope (SRFE), which is a set containing the aircraft states from where a control strategy can safely stabilize the aircraft. By safe recovery it is implied that the tran- sient response stays between prescribed limits before converging to a steady horizontal ight. The calculation of the SRFE bounds yields the worst-case initial state corresponding to each control strategy. This information is used to compare alternative recovery strategies, determine their strengths and limitations, and identify the most e ective strategy. In regard to the control law, the authors developed feedback feedforward laws based on the gain scheduling of multivariable controllers. In regard to the command law, which is the mechanism governing the exogenous signals driving the feed- forward component of the controller, we developed laws with a feedback structure that combines local stability and transient response considera- tions. The upset recovery of the Generic Transport Model, a sub-scale twin-engine jet vehicle developed by NASA Langley Research Center, is used as a case study

Determinants of synaptic integration and heterogeneity in rebound firing explored with data-driven models of deep cerebellar nucleus cells

Significant inroads have been made to understand cerebellar cortical processing but neural coding at the output stage of the cerebellum in the deep cerebellar nuclei (DCN) remains poorly understood. The DCN are unlikely to just present a relay nucleus because Purkinje cell inhibition has to be turned into an excitatory output signal, and DCN neurons exhibit complex intrinsic properties. In particular, DCN neurons exhibit a range of rebound spiking properties following hyperpolarizing current injection, raising the question how this could contribute to signal processing in behaving animals. Computer modeling presents an ideal tool to investigate how intrinsic voltage-gated conductances in DCN neurons could generate the heterogeneous firing behavior observed, and what input conditions could result in rebound responses. To enable such an investigation we built a compartmental DCN neuron model with a full dendritic morphology and appropriate active conductances. We generated a good match of our simulations with DCN current clamp data we recorded in acute slices, including the heterogeneity in the rebound responses. We then examined how inhibitory and excitatory synaptic input interacted with these intrinsic conductances to control DCN firing. We found that the output spiking of the model reflected the ongoing balance of excitatory and inhibitory input rates and that changing the level of inhibition performed an additive operation. Rebound firing following strong Purkinje cell input bursts was also possible, but only if the chloride reversal potential was more negative than −70 mV to allow de-inactivation of rebound currents. Fast rebound bursts due to T-type calcium current and slow rebounds due to persistent sodium current could be differentially regulated by synaptic input, and the pattern of these rebounds was further influenced by HCN current. Our findings suggest that active properties of DCN neurons could play a crucial role for signal processing in the cerebellum

Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis

Objective Primary sclerosing cholangitis (PSC) is a genetically complex, inflammatory bile duct disease of largely unknown aetiology often leading to liver transplantation or death. Little is known about the genetic contribution to the severity and progression of PSC. The aim of this study is to identify genetic variants associated with PSC disease progression and development of complications. Design We collected standardised PSC subphenotypes in a large cohort of 3402 patients with PSC. After quality control, we combined 130 422 single nucleotide polymorphisms of all patients-obtained using the Illumina immunochip-with their disease subphenotypes. Using logistic regression and Cox proportional hazards models, we identified genetic variants associated with binary and time-to-event PSC subphenotypes. Results We identified genetic variant rs853974 to be associated with liver transplant-free survival (p=6.07x10(-9)). Kaplan-Meier survival analysis showed a 50.9% (95% CI 41.5% to 59.5%) transplant-free survival for homozygous AA allele carriers of rs853974 compared with 72.8% (95% CI 69.6% to 75.7%) for GG carriers at 10 years after PSC diagnosis. For the candidate gene in the region, RSPO3, we demonstrated expression in key liver-resident effector cells, such as human and murine cholangiocytes and human hepatic stellate cells. Conclusion We present a large international PSC cohort, and report genetic loci associated with PSC disease progression. For liver transplant-free survival, we identified a genome-wide significant signal and demonstrated expression of the candidate gene RSPO3 in key liver-resident effector cells. This warrants further assessments of the role of this potential key PSC modifier gene.Peer reviewe

rs2735383, located at a microRNA binding site in the 3 ' UTR of NBS1, is not associated with breast cancer risk

NBS1, also known as NBN, plays an important role in maintaining genomic stability. Interestingly, rs2735383 G > C, located in a microRNA binding site in the 3'-untranslated region (UTR) of NBS1, was shown to be associated with increased susceptibility to lung and colorectal cancer. However, the relation between rs2735383 and susceptibility to breast cancer is not yet clear. Therefore, we genotyped rs2735383 in 1,170 familial non-BRCA1/2 breast cancer cases and 1,077 controls using PCR-based restriction fragment length polymorphism (RFLP-PCR) analysis, but found no association between rs2735383CC and breast cancer risk (OR = 1.214, 95% CI = 0.936-1.574, P = 0.144). Because we could not exclude a small effect size due to a limited sample size, we further analyzed imputed rs2735383 genotypes (r(2) > 0.999) of 47,640 breast cancer cases and 46,656 controls from the Breast Cancer Association Consortium (BCAC). However, rs2735383CC was not associated with overall breast cancer risk in European (OR = 1.014, 95% CI = 0.969-1.060, P = 0.556) nor in Asian women (OR = 0.998, 95% CI = 0.905-1.100, P = 0.961). Subgroup analyses by age, age at menarche, age at menopause, menopausal status, number of pregnancies, breast feeding, family history and receptor status also did not reveal a significant association. This study therefore does not support the involvement of the genotype at NBS1 rs2735383 in breast cancer susceptibility.Peer reviewe

Towards a comprehensive climate impacts assessment of solar geoengineering

Despite a growing literature on the climate response to solar geoengineering – proposals to cool the planet by increasing the planetary albedo – there has been little published on the impacts of solar geoengineering on natural and human systems such as agriculture, health, water resources, and ecosystems. An understanding of the impacts of different scenarios of solar geoengineering deployment will be crucial for informing decisions on whether and how to deploy it. Here we review the current state of knowledge about impacts of a solar geoengineered climate and identify major research gaps. We suggest that a thorough assessment of the climate impacts of a range of scenarios of solar geoengineering deployment is needed and can build upon existing frameworks. However, solar geoengineering poses a novel challenge for climate impacts research as the manner of deployment could be tailored to pursue different objectives making possible a wide range of climate outcomes. We present a number of ideas for approaches to extend the survey of climate impacts beyond standard scenarios of solar geoengineering deployment to address this challenge. Reducing the impacts of climate change is the fundamental motivator for emissions reductions and for considering whether and how to deploy solar geoengineering. This means that the active engagement of the climate impacts research community will be important for improving the overall understanding of the opportunities, challenges and risks presented by solar geoengineering

Towards a comprehensive climate impacts assessment of solar geoengineering

Despite a growing literature on the climate response to solar geoengineering—proposals to cool the planet by increasing the planetary albedo—there has been little published on the impacts of solar geoengineering on natural and human systems such as agriculture, health, water resources, and ecosystems. An understanding of the impacts of different scenarios of solar geoengineering deployment will be crucial for informing decisions on whether and how to deploy it. Here we review the current state of knowledge about impacts of a solar‐geoengineered climate and identify the major research gaps. We suggest that a thorough assessment of the climate impacts of a range of scenarios of solar geoengineering deployment is needed and can be built upon existing frameworks. However, solar geoengineering poses a novel challenge for climate impacts research as the manner of deployment could be tailored to pursue different objectives making possible a wide range of climate outcomes. We present a number of ideas for approaches to extend the survey of climate impacts beyond standard scenarios of solar geoengineering deployment to address this challenge. Reducing the impacts of climate change is the fundamental motivator for emissions reductions and for considering whether and how to deploy solar geoengineering. This means that the active engagement of the climate impacts research community will be important for improving the overall understanding of the opportunities, challenges, and risks presented by solar geoengineering

The MNCs' Role and Responsibility in Deforestation of Tropical Forests

Deforestation of tropical forests has significant ecological ramifications. The role played by the multinational corporations (MNCs) in this unprecedented modification of the environment may have foreboding consequences to all inhabitants of the globe. Cattle ranching in Central and South America has accounted for more than half of all deforestation in that region. This article examines the deforestation by MNCs in that part of the world and explores an interactive theoretical framework that can be used to analyze the complex web of political, social, and economic forces related to the phenomenon.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis

Objective Primary sclerosing cholangitis (PSC) is a genetically complex, inflammatory bile duct disease of largely unknown aetiology often leading to liver transplantation or death. Little is known about the genetic contribution to the severity and progression of PSC. The aim of this study is to identify genetic variants associated with PSC disease progression and development of complications. Design We collected standardised PSC subphenotypes in a large cohort of 3402 patients with PSC. After quality control, we combined 130 422 single nucleotide polymorphisms of all patients-obtained using the Illumina immunochip-with their disease subphenotypes. Using logistic regression and Cox proportional hazards models, we identified genetic variants associated with binary and time-to-event PSC subphenotypes. Results We identified genetic variant rs853974 to be associated with liver transplant-free survival (p=6.07x10(-9)). Kaplan-Meier survival analysis showed a 50.9% (95% CI 41.5% to 59.5%) transplant-free survival for homozygous AA allele carriers of rs853974 compared with 72.8% (95% CI 69.6% to 75.7%) for GG carriers at 10 years after PSC diagnosis. For the candidate gene in the region, RSPO3, we demonstrated expression in key liver-resident effector cells, such as human and murine cholangiocytes and human hepatic stellate cells. Conclusion We present a large international PSC cohort, and report genetic loci associated with PSC disease progression. For liver transplant-free survival, we identified a genome-wide significant signal and demonstrated expression of the candidate gene RSPO3 in key liver-resident effector cells. This warrants further assessments of the role of this potential key PSC modifier gene

Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a severe liver disease of unknown etiology leading to fibrotic destruction of the bile ducts and ultimately to the need for liver transplantation. We compared 3,789 PSC cases of European ancestry to 25,079 population controls across 130,422 SNPs genotyped using the Immunochip. We identified 12 genome-wide significant associations outside the human leukocyte antigen (HLA) complex, 9 of which were new, increasing the number of known PSC risk loci to 16. Despite comorbidity with inflammatory bowel disease (IBD) in 72% of the cases, 6 of the 12 loci showed significantly stronger association with PSC than with IBD, suggesting overlapping yet distinct genetic architectures for these two diseases. We incorporated association statistics from 7 diseases clinically occurring with PSC in the analysis and found suggestive evidence for 33 additional pleiotropic PSC risk loci. Together with network analyses, these findings add to the genetic risk map of PSC and expand on the relationship between PSC and other immune-mediated diseases