Dynamic stability and handling qualities tests on a highly augmented, statically unstable airplane

Initial envelope clearance and subsequent flight testing of a new, fully augmented airplane with an extremely high degree of static instability can place unusual demands on the flight test approach. Previous flight test experience with these kinds of airplanes is very limited or nonexistent. The safe and efficient flight testing may be further complicated by a multiplicity of control effectors that may be present on this class of airplanes. This paper describes some novel flight test and analysis techniques in the flight dynamics and handling qualities area. These techniques were utilized during the initial flight envelope clearance of the X-29A aircraft and were largely responsible for the completion of the flight controls clearance program without any incidents or significant delays

Reducing urban traffic congestion due to localized routing decisions

Balancing traffic flow by influencing drivers' route choices to alleviate congestion is becoming increasingly more appealing in urban traffic planning. Here, we introduce a discrete dynamical model comprising users who make their own routing choices on the basis of local information and those who consider routing advice based on localized inducement. We identify the formation of traffic patterns, develop a scalable optimization method for identifying control values used for user guidance, and test the effectiveness of these measures on synthetic and real-world road networks

A Recommender Model for the Personalized Adaptive CHUNK Learning System

Recommender systems attempt to influence one’s behavior based on explicit and implicit information provided by the users of the system. Users who take part in e-commerce or watch cat videos online will be familiar with this concept. Different algorithms exist that determine what objects or concepts to recommend to users, but every one of them has the similar goal of providing a good recommendation. In this context, good means that the recommendation will be user relevant suggesting accurate topics, and will influence the user’s behavior. Additionally, a good recommendation system is adaptive, consistently seeking feedback from the user. Feedback is then used to make the next recommendation better. In this work, we develop a recommendation methodology for an existing personalized learning system, where both content and teaching methodology options are presented to the user. Our methodology provides solutions to both the user and the network coldstart problems, where little up-front information is available in order to make good recommendations. Using real system data, we show how our method recommends the most relevant learning topics and styles and incorporates user feedback to improve future recommendations.Do

The effect of tobacco control policies on smoking prevalence and smoking-attributable deaths. Findings from the Netherlands SimSmoke Tobacco Control Policy Simulation Model

Aim To develop a simulation model projecting the effect of tobacco control policies in the Netherlands on smoking prevalence and smoking-attributable deaths. Design, setting and participants Netherlands SimSmoke-an adapted version of the SimSmoke simulation model of tobacco control policy-uses population, smoking rates and tobacco control policy data for the Netherlands to predict the effect of seven types of policies: taxes, smoke-free legislation, mass media, advertising bans, health warnings, cessation treatment and youth access policies. Measurements Outcome measures were smoking prevalence and smoking-attributable deaths. Findings With a comprehensive set of policies, as recommended by MPOWER, smoking prevalence can be decreased by asmuch as 21% in the first year, increasing to a 35% reduction in the next 20 years and almost 40% by 30 years. By 2040, 7706 deaths can be averted in that year alone with the stronger set of policies. Without effective tobacco control policies, almost a million lives will be lost to tobacco-related diseases between 2011 and 2040. Of those, 145 000 can be saved with a comprehensive tobacco control package. Conclusions Smoking prevalence and smoking-attributable deaths in the Netherlands can be reduced substantially through tax increases, smoke-free legislation, high-intensity media campaigns, stronger advertising bans and health warnings, comprehensive cessation treatment and youth access laws. The implementation of these FCTC/ MPOWER recommended policies could be expected to show similar or even larger relative reductions in smoking prevalence in other countries which currently have weak policies

Translation of circHGF RNA encodes an HGF protein variant promoting glioblastoma growth through stimulation of c-MET

IntroductionHGF/c-MET signaling is a significant driver of glioblastoma (GBM) growth and disease progression. Unfortunately, c-MET targeted therapies have been found to be largely ineffective suggesting additional redundant mechanisms of c-MET activation.MethodsUtilizing RNA-sequencing (RNA-seq) and ribosome profiling analyses of circular RNAs, circ-HGF (hsa_circ_0080914) was identified as markedly upregulated in primary GBM and found to potentially encode an HGF protein variant (C-HGF) 119 amino acids in length. This candidate HGF variant was characterized and evaluated for its ability to mediate c-MET activation and regulate PDX GBM cell growth, motility and invasive potential in vitro and tumor burden in intracranial xenografts in mice.ResultsAn internal ribosome entry site (IRES) was identified within the circ-HGF RNA which mediated translation of the cross-junctional ORF encoding C-HGF and was observed to be highly expressed in GBM relative to normal brain tissue. C-HGF was also found to be secreted from GBM cells and concentrated cell culture supernatants or recombinant C-HGF activated known signaling cascades downstream of c-MET. C-HGF was shown to interact directly with the c-MET receptor resulting in its autophosphorylation and activation in PDX GBM lines. Knockdown of C-HGF resulted in suppression of c-MET signaling and marked inhibition of cell growth, motility and invasiveness, whereas overexpression of C-HGF displayed the opposite effects. Additionally, modulation of C-HGF expression regulated tumor growth in intracranial xenografted PDX GBM models.ConclusionsThese results reveal an alternative mechanism of c-MET activation via a circular RNA encoded HGF protein variant which is relevant in GBM biology. Targeting C-HGF may offer a promising approach for GBM clinical management

The influence of newspaper coverage and a media campaign on smokers' support for smoke-free bars and restaurants and on secondhand smoke harm awareness: findings from the International Tobacco Control (ITC) Netherlands Survey

OBJECTIVE: To assess the influence of newspaper coverage and a media campaign about Dutch smoke-free legislation on smokers’ support for smoke-free bars and restaurants and on second-hand smoke (SHS) harm awareness. DESIGN AND MAIN OUTCOME MEASURES: A content analysis was conducted of 1,041 newspaper articles on the smoke-free legislation published in six Dutch newspapers from March 2008 until April 2009. Smokers who were regular readers of at least one of these newspapers (n = 677) were selected from the pre- and post-ban waves of the International Tobacco Control (ITC) Netherlands Survey. Exposure to newspaper coverage and to the implementation campaign were correlated with changes in smokers’ support for smoke-free bars and restaurants and SHS harm awareness. RESULTS: Most newspaper coverage was found to be negative towards the smoking ban (57%) and focused on economic aspects (59%) rather than health aspects (22%). Exposure to this coverage had a small but significantly negative effect on support for smoke-free bars and restaurants (Beta = −0.09, p = 0.013). Among higher educated smokers, exposure to positive newspaper coverage had a more positive effect on support for smoke-free bars and restaurants. In addition, exposure to the implementation campaign had a small but significantly positive effect on SHS harm awareness (Beta = 0.11, p = 0.001). CONCLUSIONS: Media attention about smoke-free legislation can influence smokers’ support for the legislation and SHS harm awareness. Tobacco control advocates should aim to establish positive media attention that puts forward the health arguments for the legislation

Cellular protection from H2O2 toxicity by Fv-Hsp70: protection via catalase and gamma-glutamyl-cysteine synthase

Heat shock proteins (HSPs), especially Hsp70 (HSPA1), have been associated with cellular protection from various cellular stresses including heat, hypoxia-ischemia, neurodegeneration, toxins, and trauma. Endogenous HSPs are often synthesized in direct response to these stresses but in many situations are inadequate in protecting cells. The present study addresses the transduction of Hsp70 into cells providing protection from acute oxidative stress by H2O2. The recombinant Fv-Hsp70 protein and two mutant Fv-Hsp70 proteins minus the ATPase domain and minus the ATPase and terminal lid domains were tested at 0.5 and 1.0 μM concentrations after two different concentrations of H2O2 treatment. All three recombinant proteins protected SH-SY5Y cells from acute H2O2 toxicity. This data indicated that the protein binding domain was responsible for cellular protection. In addition, experiments pretreating cells with inhibitors of antioxidant proteins catalase and gamma-glutamylcysteine synthase (GGCS) before H2O2 resulted in cell death despite treatment with Fv-Hsp70, implying that both enzymes were protected from acute oxidative stress after treatment with Fv-Hsp70. This study demonstrates that Fv-Hsp70 is protective in our experiments primarily by the protein-binding domain. The Hsp70 terminal lid domain was also not necessary for protection

Yield quantitative trait loci from wild tomato are predominately expressed by the shoot

Plant yield is the integrated outcome of processes taking place above and below ground. To explore genetic, environmental and developmental aspects of fruit yield in tomato, we phenotyped an introgression line (IL) population derived from a cross between the cultivated tomato (Solanum lycopersicum) and a wild species (Solanum pennellii). Both homozygous and heterozygous ILs were grown in irrigated and non-irrigated fields and evaluated for six yield components. Thirteen lines displayed transgressive segregation that increased agronomic yield consistently over 2 years and defined at least 11 independent yield-improving QTL. To determine if these QTL were expressed in the shoots or the roots of the plants, we conducted field trials of reciprocally grafted ILs; out of 13 lines with an effect on yield, 10 QTL were active in the shoot and only IL8-3 showed a consistent root effect. To further examine this unusual case, we evaluated the metabolic profiles of fruits from both the homo- and heterozygous lines for IL8-3 and compared these to those obtained from the fruit of their equivalent genotypes in the root effect population. We observed that several of these metabolic QTL, like the yield QTL, were root determined; however, further studies will be required to delineate the exact mechanism mediating this effect in this specific line. The results presented here suggest that genetic variation for root traits, in comparison to that present in the shoot, represents only a minor component in the determination of tomato fruit yield