Additional studies of quasi-optimum feedback control techniques

Quasi-optimal control technique for space vehicle attitude, bounded acceleration rendezvous in free space, and aircraft landing proble

A Combination of Metabolomics and Machine Learning Results in the Identification of a New Cyst Nematode Hatching Factor

Potato Cyst Nematodes (PCNs) are an economically important pest for potato growers. A crucial event in the life cycle of the nematode is hatching, after which the juvenile will move toward the host root and infect it. The hatching of PCNs is induced by known and unknown compounds in the root exudates of host plant species, called hatching factors (HFs, induce hatching independently), such as solanoeclepin A (solA), or hatching stimulants (HSs, enhance hatching activity of HFs). Unraveling the identity of unknown HSs and HFs and their natural variation is important for the selection of cultivars that produce low amounts of HFs and HSs, thus contributing to more sustainable agriculture. In this study, we used a new approach aimed at the identification of new HFs and HSs for PCNs in potato. Hereto, root exudates of a series of different potato cultivars were analyzed for their PCN hatch-inducing activity and their solA content. The exudates were also analyzed using untargeted metabolomics, and subsequently the data were integrated using machine learning, specifically random forest feature selection, and Pearson’s correlation testing. As expected, solA highly correlates with hatching. Furthermore, this resulted in the discovery of a number of metabolite features present in the root exudate that correlate with hatching and solA content, and one of these is a compound of m/z 526.18 that predicts hatching even better than solA with both data methods. This compound’s involvement in hatch stimulation was confirmed by the fractionation of three representative root exudates and hatching assays with the resulting fractions. Moreover, the compound shares mass fragmentation similarity with solA, and we therefore assume it has a similar structure. With this work, we show that potato likely produces a solA analogue, and we contribute to unraveling the hatch-inducing cocktail exuded by plant roots

Take the Monkey and Run

The common marmoset (Callithrix jacchus) is a small, New World primate that is used extensively in biomedical and behavioral research. This short-lived primate, with its small body size, ease of handling, and docile temperament, has emerged as a valuable model for aging and neurodegenerative research. A growing body of research has indicated exercise, aerobic exercise especially, imparts beneficial effects to normal aging. Understanding the mechanisms underlying these positive effects of exercise, and the degree to which exercise has neurotherapeutic effects, is an important research focus. Thus, developing techniques to engage marmosets in aerobic exercise would have great advantages

Effectiveness of adenoidectomy in children with recurrent upper respiratory tract infections: open randomised controlled trial

Objective To assess the effectiveness of adenoidectomy in children with recurrent upper respiratory tract infections

Design parameters for a siphon system

DHI are interested in understanding a rather unusual water extraction system that is operated by a water supply company. Typically when water is extracted from the ground a well is dug and a pump is installed in the well to push the water to the surface where it enters a distribution system of pipes. Such a system may consist of a dozen or so wells each connected to a single collection pipe. The system that DHI wish to more fully understand consists of a series of ten wells connected to a single collection pipe. The difference in the mode of operation is that the system contains no pumps in the wells. The force to collect the water comes from placing the end of the collection pipe in a tank that is continuously pumped to keep it at approximately 0.5 bar below atmospheric pressure. In this way the water is drawn out of the wells by a siphon mechanism. Such a system appears cheaper o install with fewer pumps and water supplied in this manner costs roughly half the price of water from a standard pump system. How this multiple siphon system works and how it might be controlled were the general problems of interest to the study group

Larotrectinib efficacy and safety in TRK fusion cancer: An expanded clinical dataset showing consistency in an age and tumor agnostic approach

Background: TRK fusion cancer results from gene fusions involving NTRK1, NTRK2 or NTRK3. Larotrectinib, the first selective TRK inhibitor, has demonstrated an overall response rate (ORR) of 75% with a favorable safety profile in the first 55 consecutively enrolled adult and pediatric patients with TRK fusion cancer (Drilon et al.,NEJM2018). Here, we report the clinical activity of larotrectinib in an additional 35 TRK fusion cancer patients and provide updated follow-up of the primary analysis set (PAS) of 55 patients as of 19thFeb 2018. Methods: Patients with TRK fusion cancer detected by molecular profiling from 3 larotrectinib clinical trials (NCT02122913, NCT02637687, and NCT02576431) were eligible.Larotrectinib was administered until disease progression, withdrawal, or unacceptable toxicity. Disease status was assessed using RECIST version 1.1. Results: As of Feb 2018, by independent review, 6 PRs in the PAS deepened to CRs. The median duration of response (DoR) and progression-free survival in the PAS had still not been reached, with 12.9 months median follow-up. At 1 year, 69% of responses were ongoing, 58% of patients remained progression-free and 90% of patients were alive. An additional 19 children and 25 adults (age range, 0.1-78 years) with TRK fusion cancer were enrolled after the PAS, and included cancers of the salivary gland, thyroid, lung, colon, melanoma, sarcoma, GIST and congenital mesoblastic nephroma. In 35 evaluable patients, the ORR by investigator assessment was 74% (5 CR, 21 PR, 6 SD, 2 PD, 1 not determined). In these patients, with median follow-up of 5.5 months, median DoR had not yet been reached, and 88% of responses were ongoing at 6 months, consistent with the PAS. Adverse events (AEs) were predominantly grade 1, with dizziness, increased AST/ALT, fatigue, nausea and constipation the most common AEs reported in ≥ 10% of patients. No AE of grade 3 or 4 related to larotrectinib occurred in more than 5% of patients. Conclusions: TRK fusions are detected in a broad range of tumor types. Larotrectinib is an effective age- and tumor-agnostic treatment for TRK fusion cancer with a positive safety profile. Screening patients for NTRK gene fusions in solid- and brain tumors should be actively considered

Slowdown for time inhomogeneous branching Brownian motion

We consider the maximal displacement of one dimensional branching Brownian motion with (macroscopically) time varying profiles. For monotone decreasing variances, we show that the correction from linear displacement is not logarithmic but rather proportional to $T^{1/3}$. We conjecture that this is the worse case correction possible

Evaluation of the Serotonergic Genes htr1A, htr1B, htr2A, and slc6A4 in Aggressive Behavior of Golden Retriever Dogs

Aggressive behavior displays a high heritability in our study group of Golden Retriever dogs. Alterations in brain serotonin metabolism have been described in aggressive dogs before. Here, we evaluate whether four genes of the canine serotonergic system, coding for the serotonin receptors 1A, 1B, and 2A, and the serotonin transporter, could play a major role in aggression in Golden Retrievers. We performed mutation screens, linkage analysis, an association study, and a quantitative genetic analysis. There was no systematic difference between the coding DNA sequence of the candidate genes in aggressive and non-aggressive Golden Retrievers. An affecteds-only parametric linkage analysis revealed no strong major locus effect on human-directed aggression related to the candidate genes. An analysis of 41 single nucleotide polymorphisms (SNPs) in the 1 Mb regions flanking the genes in 49 unrelated human-directed aggressive and 49 unrelated non-aggressive dogs did not show association of SNP alleles, genotypes, or haplotypes with aggression at the candidate loci. We completed our analyses with a study of the effect of variation in the candidate genes on a collection of aggression-related phenotypic measures. The effects of the candidate gene haplotypes were estimated using the Restricted Maximum Likelihood method, with the haplotypes included as fixed effects in a linear animal model. We observed no effect of the candidate gene haplotypes on a range of aggression-related phenotypes, thus extending our conclusions to several types of aggressive behavior. We conclude that it is unlikely that these genes play a major role in the variation in aggression in the Golden Retrievers that we studied. Smaller phenotypic effects of these loci could not be ruled out with our sample size.Organismic and Evolutionary Biolog

Prediction of residual pipeline resource taking into account the operation loading conditions

An effective energy approach to the evaluation of the residual service life of a pipe of oil pipeline containing a crack on its inner surface for the two-frequency loading mode of biaxial tensioncompression has been proposed. The two-frequency variations of pressure in the pipe are caused by the turbulence of the flow of oil (highfrequency), opening and closing of the gate valves, and the shutdowns of the pumps (low frequency).Предложен эффективный энергетический подход к оценке остаточного эксплуатацион­ного ресурса нефтепровода с трещиной на внутренней поверхности трубы, подверга­емой двухчастотному биаксиальному нагру­жению растяжением-сжатием. Двухчастот­ный режим изменения давления в трубопро­воде обусловлен турбулентностью потока нефти (высокочастотная составляющая), от­крыванием и закрыванием задвижек, а так­ же отключением нефтенасосов (низкочастот­ная составляющая)