Assessing the detailed time course of perceptual sensitivity change in perceptual learning.

The learning curve in perceptual learning is typically sampled in blocks of trials, which could result in imprecise and possibly biased estimates, especially when learning is rapid. Recently, Zhao, Lesmes, and Lu (2017, 2019) developed a Bayesian adaptive quick Change Detection (qCD) method to accurately, precisely, and efficiently assess the time course of perceptual sensitivity change. In this study, we implemented and tested the qCD method in assessing the learning curve in a four-alternative forced-choice global motion direction identification task in both simulations and a psychophysical experiment. The stimulus intensity in each trial was determined by the qCD, staircase or random stimulus selection (RSS) methods. Simulations showed that the accuracy (bias) and precision (standard deviation or confidence bounds) of the estimated learning curves from the qCD were much better than those obtained by the staircase and RSS method; this is true for both trial-by-trial and post hoc segment-by-segment qCD analyses. In the psychophysical experiment, the average half widths of the 68.2% credible interval of the estimated thresholds from the trial-by-trial and post hoc segment-by-segment qCD analyses were both quite small. Additionally, the overall estimates from the qCD and staircase methods matched extremely well in this task where the behavioral rate of learning is relatively slow. Our results suggest that the qCD method can precisely and accurately assess the trial-by-trial time course of perceptual learning

Effects of anesthesia on conventional and speckle tracking echocardiographic parameters in a mouse model of pressure overload

Genetically‑modified mice are widely applied in cardiovascular studies as model organisms. Echocardiography is a key tool for evaluating cardiac and hemodynamic functions in mice. The present study aimed to examine the effects of isoflurane (ISF) on conventional and speckle tracking echocardiography (STE) parameters under healthy and pathological conditions using a murine model of pressure overload. In addition, the optimal dose of ISF in the process of echocardiographic measurement, with minimum cardiac contraction depression, was investigated. Conventional echocardiographic and STE examinations were performed on 38 adult C57BL/6 male mice. The mice were divided into the following three groups: The sham (n=15); mild thoracic aortic banding (TAB; n=15); and severe TAB (n=8) groups. ISF was administered under deep anesthesia (DA; 1‑2% ISF), light anesthesia (LA; 0.5‑1% ISF) and immediately prior to the mice waking up (awake; 0‑0.5% ISF). Conventional echocardiographic parameters were preserved within the sham and mild TAB groups (P>0.05 for each parameter) under LA and awake conditions. However, under DA conditions, the majority of these parameters were reduced compared with the LA and awake conditions (P<0.05). In the severe TAB group, conventional echocardiographic parameters remained constant under LA, DA and awake conditions. STE parameters in the groups remained similar between the LA and awake conditions, but were significantly reduced under DA conditions. Therefore, conventional echocardiography and STE may be performed using LA induced with low doses of ISF, under various pathological conditions without affecting cardiac function

Interaction of hemojuvelin with neogenin results in iron accumulation in human embryonic kidney 293 cells

Type 2 hereditary hemochromatosis (HH) or juvenile hemochromatosis is an early onset, genetically heterogeneous, autosomal recessive disorder of iron overload. Type 2A HH is caused by mutations in the recently cloned hemojuvelin gene (HJV; also called HFE2) (Papanikolaou, G., Samuels, M. E., Ludwig, E. H., MacDonald, M. L., Franchini, P. L., Dube, M. P., Andres, L., MacFarlane, J., Sakellaropoulos, N., Politou, M., Nemeth, E., Thompson, J., Risler, J. K., Zaborowska, C., Babakaiff, R., Radomski, C. C., Pape, T. D., Davidas, O., Christakis, J., Brissot, P., Lockitch, G., Ganz, T., Hayden, M. R., and Goldberg, Y. P. (2004) Nat. Genet. 36, 77–82), whereas Type 2B HH is caused by mutations in hepcidin. HJV is highly expressed in both skeletal muscle and liver. Mutations in HJV are implicated in the majority of diagnosed juvenile hemochromatosis patients. In this study, we stably transfected HJV cDNA into human embryonic kidney 293 cells and characterized the processing of HJV and its effect on iron homeostasis. Our results indicate that HJV is a glycosylphosphatidylinositol-linked protein and undergoes a partial autocatalytic cleavage during its intracellular processing. HJV co-immunoprecipitated with neogenin, a receptor involved in a variety of cellular signaling processes. It did not interact with the closely related receptor DCC (deleted in Colon Cancer). In addition, the HJV G320V mutant implicated in Type 2A HH did not co-immunoprecipitate with neogenin. Immunoblot analysis of ferritin levels and transferrin-55Fe accumulation studies indicated that the HJV-induced increase in intracellular iron levels in human embryonic kidney 293 cells is dependent on the presence of neogenin in the cells, thus linking these two proteins to intracellular iron homeostasis

Optimization of maintenances following proof tests for the final element of a safety-instrumented system

2019 The Authors Safety-instrumented systems (SISs) have been widely installed to prevent accidental events and mitigate their consequences. Mechanical final elements of SISs often become vulnerable with time due to degradations, but the particulars in SIS operations and assessment impede the adaption of state-of-art research results on maintenances into this domain. This paper models the degradation of SIS final element as a stochastic process. Based on the observed information during a proof test, it is essential to determine an optimal maintenance strategy by choosing a preventive maintenance (PM) or corrective maintenance (CM), as well deciding what degree of mitigation of degradation is enough in case of a PM. When the reasonable initiation situation of a PM and the optimal maintenance degree are identified, lifetime cost of the final element can be minimized while keeping satisfying the integrity level requirement for the SIS. A numerical example is introduced to illustrate how the presenting methods are used to examine the effects of maintenance strategies on cost and the average probability of failure on demands (PFDavg) of a SIS. Intervals of the upcoming tests thus can be updated to provide maintenance crews with more clues on cost-effective tests without weakening safety

Hedge commitments and agency costs of debt: evidence from interest rate protection covenants and accounting conservatism

We provide large sample evidence that credible hedge commitments reduce the agency costs of debt and that accounting conservatism enhances hedge commitments. We examine 2,338 bank loans entered into by 263 mandatory derivative users that are contractually obligated by interest rate protection covenants, 709 voluntary derivative users, and 1,366 non-users. We show that loan contracts are more likely to include interest rate protection covenants when borrowers are less likely to maintain the hedge position once the financing is completed. We find that borrowers who credibly commit to hedge using these covenants significantly reduce their interest rates. While we do not find an average interest savings for voluntary derivative users, we do find a reduction in their loan rates when they practice conservative financial reporting. Our results suggest that accounting conservatism helps borrowers resolve shareholder-creditor conflicts by committing to maintain their hedge positions after completing debt financing.Deloitte LL

Genomic abundance is not predictive of tandem repeat localization in grass genomes.

Highly repetitive regions have historically posed a challenge when investigating sequence variation and content. High-throughput sequencing has enabled researchers to use whole-genome shotgun sequencing to estimate the abundance of repetitive sequence, and these methodologies have been recently applied to centromeres. Previous research has investigated variation in centromere repeats across eukaryotes, positing that the highest abundance tandem repeat in a genome is often the centromeric repeat. To test this assumption, we used shotgun sequencing and a bioinformatic pipeline to identify common tandem repeats across a number of grass species. We find that de novo assembly and subsequent abundance ranking of repeats can successfully identify tandem repeats with homology to known tandem repeats. Fluorescent in-situ hybridization shows that de novo assembly and ranking of repeats from non-model taxa identifies chromosome domains rich in tandem repeats both near pericentromeres and elsewhere in the genome

Mid-IR frequency measurement using an optical frequency comb and a long-distance remote frequency reference

We have built a frequency chain which enables to measure the absolute frequency of a laser emitting in the 28-31 THz frequency range and stabilized onto a molecular absorption line. The set-up uses an optical frequency comb and an ultrastable 1.55 $\mu$m frequency reference signal, transferred from LNE-SYRTE to LPL through an optical link. We are now progressing towards the stabilization of the mid-IR laser via the frequency comb and the extension of this technique to quantum cascade lasers. Such a development is very challenging for ultrahigh resolution molecular spectroscopy and fundamental tests of physics with molecules