Near-bottom seismic profiling: High lateral variability, anomalous amplitudes, and estimates of attenuation

For almost a decade the Marine Physical Laboratory of Scripps Institution of Oceanography has been conducting near‐bottom geophysical surveys involving quantitative seismic profiling. Operating initially at 4 kHz and more recently at 6 kHz, this system has provided a wealth of fine scale quantitative data on the acoustic properties of ocean sediments. Over lateral distances of a few meters, 7‐dB changes in overall reflected energy as well as 10‐dB changes from individual reflectors have been observed. Anomalously high amplitudes from deep reflectors have been commonly observed, suggesting that multilayer interference is prevalent in records from such pulsed cw profilers. This conclusion is supported by results from sediment core physical property work and related convolution modeling, as well as by the significant differences observed between 4‐ and 6‐kHz profiles. In general, however, lateral consistency has been adequate in most areas surveyed to permit good estimates of acoustic attenuation from returns from dipping reflectors and sediment wedges

Good things take time – diversity effects on tree growth shift from negative to positive during stand development in boreal forests

Long‐term grassland biodiversity experiments have shown that diversity effects on productivity tend to strengthen through time, as complementarity among coexisting species increases. But it remains less clear whether this pattern also holds for other ecosystems such as forests, and if so why.Here we explore whether diversity effects on tree growth change predictably during stand development in Finland's boreal forests. Using tree ring records from mature forests, we tested whether diameter growth trajectories of dominant tree species growing in mixture differed from those in monoculture. We then compared these results with data from the world's longest running tree diversity experiment, where the same combinations of species sampled in mature forests were planted in 1999.We found that diversity effects on tree growth strengthened progressively through time, only becoming significantly positive around 20 years after seedling establishment. This shift coincided with the period in which canopy closure occurs in these forests, at which time trees begin to interact and compete above‐ground. These temporal trends were remarkably consistent across different tree species sampled in mature forests, and broadly matched growth responses observed in the much younger experimental plots.Synthesis. Our results mirror those from grassland ecosystems and suggest that canopy closure is a key phase for promoting niche complementarity in diverse tree communities. They also provide a series of testable hypotheses for the growing number of tree diversity experiments that have been established in recent years

Deep CO₂ in the end-Triassic Central Atlantic Magmatic Province

Large Igneous Province eruptions coincide with many major Phanerozoic mass extinctions, suggesting a cause-effect relationship where volcanic degassing triggers global climatic changes. In order to fully understand this relationship, it is necessary to constrain the quantity and type of degassed magmatic volatiles, and to determine the depth of their source and the timing of eruption. Here we present direct evidence of abundant CO2 in basaltic rocks from the end-Triassic Central Atlantic Magmatic Province (CAMP), through investigation of gas exsolution bubbles preserved by melt inclusions. Our results indicate abundance of CO2 and a mantle and/or lower-middle crustal origin for at least part of the degassed carbon. The presence of deep carbon is a key control on the emplacement mode of CAMP magmas, favouring rapid eruption pulses (a few centuries each). Our estimates suggest that the amount of CO2 that each CAMP magmatic pulse injected into the end-Triassic atmosphere is comparable to the amount of anthropogenic emissions projected for the 21st century. Such large volumes of volcanic CO2 likely contributed to end-Triassic global warming and ocean acidification

Growing Correlation Length on Cooling Below the Onset of Caging in a Simulated Glass-Forming Liquid

We present a calculation of a fourth-order, time-dependent density correlation function that measures higher-order spatiotemporall correlations of the density of a liquid. From molecular dynamics simulations of a glass-forming Lennard-Jones liquid, we find that the characteristic length scale of this function has a maximum as a function of time which increases steadily beyond the characteristic length of the static pair correlation function $g(r)$ in the temperature range approaching the mode coupling temperature from above

Subacute AMD3100 treatment is not efficient in neonatal hypoxic-schemic rats

Background and Purpose: Despite the advances in treating neonatal hypoxic-ischemic encephalopathy (HIE) with induced hypothermia, the rates of severe disability are still high among survivors. Preclinical studies have indicated that cell therapies with hematopoietic stem/progenitor cells could improve neurological outcomes in HIE. In this study, we investigated whether the administration of AMD3100, a CXCR4 antagonist that mobilizes hematopoietic stem/progenitor cells into the circulation, has therapeutic effects in HIE. Methods: P10 Wistar rats of both sexes were subjected to right common carotid artery occlusion or sham procedure, and then were exposed to hypoxia for 120 minutes. Two subcutaneous injections of AMD3100 or vehicle were given on the third and fourth day after HIE. We first assessed the interindividual variability in brain atrophy after experimental HIE and vehicle treatment in a small cohort of rats. Based on this exploratory analysis, we designed and conducted an experiment to test the efficacy of AMD3100. Brain atrophy on day 21 after HIE was defined as the primary end point. Secondary efficacy end points were cognitive (T-water maze) and motor function (rotarod) on days 17 and 18 after HIE, respectively. Results: AMD3100 did not decrease the brain atrophy in animals of either sex. Cognitive impairments were not observed in the T-water maze, but male hypoxic-ischemic animals exhibited motor coordination deficits on the rotarod, which were not improved by AMD3100. A separate analysis combining data from animals of both sexes also revealed no evidence of the effectiveness of AMD3100 treatment. Conclusions: These results indicate that the subacute treatment with AMD3100 does not improve structural and functional outcomes in a rat HIE model

Early hemostatic responses to trauma identified with hierarchical clustering analysis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111900/1/jth12919.pd

Information Asymmetries between Parents and Educators in German Childcare Institutions

Economic theory predicts market failure in the market for early childhood education and care (ECEC) due to information asymmetries. We empirically investigate information asymmetries between parents and ECEC professionals in Germany, making use of a unique extension of the German Socio-Economic Panel Study (SOEP). It allows us to compare quality perceptions by parents and pedagogic staff of 734 ECEC institutions which were attended by children in SOEP households. Parents and staff were asked to rate the same quality measures. We detect considerable information asymmetries between these groups which differ across quality measures but little by parental socio-economic background or center characteristics. Our findings imply that information is not readily available to parents, an issue that should be addressed by policy-makers

Concomitant CIS on TURBT does not impact oncological outcomes in patients treated with neoadjuvant or induction chemotherapy followed by radical cystectomy

© Springer-Verlag GmbH Germany, part of Springer Nature 2018Background: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer improves all-cause and cancer specific survival. We aimed to evaluate whether the detection of carcinoma in situ (CIS) at the time of initial transurethral resection of bladder tumor (TURBT) has an oncological impact on the response to NAC prior to radical cystectomy. Patients and methods: Patients were identified retrospectively from 19 centers who received at least three cycles of NAC or induction chemotherapy for cT2-T4aN0-3M0 urothelial carcinoma of the bladder followed by radical cystectomy between 2000 and 2013. The primary and secondary outcomes were pathological response and overall survival, respectively. Multivariable analysis was performed to determine the independent predictive value of CIS on these outcomes. Results: Of 1213 patients included in the analysis, 21.8% had concomitant CIS. Baseline clinical and pathologic characteristics of the ‘CIS’ versus ‘no-CIS’ groups were similar. The pathological response did not differ between the two arms when response was defined as pT0N0 (17.9% with CIS vs 21.9% without CIS; p = 0.16) which may indicate that patients with CIS may be less sensitive to NAC or ≤ pT1N0 (42.8% with CIS vs 37.8% without CIS; p = 0.15). On Cox regression model for overall survival for the cN0 cohort, the presence of CIS was not associated with survival (HR 0.86 (95% CI 0.63–1.18; p = 0.35). The presence of LVI (HR 1.41, 95% CI 1.01–1.96; p = 0.04), hydronephrosis (HR 1.63, 95% CI 1.23–2.16; p = 0.001) and use of chemotherapy other than ddMVAC (HR 0.57, 95% CI 0.34–0.94; p = 0.03) were associated with shorter overall survival. For the whole cohort, the presence of CIS was also not associated with survival (HR 1.05 (95% CI 0.82–1.35; p = 0.70). Conclusion: In this multicenter, real-world cohort, CIS status at TURBT did not affect pathologic response to neoadjuvant or induction chemotherapy. This study is limited by its retrospective nature as well as variability in chemotherapy regimens and surveillance regimens.Peer reviewedFinal Accepted Versio

Distinct roles of extracellular domains in the Epstein-Barr virus-encoded BILF1 receptor for signaling and major histocompatibility complex class I downregulation

G protein-coupled receptors constitute the largest family of membrane proteins. As targets of >30% of the FDA-approved drugs, they are valuable for drug discovery. The receptor is composed of seven membrane-spanning helices and intracellular and extracellular domains. BILF1 is a receptor encoded by Epstein-Barr virus (EBV), which evades the host immune system by various strategies. BILF1 facilitates the virus immune evasion by downregulating MHC class I and is capable of inducing signaling-mediated tumorigenesis. BILF1 homologs from primate viruses show highly conserved extracellular domains. Here, we show that conserved residues in the extracellular domains of EBV-BILF1 are important for downregulating MHC class I and that the receptor signaling and immune evasion can be inhibited by drug-like small molecules. This suggests that BILF1 could be a target to inhibit the signaling-mediated tumorigenesis and interfere with the MHC class I downregulation, thereby facilitating virus recognition by the immune system.The Epstein-Barr virus (EBV) BILF1 gene encodes a constitutively active G protein-coupled receptor (GPCR) that downregulates major histocompatibility complex (MHC) class I and induces signaling-dependent tumorigenesis. Different BILF1 homologs display highly conserved extracellular loops (ECLs) including the conserved cysteine residues involved in disulfide bridges present in class A GPCRs (GPCR bridge between transmembrane helix 3 [TM-3] and ECL-2) and in chemokine receptors (CKR bridge between the N terminus and ECL-3). In order to investigate the roles of the conserved residues in the receptor functions, 25 mutations were created in the extracellular domains. Luciferase reporter assays and flow cytometry were used to investigate the G protein signaling and MHC class I downregulation in HEK293 cells. We find that the cysteine residues involved in the GPCR bridge are important for both signaling and MHC class I downregulation, whereas the cysteine residues in the N terminus and ECL-3 are dispensable for signaling but important for MHC class I downregulation. Multiple conserved residues in the extracellular regions are important for the receptor-induced MHC class I downregulation, but not for signaling, indicating distinct structural requirements for these two functions. In an engineered receptor containing a binding site for Zn+2 ions in a complex with an aromatic chelator (phenanthroline or bipyridine), a ligand-driven inhibition of both the receptor signaling and MHC class I downregulation was observed. Taken together, this suggests that distinct regions in EBV-BILF1 can be pharmacologically targeted to inhibit the signaling-mediated tumorigenesis and interfere with the MHC class I downregulation

Empirical Survival Jensen-Shannon Divergence as a Goodness-of-Fit Measure for Maximum Likelihood Estimation and Curve Fitting

The coefficient of determination, known as R2, is commonly used as a goodness-of-fit criterion for fitting linear models. R2 is somewhat controversial when fitting nonlinear models, although it may be generalised on a case-by-case basis to deal with specific models such as the logistic model. Assume we are fitting a parametric distribution to a data set using, say, the maximum likelihood estimation method. A general approach to measure the goodness-of-fit of the fitted parameters, which is advocated herein, is to use a non- parametric measure for comparison between the empirical distribution, comprising the raw data, and the fitted model. In particular, for this purpose we put forward the Survi- val Jensen-Shannon divergence (SJS) and its empirical counterpart (ESJS) as a metric which is bounded, and is a natural generalisation of the Jensen-Shannon divergence. We demonstrate, via a straightforward procedure making use of the ESJS, that it can be used as part of maximum likelihood estimation or curve fitting as a measure of goodness-of-fit, including the construction of a confidence interval for the fitted parametric distribution. Furthermore, we show the validity of the proposed method with simulated data, and three empirical data sets