Accessing the high-l frontier under the reduced shear approximation with k-cut cosmic shear

The precision of Stage IV cosmic shear surveys will enable us to probe smaller physical scales than ever before, however, model uncertainties from baryonic physics and non-linear structure formation will become a significant concern. The k-cut method - applying a redshift-dependent-cut after making the Bernardeau-Nishimichi-Taruya transform - can reduce sensitivity to baryonic physics; allowing Stage IV surveys to include information from increasingly higher-modes. Here we address the question of whether it can also mitigate the impact of making the reduced shear approximation; which is also important in the high-κ, small-scale regime. The standard procedure for relaxing this approximation requires the repeated evaluation of the convergence bispectrum, and consequently can be prohibitively computationally expensive when included in Monte Carlo analyses. We find that the k-cut cosmic shear procedure suppresses the w_{0}w_{a} CDM cosmological parameter biases expected from the reduced shear approximation for Stage IV experiments, when-modes up to 5000 are probed. The maximum cut required for biases from the reduced shear approximation to be below the threshold of significance is at k=5.37 h Mpc^{-1}. With this cut, the predicted 1σ constraints increase, relative to the case where the correction is directly computed, by less than 10% for all parameters. This represents a significant improvement in constraints compared to the more conservative case where only-modes up to 1500 are probed [A. Blanchard, (Euclid Collaboration), arXiv:1910.09273], and no k-cut is used. We also repeat this analysis for a hypothetical, comparable kinematic weak lensing survey. The key parts of code used for this analysis are made publicly available

Mapping Spatially Varying Additive Biases in Cosmic Shear Data

In this paper we address the challenge of extracting maps of spatially varying unknown additive biases from cosmic shear data. This is done by exploiting the isotropy of the cosmic shear field, and the anisotropy of a typical additive bias field, using an autocorrelation discrepancy map; which identifies significant non-Gaussian components of the map. We test this approach using simulations and find that the autocorrelation discrepancy map produces spatially varying features that are indicative of the additive bias field both in amplitude and spatial variation. We then apply this to the Dark Energy Survey Year 1 data, and find evidence for spatially varying additive biases of at most 0.002 on large-scales. The method can be used to empirically inform modelling of the spatially varying additive bias field in any cosmological parameter inference, and can act as a validation test for cosmic shear surveys

Factors determining short- and long-term survival after orthotopic liver homotransplantation in the dog

Without azathioprine therapy, the operative risk with orthotopic liver transplantation is small. Twenty-two of 23 animals survived 2 days or more, and 19 for 6 days or longer. All eventually died of rejection within 10 days. Changes in homograft histology and function were similar to those previously reported, with cellular infiltration and hepatocyte necrosis which was heavily concentrated in the centrilobular areas. In individual experiments, there was little evidence of immunologically induced segmental hepatic arterial or portal venous occlusion; hepatocyte loss was homogeneous, and fibrinoid vascular lesions were uncommon. There was, however, some evidence of damage to the sinusoidal endothelium by adherent mononuclear cells. The changing character of the mononuclear infiltration of the homograft was reflected by widespread proliferation of similar cells in the host lymphoid tissue. Specific changes in other host organs were not noted. Some of the biochemical and histologic alterations caused by unmodified rejection can also be produced by azathioprine. In 18 nontransplanted dogs, acute rises in SGOT, SGPT, and alkaline phosphatase, unaccompanied by hyperbilirubinemia, were noted within a few days after beginning administration of this agent. Although these abnormalities tended to regress within the 40 day period of observation, more than two thirds of the livers showed histologic evidence of centrilobular hepatocyte damage or necrosis-often with intrahepatic cholestasis, but always without mononuclear cell infiltration. The hepatotoxicity was not prevented by methionine. Weight loss and progressive anemia also occurred. Lymphoid tissue was depleted. The mortality from the toxicity study was 33 percent. The use of azathioprine to mitigate rejection increased the early mortality after homotransplantation, 32 of 116 dogs dying within the first week (28 percent), most commonly of pulmonary complications. The 84 animals living longer than 7 days had a greatly potentiated homograft survival, exceeding 25 days in 44 dogs, and 50 days in 24. Fifteen animals are still alive from 62 to 324 days postoperatively. Six dogs had all drugs stopped after 116 to 123 days. Only 1 has had a clinically evident late rejection and 5 are still alive from 63 to 204 days later. Three of these animals had repeat biopsies 77 to 182 days after cessation of therapy; one homograft which was normal at 4 months remained so 6 months later, another had an improved histologic appearance, and the third had deteriorated. The longest mean survival was in those animals receiving adjuvant therapy with L-methionine or S35-methionine, but the variability of the results was so great that a statistically significant advantage of these agents could not be demonstrated. Soon after operation red cell survival was decreased, but in chronic survivors there was no evidence of a grafthost reaction. There was great variability in the vigor of rejection, ranging from the uncontrollable (29 percent) to the clinically undetectable (23 percent). Most of the animals (49 percent) had some biochemical evidence of rejection which proved to be spontaneously reversible, to a greater or lesser degree, since intensification of immunosuppressive therapy was not required. These findings correlate well with the histologic studies. In virtually all animals, azathioprine delayed the onset of rejection but in those dying in the second and third postoperative weeks, the pathologic stigmas of rejection were very similar to the untreated controls. As in the untreated animals, the number of proliferating large pyroninophilic cells in the host's lymphoid tissues was roughly proportional to the number of mononuclear cells invading the homograft liver. After this time, the predominant histologic features in most animals were those of repair and regeneration, with either absent or relatively minor degrees or continuing destruction. Since the major rejection damage was centrizonal, the healing was most prominent in these areas with interconecting fibrosis around the central veins, centrilobular bile canalicular dilatation and cholestasis, and pseudolobule formation. In some of the homografts, increased connective tissue was also present in the portal tracts, but in others including the longest survivor there were no residual abnormalities whatever. In azathioprine-treated animals, damage to the vessels in the homograft portal tracts was found in only one liver. With electron microscopy there was some evidence of damage to the sinusoidal endothelium by adherent mononuclear cells, a finding which could be analogous to that described by Kountz and co-workers11 in the peritubular capillaries of renal homografts. If immunologically mediated hemodynamic alterations play an important role in liver homograft rejection by interrupting the blood supply to the hepatocytes, it seems most likely that they occur at this intrasinusoidal capillary level rather than in the larger vessels. © 1965

The contribution of short-term memory for sound features to speech-in-noise perception and cognition

\ua9 2024 The Author(s)Speech-in-noise (SIN) perception is a fundamental ability that declines with aging, as does general cognition. We assess whether auditory cognitive ability, in particular short-term memory for sound features, contributes to both. We examined how auditory memory for fundamental sound features, the carrier frequency and amplitude modulation rate of modulated white noise, contributes to SIN perception. We assessed SIN in 153 healthy participants with varying degrees of hearing loss using measures that require single-digit perception (the Digits-in-Noise, DIN) and sentence perception (Speech-in-Babble, SIB). Independent variables were auditory memory and a range of other factors including the Pure Tone Audiogram (PTA), a measure of dichotic pitch-in-noise perception (Huggins pitch), and demographic variables including age and sex. Multiple linear regression models were compared using Bayesian Model Comparison. The best predictor model for DIN included PTA and Huggins pitch (r2 = 0.32, p < 0.001), whereas the model for SIB included the addition of auditory memory for sound features (r2 = 0.24, p < 0.001). Further analysis demonstrated that auditory memory also explained a significant portion of the variance (28 %) in scores for a screening cognitive test for dementia. Auditory memory for non-speech sounds may therefore provide an important predictor of both SIN and cognitive ability

Isocyanide based multicomponent reactions of oxazolidines and related systems

N-Alkyloxazolidines react in a multicomponent reaction with carboxylic acids and isocyanides to give N-acyloxyethylamino acid amides. The previously reported reaction conditions were improved using a design of experiments approach (DoE). Under the optimised conditions, good yields of the N-acyloxyethylamino acid amide products are obtained both via a three- or four-component approach from N-alkylethanolamines, aldehydes/ketones, isocyanides and carboxylic acids. The reaction of oxazolidines without a nitrogen substituent was found to give either the expected Ugi products or the N-acyloxyethylamino acid amides depending on the choice of reaction conditions. Optimised reaction conditions were also developed for the ring-expansion of oxazolidines to morpholin-2-ones via reaction with an isocyanide followed by hydrolysis. The mechanistic pathway of the multicomponent reaction was briefly investigated using an O-18 labelling experiment. The carboxylic acid component can be replaced by a range of other acidic nucleophiles including thiobenzoic acid, thiophenol or 5-phenyltetrazole, which are incorporated via an alternative pathway. These latter reactions can also be applied to 2-aminotetrahydrofurans, 2-aminotetrahydropyrans or 4-hydroxybut-2-one, further extending the structural diversity of the multicomponent reaction products. (C) 2010 Elsevier Ltd. All rights reserved

Cosmic shear bias and calibration in dark energy studies

With the advent of large-scale weak lensing surveys there is a need to understand how realistic, scale-dependent systematics bias cosmic shear and dark energy measurements, and how they can be removed. Here, we show how spatially varying image distortions are convolved with the shear field, mixing convergence E and B modes, and bias the observed shear power spectrum. In practise, many of these biases can be removed by calibration to data or simulations. The uncertainty in this calibration is marginalized over, and we calculate how this propagates into parameter estimation and degrades the dark energy Figure-of-Merit. We find that noise-like biases affect dark energy measurements the most, while spikes in the bias power have the least impact. We argue that, in order to remove systematic biases in cosmic shear surveys and maintain statistical power, effort should be put into improving the accuracy of the bias calibration rather than minimizing the size of the bias. In general, this appears to be a weaker condition for bias removal. We also investigate how to minimize the size of the calibration set for a fixed reduction in the Figure-of-Merit. Our results can be used to correctly model the effect of biases and calibration on a cosmic shear survey, assess their impact on the measurement of modified gravity and dark energy models, and to optimize survey and calibration requirements

Identification of 2-Aminothiazole-4-Carboxylate Derivatives Active against Mycobacterium tuberculosis H37Rv and the β-Ketoacyl-ACP Synthase mtFabH

Background Tuberculosis (TB) is a disease which kills two million people every year and infects approximately over one-third of the world's population. The difficulty in managing tuberculosis is the prolonged treatment duration, the emergence of drug resistance and co-infection with HIV/AIDS. Tuberculosis control requires new drugs that act at novel drug targets to help combat resistant forms of Mycobacterium tuberculosis and reduce treatment duration. Methodology/Principal Findings Our approach was to modify the naturally occurring and synthetically challenging antibiotic thiolactomycin (TLM) to the more tractable 2-aminothiazole-4-carboxylate scaffold to generate compounds that mimic TLM's novel mode of action. We report here the identification of a series of compounds possessing excellent activity against M. tuberculosis H37Rv and, dissociatively, against the β-ketoacyl synthase enzyme mtFabH which is targeted by TLM. Specifically, methyl 2-amino-5-benzylthiazole-4-carboxylate was found to inhibit M. tuberculosis H37Rv with an MIC of 0.06 µg/ml (240 nM), but showed no activity against mtFabH, whereas methyl 2-(2-bromoacetamido)-5-(3-chlorophenyl)t​hiazole-4-carboxylateinhibited mtFabH with an IC50 of 0.95±0.05 µg/ml (2.43±0.13 µM) but was not active against the whole cell organism. Conclusions/Significance These findings clearly identify the 2-aminothiazole-4-carboxylate scaffold as a promising new template towards the discovery of a new class of anti-tubercular agents

Preparing for the cosmic shear data flood: Optimal data extraction and simulation requirements for stage IV dark energy experiments

Upcoming photometric lensing surveys will considerably tighten constraints on the neutrino mass and the dark energy equation of state. Nevertheless it remains an open question of how to optimally extract the information and how well the matter power spectrum must be known to obtain unbiased cosmological parameter estimates. By performing a principal component analysis (PCA), we quantify the sensitivity of 3D cosmic shear and tomography with different binning strategies to different regions of the lensing kernel and matter power spectrum, and hence the background geometry and growth of structure in the Universe. We find that a large number of equally spaced tomographic bins in redshift can extract nearly all the cosmological information without the additional computational expense of 3D cosmic shear. Meanwhile a large fraction of the information comes from small poorly understood scales in the matter power spectrum, that can lead to biases on measurements of cosmological parameters. In light of this, we define and compute a cosmology-independent measure of the bias due to imperfect knowledge of the power spectrum. For a Euclid-like survey, we find that the power spectrum must be known to an accuracy of less than 1% on scales with k ≤ 7 h     Mpc − 1 . This requirement is not absolute since the bias depends on the magnitude of modeling errors, where they occur in k − z space, and the correlation between them, all of which are specific to any particular model. We therefore compute the bias in several of the most likely modeling scenarios and introduce a general formalism and public code, RequiSim, to compute the expected bias from any nonlinear model

Nonparametric cosmology with cosmic shear

We present a method to measure the growth of structure and the background geometry of the Universe— with no a priori assumption about the underlying cosmological model. Using Canada-France-Hawaii Lensing Survey (CFHTLenS) shear data, we simultaneously reconstruct the lensing amplitude, the linear intrinsic alignment amplitude, the redshift evolving matter power spectrum, Pðk; zÞ, and the comoving distance, rðzÞ. We find that lensing predominately constrains a single global power spectrum amplitude and several comoving distance bins. Our approach can localize the precise scales (k-modes in the matter power spectrum) and redshifts where lambda-cold dark matter (LCDM) fails—if any. We find that below z ¼ 0.4, the measured comoving distance rðzÞ is higher than that expected from the Planck LCDM cosmology by ∼1.5σ, while at higher redshifts, our reconstruction is fully consistent. To validate our reconstruction, we compare LCDM parameter constraints from the standard cosmic shear likelihood analysis to those found by fitting to the nonparametric information and we find good agreement