Foregrounds for 21cm Observations of Neutral Gas at High Redshift

We investigate a number of potential foregrounds for an ambitious goal of future radio telescopes such as the Square Kilometer Array (SKA) and Low Frequency Array (LOFAR): spatial tomography of neutral gas at high redshift in 21cm emission. While the expected temperature fluctuations due to unresolved radio point sources is highly uncertain, we point out that free-free emission from the ionizing halos that reionized the universe should define a minimal bound. This emission is likely to swamp the expected brightness temperature fluctuations, making proposed detections of the angular patchwork of 21cm emission across the sky unlikely to be viable. An alternative approach is to discern the topology of reionization from spectral features due to 21cm emission along a pencil-beam slice. This requires tight control of the frequency-dependence of the beam in order to prevent foreground sources from contributing excessive variance. We also investigate potential contamination by galactic and extragalactic radio recombination lines (RRLs). These are unlikely to be show-stoppers, although little is known about the distribution of RRLs away from the Galactic plane. The mini-halo emission signal is always less than that of the IGM, making mini-halos unlikely to be detectable. If they are seen, it will be only in the very earliest stages of structure formation at high redshift, when the spin temperature of the IGM has not yet decoupled from the CMB.Comment: submitted to MNRA

Zooarchaeological and Genetic Evidence for the Origins of Domestic Cattle in Ancient China

This article reviews current evidence for the origins of domestic cattle in China. We describe two possible scenarios: 1) domestic cattle were domesticated indigenously in East Asia from the wild aurochs ( Bos primigenius), and 2) domestic cattle were domesticated elsewhere and then introduced to China. We conclude that the current zooarchaeological and genetic evidence does not support indigenous domestication within China, although it is possible that people experimented with managing wild aurochs in ways that did not lead to complete domestication. Most evidence indicates that domestic taurine cattle ( Bos taurus) were introduced to China during the third millennium b.c., and were related to cattle populations first domesticated in the Near East. Zebu cattle ( Bos indicus) entered China sometime between 2000 and 200 b.c., but much less is known about this species. The role of cattle as ritual and wealth animals seems to have been critical to their initial introduction

Repression of the Glucocorticoid Receptor Aggravates Acute Ischemic Brain Injuries in Adult Mice.

Strokes are one of the leading causes of mortality and chronic morbidity in the world, yet with only limited successful interventions available at present. Our previous studies revealed the potential role of the glucocorticoid receptor (GR) in the pathogenesis of neonatal hypoxic-ischemic encephalopathy (HIE). In the present study, we investigate the effect of GR knockdown on acute ischemic brain injuries in a model of focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO) in adult male CD1 mice. GR siRNAs and the negative control were administered via intracerebroventricular (i.c.v.) injection 48 h prior to MCAO. The cerebral infarction volume and neurobehavioral deficits were determined 48 h after MCAO. RT-qPCR was employed to assess the inflammation-related gene expression profiles in the brain before and after MCAO. Western Blotting was used to evaluate the expression levels of GR, the mineralocorticoid receptor (MR) and the brain-derived neurotrophic factor/tropomyosin receptor kinase B (BDNF/TrkB) signaling. The siRNAs treatment decreased GR, but not MR, protein expression, and significantly enhanced expression levels of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) in the brain. Of interest, GR knockdown suppressed BDNF/TrkB signaling in adult mice brains. Importantly, GR siRNA pretreatment significantly increased the infarction size and exacerbated the neurobehavioral deficits induced by MCAO in comparison to the control group. Thus, the present study demonstrates the important role of GR in the regulation of the inflammatory responses and neurotrophic BDNF/TrkB signaling pathway in acute ischemic brain injuries in adult mice, revealing a new insight into the pathogenesis and therapeutic potential in acute ischemic strokes

The inverse relationship between solar-induced fluorescence yield and photosynthetic capacity: Benefits for field phenotyping

Improving photosynthesis is considered a promising way to increase crop yield to feed a growing population. Realizing this goal requires non-destructive techniques to quantify photosynthetic variation among crop cultivars. Despite existing remote sensing-based approaches, it remains a question whether solar-induced fluorescence (SIF) can facilitate screening crop cultivars of improved photosynthetic capacity in plant breeding trials. Here we tested a hypothesis that SIF yield rather than SIF had a better relationship with the maximum electron transport rate (Jmax). Time-synchronized hyperspectral images and irradiance spectra of sunlight under clear-sky conditions were combined to estimate SIF and SIF yield, which were then correlated with ground-truth Vcmax and Jmax. With observations binned over time (i.e. group 1: 6, 7, and 12 July 2017; group 2: 31 July and 18 August 2017; and group 3: 24 and 25 July 2018), SIF yield showed a stronger negative relationship, compared with SIF, with photosynthetic variables. Using SIF yield for Jmax (Vcmax) predictions, the regression analysis exhibited an R2 of 0.62 (0.71) and root mean square error (RMSE) of 11.88 (46.86) μmol m-2 s-1 for group 1, an R2 of 0.85 (0.72) and RMSE of 13.51 (49.32) μmol m-2 s-1 for group 2, and an R2 of 0.92 (0.87) and RMSE of 15.23 (30.29) μmol m-2 s-1 for group 3. The combined use of hyperspectral images and irradiance measurements provides an alternative yet promising approach to characterization of photosynthetic parameters at plot level

The End of History? Using a Proof Assistant to Replace Language Design with Library Design

Functionality of software systems has exploded in part because of advances in programming-language support for packaging reusable functionality as libraries. Developers benefit from the uniformity that comes of exposing many interfaces in the same language, as opposed to stringing together hodgepodges of command-line tools. Domain-specific languages may be viewed as an evolution of the power of reusable interfaces, when those interfaces become so flexible as to deserve to be called programming languages. However, common approaches to domain-specific languages give up many of the hard-won advantages of library-building in a rich common language, and even the traditional approach poses significant challenges in learning new APIs. We suggest that instead of continuing to develop new domain-specific languages, our community should embrace library-based ecosystems within very expressive languages that mix programming and theorem proving. Our prototype framework Fiat, a library for the Coq proof assistant, turns languages into easily comprehensible libraries via the key idea of modularizing functionality and performance away from each other, the former via macros that desugar into higher-order logic and the latter via optimization scripts that derive efficient code from logical programs

Enrichment of clinical trials in MCI due to AD using markers of amyloid and neurodegeneration

Objective: To investigate the effect of enriching mild cognitive impairment (MCI) clinical trials using combined markers of amyloid pathology and neurodegeneration. Methods: We evaluate an implementation of the recent National Institute for Aging–Alzheimer's Association (NIA-AA) diagnostic criteria for MCI due to Alzheimer disease (AD) as inclusion criteria in clinical trials and assess the effect of enrichment with amyloid (A+), neurodegeneration (N+), and their combination (A+N+) on the rate of clinical progression, required sample sizes, and estimates of trial time and cost. Results: Enrichment based on an individual marker (A+ or N+) substantially improves all assessed trial characteristics. Combined enrichment (A+N+) further improves these results with a reduction in required sample sizes by 45% to 60%, depending on the endpoint. Conclusions: Operationalizing the NIA-AA diagnostic criteria for clinical trial screening has the potential to substantially improve the statistical power of trials in MCI due to AD by identifying a more rapidly progressing patient population

Direct Observation of Multiple Tautomers of Oxythiamine and their Recognition by the Thiamine Pyrophosphate Riboswitch

Structural diversification of canonical nucleic acid bases and nucleotide analogues by tautomerism has been proposed to be a powerful on/off switching mechanism allowing regulation of many biological processes mediated by RNA enzymes and aptamers. Despite the suspected biological importance of tautomerism, attempts to observe minor tautomeric forms in nucleic acid or hybrid nucleic acid-ligand complexes have met with challenges due to the lack of sensitive methods. Here, a combination of spectroscopic, biochemical, and computational tools probed tautomerism in the context of an RNA aptamer-ligand complex; studies involved a model ligand, oxythiamine pyrophosphate (OxyTPP), bound to the thiamine pyrophosphate (TPP) riboswitch (an RNA aptamer) as well as its unbound nonphosphorylated form, oxythiamine (OxyT). OxyTPP, similarly to canonical heteroaromatic nucleic acid bases, has a pyrimidine ring that forms hydrogen bonding interactions with the riboswitch. Tautomerism was established using two-dimensional infrared (2D IR) spectroscopy, variable temperature FTIR and NMR spectroscopies, binding isotope effects (BIEs), and computational methods. All three possible tautomers of OxyT, including the minor enol tautomer, were directly identified, and their distributions were quantitated. In the bound form, BIE data suggested that OxyTPP existed as a 4′-keto tautomer that was likely protonated at the N1′-position. These results also provide a mechanistic framework for understanding the activation of riboswitch in response to deamination of the active form of vitamin B1 (or TPP). The combination of methods reported here revealing the fine details of tautomerism can be applied to other systems where the importance of tautomerism is suspected.National Institutes of Health (U.S.) (Grant CA080024)National Institutes of Health (U.S.) (Grant CA26731)National Institutes of Health (U.S.) (Grant ES002109)National Institutes of Health (U.S.) (Grant ES007020)National Science Foundation (U.S.) (Grant CHE-1212557)Massachusetts Institute of Technology. Center for Environmental Health Sciences (National Institutes of Health (U.S.) Center Grant P30-ES002109)Massachusetts Institute of Technology. Laser Biomedical Research Center (National Institutes of Health (U.S.) Center Grant P41-EB015871)National Institutes of Health (U.S.) (Traineeship T32 ES007020)Massachusetts Institute of Technology (Poitras Pre-Doctoral Fellowship