Systems analysis of host-parasite interactions.

Parasitic diseases caused by protozoan pathogens lead to hundreds of thousands of deaths per year in addition to substantial suffering and socioeconomic decline for millions of people worldwide. The lack of effective vaccines coupled with the widespread emergence of drug-resistant parasites necessitates that the research community take an active role in understanding host-parasite infection biology in order to develop improved therapeutics. Recent advances in next-generation sequencing and the rapid development of publicly accessible genomic databases for many human pathogens have facilitated the application of systems biology to the study of host-parasite interactions. Over the past decade, these technologies have led to the discovery of many important biological processes governing parasitic disease. The integration and interpretation of high-throughput -omic data will undoubtedly generate extraordinary insight into host-parasite interaction networks essential to navigate the intricacies of these complex systems. As systems analysis continues to build the foundation for our understanding of host-parasite biology, this will provide the framework necessary to drive drug discovery research forward and accelerate the development of new antiparasitic therapies

Characterizing the metabolic phenotype of intestinal villus blunting in Zambian children with severe acute malnutrition and persistent diarrhea

Background: Environmental enteric dysfunction (EED) is widespread throughout the tropics and in children is associated with stunting and other adverse health outcomes. One of the hallmarks of EED is villus damage. In children with severe acute malnutrition (SAM) the severity of enteropathy is greater and short term mortality is high, but the metabolic consequences of enteropathy are unknown. Here, we characterize the urinary metabolic alterations associated with villus health, classic enteropathy biomarkers and anthropometric measurements in severely malnourished children in Zambia. Methods/Principal findings: We analysed 20 hospitalised children with acute malnutrition aged 6 to 23 months in Zambia. Small intestinal biopsies were assessed histologically (n = 15), anthropometric and gut function measurements were collected and the metabolic phenotypes were characterized by 1H nuclear magnetic resonance (NMR) spectroscopy. Endoscopy could not be performed on community controls children. Growth parameters were inversely correlated with enteropathy biomarkers (p = 0.011) and parameters of villus health were inversely correlated with translocation and permeability biomarkers (p = 0.000 and p = 0.015). Shorter villus height was associated with reduced abundance of metabolites related to gut microbial metabolism, energy and muscle metabolism (p = 0.034). Villus blunting was also related to increased sucrose excretion (p = 0.013). Conclusions/Significance: Intestinal villus blunting is associated with several metabolic perturbations in hospitalized children with severe undernutrition. Such alterations include altered muscle metabolism, reinforcing the link between EED and growth faltering, and a disruption in the biochemical exchange between the gut microbiota and host. These findings extend our understanding on the downstream consequences of villus blunting and provide novel non-invasive biomarkers of enteropathy dysfunction. The major limitations of this study are the lack of comparative control group and gut microbiota characterization

Observing the earliest moments of supernovae using strong gravitational lenses

We determine the viability of exploiting lensing time delays to observe strongly gravitationally lensed supernovae (gLSNe) from first light. Assuming a plausible discovery strategy, the Legacy Survey of Space and Time (LSST) and the Zwicky Transient Facility (ZTF) will discover $\sim$ 110 and $\sim$ 1 systems per year before the supernova (SN) explosion in the final image respectively. Systems will be identified $11.7^{+29.8}_{-9.3}$ days before the final explosion. We then explore the possibility of performing early-time observations for Type IIP and Type Ia SNe in LSST-discovered systems. Using a simulated Type IIP explosion, we predict that the shock breakout in one trailing image per year will peak at $\lesssim$ 24.1 mag ($\lesssim$ 23.3) in the $B$-band ($F218W$), however evolving over a timescale of $\sim$ 30 minutes. Using an analytic model of Type Ia companion interaction, we find that in the $B$-band we should observe at least one shock cooling emission event per year that peaks at $\lesssim$ 26.3 mag ($\lesssim$ 29.6) assuming all Type Ia gLSNe have a 1 M$_\odot$ red giant (main sequence) companion. We perform Bayesian analysis to investigate how well deep observations with 1 hour exposures on the European Extremely Large Telescope would discriminate between Type Ia progenitor populations. We find that if all Type Ia SNe evolved from the double-degenerate channel, then observations of the lack of early blue flux in 10 (50) trailing images would rule out more than 27% (19%) of the population having 1 M$_\odot$ main sequence companions at 95% confidence.Comment: 17 pages, 15 figures (including appendices). Accepted by MNRAS 3rd May 202

Closed forms and multi-moment maps

We extend the notion of multi-moment map to geometries defined by closed forms of arbitrary degree. We give fundamental existence and uniqueness results and discuss a number of essential examples, including geometries related to special holonomy. For forms of degree four, multi-moment maps are guaranteed to exist and are unique when the symmetry group is (3,4)-trivial, meaning that the group is connected and the third and fourth Lie algebra Betti numbers vanish. We give a structural description of some classes of (3,4)-trivial algebras and provide a number of examples.Comment: 36 page

Application of Fourier Transform Infrared Spectroscopy (FTIR) for assessing biogenic silica sample purity in geochemical analyses and palaeoenvironmental research

The development of a rapid and non-destructive method to assess purity levels in samples of biogenic silica prior to geochemical/isotope analysis remains a key objective in improving both the quality and use of such data in environmental and palaeoclimatic research. Here a Fourier Transform Infrared Spectroscopy (FTIR) mass-balance method is demonstrated for calculating levels of contamination in cleaned sediment core diatom samples from Lake Baikal, Russia. Following the selection of end-members representative of diatoms and contaminants in the analysed samples, a mass-balance model is generated to simulate the expected FTIR spectra for a given level of contamination. By fitting the sample FTIR spectra to the modelled FTIR spectra and calculating the residual spectra, the optimum best-fit model and level of contamination is obtained. When compared to X-ray Fluorescence (XRF) the FTIR method portrays the main changes in sample contamination through the core sequence, permitting its use in instances where other, destructive, techniques are not appropriate. The ability to analyse samples of <1 mg enables, for the first time, routine analyses of small sized samples. Discrepancies between FTIR and XRF measurements can be attributed to FTIR end-members not fully representing all contaminants and problems in using XRF to detect organic matter external to the diatom frustule. By analysing samples with both FTIR and XRF, these limitations can be eliminated to accurately identify contaminated samples. Future, routine use of these techniques in palaeoenvironmental research will therefore significantly reduce the number of erroneous measurements and so improve the accuracy of biogenic silica/diatom based climate reconstructions

Full phase stabilization of a Yb:fiber femtosecond frequency comb via high-bandwidth transducers

We present full phase stabilization of an amplified Yb:fiber femtosecond frequency comb using an intra-cavity electro-optic modulator and an acousto-optic modulator. These transducers provide high servo bandwidths of 580 kHz and 250 kHz for frep and fceo, producing a robust and low phase noise fiber frequency comb. The comb was self-referenced with an f - 2f interferometer and phase locked to an ultra-stable optical reference used for the JILA Sr optical clock at 698 nm, exhibiting 0.21 rad and 0.47 rad of integrated phase errors (over 1 mHz - 1 MHz) respectively. Alternatively, the comb was locked to two optical references at 698 nm and 1064 nm, obtaining 0.43 rad and 0.14 rad of integrated phase errors respectively

Biogeochemical cycling in the Bering Sea over the onset of major Northern Hemisphere glaciation

The Bering Sea is one of the most biologically productive regions in the marine system and plays a key role in regulating the flow of waters to the Arctic Ocean and into the subarctic North Pacific Ocean. Cores from IODP Expedition 323 to the Bering Sea provide the first opportunity to obtain reconstructions from the region that extend back to the Pliocene. Previous research at Bowers Ridge, south Bering Sea, has revealed stable levels of siliceous productivity over the onset of major Northern Hemisphere Glaciation (NHG) (c. 2.85-2.73 Ma). However, diatom silica isotope records of oxygen (δ18Odiatom) and silicon (δ30Sidiatom) presented here demonstrate that this interval was associated with a progressive increase in the supply of silicic acid to the region, superimposed on shift to a more dynamic environment characterized by colder temperatures and increased sea ice. This concluded at 2.58 Ma with a sharp increase in diatom productivity, further increases in photic zone nutrient availability and a permanent shift to colder sea surface conditions. These transitions are suggested to reflect a gradually more intense nutrient leakage from the subarctic northwest Pacific Ocean, with increases in productivity further aided by increased sea-ice and wind-driven mixing in the Bering Sea. In suggesting a linkage in biogeochemical cycling between the south Bering Sea and subarctic Northwest Pacific Ocean, mainly via the Kamchatka Strait, this work highlights the need to consider the inter-connectivity of these two systems when future reconstructions are carried out in the region

LIMS Instrument Package (LIP) balloon experiment: Nimbus 7 satellite correlative temperature, ozone, water vapor, and nitric acid measurements

The Limb Infrared Monitor of the Stratosphere (LIMS) LIP balloon experiment was used to obtain correlative temperature, ozone, water vapor, and nitric acid data at altitudes between 10 and 36 kilometers. The performance of the LIMS sensor flown on the Nimbus 7 Satellite was assessed. The LIP consists of the modified electrochemical concentration cell ozonesonde, the ultraviolet absorption photometric of ozone, the water vapor infrared radiometer sonde, the chemical absorption filter instrument for nitric acid vapor, and the infrared radiometer for nitric acid vapor. The limb instrument package (LIP), its correlative sensors, and the resulting data obtained from an engineering and four correlative flights are described

Coherent resonant interactions and slow light with molecules confined in photonic band-gap fibers

We investigate resonant nonlinear optical interactions and demonstrate induced transparency in acetylene molecules in a hollow-core photonic band-gap fiber at 1.5$\mu$m. The induced spectral transmission window is used to demonstrate slow-light effects, and we show that the observed broadening of the spectral features is due to collisions of the molecules with the inner walls of the fiber core. Our results illustrate that such fibers can be used to facilitate strong coherent light-matter interactions even when the optical response of the individual molecules is weak.Comment: 5 pages, 4 figure