Inclusions Among Mixed-Norm Lebesgue Spaces

A mixed LP norm of a function on a product space is the result of successive classical Lp norms in each variable, potentially with a different exponent for each. Conditions to determine when one mixed norm space is contained in another are produced, generalizing the known conditions for embeddings of Lp spaces. The two-variable problem (with four Lp exponents, two for each mixed norm) is studied extensively. The problem\u27s ``unpermuted case simply reduces to a question of Lp embeddings. The other, ``permuted case further divides, depending on the values of the Lp exponents. Often, they fit the ``Minkowski case , when Minkowski\u27s integral inequality provides an easy, complete solution. In the ``non-Minkowski case , the solution is determined by the structure of the measures in the component Lp spaces. When no measure is purely atomic, there can be no mixed-norm embedding in the non-Minkowski case, so for such measures the problem is solved. With at least one purely atomic measure, the non-Minkowski case divides further based on the structure of the measures and the values of the exponents. Various necessary conditions and sufficient conditions are found, solving a number of subcases. Other subcases are shown to be genuinely complicated, with their solutions expressed in terms of an optimization problem known to be computationally difficult. With some difficult cases already present in the two-variable problem, it is impractical to cover every case of the multivariable problem, but results are presented which fully solve some cases. When no measure is purely atomic, the multivariable problem is solved by a reduction to the Minkowski case of certain two-variable subproblems. The multivariable problem with unweighted lp spaces has a similar reduction to easy two-variable subproblems. It is conjectured that this applies more generally; that, regardless of the structures of the involved measures, when every permuted two-variable subproblem fits the Minkowski case, the full multivariable mixed norm inclusion must hold

IRE1β negatively regulates IRE1α signaling in response to endoplasmic reticulum stress

IRE1β is an ER stress sensor uniquely expressed in epithelial cells lining mucosal surfaces. Here, we show that intestinal epithelial cells expressing IRE1β have an attenuated unfolded protein response to ER stress. When modeled in HEK293 cells and with purified protein, IRE1β diminishes expression and inhibits signaling by the closely related stress sensor IRE1α. IRE1β can assemble with and inhibit IRE1α to suppress stress-induced XBP1 splicing, a key mediator of the unfolded protein response. In comparison to IRE1α, IRE1β has relatively weak XBP1 splicing activity, largely explained by a nonconserved amino acid in the kinase domain active site that impairs its phosphorylation and restricts oligomerization. This enables IRE1β to act as a dominant-negative suppressor of IRE1α and affect how barrier epithelial cells manage the response to stress at the host–environment interface

Acetyl-CoA Carboxylase Herbicide Tolerance in Bermudagrass

Contamination of newly planted bermudagrass (Cynodon spp.) varieties by undesirable off-type bermudagrass genotypes is an ever increasing concern for turf managers because selective control options are limited. In 2009, a sethoxydim {2-[1-(ethoxyimino)butyl]-5-[2-(ethylthio)propyl]-3-hydroxy-2-cyclohexen-1-one} tolerant bermudagrass genotype (93-175) was identified during herbicide screening at the University of Georgia in Tifton. The objective of this research was to assess the tolerance of 93-175 to three Acetyl-CoA carboxylase (ACCase) herbicides in comparison to the susceptible genotypes Tifway and common bermudagrass. Greenhouse and field trials were performed between August 2011 and April 2013. Factors in the field experiment included ACCase herbicides, application rates, bermudagrass genotypes, and locations. Turfgrass injury ratings taken 42 days after treatment (DAT) and during greenup the following spring supported initial preliminary findings. At the 1x rate of sethoxydim (280 g a.i. ha⁻¹), 93-175 displayed 50 to 87% less injury in comparison to the susceptible genotypes. In the spring of 2013, 93-175 plots treated with a 1x rate of sethoxydim reached 100% recovery during the same time period as non-treated controls, while common and Tifway had only recovered to 48 and 60%, respectively. The tolerance mechanism of 93-175 to sethoxydim did not confer an appreciable reduction of clethodim {(E,E)-(6)-2-[1-[[(3-chloro-2-propenyl)oxy]imino]propyl]-5-[2-(ethylthio)propyl]-3-hydroxy-2-cyclohexen- 1-one} or fluazifop {(6)-2-[4-[[5-(trifluoromethyl)-2-pyridinyl]oxy]phenoxy]propanoic acid} herbicide treatment effects. 93-175 will continue to be studied to determine transferability of herbicide tolerance to progeny and the mechanism of the observed tolerance

Prdm9, a Major Determinant of Meiotic Recombination Hotspots, Is Not Functional in Dogs and Their Wild Relatives, Wolves and Coyotes

Meiotic recombination is a fundamental process needed for the correct segregation of chromosomes during meiosis in sexually reproducing organisms. In humans, 80% of crossovers are estimated to occur at specific areas of the genome called recombination hotspots. Recently, a protein called PRDM9 was identified as a major player in determining the location of genome-wide meiotic recombination hotspots in humans and mice. The origin of this protein seems to be ancient in evolutionary time, as reflected by its fairly conserved structure in lineages that diverged over 700 million years ago. Despite its important role, there are many animal groups in which Prdm9 is absent (e.g. birds, reptiles, amphibians, diptera) and it has been suggested to have disruptive mutations and thus to be a pseudogene in dogs. Because of the dog's history through domestication and artificial selection, we wanted to confirm the presence of a disrupted Prdm9 gene in dogs and determine whether this was exclusive of this species or whether it also occurred in its wild ancestor, the wolf, and in a close relative, the coyote. We sequenced the region in the dog genome that aligned to the last exon of the human Prdm9, containing the entire zinc finger domain, in 4 dogs, 17 wolves and 2 coyotes. Our results show that the three canid species possess mutations that likely make this gene non functional. Because these mutations are shared across the three species, they must have appeared prior to the split of the wolf and the coyote, millions of years ago, and are not related to domestication. In addition, our results suggest that in these three canid species recombination does not occur at hotspots or hotspot location is controlled through a mechanism yet to be determined

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

The epithelial-specific ER stress sensor IRE1β enables host-microbiota crosstalk to affect colon goblet cell development [preprint]

Epithelial cells lining mucosal surfaces of the gastrointestinal and respiratory tracts uniquely express IRE1β (Ern2), a paralogue of the most evolutionarily conserved endoplasmic reticulum stress sensor IRE1α. How IRE1β functions at the host-environment interface and why a second IRE1 paralogue evolved remain incompletely understood. Using conventionally raised and germ-free Ern2-/- mice, we found that IRE1β was required for microbiota-induced goblet cell maturation and mucus barrier assembly in the colon. This occurred only after colonization of the alimentary tract with normal gut microflora, which induced IRE1β expression. IRE1β acted by splicing Xbp1 mRNA to expand ER function and prevent ER stress in goblet cells. Although IRE1α can also splice Xbp1 mRNA, it did not act redundantly to IRE1β in this context. By regulating assembly of the colon mucus layer, IRE1β further shaped the composition of the gut microbiota. Mice lacking IRE1β had a dysbiotic microbial community that failed to induce goblet cell development when transferred into germ-free wild type mice. These results show that IRE1β evolved at mucosal surfaces to mediate crosstalk between gut microbes and the colonic epithelium required for normal homeostasis and host defense