A Lower Bound on List Size for List Decoding

A q-ary error-correcting code C ⊆ {1,2,...,q}n is said to be list decodable to radius ρ with list size L if every Hamming ball of radius ρ contains at most L codewords of C. We prove that in order for a q -ary code to be list-decodable up to radius (1-1/q)(1- ε)n, we must have L = Ω(1/ ε2) . Specifically, we prove that there exists a constant cq > 0 and a function fq such that for small enough ε > 0, if C is list-decodable to radius (1-1/q)(1- ε)n with list size cq/ ε2, then C has at most fq( ε) codewords, independent of n . This result is asymptotically tight (treating q as a constant), since such codes with an exponential (in n ) number of codewords are known for list size L = O(1/ ε2). A result similar to ours is implicit in Blinovsky ( Problems of Information Transmission, 1986) for the binary (q=2) case. Our proof is simpler and works for all alphabet sizes, and provides more intuition for why the lower bound arises.Engineering and Applied Science

Most Likely Transformations

We propose and study properties of maximum likelihood estimators in the class of conditional transformation models. Based on a suitable explicit parameterisation of the unconditional or conditional transformation function, we establish a cascade of increasingly complex transformation models that can be estimated, compared and analysed in the maximum likelihood framework. Models for the unconditional or conditional distribution function of any univariate response variable can be set-up and estimated in the same theoretical and computational framework simply by choosing an appropriate transformation function and parameterisation thereof. The ability to evaluate the distribution function directly allows us to estimate models based on the exact likelihood, especially in the presence of random censoring or truncation. For discrete and continuous responses, we establish the asymptotic normality of the proposed estimators. A reference software implementation of maximum likelihood-based estimation for conditional transformation models allowing the same flexibility as the theory developed here was employed to illustrate the wide range of possible applications.Comment: Accepted for publication by the Scandinavian Journal of Statistics 2017-06-1

Active and diverse viruses persist in the deep sub-seafloor sediments over thousands of years

Viruses are ubiquitous and cause significant mortality in marine bacterial and archaeal communities. Little is known about the role of viruses in the sub-seafloor biosphere, which hosts a large fraction of all microbes on Earth. We quantified and characterized viruses in sediments from the Baltic Sea. The results show that the Baltic Sea sub-seafloor biosphere harbors highly abundant viruses with densities up to 1.8 × 1010 viruses cm−3. High potential viral production down to 37 meters below seafloor in ca. 6000-years-old sediments and infected prokaryotic cells visible by transmission electron microscopy demonstrate active viral infection. Morphological and molecular data indicate that the highly diverse community of viruses includes both allochthonous input from the overlying seawater and autochthonous production. The detection of cyanophage-like sequences showed that viruses of phototrophic hosts may persist in marine sediments for thousands of years. Our results imply that viruses influence sub-seafloor microbial community dynamics and thereby affect biogeochemical processes in the sub-seafloor biosphere

Simultaneous evaluation of treatment efficacy and toxicity for bispecific T-cell engager therapeutics in a humanized mouse model.

Immuno-oncology (IO)-based therapies such as checkpoint inhibitors, bi-specific antibodies, and CAR-T-cell therapies have shown significant success in the treat- ment of several cancer indications. However, these therapies can result in the de- velopment of severe adverse events, including cytokine release syndrome (CRS). Currently, there is a paucity of in vivo models that can evaluate dose-response relationships for both tumor control and CRS-related safety issues. We tested an in vivo PBMC humanized mouse model to assess both treatment efficacy against specific tumors and the concurrent cytokine release profiles for individual human donors after treatment with a CD19xCD3 bispecific T-cell engager (BiTE). Using this model, we evaluated tumor burden, T-cell activation, and cytokine release in response to bispecific T-cell-engaging antibody in humanized mice generated with different PBMC donors. The results show that PBMC engrafted NOD-scid Il2rgnull mice lacking expression of mouse MHC class I and II (NSG-MHC-DKO mice) and implanted with a tumor xenograft predict both efficacy for tumor control by CD19xCD3 BiTE and stimulated cytokine release. Moreover, our find- ings indicate that this PBMC-engrafted model captures variability among donors for tumor control and cytokine release following treatment. Tumor control and cytokine release were reproducible for the same PBMC donor in separate experi- ments. The PBMC humanized mouse model described here is a sensitive and re- producible platform that identifies specific patient/cancer/therapy combinations for treatment efficacy and development of complications

The transcriptional programme controlled by Runx1 during early embryonic blood development

AbstractTranscription factors have long been recognised as powerful regulators of mammalian development yet it is largely unknown how individual key regulators operate within wider regulatory networks. Here we have used a combination of global gene expression and chromatin-immunoprecipitation approaches during the early stages of haematopoietic development to define the transcriptional programme controlled by Runx1, an essential regulator of blood cell specification. Integrated analysis of these complementary genome-wide datasets allowed us to construct a global regulatory network model, which suggested that key regulators are activated sequentially during blood specification, but will ultimately collaborate to control many haematopoietically expressed genes. Using the CD41/integrin alpha 2b gene as a model, cellular and in vivo studies showed that CD41 is controlled by both Scl/Tal1 and Runx1 in fully specified blood cells, and initiation of CD41 expression in E7.5 embryos is severely compromised in the absence of Runx1. Taken together, this study represents the first global analysis of the transcriptional programme controlled by any key haematopoietic regulator during the process of early blood cell specification. Moreover, the concept of interplay between sequentially deployed core regulators is likely to represent a design principle widely applicable to the transcriptional control of mammalian development