Dipole-Coupled Neutrissimo Explanations of the MiniBooNE Excess Including Constraints from MINERvA Data

We revisit models of heavy neutral leptons (neutrissimos) with transition magnetic moments as explanations of the $4.8\sigma$ excess of electron-like events at MiniBooNE. We perform a detailed Monte Carlo-based analysis to re-examine the preferred regions in the model parameter space to explain MiniBooNE, considering also potential contributions from oscillations due to an eV-scale sterile neutrino. We then derive robust constraints on the model using neutrino-electron elastic scattering data from MINERvA. We find that MINERvA rules out a large region of parameter space, but allowed solutions exist at the $2\sigma$ confidence level. A dedicated MINERvA analysis would likely be able to probe the entire region of preference of MiniBooNE in this model.Comment: 14 page

Confirmation that “Brachyspira hampsonii” clade I (Canadian strain 30599) causes mucohemorrhagic diarrhea and colitis in experimentally infected pigs

BACKGROUND: “Brachyspira hampsonii”, discovered in North America in 2010 associated with dysentery-like illness, is an economically relevant swine pathogen resulting in decreased feed efficiency and increased morbidity, mortality and medication usage. “B. hampsonii” clade II strain 30446 has been shown to be causally associated with mucohemorrhagic diarrhea and colitis. Our objectives were to determine if “Brachyspira hampsonii” clade I strain 30599 is pathogenic to pigs, and to evaluate the relative diagnostic performance of three ante mortem sampling methodologies (direct PCR on feces, PCR on rectal GenoTube Livestock swabs, Brachyspira culture from rectal swabs). Five-week old pigs were intragastrically inoculated thrice with 10(8) genomic equivalents "B. hampsonii" (n = 12), or served as sham controls (n = 6). Feces were sampled and consistency assessed daily. Necropsies were performed 24 h after peak clinical signs. RESULTS: One pig died due to unrelated illness. Nine of 11 inoculated pigs, but no controls, developed mucoid or mucohemorrhagic diarrhea (MHD). Characteristic lesions of swine dysentery were observed in large intestine. “B. hampsonii” strain 30599 DNA was detected by qPCR in feces of all inoculated pigs for up to 6 days prior to the onset of MHD. The organism was isolated from the feces and colons of pigs demonstrating MHD, but not from controls. B. intermedia was isolated from inoculated pigs without MHD, and from 5 of 6 controls. CONCLUSIONS: We conclude that “Brachyspira hampsonii” clade I strain 30599 is pathogenic and causes mucohemorrhagic diarrhea and colitis in susceptible pigs. Moreover, the three sampling methodologies performed similarly. GenoTube Livestock, a forensic swab designed to preserve DNA during shipping is a useful tool especially in settings where timely transport of diagnostic samples is challenging

Harvey: A Greybox Fuzzer for Smart Contracts

We present Harvey, an industrial greybox fuzzer for smart contracts, which are programs managing accounts on a blockchain. Greybox fuzzing is a lightweight test-generation approach that effectively detects bugs and security vulnerabilities. However, greybox fuzzers randomly mutate program inputs to exercise new paths; this makes it challenging to cover code that is guarded by narrow checks, which are satisfied by no more than a few input values. Moreover, most real-world smart contracts transition through many different states during their lifetime, e.g., for every bid in an auction. To explore these states and thereby detect deep vulnerabilities, a greybox fuzzer would need to generate sequences of contract transactions, e.g., by creating bids from multiple users, while at the same time keeping the search space and test suite tractable. In this experience paper, we explain how Harvey alleviates both challenges with two key fuzzing techniques and distill the main lessons learned. First, Harvey extends standard greybox fuzzing with a method for predicting new inputs that are more likely to cover new paths or reveal vulnerabilities in smart contracts. Second, it fuzzes transaction sequences in a targeted and demand-driven way. We have evaluated our approach on 27 real-world contracts. Our experiments show that the underlying techniques significantly increase Harvey's effectiveness in achieving high coverage and detecting vulnerabilities, in most cases orders-of-magnitude faster; they also reveal new insights about contract code.Comment: arXiv admin note: substantial text overlap with arXiv:1807.0787

The benefits and challenges of using crowdfunding to facilitate community-led projects in the context of digital civics

Digital technology is increasingly being used to bring citizens and communities together to address local concerns. While a variety of approaches have been developed that allow citizens and communities to improve their local communities, these approaches are often financially unsustainable. In this paper, we describe our exploration of crowdfunding as an alternative approach to funding and sustaining community-led projects in the context of digital civics. Through our analysis of four community-led crowdfunding projects, we explore the merits of crowdfunding in this context, demonstrating that it can a) provide an alternative funding mechanism suitable for financing some community-led projects, b) create a sense of empowerment and ownership, and c) increase community awareness. By reflecting on our experiences, we identify four key challenges to utilising crowdfunding to support community-led projects in the context digital civics. We also provide advice specific to crowdfunding in the context of digital civics, before discussing the role of crowdfunding within digital civics. By addressing these challenges, we will be able to better support community groups crowdfund for the public good

Development and evaluation of a porcine in vitro colon organ culture technique

The intestinal mucosa comprises a complex assemblage of specialized tissues that interact in numerous ways. In vitro cell culture models are generally focused on recreating a specific characteristic of this organ and do not account for the many interactions between the different tissues. In vitro organ culture (IVOC) methods offer a way to overcome these limitations, but prolonging cell viability is essential. This study aimed to determine the feasibility and optimal conditions for in vitro culture of swine colonic mucosa for use as an enteric pathogen infection model. Explants (n = 168) from commercial pigs (n = 12), aged 5 to 10 wk, were used to assess the impact of various culture protocols on explant viability. Explants were cultured for up to 5 d and formalin fixed at 24-h intervals. Following establishment of the culture protocol, explants (n = 208) from 13 pigs were evaluated at Day 0 and 5 of culture. Assessment of viability was based on histological changes (tissue architecture evaluated by H&E, immunostaining of cell proliferation marker Ki-67) and expression of genes encoding IL-1α, IL-8, TNF-α, IFN-γ, and e-cadherin. After 5 d in culture, 20% of explants displayed over 80% of epithelial coverage, whereas 31% of explants had more than 50% of their surface covered by columnar epithelium, and 81% had crypts but with a decreased number of Ki-67-positive cells when compared to Day 0. Notably, large variability in explant quality was observed between donor pigs. Best possible explants were obtained from the distal colon of pigs, processed immediately after euthanasia, cultured at the liquid-tissue-gas interface in media supplemented with a mixture of antibiotics and antifungals and an oxygen-rich gas mix

Development and evaluation of a porcine in vitro colon organ culture technique

The intestinal mucosa comprises a complex assemblage of specialized tissues that interact in numerous ways. In vitro cell culture models are generally focused on recreating a specific characteristic of this organ and do not account for the many interactions between the different tissues. In vitro organ culture (IVOC) methods offer a way to overcome these limitations, but prolonging cell viability is essential. This study aimed to determine the feasibility and optimal conditions for in vitro culture of swine colonic mucosa for use as an enteric pathogen infection model. Explants (n = 168) from commercial pigs (n = 12), aged 5 to 10 wk, were used to assess the impact of various culture protocols on explant viability. Explants were cultured for up to 5 d and formalin fixed at 24-h intervals. Following establishment of the culture protocol, explants (n = 208) from 13 pigs were evaluated at Day 0 and 5 of culture. Assessment of viability was based on histological changes (tissue architecture evaluated by H&E, immunostaining of cell proliferation marker Ki-67) and expression of genes encoding IL-1α, IL-8, TNF-α, IFN-γ, and e-cadherin. After 5 d in culture, 20% of explants displayed over 80% of epithelial coverage, whereas 31% of explants had more than 50% of their surface covered by columnar epithelium, and 81% had crypts but with a decreased number of Ki-67-positive cells when compared to Day 0. Notably, large variability in explant quality was observed between donor pigs. Best possible explants were obtained from the distal colon of pigs, processed immediately after euthanasia, cultured at the liquid-tissue-gas interface in media supplemented with a mixture of antibiotics and antifungals and an oxygen-rich gas mix

Microbiota profile clustering based on Bray-Curtis dissimilarity calculated from abundance of 1141 OTU sequences (dendrogram, left panel), and proportional abundance of major phyla (stacked bar charts, right panel) in each microbiome.

<p>(A) 0 dpi, (B) terminal day.</p

Bacteroidetes and Firmicutes in the fecal microbiota of inoculated pigs at termination.

a,b<p>Superscript letters within a row indicate significant differences.</p><p>Bacteroidetes and Firmicutes in the fecal microbiota of inoculated pigs at termination.</p

In Vitro Porcine Colon Culture

Models have been extensively used to investigate disease pathogenesis. Animal models are costly, require extensive logistics for animal care, and samples are not always suitable for different analytical techniques or to answer the research question. In vitro cell culture models are generally focused on recreating a specific characteristic of an organ, and are limited to a single cell population that does not display the characteristic tissue architecture of the source organ. In addition, such models do not account for the many interactions between pathogens and the diverse cell subsets that are normally present in a given organ. Conclusions based on conventional 2D cell culture methods are limited, requiring extrapolation from a reductionist model to understand in vivo events. In vitro organ culture (IVOC) offers a way to overcome some of these limitations. Explants conserve important in vivo characteristics, such as different cell types and complex tissue architecture. This in vitro (ex vivo) organ culture protocol of the swine large intestine aims at maintaining viable colonic mucosa for up to 5 days. The protocol described herein applies a combination of methods used for immortalized cell culture and stem cell stimulation to support the physiological cellular flow inherent of the intestinal mucosa. Required equipment includes a hyperoxic chamber and culture at the air–liquid interface