DBI Realizations of the Pseudo-Conformal Universe and Galilean Genesis Scenarios

The pseudo-conformal universe is an alternative to inflation in which the early universe is described by a conformal field theory on approximately flat space-time. The fields develop time-dependent expectation values, spontaneously breaking the conformal symmetries to a de Sitter subalgebra, and fields of conformal weight zero acquire a scale invariant spectrum of perturbations. In this paper, we show that the pseudo-conformal scenario can be naturally realized within theories that would ordinarily be of interest for DBI inflation, such as the world-volume theory of a probe brane in an AdS bulk space-time. In this approach, the weight zero spectator field can be associated with a geometric flat direction in the bulk, and its scale invariance is protected by a shift symmetry.Comment: 34 page

The Bases of Association Rules of High Confidence

We develop a new approach for distributed computing of the association rules of high confidence in a binary table. It is derived from the D-basis algorithm in K. Adaricheva and J.B. Nation (TCS 2017), which is performed on multiple sub-tables of a table given by removing several rows at a time. The set of rules is then aggregated using the same approach as the D-basis is retrieved from a larger set of implications. This allows to obtain a basis of association rules of high confidence, which can be used for ranking all attributes of the table with respect to a given fixed attribute using the relevance parameter introduced in K. Adaricheva et al. (Proceedings of ICFCA-2015). This paper focuses on the technical implementation of the new algorithm. Some testing results are performed on transaction data and medical data.Comment: Presented at DTMN, Sydney, Australia, July 28, 201

Does lowering a fever >101F in children improve clinical outcomes?

Treating fever significantly increases comfort, activity, feeding, and fluid intake and decreases the patient's temperature compared with placebo (strength of recommendation (SOR): A, multiple randomized controlled trials [RCTs]). It doesn't shorten or prolong the overall duration of illness or reduce the recurrence of febrile seizures (SOR: A, multiple RCTs). In patients with varicella, reducing fever prolongs the time it takes for lesions to crust, but doesn't appear to cause group A streptococcal necrotizing fasciitis (SOR: B, multiple prospective cohorts)

Prodrug Activation in Staphylococci and the Implications for Antimicrobial Development

Antibiotic resistance is an increasing concern for global health care, with some estimates suggesting that 10 million people will die from antibiotic resistant infections in the year 2050. Fueling this prospect, few antimicrobials are being actively developed and recently commercial entities have fled from the development of new anti-infectives. New antimicrobials and drug development strategies are urgently needed to revitalize this critical pipeline. While many putative antibiotics demonstrate promising in vitro potency, they routinely fail in vivo due to poor drug-like properties (e.g. oral bioavailability, serum-half life, toxicity) resulting in overly expensive drug development pipelines. Fortunately, drug-like properties can be modified through the addition of chemical protecting groups to create “prodrugs”. Lipophilic prodrugging strategies have been primarily deployed to remedy poor oral absorption but have also been utilized as a means of specifically delivering active drug to specific cells and tissue types. Here we demonstrate that lipophilic prodrugging of phosphonate antibiotics through a carboxy ester modification increases membrane permeability and enhances antimicrobial potency. Unfortunately, many lipophilic prodrugging strategies are rapidly cleaved in vivo by serum esterases rendering these potency and transport gains useless during clinical settings. Using three species of staphylococci, we identify and biochemically characterize two esterases, GloB and FrmB responsible for the activation of carboxy ester prodrugs. Additionally, we solve the three-dimensional structures of both GloB and FrmB, facilitating additional structure-guided design of promoieties. Finally, we characterize the substrate specificity of human and mouse sera, enabling the development of promoieties which are selectively activated by microbial species. These findings not only allow the development of novel anti-staphylococcals but lay the framework for identification of microbial-specific prodrug design and design of long-lasting serum prodrugs. As lipophilic prodrugging expands the number of compounds that are membrane permeable, we expect that this approach will facilitate an expansion of the number of potential drugs

Governor Patrick Signs Bill to Control Health Care Costs

Surveys of foliar endophytes from the Acadian forest region over the past three decades have identified numerous phylogenetically diverse fungi producing natural products toxic to forest pests and diseases. The life histories of some conifer endophytes can be restricted to plant foliage or may include saprotrophic phases on other plants tissues or even alternate hosts. Considering the potentially broad host preferences of conifer endophytes we explored fungi isolated from understory species and their metabolites as part of an ongoing investigation of fungal biodiversity from the Acadian forest. We report a hitherto unidentified Xylariomycetidae species isolated from symptomatic Labrador tea (Rhododendron groenlandicum) leaves and mountain laurel (Kalmia latifolia) collected in coastal southern New Brunswick, Canada. Morphological and phylogenetic evidence demonstrated the unknown species was a novel Synnemapestaloides (Sporocadaceae) species, described here as Syn. ericacearum. A preliminary screening assay indicated that the culture filtrate extract of the new species was potently antifungal towards the biotrophic pathogen Microbotryum violaceum, warranting an investigation of its natural products. Two natural products possessing a rare 1,3-benzodioxin-4-one scaffold, synnemadoxins A-B (1-2), and their postulated precursor, synnemadiacid A (3), were characterized as new structures and assessed for antimicrobial activity. All isolated compounds elicited in vitro inhibitory antifungal activity towards M. violaceum at 2.3 μg mL-1 and moderate antibiotic activity. Further, the characterization of synnemadoxins A-B provided a perspective on the biosynthesis of some related 1,3-benzodioxin-4-ones produced by other fungi within the Xylariales

Fundamental Characteristics of AAA+ Protein Family Structure and Function

Many complex cellular events depend on multiprotein complexes known as molecular machines to efficiently couple the energy derived from adenosine triphosphate hydrolysis to the generation of mechanical force. Members of the AAA+ ATPase superfamily (ATPases Associated with various cellular Activities) are critical components of many molecular machines. AAA+ proteins are defined by conserved modules that precisely position the active site elements of two adjacent subunits to catalyze ATP hydrolysis. In many cases, AAA+ proteins form a ring structure that translocates a polymeric substrate through the central channel using specialized loops that project into the central channel. We discuss the major features of AAA+ protein structure and function with an emphasis on pivotal aspects elucidated with archaeal proteins

Use of cumulative incidence of novel influenza A/H1N1 in foreign travelers to estimate lower bounds on cumulative incidence in Mexico

Background: An accurate estimate of the total number of cases and severity of illness of an emerging infectious disease is required both to define the burden of the epidemic and to determine the severity of disease. When a novel pathogen first appears, affected individuals with severe symptoms are more likely to be diagnosed. Accordingly, the total number of cases will be underestimated and disease severity overestimated. This problem is manifest in the current epidemic of novel influenza A/H1N1. Methods and Results: We used a simple approach to leverage measures of incident influenza A/H1N1 among a relatively small and well observed group of US, UK, Spanish and Canadian travelers who had visited Mexico to estimate the incidence among a much larger and less well surveyed population of Mexican residents. We estimate that a minimum of 113,000 to 375,000 cases of novel influenza A/H1N1 have occurred in Mexicans during the month of April, 2009. Such an estimate serves as a lower bound because it does not account for underreporting of cases in travelers or for nonrandom mixing between Mexican residents and visitors, which together could increase the estimates by more than an order of magnitude. Conclusions: We find that the number of cases in Mexican residents may exceed the number of confirmed cases by two to three orders of magnitude. While the extent of disease spread is greater than previously appreciated, our estimate suggests that severe disease is uncommon since the total number of cases is likely to be much larger than those of confirmed cases