Fighting Bandits with a New Kind of Smoothness

We define a novel family of algorithms for the adversarial multi-armed bandit problem, and provide a simple analysis technique based on convex smoothing. We prove two main results. First, we show that regularization via the \emph{Tsallis entropy}, which includes EXP3 as a special case, achieves the $\Theta(\sqrt{TN})$ minimax regret. Second, we show that a wide class of perturbation methods achieve a near-optimal regret as low as $O(\sqrt{TN \log N})$ if the perturbation distribution has a bounded hazard rate. For example, the Gumbel, Weibull, Frechet, Pareto, and Gamma distributions all satisfy this key property.Comment: In Proceedings of NIPS, 201

Generalized Evidence Theory

Conflict management is still an open issue in the application of Dempster Shafer evidence theory. A lot of works have been presented to address this issue. In this paper, a new theory, called as generalized evidence theory (GET), is proposed. Compared with existing methods, GET assumes that the general situation is in open world due to the uncertainty and incomplete knowledge. The conflicting evidence is handled under the framework of GET. It is shown that the new theory can explain and deal with the conflicting evidence in a more reasonable way.Comment: 39 pages, 5 figure

Delineation of the Pasteurellaceae-specific GbpA-family of glutathione-binding proteins

<p>Abstract</p> <p>Background</p> <p>The Gram-negative bacterium <it>Haemophilus influenzae </it>is a glutathione auxotroph and acquires the redox-active tripeptide by import. The dedicated glutathione transporter belongs to the ATP-binding cassette (ABC)-transporter superfamily and displays more than 60% overall sequence identity with the well-studied dipeptide (Dpp) permease of <it>Escherichia coli</it>. The solute binding protein (SBP) that mediates glutathione transport in <it>H. influenzae </it>is a lipoprotein termed GbpA and is 54% identical to <it>E. coli </it>DppA, a well-studied member of family 5 SBP's. The discovery linking GbpA to glutathione import came rather unexpectedly as this import-priming SBP was previously annotated as a heme-binding protein (HbpA), and was thought to mediate heme acquisition. Nonetheless, although many SBP's have been implicated in more than one function, a prominent physiological role for GbpA and its partner permease in heme acquisition appears to be very unlikely. Here, we sought to characterize five representative GbpA homologs in an effort to delineate the novel GbpA-family of glutathione-specific family 5 SBPs and to further clarify their functional role in terms of ligand preferences.</p> <p>Results</p> <p>Lipoprotein and non-lipoprotein GbpA homologs were expressed in soluble form and substrate specificity was evaluated via a number of ligand binding assays. A physiologically insignificant affinity for hemin was observed for all five GbpA homologous test proteins. Three out of five test proteins were found to bind glutathione and some of its physiologically relevant derivatives with low- or submicromolar affinity. None of the tested SBP family 5 allocrites interacted with the remaining two GbpA test proteins. Structure-based sequence alignments and phylogenetic analysis show that the two binding-inert GbpA homologs clearly form a separate phylogenetic cluster. To elucidate a structure-function rationale for this phylogenetic differentiation, we determined the crystal structure of one of the GbpA family outliers from <it>H. parasuis</it>. Comparisons thereof with the previously determined structure of GbpA in complex with oxidized glutathione reveals the structural basis for the lack of allocrite binding capacity, thereby explaining the outlier behavior.</p> <p>Conclusions</p> <p>Taken together, our studies provide for the first time a collective functional look on a novel, <it>Pasteurellaceae</it>-specific, SBP subfamily of glutathione binding proteins, which we now term GbpA proteins. Our studies strongly implicate GbpA family SBPs in the priming step of ABC-transporter-mediated translocation of useful forms of glutathione across the inner membrane, and rule out a general role for GbpA proteins in heme acquisition.</p

Protecting the Viability of the Small Donor in Modern Elections

Campaign finance reform stands as one of the most important issues in today’s modern elections. From national to municipal contests, the influx of large donations places wealthy individuals—and interests—at odds with the average voter. Over the years, volumes of academic and legislative reforms have been proposed that encompass a wide range of electoral subject matter. From Citizens United to Federal Elections Commission (FEC) control mechanisms, solutions on how to change our campaign finance regulatory regime cover a large and diverse area of law and policy. However, the central theme throughout these reforms is maximizing transparency and curbing the undue influence of candidates through large donations

Perdeuterated GbpA Enables Neutron Scattering Experiments of a Lytic Polysaccharide Monooxygenase

publishedVersio

Virulence of Streptococcus mutans : an intrafamilial cohort study on transmission of genotypes

The main aims of this cohort study were to measure the intrafamilial risk of transmission, sharing and stability of the most virulent S. mutans genotypes. A total of 392 clinical isolates of S. mutans obtained from caries-active adults and genotyped to evaluate their transmissibility over time. After extraction of the chromosomal DNA, PCR were performed to detect the genes involved in the production of GbpA (gbpA) and mutacin types I, II, III and IV (mutAI, mutAII, mutAIII and mutAIV). The gbpA, mutAI, mutAII, mutAIII and mutAIV genes were detected in 77.3, 12.5, 51, 16.6 and 89.8% of S. mutans isolates, respectively. The virulence of S. mutans was associated with its transmission (P< 0.01) and stability (P = 0.01), with the most virulent genotypes having higher transmissibility (RR = 1.83, 95% CI 1.44 to 2.32) and higher stability in the oral cavity (RR = 1.52, 95% CI 1.06 to 2.19). Genotypes with the genetic information to synthesize GbpA and mutacins present an important ecological advantage in the process of colonization by S. mutans; they remain stable among the oral microbiota of the host and favor intrafamilial transmission

Tangled up in fibers: How a lytic polysaccharide monooxygenase binds its chitin substrate

submittedVersio

Camostat mesylate inhibits SARS-CoV-2 activation by TMPRSS2-related proteases and its metabolite GBPA exerts antiviral activity

Background: Antivirals are needed to combat the COVID-19 pandemic, which is caused by SARS-CoV-2. The clinically-proven protease inhibitor Camostat mesylate inhibits SARS-CoV-2 infection by blocking the virus-activating host cell protease TMPRSS2. However, antiviral activity of Camostat mesylate metabolites and potential viral resistance have not been analyzed. Moreover, antiviral activity of Camostat mesylate in human lung tissue remains to be demonstrated. Methods: We used recombinant TMPRSS2, reporter particles bearing the spike protein of SARS-CoV-2 or authentic SARS-CoV-2 to assess inhibition of TMPRSS2 and viral entry, respectively, by Camostat mesylate and its metabolite GBPA. Findings: We show that several TMPRSS2-related proteases activate SARS-CoV-2 and that two, TMPRSS11D and TMPRSS13, are robustly expressed in the upper respiratory tract. However, entry mediated by these proteases was blocked by Camostat mesylate. The Camostat metabolite GBPA inhibited recombinant TMPRSS2 with reduced efficiency as compared to Camostat mesylate. In contrast, both inhibitors exhibited similar antiviral activity and this correlated with the rapid conversion of Camostat mesylate into GBPA in the presence of serum. Finally, Camostat mesylate and GBPA blocked SARS-CoV-2 spread in human lung tissue ex vivo and the related protease inhibitor Nafamostat mesylate exerted augmented antiviral activity. Interpretation: Our results suggest that SARS-CoV-2 can use TMPRSS2 and closely related proteases for spread in the upper respiratory tract and that spread in the human lung can be blocked by Camostat mesylate and its metabolite GBPA