Potentiating antibacterial activity by predictably enhancing endogenous microbial ROS production

The ever-increasing incidence of antibiotic-resistant infections combined with a weak pipeline of new antibiotics has created a global public health crisis1. Accordingly, novel strategies for enhancing our antibiotic arsenal are needed. As antibiotics kill bacteria in part by inducing reactive oxygen species (ROS)2–4, we reasoned that targeting microbial ROS production might potentiate antibiotic activity. Here we show that ROS production can be predictably enhanced in Escherichia coli, increasing the bacteria’s susceptibility to oxidative attack. We developed an ensemble, genome-scale metabolic modeling approach capable of predicting ROS production in E. coli. The metabolic network was systematically perturbed and its flux distribution analyzed to identify targets predicted to increase ROS production. In silico–predicted targets were experimentally validated and shown to confer increased susceptibility to oxidants. Validated targets also increased susceptibility to killing by antibiotics. This work establishes a systems-based method to tune ROS production in bacteria and demonstrates that increased microbial ROS production can potentiate killing by oxidants and antibiotics

Ideological Labels in America

This paper extends Ellis and Stimson’s (Ideology in America. New York: Cambridge UniversityPress, 2012) study of the operational-symbolic paradox using issue-level measures of ideological incongruence based on respondent positions and symbolic labels for these positions across 14 issues. Like Ellis and Stimson, we find that substantial numbers—over 30 %—of Americans experience conflicted conservatism. Our issue-level data reveal, furthermore, that conflicted conservatism is most common on the issues of education and welfare spending. In addition, we also find that 20 % of Americans exhibit conflicted liberalism. We then replicate Ellis and Stimson’s finding that conflicted conservatism is associated with low sophistication and religiosity, but also find that it is associated with being socialized in a post-1960s generation and using Fox News as a main news source. Finally, we show the important role played by identities, with both conflicted conservatism and conflicted liberalism linked with partisan and ideological identities, and conflicted liberalism additionally associated with ethnic identities

Measurement of the WW and WZ production cross section using final states with a charged lepton and heavy-flavor jets in the full CDF Run II data set

Citation: Aaltonen, T., Amerio, S., Amidei, D., Anastassov, A., Annovi, A., Antos, J., . . . Zucchelli, S. (2016). Measurement of the WW and WZ production cross section using final states with a charged lepton and heavy-flavor jets in the full CDF Run II data set. Physical Review D - Particles, Fields, Gravitation and Cosmology, 94(3). doi:10.1103/PhysRevD.94.032008We present a measurement of the total WW and WZ production cross sections in pp collision at s=1.96 TeV, in a final state consistent with leptonic W boson decay and jets originating from heavy-flavor quarks from either a W or a Z boson decay. This analysis uses the full data set collected with the CDF II detector during Run II of the Tevatron collider, corresponding to an integrated luminosity of 9.4 fb-1. An analysis of the dijet mass spectrum provides 3.7? evidence of the summed production processes of either WW or WZ bosons with a measured total cross section of ?WW+WZ=13.7±3.9 pb. Independent measurements of the WW and WZ production cross sections are allowed by the different heavy-flavor decay patterns of the W and Z bosons and by the analysis of secondary-decay vertices reconstructed within heavy-flavor jets. The productions of WW and of WZ dibosons are independently seen with significances of 2.9? and 2.1?, respectively, with total cross sections of ?WW=9.4±4.2 pb and ?WZ=3.7-2.2+2.5 pb. The measurements are consistent with standard-model predictions. © 2016 American Physical Society

ass and lifetime measurements of bottom and charm baryons in ppˉp\bar p collisions at $\sqrt{s}= 1.96 TeV

We report on mass and lifetime measurements of several ground state charmed and bottom baryons, using a data sample corresponding to 9.6 $\textrm{fb}^{-1}$ from $p\bar p$ collisions at $\sqrt{s}=1.96$ TeV, and recorded with the Collider Detector at Fermilab. Baryon candidates are reconstructed from data collected with an online event selection designed for the collection of long-lifetime heavy-flavor decay products and a second event selection designed to collect $J/\psi \rightarrow \mu^+ \, \mu^-$ candidates. First evidence for the process $\Omega_b^- \rightarrow \Omega_c^0 \, \pi^-$ is presented with a significance of $3.3\sigma$. We measure the following baryon masses: \begin{eqnarray} M(\Xi_c^{0}) = 2470.85\pm0.24(stat)\pm0.55(syst) \, MeV/c^2, \nonumber M(\Xi_c^{+}) = 2468.00\pm0.18(stat)\pm0.51(syst) \, MeV/c^2, \nonumber \\ M(\Lambda_b) = 5620.15\pm0.31(stat)\pm0.47(syst) \, MeV/c^2, \nonumber \\ M(\Xi_b^-) = 5793.4\pm1.8(stat)\pm0.7(syst) \, MeV/c^2, \nonumber \\ M(\Xi_b^0) = 5788.7\pm4.3(stat)\pm1.4(syst) \, MeV/c^2, \, and \nonumber \\ M(\Omega_b^-) = 6047.5\pm3.8(stat)\pm0.6(syst) \, MeV/c^2. \nonumber \end{eqnarray} The isospin splitting of the $\Xi_b^{-,0}$ states is found to be $M(\Xi_b^-)-M(\Xi_b^0)=4.7\pm4.7(stat)\pm0.7(syst)$ MeV/$c^2$. The isospin splitting of the $\Xi_c^{0,+}$ states is found to be $M(\Xi_c^0)-M(\Xi_c^+)$ = $2.85\pm0.30(stat)\pm0.04(syst)$ MeV/$c^2$. The following lifetime measurements are made: \begin{eqnarray} \tau(\Lambda_b) = 1.565\pm0.035(stat)\pm0.020(syst) \, ps, \nonumber \\ \tau(\Xi_b^-) = 1.32\pm0.14(stat)\pm0.02(syst) \, ps, \nonumber \\ \tau(\Omega_b^-) = 1.66^{+0.53}_{-0.40}(stat)\pm0.02(syst) \, ps. \nonumber \end{eqnarray

Appeals to evidence for the resolution of wicked problems: the origins and mechanisms of evidentiary bias

Wicked policy problems are often said to be characterized by their ‘intractability’, whereby appeals to evidence are unable to provide policy resolution. Advocates for ‘Evidence Based Policy’ (EBP) often lament these situations as representing the misuse of evidence for strategic ends, while critical policy studies authors counter that policy decisions are fundamentally about competing values, with the (blind) embrace of technical evidence depoliticizing political decisions. This paper aims to help resolve these conflicts and, in doing so, consider how to address this particular feature of problem wickedness. Specifically the paper delineates two forms of evidentiary bias that drive intractability, each of which is reflected by contrasting positions in the EBP debates: ‘technical bias’ - referring to invalid uses of evidence; and ‘issue bias’ - referring to how pieces of evidence direct policy agendas to particular concerns. Drawing on the fields of policy studies and cognitive psychology, the paper explores the ways in which competing interests and values manifest in these forms of bias, and shape evidence utilization through different mechanisms. The paper presents a conceptual framework reflecting on how the nature of policy problems in terms of their complexity, contestation, and polarization can help identify the potential origins and mechanisms of evidentiary bias leading to intractability in some wicked policy debates. The discussion reflects on whether being better informed about such mechanisms permit future work that may lead to strategies to mitigate or overcome such intractability in the future

Confirmation bias in the utilization of others' opinion strength

Humans tend to discount information that undermines past choices and judgments. This confirmation bias has significant impact on domains ranging from politics to science and education. Little is known about the mechanisms underlying this fundamental characteristic of belief formation. Here we report a mechanism underlying the confirmation bias. Specifically, we provide evidence for a failure to use the strength of others' disconfirming opinions to alter confidence in judgments, but adequate use when opinions are confirmatory. This bias is related to reduced neural sensitivity to the strength of others' opinions in the posterior medial prefrontal cortex when opinions are disconfirming. Our results demonstrate that existing judgments alter the neural representation of information strength, leaving the individual less likely to alter opinions in the face of disagreement

Strategies for recruiting Hispanic women into a prospective cohort study of modifiable risk factors for gestational diabetes mellitus

BACKGROUND: The purpose of this article was to describe effective strategies for recruitment of Hispanic women into a prospective cohort study of modifiable risk factors for gestational diabetes mellitus (GDM). Although Hispanic women have two to four times the risk of developing GDM compared with non-Hispanic white women, few GDM prevention studies have included Hispanic women. METHODS: The study was conducted in the ambulatory obstetrical practices of Baystate Medical Center located in a socioeconomically and ethnically diverse city in Massachusetts. The study employed a range of strategies to recruit Hispanic women based on a review of the literature as well as prior experience with the study population. RESULTS: Over a period of 32 months, a total of 851 Hispanic prenatal care patients were recruited. Among eligible women, 52.4% agreed to participate. Participants were young (70% <25 years), with low levels of education, and on public health insurance (81.5%); 88% were unmarried. Study design features such as use of bilingual recruiters, a flexible recruitment process, training recruiters to be culturally sensitive, use of culturally tailored materials, prescreening participants, participant compensation, seeking the cooperation of clinic staff, and continuous monitoring of recruitment goals emerged as important issues influencing recruitment. CONCLUSIONS: Findings suggest that investigators can successfully recruit pregnant women from ethnic minority groups of low socioeconomic status into observational studies. The study provides culturally appropriate recruitment strategies useful for practice-based settings recruiting Hispanic research participation

Measurement of sin2 θlept eff using eþe− pairs from γ=Z bosons produced in pp collisions at a center-of-momentum energy of 1.96 TeV

At the Fermilab Tevatron proton-antiproton (pp¯) collider, Drell-Yan lepton pairs are produced in the process pp¯→e+e−+X through an intermediate γ∗/Z boson. The forward-backward asymmetry in the polar-angle distribution of the e− as a function of the e+e−-pair mass is used to obtain sin2θlepteff, the effective leptonic determination of the electroweak-mixing parameter sin2θW. The measurement sample, recorded by the Collider Detector at Fermilab (CDF), corresponds to 9.4  fb−1 of integrated luminosity from pp¯ collisions at a center-of-momentum energy of 1.96 TeV, and is the full CDF Run II data set. The value of sin2θlepteff is found to be 0.23248±0.00053. The combination with the previous CDF measurement based on μ+μ− pairs yields sin2θlepteff=0.23221±0.00046. This result, when interpreted within the specified context of the standard model assuming sin2θW=1−M2W/M2Z and that the W- and Z-boson masses are on-shell, yields sin2θW=0.22400±0.00045, or equivalently a W-boson mass of 80.328±0.024  GeV/c2

Nonlinear beam self-cleaning in a coupled cavity composite laser based on multimode fiber

We study a coupled cavity laser configuration where a passively Q-switched Nd:YAG microchip laser is combined with an extended cavity, including a doped multimode fiber. For appropriate coupling levels with the extended cavity, we observed that beam selfcleaning was induced in the multimode fiber thanks to nonlinear modal coupling, leading to a quasi-single mode laser output. In the regime of beam self-cleaning, laser pulse duration was reduced from 525 to 225 ps. We also observed a Q-switched mode-locked operation, where spatial self-cleaning was accompanied by far-detuned nonlinear frequency conversion in the active multimode fiber

Improving the clinical assessment of consciousness with advances in electrophysiological and neuroimaging techniques

In clinical neurology, a comprehensive understanding of consciousness has been regarded as an abstract concept - best left to philosophers. However, times are changing and the need to clinically assess consciousness is increasingly becoming a real-world, practical challenge. Current methods for evaluating altered levels of consciousness are highly reliant on either behavioural measures or anatomical imaging. While these methods have some utility, estimates of misdiagnosis are worrisome (as high as 43%) - clearly this is a major clinical problem. The solution must involve objective, physiologically based measures that do not rely on behaviour. This paper reviews recent advances in physiologically based measures that enable better evaluation of consciousness states (coma, vegetative state, minimally conscious state, and locked in syndrome). Based on the evidence to-date, electroencephalographic and neuroimaging based assessments of consciousness provide valuable information for evaluation of residual function, formation of differential diagnoses, and estimation of prognosis