A Shift in Central Metabolism Accompanies Virulence Activation in Pseudomonas aeruginosa.

The availability of energy has significant impact on cell physiology. However, the role of cellular metabolism in bacterial pathogenesis is not understood. We investigated the dynamics of central metabolism during virulence induction by surface sensing and quorum sensing in early-stage biofilms of the multidrug-resistant bacterium Pseudomonas aeruginosa We established a metabolic profile for P. aeruginosa using fluorescence lifetime imaging microscopy (FLIM), which reports the activity of NADH in live cells. We identified a critical growth transition period during which virulence is activated. We performed FLIM measurements and direct measurements of NADH and NAD+ concentrations during this period. Here, planktonic (low-virulence) and surface-attached (virulence-activated) populations diverged into distinct metabolic states, with the surface-attached population exhibiting FLIM lifetimes that were associated with lower levels of enzyme-bound NADH and decreasing total NAD(H) production. We inhibited virulence by perturbing central metabolism using citrate and pyruvate, which further decreased the enzyme-bound NADH fraction and total NAD(H) production and suggested the involvement of the glyoxylate pathway in virulence activation in surface-attached populations. In addition, we induced virulence at an earlier time using the electron transport chain oxidase inhibitor antimycin A. Our results demonstrate the use of FLIM to noninvasively measure NADH dynamics in biofilms and suggest a model in which a metabolic rearrangement accompanies the virulence activation period.IMPORTANCE The rise of antibiotic resistance requires the development of new strategies to combat bacterial infection and pathogenesis. A major direction has been the development of drugs that broadly target virulence. However, few targets have been identified due to the species-specific nature of many virulence regulators. The lack of a virulence regulator that is conserved across species has presented a further challenge to the development of therapeutics. Here, we identify that NADH activity has an important role in the induction of virulence in the pathogen P. aeruginosa This finding, coupled with the ubiquity of NADH in bacterial pathogens, opens up the possibility of targeting enzymes that process NADH as a potential broad antivirulence approach

Dynamic simulation of a mobile manipulator with joint friction.

Mission criticality in disaster search and rescue robotics highlights the requirement of specialized equipment. Specialized manipulators that can be mounted on existing mobile platforms can improve rescue process. However specialized manipulators capable of lifting heavy loads are not yet available. Moreover, effect of joint friction in these manipulators requires further analysis. To address these issues, concepts of model based design and concurrent engineering are applied to develop a virtual prototype of the manipulator mechanism. Closed loop manipulator mechanism actuated by prismatic actuators is proposed herein. The mechanics model of the manipulator is presented here as a set of equations and as multibody models. Mechanistic simulation of the virtual prototype has been conducted and the results are presented. Combined friction model that comprises Coulomb, viscous and Stribeck friction is used to compute frictional forces and torques generated at each one degree of freedom translational and rotational joints. Multidisciplinary approach employed in this work improves product design cycle time for complex mechanisms. Kinematic and dynamic parameters are presented in this paper. Friction forces and torques from simulation are also presented in addition to the visual representation of the virtual prototype

Attributes and Implications of Gender Discriminations in Women’s Education in a Rural Area of Coimbatore, Tamil Nadu: the Findings of Focus Group Discussions

India is a fast-growing economy and the scientific and technical advancements in the county have tremendously improved. But when we look at the state of women in our country, we are very backward and women are subjected to severe gender discriminations. This is evident from our falling sex ratio, gender gap in education, employment, health status and the high rates of violence against women. There are many reasons for this unfortunate status of women in our country. Our social norms, cultural beliefs and the patriarchal mindset have made women vulnerable and deprived of freedom and wellbeing

Power Generalized KM-Transformation for Non-Monotone Failure Rate Distribution

Lifetime models with a non-monotone hazard rate $\hspace{0.12cm}$ function have a wide range of applications in engineering and lifetime data analysis. There are different bathtub shaped failure rate models that are available in reliability literature. Kavya and Manoharan (2021) introduced a new transformation called KM-transformation which was found to be more useful in reliability and lifetime data analysis. Power generalization technique would be the best approach to deal with a system whose components are connected in series, in which the distribution of the component is KM-transformation of any lifetime model. In this article, we introduce a new lifetime model, Power Generalized KM-Transformation (PGKM) for Non-Monotone Failure Rate Distribution, which shows monotone and non-monotone behavior for the hazard rate function for different choices of values of parameters. We derive the moments, moment generating function, characteristic function, quantiles, entropy etc of the proposed distribution. Distributions of minimum and maximum are obtained. Estimation of parameters of the distribution is performed via maximum likelihood method. A simulation study is performed to validate the maximum likelihood estimator (MLE). Analysis of three sets of real data are given

Effect of turmeric and curcumin on BP-DNA adducts

Many human cancers that are widely prevalent today can be prevented through modifications in life-styles, of which diet appears to be an important agent. Several dietary constituents modulate the process of carcinogenesis and prevent genotoxicity. Many plant constituents including turmeric appear to be potent antimutagens and antioxidants. Therefore the modulatory effects of turmeric and curcumin on the levels of benzo[a]pyrene induced DNA adducts in the livers of rats were studied by the newly developed 32P-postlabelling assay method. Turmeric when fed at 0.1, 0.5 and 3% and the active principle of turmeric (curcumin) when fed at a level of 0.03% in the diet for 4 weeks significantly reduced the level of BP-DNA adducts including the major adduct dG-N2-BP, formed within 24 h in response to a single i.p. injection of benzo[a]pyrene. The significance of these effects in terms of the potential anticarcinogenic effects of turmeric is discussed. Further, these results strengthen the various other biological effects of turmeric which have direct relevance to anticarcinogenesis and chemoprevention

Distinct phase-amplitude couplings distinguish cognitive processes in human attention

Abstract Spatial attention is the cognitive function that coordinates the selection of visual stimuli with appropriate behavioral responses. Recent studies have reported that phase-amplitude coupling (PAC) of low and high frequencies covaries with spatial attention, but differ on the direction of covariation and the frequency ranges involved. We hypothesized that distinct phase-amplitude frequency pairs have differentiable contributions during tasks that manipulate spatial attention. We investigated this hypothesis with electrocorticography (ECoG) recordings from participants who engaged in a cued spatial attention task. To understand the contribution of PAC to spatial attention we classified cortical sites by their relationship to spatial variables or behavioral performance. Local neural activity in spatial sites was sensitive to spatial variables in the task, while local neural activity in behavioral sites correlated with reaction time. We found two PAC frequency clusters that covaried with different aspects of the task. During a period of cued attention, delta-phase/high-gamma (DH) PAC was sensitive to cue direction in spatial sites. In contrast, theta-alpha-phase/beta-low-gamma-amplitude (TABL) PAC robustly correlated with future reaction times in behavioral sites. Finally, we investigated the origins of TABL PAC and found it corresponded to behaviorally relevant, sharp waveforms, which were also coupled to a low frequency rhythm. We conclude that TABL and DH PAC correspond to distinct mechanisms during spatial attention tasks and that sharp waveforms are elements of a coupled dynamical process

Why do gallium clusters have a higher melting point than the bulk?

Density functional molecular dynamical simulations have been performed on Ga$_{17}$ and Ga$_{13}$ clusters to understand the recently observed higher-than-bulk melting temperatures in small gallium clusters [Breaux {\em et al.}, Phys. Rev. Lett. {\bf 91}, 215508 (2003)]. The specific-heat curve, calculated with the multiple-histogram technique, shows the melting temperature to be well above the bulk melting point of 303 K, viz. around 650 K and 1400 K for Ga$_{17}$ and Ga$_{13}$, respectively. The higher-than-bulk melting temperatures are attributed mainly to the covalent bonding in these clusters, in contrast with the covalent-metallic bonding in the bulk.Comment: 4 pages, including 6 figures. accepted for publication in Phys. Rev. Let

Pair production of charged Higgs bosons in the Left-Right Twin Higgs model at the ILC and LHC

Left-Right twin Higgs(LRTH) model predicts the existence of a pair of charged Higgs $\phi^{\pm}$. In this paper, we study the production of the charged Higgs bosons pair $\phi^{\pm}$ via the process $e^{+}e^{-}\to \phi^{+}\phi^{-}$ at the International Linear Collider(ILC). The numerical results show that the production rates are at the level of several tens fb, this process can produce the adequate distinct multi-jet final states and the SM background can be efficiently reduced. We also discuss the charged Higgs boson pair production via the process $q\bar{q}\to \phi^{+}\phi^{-}$ at the $CERN$ Large Hadron Collider(LHC) and estimate there production rates. We find that, as long as the charged Higgs bosons are not too heavy, they can be abundantly produced at the LHC. The possible signatures of these new particles might be detected at the ILC and LHC experiments.Comment: 15 pages, 5 figures, discussion extended, reference added, typos fixed, revised version to be published in Eur.Phys.J.