Genomic Correlates of Virulence Attenuation in the Deadly Amphibian Chytrid Fungus, Batrachochytrium dendrobatidis.

Emerging infectious diseasespose a significant threat to global health, but predicting disease outcomes for particular species can be complicated when pathogen virulence varies across space, time, or hosts. The pathogenic chytrid fungus Batrachochytrium dendrobatidis (Bd) has caused worldwide declines in frog populations. Not only do Bd isolates from wild populations vary in virulence, but virulence shifts can occur over short timescales when Bd is maintained in the laboratory. We leveraged changes in Bd virulence over multiple generations of passage to better understand mechanisms of pathogen virulence. We conducted whole-genome resequencing of two samples of the same Bd isolate, differing only in passage history, to identify genomic processes associated with virulence attenuation. The isolate with shorter passage history (and greater virulence) had greater chromosome copy numbers than the isolate maintained in culture for longer, suggesting that virulence attenuation may be associated with loss of chromosome copies. Our results suggest that genomic processes proposed as mechanisms for rapid evolution in Bd are correlated with virulence attenuation in laboratory culture within a single lineage of Bd. Moreover, these genomic processes can occur over extremely short timescales. On a practical level, our results underscore the importance of immediately cryo-archiving new Bd isolates and using fresh isolates, rather than samples cultured in the laboratory for long periods, for laboratory infection experiments. Finally, when attempting to predict disease outcomes for this ecologically important pathogen, it is critical to consider existing variation in virulence among isolates and the potential for shifts in virulence over short timescales

Prolonged Survival in Patients with Lung Cancer with Diabetes Mellitus

IntroductionPatients with lung cancer have a high frequency of comorbidity. Data on the impact of diabetes mellitus, the most frequent endocrine disorder, on the prognosis of lung cancer are conflicting. The aim was to investigate the impact of diabetes mellitus on survival in lung cancer.MethodWe analyzed data from a cohort, the Nord-Trøndelag Health Study (HUNT study) linked to the Norwegian Cancer Registry and controlled the results using two lung cancer studies, the Pemetrexed Gemcitabine study and the Norwegian Lung Cancer Biobank. Survival in lung cancer with and without diabetes mellitus was compared using the Kaplan-Meier method and Cox regression model for each study and the studies combined.ResultsOne thousand six hundred seventy-seven cases of lung cancer were included, 1031 from HUNT study, 436 from the Pemetrexed Gemcitabine study, and 210 from the Norwegian Lung Cancer Biobank registry, and among these 77 patients had diabetes mellitus. In the combined analysis, patients with lung cancer with diabetes mellitus had increased survival compared with those without (p = 0.005). The 1-, 2-, and 3-year survival in patients with lung cancer with and without diabetes mellitus were 43% versus 28%, 19% versus 11%, and 3% versus 1%, respectively. Adjusting for age, gender, histology, and stage of disease in the Cox regression model, the hazard ratio for survival in patients with lung cancer with diabetes mellitus was 0.55 (95% CI, 0.41–0.75) as compared with without.ConclusionPatients with lung cancer with diabetes mellitus have an increased survival compared with those without diabetes mellitus

Shrinking-Hole Colloidal Lithography: Self-Aligned Nanofabrication of Complex Plasmonic Nanoantennas

Plasmonic nanoantennas create locally strongly enhanced electric fields in so-called hot spots. To place a relevant nanoobject with high accuracy in such a hot spot is crucial to fully capitalize on the potential of nanoantennas to control, detect, and enhance processes at the nanoscale. With state-of-the-art nanofabrication, in particular when several materials are to be used, small gaps between antenna elements are sought, and large surface areas are to be patterned, this is a grand challenge. Here we introduce self-aligned, bottom-up and self-assembly based Shrinking-Hole Colloidal Lithography, which provides (i) unique control of the size and position of subsequently deposited particles forming the nanoantenna itself, and (ii) allows delivery of nanoobjects consisting of a material of choice to the antenna hot spot, all in a single lithography step and, if desired, uniformly covering several square centimeters of surface. We illustrate the functionality of SHCL nanoantenna arrangements by (i) an optical hydrogen sensor exploiting the polarization dependent sensitivity of an Au-Pd nanoantenna ensemble; and (ii) single particle hydrogen sensing with an Au dimer nanoantenna with a small Pd nanoparticle in the hot spot

Asthma, asthma control and risk of ischemic stroke:The HUNT study

Background: Asthma, a chronic inflammatory airway disease, shares common pathophysiological mechanisms with ischemic stroke. The aim of the study is to assess the association between asthma, levels of asthma control and ischemic stroke risk in men and women and by smoking habits. Methods: This prospective population-based cohort study utilized data on 58 712 adults from HUNT Study in Norway free from stroke. Self-reported asthma was categorized as ever asthma, non-active asthma and active asthma (i.e., being on asthma medication within 12 months of the baseline). Asthma control was defined ac-cording to the Global Initiative for Asthma questionnaire and was categorized into controlled and not controlled asthma. Stroke was ascertained by linking HUNT data with Nord-Trøndelag hospital records and the Norwegian Patient Registry. Results: During a mean follow-up of 17.3 �5.3 years, 2619 participants (4.5%) had a first stroke. Not controlled asthma was associated with a modest increased risk of stroke (adjusted HR 1.34, 95%CI 1.03–1.73). Subgroup analyses revealed that the respective association was stronger among those with history of smoking (HR 1.48, 95%CI 1.10–2.00) and males (HR 1.55, 95%CI 1.12–2.16) while absent in non-smokers (HR 1.02, 95%CI 0.61–1.70) and females (HR 1.05, 95%CI 0.69–1.60). Likewise, active asthma was associated with similar increased stroke risk among smokers and males and absent in non-smokers and females. Conclusions: Symptomatic and active asthma was associated with a modest increased relative risk for ischemic stroke in smokers and males. Future studies should clarify the difference in risks and mechanisms between different phenotypes of asthma

Unravelling CO oxidation reaction kinetics on single Pd nanoparticles in nanoconfinement using a nanofluidic reactor and DSMC simulations

Steady state catalytic oxidation of CO in nanofluidic channels decorated with Pd nano particles was studied using the Direct Simulation Monte Carlo (DSMC) method. Diffusion, collision, adsorption, desorption and reaction processes are simulated simultaneously. The influence of various adsorption (sticking coefficient, saturation coverage), desorption (activation energy, pre-exponential factor) and reaction (activation barrier) parameters on the final CO2 turnover are determined. These effects are considered to tune DSMC surface reaction model with respect to the experimental results. With DSMC, it was possible to get insights on reactivity of the individual Pd particles and the resulting varying reaction conditions along the channel due to local conversion effects. From the local coverages, the limit of CO:O2 inlet ratio to get maximum CO2 turnover without poisoning the catalyst with CO were determined. The approach paves the way to accurately represent micro- and nanoscale flows at the same system size as that of experiments

Bulk-Processed Plasmonic Plastic Nanocomposite Materials for Optical Hydrogen Detection

Conspectus Sensors are ubiquitous, andtheir importanceis only going to increaseacross many areas of modern technology. In this respect, hydrogengas (H-2) sensors are no exception since they allow mitigationof the inherent safety risks associated with mixtures of H-2 and air. The deployment of H-2 technologies is rapidlyaccelerating in emerging energy, transport, and green steel-makingsectors, where not only safety but also process monitoring sensorsare in high demand. To meet this demand, cost-effective and scalableroutes for mass production of sensing materials are required. Here,the state-of-the-art often resorts to processes derived from the microelectronicsindustry where surface-based micro- and nanofabrication are the methodsof choice and where (H-2) sensor manufacturing is no exception. In this Account, we discuss how our recent efforts to develop sensorsbased on plasmonic plastics may complement the current state-of-the-art.We explore a new H-2 sensor paradigm, established througha series of recent publications, that combines (i) the plasmonic opticalH(2) detection principle and (ii) bulk-processed nanocompositematerials. In particular, plasmonic plastic nanocomposite sensingmaterials are described that comprise plasmonic H-2-sensitivecolloidally synthesized nanoparticles dispersed in a polymer matrixand enable the additive manufacturing of H-2 sensors ina cost-effective and scalable way. We first discuss the concept ofplasmonic plastic nanocomposite materials for the additive manufacturingof an active plasmonic sensing material on the basis of the threekey components that require individual and concerted optimization:(i) the plasmonic sensing metal nanoparticles, (ii) the surfactant/stabilizermolecules on the nanoparticle surface from colloidal synthesis, and(iii) the polymer matrix. We then introduce the working principleof plasmonic H-2 detection, which relies on the selectiveabsorption of H species into hydride-forming metal nanoparticles that,in turn, induces distinct changes in their optical plasmonic signaturein proportion to the H-2 concentration in the local atmosphere.Subsequently, we assess the roles of the key components of a plasmonicplastic for H-2 sensing, where we have established that(i) alloying Pd with Au and Cu eliminates hysteresis and introducesintrinsic deactivation resistance at ambient conditions, (ii) surfactant/stabilizermolecules can significantly accelerate and decelerate H-2 sorption and thus sensor response, and (iii) polymer coatings acceleratesensor response, reduce the limit of detection (LoD), and enable molecularfiltering for sensor operation in chemically challenging environments.Based on these insights, we discuss the rational development and detailedcharacterization of bulk-processed plasmonic plastics based on glassyand fluorinated matrix polymers and on tailored flow-chemistry-basedsynthesis of Pd and PdAu alloy colloidal nanoparticles with optimizedstabilizer molecules. In their champion implementation, they enablehighly stable H-2 sensors with response times in the 2 srange and an LoD of few 10 ppm of H-2. To put plasmonicplastics in a wider perspective, we also report their implementationusing different polymer matrix materials that can be used for 3D printingand (an)isotropic Au nanoparticles that enable the manufacturing ofmacroscopic plasmonic objects with, if required, dichroic opticalproperties and in amounts that can be readily upscaled. We advertisethat melt processing of plasmonic plastic nanocomposites is a viableroute toward the realization of plasmonic objects and sensors, producedby scalable colloidal synthesis and additive manufacturing techniques

Living on the edge of stability, the limits of the nuclear landscape

A first-principles description of nuclear systems along the drip lines presents a substantial theoretical and computational challenge. In this paper, we discuss the nuclear theory roadmap, some of the key theoretical approaches, and present selected results with a focus on long isotopic chains. An important conclusion, which consistently emerges from these theoretical analyses, is that three-nucleon forces are crucial for both global nuclear properties and detailed nuclear structure, and that many-body correlations due to the coupling to the particle continuum are essential as one approaches particle drip lines. In the quest for a comprehensive nuclear theory, high performance computing plays a key role.Comment: Contribution to proceedings of Nobel Symposium 152: Physics with radioactive beams, June 2012, Gothenburg, Swede

Non-Fermi liquid normal state of the Heavy Fermion superconductor UBe13

Non-Fermi liquid (NFL) behavior in the normal state of the heavy-fermion superconductor UBe13 is studied by means of low-temperature measurements of the specific heat, C, and electrical resistivity, \rho, on a high-quality single crystal in magnetic fields up to 15.5 T. At B=0, unconventional superconductivity forms at Tc=0.9 K out of an incoherent state, characterized by a large and strongly temperature dependent \rho(T). In the magnetic field interval 4 T \leq B \leq 10 T, \rho(T) follows a T^3/2 behavior for Tc(B)\leq T \leq 1 K, while \rho is proportional to T at higher temperatures. Corresponding Non-Fermi liquid behavior is observed in C/T as well and hints at a nearby antiferromagnetic (AF) quantum critical point (QCP) covered by the superconducting state. We speculate that the suppression of short-range AF correlations observed by thermal expansion and specific heat measurements below T_L \simeq 0.7 K (B=0) yields a field-induced QCP, T_L \to 0, at B=4.5 T.Comment: Presented at the M2S-2003 conference in Rio / Brazi