Complex Precipitation Pathways in Multi-Component Alloys

One usual way to strengthen a metal is to add alloying elements and to control the size and the density of the precipitates obtained. However, precipitation in multicomponent alloys can take complex pathways depending on the relative diffusivity of solute atoms and on the relative driving forces involved. In Al-Zr-Sc alloys, atomic simulations based on first-principle calculations combined with various complementary experimental approaches working at different scales reveal a strongly inhomogeneous structure of the precipitates: owing to the much faster diffusivity of Sc compared with Zr in the solid solution, and to the absence of Zr and Sc diffusion inside the precipitates, the precipitate core is mostly Sc-rich, whereas the external shell is Zr-rich. This explains previous observations of an enhanced nucleation rate in Al-Zr-Sc alloys compared with binary Al-Sc alloys, along with much higher resistance to Ostwald ripening, two features of the utmost importance in the field of light high-strength materials

The effect of Ni:Co ratio on the elemental phase partitioning in γ-γ′ Ni-Co-Al-Ti-Cr alloys

Atom probe tomography has been used to characterise the effect of varying Ni:Co ratio on elemental phase partitioning at 800 °C in γ-γ′ alloys derived from the Ni-Co-Al-Ti-Cr system. In all alloys tested, Al and Ti were found to partition preferentially to the γ′ phase, whereas Co and Cr partitioned preferentially to the γ phase. However, above a critical Co content (~19 at.%), the extent of partitioning of Al and Ti to the γ′ phase reduced. Conversely, Cr partitioned more strongly to the γ phase with Co additions of up to ~19 at.%, above which this preferential segregation was less pronounced. This non-monotonic trend of elemental partitioning behaviour with increasing Co concentration was attributed to a transition in the chemistry of the L1$_2$ γ′ phase from Ni$_3$(Ti, Al) to (Ni, Co)$_3$(Ti, Al) and thus to a change in its solute solubility.This work was supported by the Rolls-Royce EPSRC Strategic Partnership under EP/H022309/1 and EP/M005607/1, by the University of Michigan College of Engineering (funding) and by the Michigan Center for Materials Characterization (instruments)

Variability of protein level and phosphorylation status caused by biopsy protocol design in human skeletal muscle analyses

<p>Abstract</p> <p>Background</p> <p>Bergström needle biopsy is widely used to sample skeletal muscle in order to study cell signaling directly in human tissue. Consequences of the biopsy protocol design on muscle protein quantity and quality remain unclear. The aim of the present study was to assess the impact of different events surrounding biopsy protocol on the stability of the Western blot signal of eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), Akt, glycogen synthase kinase-3β (GSK-3β), muscle RING finger protein 1 (MuRF1) and p70 S6 kinase (p70 S6K). Six healthy subjects underwent four biopsies of the <it>vastus lateralis</it>, distributed into two distinct visits spaced by 48 hrs. At visit 1, a basal biopsy in the right leg was performed in the morning (R1) followed by a second in the left leg in the afternoon (AF). At visit 2, a second basal biopsy (R2) was collected from the right leg. Low intensity mobilization (3 × 20 right leg extensions) was performed and a final biopsy (Mob) was collected using the same incision site as R2.</p> <p>Results</p> <p>Akt and p70 S6K phosphorylation levels were increased by 83% when AF biopsy was compared to R1. Mob condition induced important phosphorylation of p70 S6K when compared to R2. Comparison of R1 and R2 biopsies revealed a relative stability of the signal for both total and phosphorylated proteins.</p> <p>Conclusions</p> <p>This study highlights the importance to standardize muscle biopsy protocols in order to minimize the method-induced variation when analyzing Western blot signals.</p

PRO development: rigorous qualitative research as the crucial foundation

Recently published articles have described criteria to assess qualitative research in the health field in general, but very few articles have delineated qualitative methods to be used in the development of Patient-Reported Outcomes (PROs). In fact, how PROs are developed with subject input through focus groups and interviews has been given relatively short shrift in the PRO literature when compared to the plethora of quantitative articles on the psychometric properties of PROs. If documented at all, most PRO validation articles give little for the reader to evaluate the content validity of the measures and the credibility and trustworthiness of the methods used to develop them. Increasingly, however, scientists and authorities want to be assured that PRO items and scales have meaning and relevance to subjects. This article was developed by an international, interdisciplinary group of psychologists, psychometricians, regulatory experts, a physician, and a sociologist. It presents rigorous and appropriate qualitative research methods for developing PROs with content validity. The approach described combines an overarching phenomenological theoretical framework with grounded theory data collection and analysis methods to yield PRO items and scales that have content validity

A prospective study of decline in fat free mass and skeletal muscle strength in chronic obstructive pulmonary disease

BACKGROUND: Skeletal muscle depletion is an important complication of chronic obstructive pulmonary disease (COPD) but little prospective data exists about the rate at which it occurs and the factors that promote its development. We therefore prospectively investigated the impact of disease severity, exacerbation frequency and treatment with corticosteroids on change in body composition and maximum isometric quadriceps strength (QMVC) over one year. METHODS: 64 patients with stable COPD (FEV(1 )mean (SD) 35.8(18.4) %predicted) were recruited from clinic and studied on two occasions one year apart. Fat free mass was determined using bioelectrical impedance analysis and a disease specific regression equation. RESULTS: QMVC fell from 34.8(1.5) kg to 33.3(1.5) kg (p = 0.04). The decline in quadriceps strength was greatest in those with the highest strength at baseline (R -0.28 p = 0.02) and was not correlated with lung function, exacerbation frequency or steroid treatment. Decline in fat free mass was similarly higher in those with largest FFM at baseline (R = -0.31 p = 0.01) but was more strongly correlated with greater gas trapping (R = -0.4 p = 0.001). Patients with frequent exacerbations (>1 per year) (n = 36) experienced a greater decline in fat free mass compared to infrequent exacerbators (n = 28) -1.3(3.7)kg vs. +1.2(3.1)kg (p = 0.005), as did patients on maintenance oral steroids (n = 8) -2.8(3.3) kg vs. +0.2(3.5) kg (p = 0.024) whereas in those who stopped smoking (n = 7) fat free mass increased; +2.7(3.1) kg vs. -0.51(3.5) kg (p = 0.026). CONCLUSION: Decline in fat free mass in COPD is associated with worse lung function, continued cigarette consumption and frequent exacerbations. Factors predicting progression of quadriceps weakness could not be identified from the present cohort

Extracellular DNA Chelates Cations and Induces Antibiotic Resistance in Pseudomonas aeruginosa Biofilms

Biofilms are surface-adhered bacterial communities encased in an extracellular matrix composed of DNA, bacterial polysaccharides and proteins, which are up to 1000-fold more antibiotic resistant than planktonic cultures. To date, extracellular DNA has been shown to function as a structural support to maintain Pseudomonas aeruginosa biofilm architecture. Here we show that DNA is a multifaceted component of P. aeruginosa biofilms. At physiologically relevant concentrations, extracellular DNA has antimicrobial activity, causing cell lysis by chelating cations that stabilize lipopolysaccharide (LPS) and the outer membrane (OM). DNA-mediated killing occurred within minutes, as a result of perturbation of both the outer and inner membrane (IM) and the release of cytoplasmic contents, including genomic DNA. Sub-inhibitory concentrations of DNA created a cation-limited environment that resulted in induction of the PhoPQ- and PmrAB-regulated cationic antimicrobial peptide resistance operon PA3552–PA3559 in P. aeruginosa. Furthermore, DNA-induced expression of this operon resulted in up to 2560-fold increased resistance to cationic antimicrobial peptides and 640-fold increased resistance to aminoglycosides, but had no effect on β-lactam and fluoroquinolone resistance. Thus, the presence of extracellular DNA in the biofilm matrix contributes to cation gradients, genomic DNA release and inducible antibiotic resistance. DNA-rich environments, including biofilms and other infection sites like the CF lung, are likely the in vivo environments where extracellular pathogens such as P. aeruginosa encounter cation limitation

Drosophila melanogaster as an Animal Model for the Study of Pseudomonas aeruginosa Biofilm Infections In Vivo

Pseudomonas aeruginosa is an opportunistic pathogen capable of causing both acute and chronic infections in susceptible hosts. Chronic P. aeruginosa infections are thought to be caused by bacterial biofilms. Biofilms are highly structured, multicellular, microbial communities encased in an extracellular matrix that enable long-term survival in the host. The aim of this research was to develop an animal model that would allow an in vivo study of P. aeruginosa biofilm infections in a Drosophila melanogaster host. At 24 h post oral infection of Drosophila, P. aeruginosa biofilms localized to and were visualized in dissected Drosophila crops. These biofilms had a characteristic aggregate structure and an extracellular matrix composed of DNA and exopolysaccharide. P. aeruginosa cells recovered from in vivo grown biofilms had increased antibiotic resistance relative to planktonically grown cells. In vivo, biofilm formation was dependent on expression of the pel exopolysaccharide genes, as a pelB::lux mutant failed to form biofilms. The pelB::lux mutant was significantly more virulent than PAO1, while a hyperbiofilm strain (PAZHI3) demonstrated significantly less virulence than PAO1, as indicated by survival of infected flies at day 14 postinfection. Biofilm formation, by strains PAO1 and PAZHI3, in the crop was associated with induction of diptericin, cecropin A1 and drosomycin antimicrobial peptide gene expression 24 h postinfection. In contrast, infection with the non-biofilm forming strain pelB::lux resulted in decreased AMP gene expression in the fly. In summary, these results provide novel insights into host-pathogen interactions during P. aeruginosa oral infection of Drosophila and highlight the use of Drosophila as an infection model that permits the study of P. aeruginosa biofilms in vivo