Shape-induced force fields in optical trapping

Advances in optical tweezers, coupled with the proliferation of two-photon polymerization systems, mean that it is now becoming routine to fabricate and trap non-spherical particles. The shaping of both light beams and particles allows fine control over the flow of momentum from the optical to mechanical regimes. However, understanding and predicting the behaviour of such systems is highly complex in comparison with the traditional optically trapped microsphere. In this Article, we present a conceptually new and simple approach based on the nature of the optical force density. We illustrate the method through the design and fabrication of a shaped particle capable of acting as a passive force clamp, and we demonstrate its use as an optically trapped probe for imaging surface topography. Further applications of the design rules highlighted here may lead to new sensors for probing biomolecule mechanics, as well as to the development of optically actuated micromachines

The rsmS (ybaM) mutation causes bypass suppression of the RsmAB post-transcriptional virulence regulation system in enterobacterial phytopathogens.

Plant cell wall degrading enzymes (PCWDEs) are the primary virulence determinants of soft rotting bacteria such as the potato pathogen, Pectobacterium atrosepticum. The regulation of secondary metabolite (Rsm) system controls production of PCWDEs in response to changing nutrient conditions. This work identified a new suppressor of an rsmB mutation - ECA1172 or rsmS (rsmB suppressor). Mutants defective in rsmB (encoding a small regulatory RNA), show reduced elaboration of the quorum sensing molecule (N-3-oxohexanoyl-homoserine lactone; OHHL) and PCWDEs. However, OHHL and PCWDE production were partially restored in an rsmB, rsmS double mutant. Single rsmS mutants, overproduced PCWDEs and OHHL relative to wild type P. atrosepticum and exhibited hypervirulence in potato. RsmS overproduction also resulted in increased PCWDEs and OHHL. Homology searches revealed rsmS conservation across pathogens such as Escherichia coli (ybaM), Dickeya solani, Klebsiella pneumoniae and Shigella flexneri. An rsmS mutant of Pectobacterium carotovorum ATCC39048 showed bypass of rsmB-dependent repression of PCWDEs and OHHL production. P. carotovorum ATCC39048 produces the β-lactam antibiotic, 1-carbapen-2-em-3-carboxylic acid (a carbapenem). Production of the antibiotic was repressed in an rsmB mutant but partially restored in an rsmB, rsmS double mutant. This work highlights the importance of RsmS, as a conserved pleiotropic regulator of virulence and antibiotic biosynthesis.James Hutton Institut

A deep search for metals near redshift 7: The line of sight towards ULAS J1120+0641

We present a search for metal absorption line systems at the highest redshifts to date using a deep (30h) VLT/X-Shooter spectrum of the z = 7.084 quasi-stellar object (QSO) ULAS J1120+0641. We detect seven intervening systems at z > 5.5, with the highest-redshift system being a C IV absorber at z = 6.51. We find tentative evidence that the mass density of C IV remains flat or declines with redshift at z < 6, while the number density of C II systems remains relatively flat over 5 < z < 7. These trends are broadly consistent with models of chemical enrichment by star formation-driven winds that include a softening of the ultraviolet background towards higher redshifts. We find a larger number of weak ( W_rest < 0.3A ) Mg II systems over 5.9 < z < 7.0 than predicted by a power-law fit to the number density of stronger systems. This is consistent with trends in the number density of weak Mg II systems at z = 2.5, and suggests that the mechanisms that create these absorbers are already in place at z = 7. Finally, we investigate the associated narrow Si IV, C IV, and N V absorbers located near the QSO redshift, and find that at least one component shows evidence of partial covering of the continuum source

Gender-related differences in physiologic color space: a functional transcranial Doppler (fTCD) study

Simultaneous color contrast and color constancy are memory processes associated with color vision, however, the gender-related differences of 'physiologic color space' remains unknown. Color processing was studied in 16 (8 men and 8 women) right-handed healthy subjects using functional transcranial Doppler (fTCD) technique. Mean flow velocity (MFV) was recorded in both right (RMCA) and left (LMCA) middle cerebral arteries in dark and white light conditions, and during color (blue and yellow) stimulations. The data was plotted in a 3D quadratic curve fit to derive a 'physiologic color space' showing the effects of luminance and chromatic contrasts. In men, wavelength-differencing of opponent pairs (yellow-blue) was adjudged by changes in the RMCA MFV for Yellow plotted on the Y-axis, and the RMCA MFV for Blue plotted on the X-axis. In women, frequency-differencing for opponent pairs (blue-yellow) was adjudged by changes in the LMCA MFV for Yellow plotted on the Y-axis, and the LMCA MFV for Blue plotted on the X-axis. The luminance effect on the LMCA MFV in response to white light with the highest luminous flux, was plotted on the (Z - axis), in both men and women. The 3D-color space for women was a mirror-image of that for men, and showed enhanced color constancy. The exponential function model was applied to the data in men, while the logarithmic function model was applied to the data in women. Color space determination may be useful in the study of color memory, adaptive neuroplasticity, cognitive impairment in stroke and neurodegenerative diseases

Anti-prion drug mPPIg5 inhibits PrP(C) conversion to PrP(Sc).

Prion diseases, also known as transmissible spongiform encephalopathies, are a group of fatal neurodegenerative diseases that include scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle and Creutzfeldt-Jakob disease (CJD) in humans. The 'protein only hypothesis' advocates that PrP(Sc), an abnormal isoform of the cellular protein PrP(C), is the main and possibly sole component of prion infectious agents. Currently, no effective therapy exists for these diseases at the symptomatic phase for either humans or animals, though a number of compounds have demonstrated the ability to eliminate PrPSc in cell culture models. Of particular interest are synthetic polymers known as dendrimers which possess the unique ability to eliminate PrP(Sc) in both an intracellular and in vitro setting. The efficacy and mode of action of the novel anti-prion dendrimer mPPIg5 was investigated through the creation of a number of innovative bio-assays based upon the scrapie cell assay. These assays were used to demonstrate that mPPIg5 is a highly effective anti-prion drug which acts, at least in part, through the inhibition of PrP(C) to PrP(Sc) conversion. Understanding how a drug works is a vital component in maximising its performance. By establishing the efficacy and method of action of mPPIg5, this study will help determine which drugs are most likely to enhance this effect and also aid the design of dendrimers with anti-prion capabilities for the future

Soccer activity profile of altitude versus sea-level natives during acclimatisation to 3600 m (ISA3600)

Objectives We investigated the effect of high altitude on the match activity profile of elite youth high altitude and sea level residents.Methods Twenty Sea Level (Australian) and 19 Altitude-resident (Bolivian) soccer players played five games, two near sea level (430 m) and three in La Paz (3600 m). Match activity profile was quantified via global positioning system with the peak 5 min period for distance ((D5peak)) and high velocity running (>4.17 m/s, HIVR5peak); as well as the 5 min period immediately subsequent to the peak for both distance (D5sub) and high-velocity running (HIVR5sub) identified using a rolling 5 min epoch. The games at 3600 m were compared with the average of the two near sea-level games.Results The total distance per minute was reduced by a small magnitude in the first match at altitude in both teams, without any change in low-velocity running. There were variable changes in HiVR, D5peak and HiVR5peak from match to match for each team. There were within-team reductions in D5peak in each game at altitude compared with those at near sea level, and this reduction was greater by a small magnitude in Australians than Bolivians in game 4. The effect of altitude on HiVR5peak was moderately lower in Australians compared with Bolivians in game 3. There was no clear difference in the effect of altitude on maximal accelerations between teams.Conclusions High altitude reduces the distance covered by elite youth soccer players during matches. Neither 13 days of acclimatisation nor lifelong residence at high altitude protects against detrimental effects of altitude on match activity profile

Cohort study of Western Australia computed tomography utilisation patterns and their policy implications

Background: Computed tomography (CT) scanning is a relatively high radiation dose diagnostic imaging modality with increasing concerns about radiation exposure burden at the population level in scientific literature. This study examined the epidemiology of adult CT utilisation in Western Australia (WA) in both the public hospital and private practice settings, and the policy implications. Methods: Retrospective cohort design using aggregate adult CT data from WA public hospitals and Medical Benefits Schedule (MBS) (mid-2006 to mid-2012). CT scanning trends by sex, age, provider setting and anatomical areas were explored using crude CT scanning rates, age-standardised CT scanning rates and Poisson regression modelling. Results: From mid-2006 to mid-2012 the WA adult CT scanning rate was 129 scans per 1,000 person-years (PY). Females were consistently scanned at a higher rate than males. Patients over 65 years presented the highest scanning rates (over 300 scans per 1,000 PY). Private practice accounted for 73% of adult CT scans, comprising the majority in every anatomical area. In the private setting females predominately held higher age-standardised CT scanning rates than males. This trend reversed in the public hospital setting. Patients over 85 years in the public hospital setting were the most likely age group CT scanned in nine of ten anatomical areas. Patients in the private practice setting aged 85+ years were relatively less prominent across every anatomical area, and the least likely age group scanned in facial bones and multiple areas CT scans.Conclusion: In comparison to the public hospital setting, the MBS subsidised private sector tended to service females and relatively younger patients with a more diverse range of anatomical areas, constituting the majority of CT scans performed in WA. Patient risk and subsequent burden is greater for females, lower ages and some anatomical areas. In the context of a national health system, Australia has various avenues to monitor radiation exposure levels, improve physician training and modify funding mechanisms to ensure individual and population medical radiation exposure is as low as reasonably achievable

Characterization of disease course and remission in early seropositive rheumatoid arthritis: results from the TACERA longitudinal cohort study

Background: To characterise disease course and remission in a longitudinal observational study of newly diagnosed, initially treatment-naïve patients with seropositive rheumatoid arthritis (RA). Methods: Patients with early untreated seropositive RA were recruited from 28 UK centres. Multiple clinical and laboratory measures were collected every 3 months for up to 18 months. Disease activity was measured using the 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) and Simplified Disease Activity Index (SDAI). Logistic regression models examined clinical predictors of 6-month remission and latent class mixed models characterised disease course. Results: We enrolled 275 patients of whom 267 met full eligibility and provided baseline data. According to SDAI definition, 24.3% attained 6-month remission. Lower baseline Health Assessment Questionnaire (HAQ) and SDAI predicted 6-month remission (p = 0.013 and 0.011). Alcohol intake and baseline prescribing of methotrexate with a second disease-modifying antirheumatic drug (DMARD; vs monotherapy without glucocorticoids) were also predictive. Three distinct SDAI trajectory subpopulations emerged; corresponding to an inadequate responder group (6.5%), and higher and lower baseline activity responder groups (22.4% and 71.1%). Baseline HAQ and Short Form-36 Health Survey – Mental Component Score (SF-36 MCS) distinguished these groups. In addition, a number of baseline clinical predictors correlated with disease activity severity within subpopulations. Beneficial effects of alcohol intake were found across subpopulations. Conclusion: Three distinct disease trajectory subpopulations were identified. Differential effects of functional and mental well-being, alcohol consumption, and baseline RA medication prescribing on disease activity severity were found across subpopulations. Heterogeneity across trajectories cannot be fully explained by baseline clinical predictors. We hypothesise that biological markers collected early in disease course (within 6 months) may help patient management and better targeting of existing and novel therapies