Effects of octane on the fatty acid composition and transition temperature of Pseudomonas oleovorans membrane lipids during growth in two-liquid-phase continuous cultures

Growth of Pseudomonas oleovorans GPol in continuous culture containing a bulk n-octane phase resulted in changes of the fatty acid composition of the membrane lipids. Compared to citrate-grown cells, the ratio of C18 to C16 fatty acids and the ratio of unsaturated to saturated fatty acids increased as a result of growth on octane. Trans-unsaturated fatty acids, which are rarely found in bacteria, were formed during continuous growth of P. oleovorans on octane. Moreover, the mean acyl chain length and unsaturated fatty acids also increased as the growth rates increased both in octane-grown and citrate-grown cells. Differential scanning calorimetry measurements of extracted lipids showed the transition temperature of membrane lipids from octane-grown cells increased from about 24°C to 32°C as the growth rate increased, whereas cells grown on citrate showed a constant transition temperature of about 6°C at all growth rates tested, indicating a decrease of membrane lipid fluidity in octane-grown cells. Because alkanes are known to increase bilayer fluidity by intercalating between lipid fatty acyl chains, the increased transition temperature of the lipids of cells grown on octane may be a physiological response of P. oleovorans to compensate for the direct effects of octane on its cellular membranes.

Ultra-deep Large Binocular Camera U-band Imaging of the GOODS-North Field: Depth vs. Resolution

We present a study of the trade-off between depth and resolution using a large number of U-band imaging observations in the GOODS-North field (Giavalisco et al. 2004) from the Large Binocular Camera (LBC) on the Large Binocular Telescope (LBT). Having acquired over 30 hours of data (315 images with 5-6 mins exposures), we generated multiple image mosaics, starting with the best atmospheric seeing images (FWHM $\lesssim$0.8"), which constitute $\sim$10% of the total data set. For subsequent mosaics, we added in data with larger seeing values until the final, deepest mosaic included all images with FWHM $\lesssim$1.8" ($\sim$94% of the total data set). From the mosaics, we made object catalogs to compare the optimal-resolution, yet shallower image to the lower-resolution but deeper image. We show that the number counts for both images are $\sim$90% complete to $U_{AB}$ $\lesssim26$. Fainter than $U_{AB}$$\sim$ 27, the object counts from the optimal-resolution image start to drop-off dramatically (90% between $U_{AB}$ = 27 and 28 mag), while the deepest image with better surface-brightness sensitivity ($\mu^{AB}_{U}$$\lesssim$ 32 mag arcsec$^{-2}$) show a more gradual drop (10% between $U_{AB}$ $\simeq$ 27 and 28 mag). For the brightest galaxies within the GOODS-N field, structure and clumpy features within the galaxies are more prominent in the optimal-resolution image compared to the deeper mosaics. Finally, we find - for 220 brighter galaxies with $U_{AB}$$\lesssim$ 24 mag - only marginal differences in total flux between the optimal-resolution and lower-resolution light-profiles to $\mu^{AB}_{U}$$\lesssim$ 32 mag arcsec$^{-2}$. In only 10% of the cases are the total-flux differences larger than 0.5 mag. This helps constrain how much flux can be missed from galaxy outskirts, which is important for studies of the Extragalactic Background Light.Comment: 24 pages, 14 figures, submitted to PASP, comments welcom

Reducing prescribing errors through creatinine clearance alert redesign

Background Literature has shown that computerized creatinine clearance alerts reduce errors during prescribing, and applying human factors principles may further reduce errors. Our objective was to apply human factors principles to creatinine clearance alert design and assess whether the redesigned alerts increase usability and reduce prescribing errors compared with the original alerts. Methods Twenty Veterans Affairs (VA) outpatient providers (14 physicians, 2 nurse practitioners, and 4 clinical pharmacists) completed 2 usability sessions in a counterbalanced study to evaluate original and redesigned alerts. Each session consisted of fictional patient scenarios with 3 medications that warranted prescribing changes because of renal impairment, each associated with creatinine clearance alerts. Quantitative and qualitative data were collected to assess alert usability and the occurrence of prescribing errors. Results There were 43% fewer prescribing errors with the redesigned alerts compared with the original alerts (P = .001). Compared with the original alerts, redesigned alerts significantly reduced prescribing errors for allopurinol and ibuprofen (85% vs 40% and 65% vs 25%, P = .012 and P = .008, respectively), but not for spironolactone (85% vs 65%). Nine providers (45%) voiced confusion about why the alert was appearing when they encountered the original alert design. When laboratory links were presented on the redesigned alert, laboratory information was accessed 3.5 times more frequently. Conclusions Although prescribing errors were high with both alert designs, the redesigned alerts significantly improved prescribing outcomes. This investigation provides some of the first evidence on how alerts may be designed to support safer prescribing for patients with renal impairment

PAMELA, DAMA, INTEGRAL and Signatures of Metastable Excited WIMPs

Models of dark matter with ~ GeV scale force mediators provide attractive explanations of many high energy anomalies, including PAMELA, ATIC, and the WMAP haze. At the same time, by exploiting the ~ MeV scale excited states that are automatically present in such theories, these models naturally explain the DAMA/LIBRA and INTEGRAL signals through the inelastic dark matter (iDM) and exciting dark matter (XDM) scenarios, respectively. Interestingly, with only weak kinetic mixing to hypercharge to mediate decays, the lifetime of excited states with delta < 2 m_e is longer than the age of the universe. The fractional relic abundance of these excited states depends on the temperature of kinetic decoupling, but can be appreciable. There could easily be other mechanisms for rapid decay, but the consequences of such long-lived states are intriguing. We find that CDMS constrains the fractional relic population of ~100 keV states to be <~ 10^-2, for a 1 TeV WIMP with sigma_n = 10^-40 cm^2. Upcoming searches at CDMS, as well as xenon, silicon, and argon targets, can push this limit significantly lower. We also consider the possibility that the DAMA excitation occurs from a metastable state into the XDM state, which decays via e+e- emission, which allows lighter states to explain the INTEGRAL signal due to the small kinetic energies required. Such models yield dramatic signals from down-scattering, with spectra peaking at high energies, sometimes as high as ~1 MeV, well outside the usual search windows. Such signals would be visible at future Ar and Si experiments, and may be visible at Ge and Xe experiments. We also consider other XDM models involving ~ 500 keV metastable states, and find they can allow lighter WIMPs to explain INTEGRAL as well.Comment: 22 pages, 7 figure

Limits to sustained energy intake XII : is the poor relation between resting metabolic rate and reproductive performance because resting metabolism is not a repeatable trait?

Peer reviewedPublisher PD

Analytical and Biological Characterization of Supercoiled Plasmids Purified by Various Chromatographic Techniques

This is the publisher's version, also available electronically from http://online.liebertpub.com/doi/abs/10.1089/dna.2005.24.819Supercoiled plasmids are an important component of gene-based delivery vehicles. A number of production methods for clinical applications have been developed, each resulting in very high-quality product with low levels of residual contaminants. There is, however, no consensus on the optimal methods to characterize plasmid quality, and further, to determine if these methods are predictive of either product stability or biological activity. We have produced two plasmids using four production purification methodologies based on PolyFlo® and hydrophobic interaction chromatography (HIC), either alone or in tandem processes. In each case, the product was analyzed using standard molecular biological methods. We also performed a number of biophysical analyses such as dynamic light scattering (DLS), circular dichroism (CD), Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). Minimal differences were detected among the preparations based on the more standard molecular biological methods. Some small differences were detected, however, using biophysical techniques, particularly FTIR and DSC, which may reflect small variations in plasmid tertiary structure and thermal stability. Stability after heat exposure at 60°C, exposure to fetal bovine serum and long-term storage at 4°C varied between plasmids. One plasmid showed no difference in stability depending on the production process, but the other showed significant differences. Evaluation in vivo in models for gene immunization and gene therapy showed significant differences in the response depending on the method of purification. Preparations using a tandem process of PolyFlo used in two separation modes provided higher biological activity compared to a tandem HIC/PolyFlo process or either resin used alone in a single column process. These data indicate that the process by which supercoiled plasmids are made can influence plasmid stability and biological activity and emphasize the need for more rigorous methods to evaluate supercoiled plasmids as gene-delivery vehicles

Dark Matter Direct Detection with Non-Maxwellian Velocity Structure

The velocity distribution function of dark matter particles is expected to show significant departures from a Maxwell-Boltzmann distribution. This can have profound effects on the predicted dark matter - nucleon scattering rates in direct detection experiments, especially for dark matter models in which the scattering is sensitive to the high velocity tail of the distribution, such as inelastic dark matter (iDM) or light (few GeV) dark matter (LDM), and for experiments that require high energy recoil events, such as many directionally sensitive experiments. Here we determine the velocity distribution functions from two of the highest resolution numerical simulations of Galactic dark matter structure (Via Lactea II and GHALO), and study the effects for these scenarios. For directional detection, we find that the observed departures from Maxwell-Boltzmann increase the contrast of the signal and change the typical direction of incoming DM particles. For iDM, the expected signals at direct detection experiments are changed dramatically: the annual modulation can be enhanced by more than a factor two, and the relative rates of DAMA compared to CDMS can change by an order of magnitude, while those compared to CRESST can change by a factor of two. The spectrum of the signal can also change dramatically, with many features arising due to substructure. For LDM the spectral effects are smaller, but changes do arise that improve the compatibility with existing experiments. We find that the phase of the modulation can depend upon energy, which would help discriminate against background should it be found.Comment: 34 pages, 16 figures, submitted to JCAP. Tables of g(v_min), the integral of f(v)/v from v_min to infinity, derived from our simulations, are available for download at http://astro.berkeley.edu/~mqk/dmdd

CPDB: a database of circular permutation in proteins

Circular permutation (CP) in a protein can be considered as if its sequence were circularized followed by a creation of termini at a new location. Since the first observation of CP in 1979, a substantial number of studies have concluded that circular permutants (CPs) usually retain native structures and functions, sometimes with increased stability or functional diversity. Although this interesting property has made CP useful in many protein engineering and folding researches, large-scale collections of CP-related information were not available until this study. Here we describe CPDB, the first CP DataBase. The organizational principle of CPDB is a hierarchical categorization in which pairs of circular permutants are grouped into CP clusters, which are further grouped into folds and in turn classes. Additions to CPDB include a useful set of tools and resources for the identification, characterization, comparison and visualization of CP. Besides, several viable CP site prediction methods are implemented and assessed in CPDB. This database can be useful in protein folding and evolution studies, the discovery of novel protein structural and functional relationships, and facilitating the production of new CPs with unique biotechnical or industrial interests. The CPDB database can be accessed at http://sarst.life.nthu.edu.tw/cpd

Attribution of responsibility for sexual crimes beyond individual actors – construction of responsibility of offenders, victims and society in laypersons’ explanations

This study analyses laypersons’ explanations for sexual violence. It focusses on how the responsibility for sexual crimes is constructed and attributed, and moreover, what kind of effect this has on the attribution of blame. The research data consist of 105 opinion pieces published in the leading Finnish newspaper since the beginning of the 21st century. The theory-driven qualitative analysis utilises attribution theory and focusses on laypersons’ interpretations and explanations for unusual acts and events deviating from social norms. Attribution theory is commonly utilised in relation to micro-level actors, the offender and the victim, whereas in this article, it is broadened to include also society as a macro-level actor. The analysis reveals that the construction of responsibility derives from (I) the chronological presentation and explanation of sexual crimes; especially (II) the causality attached to chronological phases, which emphasises the victim’s actions prior to the crime; and (III) the construction of active female agency against male passivity or absence of the perpetrator. Moreover, blame is based on a combination of active agency, produced in the analysed explanations, and stereotypical features connected to female gender (e.g. rape myths)

Applying human factors principles to alert design increases efficiency and reduces prescribing errors in a scenario-based simulation

OBJECTIVE: To apply human factors engineering principles to improve alert interface design. We hypothesized that incorporating human factors principles into alerts would improve usability, reduce workload for prescribers, and reduce prescribing errors. MATERIALS AND METHODS: We performed a scenario-based simulation study using a counterbalanced, crossover design with 20 Veterans Affairs prescribers to compare original versus redesigned alerts. We redesigned drug-allergy, drug-drug interaction, and drug-disease alerts based upon human factors principles. We assessed usability (learnability of redesign, efficiency, satisfaction, and usability errors), perceived workload, and prescribing errors. RESULTS: Although prescribers received no training on the design changes, prescribers were able to resolve redesigned alerts more efficiently (median (IQR): 56 (47) s) compared to the original alerts (85 (71) s; p=0.015). In addition, prescribers rated redesigned alerts significantly higher than original alerts across several dimensions of satisfaction. Redesigned alerts led to a modest but significant reduction in workload (p=0.042) and significantly reduced the number of prescribing errors per prescriber (median (range): 2 (1-5) compared to original alerts: 4 (1-7); p=0.024). DISCUSSION: Aspects of the redesigned alerts that likely contributed to better prescribing include design modifications that reduced usability-related errors, providing clinical data closer to the point of decision, and displaying alert text in a tabular format. Displaying alert text in a tabular format may help prescribers extract information quickly and thereby increase responsiveness to alerts. CONCLUSIONS: This simulation study provides evidence that applying human factors design principles to medication alerts can improve usability and prescribing outcomes