iRFP is a real time marker for transformation based assays in high content screening

Anchorage independent growth is one of the hallmarks of oncogenic transformation. Here we show that infrared fluorescent protein (iRFP) based assays allow accurate and unbiased determination of colony formation and anchorage independent growth over time. This protocol is particularly compatible with high throughput systems, in contrast to traditional methods which are often labor-intensive, subjective to bias and do not allow further analysis using the same cells. Transformation in a single layer soft agar assay could be documented as early as 2 to 3 days in a 96 well format, which can be easily combined with standard transfection, infection and compound screening setups to allow for high throughput screening to identify therapeutic targets

Polarization reversal via a transient relaxor state in nonergodic relaxors near freezing temperature

Among the unresolved issues in the study of relaxor ferroelectrics is the role of freezing temperature, across which the dynamics of polarization reversal in relaxor ferroelectrics changes. The presence of this freezing temperature is best manifested by the appearance of a double polarization hysteresis loop just above the freezing temperature. Given that the polarization pinching evolving into a double hysteresis starts well below the freezing temperature, there exists a transient temperature regime between the nonergodic and the ergodic relaxor states. To clarify the role of the freezing temperature on the pinching, the polarization reversal near the freezing temperature of relaxor (Pb1-xLax)(Zr1-yTy)(1-x/4)O-3 (PLZT) was monitored using three in situ electric field methods: electrocaloric effect, neutron diffraction, and transmission electron microscopy. We demonstrate that the pinching results from a two-step process, 1) domain detexturization in the ferroelectric state and 2) miniaturization of domains. This observation explains the recently reported gap between the depolarization temperature T-d and the ferroelectric-torelaxor transition temperature TF-R in lead-free relaxors. We further show that T-d and TF-R, which have long been considered identical in lead-based relaxors, are not the same. The current study suggests that the mismatch between T-d and TF-R is an inherent feature in both lead-based and lead-free relaxor ferroelectrics

Energy drink use, problem drinking and drinking motives in a diverse sample of Alaskan college students

Background. Recent research has identified the use of caffeinated energy drinks as a common, potentially risky behaviour among college students that is linked to alcohol misuse and consequences. Research also suggests that energy drink consumption is related to other risky behaviours such as tobacco use, marijuana use and risky sexual activity. Objective. This research sought to examine the associations between frequency of energy drink consumption and problematic alcohol use, alcohol-related consequences, symptoms of alcohol dependence and drinking motives in an ethnically diverse sample of college students in Alaska. We also sought to examine whether ethnic group moderated these associations in the present sample of White, Alaska Native/American Indian and other ethnic minority college students. Design. A paper-and-pencil self-report questionnaire was completed by a sample of 298 college students. Analysis of covariance (ANCOVA) was used to examine the effects of energy drink use, ethnic group and energy drink by ethnic group interactions on alcohol outcomes after controlling for variance attributed to gender, age and frequency of binge drinking. Results. Greater energy drink consumption was significantly associated with greater hazardous drinking, alcohol consequences, alcohol dependence symptoms, drinking for enhancement motives and drinking to cope. There were no main effects of ethnic group, and there were no significant energy drink by ethnic group interactions. Conclusion. These findings replicate those of other studies examining the associations between energy drink use and alcohol problems, but contrary to previous research we did not find ethnic minority status to be protective. It is possible that energy drink consumption may serve as a marker for other health risk behaviours among students of various ethnic groups

Preserving Madagascar's Natural Heritage: The Importance of Keeping the Island's Vertebrate Fossils in the Public Domain

No Abstrac

Gene expression drives the evolution of dominance.

Dominance is a fundamental concept in molecular genetics and has implications for understanding patterns of genetic variation, evolution, and complex traits. However, despite its importance, the degree of dominance in natural populations is poorly quantified. Here, we leverage multiple mating systems in natural populations of Arabidopsis to co-estimate the distribution of fitness effects and dominance coefficients of new amino acid changing mutations. We find that more deleterious mutations are more likely to be recessive than less deleterious mutations. Further, this pattern holds across gene categories, but varies with the connectivity and expression patterns of genes. Our work argues that dominance arises as a consequence of the functional importance of genes and their optimal expression levels

Negotiation in strategy making teams : group support systems and the process of cognitive change

This paper reports on the use of a Group Support System (GSS) to explore at a micro level some of the processes manifested when a group is negotiating strategy-processes of social and psychological negotiation. It is based on data from a series of interventions with senior management teams of three operating companies comprising a multi-national organization, and with a joint meeting subsequently involving all of the previous participants. The meetings were concerned with negotiating a new strategy for the global organization. The research involved the analysis of detailed time series data logs that exist as a result of using a GSS that is a reflection of cognitive theory

Bedside Interactions from the Other Side of the Bedrail

To assess the importance to patients of various aspects of bedside interactions with physician teams. Design : Cross-sectional survey. Setting : VA hospital. Patients : Ninety-seven medical inpatients. Intervention : Survey of 44 questions including short answer, multiple choice, and Likert-type questions. Measurements and Main Results : Data analysis included descriptive statistics. The sample was predominantly male, with a mean age of 62. Overall satisfaction with the hospital experience and with the team of doctors were both high (95% and 96% reported being very or mostly satisfied, respectively). Patients reported learning about several issues during their interactions with the teams; the 3 most highly rated areas were new problems, tests that will be done, and treatments that will be done. Most patients (76%) felt that their teams cared about them very much. Patients were made comfortable when the team showed that they cared, listened, and appeared relaxed (reported by 63%, 57%, and 54%, respectively). Patients were made uncomfortable by the team using language they did not understand (22%) and when several people examined them at once (13%). Many (58%) patients felt personally involved in teaching. The majority of patients liked having medical students and residents involved in their care (69% and 64%, respectively). Conclusions : Patients have much to teach about what is important about interacting with physician teams. Although patients' reactions to team interactions are generally positive, patients are different with respect to what makes them comfortable and uncomfortable. Taking their preferences into account could improve the experience of being in a teaching hospital.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75456/1/j.1525-1497.2005.40192.x.pd

The Social Contagion Effect of Marijuana Use among Adolescents

Research on adolescent substance use has consistently identified a strong relationship between adolescent behavior and the behavior of their peers. However, peer effects are difficult to estimate and causal interpretations must be undertaken with caution since individuals in most cases choose with whom to associate. In this paper we seek to empirically quantify the causal role of peer social networks in explaining marijuana usage among adolescents.Using data from a nationally representative sample of adolescents we utilize a multivariate structural model with school-level fixed effects to account for the problems of contextual effects, correlated effects and peer selections to purge the potential biases from the estimates of peer influence. Our peer group measures are drawn not only from the nomination of close friends (N = 6,377), but also from classmates (N = 19,335). Marijuana usage among the peer groups were constructed using the peers' own report of their marijuana consumption. Controlling for parent level characteristics, and other demographic parameters, we find that a 10% increase in the proportion of close friends and classmates who use marijuana increases the probability that an individual chooses to use marijuana by 5%.Our findings indicate that peer effects are important determinants of marijuana use even after controlling for potential biases We also found evidence to show that the influence of close friends and the more exogenous classmates are quite similar in magnitude under our preferred specification, supporting theory predicting the importance of peer influence. Effective policy aimed at reducing marijuana usage among adolescents would consider these significant peer effects

RETRACTED ARTICLE: Age-dependent Increase in Desmosterol Restores DRM Formation and Membrane-related Functions in Cholesterol-free DHCR24−/− Mice

Cholesterol is a prominent modulator of the integrity and functional activity of physiological membranes and the most abundant sterol in the mammalian brain. DHCR24-knock-out mice lack cholesterol and accumulate desmosterol with age. Here we demonstrate that brain cholesterol deficiency in 3-week-old DHCR24−/− mice was associated with altered membrane composition including disrupted detergent-resistant membrane domain (DRM) structure. Furthermore, membrane-related functions differed extensively in the brains of these mice, resulting in lower plasmin activity, decreased β-secretase activity and diminished Aβ generation. Age-dependent accumulation and integration of desmosterol in brain membranes of 16-week-old DHCR24−/− mice led to the formation of desmosterol-containing DRMs and rescued the observed membrane-related functional deficits. Our data provide evidence that an alternate sterol, desmosterol, can facilitate processes that are normally cholesterol-dependent including formation of DRMs from mouse brain extracts, membrane receptor ligand binding and activation, and regulation of membrane protein proteolytic activity. These data indicate that desmosterol can replace cholesterol in membrane-related functions in the DHCR24−/− mouse

Life cycle (well-to-wheel) energy and environmental assessment of natural gas as transportation fuel in Pakistan

Consumers and organizations worldwide are searching for low-carbon alternatives to conventional gasoline and diesel vehicles to reduce greenhouse gas (GHG) emissions and their impact on the environment. Natural gas as an alternative transportation fuel has made significant inroads in the light and heavy duty vehicles market over the last fifteen years. In a sustainable development view, both vehicle emissions and energy supply chain analysis from well-to-wheel must be addressed. The aim of this research is to provide a Well-to-Wheel (WtW) assessment of energy consumptions and GHG emissions for 25 combinations of automotive fuel and matching powertrain systems, with a special focus on the natural gas pathways. Although several well-to-wheel studies available in literature are comprehensive in relation to developed countries’ conditions, it is problematic to apply the results to developing countries fuel markets, since the local fuel conditions and respective vehicle powertrain technologies are considerably different. This study deal with a comparative well-to-wheel analysis of natural gas, diesel and gasoline fuels looking at the Pakistanis situation but the models and approaches for this study can be applied to other countries having similar characteristics, as long as all the assumptions are well defined and modified to find a substitute automotive energy source and establish an energy policy in a specific region. The well-to-tank step was made using the GREET model, developed by the U.S. Argonne National Laboratory while tank-to-wheel analysis was performed using AVL Cruise, a commercially-available backward vehicle simulator. Later both stages were integrated in a well-to-wheel stage where relevant indexes were proposed and discussed. The results indicate that natural gas vehicles are 5 – 17% and 23 – 36% less fuel efficient, depending on the engine technology employed as compared to gasoline and diesel powertrain, respectively. Natural gas appears as an environmental efficient pathway regarding GHG emissions, especially compared to gasoline. In addition, using 20-year GWPs instead of 100-year GWPs increases WtW GHG emissions by 19–26% for natural gas pathways