Rb induces a proliferative arrest and curtails Brn-2 expression in retinoblastoma cells

BACKGROUND: Retinoblastoma is caused by loss of the Rb protein in early retinal cells. Although numerous Rb functions have been identified, Rb effects that specifically relate to the suppression of retinoblastoma have not been defined. RESULTS: In this study, we examined the effects of restoring Rb to Y79 retinoblastoma cells, using novel retroviral and lentiviral vectors that co-express green fluorescent protein (GFP). The lentiviral vector permitted transduction with sufficient efficiency to perform biochemical analyses. Wild type Rb (Rb(WT)) and to a lesser extent the low penetrance mutant Rb(661W )induced a G0/G1 arrest associated with induction of p27(KIP1 )and repression of cyclin E1 and cyclin E2. Microarray analyses revealed that in addition to down-regulating E2F-responsive genes, Rb repressed expression of Brn-2 (POU3F2), which is implicated as an important transcriptional regulator in retinal progenitor cells and other neuroendocrine cell types. The repression of Brn-2 was a specific Rb effect, as ectopic p27 induced a G0/G1 block, but enhanced, rather than repressed, Brn-2 expression. CONCLUSION: In addition to Rb effects that occur in many cell types, Rb regulates a gene that selectively governs the behavior of late retinal progenitors and related cells

Constructing Mutually Unbiased Bases in Dimension Six

The density matrix of a qudit may be reconstructed with optimal efficiency if the expectation values of a specific set of observables are known. In dimension six, the required observables only exist if it is possible to identify six mutually unbiased complex 6x6 Hadamard matrices. Prescribing a first Hadamard matrix, we construct all others mutually unbiased to it, using algebraic computations performed by a computer program. We repeat this calculation many times, sampling all known complex Hadamard matrices, and we never find more than two that are mutually unbiased. This result adds considerable support to the conjecture that no seven mutually unbiased bases exist in dimension six.Comment: As published version. Added discussion of the impact of numerical approximations and corrected the number of triples existing for non-affine families (cf Table 3

The Dependence of Galaxy Shape on Luminosity and Surface Brightness Profile

For a sample of 96,951 galaxies from the Sloan Digital Sky Survey Data Release 3, we study the distribution of apparent axis ratios as a function of r-band absolute magnitude and surface brightness profile type. We use the parameter fracDeV to quantify the profile type (fracDeV = 1 for a de Vaucouleurs profile; fracDeV = 0 for an exponential profile). When the apparent axis ratio q_{am} is estimated from the moments of the light distribution, the roundest galaxies are very bright (M_r \sim -23) de Vaucouleurs galaxies and the flattest are modestly bright (M_r \sim -18) exponential galaxies. When the apparent axis ratio q_{25} is estimated from the axis ratio of the 25 mag/arcsec^2 isophote, we find that de Vaucouleurs galaxies are flatter than exponential galaxies of the same absolute magnitude. For a given surface brightness profile type, very bright galaxies are rounder, on average, than fainter galaxies. We deconvolve the distributions of apparent axis ratios to find the distribution of the intrinsic short-to-long axis ratio gamma, assuming constant triaxiality T. For all profile types and luminosities, the distribution of apparent axis ratios is inconsistent with a population of oblate spheroids, but is usually consistent with a population of prolate spheroids. Bright galaxies with a de Vaucouleurs profile (M_r < -21.84, fracDeV > 0.9) have a distribution of q_{am} that is consistent with triaxiality in the range 0.4 < T < 0.8, with mean intrinsic axis ratio 0.66 < gamma < 0.69. The fainter de Vaucouleurs galaxies are best fit with prolate spheroids (T = 1) with mean axis ratio gamma = 0.51.Comment: 32 pages, 12 figures, to appear in Ap

A case-based framework for leveraging nutrigenomics knowledge and personal nutrition counseling

Paper presented at the 7th European Conference in Case-Based Reasoning, Madrid, Spain.NutriGenomics is the bioscience that links the way nutrients and other dietary components shape genetic activity. It builds on the success of Human Genome Project by applying systems biology methods to explain how the molecular components of food, supplements and pharmaceuticals dynamically influence and shape the activity of genomic subsystems, which in turn define how a person can stay healthy or become ill. Applying NutriGenomics knowledge is done through Directive Genomics, which develops purposeful dietary strategies that influence gene expression at the individual level with the goal of better genetic function and health. This paper proposes a case-based framework for leveraging nutrigenomics knowledge and Directive Genomics applications. The unique features of the proposed system include a selfmaintained distributed case base structure and a CBR-based nutrition counseling module that can learn, adapt, and maintain its case base via the integrated distributed case bases as well as external resources

Safety, tolerability, and impact on allergic inflammation of autologous E.coli autovaccine in the treatment of house dust mite asthma - a prospective open clinical trial

Background: Asthma is increasing worldwide and results from a complex immunological interaction between genetic susceptibility and environmental factors. Autovaccination with E. coli induces a strong TH-1 immune response, thus offering an option for the treatment of allergic diseases. Methods: Prospective open trial on safety, tolerability, and impact on allergic inflammation of an autologous E.coli autovaccine in intermittent or mild persistent house dust mite asthma. Determination of exhaled nitric monoxide (eNO) before and after bronchial mite challenge initially and after nine months of autovaccination. Results: Median eNO increase after autovaccination was significantly smaller (from 27.3 to 33.8 ppb; p=0.334) compared to initial values (from 32.6 to 42.2 ppb; p=0.046) (p=0.034). In nine subjects and a total of 306 injections, we observed 101 episodes of local erythema (33.3%; median of maximal diameter 2.5 cm), 95 episodes of local swelling (31.1%; median of maximal diameter 3 cm), and 27 episodes of local pain (8.8%). Four subjects reported itching at the injection site with a total of 30 episodes (9.8%). We observed no serious adverse events. All organ functions (inclusive electrocardiogramm) and laboratory testing of the blood (clinical chemistry, hematology) and the urine (screening test, B-microglobuline) were within normal limits. Vital signs undulated within the physiological variability. Conclusion: The administration of autologous autovacine for the treatment of house dust mite asthma resulted in a reduction of the eNO increase upon bronchial mite challenge. In nine subjects and 306 injections, only a few mild local reactions and no systemic severe adverse events were observed. EudraCT Nr. 2005-005534-12 ClinicalTrials.gov ID NCT0067720

Auditory Enhancement and Second Language Experience in Spanish and English Weighting of Secondary Voicing Cues

The role of secondary cues in voicing categorization was investigated in three listener groups: Monolingual English (n=20) and Spanish speakers (n=20), and Spanish speakers with significant English experience (n=16). Results showed that, in all three groups, participants used onset f0 in making voicing decisions only in the positive voice onset time (VOT) range (short lag and long lag tokens), while there was no effect of onset f0 on voicing categorization within the negative VOT range (voicing lead tokens) for any of the participant groups. These results support an auditory enhancement view of perceptual cue weighting: Onset f0 serves as a secondary cue to voicing only in the positive VOT range where it is not overshadowed by the presence of pre-voicing. Moreover, results showed that Spanish learners of English gave a significantly greater weight to onset f0 in their voicing decisions than did listeners in either of the other two groups. This result supports the view that learners may overweight secondary cues to distinguish between non-native categories that are assimilated to the same native category on the basis of a primary cue

Safety of medication use in primary care

© 2014 Royal Pharmaceutical Society.BACKGROUND: Medication errors are one of the leading causes of harmin health care. Review and analysis of errors have often emphasized their preventable nature and potential for reoccurrence. Of the few error studies conducted in primary care to date, most have focused on evaluating individual parts of the medicines management system. Studying individual parts of the system does not provide a complete perspective and may further weaken the evidence and undermine interventions.AIM AND OBJECTIVES: The aim of this review is to estimate the scale of medication errors as a problem across the medicines management system in primary care. Objectives were: To review studies addressing the rates of medication errors, and To identify studies on interventions to prevent medication errors in primary care.METHODS: A systematic search of the literature was performed in PubMed (MEDLINE), International Pharmaceutical Abstracts (IPA), Embase, PsycINFO, PASCAL, Science Direct, Scopus, Web of Knowledge, and CINAHL PLUS from 1999 to November, 2012. Bibliographies of relevant publications were searched for additional studies.KEY FINDINGS: Thirty-three studies estimating the incidence of medication errors and thirty-six studies evaluating the impact of error-prevention interventions in primary care were reviewed. This review demonstrated that medication errors are common, with error rates between 90%, depending on the part of the system studied, and the definitions and methods used. The prescribing stage is the most susceptible, and that the elderly (over 65 years), and children (under 18 years) are more likely to experience significant errors. Individual interventions demonstrated marginal improvements in medication safety when implemented on their own.CONCLUSION: Targeting the more susceptible population groups and the most dangerous aspects of the system may be a more effective approach to error management and prevention. Co-implementation of existing interventions at points within the system may offer time- and cost-effective options to improving medication safety in primary care.Peer reviewe

A guided tour of asynchronous cellular automata

Research on asynchronous cellular automata has received a great amount of attention these last years and has turned to a thriving field. We survey the recent research that has been carried out on this topic and present a wide state of the art where computing and modelling issues are both represented.Comment: To appear in the Journal of Cellular Automat