Deficiency of rds/peripherin causes photoreceptor death in mouse models of digenic and dominant retinitis pigmentosa

Retinitis pigmentosa (RP) is a group of inherited blinding diseases caused by mutations in multiple genes including RDS. RDS encodes rds/peripherin (rds), a 36-kDa glycoprotein in the rims of rod and cone outer-segment (OS) discs. Rom1 is related to rds with similar membrane topology and the identical distribution in OS. In contrast to RDS, no mutations in ROM1 alone have been associated with retinal disease. However, an unusual digenic form of RP has been described. Affected individuals in several families were doubly heterozygous for a mutation in RDS causing a leucine 185 to proline substitution in rds (L185P) and a null mutation in ROM1. Neither mutation alone caused clinical abnormalities. Here, we generated transgenic/knockout mice that duplicate the amino acid substitutions and predicted levels of rds and rom1 in patients with RDS-mediated digenic and dominant RP. Photoreceptor degeneration in the mouse model of digenic RP was faster than in the wild-type and monogenic controls by histological, electroretinographic, and biochemical analysis. We observed a positive correlation between the rate of photoreceptor loss and the extent of OS disorganization in mice of several genotypes. Photoreceptor degeneration in RDS-mediated RP appears to be caused by a simple deficiency of rds and rom1. The critical threshold for the combined abundance of rds and rom1 is ≈60% of wild type. Below this value, the extent of OS disorganization results in clinically significant photoreceptor degeneration.

Dietary lipids and calorie restriction affect mammary tumor incidence and gene expression in mouse mammary tumor virus/v-Ha-ras transgenic mice.

We have studied the effects of food restriction (FR) and substitution of fish oil (FO; omega 3) for corn oil (CO; omega 6) on breast tumor incidence and survival in mouse mammary tumor virus/v-Ha-ras transgenic (Onco) mice. The diets were as follows: group 1, 5% (wt/wt) CO fed ad libitum (AL); group 2, 5% CO, restricted calories (40% fewer calories than AL; FR); group 3, 20% CO fed AL; and group 4, 20% FO fed AL. After 3 years, 40% of FR Onco (group 2) mice were alive, whereas there were no survivors in the other three groups. Similarly, tumor incidence was reduced to 27% (5 out of 18) in FR animals (group 2), whereas it was 83% (11 out of 13) in group 1 mice, 89% (16 out of 18) in group 3 mice, and 71% (10 out of 14) in group 4 mice. These protective effects of FR on survival and tumor incidence were paralleled by higher expression of the tumor suppressor gene p53 (wild type) and free-radical scavenging enzymes (catalase and superoxide dismutase) in breast tumors. Immunoblotting showed less ras gene product, p21, and increased p53 levels in the tumors of FR mice. In addition, FR decreased RNA levels of c-erbB-2, interleukin 6, and the transgene v-Ha-ras in tumors. In contrast, analysis of hepatic mRNA from tumor-bearing FR mice revealed higher expression of catalase, glutathione peroxidase, and superoxide dismutase. Survival and tumor incidence were not influenced significantly by dietary supplementation with FO in place of CO. Taken together, our studies suggest that moderate restriction of energy intake significantly inhibited the development of mammary tumors and altered expression of cytokines, oncogenes, and free-radical scavenging enzymes.

Party Elites and the Search for Credibility : Plaid Cymru and the SNP as New Parties of Government

Peer reviewed

On the time to reach a critical number of infections in epidemic models with infective and susceptible immigrants.

In this paper we examine the time T to reach a critical number K0 of infections during an outbreak in an epidemic model with infective and susceptible immigrants. The underlying process X, which was first introduced by Ridler-Rowe (1967), is related to recurrent diseases and it appears to be analytically intractable. We present an approximating model inspired from the use of extreme values, and we derive formulae for the Laplace-Stieltjes transform of T and its moments, which are evaluated by using an iterative procedure. Numerical examples are presented to illustrate the effects of the contact and removal rates on the expected values of T and the threshold K0, when the initial time instant corresponds to an invasion time. We also study the exact reproduction number Rexact,0 and the population transmission number Rp, which are random versions of the basic reproduction number R0.

USLE and WEPP Soil Erosion Models: Their Applicability and Use in Generating Cover Values to Stabilize Soil in the Los Alamos, New Mexico Area

Soil erosion is a naturally occurring process that involves the detachment, transport, and deposition of soil particles. Disturbances such as thinning and wildfire can reduce cover greatly and increase erosion rates. Forest managers may use erosion prediction tools, such as the Universal Soil Loss Equation (USLE) and Water Erosion Prediction Project (WEPP) to estimate erosion rates and develop techniques to manage erosion. However, it is important to understand the differences and the applications of each model. Erosion rates were generated by each model and the model most applicable to the study site, Los Alamos, New Mexico was determined. It was also used to find the amount of cover needed to stabilize soil. The USLE is a simpler model and less complicated than a computer model like WEPP, and thus easier to manipulate to estimate cover values. Predicted cover values were compared to field cover values. Cover is necessary to establish effective erosion control guidelines.

Bayesian models for finding and grouping junctions

In this paper, we propose two Bayesian methods for detecting and grouping junctions. Our junction detection method evolves from the Kona approach, and it is based on a competitive greedy procedure inspired in the region competition method. Then, junction grouping is accomplished by finding connecting paths between pairs of junctions. Path searching is performed by applying a Bayesian A* algorithm that has been recently proposed. Both methods are efficient and robust, and they are tested with synthetic and real images.

Question answering and multi-search engines in geo-temporal information retrieval

In this paper we present a complete system for the treatment of both geographical and temporal dimensions in text and its application to information retrieval. This system has been evaluated in both the GeoTime task of the 8th and 9th NTCIR workshop in the years 2010 and 2011 respectively, making it possible to compare the system to contemporary approaches to the topic. In order to participate in this task we have added the temporal dimension to our GIR system. The system proposed here has a modular architecture in order to add or modify features. In the development of this system, we have followed a QA-based approach as well as multi-search engines to improve the system performance.

THE DARK PERSONALITY AND JOB SUCCESS IN THE UNITED STATES ARMY: USE OF INTERPERSONAL MANIPULATION IN THE WORKPLACE

This dissertation relates job desires and outcomes to the Dark Personality (Psychopathy, Machiavellianism, Narcissism, Low Agreeableness, Low Honesty-Humility) in the United States Army. It purports that individuals high on the Dark Personality desire more power, money, and status, and that they obtain jobs that afford them these luxuries by using manipulation at work. Two pilot studies used samples of United States Army members to create and test index variables: Dark Personality, Total Manipulation in the workplace, Desire for Job Success, and Total Job Success in the Army. Individual personality traits, manipulation tactics, and job desires were examined in secondary analyses. Using a sample of 468 United States Army Members, central analyses indicated that Army members high on the Dark Personality desired Job Success. Likewise, army members higher on the Dark Personality used more Manipulation tactics at work, including the egregious tactics. Yet, using more Manipulation tactics at work predicted lower levels of Job Success in the Army. Most manipulation tactics had a negative impact on Job Success, with the exception of soft tactics like Reason and Responsibility Invocation. Together, these results indicate that selective use of soft manipulation predicted Job Success, but use of more manipulation tactics predicted less Job Success in the Army. Curvilinear results indicated that being either very low or very high on the Dark Personality predicted more Job Success in the Army, whereas having intermediate levels of the Dark Personality predicted less Job Success. Finally, possessing the Dark Personality and using more Manipulation tactics at work, together, predicted less Job Success in the Army. Collectively, the results indicate that army members with intermediate levels of the Dark Personality want more powerful and high paying jobs, yet their strategy of manipulating their coworkers to move up the job ladder does not result in higher ranking, higher paying Army positions. However, Army members highest on the Dark Personality achieved job success, defying the maladaptive influence that antisocial personality traits and manipulative behaviour had on job success for most Army members. Therefore, this dissertation indicates that successful corporate scoundrels exist in the Army, but there are few of them.