Particle Dark Matter Constraints from the Draco Dwarf Galaxy

It is widely thought that neutralinos, the lightest supersymmetric particles, could comprise most of the dark matter. If so, then dark halos will emit radio and gamma ray signals initiated by neutralino annihilation. A particularly promising place to look for these indicators is at the center of the local group dwarf spheroidal galaxy Draco, and recent measurements of the motion of its stars have revealed it to be an even better target for dark matter detection than previously thought. We compute limits on WIMP properties for various models of Draco's dark matter halo. We find that if the halo is nearly isothermal, as the new measurements indicate, then current gamma ray flux limits prohibit much of the neutralino parameter space. If Draco has a moderate magnetic field, then current radio limits can rule out more of it. These results are appreciably stronger than other current constraints, and so acquiring more detailed data on Draco's density profile becomes one of the most promising avenues for identifying dark matter.Comment: 13 pages, 6 figure

Exploiting RAS Nucleotide Cycling as a Strategy for Drugging RAS-Driven Cancers

Oncogenic mutations in RAS genes result in the elevation of cellular active RAS protein levels and increased signal propagation through downstream pathways that drive tumor cell proliferation and survival. These gain-of-function mutations drive over 30% of all human cancers, presenting promising therapeutic potential for RAS inhibitors. However, many have deemed RAS “undruggable” after nearly 40 years of failed drug discovery campaigns aimed at identifying a RAS inhibitor with clinical activity. Here we review RAS nucleotide cycling and the opportunities that RAS biochemistry presents for developing novel RAS inhibitory compounds. Additionally, compounds that have been identified to inhibit RAS by exploiting various aspects of RAS biology and biochemistry will be covered. Our current understanding of the biochemical properties of RAS, along with reports of direct-binding inhibitors, both provide insight on viable strategies for the discovery of novel clinical candidates with RAS inhibitory activity

Improving the efficiency of HIV testing with peer recruitment, financial incentives, and the involvement of persons living with HIV infection.

The authors piloted an HIV testing and counseling (HTC) approach using respondent-driven sampling (RDS), financial incentives, and persons living with HIV infection (PLHIV).Eligible participants were aged 30-60 years, African American or black, and residents of Oakland, CA. Participants were tested for HIV infection and asked to refer up to 3 others. The authors compared the efficiency of RDS to conventional outreach-based HTC with the number needed to screen (NNS). They evaluated the effect of 2 randomly allocated recruitment incentives on the enrollment of high-risk or HIV-positive network associates: a flat incentive ($20) for eligible recruits or a conditional incentive ($10-35) for eligible recruits in priority groups, such as first-time testers.Forty-eight participants (10 PLHIV and 38 HIV negative) initiated recruitment chains resulting in 243 network associates. Nine (3.7%) participants tested HIV positive, of whom 7 (78%) were previously recognized. RDS was more efficient than conventional HTC at identifying any PLHIV (new or previously recognized; RDS: NNS = 27, 95% CI: 14 to 59; conventional: NNS = 154, 95% CI: 95 to 270). There was no difference between the 2 incentive groups in the likelihood of recruiting at least 1 high-risk HIV-negative or HIV-positive network associate (adjusted odds ratio = 0.89, 95% CI: 0.06 to 13.06) or in total number of high-risk HIV-negative or HIV-positive associates (adjusted odds ratio = 0.79, 95% CI: 0.23 to 2.71).Social network HTC strategies may increase demand for HTC and efficiently identify PLHIV. The flat incentive was as successful as the conditional incentive for recruiting high-risk individuals. Unexpectedly, this method also reidentified PLHIV aware of their status

Improving the efficiency of HIV testing with peer recruitment, financial incentives, and the involvement of persons living with HIV infection.

The authors piloted an HIV testing and counseling (HTC) approach using respondent-driven sampling (RDS), financial incentives, and persons living with HIV infection (PLHIV).Eligible participants were aged 30-60 years, African American or black, and residents of Oakland, CA. Participants were tested for HIV infection and asked to refer up to 3 others. The authors compared the efficiency of RDS to conventional outreach-based HTC with the number needed to screen (NNS). They evaluated the effect of 2 randomly allocated recruitment incentives on the enrollment of high-risk or HIV-positive network associates: a flat incentive ($20) for eligible recruits or a conditional incentive ($10-35) for eligible recruits in priority groups, such as first-time testers.Forty-eight participants (10 PLHIV and 38 HIV negative) initiated recruitment chains resulting in 243 network associates. Nine (3.7%) participants tested HIV positive, of whom 7 (78%) were previously recognized. RDS was more efficient than conventional HTC at identifying any PLHIV (new or previously recognized; RDS: NNS = 27, 95% CI: 14 to 59; conventional: NNS = 154, 95% CI: 95 to 270). There was no difference between the 2 incentive groups in the likelihood of recruiting at least 1 high-risk HIV-negative or HIV-positive network associate (adjusted odds ratio = 0.89, 95% CI: 0.06 to 13.06) or in total number of high-risk HIV-negative or HIV-positive associates (adjusted odds ratio = 0.79, 95% CI: 0.23 to 2.71).Social network HTC strategies may increase demand for HTC and efficiently identify PLHIV. The flat incentive was as successful as the conditional incentive for recruiting high-risk individuals. Unexpectedly, this method also reidentified PLHIV aware of their status