The Mass of the Candidate Exoplanet Companion to HD136118 from Hubble Space Telescope Astrometry and High-Precision Radial Velocities

We use Hubble Space Telescope Fine Guidance Sensor astrometry and high-cadence radial velocities for HD136118 from the HET with archival data from Lick to determine the complete set of orbital parameters for HD136118b. We find an orbital inclination for the candidate exoplanet of i_{b} = 163.1 +- 3.0 deg. This establishes the actual mass of the object, M_{b} = 42^{+11}_{-18} MJup, in contrast to the minimum mass determined from the radial velocity data only, M_{b}sin{i} ~ 12 MJup. Therefore, the low-mass companion to HD 136118 is now identified as a likely brown dwarf residing in the "brown dwarf desert".Comment: 35 pages, 12 figures, 10 tables. Accepted for publication in Astrophysical Journa

Detection of a Third Planet in the HD 74156 System Using the Hobby-Eberly Telescope

We report the discovery of a third planetary mass companion to the G0 star HD 74156. High precision radial velocity measurements made with the Hobby-Eberly Telescope aided the detection of this object. The best fit triple Keplerian model to all the available velocity data yields an orbital period of 347 days and minimum mass of 0.4 M_Jup for the new planet. We determine revised orbital periods of 51.7 and 2477 days, and minimum masses of 1.9 and 8.0 M_Jup respectively for the previously known planets. Preliminary calculations indicate that the derived orbits are stable, although all three planets have significant orbital eccentricities (e = 0.64, 0.43, and 0.25). With our detection, HD 74156 becomes the eighth normal star known to host three or more planets. Further study of this system's dynamical characteristics will likely give important insight to planet formation and evolutionary processes.Comment: 24 pages, 4 tables, 6 figures. Accepted for publication in ApJ. V2 fixed table 4 page overrun. V3 added reference

Consumers' intention to use health recommendation systems to receive personalized nutrition advice

Background: Sophisticated recommendation systems are used more and more in the health sector to assist consumers in healthy decision making. In this study we investigate consumers' evaluation of hypothetical health recommendation systems that provide personalized nutrition advice. We examine consumers' intention to use such a health recommendation system as a function of options related to the underlying system (e.g. the type of company that generates the advice) as well as intermediaries (e.g. general practitioner) that might assist in using the system. We further explore if the effect of both the system and intermediaries on intention to use a health recommendation system are mediated by consumers' perceived effort, privacy risk, usefulness and enjoyment. Methods. 204 respondents from a consumer panel in the Netherlands participated. The data were collected by means of a questionnaire. Each respondent evaluated three hypothetical health recommendation systems on validated multi-scale measures of effort, privacy risk, usefulness, enjoyment and intention to use the system. To test the hypothesized relationships we used regression analyses. Results: We find evidence that the options related to the underlying system as well as the intermediaries involved influence consumers' intention to use such a health recommendation system and that these effects are mediated by perceptions of effort, privacy risk, usefulness and enjoyment. Also, we find that consumers value usefulness of a system more and enjoyment less when a general practitioner advices them to use a health recommendation system than if they use it out of their own curiosity. Conclusions: We developed and tested a model of consumers' intention to use a health recommendation system. We found that intermediaries play an important role in how consumers evaluate such a system over and above options of the underlying system that is used to generate the recommendation. Also, health-related information services seem to rely on endorsement by the medical sector. This has considerable implications for the distribution as well as the communication channels of health recommendation systems which may be quite difficult to put into practice outside traditional health service channels

Choice of resident costimulatory molecule can influence cell fate in human naïve CD4+ T cell differentiation

With antigen stimulation, naïve CD4+ T cells differentiate to several effector or memory cell populations, and cytokines contribute to differentiation outcome. Several proteins on these cells receive costimulatory signals, but a systematic comparison of their differential effects on naïve T cell differentiation has not been conducted. Two costimulatory proteins, CD28 and ICAM-1, resident on human naïve CD4+ T cells were compared for participation in differentiation. Under controlled conditions, and with no added cytokines, costimulation through either CD3+CD28 or CD3+ICAM-1 induced differentiation to T effector and T memory cells. In contrast, costimulation through CD3+ICAM-1 induced differentiation to Treg cells whereas costimulation through CD3+CD28 did not

Ubiquitination and degradation of SUMO1 by small-molecule degraders extends survival of mice with patient-derived tumors

Discovery of small-molecule degraders that activate ubiquitin ligase–mediated ubiquitination and degradation of targeted oncoproteins in cancer cells has been an elusive therapeutic strategy. Here, we report a cancer cell–based drug screen of the NCI drug-like compounds library that enabled identification of small-molecule degraders of the small ubiquitin-related modifier 1 (SUMO1). Structure-activity relationship studies of analogs of the hit compound CPD1 led to identification of a lead compound HB007 with improved properties and anticancer potency in vitro and in vivo. A genome-scale CRISPR-Cas9 knockout screen identified the substrate receptor F-box protein 42 (FBXO42) of cullin 1 (CUL1) E3 ubiquitin ligase as required for HB007 activity. Using HB007 pull-down proteomics assays, we pinpointed HB007’s binding protein as the cytoplasmic activation/proliferation-associated protein 1 (CAPRIN1). Biolayer interferometry and compound competitive immunoblot assays confirmed the selectivity of HB007’s binding to CAPRIN1. When bound to CAPRIN1, HB007 induced the interaction of CAPRIN1 with FBXO42. FBXO42 then recruited SUMO1 to the CAPRIN1-CUL1-FBXO42 ubiquitin ligase complex, where SUMO1 was ubiquitinated in several of human cancer cells. HB007 selectively degraded SUMO1 in patient tumor–derived xenografts implanted into mice. Systemic administration of HB007 inhibited the progression of patient-derived brain, breast, colon, and lung cancers in mice and increased survival of the animals. This cancer cell–based screening approach enabled discovery of a small-molecule degrader of SUMO1 and may be useful for identifying other small-molecule degraders of oncoproteins