Strain‐Promoted Cycloadditions in Lipid Bilayers Triggered by Liposome Fusion

Due to the variety of roles served by the cell membrane, its composition and structure are complex, making it difficult to study. Bioorthogonal reactions, such as the strain promoted azide-alkyne cycloaddition (SPAAC), are powerful tools for exploring the function of biomolecules in their native environment but have been largely unexplored within the context of lipid bilayers. Here, we developed a new approach to study the SPAAC reaction in liposomal membranes using azide- and strained alkyne-functionalized Förster resonance energy transfer (FRET) dye pairs. This study represents the first characterization of the SPAAC reaction between diffusing molecules inside liposomal membranes. Potential applications of this work include in situ bioorthogonal labeling of membrane proteins, improved understanding of membrane dynamics and fluidity, and the generation of new probes for biosensing assays

Location matters:Valuing firm-specific nonmarket risk in the global mining industry

Research summary Using collective action and social movement theory, we investigate the potential incentives and ability of stakeholders to engage in collective action that can increase firm-specific nonmarket risk of mining companies. We argue that proximity to the nearest environmentally sensitive water source increases the probability that local stakeholders will take collective actions that impose material costs on the focal mine. We hypothesize that stock markets recognize this nonmarket risk and apply a discount on announcements related to mines located near such areas, and that these risks are moderated by the type of mineral, the nature of the water source, and the strength of host country institutions. Using a unique data set and an event study method, we find support for most of our arguments. Managerial summary We argue that mines located near environmentally sensitive water sources are subject to nonmarket risks arising from the potential collective actions of local stakeholders and their allies. Stakeholder mobilization can impose material costs on a mine in the form of delays, regulatory hurdles, and closure. We find that stock markets recognize these nonmarket risks and apply a discount on announcements by mining companies whose mines are located near environmentally sensitive water sources, particularly rivers. However, we also find that investor reaction is stronger in countries with strong institutions that support collective action. Thus, nonmarket risk management is important even in countries that are typically characterized by low political and institutional risks. We discuss the degree to which these results can be generalized beyond mining

Effect of a behavioral intervention for underserved preschool-age children on change in body mass index: A randomized clinical trial

IMPORTANCE Prevention of obesity during childhood is critical for children in underserved populations, for whom obesity prevalence and risk of chronic disease are highest. OBJECTIVE To test the effect of a multicomponent behavioral intervention on child body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) growth trajectories over 36 months among preschool-age children at risk for obesity. DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial assigned 610 parent-child pairs from underserved communities in Nashville, Tennessee, to a 36-month intervention targeting health behaviors or a school-readiness control. Eligible children were between ages 3 and 5 years and at risk for obesity but not yet obese. Enrollment occurred from August 2012 to May 2014; 36-month follow-up occurred from October 2015 to June 2017. INTERVENTIONS The intervention (n = 304 pairs) was a 36-month family-based, community-centered program, consisting of 12 weekly skills-building sessions, followed by monthly coaching telephone calls for 9 months, and a 24-month sustainability phase providing cues to action. The control (n = 306 pairs) consisted of 6 school-readiness sessions delivered over the 36-month study, conducted by the Nashville Public Library. MAIN OUTCOMES AND MEASURES The primary outcome was child BMI trajectory over 36 months. Seven prespecified secondary outcomes included parent-reported child dietary intake and community center use. The Benjamini-Hochberg procedure corrected for multiple comparisons. RESULTS Participants were predominantly Latino (91.4%). At baseline, the mean (SD) child age was 4.3 (0.9) years; 51.9% were female. Household income was below $25 000 for 56.7% of families. Retention was 90.2%. At 36 months, the mean (SD) child BMI was 17.8 (2.2) in the intervention group and 17.8 (2.1) in the control group. No significant difference existed in the primary outcome of BMI trajectory over 36 months (P = .39). The intervention group children had a lower mean caloric intake (1227 kcal/d) compared with control group children (1323 kcal/d) (adjusted difference, −99.4 kcal [95% CI, −160.7 to −38.0]; corrected P = .003). Intervention group parents used community centers with their children more than control group parents (56.8% in intervention; 44.4% in control) (risk ratio, 1.29 [95% CI, 1.08 to 1.53]; corrected P = .006). CONCLUSIONS AND RELEVANCE A 36-month multicomponent behavioral intervention did not change BMI trajectory among underserved preschool-age children in Nashville, Tennessee, compared with a control program. Whether there would be effectiveness for other types of behavioral interventions or implementation in other cities would require further research

Searching for star-planet magnetic interaction in CoRoT observations

Close-in massive planets interact with their host stars through tidal and magnetic mechanisms. In this paper, we review circumstantial evidence for star-planet interaction as revealed by the photospheric magnetic activity in some of the CoRoT planet-hosting stars, notably CoRoT-2, CoRoT-4, and CoRoT-6. The phenomena are discussed in the general framework of activity-induced features in stars accompanied by hot Jupiters. The theoretical mechanisms proposed to explain the activity enhancements possibly related with hot Jupiter are also briefly reviewed with an emphasis on the possible effects at photospheric level. The unique advantages of CoRoT and Kepler observations to test these models are pointed out.Comment: Invited review paper accepted by Astrophysics and Space Science, 13 pages, 5 figure

Differences in somatic TP53 mutation type in breast tumors by race and receptor status

Purpose: Somatic driver mutations in TP53 are associated with triple-negative breast cancer (TNBC) and poorer outcomes. Breast cancers in women of African ancestry (AA) are more likely to be TNBC and have somatic TP53 mutations than cancers in non-Hispanic White (NHW) women. Missense driver mutations in TP53 have varied functional impact including loss-of-function (LOF) or gain-of-function (GOF) activity, and dominant negative (DNE) effects. We aimed to determine if there were differences in somatic TP53 mutation types by patient ancestry or TNBC status. Methods: We identified breast cancer datasets with somatic TP53 mutation data, ancestry, age, and hormone receptor status. Mutations were classified for functional impact using published data and type of mutation. We assessed differences using Fisher’s exact test. Results: From 96 breast cancer studies, we identified 2964 women with somatic TP53 mutations: 715 (24.1%) Asian, 258 (8.7%) AA, 1931 (65.2%) NHW, and 60 (2%) Latina. The distribution of TP53 mutation type was similar by ancestry. However, 35.8% of tumors from NHW individuals had GOF mutations compared to 29% from AA individuals (p = 0.04). Mutations with DNE activity were positively associated with TNBC (OR 1.37, p = 0.03) and estrogen receptor (ER) negative status (OR 1.38; p = 0.005). Conclusions: Somatic TP53 mutation types did not differ by ancestry overall, but GOF mutations were more common in NHW women than AA women. ER-negative and TNBC tumors are less likely to have DNE+ TP53 mutations which could reflect biological processes. Larger cohorts and functional studies are needed to further elucidate these findings

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR