A newly modified fast temperature-stepping thermodenuder (TD) was coupled to a High Resolution Time-of-Flight Aerosol Mass Spectrometer for rapid determination of chemically resolved volatility of ...organic aerosols (OA) emitted from individual sources. The TD-AMS system was used to characterize primary OA (POA) from biomass burning, trash burning surrogates (paper and plastic), and meat cooking as well as chamber-generated secondary OA (SOA) from α-pinene and gasoline vapor. Almost all atmospheric models represent POA as nonvolatile, with no allowance for evaporation upon heating or dilution, or condensation upon cooling. Our results indicate that all OAs observed show semivolatile behavior and that most POAs characterized here were at least as volatile as SOA measured in urban environments. Biomass-burning OA (BBOA) exhibited a wide range of volatilities, but more often showed volatility similar to urban OA. Paper-burning resembles some types of BBOA because of its relatively high volatility and intermediate atomic oxygen-to-carbon (O/C) ratio, while meat-cooking OAs (MCOA) have consistently lower volatility than ambient OA. Chamber-generated SOA under the relatively high concentrations used in traditional experiments was significantly more volatile than urban SOA, challenging extrapolation of traditional laboratory volatility measurements to the atmosphere. Most OAs sampled show increasing O/C ratio and decreasing H/C (hydrogen-to-carbon) ratio with temperature, further indicating that more oxygenated OA components are typically less volatile. Future experiments should systematically explore a wider range of mass concentrations to more fully characterize the volatility distributions of these OAs.
Abstract Relativistic electron-positron plasmas are ubiquitous in extreme astrophysical environments such as black-hole and neutron-star magnetospheres, where accretion-powered jets and pulsar winds ...are expected to be enriched with electron-positron pairs. Their role in the dynamics of such environments is in many cases believed to be fundamental, but their behavior differs significantly from typical electron-ion plasmas due to the matter-antimatter symmetry of the charged components. So far, our experimental inability to produce large yields of positrons in quasi-neutral beams has restricted the understanding of electron-positron pair plasmas to simple numerical and analytical studies, which are rather limited. We present the first experimental results confirming the generation of high-density, quasi-neutral, relativistic electron-positron pair beams using the 440 GeV/c beam at CERN’s Super Proton Synchrotron (SPS) accelerator. Monte Carlo simulations agree well with the experimental data and show that the characteristic scales necessary for collective plasma behavior, such as the Debye length and the collisionless skin depth, are exceeded by the measured size of the produced pair beams. Our work opens up the possibility of directly probing the microphysics of pair plasmas beyond quasi-linear evolution into regimes that are challenging to simulate or measure via astronomical observations.
Chemical genetics has arisen as a powerful approach for identifying novel anti-cancer agents. However, a major bottleneck of this approach is identifying the targets of lead compounds that arise from ...screens. Here, we coupled the synthesis and screening of fragment-based cysteine-reactive covalent ligands with activity-based protein profiling (ABPP) chemoproteomic approaches to identify compounds that impair colorectal cancer pathogenicity and map the druggable hotspots targeted by these hits. Through this coupled approach, we discovered a cysteine-reactive acrylamide DKM 3-30 that significantly impaired colorectal cancer cell pathogenicity through targeting C1101 on reticulon 4 (RTN4). While little is known about the role of RTN4 in colorectal cancer, this protein has been established as a critical mediator of endoplasmic reticulum tubular network formation. We show here that covalent modification of C1101 on RTN4 by DKM 3-30 or genetic knockdown of RTN4 impairs endoplasmic reticulum and nuclear envelope morphology as well as colorectal cancer pathogenicity. We thus put forth RTN4 as a potential novel colorectal cancer therapeutic target and reveal a unique druggable hotspot within RTN4 that can be targeted by covalent ligands to impair colorectal cancer pathogenicity. Our results underscore the utility of coupling the screening of fragment-based covalent ligands with isoTOP-ABPP platforms for mining the proteome for novel druggable nodes that can be targeted for cancer therapy.
Untreated hypothyroidism is associated with acquired von Willebrand syndrome, and hyperthyroidism is associated with increased thrombosis risk. However, the causal effects of thyroid function on ...hemostasis, coagulation, and fibrinolysis are unknown.
In a two-sample Mendelian randomization (MR) study with genome-wide association variants, we assessed causality of genetically predicted hypothyroidism (
= 134,641), normal-range thyrotropin (TSH;
= 54,288) and free thyroxine (fT4) (
= 49,269), hyperthyroidism (
= 51,823), and thyroid peroxidase antibody positivity (
= 25,821) on coagulation (activated partial thromboplastin time, von Willebrand factor VWF, factor VIII FVIII, prothrombin time, factor VII, fibrinogen) and fibrinolysis (D-dimer, tissue plasminogen activator TPA, plasminogen activator inhibitor-1) from the CHARGE Hemostasis Consortium (
= 2583-120,246). Inverse-variance-weighted random effects were the main MR analysis followed by sensitivity analyses. Two-sided
< 0.05 was nominally significant, and
< 0.0011 = 0.05/(5 exposures × 9 outcomes) was Bonferroni significant for the main MR analysis.
Genetically increased TSH was associated with decreased VWF β(SE) = -0.020(0.006),
= 0.001 and with decreased fibrinogen β(SE) = -0.008(0.002),
= 0.001. Genetically increased fT4 was associated with increased VWF β(SE) = 0.028(0.011),
= 0.012. Genetically predicted hyperthyroidism was associated with increased VWF β(SE) = 0.012(0.004),
= 0.006 and increased FVIII β(SE) = 0.013(0.005),
= 0.007. Genetically predicted hypothyroidism and hyperthyroidism were associated with decreased TPA β(SE) = -0.009(0.024),
= 0.024 and increased TPA β(SE) = 0.022(0.008),
= 0.008, respectively. MR sensitivity analyses showed similar direction but lower precision. Other coagulation and fibrinolytic factors were inconclusive.
In the largest genetic studies currently available, genetically increased TSH and fT4 may be associated with decreased and increased synthesis of VWF, respectively. Since Bonferroni correction may be too conservative given the correlation between the analyzed traits, we cannot reject nominal associations of thyroid traits with coagulation or fibrinolytic factors.
Calcium intake is critical for adequate bone mineralization in adolescence, but it is usually inadequate in US adolescents. A strategy to maximize bone mineralization is to increase calcium ...absorption, which could be achieved by soluble corn fiber (SCF). There are no studies determining the long-term effects of SCF on bone mass in children.
To determine the effect of one-year SCF supplementation compared to placebo on bone mass and bone biomarkers in children with low habitual calcium intake. We hypothesize that SCF supplementation will result in a higher bone mineral content and higher levels of bone formation and lower bone resorption biomarkers.
240 healthy children (10–13 years), with usual low calcium intake, will be randomized to four experimental groups for 1 year: (1) SCF (12 g/d); (2) SCF (12 g/d) + 600 mg/d of calcium; (3) Placebo (maltodextrin); and (4) Placebo +600 mg/d of calcium. The supplements have been pre-mixed with a flavored powder beverage and participants will only need to dilute it in water and drink this twice per day. Bone will be measured using dual energy x-ray absorptiometry (DXA) at baseline, 6 and 12 months. Serum bone biomarkers will be measured at baseline and at 12 months.
If supplementing diets with SCF lead to higher bone mass during adolescence, this could help achieve the genetic potential for PBM and to start adult life with stronger bones. If successful, SCF can be incorporated into diets for promoting bone health in adolescents.
An experimental scheme is presented for generating low-divergence, ultradense, relativistic, electron-positron beams using 400 GeV/c protons available at facilities such as HiRadMat and AWAKE at ...CERN. Preliminary Monte Carlo and particle-in-cell simulations demonstrate the possibility of generating beams containing 10(13)-10(14) electron-positron pairs at sufficiently high densities to drive collisionless beam-plasma instabilities, which are expected to play an important role in magnetic field generation and the related radiation signatures of relativistic astrophysical phenomena. The pair beams are quasineutral, with size exceeding several skin depths in all dimensions, allowing the examination of the effect of competition between transverse and longitudinal instability modes on the growth of magnetic fields. Furthermore, the presented scheme allows for the possibility of controlling the relative density of hadrons to electron-positron pairs in the beam, making it possible to explore the parameter spaces for different astrophysical environments.
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