Ultrabright Electron Bunch Injection in a Plasma Wakefield Driven by a Superluminal Flying Focus Electron Beam.

We propose a new method for self-injection of high-quality electron bunches in the plasma wakefield structure in the blowout regime utilizing a "flying focus" produced by a drive beam with an energy chirp. In a flying focus the speed of the density centroid of the drive bunch can be superluminal or subluminal by utilizing the chromatic dependence of the focusing optics. We first derive the focal velocity and the characteristic length of the focal spot in terms of the focal length and an energy chirp. We then demonstrate using multidimensional particle-in-cell simulations that a wake driven by a superluminally propagating flying focus of an electron beam can generate GeV-level electron bunches with ultralow normalized slice emittance (∼30 nm rad), high current (∼17 kA), low slice energy spread (∼0.1%), and therefore high normalized brightness (>10^{19} A/m^{2}/rad^{2}) in a plasma of density ∼10^{19} cm^{-3}. The injection process is highly controllable and tunable by changing the focal velocity and shaping the drive beam current. Near-term experiments at FACET II where the capabilities to generate tens of kA, <10 fs drivers are planned, could potentially produce beams with brightness near 10^{20} A/m^{2}/rad^{2}.

Improved Limit on Tensor Currents in the Weak Interaction from

The electroweak interaction in the standard model is described by a pure vector-axial-vector structure, though any Lorentz-invariant component could contribute. In this Letter, we present the most precise measurement of tensor currents in the low-energy regime by examining the ß-ν[over ¯] correlation of trapped ^{8}Li ions with the Beta-decay Paul Trap. We find a_{ßν}=-0.3325±0.0013_{stat}±0.0019_{syst} at 1σ for the case of coupling to right-handed neutrinos (C_{T}=-C_{T}^{'}), which is consistent with the standard model prediction.

Large contribution of natural aerosols to uncertainty in indirect forcing.

The effect of anthropogenic aerosols on cloud droplet concentrations and radiative properties is the source of one of the largest uncertainties in the radiative forcing of climate over the industrial period. This uncertainty affects our ability to estimate how sensitive the climate is to greenhouse gas emissions. Here we perform a sensitivity analysis on a global model to quantify the uncertainty in cloud radiative forcing over the industrial period caused by uncertainties in aerosol emissions and processes. Our results show that 45 per cent of the variance of aerosol forcing since about 1750 arises from uncertainties in natural emissions of volcanic sulphur dioxide, marine dimethylsulphide, biogenic volatile organic carbon, biomass burning and sea spray. Only 34 per cent of the variance is associated with anthropogenic emissions. The results point to the importance of understanding pristine pre-industrial-like environments, with natural aerosols only, and suggest that improved measurements and evaluation of simulated aerosols in polluted present-day conditions will not necessarily result in commensurate reductions in the uncertainty of forcing estimates.

Assessing the influence of secondary organic versus primary carbonaceous aerosols on long-range atmospheric polycyclic aromatic hydrocarbon transport.

We use the chemical transport model GEOS-Chem to evaluate the hypothesis that atmospheric polycyclic aromatic hydrocarbons (PAHs) are trapped in secondary organic aerosol (SOA) as it forms. We test the ability of three different partitioning configurations within the model to reproduce observed total concentrations in the midlatitudes and the Arctic as well as midlatitude gas-particle phase distributions. The configurations tested are (1) the GEOS-Chem default configuration, which uses instantaneous equilibrium partitioning to divide PAHs among the gas phase, a primary organic matter (OM) phase (absorptive), and a black carbon (BC) phase (adsorptive), (2) an SOA configuration in which PAHs are trapped in SOA when emitted and slowly evaporate from SOA thereafter, and (3) a configuration in which PAHs are trapped in primary OM/BC upon emission and subsequently slowly evaporate. We also test the influence of changing the fraction of PAHs available for particle-phase oxidation. Trapping PAHs in SOA particles upon formation and protecting against particle-phase oxidation (2) better simulates observed remote concentrations compared to our default configuration (1). However, simulating adsorptive partitioning to BC is required to reproduce the magnitude and seasonal pattern of gas-particle phase distributions. Thus, the last configuration (3) results in the best agreement between observed and simulated concentration/phase distribution data. The importance of BC rather than SOA to PAH transport is consistent with strong observational evidence that PAHs and BC are coemitted.

A novel, noninvasive transdermal fluid sampling methodology: IGF-I measurement following exercise.

This study tested the hypothesis that transdermal fluid (TDF) provides a more sensitive and accurate measure of exercise-induced increases in insulin-like growth factor-I (IGF-I) than serum, and that these increases are detectable proximal, but not distal, to the exercising muscle. A novel, noninvasive methodology was used to collect TDF, followed by sampling of total IGF-I (tIGF-I) and free IGF-I (fIGF-I) in TDF and serum following an acute bout of exercise. Experiment 1: eight men (23 ± 3 yrs, 79 ± 7 kg) underwent two conditions (resting and 60 min of cycling exercise at 60% Vo(2)(peak)) in which serum and forearm TDF were collected for comparison. There were no significant changes in tIGF-I or fIGF-I in TDF obtained from the forearm or from serum following exercise (P > 0.05); however, the proportion of fIGF-I to tIGF-I in TDF was approximately fourfold greater than that of serum (P ≤ 0.05). These data suggest that changes in TDF IGF-I are not evident when TDF is sampled distal from the working tissue. To determine whether exercise-induced increases in local IGF-I could be detected when TDF was sampled directly over the active muscle group, we performed a second experiment. Experiment 2: fourteen subjects (22 ± 4 yr, 68 ± 11 kg) underwent an acute plyometric exercise condition consisting of 10 sets of 10 plyometric jumps with 2-min rest between sets. We observed a significant increase in TDF tIGF-I following exercise (P ≤ 0.05) but no change in serum tIGF-I (P > 0.05). Overall, these data suggest that TDF may provide a noninvasive means of monitoring acute exercise-induced changes in local IGF-I when sampled in proximity to exercising muscles. Moreover, our finding that the proportion of free to tIGF-I was greater in TDF than in serum suggests that changes in local IGF-I may be captured more readily using this system.

The future of scientific journals. A computer-based system will enable a subscriber to receive a personalized stream of papers.

Since many of the problems that beset readers, authors, and publishers of scientific journals are caused by the growth of science or by the frailties of human nature, we cannot hope for complete solutions. In an effort to make progress, within the framework of the possible, we propose that journals stop binding papers into issues and, instead, distribute to each subscriber a personalized stream of papers, abstracts, and titles. This type of distribution, which has been made possible by the advent of high-speed computers, would not affect the traditional roles of editors, referees, and libraries. We also propose that journals recognize the need for very rapid communication in certain fields, and meet the threat of public preprint-exchange systems in these fields by themselves publishing preprints in an appropriately limited manner.

Relationship between growth hormone in vivo bioactivity, the insulin-like growth factor-I system and bone mineral density in young, physically fit men and women.

CONTEXT: Bone mineral density (BMD) is influenced by growth factors, such as growth hormone (GH) and insulin-like growth factor-I (IGF-I). The in vivo bioassay for GH (bioGH) provides a more physiologically relevant measurement than an in vitro immunoassay, since bioGH is quantified on a biological outcome. OBJECTIVE: To determine if bioGH and components of the IGF-I system were associated with BMD in age-matched men (M; n=41, 19.1+/-0.2 year, 70+/-3 kg, 163+/-25 cm) and women (W; n=39, 18.6+/-0.3 year, 66+/-3 kg, 141+/-15 cm). DESIGN: Blood was analyzed for growth-related hormones [bioGH, immunoreactive growth hormone (iGH), IGF-I and associated binding proteins], and BMD was measured by pDXA, pQCT, and central DXA (spine, hip). For the bioGH assay, hypophysectomizied female Sprague-Dawley rats were injected with a s.c. bolus of either a GH standard or unknown (each subject's plasma) in four daily injections. The tibia was then examined for epiphyseal growth plate width from which bioGH concentrations were extrapolated. RESULTS: M had greater (P<0.05) calcaneal BMD when measured by pDXA (M: 1.27+/-0.02; W: 1.14+/-0.02 g/cm2), while pQCT-assessed BMD at the tibia was not different (M: 777+/-16; W: 799+/-16 g/cm2). bioGH was similar between M (5388+/-800 microg/L) and W (4282+/-643 microg/L) and was not correlated with BMD. The only BMD-related biomarkers in women were acid-labile subunit (ALS; r=0.40) and IGFBP-3 (r=0.42) with DXA-measured spine and femoral neck BMD, and ALS (r=0.47) with pQCT-assessed tibial BMD and cortical thickness, respectively. CONCLUSION: Although bioGH was not associated with BMD, IGF-I and associated binding proteins (IGFBP-3 and ALS) emerged as correlates in W only.

Ambient Particulate Matter Size Distributions Drive Regional and Global Variability in Particle Deposition in the Respiratory Tract.

Human exposure to airborne particulate matter (PM) increases the risk of negative health outcomes; however, substantial uncertainty remains in quantifying these exposure-response relationships. In particular, relating increased risk of mortality to exposure to PM with diameters smaller than 2.5 µm (PM2.5) neglects variability in the underlying size distribution of PM2.5 exposure and size-resolved deposition in human airways. In this study, we combine a size-resolved respiratory particle-deposition model with a global size-resolved aerosol model to estimate the variability in particle deposition along the respiratory tract due to variability in ambient PM size distributions. We find that the ratio of deposited PM mass in the tracheobronchial and alveolar regions per unit ambient PM2.5 exposure (deposition ratio and DRTB + AV) varies by 20-30% between populated regions due to variability in ambient PM size distributions. Furthermore, DRTB + AV can vary by as high as a factor of 4 between the fossil-fuel-dominated region of the Eastern United States and the desert-dust-dominated region of North Africa. When considering individual PM species, such as sulfate or organic matter, we still find variability in the DRTB + AV on the order of 30% due to regional variability in the size distribution. Finally, the spatial distribution of DRTB + AV based on number or surface area is substantially different than the DRTB + AV based on mass. These results suggest that regional variability in ambient aerosol size distributions drive variability in PM deposition in the body, which may lead to variability in the health response from exposure to PM2.5.

Quantifying the Contribution to Uncertainty in Mortality Attributed to Household, Ambient, and Joint Exposure to PM2.5 From Residential Solid Fuel Use.

While there have been substantial efforts to quantify the health burden of exposure to PM2.5 from solid fuel use (SFU), the sensitivity of mortality estimates to uncertainties in input parameters has not been quantified. Moreover, previous studies separate mortality from household and ambient air pollution. In this study, we develop a new estimate of mortality attributable to SFU due to the joint exposure from household and ambient PM2.5 pollution and perform a variance-based sensitivity analysis on mortality attributable to SFU. In the joint exposure calculation, we estimate 2.81 (95% confidence interval: 2.48-3.28) million premature deaths in 2015 attributed to PM2.5 from SFU, which is 580,000 (18%) fewer deaths than would be calculated by summing separate household and ambient mortality calculations. Regarding the sources of uncertainties in these estimates, in China, India, and Latin America, we find that 53-56% of the uncertainty in mortality attributable to SFU is due to uncertainty in the percent of the population using solid fuels and 42-50% from the concentration-response function. In sub-Saharan Africa, baseline mortality rate (72%) and the concentration-response function (33%) dominate the uncertainty space. Conversely, the sum of the variance contributed by ambient and household PM2.5 exposure ranges between 15 and 38% across all regions (the percentages do not sum to 100% as some uncertainty is shared between parameters). Our findings suggest that future studies should focus on more precise quantification of solid fuel use and the concentration-response relationship to PM2.5, as well as mortality rates in Africa.

Future Fire Impacts on Smoke Concentrations, Visibility, and Health in the Contiguous United States.

Fine particulate matter (PM2.5) from U.S. anthropogenic sources is decreasing. However, previous studies have predicted that PM2.5 emissions from wildfires will increase in the midcentury to next century, potentially offsetting improvements gained by continued reductions in anthropogenic emissions. Therefore, some regions could experience worse air quality, degraded visibility, and increases in population-level exposure. We use global climate model simulations to estimate the impacts of changing fire emissions on air quality, visibility, and premature deaths in the middle and late 21st century. We find that PM2.5 concentrations will decrease overall in the contiguous United States (CONUS) due to decreasing anthropogenic emissions (total PM2.5 decreases by 3% in Representative Concentration Pathway [RCP] 8.5 and 34% in RCP4.5 by 2100), but increasing fire-related PM2.5 (fire-related PM2.5 increases by 55% in RCP4.5 and 190% in RCP8.5 by 2100) offsets these benefits and causes increases in total PM2.5 in some regions. We predict that the average visibility will improve across the CONUS, but fire-related PM2.5 will reduce visibility on the worst days in western and southeastern U.S. regions. We estimate that the number of deaths attributable to total PM2.5 will decrease in both the RCP4.5 and RCP8.5 scenarios (from 6% to 4-5%), but the absolute number of premature deaths attributable to fire-related PM2.5 will double compared to early 21st century. We provide the first estimates of future smoke health and visibility impacts using a prognostic land-fire model. Our results suggest the importance of using realistic fire emissions in future air quality projections.

Contribution of Arctic seabird-colony ammonia to atmospheric particles and cloud-albedo radiative effect.

The Arctic region is vulnerable to climate change and able to affect global climate. The summertime Arctic atmosphere is pristine and strongly influenced by natural regional emissions, which have poorly understood climate impacts related to atmospheric particles and clouds. Here we show that ammonia from seabird-colony guano is a key factor contributing to bursts of newly formed particles, which are observed every summer in the near-surface atmosphere at Alert, Nunavut, Canada. Our chemical-transport model simulations indicate that the pan-Arctic seabird-influenced particles can grow by sulfuric acid and organic vapour condensation to diameters sufficiently large to promote pan-Arctic cloud-droplet formation in the clean Arctic summertime. We calculate that the resultant cooling tendencies could be large (about -0.5 W m-2 pan-Arctic-mean cooling), exceeding -1 W m-2 near the largest seabird colonies due to the effects of seabird-influenced particles on cloud albedo. These coupled ecological-chemical processes may be susceptible to Arctic warming and industrialization.

Repair of helix-stabilizing anthramycin-N2 guanine DNA adducts by UVRA and UVRB proteins.

The transfectivity of anthramycin (Atm)-modified phi X174 replicative form (RF) DNA in Escherichia coli is lower in uvrA and uvrB mutant cells but much higher in uvrC mutant cells compared to wild-type cells. Pretreatment of the Atm-modified phage DNA with purified UVRA and UVRB significantly increases the transfectivity of the DNA in uvrA or uvrB mutant cells. This pretreatment greatly reduces the UVRABC nuclease-sensitive sites (UNSS) and Atm-induced absorbance at 343 nm in the Atm-modified DNA without producing apurinic sites. The reduction of UNSS is proportional to the concentrations of UVRA and UVRB and the enzyme-DNA incubation time and requires ATP. We conclude that there are two different mechanisms for repairing Atm-N2 guanine adducts by UVR proteins: (1) UVRA and UVRB bind to the Atm-N2 guanine double-stranded DNA region and consequently release the Atm from the adducted guanine; (2) UVRABC makes an incision at both sides of the Atm-DNA adduct. The latter mechanism produces potentially lethal double-strand DNA breaks in Atm-modified phi X174 RF DNA in vitro.

Mutational analysis of the transferrin receptor reveals overlapping HFE and transferrin binding sites.

The transferrin receptor (TfR) binds two proteins critical for iron metabolism: transferrin (Tf) and HFE, the protein mutated in hereditary hemochromatosis. Previous results demonstrated that Tf and HFE compete for binding to TfR, suggesting that Tf and HFE bind to the same or an overlapping site on TfR. TfR is a homodimer that binds one Tf per polypeptide chain (2:2, TfR/Tf stoichiometry), whereas both 2:1 and 2:2 TfR/HFE stoichiometries have been observed. In order to more fully characterize the interaction between HFE and TfR, we determined the binding stoichiometry using equilibrium gel-filtration and analytical ultracentrifugation. Both techniques indicate that a 2:2 TfR/HFE complex can form at submicromolar concentrations in solution, consistent with the hypothesis that HFE competes for Tf binding to TfR by blocking the Tf binding site rather than by exerting an allosteric effect. To determine whether the Tf and HFE binding sites on TfR overlap, residues at the HFE binding site on TfR were identified from the 2.8 A resolution HFE-TfR co-crystal structure, then mutated and tested for their effects on HFE and Tf binding. The binding affinities of soluble TfR mutants for HFE and Tf were determined using a surface plasmon resonance assay. Substitutions of five TfR residues at the HFE binding site (L619A, R629A, Y643A, G647A and F650Q) resulted in significant reductions in Tf binding affinity. The findings that both HFE and Tf form 2:2 complexes with TfR and that mutations at the HFE binding site affect Tf binding support a model in which HFE and Tf compete for overlapping binding sites on TfR.

Transmission of tuberculosis to hospital workers by a patient with AIDS.

A patient with acquired immunodeficiency syndrome (AIDS) was admitted to a hospital with cough and fever and after 29 days was transferred to a hospice. He was eventually shown to have active pulmonary tuberculosis. This diagnosis was obscured clinically by simultaneous infection with Pneumocystis carinii and Mycobacterium avium complex (MAC). Laboratory recognition of Mycobacterium tuberculosis was delayed because of overgrowth of cultures by MAC but was later established using DNA probe techniques. Thirty (19 percent) of 158 health care workers who had been exposed to this patient had conversion of their tuberculin skin tests. Diagnostic difficulties and nosocomial transmission of tuberculosis may occur when patients with AIDS have mixed mycobacterial infections.