We measure stability of two-dimensional granular mixtures in a rotating drum and relate grain configurations to stability. We use two types of grains which differ in both size and shape, with the larger grains reaching a larger average angle before an avalanche. In our mixtures, the smaller grains cluster near the center of the drum, while the larger grains remain near the outer edge, a pattern suggesting that grain size rather than avalanche angle determines the segregation behavior. One consequence of the size segregation is that the smaller grains heavily influence the stability of the heap. We find that the maximum angle of stability is a non-linear function of composition, changing particularly rapidly when small grains are first added to a homogeneous pile of large grains. We conclude that the grain configuration within the central portion of the heap plays a prominent role in stability.

We develop an observation system that quantifies the duration, intensity, and frequency of children's physical activities. We use this system to assess the level and tempo of energy expenditure under free-ranging, natural conditions experienced by 15 children aged 6-10 yr in southern California. Observations were recorded every 3 s during 4-h time blocks from 8:00 a.m.-8:00 p.m. Agreement among observers using the coding system was 91%. Using indirect calorimetry, calibration studies in the laboratory determined VO2 (ml.min-1.min-1) during each coded activity, and activities were categorized by intensity (low, medium, or high). Subjects were found to engage in activities of low intensity 77.1% of time and activities of high intensity 3.1% of time. The median duration of low and medium intensity activities was 6 s, of high intensity activities only 3 s with 95% lasting less than 15 s. Children engaged in very short bursts of intense physical activity interspersed with varying intervals of low and moderate intensity. These findings may be important for discovering how children's activity patterns under natural conditions influence physiological processes leading to growth and development. This study demonstrates the advantages of using an observational system that captures more than the intensity and frequency of children's activities to include duration and the length of intervals between activities of varying intensity.

Data for the tropical upper troposphere (8-12 km, 20° N-20° S) collected during NASA's Pacific Exploratory Missions have been used to carry out a detailed examination of the photochemical processes controlling HOx (OH+HO2). Of particular significance is the availability of measurements of nonmethane hydrocarbons, oxygenated hydrocarbons (i.e., acetone, methanol, and ethanol) and peroxides (i.e., H2O2 and CH3OOH). These observations have provided constraints on model calculations permitting an assessment of the potential impact of these species on the levels of HOx, CH3O2, CH2O, as well as ozone budget parameters. Sensitivity calculations using a time-dependent photochemical box model show that when constrained by measured values of the above oxygenated species, model estimated HOx levels are elevated relative to unconstrained calculations. The impact of constraining these species was found to increase with altitude, reflecting the systematic roll-off in water vapor mixing ratios with altitude. At 11-12 km, overall increases in HOx approached a factor of 2 with somewhat larger increases being found for gross and net photochemical production of ozone. While significant, the impact on HOx due to peroxides appears to be less than previously estimated. In particular, observations of elevated H2O2 levels may be more influenced by local photochemistry than by convective transport. Issues related to the uncertainty in high-altitude water vapor levels and the possibility of other contributing sources of HOx are discussed. Finally, it is noted that the uncertainties in gas kinetic rate coefficients at the low temperatures of the upper troposphere and as well as OH sensor calibrations should be areas of continued investigation. Copyright 1999 by the American Geophysical Union.

Airborne observations of NO during the Subsonics Assessment Ozone and Nitrogen Oxides Experiment (SONEX) reveal episodes of high NOx in the upper troposphere believed to be associated with lightning. Linkage to specific periods of lightning activity is possible through back trajectories and data from the National Lightning Detection Network. Lagrangian model calculations are used to explore the evolution of these high NOx plumes over the 1-2 days between their introduction and subsequent sampling by NASA's DC-8 aircraft. Simulations include expected changes in HNO3, H2O2, CH3OOH, HO2, and OH. Depending on the time of injection and dilution rate, initial NOx concentrations are estimated to range from 1 to 7 ppbv. Similar to many previous studies, simulated HNO3 concentrations tend to be greater than observations. Several possible explanations for this difference are explored. H2O2 observations are shown to be consistent with removal in convective activity. While it is possible that upper tropospheric CH3OOH is enhanced by convection, simulations show such increases in CH3OOH can be short-lived (e.g., < 12 hours) with no perceptible trace remaining at the time of sampling. High NO levels further prevent elevated levels of CH3OOH from propagating into increases in H2O2. HO2 is suppressed through reaction with NO in all cases. Simulated increases in OH exceeded a factor of 2 for some cases, but for the highest NOx levels, loss of OH via OH+NO2 offset production from HO2+NO. Additional increases in OH of 30-60% could result from convection of CH3OOH. A final point of discussion concerns how the chemistry within these plumes, their long-range transport, and their potential importance in sustaining background NOx far from source regions present a challenge to global and regional model simulations. Copyright 2000 by the American Geophysical Union.

The measurement of OH reactivity, the inverse of the OH lifetime, provides a powerful tool to investigate atmospheric photochemistry. A new airborne OH reactivity instrument was designed and deployed for the first time on the NASA DC-8 aircraft during the second phase of Intercontinental Chemical Transport Experiment-B (INTEX-B) campaign, which was focused on the Asian pollution outflow over Pacific Ocean and was based in Hawaii and Alaska. The OH reactivity was measured by adding OH, generated by photolyzing water vapor with 185 nm UV light in a moveable wand, to the flow of ambient air in a flow tube and measuring the OH signal with laser induced fluorescence. As the wand was pulled back away from the OH detector, the OH signal decay was recorded; the slope of -Delta 1n(signal)/Delta time was the OH reactivity. The overall absolute uncertainty at the 2 sigma confidence levels is about 1 s(-1) at low altitudes (for decay about 6 s(-1)), and 0.7 s(-1) at high altitudes (for decay about 2 s(-1)). From the median vertical profile obtained in the second phase of INTEX-B, the measured OH reactivity (4.0 +/- 1.0 s(-1)) is higher than the OH reactivity calculated from assuming that OH was in steady state (3.3 +/- 0.8 s(-1)), and even higher than the OH reactivity that was calculated from the total measurements of all OH reactants (1.6 +/- 0.4 s(-1)). Model calculations show that the missing OH reactivity is consistent with the over-predicted OH and under-predicted HCHO in the boundary layer and lower troposphere. The over-predicted OH and under-predicted HCHO suggest that the missing OH sinks are most likely related to some highly reactive VOCs that have HCHO as an oxidation product.

BACKGROUND: Sasanlimab is an antibody to the programmed cell death protein 1 receptor. We report updated data of subcutaneous sasanlimab in non-small-cell lung cancer (NSCLC) and urothelial carcinoma dose expansion cohorts from a first-in-human phase Ib/II study. PATIENTS AND METHODS: Patients were ≥18 years of age with NSCLC or urothelial carcinoma, and no prior immunotherapies, who progressed on or were intolerant to systemic therapy, or for whom systemic therapy was refused or unavailable. Patients received subcutaneous sasanlimab at 300 mg every 4 weeks (q4w). Primary objectives were to evaluate safety, tolerability, and clinical efficacy by objective response rate (ORR). RESULTS: Sixty-eight and 38 patients with NSCLC and urothelial carcinoma, respectively, received subcutaneous sasanlimab. Overall, sasanlimab was well tolerated; 13.2% of patients experienced grade ≥3 treatment-related adverse events. Confirmed ORR was 16.4% and 18.4% in the NSCLC and urothelial carcinoma cohorts, respectively. ORR was generally higher in patients with high programmed death-ligand 1 (PD-L1) expression (≥25%) and high tumor mutational burden (TMB; >75%). In the NSCLC and urothelial carcinoma cohorts, median progression-free survival (PFS) was 3.7 and 2.9 months, respectively; corresponding median overall survival (OS) was 14.7 and 10.9 months. Overall, longer median PFS and OS correlated with high PD-L1 expression and high TMB. Longer median PFS and OS were also associated with T-cell inflamed gene signature in the urothelial carcinoma cohort. CONCLUSIONS: Subcutaneous sasanlimab at 300 mg q4w was well tolerated with promising clinical efficacy observed. Phase II and III clinical trials of sasanlimab are ongoing to validate clinical benefit. Subcutaneous sasanlimab may be a potential treatment option for patients with NSCLC or urothelial carcinoma.

The first direct in situ measurements of HO₂NO₂ in the upper troposphere were performed from the NASA DC-8 during the Intercontinental Chemical Transport Experiment–North America 2004 with a chemical ionization mass spectrometer (CIMS). These measurements provide an independent diagnostic of HO_x chemistry in the free troposphere and complement direct observations of HO_x, because of the dual dependency of HO₂NO₂ on HO_x and NO_x. On average, the highest HO₂NO₂ mixing ratio of 76 pptv (median = 77 pptv,σ = 39 pptv) was observed at altitudes of 8–9 km. Simple steady state calculations of HO₂NO₂, constrained by measurements of HO_x, NO_x, and J values, are in good agreement (slope = 0.90, R² = 0.60, and z = 5.5–7.5 km) with measurements in the midtroposphere where thermal decomposition is the major loss process. Above 8 km the calculated steady state HO₂NO₂ is in poor agreement with observed values (R² = 0.20) and is typically larger by a factor of 2.4. Conversely, steady state calculations using model-derived HO_x show reasonable agreement with the observed HO₂NO₂ in both the midtroposphere (slope = 0.96, intercept = 7.0, and R² = 0.63) and upper troposphere (slope = 0.80, intercept = 32.2, and R² = 0.58). These results indicate that observed HO₂ and HO₂NO₂ are in poor agreement in the upper troposphere but that HO₂NO₂ levels are consistent with current photochemical theory.