The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Characterization of the Proteostasis Roles of Glycerol Accumulation, Protein Degradation and Protein Synthesis during Osmotic Stress in C. elegans

Exposure of C. elegans to hypertonic stress-induced water loss causes rapid and widespread cellular protein damage. Survival in hypertonic environments depends critically on the ability of worm cells to detect and degrade misfolded and aggregated proteins. Acclimation of C. elegans to mild hypertonic stress suppresses protein damage and increases survival under more extreme hypertonic conditions. Suppression of protein damage in acclimated worms could be due to 1) accumulation of the chemical chaperone glycerol, 2) upregulation of protein degradation activity, and/or 3) increases in molecular chaperoning capacity of the cell. Glycerol and other chemical chaperones are widely thought to protect proteins from hypertonicity-induced damage. However, protein damage is unaffected by gene mutations that inhibit glycerol accumulation or that cause dramatic constitutive elevation of glycerol levels. Pharmacological or RNAi inhibition of proteasome and lyosome function and measurements of cellular protein degradation activity demonstrated that upregulation of protein degradation mechanisms plays no role in acclimation. Thus, changes in molecular chaperone capacity must be responsible for suppressing protein damage in acclimated worms. Transcriptional changes in chaperone expression have not been detected in C. elegans exposed to hypertonic stress. However, acclimation to mild hypertonicity inhibits protein synthesis 50–70%, which is expected to increase chaperone availability for coping with damage to existing proteins. Consistent with this idea, we found that RNAi silencing of essential translational components or acute exposure to cycloheximide results in a 50–80% suppression of hypertonicity-induced aggregation of polyglutamine-YFP (Q35::YFP). Dietary changes that increase protein production also increase Q35::YFP aggregation 70–180%. Our results demonstrate directly for the first time that inhibition of protein translation protects extant proteins from damage brought about by an environmental stressor, demonstrate important differences in aging- versus stress-induced protein damage, and challenge the widely held view that chemical chaperones are accumulated during hypertonic stress to protect protein structure/function

Customer Interaction and Innovation in Hybrid Offerings:Investigating Moderation and Mediation Effects for Goods and Services Innovation

Hybrid offerings are bundles of goods and services offerings provided by the same firm. Bundling value offerings affects how firms innovate, interact with customers, and customize their goods and services. However, it remains unclear how customer interaction might drive the innovation performance of various bundled components. Therefore, this study investigates the effects of customer interactions and service customization on both goods and services innovations in a hybrid offering context, using a unique data set of 146 information technology and manufacturing firms. Customer interaction appears beneficial to both goods and services innovation in a hybrid offerings context, but service customization has different direct effects on goods versus services innovation. As a potential mediator, customer knowledge mobilization resources exert different effects on the goods and services elements of hybrid offerings. Furthermore, for high-interaction customers, medium levels of technical modularity lead to most favorable innovation outcomes for services innovation. The results thus suggest that providers of hybrid offerings should foster customer interactions, to drive the innovation performance of the good and service components, while still making sure to implement service customization strategies. These findings have notable implications for service innovation research

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Nonselective NOS inhibition blunts the sweat response to exercise in a warm environment

The role of nitric oxide synthase (NOS) inhibition in modulating human thermoregulatory control of sweating and cutaneous dilation was examined in 10 subjects (5 men and 5 women). Three intradermal microdialysis probes were placed in nonglabrous skin of the dorsum of the forearm. The control site was perfused with 0.9% saline, while the two remaining sites were perfused with a nonselective NOS inhibitor: 10 mM NG-nitro-l-arginine (l-NAME) or 10 mM NG-monomethyl-l-arginine (l-NMMA). Local sweat rate (SR) and skin blood flow (laser-Doppler velocimetry) were monitored directly over the path of the intradermal microdialysis probe while arterial blood pressure was measured in the opposite arm noninvasively. Thermoregulatory responses were induced by cycle ergometer exercise (60% peak oxygen consumption) in a warm environment (30°C). Esophageal temperature increased 1.5 ± 0.2°C during the 30 min of exercise. The cutaneous dilator response between 5 and 30 min of exercise in the heat was attenuated by both 10 mM l-NAME and 10 mM l-NMMA (P < 0.05). However, 10 mM l-NAME was more effective in blunting the rise in cutaneous vascular conductance during exercise than l-NMMA (P < 0.05). NOS inhibition also reduced the rise in local SR between 10 and 30 min of exercise (P < 0.05). In this case, 10 mM l-NMMA was more effective in limiting the increase in local SR than 10 mM l-NAME (P < 0.05). We conclude that local production of nitric oxide in the skin or around the sweat gland augments local SR and cutaneous dilation during exercise in the heat

Sex differences in fitness outcomes among minority youth after participation in a park-based after-school program

This study aimed to describe sex differences in fitness outcomes after participation in Fit2Play, a park-based after-school health and wellness program. Youth who participated in Fit2Play for either 1, 2, or 3 school years between 2010 and 2016 (n = 2129, mean age 9.1 years, 52% Hispanic, 48% non-Hispanic black, 54% male) were tested via a comprehensive fitness battery at the beginning/end of the school year(s). Effects of length of Fit2Play participation on fitness outcomes were assessed via three-level repeated measures analysis stratified by sex and adjusted for child sociodemographics, weight category, area poverty, and year. Significant improvements for boys and girls were found in the Progressive Aerobic Cardiovascular Endurance Run (P < .01 for girls, P < .001 for boys), 400 meter run tests (P < .001 for girls, P < .01 for boys), and push-ups (P < .01 for both), with dose-response trends for girls after up to 3 years of Fit2Play participation. From baseline to 1, 2, and 3 years of participation, girls demonstrated 8%, 14%, and 23% mean improvement in 400 meter run times versus 9%, 9%, and 17% for boys, respectively (P < .001 for all). Dose-response improvements were also found in girls for PACER scores and sit-ups. After-school physical activity programs can improve fitness in all youth, and particularly girls with increased years of participation. Further research should examine sex differences in the effects of park-/community-based programs to reduce sex disparities in fitness, particularly in light of the current youth obesity epidemic