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Comets are relatively-pristine remnants of the original planetesimals that were ejected from the planetary region in the late stages of planetary formation. The Oort cloud comet C/2014 UN271, hereafter UN271, is ~140 km in diameter [1,2,3], large enough that it could be an intact example of a planetesimal that formed in the protoplanetary disk before being ejected into the Oort cloud [4]. UN271 is currently beyond 17 au from the Sun as it moves to a periheliondistance of 11 au in 2031. Given its large heliocentric distance the temperatures on and below its surface are too low for efficient sublimation of water ice. It is likely that its activity is driven by hypervolatiles such as CO or CO2 and not H2O [1,5]. It is dynamically new on its first inbound trip to the Solar System's planetary region [6] providing the rare opportunity to study the volatile content of one of the original planetesimals in a pristine state. We present JWST/NIRSpec prism IFU [7] observations of UN271 with R~100 covering the spectral range where we can detect emission features from the vibrational bands of the gas-phase all the main volatiles found in comets (such as CO2, CO and C2H6). Moreover, this range also includes absorption bands of solid-phase water-ice grains [8,9]. Our observations, taken on December 22, 2022, when the comet was at 18.6 au from the Sun, provides constraints on the comet's CO and CO2 production rates, the activity driving mechanism [5], the presence and nature of water-ice grains in its coma and can be compared with similar spectra of Kuiper Belt bodies [10]. [1] Bernardinelli et al. 2021, ApJL, 921:L37, 14pp., [2] Lellouch et al. 2022, A&A, 659, L1., [3] Hui et al. 2022, ApJL, 929:L12, 7pp., [4] Nesvorny et al. 2019, Nature Astronomy, 3, p. 808-812., [5] Meech & Svoren 2004, Comets II, p. 317-335., [6] Dybczyński & Królikowska 2022, A&A in press, [7] Jakobsen et al. 2022, A&A, in press., [8] Villanueva et al. 2018, Journal of Quantitative Spectroscopy and Radiative Transfer, 217, p. 86-104., [9] Protopapa et al. 2014, Icarus 238, 191–204., [10] Barucci & Merlin, 2020, The trans-Neptunian Solar System, Elsvier, p. 109-126 [

We present the highest fidelity spectrum to date of a planetary-mass object. VHS 1256 b is a, The Astrophysical Journal Letters, 946 (1), ISSN:1967-2014, ISSN:2041-8213

Bulletin of the AAS, 55 (2), AAS241 Abstracts

Reasoning in a complex and ambiguous environment is a key goal for Reinforcement Learning (RL) agents. While some sophisticated RL agents can successfully solve difficult tasks, they require a large amount of training data and often struggle to generalize to new unseen environments and new tasks. On the other hand, Large Scale Language Models (LSLMs) have exhibited strong reasoning ability and the ability to to adapt to new tasks through in-context learning. However, LSLMs do not inherently have the ability to interrogate or intervene on the environment. In this work, we investigate how to combine these complementary abilities in a single system consisting of three parts: a Planner, an Actor, and a Reporter. The Planner is a pre-trained language model that can issue commands to a simple embodied agent (the Actor), while the Reporter communicates with the Planner to inform its next command. We present a set of tasks that require reasoning, test this system's ability to generalize zero-shot and investigate failure cases, and demonstrate how components of this system can be trained with reinforcement-learning to improve performance., Comment: Presented at NeurIPS 2022 Language and Reinforcement Learning Workshop (best paper) and NeurIPS 2022 Foundation Models for Decision Making Workshop. 4 pages main; 14 pages total (including references and appendix); 3 figures

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 figures

A fundamental ability of an intelligent web-based agent is seeking out and acquiring new information. Internet search engines reliably find the correct vicinity but the top results may be a few links away from the desired target. A complementary approach is navigation via hyperlinks, employing a policy that comprehends local content and selects a link that moves it closer to the target. In this paper, we show that behavioral cloning of randomly sampled trajectories is sufficient to learn an effective link selection policy. We demonstrate the approach on a graph version of Wikipedia with 38M nodes and 387M edges. The model is able to efficiently navigate between nodes 5 and 20 steps apart 96% and 92% of the time, respectively. We then use the resulting embeddings and policy in downstream fact verification and question answering tasks where, in combination with basic TF-IDF search and ranking methods, they are competitive results to the state-of-the-art methods.

We present JWST Early Release Science (ERS) coronagraphic observations of the super-Jupiter exoplanet, HIP 65426 b, with the Near-Infrared Camera (NIRCam) from 2-5 $\mu$m, and with the Mid-Infrared Instrument (MIRI) from 11-16 $\mu$m. At a separation of $\sim$0.82" (86$^{+116}_{-31}$ au), HIP 65426 b is clearly detected in all seven of our observational filters, representing the first images of an exoplanet to be obtained by JWST, and the first ever direct detection of an exoplanet beyond 5 $\mu$m. These observations demonstrate that JWST is exceeding its nominal predicted performance by up to a factor of 10, depending on separation and subtraction method, with measured 5$\sigma$ contrast limits of $\sim$1$\times10^{-5}$ and $\sim$2$\times10^{-4}$ at 1" for NIRCam at 4.4 $\mu$m and MIRI at 11.3 $\mu$m, respectively. These contrast limits provide sensitivity to sub-Jupiter companions with masses as low as 0.3$M_\mathrm{Jup}$ beyond separations of $\sim$100 au. Together with existing ground-based near-infrared data, the JWST photometry are well fit by a BT-SETTL atmospheric model from 1-16 $\mu$m, and span $\sim$97% of HIP 65426 b's luminous range. Independent of the choice of model atmosphere we measure an empirical bolometric luminosity that is tightly constrained between $\mathrm{log}\!\left(L_\mathrm{bol}/L_{\odot}\right)$=-4.31 to $-$4.14, which in turn provides a robust mass constraint of 7.1$\pm$1.2 $M_\mathrm{Jup}$. In totality, these observations confirm that JWST presents a powerful and exciting opportunity to characterise the population of exoplanets amenable to high-contrast imaging in greater detail., Comment: 35 pages, 16 figures, 4 tables, 1 wonderful telescope; Submitted to AAS Journals

With new coronavirus disease 2019 (COVID-19) vaccines authorized by the U.S. Food and Drug Administration and likely more to come, the (extraordinarily complex) logistics of deploying them have gotten underway. Public health officials across the country face a daunting task: convincing the majority of individuals to queue up for shots while also maintaining a steady supply of doses and efficient appointment sign-ups. The road ahead is still long and, even with increasing vaccination, will still require adherence with other effective public health behaviors, such as mask-wearing. This article addresses the importance of effectively matching the message, the audience, and the sender for messages to promote uptake of vaccination and of such behaviors as mask-wearing. It offers suggestions about how to leverage such factors as variations in risk perception and variation among U.S. subcultures regarding tendencies to follow rules and to act for the good of the group. The authors also review evidence that suggests health messages should engage directly with misinformation to refute it.

Military personnel, police officers, firefighters, and other first responders must prepare for and respond to life-threatening crises on a daily basis. This lifestyle places stress on personnel, and particularly so on military personnel who may be isolated from support systems and other resources. The authors conducted a systematic review of studies of interventions designed to prevent, identify, and manage acute occupational stress among military, law enforcement, and first responders. The body of evidence consisted of 38 controlled trials, 35 cohort comparisons, and 42 case studies with no comparison group, reported in 136 publications. Interventions consisted of resilience training, stress inoculation with biofeedback, mindfulness, psychological first aid, front-line mental health centers, two- to seven-day restoration programs, debriefing (including critical incident stress debriefing), third-location decompression, postdeployment mental health screening, reintegration programs, and family-centered programs. Study limitations (risk of bias), directness, consistency, precision, and publication bias were considered in rating the quality of evidence for each outcome area. Overall, interventions had positive effects on return to duty, absenteeism, and distress. However, there was no significant impact on symptoms of psychological disorders such as PTSD, depression, and anxiety. Because of study limitations, inconsistency of results, indirectness, and possible publication bias, there was insufficient evidence to form conclusions about the effects of most specific intervention types, components, settings, or specific populations.

While beta Pic is known to host silicates in ring-like structures, whether the properties of these silicate dust vary with stellocentric distance remains an open question. We re-analyze the beta Pictoris debris disk spectrum from the Spitzer Infrared Spectrograph (IRS) and a new IRTF/SpeX spectrum to investigate trends in Fe/Mg ratio, shape, and crystallinity in grains as a function of wavelength, a proxy for stellocentric distance. By analyzing a re-calibrated and re-extracted spectrum, we identify a new 18 micron forsterite emission feature and recover a 23 micron forsterite emission feature with a substantially larger line-to-continuum ratio than previously reported. We find that these prominent spectral features are primarily produced by small submicron-sized grains, which are continuously generated and replenished from planetesimal collisions in the disk and can elucidate their parent bodies' composition. We discover three trends about these small grains: as stellocentric distance increases, (1) small silicate grains become more crystalline (less amorphous), (2) they become more irregular in shape, and (3) for crystalline silicate grains, the Fe/Mg ratio decreases. Applying these trends to beta Pic's planetary architecture, we find that the dust population exterior to the orbits of beta Pic b and c differs substantially in crystallinity and shape. We also find a tentative 3-5 micron dust excess due to spatially unresolved hot dust emission close to the star. From our findings, we infer that the surfaces of large planetesimals are more Fe-rich and collisionally-processed closer to the star but more Fe-poor and primordial farther from the star., Comment: 19 pages, 12 figures, Accepted for Publication in ApJ

Spatially resolved images of debris disks are necessary to determine disk geometric properties and the scattering phase function (SPF) which quantifies the brightness of the scattered light as a function of phase angle. The combination of high contrast and high angular resolution imaging is required to obtain these unique and important probes of debris disks, and we report on an adaptive optics 1.25-2.2 micron imaging survey of 17 high infrared excess debris disks observed with a Gemini Large and Long Program (LLP) utilizing the Gemini Planet Imager (GPI). The sample is composed of stars ranging in ages of 10-500 Myr and spectral types A-G. We explore quantitatively whether most debris disks are characterized by a similar SPF as suggested by previous studies. The SPF depends on important dust properties such as grain size distribution and porosity that are linked to the frequency of collisions that generate small grains and promote compactification of grains. To-date, only a very limited number of SPF measurements have been made, and there has been no uniform study modeling the geometry and SPFs of even a modest sample of debris disks using a consistent methodology. Additionally, we investigate and compare geometric properties of these systems such as radial extent and vertical thickness. By determining the best-fitting models for these systems, the disk scale height, SPFs, and dust properties can be estimated and compared between host stars of different ages and masses, as well as examples from the Solar System.

We present visible and mid-infrared imagery and photometry of temporary Jovian co-orbital comet P/2019 LD₂ taken with Hubble Space Telescope/Wide Field Camera 3 (HST/WFC3), Spitzer Space Telescope/Infrared Array Camera (Spitzer/IRAC), and the GROWTH telescope network, visible spectroscopy from Keck/Low-Resolution Imaging Spectrometer (LRIS), and archival Zwicky Transient Facility observations taken between 2019 April and 2020 August. Our observations indicate that the nucleus of LD₂ has a radius between 0.2 and 1.8 km assuming a 0.08 albedo and a coma dominated by ~100 μm-scale dust ejected at ~1 m s⁻¹ speeds with a ~1' jet pointing in the southwest direction. LD₂ experienced a total dust mass loss of ~10⁸ kg at a loss rate of ~6 kg s⁻¹ with Afρ/cross section varying between ~85 cm/125 km² and ~200 cm/310 km² from 2019 April 9 to 2019 November 8. If the increase in Afρ/cross section remained constant, it implies LD₂'s activity began ~2018 November when within 4.8 au of the Sun, implying the onset of H₂O sublimation. We measure CO/CO₂ gas production of ≾10²⁷ mol s⁻¹/≾10²⁶ mol s⁻¹ from our 4.5 μm Spitzer observations; g–r = 0.59 ± 0.03, r–i = 0.18 ± 0.05, and i–z = 0.01 ± 0.07 from GROWTH observations; and H₂O gas production of ≾80 kg s⁻¹ scaling from our estimated C₂ production of Q_(C₂) ≾7.5×10²⁴ mol s⁻¹ from Keck/LRIS spectroscopy. We determine that the long-term orbit of LD₂ is similar to Jupiter-family comets having close encounters with Jupiter within ~0.5 Hill radius in the last ~3 y and within 0.8 Hill radius in ~9 y. Additionally, 78.8% of our orbital clones are ejected from the solar system within 1 × 10⁶ yr, having a dynamical half-life of 3.4 × 10⁵ yr.

We present visible and mid-infrared imagery and photometry of temporary Jovian co-orbital comet P/2019 LD$_2$ taken with HST/WFC3, Spitzer/IRAC, the GROWTH telescope network, visible spectroscopy from Keck/LRIS and archival ZTF observations taken between 2019 April and 2020 August. Our observations indicate that the nucleus of LD$_2$ has a radius between 0.2-1.8 km assuming a 0.08 albedo and a coma dominated by $\sim$100$\mu$ m-scale dust ejected at $\sim$1 m/s speeds with a $\sim$1'' jet pointing in the SW direction. LD$_2$ experienced a total dust mass loss of $\sim$10$^8$ kg at a loss rate of $\sim$6 kg/s with Af$\rho$/cross-section varying between $\sim$85 cm/125 km$^2$ and $\sim$200 cm/310 km$^2$ from 2019 April 9 to 2019 Nov 8. If the increase in Af$\rho$/cross-section remained constant, it implies LD$_2$'s activity began $\sim$2018 November when within 4.8 au of the Sun, implying the onset of H$_2$O sublimation. We measure CO/CO$_2$ gas production of $\lesssim$10$^{27}$ mol/s /$\lesssim$10$^{26}$ mol/s from our 4.5 $\mu$m Spitzer observations, $g$-$r$ = 0.59$\pm$0.03, $r$-$i$ = 0.18$\pm$0.05, $i$-$z$ = 0.01$\pm$0.07 from GROWTH observations, H$_2$O gas production of $\lesssim$80 kg/s scaling from our estimated $C_2$ production of $Q_{C_2}\lesssim$7.5$\times10^{24}$ mol/s from Keck/LRIS spectroscopy. We determine that the long-term orbit of LD$_2$ is similar to Jupiter family comets having close encounters with Jupiter within $\sim$0.5 Hill radius in the last $\sim$3 y, within 0.8 Hill radius in $\sim$9 y. Additionally, 78.8$\%$ of our orbital clones are ejected from the Solar System within $1 \times 10^{6}$ years having a dynamical half-life of 3.4 $\times 10^5$ years., Comment: 28 pages, 8 figures, 2 Tables, accepted for publication in AJ

SHP2 is a nonreceptor protein tyrosine phosphatase encoded by the PTPN11 gene and is involved in cell growth and differentiation via the MAPK signaling pathway. SHP2 also plays an important role in the programed cell death pathway (PD-1/PD-L1). As an oncoprotein as well as a potential immunomodulator, controlling SHP2 activity is of high therapeutic interest. As part of our comprehensive program targeting SHP2, we identified multiple allosteric binding modes of inhibition and optimized numerous chemical scaffolds in parallel. In this drug annotation report, we detail the identification and optimization of the pyrazine class of allosteric SHP2 inhibitors. Structure and property based drug design enabled the identification of protein-ligand interactions, potent cellular inhibition, control of physicochemical, pharmaceutical and selectivity properties, and potent in vivo antitumor activity. These studies culminated in the discovery of TNO155, (3S,4S)-8-(6-amino-5-((2-amino-3-chloropyridin-4-yl)thio)pyrazin-2-yl)-3-methyl-2-oxa-8-azaspiro[4.5]decan-4-amine (1), a highly potent, selective, orally efficacious, and first-in-class SHP2 inhibitor currently in clinical trials for cancer.

This systematic review addresses the question: What are the effects of medication-assisted treatment (MAT) that use buprenorphine, buprenorphine combined with naloxone, methadone, or naltrexone for opioid use disorder (OUD) on functional outcomes compared with wait-list, placebo, treatment without medication, any other comparator, or each other (e.g., buprenorphine versus naltrexone)? Functional outcomes investigated included cognitive (e.g., memory), physical (e.g., fatigue), occupational (e.g., employment status), social/behavioral (e.g., criminal activity), and neurological (e.g., balance) function. The authors searched five scientific research databases from inception to 2017 and reference mined existing reviews. Two independent literature reviewers screened 6,292 citations; 1,327 full-text publications were reviewed in detail and 37 studies met inclusion criteria. Critical appraisals assessed studies in detail, and quality of evidence was rated using established criteria. Results were synthesized in meta-analyses and presented in comprehensive evidence tables. Although MAT patients performed significantly better on some functional outcomes than persons with OUD who did not receive MAT, MAT patients performed worse on several cognitive measures than did matched “healthy” controls with no history of substance use disorder (SUD) or OUD. Because of the moderate-to-high risk of bias of most studies, quality of evidence is low or very low for all findings. The small number of studies reporting on outcomes of interest and the weaknesses in the body of evidence prevent making strong conclusions about MAT effects on functional outcomes. The literature shows that more research is needed that targets functional outcomes specifically, and there is, in particular, a lack of research evaluating potential differences in functional effects among medication types, the route of administration, treatment modality, and length of treatment.

The deformation pattern of the paleoshorelines of extinct Lake Bonneville were among the first features to indicate that Earth's interior responds viscoelastically to changes in surface loads (Gilbert, 1885). Here we revisit and extend this classic study of isostatic rebound with updated lake chronologies for Lake Bonneville and Lake Lahontan as well as revised elevation datasets of shoreline features. The first order domal pattern in the shoreline elevations can be explained by rebound associated with the removal of the lake load. We employ an iterative scheme to calculate the viscoelastic lake rebound, which accounts for the deformation of the solid Earth and gravity field, to calculate a lake load that is consistent with the load-deformed paleotopography. We find that the domal deformation requires a regional Earth structure that exhibits a thin elastic thickness of the lithosphere (15–25 km) and low sublithospheric Maxwell viscosity (∼1019 Pa s). After correcting for rebound due to the lake load, shoreline feature elevations reveal a statistically significant northward dipping trend. We attribute this trend to continent-scale deformation caused by the ice peripheral bulge of the Laurentide ice sheet, and take advantage of the position of these lakes on the distal flank of the peripheral bulge to provide new insights on mantle viscosity and Laurentide ice sheet reconstructions. We perform ice loading calculations to quantify the deformation of the solid Earth, gravity field, and rotation axis that is caused by the growth and demise of the Laurentide ice sheet. We test three different ice reconstructions paired with a suite of viscosity profiles and confirm that the revealed trend can be explained by deformation associated with the Laurentide ice sheet when low viscosities below the asthenosphere are adopted. We obtain best fits to shoreline data using ice models that do not have the majority of ice in the eastern sectors of the Laurentide ice sheet, with the caveat that this result can be affected by lateral variations in viscosity. We show that pluvial lakes in the western United States can place valuable constraints on the Laurentide ice sheet, the shape of its peripheral bulge, and the underlying mantle viscosity.

Slides for the Growing Healthy Labs workshop held at the Department of Geosciences of Princeton University in May 2019. Created and facilitated by Christine Y. Chen. Google Slides version can be accessed via https://bit.ly/GrowingHealthyLabs.WORKSHOP DESCRIPTIONA healthy work environment is fundamental to good science, but we rarely discuss strategies for how to create and maintain one. Despite measurable and empirically-supported benefits associated with effective leadership, management, and mentorship for both advisors and trainees, most faculty are rarely trained in these skills. As a result, academic teams can lose time to unproductive interpersonal issues, lack of motivation, and unnecessary conflict. These problems can lead to high costs in terms of money, productivity, mental health, and retention of talent, and often disproportionally impact students from groups underrepresented in STEM fields.In response, [SPONSORING ORGANIZATION] is pleased to offer a workshop on effective lab and personnel management for graduate students and post-doctoral researchers. The goal of this workshop is to help future principal investigators (PIs) become more effective at managing their research groups and creating inclusive spaces that develop excellent science and scientists.In this workshop, participants willlearn about recent research on the impact of leadership and lab culture on productivity and overall group well-beingconsider and discuss common evidence-based "best practice" strategies for effective personnel management share ideas and practice strategies for good supervision of trainees with other participantsleave with additional resources for future self-education and formal trainingSLIDES DESCRIPTIONThere are 91 slides in total. The table of contents is as follows:• Introduction — Why is this important? [Slides 3-18]• Workshop Objectives, Agenda, & Icebreaker [Slides 19-26]• Active Role Play Activity: Advisor-Advisee Meeting [Slides 27-37], using a modified version of a role play designed by the National Center for Professional & Research Ethics• Strategies for Communicating Expectations [Slides 38-58]• Psychological Safety — What is it? Do you experience it? [Slides 59-64]• Conflict — What is it and why should we embrace it? [Slides 65-77]• Active Listening — small group discussion [Slides 78-85]• Further Resources for Self-Education [Slides 86-93]• Parting Words [Slide 94]ABOUT THE FACILITATORChristine Y. Chen is a postdoctoral fellow in the Division of Geological and Planetary Sciences at Caltech. She completed her PhD in Geology from MIT in 2019. While at MIT, she served as a graduate student mediator through the Resources for Easing Friction and Stress (REFS) program at MIT, in which students provide low barrier, informal, confidential services to their peers in conflict management. In this capacity, she underwent extensive training in conflict management and mediation through the Conflict Management@MIT program and has created and facilitated workshops on creating healthy research environments in academia. For her dedication to empowering her fellow students to develop as leaders and being an active mentor and coach to peers within the MIT community, she was awarded the MIT Larry G. Benedict Leadership Institute Award in 2019. When she isn't agonizing over the state of the world, Christine can be found pouring over tufa deposits as part of her geological research studying ancient lake basins in the western United States and central Andes.

We present visible and mid-infrared imagery and photometry of temporary Jovian co-orbital comet P/2019 LD$_2$ taken with HST/WFC3, Spitzer/IRAC, the GROWTH telescope network, visible spectroscopy from Keck/LRIS and archival ZTF observations taken between 2019 April and 2020 August. Our observations indicate that the nucleus of LD$_2$ has a radius between 0.2-1.8 km assuming a 0.08 albedo and a coma dominated by $\sim$100$��$ m-scale dust ejected at $\sim$1 m/s speeds with a $\sim$1'' jet pointing in the SW direction. LD$_2$ experienced a total dust mass loss of $\sim$10$^8$ kg at a loss rate of $\sim$6 kg/s with Af$��$/cross-section varying between $\sim$85 cm/125 km$^2$ and $\sim$200 cm/310 km$^2$ from 2019 April 9 to 2019 Nov 8. If the increase in Af$��$/cross-section remained constant, it implies LD$_2$'s activity began $\sim$2018 November when within 4.8 au of the Sun, implying the onset of H$_2$O sublimation. We measure CO/CO$_2$ gas production of $\lesssim$10$^{27}$ mol/s /$\lesssim$10$^{26}$ mol/s from our 4.5 $��$m Spitzer observations, $g$-$r$ = 0.59$\pm$0.03, $r$-$i$ = 0.18$\pm$0.05, $i$-$z$ = 0.01$\pm$0.07 from GROWTH observations, H$_2$O gas production of $\lesssim$80 kg/s scaling from our estimated $C_2$ production of $Q_{C_2}\lesssim$7.5$\times10^{24}$ mol/s from Keck/LRIS spectroscopy. We determine that the long-term orbit of LD$_2$ is similar to Jupiter family comets having close encounters with Jupiter within $\sim$0.5 Hill radius in the last $\sim$3 y, within 0.8 Hill radius in $\sim$9 y. Additionally, 78.8$\%$ of our orbital clones are ejected from the Solar System within $1 \times 10^{6}$ years having a dynamical half-life of 3.4 $\times 10^5$ years., 28 pages, 8 figures, 2 Tables, accepted for publication in AJ

*----- NOTE: This paper has been accepted in Quaternary Science Reviews as of June 8, 2020 -----* Deep sediment cores from long-lived lake basins are fundamental records of paleoenvironmental history, but the power of these reconstructions has often been limited by poor age control. Uranium-thorium (U-Th) dating has the potential to fill a gap in current geochronological tools available for such sediment archives. We present our systematic approach to U-Th date carbonate-rich sediments from the ~100 m drill core from Lake Junín, Peru. The results form the foundation of an age-depth model spanning ~700 kyrs. High uranium concentrations (0.3--4 ppm) of these sediments allow us to date smaller quantities of material, giving us the opportunity to improve sample selection by avoiding detrital contamination, the greatest factor limiting the success of previous U-Th dating efforts in other lake basins. The dates from 174 analyses on 55 bulk carbonate samples revealed significant scatter that could not be resolved with traditional isochrons, suggesting that at least some of the sediments have not remained closed systems. To understand the source of noise in the geochronological data, we first apply threshold criteria that screen samples by their U/Th ratio, reproducibility, and d234U initial value. We then compare these results with facies types, trace element concentrations, carbonate and total organic carbon content, color reflectance, mineralogy, and ostracode shell color to investigate the causes of open system behavior. We find that the greatest impediment to U-Th dating of these sediments is not detrital contamination, but rather post-depositional remobilization of uranium. After examining U-Th data in these contexts, we identify samples that have likely experienced the least amount of alteration, and use dates from those samples as constraints for the age-depth model. Our work has several lessons for future attempts to U-Th date lake sediments, namely that the samples geologic context is equally important as the accuracy and precision of analytical measurements when determining the age of sample materials. In addition, we caution that significant geologic scatter may remain undetected if not for labor intensive tests of reproducibility achieved through replication. As a result of this work, the deep sediment core from Lake Junín is the only continuous record in the tropical Andes spanning multiple glacial cycles that is constrained entirely by independent radiometric dates.

A sediment core spanning the last ~50 ka from Lake Junín (Peru) in the tropical Andes reveals abrupt climatic events on a centennial-millennial time scale. These events, which involved the near-complete disappearance of glaciers below 4700 masl in the eastern Andean cordillera and major reductions in the level of Peru’s second largest lake, occurred during the abrupt warmings recorded in Greenland ice cores known as Dansgaard-Oeschger (DO) interstadials. Lake Junín is the first record to document the response of Andean glaciers to serial DO events, and also reveals the magnitude of the hydroclimatic disruptions in the highest reaches of the Amazon Basin that were caused by a weakening of the South American summer monsoon during abrupt arctic warming. Ongoing warming in the Arctic could lead to significant reductions in the precipitation-evaporation balance in the tropical Andes with deleterious effects on the sustainability of a densely populated region of South America.

While adding the structural features that are more favored by on-target activity is the more common strategy in selectivity optimization, the opposite strategy of subtracting the structural features that contribute more to off-target activity can also be very effective. Reported here is our successful effort of improving the kinase selectivity of type II maternal embryonic leucine zipper kinase inhibitors by applying these two complementary approaches together, which clearly demonstrates the powerful synergy between them.

The Space Infrared Telescope for Cosmology and Astrophysics (SPICA) will conduct sensitive observations of the Universe at mid- and far-Infrared wavelengths. A NASA-led contribution is proposed to further enhance SPICA’s capabilities, broadening its scientific scope, and to allow US community access to key programs and general observing time.

Cold debris disks (T$, Comment: 8 pages, with 3 figures. White Paper submitted in response to Astro 2020 Science White paper call. Co-signers on this work are: Vanessa Bailey (JPL), William C. Danchi (GSFC), Laurent Pueyo (STScI), Marshall Perrin (STScI), Bin Ren (STScI), Aki Roberge (GSFC), Glenn Schneider (U. of Arizona), Jordan Steckloff (PSI)

Existing computer vision technologies in artwork recognition focus mainly on instance retrieval or coarse-grained attribute classification. In this work, we present a novel dataset for fine-grained artwork attribute recognition. The images in the dataset are professional photographs of classic artworks from the Metropolitan Museum of Art, and annotations are curated and verified by world-class museum experts. In addition, we also present the iMet Collection 2019 Challenge as part of the FGVC6 workshop. Through the competition, we aim to spur the enthusiasm of the fine-grained visual recognition research community and advance the state-of-the-art in digital curation of museum collections., 3 pages, 4 figures

eid: 69 adsurl: https://ui.adsabs.harvard.edu/abs/2019BAAS...51c..69G adsnote: Provided by the SAO/NASA Astrophysics Data System ispartof: Bulletin of the American Astronomical Society vol:51 issue:3 status: published

Debris disks are exoplanetary systems containing planets, minor bodies (such as asteroids and comets) and debris dust. Unseen planets are presumed to perturb the minor bodies into crossing orbits, generating small dust grains that are detected via remote sensing. Debris disks have been discovered around main sequence stars of a variety of ages (from 10 Myr to several Gyr) and stellar spectral types (from early A-type to M-type stars). As a result, they serve as excellent laboratories for understanding whether the architecture and the evolution of our Solar System is common or rare. This white paper addresses two outstanding questions in debris disk science: (1) Are debris disk minor bodies similar to asteroids and comets in our Solar System? (2) Do planets separate circumstellar material into distinct reservoirs and/or mix material during planet migration? We anticipate that SOFIA/HIRMES, JWST, and WFIRST/CGI will greatly improve our understanding of debris disk composition, enabling the astronomical community to answer these questions. However, we note that despite their observational power, these facilities will not provide large numbers of detections or detailed characterization of cold ices and silicates in the Trans Neptunian zone. Origins Space Telescope is needed to revolutionize our understanding of the bulk composition and mixing in exoplanetary systems., Science white paper submitted to the Astro2020 Decadal Survey

We present a new initiative by the Women in Astronomy Forum at Space Telescope Science Institute (STScI) to increase gender diversity and inclusion in STScI's scientific committees and the activities they generate. This initiative offers new and uniform guidelines on binary gender representation goals for each committee and recommendations on how to achieve them in a homogeneous way, as well as metrics and tools to track progress towards defined goals. While the new guidelines presented in the paper focus on binary gender representation, they can be adapted and implemented to support all minority groups. By creating diverse committees and making them aware of, and trained on implicit bias, we expect to create a diverse outcome in the activities they generate, which, in turn, will advance science further and faster., Comment: 9 pages, 2 figures, Atro2020 state of profession white paper

Supplemental material, MDM_Appendix_A._online_supp for Using an Online Modified-Delphi Approach to Engage Patients and Caregivers in Determining the Patient-Centeredness of Duchenne Muscular Dystrophy Care Considerations by Dmitry Khodyakov, Sean Grant, Brian Denger, Kathi Kinnett, Ann Martin, Marika Booth, Courtney Armstrong, Emily Dao, Christine Chen, Ian Coulter, Holly Peay, Glen Hazlewood and Natalie Street in Medical Decision Making

Emerging evidence have posited that dysregulated microglia impair clearance and containment of amyloid-β (Aβ) species in the brain, resulting in aberrant buildup of Aβ and onset of Alzheimer's disease (AD). Hematopoietic cell kinase (Hck) is one of the key regulators of phagocytosis among the Src family tyrosine kinases (SFKs) in myeloid cells, and its expression is found to be significantly altered in AD brains. However, the role of Hck signaling in AD pathogenesis is unknown. We employed pharmacological inhibition and genetic ablation of Hck in BV2 microglial cells and J20 mouse model of AD, respectively, to evaluate the impact of Hck deficiency on Aβ-stimulated microglial phagocytosis, Aβ clearance, and resultant AD-like neuropathology. Our in vitro data reveal that pharmacological inhibition of SFKs/Hck in BV2 cells and genetic ablation of their downstream kinase, spleen tyrosine kinase (Syk), in primary microglia significantly attenuate Aβ oligomers-stimulated microglial phagocytosis. Whereas in Hck-deficient J20 mice, we observed exacerbated Aβ plaque burden, reduced microglial coverage, containment, and phagocytosis of Aβ plaques, and induced iNOS expression in plaque-associated microglial clusters. These multifactorial changes in microglial activities led to attenuated PSD95 levels in hippocampal DG and CA3 regions, but did not alter the postsynaptic dendritic spine morphology at the CA1 region nor cognitive function of the mice. Hck inhibition thus accelerates early stage AD-like neuropathology by dysregulating microglial function and inducing neuroinflammation. Our data implicate that Hck pathway plays a prominent role in regulating microglial neuroprotective function during the early stage of AD development.

Multi-wavelength observations have painted a detailed picture of the inner regions of protoplanetary disks, characterizing the structure and properties of dust from the sublimation radius to the terrestrial planet zone and the kinematics of gas either accreting onto the star or outflowing from the disk. The excellent sensitivity and angular resolution of the James Webb Space Telescope (JWST) at near- to mid-infrared wavelengths are poised to revolutionize our understanding of the inner regions of protoplanetary disks. Specifically, JWST will enable detailed characterization of faint and young protoplanetary disks and demographic studies of more distant objects, including disks in the metal-poor Large Magellanic Cloud. In addition, medium resolution spectroscopy (R~3000) using the integral field units will enable mapping molecular and atomic line emission across disks. Indeed, Guaranteed Time Observer (GTO) and Early Release Science (ERS) teams have already submitted observing programs detailing their plans. I will present the JWST capabilities for observing protoplanetary disks using specific GTO and ERS programs to illustrate how observations can be planned.

SHP2 is a nonreceptor protein tyrosine phosphatase (PTP) encoded by the PTPN11 gene involved in cell growth and differentiation via the MAPK signaling pathway. SHP2 also purportedly plays an important role in the programmed cell death pathway (PD-1/PD-L1). Because it is an oncoprotein associated with multiple cancer-related diseases, as well as a potential immunomodulator, controlling SHP2 activity is of significant therapeutic interest. Recently in our laboratories, a small molecule inhibitor of SHP2 was identified as an allosteric modulator that stabilizes the autoinhibited conformation of SHP2. A high throughput screen was performed to identify progressable chemical matter, and X-ray crystallography revealed the location of binding in a previously undisclosed allosteric binding pocket. Structure-based drug design was employed to optimize for SHP2 inhibition, and several new protein-ligand interactions were characterized. These studies culminated in the discovery of 6-(4-amino-4-methylpiperidin-1-yl)-3-(2,3-dichlorophenyl)pyrazin-2-amine (SHP099, 1), a potent, selective, orally bioavailable, and efficacious SHP2 inhibitor.

SHP099, a selective inhibitor of signalling meditator SHP2 with drug-like properties, has an allosteric mechanism of action whereby it stabilizes SHP2 in an auto-inhibited conformation, and suppresses RAS–ERK signalling and proliferation in receptor-tyrosine-kinase-driven cancer cell lines and mouse tumour xenograft models. The tyrosine phosphatase SHP2 is a key mediator of receptor tyrosine kinase (RTK) signalling, as well as being important in immune checkpoint pathways. Reduction of SHP2 activity suppresses tumour cell growth, and SHP2 is a potential, but so far elusive, therapeutic target in cancer. Pascal Fortin and colleagues report the development of a selective SHP2 inhibitor with drug-like properties. The inhibitor, SHP099, has an allosteric mechanism of action whereby it stabilizes SHP2 in an auto-inhibited conformation. It also suppresses RAS–ERK signalling to inhibit RTK-driven proliferation in human cancer cell lines and mouse tumour xenograft models. The non-receptor protein tyrosine phosphatase SHP2, encoded by PTPN11, has an important role in signal transduction downstream of growth factor receptor signalling and was the first reported oncogenic tyrosine phosphatase1. Activating mutations of SHP2 have been associated with developmental pathologies such as Noonan syndrome and are found in multiple cancer types, including leukaemia, lung and breast cancer and neuroblastoma1,2,3,4,5. SHP2 is ubiquitously expressed and regulates cell survival and proliferation primarily through activation of the RAS–ERK signalling pathway2,3. It is also a key mediator of the programmed cell death 1 (PD-1) and B- and T-lymphocyte attenuator (BTLA) immune checkpoint pathways6,7. Reduction of SHP2 activity suppresses tumour cell growth and is a potential target of cancer therapy8,9. Here we report the discovery of a highly potent (IC50 = 0.071 μM), selective and orally bioavailable small-molecule SHP2 inhibitor, SHP099, that stabilizes SHP2 in an auto-inhibited conformation. SHP099 concurrently binds to the interface of the N-terminal SH2, C-terminal SH2, and protein tyrosine phosphatase domains, thus inhibiting SHP2 activity through an allosteric mechanism. SHP099 suppresses RAS–ERK signalling to inhibit the proliferation of receptor-tyrosine-kinase-driven human cancer cells in vitro and is efficacious in mouse tumour xenograft models. Together, these data demonstrate that pharmacological inhibition of SHP2 is a valid therapeutic approach for the treatment of cancers.

SPHEREx is a proposed NASA MIDEX mission selected for Phase A study. SPHEREx would carry out the first all-sky spectral survey in the near infrared. At the end of its two-year mission, SPHEREx would obtain 0.75-to-5$��$m spectra of every 6.2 arcsec pixel on the sky, with spectral resolution R>35 and a 5-$��$ sensitivity AB$>$19 per spectral/spatial resolution element. More details concerning SPHEREx are available at http://spherex.caltech.edu. The SPHEREx team has proposed three specific science investigations to be carried out with this unique data set: cosmic inflation, interstellar and circumstellar ices, and the extra-galactic background light. Though these three themes are undoubtedly compelling, they are far from exhausting the scientific output of SPHEREx. Indeed, SPHEREx would create a unique all-sky spectral database including spectra of very large numbers of astronomical and solar system targets, including both extended and diffuse sources. These spectra would enable a wide variety of investigations, and the SPHEREx team is dedicated to making the data available to the community to enable these investigations, which we refer to as Legacy Science. To that end, we have sponsored two workshops for the general scientific community to identify the most interesting Legacy Science themes and to ensure that the SPHEREx data products are responsive to their needs. In February of 2016, some 50 scientists from all fields met in Pasadena to develop these themes and to understand their implications for the SPHEREx mission. The 2016 workshop highlighted many synergies between SPHEREx and other contemporaneous astronomical missions, facilities, and databases. Consequently, in January 2018 we convened a second workshop at the Center for Astrophysics in Cambridge to focus specifically on these synergies. This white paper reports on the results of the 2018 SPHEREx workshop., 50 pages, 24 figures, more details at http://spherex.caltech.edu

As technology moves toward encryption, law enforcement has turned to creative methods to apprehend criminals attempting to hide or obscure their digital wrongdoings. One such method is the network investigative technique (NIT), which essentially operates by sending a tracking program to users’ computer systems to uncover their real IP addresses. Judges can authorize the deployment of NITs through warrants. With the jurisdictional hurdle limiting the reach of such warrants removed by the recent change in Rule 41 of the Federal Rules of Criminal Procedure, the usage of NITs is certain to become more commonplace. However, courts are uncertain about how to treat evidence obtained through NITs, especially with respect to whether defendants are entitled to the full NIT code used against them in the course of discovery. If defendants can access the full code, they could threaten to divulge it to the general public unless prosecutors drop the criminal charges. But if prevented from accessing the code under any circumstances, defendants may be locked into an unfair trial. This Note suggests that courts will need to reformulate the test traditionally used to balance the government’s interests and defendants’ due process rights with regard to sensitive or confidential information to create a general presumption against releasing the full NIT code., Science and Technology Law Review, Vol 19 No 1: 2017-2018

Technology is increasingly used -- unintentionally (misinformation) or intentionally (disinformation) -- to spread false information at scale, with potentially broad-reaching societal effects. For example, technology enables increasingly realistic false images and videos, and hyper-personal targeting means different people may see different versions of reality. This report is the culmination of a PhD-level special topics course (https://courses.cs.washington.edu/courses/cse599b/18au/) in Computer Science & Engineering at the University of Washington's Paul G. Allen School in the fall of 2018. The goals of this course were to study (1) how technologies and today's technical platforms enable and support the creation and spread of such mis- and disinformation, as well as (2) how technical approaches could be used to mitigate these issues. In this report, we summarize the space of technology-enabled mis- and disinformation based on our investigations, and then surface our lessons and recommendations for technologists, researchers, platform designers, policymakers, and users.

Figure S1. Quality control metrics for stored specimens. Representative FACS analysis for FITC bound CD4 (A) and APC bound CD8 cells (B). Panel C displays the FACS confirmed purity of all specimens, with case and control samples represented by red and blue triangles respectively. (DOCX 100 kb)

Table S1. Cases recruited and attendance for all 6 time points (DOCX 160 kb)

Table S1. Baseline Characteristics of Medicare Patients with a Unilateral Transfemoral Amputation, 2011â 2014. (DOCX 50Â kb)

The debris disk around $��$~Pictoris is known to contain gas. Previous ALMA observations revealed a CO belt at $\sim$85 au with a distinct clump, interpreted as a location of enhanced gas production. Photodissociation converts CO into C and O within $\sim$50 years. We resolve CI emission at 492 GHz using ALMA and study its spatial distribution. CI shows the same clump as seen for CO. This is surprising, as C is expected to quickly spread in azimuth. We derive a low C mass (between $5\times10^{-4}$ and $3.1\times10^{-3}$ M$_\oplus$), indicating that gas production started only recently (within $\sim$5000 years). No evidence is seen for an atomic accretion disk inwards of the CO belt, perhaps because the gas did not yet have time to spread radially. The fact that C and CO share the same asymmetry argues against a previously proposed scenario where the clump is due to an outward migrating planet trapping planetesimals in an resonance; nor can the observations be explained by an eccentric planetesimal belt secularly forced by a planet. Instead, we suggest that the dust and gas disks should be eccentric. Such a configuration, we further speculate, might be produced by a recent tidal disruption event. Assuming that the disrupted body has had a CO mass fraction of 10%, its total mass would be $\gtrsim$3 $M_\mathrm{Moon}$., 30 pages, 15 figures, accepted by ApJ

Virtual and augmented reality technologies have seen significant growth in the past few years. A key component of such systems is the ability to track the pose of head mounted displays and controllers in 3D space. We tackle the problem of efficient 6-DoF tracking of a handheld controller from egocentric camera perspectives. We collected the HMD Controller dataset which consist of over 540,000 stereo image pairs labelled with the full 6-DoF pose of the handheld controller. Our proposed SSD-AF-Stereo3D model achieves a mean average error of 33.5 millimeters in 3D keypoint prediction and is used in conjunction with an IMU sensor on the controller to enable 6-DoF tracking. We also present results on approaches for model based full 6-DoF tracking. All our models operate under the strict constraints of real time mobile CPU inference.

Figure S2. Effect of batch correction on 195 samples (2 samples of the 197 were removed). Three parameters (Flowcell ID, Gender and Ethnicity) were used to remove confounding effects in edgeR. PC1 contributes the greatest amount of variance and is largely attributed to Flowcell ID, which accounts for most of the variance in sequencing experiments. (DOCX 384 kb)

Mobile virtual reality (VR) head mounted displays (HMD) have become popular among consumers in recent years. In this work, we demonstrate real-time egocentric hand gesture detection and localization on mobile HMDs. Our main contributions are: 1) A novel mixed-reality data collection tool to automatic annotate bounding boxes and gesture labels; 2) The largest-to-date egocentric hand gesture and bounding box dataset with more than 400,000 annotated frames; 3) A neural network that runs real time on modern mobile CPUs, and achieves higher than 76% precision on gesture recognition across 8 classes., Extended Abstract NIPS 2017 Machine Learning on the Phone and other Consumer Devices Workshop

The Gemini Planet Imager Exoplanet Survey (GPIES) is a 600-star survey for young Jovian-mass exoplanets at Solar System scales. To date, GPIES has imaged six exoplanets and four brown dwarfs and has developed the data reduction tools necessary to characterize these companions. GPI is therefore building up a uniform library of 1 to 2.4 micron near-infrared low-resolution spectra of young substellar objects. A more thorough comparison with libraries of field and young brown dwarf near-infrared spectra is now possible to detail similarities and difference between the two families. I will present the current status of the library, discuss how these objects sample different regimes of atmospheric properties, and how similar they are to young free-floating planetary mass objects. I will also show the orbits of these companions and discuss what inferences we can make from their dynamics.

Using the Gemini Planet Imager (GPI) located at Gemini South, we measured the near-infrared (1.0-2.4 micron) spectrum of the planetary companion to the nearby, young star $��$ Pictoris. We compare the spectrum obtained with currently published model grids and with known substellar objects and present the best matching models as well as the best matching observed objects. Comparing the empirical measurement of the bolometric luminosity to evolutionary models, we find a mass of $12.9\pm0.2$ $\mathcal{M}_\mathrm{Jup}$, an effective temperature of $1724\pm15$ K, a radius of $1.46\pm0.01$ $\mathcal{R}_\mathrm{Jup}$, and a surface gravity of $\log g = 4.18\pm0.01$ [dex] (cgs). The stated uncertainties are statistical errors only, and do not incorporate any uncertainty on the evolutionary models. Using atmospheric models, we find an effective temperature of $1700-1800$ K and a surface gravity of $\log g = 3.5$-$4.0$ [dex] depending upon model. These values agree well with other publications and with "hot-start" predictions from planetary evolution models. Further, we find that the spectrum of $��$ Pic b best matches a low-surface gravity L2$\pm$1 brown dwarf. Finally comparing the spectrum to field brown dwarfs we find the the spectrum best matches 2MASS J04062677-381210 and 2MASS J03552337+1133437., 21 pages, 11 figures, Accepted to AJ

© 2016. The American Astronomical Society. All rights reserved. A principal scientific goal of the Gemini Planet Imager (GPI) is obtaining milliarcsecond astrometry to constrain exoplanet orbits. However, astrometry of directly imaged exoplanets is subject to biases, systematic errors, and speckle noise. Here, we describe an analytical procedure to forward model the signal of an exoplanet that accounts for both the observing strategy (angular and spectral differential imaging) and the data reduction method (Karhunen-Loève Image Projection algorithm). We use this forward model to measure the position of an exoplanet in a Bayesian framework employing Gaussian processes and Markov-chain Monte Carlo to account for correlated noise. In the case of GPI data on β Pic b, this technique, which we call Bayesian KLIP-FM Astrometry (BKA), outperforms previous techniques and yields 1σ errors at or below the one milliarcsecond level. We validate BKA by fitting a Keplerian orbit to 12 GPI observations along with previous astrometry from other instruments. The statistical properties of the residuals confirm that BKA is accurate and correctly estimates astrometric errors. Our constraints on the orbit of β Pic b firmly rule out the possibility of a transit of the planet at 10-σ significance. However, we confirm that the Hill sphere of β Pic b will transit, giving us a rare chance to probe the circumplanetary environment of a young, evolving exoplanet. We provide an ephemeris for photometric monitoring of the Hill sphere transit event, which will begin at the start of April in 2017 and finish at the end of January in 2018.

A principal scientific goal of the Gemini Planet Imager (GPI) is obtaining milliarcsecond astrometry to constrain exoplanet orbits. However, astrometry of directly imaged exoplanets is subject to biases, systematic errors, and speckle noise. Here we describe an analytical procedure to forward model the signal of an exoplanet that accounts for both the observing strategy (angular and spectral differential imaging) and the data reduction method (Karhunen-Lo��ve Image Projection algorithm). We use this forward model to measure the position of an exoplanet in a Bayesian framework employing Gaussian processes and Markov chain Monte Carlo (MCMC) to account for correlated noise. In the case of GPI data on $��$ Pic b, this technique, which we call Bayesian KLIP-FM Astrometry (BKA), outperforms previous techniques and yields 1$��$-errors at or below the one milliarcsecond level. We validate BKA by fitting a Keplerian orbit to twelve GPI observations along with previous astrometry from other instruments. The statistical properties of the residuals confirm that BKA is accurate and correctly estimates astrometric errors. Our constraints on the orbit of $��$ Pic b firmly rule out the possibility of a transit of the planet at 10-$��$ significance. However, we confirm that the Hill sphere of $��$ Pic b will transit, giving us a rare chance to probe the circumplanetary environment of a young, evolving exoplanet. We provide an ephemeris for photometric monitoring of the Hill sphere transit event, which will begin at the start of April in 2017 and finish at the end of January in 2018., 18 pages, 7 figures. Accepted to AJ. v2 corrects an error in plotting the full size of the Hill sphere in Figure 6