Visually guided and context-dependent spatial navigation in the translucent fish Danionella cerebrum.

Danionella cerebrum (DC) is a promising vertebrate animal model for systems neuroscience due to its small adult brain volume and inherent optical transparency, but the scope of their cognitive abilities remains an area of active research. In this work, we established a behavioral paradigm to study visual spatial navigation in DC and investigate their navigational capabilities and strategies. We initially observed that adult DC exhibit strong negative phototaxis in groups but less so as individuals. Using their dark preference as a motivator, we designed a spatial navigation task inspired by the Morris water maze. Through a series of environmental cue manipulations, we found that DC utilize visual cues to anticipate a reward location and found evidence for landmark-based navigational strategies wherein DC could use both proximal and distal visual cues. When subsets of proximal visual cues were occluded, DC were capable of using distant contextual visual information to solve the task, providing evidence for allocentric spatial navigation. Without proximal visual cues, DC tended to seek out a direct line of sight with at least one distal visual cue while maintaining a positional bias toward the reward location. In total, our behavioral results suggest that DC can be used to study the neural mechanisms underlying spatial navigation with cellular resolution imaging across an adult vertebrate brain.

Multiomics characterization of cell type repertoires for urine liquid biopsies.

Urine is assayed alongside blood in medicine, yet current clinical diagnostic tests utilize only a small fraction of its total biomolecular repertoire, potentially foregoing high-resolution insights into human health and disease. In this work, we characterized the joint landscapes of transcriptomic and metabolomic signals in human urine. We also compared the urine transcriptome to plasma cell-free RNA, identifying a distinct cell type repertoire and enrichment for metabolic signal. Untargeted metabolomic measurements identified a complementary set of pathways to the transcriptomic analysis. Our findings suggest that urine is a promising biofluid yielding prognostic and detailed insights for hard-to-biopsy tissues with low representation in the blood, offering promise for a new generation of liquid biopsies.

Unraveling Abusive Supervision Climate in Aircrew Workplaces: The Roles of Temporary Organizational Features, Trust, and Gender Dynamics.

This study aims to advance the theoretical understanding of the contextual antecedents underlying abusive supervision. It provides a fresh perspective on how subordinates' perceptions of an abusive supervision climate are shaped in temporary work environments. By developing a robust model, this research examines the relationships between temporary organizational characteristics (i.e., temporariness and membership flexibility), trust in ad-hoc supervisors, and perceived abusive supervision climates. We tested the hypothesized model using data from 340 aircrew engaged in temporary and constantly shifting supervisor-subordinate relationships. The results revealed that: (a) temporariness has a direct negative relationship with trust in ad-hoc supervisors, whereas membership flexibility positively affects this trust; (b) the link between temporariness/membership flexibility and a perceived abusive supervision climate is mediated by trust in ad-hoc supervisors. Furthermore, this study highlights gender interactions in a transactional context, indicating that: (c) females perceive a stronger negative association between trust and abusive supervision climates compared to males; and (d) the relationship between temporariness/membership flexibility and trust in ad-hoc supervisors is significant for women and men, respectively. In conclusion, this study underscores the importance of considering the unique organizational characteristics of temporary work settings when examining abusive supervision. It also emphasizes the role of gender in shaping subordinates' perceptions of a workplace victimization climate, particularly in situations where leader-member exchanges are ephemeral and contractual.

Redirecting Nonurgent Patients From the Pediatric Emergency Department to Their Pediatrician Office for a Same-Day Visit-A Quality Improvement Initiative.

OBJECTIVES: Providing high-quality care in the appropriate setting to optimize value is a worthy goal of an efficient health system. Consequences of managing nonurgent complaints in the emergency department (ED) have been described including inefficiency, loss of the primary care-patient relationship, and delayed care for other ED patients. The purpose of this initiative was to redirect nonurgent patients arriving in the ED to their primary care office for a same-day visit, and the SMART AIM was to increase redirected patients from 0% of those eligible to 30% in a 12-month period. METHODS: The setting was a pediatric ED (PED) and primary care office of a tertiary care pediatric medical system. The initiative utilized the electronic health record to identify and mediate the redirection of patients to the patient's primary care office after ED triage. The primary measurement was the percentage of eligible patients redirected. Additional measures included health benefits during the primary care visit (vaccines, well-visits) and a balancing measure of patients returned to the PED. RESULTS: The SMART AIM of >30% redirection was achieved and sustained with a final redirection rate of 46%. In total, 216 of 518 eligible patients were redirected, with zero untoward outcomes. The encounter time for redirected patients was similar for those who remained in the PED, and additional health benefits were appreciated for redirected patients. CONCLUSIONS: This initiative redirected nonurgent patients efficiently from a PED setting to their primary care office. The process is beneficial to patients and families and supports the patient-centered medical home. The balancing measure of no harm done to patients who accepted redirect reinforced the reliability of PED triage. The benefits achieved through the project highlight the value of the primary care-patient relationship and the continued need to improve access for patients and families.

An Efficient Framework for Video Documentation of Bladder Lesions for Cystoscopy: A Proof-of-Concept Study.

Processing full-length cystoscopy videos is challenging for documentation and research purposes. We therefore designed a surgeon-guided framework to extract short video clips with bladder lesions for more efficient content navigation and extraction. Screenshots of bladder lesions were captured during transurethral resection of bladder tumor, then manually labeled according to case identification, date, lesion location, imaging modality, and pathology. The framework used the screenshot to search for and extract a corresponding 10-seconds video clip. Each video clip included a one-second space holder with a QR barcode informing the video content. The success of the framework was measured by the secondary use of these short clips and the reduction of storage volume required for video materials. From 86 cases, the framework successfully generated 249 video clips from 230 screenshots, with 14 erroneous video clips from 8 screenshots excluded. The HIPPA-compliant barcodes provided information of video contents with a 100% data completeness. A web-based educational gallery was curated with various diagnostic categories and annotated frame sequences. Compared with the unedited videos, the informative short video clips reduced the storage volume by 99.5%. In conclusion, our framework expedites the generation of visual contents with surgeon's instruction for cystoscopy and potential incorporation of video data towards applications including clinical documentation, education, and research.

Ames-2021 CO2 Dipole Moment Surface and IR Line Lists: Toward 0.1% Uncertainty for CO2 IR Intensities.

A highly accurate CO2 ab initio dipole moment surface (DMS), Ames-2021, is reported along with 12C16O2 infrared (IR) intensity comparisons approaching a 1-4‰ level of agreement and uncertainty. The Ames-2021 DMS was accurately fitted from CCSD(T) finite-field dipoles computed with the aug-cc-pVXZ (X = T, Q, 5) basis for C atom and the d-aug-cc-pVXZ (X = T, Q, 5) basis for O atoms, and extrapolated to the one particle basis set limit. Fitting σrms is 3.8 × 10-7 au for 4443 geometries below 15 000 cm-1. The corresponding IR intensity, SAmes-2021, are computed using the Ames-2 potential energy surface (PES), which is the best PES available for CO2. Compared to high accuracy IR studies for 2001i-00001 and 3001i-00001 bands, SAmes-2021 matches NIST experiment-based intensities [SNIST-HIT16 or SHIT20] to -1.0 ± 1.3‰, or matches DLR experiment-based intensities [SDLR-HIT16/UCL/Ames] to 1.9 ± 3.7‰. This indicates the systematic deviations and uncertainties have been significantly reduced in SAmes-2021. The SUCL2015 (or SHITRAN2016) have larger deviations (vs SDLR) and uncertainties (vs SDLR, SNIST) which are attributed to the less accurate Ames-1 PES adopted in UCL-296 line list calculation. The SAmes-2021 intensity of 12C16O2 and 13C16O2 is utilized to derive new absolute 13C/12C ratios for Vienna PeeDee Belemnite (VPDB) with uncertainty reduced by 1/3 or 2/3. Further evaluation of SAmes-2021 intensities are carried out on those CO2 bands discussed in the HITRAN2020 update paper. Consistent improvements and better accuracies are found in band-by-band analysis, except for those bands strongly affected by Coriolis couplings, or very weak bands measured with relatively larger experimental uncertainties. The Ames-2021 296 K IR line lists are generated for 13 CO2 isotopologues, with 18 000 cm-1 and S296 K > 1 × 10-31 cm/molecule cutoff and then combined with CDSD line positions (except 14C16O2). The Ames-2021 DMS and 296 K IR line lists represent a major improvement over previous CO2 theoretical IR intensity studies, including Ames-2016, UCL-296, and recent UCL DMS 2021 update. A real 1 permille level of agreement and uncertainty will definitely require both more accurate PES and more accurate DMS.

Energy Landscape and Structural and Spectroscopic Characterization of Diazirine and Its Cyclic Isomers.

Identifying new nitrogenated hydrocarbon molecules in the interstellar medium (ISM) is challenging because of the lack of comprehensive spectroscopic data from experiments. In this computational work, we focus on investigating the structures, relative energies, spectroscopic constants, and energy landscape of the cyclic isomers of diazirine (c-CH2N2) using ab initio quantum chemical methods. Density functional theory (DFT) methods and coupled cluster theory with singles and doubles including perturbative triples [CCSD(T)] and CCSD(T) with the explicitly correlated F12b correction [CCSD(T)-F12b] were employed for this purpose along with large correlation consistent cc-pVTZ, cc-pVQZ, and cc-pV5Z basis sets. Harmonic vibrational frequencies, infrared vibrational intensities, rotational constants, and dipole moments are reported. Anharmonic vibrational fundamentals along with centrifugal distortion constants, and vibration-rotation interaction constants are also reported for all the cyclic isomers. The energies computed with the CCSD(T) and CCSD(T)-F12b methods were extrapolated to the one-particle complete basis set (CBS) limit following a three-point formula. At the CCSD(T)-F12b/CBS level of theory, the 3,3H-diazirine (c-CH2N2) is the lowest energy cyclic isomer followed by 1,3H-diazirine, (E)-1,2H-diazirine, and (Z)-1,2H-diazirine, which are 20.1, 47.8, and 51.3 kcal mol-1 above the 3,3H-diazirine, respectively. Accurate structures and spectroscopic constants that are reported here could be useful for future identification of these cyclic nitrogenated organic molecules in the interstellar medium or circumstellar disks.

Anharmonicity and the IR Emission Spectrum of Neutral Interstellar PAH Molecules.

The characteristics of the CH stretching and out-of-plane bending modes in polycyclic aromatic hydrocarbon molecules are investigated using anharmonic density functional theory (DFT) coupled to a vibrational second-order perturbation treatment taking resonance effects into account. The results are used to calculate the infrared emission spectrum of vibrationally excited species in the collision-less environment of interstellar space. This model follows the energy cascade as the molecules relax after the absorption of a UV photon in order to calculate the detailed profiles of the infrared bands. The results are validated against elegant laboratory spectra of polycyclic aromatic hydrocarbon absorption and emission spectra obtained in molecular beams. The factors which influence the peak position, spectral detail, and relative strength of the CH stretching and out-of-plane bending modes are investigated, and detailed profiles for these modes are derived. These are compared to observations of astronomical objects in space, and the implications for our understanding of the characteristics of the molecular inventory of space are assessed.

Effectiveness of reduced- versus standard-dose radiotherapy on survival and radiation-associated toxicity in patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma: a systematic review protocol.

OBJECTIVE: The objective of this review is to investigate overall survival in patients with human papillomavirus positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC) comparing standard- versus reduced-dose radiotherapy. INTRODUCTION: The improved survival of patients with HPV+ compared to HPV-negative OPSCC has raised the question of reducing the total radiation treatment dose delivered to patients with HPV+ OPSCC. A de-escalated radiotherapy protocol may provide equal oncological benefit, with reduced adverse events/toxicity. INCLUSION CRITERIA: We will include any adult patients aged 18years or older who have undergone curative intent treatment for HPV+ OPSCC. These patients can be at any stage at the time treatment is initiated. Exclusion criteria are as follows: pre-clinical or animal studies, patients with non-squamous cell carcinoma lesions of the oropharynx, patients with primary lesions in other head and neck sites, or patients receiving palliative treatment. METHODS: A three-step search strategy will be used to identify relevant articles for inclusion through MEDLINE, CINAHL, Embase, Web of Science, Scopus, and gray literature sources. These articles will be assessed against our inclusion and exclusion criteria at the title and abstract level as well as at full-text level. Remaining studies will be critically appraised based on their trial design. Data extraction will occur for all studies and, where possible, will be pooled with statistical meta-analysis. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42021252161.

Modeling the infrared cascade spectra of small PAHs: the 11.2 µm band.

The profile of the 11.2 µm feature of the infrared (IR) cascade emission spectra of polycyclic aromatic hydrocarbon (PAH) molecules is investigated using a vibrational anharmonic method. Several factors are found to affect the profile including: the energy of the initially absorbed ultraviolet (UV) photon, the density of vibrational states, the anharmonic nature of the vibrational modes, the relative intensities of the vibrational modes, the rotational temperature of the molecule, and blending with nearby features. Each of these factors is explored independently and influence either the red or blue wing of the 11.2 µm feature. The majority impact solely the red wing, with the only factor altering the blue wing being the rotational temperature.

Fundamental Vibrational Frequencies and Spectroscopic Constants of Substituted Cyclopropenylidene (c-C3HX, X = F, Cl, CN).

The recent detection of ethynyl-functionalized cyclopropenylidene (c-C3HC2H) has initiated the search for other functional forms of cyclopropenylidene (c-C3H2) in space. There is existing gas-phase rotational spectroscopic data for cyano-cyclopropenylidene (c-C3HCN), but the present work provides the first anharmonic vibrational spectral data for that molecule, as well as the first full set of both rotational and vibrational spectroscopic data for fluoro- and chloro-cyclopropenylidenes (c-C3HF and c-C3HCl). All three molecules have fundamental vibrational frequencies with substantial infrared intensities. Namely, c-C3HCN has a moderately intense fundamental frequency at 1244.4 cm-1, while c-C3HF has two large intensity modes at 1765.4 and 1125.3 cm-1 and c-C3HCl again has two large intensity modes at 1692.0 and 1062.5 cm-1. All of these frequencies are well within the spectral range covered by the high-resolution EXES instrument on NASA's Stratospheric Observatory for Infrared Astronomy (SOFIA). Further, all three molecules have dipole moments of around 3.0 D in line with c-C3H2, enabling them to be observed by pure rotational spectroscopy, as well. Thus, the rovibrational spectral data presented herein should assist with future laboratory studies of functionalized cyclopropenylidenes and may lead to their interstellar or circumstellar detection.

Bladder cancer risk stratification using a urinary mRNA biomarker panel - A path towards cystoscopy triaging.

OBJECTIVES: The risk of bladder cancer (BCa) diagnosis and recurrence necessitates cystoscopy. Improved risk stratification may inform personalized triage and surveillance strategies. We aim to develop a urinary mRNA biomarker panel for risk stratification in patients undergoing BCa screening and surveillance. METHODS AND MATERIALS: Urine samples were collected from patients undergoing cystoscopy for BCa screening or surveillance. In patients who underwent transurethral resection of bladder tumor, urine samples were categorized based on tumor histopathology, size, and focality. Subjects with intermediate and high-risk BCa based on American Urological Association (AUA) guideline for non-muscle invasive bladder cancer were classified as "increased-risk"; those with no cancer and AUA low-risk BCa were classified as "low-risk". Urine was evaluated for ROBO1, WNT5A, CDC42BPB, ABL1, CRH, IGF2, ANXA10, and UPK1B expression. A diagnostic model to detect "increased-risk" BCa was created using forward logistic regression analysis of cycle threshold values. Model validation was performed with ten-fold cross-validation. Sensitivity and specificity for detection of "increased-risk" BCa was determined and net benefit analysis performed. RESULTS: Urine samples (n = 257) were collected from 177 patients (95 screening, 76 surveillance, 6 both). There were 65 diagnoses of BCa (12 low, 22 intermediate, 31 high risk). ROBO1, CRH, and IGF2 expression correlated with "increased-risk" disease yielding sensitivity of 92.5% (95% CI, 84.9%-98.1%) and specificity of 73.5% (95% CI, 67.7-79.9%). The overall calculated standardized net benefit of the model was 0.81 (95%CI, 0.71-0.90). CONCLUSIONS: A 3-marker urinary mRNA panel allows for non-invasive identification of "increased-risk" BCa and with further validation may prove to be a tool to reduce the need for cystoscopies in low-risk patients.

What It Takes to Compute Highly Accurate Rovibrational Line Lists for Use in Astrochemistry.

ConspectusWe review the Best Theory + Reliable High-Resolution Experiment (BTRHE) strategy for obtaining highly accurate molecular rovibrational line lists with InfraRed (IR) intensities. The need for highly accurate molecular rovibrational line lists is twofold: (a) assignment of the many rovibrational lines for common stable molecules especially those that exhibit a large amplitude motion, such as NH3, or have a high density of states such as SO2; and (b) characterization of the atmospheres of exoplanets, which will be one of the main areas of research in astronomy in the coming decades. The first motivation arises due to the need to eliminate lines due to common molecules in an astronomical observation in order to identify lines from new molecules, while the second motivation arises due to the need to obtain accurate molecular opacities in order to characterize the atmosphere of an exoplanet. The BTRHE strategy first consists of using high-quality ab initio quantum-chemical methods to obtain a global potential energy surface (PES) and dipole moment surface (DMS) that contains the proper physics. The global PES is then refined using a subset of the reliable high-resolution experimental data. The refined PES then gives energy-level predictions to an accuracy similar to the reproduction accuracy of the experimental data used in the refinement step in the interpolation region (i.e., within the range of the experimental data used in the refinement step). The accuracy of the energy levels will slowly degrade as they are extrapolated to spectral regions beyond the high-resolution experimental data used in the refinement step. However, because the degradation is slow, the predicted energy levels can be used to assign new high-resolution experiments, and the data from these can then be used in a subsequent refinement step. In this way, the global PES eventually can yield highly accurate energy levels for all desired spectral regions including to very high energies and high J values. We show that IR intensities computed with the BTRHE rovibrational wave functions and the DMS can be very accurate provided one has minimized the fitting error of the DMS and tested the completeness of the DMS. Some examples of our work on NH3, CO2, and SO2 are given to highlight the usefulness of the BTRHE strategy and to provide ideas on how to further improve its predictive power in the future. In particular, it is shown how successive refinement steps, once new high-resolution data are available, can lead to PESs that yield highly accurate transition energies to larger spectral regions. The importance of including nonadiabatic corrections to reduce the J-dependence of errors for H-containing molecules is shown with work on NH3. Another very important aspect of the BTRHE approach is the consistency across isotopologues, which allows for highly accurate line lists for any isotopologue once one is obtained for the main isotopologue (which has more high-resolution data available for refinement).

Highly-accurate quartic force fields for the prediction of anharmonic rotational constants and fundamental vibrational frequencies.

The CcCR quartic force field (QFF) methodology is capable of computing B0 and C0 rotational constants to within 35 MHz (0.14%) of experiment for triatomic and larger molecules with at least two heavy atoms. Additionally, the same constants for molecules with four or more atoms agree to within 20 MHz (0.12%) of experiment for the current test set. This work also supports previous claims that the same QFF methodology can produce fundamental vibrational frequencies with a deviation less than 5.7 cm-1 from experiment. Consequently, this approach of augmenting complete basis set extrapolated energies with treatments of core electron correlation and scalar relativity produces some of the most accurate rovibrational spectroscopic data available.

The unsolved issue with out-of-plane bending frequencies for CC multiply bonded systems.

More than 30 years ago two groups independently identified a problem in the calculation of the out-of-plane bending (OPB) vibrational frequencies for the ethylene molecule using correlated electronic structure methods. Several studies have been done in the meantime to try and understand and resolve this issue. In so doing this problem has been found to be far more insidious than previously realized for acetylene-like and benzene-like molecules, which can become non-linear and non-planar, respectively. The one common feature that all molecules with this problem have is that they contain CC multiple bonds, and so this has been called the "CC multiple bond OPB frequency issue" or "the CC OPB problem." Various explanations for this problem have been advanced such as basis set superposition error, basis set incompleteness error, linear dependences in the basis set, proper balancing of the basis set between saturation and inclusion of higher angular momentum functions, etc. and possible solutions have arisen from these suggestions. All of these proposed solutions, however, amount to one main point connecting them all: modifying the one-particle basis set in some way. None of the explanations that have been advanced, however, really fit all of the data for all of the molecules where this problem has been identified, and importantly, none of these diagnostic tests have been applied to similar molecules where this issue does not appear. In this review, the studies over the last 30 plus years are discussed and relevant data from each of these is compared and contrasted. It is hoped that by collecting and analyzing the data from these studies a path forward to understanding and resolving this issue will become evident.

Molecular growth upon ionization of van der Waals clusters containing HCCH and HCN is a pathway to prebiotic molecules.

The growth mechanisms of organic molecules in an ionizing environment such as the interstellar medium are not completely understood. Here we examine by means of ab initio molecular dynamics (AIMD) simulations and density functional theory (DFT) computations the possibility of bond formation and molecular growth upon ionization of van der Waals clusters of pure HCN clusters, and mixed clusters of HCN and HCCH, both of which are widespread in the interstellar medium. Ionization of van der Waals clusters can potentially lead to growth in low temperature and low-density environments. Our results show, that upon ionization of the pure HCN clusters, strongly bound stable structures are formed that contain NH bonds, and growth beyond pairwise HCN molecules is seen only in a small percentage of cases. In contrast, mixed clusters, where HCCH is preferentially ionized over HCN, can grow up to 3 or 4 units long with new carbon-carbon and carbon-nitrogen covalent bonds. Moreover, cyclic molecules formed, such as the radical cation of pyridine, which is a prebiotic molecule. The results presented here are significant as they provide a feasible pathway for molecular growth of small organic molecules containing both carbon and nitrogen in cold and relatively denser environments such as in dense molecular clouds but closer to the photo-dissociation regions, and protoplanetary disks. In the mechanism we propose, first, a neutral van der Waals cluster is formed. Once the cluster is formed it can undergo photoionization which leads to chemical reactivity without any reaction barrier.

Overcoming the out-of-plane bending issue in an aromatic hydrocarbon: the anharmonic vibrational frequencies of c-(CH)C3H2.

The challenges associated with the out-of-plane bending problem in multiply-bonded hydrocarbon molecules can be mitigated in quartic force field analyses by varying the step size in the out-of-plane coordinates. Carbon is a highly prevalent element in astronomical and terrestrial environments, but this major piece of its spectra has eluded theoretical examinations for decades. Earlier explanations for this problem focused on method and basis set issues, while this work seeks to corroborate the recent diagnosis as a numerical instability problem related to the generation of the potential energy surface. Explicit anharmonic frequencies for c-(CH)C3H2+ are computed using a quartic force field and the CCSD(T)-F12b method with cc-pVDZ-F12, cc-pVTZ-F12, and aug-cc-pVTZ basis sets. The first of these is shown to offer accuracy comparable to that of the latter two with a substantial reduction in computational time. Additionally, c-(CH)C3H2+ is shown to have two fundamental frequencies at the onset of the interstellar unidentified infrared bands, at 5.134 and 6.088 µm or 1947.9 and 1642.6 cm-1, respectively. This suggests that the results in the present study should assist in the attribution of parts of these aromatic bands, as well as provide data in support of the laboratory or astronomical detection of c-(CH)C3H2+.

Climate Metrics for C1-C4 Hydrofluorocarbons (HFCs).

Hydrofluorocarbons (HFCs) are potent greenhouse gases that are potential substitutes for ozone depleting substances. The Kigali amendment lists 17 HFCs that are currently in commercial use to be regulated under the Montreal Protocol. Future commercial applications may explore the use of other HFCs, most of which currently lack an evaluation of their climate metrics. In this work, atmospheric lifetimes, radiative efficiencies (REs), global warming potentials (GWPs), and global temperature change potentials (GTPs) for all saturated HFCs with fewer than 5 carbon atoms are estimated to help guide future usage and policy decisions. Atmospheric lifetimes were estimated using a structure activity relationship (SAR) for OH radical reactivity and estimated O(1D) reactivity. Radiative metrics were obtained using theoretically calculated infrared absorption spectra that were presented in a previous work. Calculations for some additional HFCs not included in the previous work were performed in this work. The HFCs display unique infrared spectra with strong absorption in the Earth's atmospheric infrared window region, primarily due to the C-F stretching vibration. Results from this study show that the HFC global atmospheric lifetimes and REs are dependent upon their H atom content and molecular structure. Therefore, the HFC radiative metric evaluation requires a case-by-case evaluation. A thorough experimental evaluation of a targeted HFC's atmospheric lifetime and climate metrics is always highly recommended. However, in cases where it is experimentally difficult to separate isomers, the new results from this study should help guide the experiments, as well as provide relevant climate metrics with uncertainties and policy relevant data.

Prebiotic Astrochemistry and the Formation of Molecules of Astrobiological Interest in Interstellar Clouds and Protostellar Disks.

Despite the generally hostile nature of the environments involved, chemistry does occur in space. Molecules are seen in environments that span a wide range of physical and chemical conditions and that clearly were created by a multitude of chemical processes, many of which differ substantially from those associated with traditional equilibrium chemistry. The wide range of environmental conditions and processes involved with chemistry in space yields complex populations of materials, and because the elements H, C, O, and N are among the most abundant in the universe, many of these are organic in nature, including some of direct astrobiological interest. Much of this chemistry occurs in "dense" interstellar clouds and protostellar disks surrounding forming stars because these environments have higher relative densities and more benign radiation fields than in stellar ejectae or the diffuse interstellar medium. Because these are the environments in which new planetary systems form, some of the chemical species made in these environments are expected to be delivered to the surfaces of planets where they can potentially play key roles in the origin of life. Because these chemical processes are universal and should occur in these environments wherever they are found, this implies that some of the starting materials for life are likely to be widely distributed throughout the universe.

Capillary-Based and Stokes-Based Trapping of Serial Sections for Scalable 3D-EM Connectomics.

Serial section electron microscopy (ssEM), a technique where volumes of tissue can be anatomically reconstructed by imaging consecutive tissue slices, has proven to be a powerful tool for the investigation of brain anatomy. Between the process of cutting the slices, or "sections," and imaging them, however, handling 10°-106 delicate sections remains a bottleneck in ssEM, especially for batches in the "mesoscale" regime, i.e., 102-103 sections. We present a tissue section handling device that transports and positions sections, accurately and repeatability, for automated, robotic section pick-up and placement onto an imaging substrate. The device interfaces with a conventional ultramicrotomy diamond knife, accomplishing in-line, exact-constraint trapping of sections with 100-µm repeatability. An associated mathematical model includes capillary-based and Stokes-based forces, accurately describing observed behavior and fundamentally extends the modeling of water-air interface forces. Using the device, we demonstrate and describe the limits of reliable handling of hundreds of slices onto a variety of electron and light microscopy substrates without significant defects (n = 8 datasets composed of 126 serial sections in an automated fashion with an average loss rate and throughput of 0.50% and 63 s/section, respectively. In total, this work represents an automated mesoscale serial sectioning system for scalable 3D-EM connectomics.