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The Blood Profiling Atlas in Cancer (BLOODPAC) Consortium is a collaborative effort involving stakeholders from the public, industry, academia, and regulatory agencies focused on developing shared best practices on liquid biopsy. This report describes the results from the JFDI (Just Freaking Do It) study, a BLOODPAC initiative to develop standards on the use of contrived materials mimicking cell-free circulating tumor DNA, to comparatively evaluate clinical laboratory testing procedures. Nine independent laboratories tested the concordance, sensitivity, and specificity of commercially available contrived materials with known variant-allele frequencies (VAFs) ranging from 0.1% to 5.0%. Each participating laboratory utilized its own proprietary evaluation procedures. The results demonstrated high levels of concordance and sensitivity at VAFs of >0.1%, but reduced concordance and sensitivity at a VAF of 0.1%; these findings were similar to those from previous studies, suggesting that commercially available contrived materials can support the evaluation of testing procedures across multiple technologies. Such materials may enable more objective comparisons of results on materials formulated in-house at each center in multicenter trials. A unique goal of the collaborative effort was to develop a data resource, the BLOODPAC Data Commons, now available to the liquid-biopsy community for further study. This resource can be used to support independent evaluations of results, data extension through data integration and new studies, and retrospective evaluation of data collection.

From May through July 2020, Arizona was a global hotspot for new COVID-19 cases. In response to the surge of cases, local public health departments looked for innovative ways to form external partnerships to address their staffing needs. In collaboration with the Maricopa County Department of Public Health, the Arizona State University Student Outbreak Response Team (SORT) created and implemented a virtual call center to conduct public health case investigations for COVID-19. SORT officially launched a dedicated COVID-19 case investigation program after 3 weeks of program design and training. From June 29 through November 8, 2020, SORT recruited and trained 218 case investigators, completed 5000 case patient interviews, and closed 10 000 cases. Our team also developed process improvements to address disparities in case investigation timeliness. A strong infrastructure designed to accommodate remote case investigations, paired with a large workforce, enabled SORT to provide additional surge capacity for the county’s high volume of cases. University-driven multidisciplinary case investigator teams working in partnership with state, tribal, and local public health staff members can be an effective tool for supporting a diverse and growing public health workforce. We discuss the essential design factors involved in building a university program to complement local COVID-19 response efforts, including workflows for case management, volunteer case investigator recruitment and training, secure technology platforms for conducting case investigations remotely, and robust data-tracking procedures for maintaining quality control and timely case reporting.

Seasonal estrous of small ruminants can hinder overall reproductive efficiency of holistic management strategies involving sheep and goats. The objective of this study was to quantify the effect of increased melatonin containing feed ingredients on ovarian function during seasonal anestrus. Ovarian follicle number and follicle sizes were evaluated on Spanish × Boer cross does and Rambouillet ewes amounts of lineseed meal in the treatment diet (P30DIET) or an isocoloric and isonitrogenous control diet (CON). The P30DIET contained 2.5% linseed meal which contained increased melatonin (Manchester et al. 2000). At d -18 ewes and does were stratified by age into treatment groups and the P30DIET and CON diets were supplemented (0.91 kg and 0.68 kg per animal per day for sheep and goats, respectively). Synchronization protocols were administered at d 0 for both groups and ovarian ultrasound measures were collected 48 h after the removal of the controlled internal drug release device (CIDR). Mixed model procedures of SAS were used to analyze the number of dominant follicles that were present following the synchronization protocols. The number of dominant follicles observed in the P30DIET goats was significantly greater than the CON consuming goats (P < 0.05). Least Squares Means estimates (LSMEANS) in the P30DIET were 1.5 ± 0.20 as compared with CON goats (0.91 ± .21). These data suggest that flushing small ruminants with greater linseed meal during the seasonal anestrus period can increase the number of dominant follicles therefore implying an improvement in reproductive efficiency in holistic management strategies of small ruminants.

Direct infusion shotgun proteome analysis (DISPA) is a new paradigm for expedited mass spectrometry-based proteomics, but the original data analysis workflow was onerous. Here, we introduce CsoDIAq, a user-friendly software package for the identification and quantification of peptides and proteins from DISPA data. In addition to establishing a complete and automated analysis workflow with a graphical user interface, CsoDIAq introduces algorithmic concepts to spectrum-spectrum matching to improve peptide identification speed and sensitivity. These include spectra pooling to reduce search time complexity and a new spectrum–spectrum match score called match count and cosine, which improves target discrimination in a target-decoy analysis. Fragment mass tolerance correction also increased the number of peptide identifications. Finally, we adapt CsoDIAq to standard LC–MS DIA and show that it outperforms other spectrum–spectrum matching software.

Pressure and stress perturbations associated with volcanic activity and geothermal production can modify the porosity and permeability of volcanic rock, influencing hydrothermal convection, the distribution of pore fluids and pressures, and the ease of magma outgassing. However, porosity and permeability data for volcanic rock as a function of pressure and stress are rare. We focus here on three porous tuffs from Krafla volcano (Iceland). Triaxial deformation experiments showed that, despite their very similar porosities, the mechanical behavior of the three tuffs differs. Tuffs with a greater abundance of phyllosilicates and zeolites require lower stresses for inelastic behavior. Under hydrostatic conditions, porosity and permeability decrease as a function of increasing effective pressure, with larger decreases measured at pressures above that required for cataclastic pore collapse. During differential loading in the ductile regime, permeability evolution depends on initial microstructure, particularly the initial void space tortuosity. Cataclastic pore collapse can disrupt the low‐tortuosity porosity structure of high‐permeability tuffs, reducing permeability, but does not particularly influence the already tortuous porosity structure of low‐permeability tuffs, for which permeability can even increase. Increases in permeability during compaction, not observed for other porous rocks, are interpreted as a result of a decrease in void space tortuosity as microcracks surrounding collapsed pores connect adjacent pores. Our data underscore the importance of initial microstructure on permeability evolution in volcanic rock. Our data can be used to better understand and model fluid flow at geothermal reservoirs and volcanoes, important to optimize geothermal exploitation and understand and mitigate volcanic hazards. The volcanic rocks within a volcano or geothermal reservoir are frequently subject to changes in pressure and stress. Understanding whether pressures and stresses increase or decrease permeability, and by how much, is important for understanding volcano behavior and to maximize the efficiency of a geothermal reservoir. We performed experiments in which we measured the permeability evolution of porous volcanic rocks, three tuffs, as a function of pressure and stress. We also characterized their mechanical behavior. We first show that their mechanical behavior depends on composition: the more clay minerals and chlorite present, the weaker the tuff. We then show that increasing hydrostatic pressure (i.e., depth) decreases their permeability, but that differential loading in the ductile regime can either decrease or increase permeability. Rock permeability usually decreases during deformation in the ductile regime, and so the latter result is surprising. The observed differences in permeability evolution during ductile deformation is attributed to microstructural differences between the tuffs. However, changes in permeability as a function of pressure and stress are small when compared to other rocks, suggesting that tuff may help to maintain hydrothermal circulation in volcanoes and geothermal reservoirs, with attendant consequences for volcanic hazards and geothermal energy exploitation. Tuffs are likely weakened by the presence clay minerals, chlorite, and zeolites due to a reduction in fracture toughnessPermeability of tuff decreases during hydrostatic pressurization, particularly following the onset of inelastic hydrostatic compactionPermeability of tuff can increase during ductile deformation due to flow‐parallel microcracks that form surrounding collapsed pores Tuffs are likely weakened by the presence clay minerals, chlorite, and zeolites due to a reduction in fracture toughness Permeability of tuff decreases during hydrostatic pressurization, particularly following the onset of inelastic hydrostatic compaction Permeability of tuff can increase during ductile deformation due to flow‐parallel microcracks that form surrounding collapsed pores

Tumor-infiltrating regulatory T cells (TI-Tregs) elicit immunosuppressive effects in the tumor microenvironment (TME) leading to accelerated tumor growth and resistance to immunotherapies against solid tumors. Here, we demonstrate that poly-(ADP-ribose)-polymerase-11 (PARP11) is an essential regulator of immunosuppressive activities of TI-Tregs. Expression of PARP11 correlates with TI-Treg cell numbers and poor responses to immune checkpoint blockade (ICB) in human patients with cancer. Tumor-derived factors including adenosine and prostaglandin E2 induce PARP11 in TI-Tregs. Knockout of PARP11 in the cells of the TME or treatment of tumor-bearing mice with selective PARP11 inhibitor ITK7 inactivates TI-Tregs and reinvigorates anti-tumor immune responses. Accordingly, ITK7 decelerates tumor growth and significantly increases the efficacy of anti-tumor immunotherapies including ICB and adoptive transfer of chimeric antigen receptor (CAR) T cells. These results characterize PARP11 as a key driver of TI-Treg activities and a major regulator of immunosuppressive TME and argue for targeting PARP11 to augment anti-cancer immunotherapies.

The North Atlantic is a region of enhanced biogeochemical and climatological importance for the global ocean as it is the site of one of the largest seasonal phytoplankton blooms on the planet. However, there is a lack of understanding of how phytoplankton size influences bloom dynamics and associated nutrient utilization rates, particularly during the decline phase when export to the deep ocean is especially pronounced. Here, we evaluate trends in size‐fractionated carbon, nitrogen, and silicic acid uptake rates in conjunction with environmental parameters to assess these dynamics. In our study, the decline phase of the bloom continued to be highly productive with net primary production (NPP) ranging from 36.4 to 146.6 mmol C m−2d−1and approximately 54% of primary production being driven by large phytoplankton cells (≥5 μm) that were primarily utilizing nitrate (mean f‐ratio of 0.77). Entrainment of silicic acid related to deepening of the mixed layer caused by storms increased silicic acid uptake rates to 2.0–5.7 mmol Si m−2d−1without concomitant increases in NPP by large cells (silicic acid to carbon uptake ratios averaged 0.12). A companion study in the North Pacific allowed for paired evaluation of these regions. Our results suggest that in highly productive regions where phytoplankton biomass and productivity is distributed across a broad range of cell sizes, such as the North Atlantic, size itself has a stronger influence on nutrient cycling and potential carbon export relative to regions with lower production and a predominance of small (<5 μm) cells, such as the North Pacific. The North Atlantic Ocean experiences a seasonal bloom of phytoplankton. This bloom represents one of the largest removals of anthropogenic carbon to the deep ocean on the planet. Here, we seek to better quantify the mechanisms of this removal by characterizing the amount and composition of phytoplankton present and how much primary production they are engaging in. We sampled during the decline phase of the spring bloom and found the region to be characterized by mostly large phytoplankton primarily utilizing nitrate. When compared to a companion study in the North Pacific, this study confirms the important role cell size and nutrient availability play in determining the degree of productivity in both high and low primary production oceanic regions. The decline phase of the North Atlantic spring bloom exhibits transitions in the balance between small and large size‐fractionated primary production dynamicsDuring the bloom decline, diatoms  contribute less to primary production but remain a substantial component of phytoplankton biomassPhytoplankton size is a substantial control on ecosystem dynamics in endmember oceanic productivity‐export systems The decline phase of the North Atlantic spring bloom exhibits transitions in the balance between small and large size‐fractionated primary production dynamics During the bloom decline, diatoms  contribute less to primary production but remain a substantial component of phytoplankton biomass Phytoplankton size is a substantial control on ecosystem dynamics in endmember oceanic productivity‐export systems