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We present CloudFlex, an open-source tool for predicting absorption-line signatures of cool gas in galaxy halos with small-scale structure. Motivated by analyses of ∼104 K material in hydrodynamical simulations of turbulent, multiphase media, we model cool gas structures as complexes of cloudlets sampled from a power-law distribution of mass ∝ m cl − α with velocities drawn from a turbulent velocity field. The user may specify α, the lower limit of the cloudlet mass distribution ( m cl , min ), and several other parameters that set the mass, size, and velocity distribution of the complex. This permits investigation of the relation between these parameters and absorption-line observables. As a proof-of-concept, we calculate the Mg ii λ 2796 absorption induced by the cloudlets in background quasi-stellar object (QSO) spectra. We demonstrate that, at fixed metallicity, the covering fraction of sight lines with equivalent widths W 2796 < 0.3 Å increases significantly with decreasing m cl , min , cloudlet number density (n cl), and complex size. We then use this framework to predict the halo-scale W 2796 distribution around ∼ L * galaxies. We show that the observed incidences of W 2796 > 0.3 Å sight lines with impact parameters 10 kpc < R ⊥ < 50 kpc in projected QSO–galaxy studies are consistent with our model over much of parameter space. However, they are underpredicted by models with m cl , min ≥ 100 M ⊙ and n cl ≥ 0.03 cm−3, in keeping with a picture in which the inner cool circumgalactic medium (CGM) is dominated by numerous low-mass cloudlets (m cl ≲ 100 M ⊙) with a volume filling factor ≲1%. When used to model absorption-line data sets built from multi-sight line and/or spatially extended background probes, CloudFlex enables detailed constraints on the size and velocity distributions of structures comprising the photoionized CGM. [ABSTRACT FROM AUTHOR]

Recent research has demonstrated that additive manufacturing (AM) can be used to produce directionally sensitive high explosives (HEs), but detonation wave propagation in AM HEs with variable internal structure has not been studied. In this work, samples were printed using a 73 wt. % octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine-based HE ink. Flash x-ray radiography imaging was used to observe density changes in two imaging planes of each sample during detonation, and high-speed imaging was used to calculate the detonation velocity at the HE surface. The detonation front initially appears to fail in internal channel regions of the HE, but late reactions occurred in two samples, which increased the material bulk density by 2.8%, possibly due to shock convergence phenomena. The calculated detonation wave pressure similarly increased, but the accuracy of the results is uncertain because of the deviation of the low bulk density printed samples from the cast charge principal isentrope. This work demonstrates that structure can be effectively utilized to guide detonation wave propagation through HE charges. [ABSTRACT FROM AUTHOR]

Benchtop pulsed x-ray systems are commonly used to record dynamic material data on the order of nanoseconds, but pulse timing is often difficult to accurately determine. This study demonstrates that commercially available photodiodes can be used effectively for direct x-ray pulse detection without the need for visible light scintillators. X-ray pulses from four commercially available flash x-ray systems were quantified using one silicon and two indium gallium arsenide (InGaAs) photodiodes. The measured InGaAs pulse durations were strongly dependent on radiation dose in the non-linear operating regime, so the photodiodes were shielded to operate below the 2.5 V non-linear regime threshold. The average pulse duration and pulse arrival time jitter of the photodiodes for each x-ray source were within several nanoseconds with the exception of two sets of measurements that were affected by low instrument sensitivity and electrical noise. These results show that InGaAs photodiodes can be used as effective and repeatable stand-alone timing diagnostics for x-ray pulses as short as 20 ns or less. [ABSTRACT FROM AUTHOR]

Background Anal intraepithelial neoplasia grade III is a precursor to squamous cell carcinoma of the anus for which rates are nearly 20-fold higher in people with HIV than in the general population in the United States. We describe trends in anal intraepithelial neoplasia grade III diagnosis and risk of squamous cell carcinoma of the anus following anal intraepithelial neoplasia grade III by HIV status and sex. Methods We used data from a population-based linkage between cancer and HIV registries in 11 US states; Puerto Rico; and Washington, DC, during 1996-2019. We identified all individuals with a diagnosis of anal intraepithelial neoplasia grade III and determined their HIV status. We estimated the average annual percentage change of anal intraepithelial neoplasia grade III using Poisson regression stratified by HIV status and sex. We estimated the 5-year cumulative incidence of squamous cell carcinoma of the anus following an anal intraepithelial neoplasia grade III diagnosis stratified by sex, HIV status, and prior AIDS diagnosis. Results Among people with HIV, average annual percentage changes for anal intraepithelial neoplasia grade III were 15% (95% confidence interval [CI] = 12% to 17%) per year among females and 12% (95% CI = 11% to 14%) among males. Average annual percentage changes for those without HIV were 8% (95% CI = 7% to 8%) for females and 8% (95% CI = 6% to 9%) for males. Among people with HIV, a prior AIDS diagnosis was associated with a 2.7-fold (95% CI = 2.23 to 3.40) and 1.9-fold (95% CI = 1.72 to 2.02) increased risk of anal intraepithelial neoplasia grade III diagnosis for females and males, respectively. Five-year cumulative incidence of squamous cell carcinoma of the anus following anal intraepithelial neoplasia grade III for people with HIV with a prior AIDS diagnosis were 3.4% and 3.7% for females and males, respectively. Conclusions Rates of anal intraepithelial neoplasia grade III diagnoses have increased since 1996, particularly for people with HIV, likely influenced by increased screening. A prior AIDS diagnosis was strongly associated with risk of anal intraepithelial neoplasia grade III diagnosis. [ABSTRACT FROM AUTHOR]

The benefit of ovarian superstimulation using exogenous FSH before ovum pick-up (OPU) and in vitro embryo production (IVEP) has been the subject of conflicting results. The objective of the present study, therefore, was to evaluate the effect of use and dose of porcine FSH (p-FSH) before OPU/IVEP on ovarian response and embryo production in pregnant heifers. Pregnant Holstein heifers (n = 48) were randomly assigned to receive 0, 160, or 300 mg NIH-FSH-P1 in a crossover design. Ovum pick-up was performed at 49, 63, and 77 d of gestation with a 14 d "washout" between OPU sessions. Follicle ablation was performed on D 0 (p.m.) and p-FSH treatments, consisting of 4 decreasing dose injections administered 12 h apart, were initiated 36 h after follicle ablation (d 2 a.m.). Heifers underwent OPU on D 5 (a.m.), 40 h after the last p-FSH treatment, and cumulus oocyte complexes (COC) were subjected to IVEP procedures. Differences between treatment groups were evaluated using generalized linear mixed models. There were quadratic effects of treatment on both number and percentage of small (<6 mm), medium (6–10 mm), and large (>10 mm) follicles. Number and percentage of medium follicles increased with increasing p-FSH dosages, although the magnitude of the change was greater between 0 and 160 mg, than between 160 and 300 mg of p-FSH. Total number of follicles, number of COC recovered and number of viable COC increased linearly with increasing p-FSH dose. Conversely, there was no evidence for an effect of p-FSH dose on COC recovery percentage nor the percentage of viable COC. Cleavage percentage, number of cleaved oocytes, blastocyst percentage, and number of blastocysts increased linearly with increasing p-FSH dose. In conclusion, use of p-FSH before OPU resulted in greater superstimulatory response and oocyte competence which in turn increased IVEP. Furthermore, these effects were dose dependent such that use of a greater dose of p-FSH up to 300 mg progressively increased embryo yield. [ABSTRACT FROM AUTHOR]

Background: The prevalence of substance use in people with HIV (PWH) in the United States is higher than in the general population and is an important driver of HIV-related outcomes. We sought to assess if previously identified genetic associations that contribute to substance use are also observed in a population of PWH. Methods: We performed genome-wide association studies (GWAS) of alcohol, smoking, and cannabis use phenotypes in a multi-ancestry population of 7,542 PWH from the Center for AIDS Research Network of Integrated Clinical Systems (CNICS). We conducted multi-ancestry GWAS for individuals of African (n = 3,748), Admixed American (n = 1,334), and European (n = 2,460) ancestry. Phenotype data were self-reported and collected using patient reported outcomes (PROs) and three questions from AUDIT-C, an alcohol screening tool. We analyzed nine phenotypes: 1) frequency of alcohol consumption, 2) typical number of drinks on a day when drinking alcohol, 3) frequency of five or more alcoholic drinks in a 30-day period, 4) smoking initiation, 5) smoking cessation, 6) cigarettes per day, 7) cannabis use initiation, 8) cannabis use cessation, 9) frequency of cannabis use during the previous 30 days. For each phenotype we considered a) variants previously identified as associated with a substance use trait and b) novel associations. Results: We observed evidence for effects of previously reported single nucleotide polymorphisms (SNPs) related to alcohol (rs1229984, p = 0.001), tobacco (rs11783093, p = 2.22E-4), and cannabis use (rs2875907, p = 0.005). We also report two novel loci (19p13.2, p = 1.3E-8; and 20p11.21, p = 2.1E-8) associated with cannabis use cessation. Conclusions: Our analyses contribute to understanding the genetic bases of substance use in a population with relatively higher rates of use compared to the general population. [ABSTRACT FROM AUTHOR]

Treatment of screen-detected anal high-grade squamous intraepithelial lesions has been shown to effectively reduce the incidence of invasive anal cancer in people with HIV. We provide population-based estimates of cumulative incidence of anal cancer by risk group and age at HIV or AIDS diagnosis. The 0- to 10-year cumulative incidence of anal cancer for men who have sex with men and are younger than 30 years of age at HIV diagnosis was 0.17% (95% confidence interval [CI] = 0.13% to 0.20%) compared with 0.04% (95% CI = 0.02% to 0.06%) in other men and 0.03% (95% CI = 0.01% to 0.04%) in women. For men who have sex with men and have a diagnosis of AIDS and are younger than 30 years of age, the 0- to 10-year cumulative incidence was 0.35% (95% CI = 0.28% to 0.41%). Among people with HIV, men who have sex with men are at the greatest risk of anal cancer, and those with a diagnosis of AIDS had higher risk than those without AIDS. These estimates may inform recommendations for priority populations that could benefit most from anal cancer screening and treatment. [ABSTRACT FROM AUTHOR]

Counseling governing bodies have clearly defined what should be prioritized in multicultural counseling courses, including students' multicultural knowledge and awareness; however, best practice regarding how to teach these multicultural concepts has largely been left up to the counselor educator. This phenomenological study explored the lived experience of master's level counseling students who participated in weekly expressive arts activities as a part of a diversity class and offers a best practice model for implementing ethical and effective experiential learning using expressive arts techniques. [ABSTRACT FROM AUTHOR]

The actual interaction between signaling species in cellular processes is often more important than their expression levels. Förster resonance energy transfer (FRET) is a popular tool for studying molecular interactions, since it is highly sensitive to proximity in the range of 2–10 nm. Spectral spillover-corrected quantitative (3-cube) FRET is a cost effective and versatile approach, which can be applied in flow cytometry and various modalities of fluorescence microscopy, but may be hampered by varying levels of autofluorescence. Here, we have implemented pixel-by-pixel autofluorescence correction in microscopy FRET measurements, exploiting cell-free calibration standards void of autofluorescence that allow the correct determination of all spectral spillover factors. We also present an ImageJ/Fiji plugin for interactive analysis of single images as well as automatic creation of quantitative FRET efficiency maps from large image sets. For validation, we used bead and cell based FRET models covering a range of signal to autofluorescence ratios and FRET efficiencies and compared the approach with conventional average autofluorescence/background correction. Pixel-by-pixel autofluorescence correction proved to be superior in the accuracy of results, particularly for samples with spatially varying autofluorescence and low fluorescence to autofluorescence ratios, the latter often being the case for physiological expression levels. [ABSTRACT FROM AUTHOR]

Landings in 2019 for North-Eastern Nova Scotia (N-ENS) and South-Eastern Nova Scotia (S-ENS) were 629 t and 6,632 t, respectively, representing a decrease of 15% (N-ENS) and an increase of 9% (S-ENS) relative to the previous year. Total Allowable Catches in 2019 were 631 t, 6,632 t, and 0 t in N-ENS, S-ENS, and 4X, respectively. Due to low commercial biomass levels, there was no allowable catch in 4X for the 2018-19 season. Non-standardized catch rates in 2019 were 87 kg/trap haul in N-ENS and 105 kg/trap haul in S-ENS--which relative to the previous year represents an increase of 40% (N-ENS) and a decrease of 9% (S-ENS). The capture of soft-shelled Snow Crab in N-ENS decreased to 5% from approximately 25% in 2018. In S-ENS, the relative occurrence of soft-shell Snow Crab was approximately 2%, consistent with 2018. Soft-shell discard rates in 4X are traditionally very low, due to season timing. Bycatch of non-target species is extremely low (< 0.4%) in all Crab Fishing Areas (CFAs). In both N-ENS and S-ENS, moderate internal recruitment to the fishery is expected for next year (and likely for 2-4 years) based on size-frequency histograms. Based on survey catches, CFA 4X shows limited potential for substantial internal recruitment to the fishery for the next 4-5 years. Movement is potentially an important source of 4X Snow Crab. In all CFAs, there was a substantial recruitment of females into the mature segment of the population from 2016-2018. Mature Snow Crab densities are now declining but small Snow Crab (< 40mm carapace width) resulting from this period of increased egg production are now observed in all areas in both sexes. These population characteristics are tempered by a number of uncertainties, including the influence of predation and rapid temperature swings (especially in CFA 4X and parts of CFA 24). Both can have direct and indirect influences upon Snow Crab, which are cold-water stenotherms. Predation from halibut is a potentially large and increasing source of natural mortality for Snow Crab on the Scotian Shelf. A new peer-reviewed assessment methodology, conditional auto-regressive spatio-temporal model (carstm), has been adopted that incorporates both survey catches and ecosystem covariates to estimate a commercial Snow Crab abundance index. This index is coupled with a population-dynamics fishery model to determine fishable biomass. The modelled post-fishery fishable biomass index of Snow Crab in N-ENS was estimated to be 4,460 t, relative to 3,299 t in 2018. In S-ENS, the post-fishery fishable biomass index was 54,408 t, relative to 44,705 t in 2018. In 4X, the pre-fishery fishable biomass was 418 t, relative to 428 t in 2018. The N-ENS fishing mortality (F) in 2019 has been estimated to have been 0.14 (exploitation rate 0.13), a decrease from 0.22 in 2018. The S-ENS fishing mortality (F) in 2019 has been estimated to have been 0.12 (exploitation rate 0.13), a decrease from .13 in 2018. The F for 4X in 2018-2019 was 0 as there was no commercial fishery. With expected increasing recruitment for both N- and S-ENS, coupled with falling F over recent years, possibilities for harvest strategy is less limited. Additional work is required to determine more applicable (than current survey-based) Harvest Control Rules and associated management measures in 4X. [ABSTRACT FROM AUTHOR]

Observational studies have shown higher folate consumption to be associated with lower risk of colorectal cancer (CRC). Understanding whether and how genetic risk factors interact with folate could further elucidate the underlying mechanism. Aggregating functionally relevant genetic variants in set-based variant testing has higher power to detect gene–environment (G × E) interactions and may provide information on the underlying biological pathway. We investigated interactions between folate consumption and predicted gene expression on colorectal cancer risk across the genome. We used variant weights from the PrediXcan models of colon tissue-specific gene expression as a priori variant information for a set-based G × E approach. We harmonized total folate intake (mcg/day) based on dietary intake and supplemental use across cohort and case–control studies and calculated sex and study specific quantiles. Analyses were performed using a mixed effects score tests for interactions between folate and genetically predicted expression of 4839 genes with available genetically predicted expression. We pooled results across 23 studies for a total of 13,498 cases with colorectal tumors and 13,918 controls of European ancestry. We used a false discovery rate of 0.2 to identify genes with suggestive evidence of an interaction. We found suggestive evidence of interaction with folate intake on CRC risk for genes including glutathione S-Transferase Alpha 1 (GSTA1; p = 4.3E−4), Tonsuko Like, DNA Repair Protein (TONSL; p = 4.3E−4), and Aspartylglucosaminidase (AGA: p = 4.5E−4). We identified three genes involved in preventing or repairing DNA damage that may interact with folate consumption to alter CRC risk. Glutathione is an antioxidant, preventing cellular damage and is a downstream metabolite of homocysteine and metabolized by GSTA1. TONSL is part of a complex that functions in the recovery of double strand breaks and AGA plays a role in lysosomal breakdown of glycoprotein. [ABSTRACT FROM AUTHOR]

The objective of the present study was to evaluate effects of synchronization of timing of follicle wave emergence, before ovarian superstimulation and ovum pick-up (OPU), on ovarian response and embryo production in pregnant heifers. Pregnant (47–69 days of gestation) Holstein heifers (n = 64), 19.0 ± 0.3 months of age, were assigned in a completely randomized design to one of two groups: synchronization of follicular wave emergence using follicle ablation (Synchronized) or untreated control (Non-synchronized). Superstimulatory treatments consisting of 160 mg (280 IU) of porcine follicle stimulating hormone (p-FSH), administered in four decreasing dose treatments 12 h apart, were initiated 36 h after follicle ablation or at random stages of the follicular wave in heifers of the Synchronized and Non-synchronized group, respectively. Ovum pick-up was performed in all heifers 40 h after the last p-FSH administration and retrieved cumulus oocyte complexes (COCs) were subjected to in vitro embryo production (IVEP) procedures. Ultrasonography was performed immediately before OPU to determine number and size of ovarian follicles. Differences in treatment responses between groups were evaluated using generalized linear mixed models. Total number of follicles at the time of OPU was not different between treatment groups (P = 0.61), however, the number of small follicles (<6 mm) was greater (P = 0.05) in heifers of the Non-synchronized group, whereas number of medium size follicles (6–10 mm) tended (P = 0.09) to be greater in heifers of the Synchronized group. Heifers in the Synchronized group had a greater (P = 0.01) percentage of medium sized follicles and a lesser (P = 0.01) percentage of smaller sized follicles than heifers in the Non-synchronized group. There were no differences (P > 0.15) in total number of recovered COCs, or number of viable COCs between groups. Cleavage percentage (84.5% and 72.8%) and blastocyst percentage (48.2% and 33.4%) were greater (P < 0.01) in heifers of the Synchronized than Non-synchronized group, respectively. As a result, mean number of blastocysts per OPU/heifer was greater (P = 0.006) in the heifers of the Synchronized (8.9 ± 1.0) than the Non-synchronized (5.5 ± 0.9) group. In conclusion, synchronizing the time of follicle wave emergence in pregnant heifers, prior to ovarian superstimulation with FSH and OPU results in a greater superstimulatory response and oocyte competence leading to greater embryo production. 1. Synchronization of follicle wave emergence before superstimulation improves ovarian response. 2. Superstimulation initiated at wave emergence increases developmental competence and embryo quality. 3. Initiation of exogenous FSH at follicle wave emergence improves IVEP in pregnant heifers. [ABSTRACT FROM AUTHOR]

This study assessed the Moral Injury Symptoms Scale – Military Version – Short Form's (MISS-M-SF) factor structure and construct validity. Participants included 3650 combat-deployed U.S. veterans who answered all 10 MISS-M-SF items from the sixth wave of The Veterans Metric Initiative (TVMI). EFA results suggested a two-factor solution, based on item wording, fit best. CFA results indicated a bifactor model (one general factor and two method factors, based on item wording) fit best. Further investigation revealed that a one-factor model could be used despite the data's multidimensionality. Item-level analyses revealed four items represented the general factor exceptionally well, potentially simplifying assessment in research and clinical applications. Construct validity was also demonstrated through moderate to high correlations with conceptually related measures. [ABSTRACT FROM AUTHOR]

We search for γ-ray emission from 114 Galactic high-mass X-ray binaries, including four well studied catalogued sources, in 12.5 yr of Fermi -LAT data in conjunction with the 10-yr point source catalogue. Where a γ-ray excess appears to be spatially coincident with an X-ray binary, further investigation is performed to ascertain whether this excess is the product of physical processes within the binary system itself. We identify γ-ray excesses coincident with 20 high-mass X-ray binaries where there is little or no prior evidence for γ-ray emission. However, we find that many of these are false positives caused by source confusion or the γ-ray background. None the less, tentative but promising indicators of γ-ray emission are identified for several new systems, notably including 1A 0535+262, RX J2030.5+4751, and SAX J1324.4−6200. [ABSTRACT FROM AUTHOR]

Muco-obstructive lung diseases are typically associated with high risks of COVID-19 severity; however, allergic asthma showed reduced susceptibility. To investigate viral spread, primary human airway epithelial (HAE) cell cultures were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and host-virus interactions were examined via electron microscopy, immunohistochemistry, RNA in situ hybridization, and gene expression analyses. In HAE cell cultures, angiotensin-converting enzyme 2 (ACE2) expression governed cell tropism and viral load and was up-regulated by infection. Electron microscopy identified intense viral egress from infected ciliated cells and severe cytopathogenesis, culminating in the shedding of ciliated cells packed with virions, providing a large viral reservoir for spread and transmission. Intracellular stores of MUC5AC, a major airway mucin involved in asthma, were rapidly depleted, likely to trap viruses. To mimic asthmatic airways, HAE cells were treated with interleukin-13 (IL-13), which reduced viral titers, viral messenger RNA, and cell shedding, and significantly diminished the number of infected cells. Although mucus hyperproduction played a shielding role, IL-13-treated cells maintained a degree of protection despite the removal of mucus. Using Gene Expression Omnibus databases, bulk RNA-sequencing analyses revealed that IL-13 up-regulated genes controlling glycoprotein synthesis, ion transport, and antiviral processes (albeit not the typical interferon-induced genes) and down-regulated genes involved in cilial function and ribosomal processing. More precisely, we showed that IL-13 reduced ACE2 expression, intracellular viral load, and cell-to-cell transmission while increasing the cilial keratan sulfate coating. In conclusion, intense viral and cell shedding caused by SARS-CoV-2 infection was attenuated by IL-13, which affected viral entry, replication, and spread. [ABSTRACT FROM AUTHOR]

Chromium (Cr) has been recognized as a promising diffusion barrier candidate to mitigate the Fuel Cladding Chemical Interaction (FCCI) failure in metallic fuels for sodium-cooled fast reactor. This paper, for the first time, conducted an in-depth post-irradiation examination of the microstructure and composition evolution, and micromechanics of the Cr diffusion barrier in U-10Zr fuel/HT9 cladding irradiated in the Advanced Test Reactor (ATR) to 8.7% burnup at an averaged Peak Inner Cladding Temperature of 540–550 °C. Transmission Electron Microscope (TEM) characterization confirmed the preferential intergranular diffusion of Zr and U in the Cr diffusion barrier, suggesting that grain boundaries served as fast path for the diffusion of Zr and U into the Cr diffusion barrier. The interaction zone is dominated by nano crystalline α- ZrCr 2 Laves phase. Despite the interaction, there is no microcracks being observed in the preserved Cr diffusion barrier and HT9 cladding, serving as a good barrier to mitigate FCCI under the studied in-reactor irradiation conditions. High density cavities in uniform distribution are observed inside Cr grains, nano particles contains Cr, Mn, and O are confirmed by Electron Energy Loss Spectroscopy (EELS) analysis. However, it is unclear whether the cavities will become an issue to the barrier integrity at higher burnup. In-situ Scanning Electron Microscopy (SEM) micro-tensile testing uncovered mechanical softening in the HT9 cladding nearing the Cr diffusion barrier, possibly due to the coarsening of lath structure and carbides precipitates. [ABSTRACT FROM AUTHOR]

We demonstrate catalytic organic synthesis by Resonant Acoustic Mixing (RAM): a mechanochemical methodology that does not require bulk solvent or milling media. Using as model reactions ruthenium‐catalyzed ring‐closing metathesis and copper‐catalyzed sulfonamide‐isocyanate coupling, RAM mechanosynthesis is shown to be faster, operationally simpler than conventional ball‐milling, while also providing the first example of a mechanochemical strategy for ruthenium‐catalyzed ene‐yne metathesis. Reactions by RAM are readily and directly scaled‐up without any significant changes in reaction conditions, as shown by the straightforward 200‐fold scaling‐up of the synthesis of the antidiabetic drug Tolbutamide, from hundreds of milligrams directly to 30 grams. [ABSTRACT FROM AUTHOR]

We demonstrate catalytic organic synthesis by Resonant Acoustic Mixing (RAM): a mechanochemical methodology that does not require bulk solvent or milling media. Using as model reactions ruthenium‐catalyzed ring‐closing metathesis and copper‐catalyzed sulfonamide‐isocyanate coupling, RAM mechanosynthesis is shown to be faster, operationally simpler than conventional ball‐milling, while also providing the first example of a mechanochemical strategy for ruthenium‐catalyzed ene‐yne metathesis. Reactions by RAM are readily and directly scaled‐up without any significant changes in reaction conditions, as shown by the straightforward 200‐fold scaling‐up of the synthesis of the antidiabetic drug Tolbutamide, from hundreds of milligrams directly to 30 grams. [ABSTRACT FROM AUTHOR]

The 1967 attempt of structural analysis of the solid-state complex of caffeine and pyrogallol was a pioneering structural investigation in the supramolecular chemistry of caffeine, of what today would easily be considered an archetype of a model pharmaceutical cocrystal. Re-investigating this historically important system demonstrates that this long overlooked complex is most likely a tetrahydrate with a different structure and composition than initially proposed, and provides the crystal structure of the anhydrous cocrystal. [ABSTRACT FROM AUTHOR]

In the United States, millions of adults use electronic cigarettes (e-cigs), and a majority of these users are former or current cigarette smokers. It is unclear, whether prior smoking status affects biological responses induced by e-cigs. In this study, differentiated human nasal epithelial cells (hNECs) from nonsmokers and smokers at air-liquid interface were acutely exposed to the e-cig generated aerosols of humectants, propylene glycol (PG), and glycerol (GLY). Mucin levels were examined in the apical washes, and cytokine levels were assessed in the basolateral supernatants 24 h postexposure. The aerosol from the GLY exposure increased mucin 5, subtype AC (MUC5AC) levels in the apical wash of hNECs from nonsmokers, but not smokers. However, the aerosol from GLY induced pro-inflammatory responses in hNECs from smokers. We also exposed hNECs from nonsmokers and smokers to e-cig generated aerosol from PG:GLY with freebase nicotine or nicotine salt. The PG:GLY with freebase nicotine exposure increased MUC5AC and mucin 5, subtype B (MUC5B) levels in hNECs from nonsmokers, but the nicotine salt exposure did not. The PG:GLY with nicotine salt exposure increased pro-inflammatory cytokines in hNECs from smokers, which was not seen with the freebase nicotine exposure. Taken together, these data indicate that the e-cig generated aerosols from the humectants, mostly GLY, and the type of nicotine used cause differential effects in airway epithelial cells from nonsmokers and smokers. As e-cig use is increasing, it is important to understand that the biological effects of e-cig use are likely dependent on prior cigarette smoke exposure. [ABSTRACT FROM AUTHOR]

A multiproxy record from a fast‐growing stalagmite reveals variable hydroclimate on the California coast across the 8.2 kyr event and a precursor event likely caused by initial drainage of proglacial Lake Agassiz. Using speleothem δ44Ca, we develop the first semiquantitative estimates of paleorainfall variability for California through calibration with measurements of the modern climate and cave environment. We find that the magnitude of rainfall variability during the 8.2 kyr event approached the multiyear variability observable in the recent past (1950–2019) and the magnitude of variability during the precursor event likely exceeded this range. Additionally, we observe other instances of multidecadal variability comparable in magnitude to the precursor event during the record. Our work suggests that speleothem calcium isotope ratios are a powerful semiquantitative means to reconstruct paleorainfall, although numerous factors must be assessed in each cave system before applying this approach. Plain Language Summary: Modeling of future climate suggests that California may experience increased frequency of both extremely wet and extremely dry periods in the 21st century, leading to the emergence of "climate whiplash" phenomena which would significantly stress the state's water‐sensitive infrastructure. Understanding hydroclimate changes in California's past can help planners prepare for extremes that may be more severe than those of the historical record. However, existing paleoclimate records are often limited to qualitative interpretations of hydroclimate change, restricting their usefulness. We present new calcium isotope measurements from a California stalagmite that grew from 6,900 to 8,600 years ago, revealing variability in rainfall amounts on the California coast during and surrounding the 8.2 kyr event, an abrupt cold snap noted in other global paleoclimate records 8,200 years ago. We generate semiquantitative estimates of annual rainfall rates during the 8.2 kyr event period and compare them with modern annual rainfall amounts, finding that the magnitude of rainfall variability during and surrounding the 8.2 kyr event approaches and in some cases exceeds that of California today. This work indicates that California may have experienced even more intense "climate whiplash" phenomena in the past than during recent decades, suggesting that future planning may need to consider greater wet and dry extremes. Key Points: The first semiquantitative estimates of paleorainfall rates from Ca isotope ratios measured in a California stalagmiteThe magnitude of rainfall variability in coastal California during the 8.2 kyr and precursor event approaches/exceeds that of recent decadesStalagmite Ca isotope ratios facilitate more direct comparison of paleorainfall with modern climate data, but important questions remain [ABSTRACT FROM AUTHOR]

In 2018, landings of Snow Crab (Chionoecetes opilio) for North-Eastern Nova Scotia (N-ENS) and South-Eastern Nova Scotia (S-ENS) were 742 t and 6,064 t, respectively, and were 55 t in 4X for the 2016-2017 season, representing decreases of 9% (N-ENS), 10% (S-ENS), and 31% (4X) relative to the previous year. Total Allowable Catches (TACs) in 2018 were 786 t, 6,057 t, and 110 t in N-ENS, S-ENS, and 4X, respectively. The TAC was not reached in N-ENS or 4X. Non-standardized catch rates in 2018 were 62 kg/trap haul in N-ENS, 116 kg/trap haul in S-ENS, and 12 kg/trap haul in 4X in 2017-2018--which, relative to the previous year, represents a decrease of 31% (N-ENS), an increase of 23% (S-ENS), and a decrease of 52% (4X). The capture of soft-shelled crab in N-ENS increased to 25% from approximately 5% in 2017, almost exclusively during the summer fishery. In S-ENS, the relative occurrence of softshell crab was 1.6% for the 2018 season. Soft-shell discard rates in 4X remain very low, due to the timing of the season. Bycatch of non-target species is extremely low (< 0.4%) in all Crab Fishing Areas (CFAs). In both N-ENS and S-ENS, moderate internal recruitment to the fishery is expected for next year (and likely for 3-4 years) based on size-frequency histograms. In CFA 4X, there appears to be limited potential for both internal (low sub-legal numbers of crab) and external (immigration from neighbouring areas) recruitment to the fishery. Since 2016, there has been a substantial recruitment of female crab into the mature segment of the population in all CFAs. The potential population benefits of the maturation/recruitment of both sexes are tempered by a number of uncertainties, including the influence of predation and temperature changes (especially in CFA 4X and parts of CFA 24). Predation from Atlantic Halibut is a potentially large and increasing source of natural mortality for Snow Crab on the Scotian Shelf. The results from the current spatiotemporal models of variability (stmv) modelling approach produce abundance estimates with very little inter-annual variability, particularly in N- and S-ENS. This hyper-stability is incongruous with the temporal abundance trends observed in geometric mean survey catch densities, length frequencies, catch rates, etc. This disparity from other data suggests caution is warranted when using the modelled biomass and fishery mortality estimates. The modelled post-fishery fishable biomass index of Snow Crab in N-ENS was estimated to be 3,203 t, relative to 3,358 in 2017. In S-ENS, the post-fishery fishable biomass index was 33,190 t, relative to 32,040 t in 2017. In 4X, the pre-fishery fishable biomass was 403 t, relative to 354 t in 2017. The N-ENS fishing mortality (F) estimate for 2018 is 0.24, an increase from 0.17 in 2017. The S-ENS F estimate for 2018 is 0.22, a decrease from 0.26 in 2017. The 4X F estimate for 2017-2018 is 0.23 (exploitation rate 0.21), a decrease from 0.26 in 2016-2017. In N-ENS, the fishery removals for the past two seasons appear to have been an overly aggressive harvest strategy, as catch rates have fallen and the 2018 TAC was not reached. A more conservative harvest approach in N-ENS could stabilize catch rates, protect incoming recruitment, and allow commercial biomass to rebuild. Substantial TAC reductions over the past three seasons have helped maintain stable fishery performance in S-ENS in spite of contracting habitat, reduced recruitment, and increased predation. Geometric mean catches from the survey are stable and, based on stock structure, increased recruitment to the fishery is likely to occur for the upcoming season. A moderately more aggressive harvest strategy can be considered. Habitat in CFA 4X is "marginal" relative to the other CFAs. Low internal recruitment and the large inter-annual temperature variations increases the uncertainty associated with this area. The Snow Crab population has not rebounded from an extreme warm-water even in 2012-2013. A zero TAC was set for the 2018-19 fishing season due to low commercial biomass. Survey catches indicate that 4X commercial biomass levels remain very low but have improved. [ABSTRACT FROM AUTHOR]

Evidence-based research supports the incorporation of creative techniques in counselor supervision. There are numerous methods of implementing creative techniques within the supervisory process; sandtray is one such tool. This qualitative article discusses the power of creative approaches for supervision, explains how creative techniques assist supervisors in providing meaningful supervision, and reviews current literature supporting these arguments. This study involved the supervision of master's-level counseling students by doctoral-level counseling supervisors. Supervisors used sandtray during initial, mid-term, and final supervisory sessions. Data included student journal entries, supervisor case notes, photos of sandtrays, and video recordings of sessions. Results of the study are discussed along with clinical implications and recommendations for future research. [ABSTRACT FROM AUTHOR]

Research has shown that using acoustic radiation modes combined with surface velocity measurements provide an accurate method of measuring the radiated sound power from vibrating plates. This paper investigates the extension of this method to acoustically radiating cylindrical structures. The mathematical formulations of the radiation resistance matrix and the accompanying acoustic radiation modes of a baffled cylinder are developed. Computational sound power calculations using the vibration-based radiation mode (VBRM) method and the boundary element method are then compared and shown to have good agreement. Experimental surface velocity measurements of a cylinder are taken using a scanning laser Doppler vibrometer and the VBRM method is used to calculate sound power. The results are compared to sound power measurements taken using ISO 3741. [ABSTRACT FROM AUTHOR]

We provide an overview of chemical transformations that proceed spontaneously, by mixing of initially solid reactants, and are accelerated and/or directed through gentle stimuli in the form of mild heating, exposure to diverse gas or vapour environments, brief mechanical milling, and/or the presence of catalysts. This broad overview illustrates how such accelerated ageing (AA) reactions could provide a route to develop operationally simple, as well as safe, inexpensive and materials- and energy-efficient processes for the environmentally-friendly synthesis of diverse organic and metal–organic materials and molecules. [ABSTRACT FROM AUTHOR]

Tropical montane cloud forests support abundant epiphytic vascular plant communities that serve important ecosystem functions, but their reliance on atmospheric inputs of water may make them susceptible to the drying effects of rising cloud bases and more frequent droughts.We conducted a common garden experiment to explore the combined effects of decreasing cloud influence—lower humidity, warmer temperature, brighter light—and meteorological drought (i.e. absence of rain) on the physiology and morphology of vascular epiphytes native to primary forests of Monteverde, Costa Rica. The epiphytes, which exhibited C3 photosynthesis, were sourced from a lower montane cloud forest (CF) or a rainforest (RF) below the current cloud base and transplanted into nearby shadehouses (CF or RF shadehouse respectively). Vapour pressure deficit (VPD) and light availability, measured as photosynthetically active radiation, were 2.5 and 3.1 times higher in the RF than the CF shadehouse. Half of the plants were subjected to a severe 4‐week drought followed by a recovery period, and the other half were watered controls.Plants subjected to low VPD/light conditions of the CF shadehouse were physiologically and morphologically resistant to the drought treatment. However, compared to control plants, both sources of plants subjected to high VPD/light conditions of the RF shadehouse experienced declines in maximum net photosynthesis (Amax), stomatal conductance (gs) and the proportion of healthy leaves (those not exhibiting chlorosis, desiccation or necrosis). At peak drought, leaves from the RF were 19% thinner than controls. Within 7–14 days after rewatering, Amax, gs and leaf health recovered to nearly the levels of controls. Growth rate, mortality and phenology were unaffected by the treatments.The divergent responses to drought in the CF versus RF shadehouses, combined with the recovery in the RF shadehouse, indicate that these epiphytes possess adaptive properties that confer low resistance, but high recovery capacity, to episodes of short‐term drought over a range of cloud influence. In addition, the reduction in Amax suggests stomatal regulation that favours water conservation over carbon acquisition, a strategy that may inform epiphyte responses to rising clouds and increasing drought frequency expected in the long term. A free Plain Language Summary can be found within the Supporting Information of this article. [ABSTRACT FROM AUTHOR]

Moral injury (MI) may occur in the context of committing transgressions (i.e., self-directed MI reactions), witnessing transgressions, or being the victims of others' transgressions (i.e., other-directed MI reactions) that violate an individual's moral principles. Veterans with MI may experience impaired social well-being (SWB). Studies on MI and veterans' SWB have focused almost exclusively on social support and used cross-sectional data. The present study used growth curve analyses to examine the associations between self- and other-directed MI reactions and veterans' levels of social support, social functioning, social activities, and social satisfaction over the first 18 to 21 months of their transition to civilian life (N = 9,566). The results demonstrated declines in all SWB outcomes, with self- and other-directed MI reactions having differential effects. Higher versus lower levels of other-directed MI reactions were related to lower baseline scores on all SWB outcomes, βs = -.06 to -.20, and steeper declines over time in social functioning, β = -.09, and social satisfaction, β = -.10. Higher versus lower levels of self-directed MI reactions were related to lower baseline levels of social functioning, β = -.07, but higher baseline levels of social activity, β = .04. Higher versus lower levels of self-directed MI reactions were related to a steeper decline in social activity over time, β = -.10. These findings present a more nuanced picture than that depicted by current MI theoretical frameworks and support further research to uncover moderators of the associations between self- and other-directed MI reactions and SWB outcomes. [ABSTRACT FROM AUTHOR]

Radio galaxies are uncommon γ-ray emitters, and only low-redshift radio galaxies are detected with the Fermi Large Area Telescope (Fermi -LAT). However, they offer potential insights into the emission mechanisms of active galaxies, particularly as the alignment of their jets with respect to the Earth means that, unlike blazars, their emission is not necessarily jet dominated. We use the Fermi -LAT data to perform an unbiased survey of 78 radio galaxies from the Bologna complete sample in order to search for new γ-ray-emitting radio galaxies. We observe statistically significant γ-ray emission from four of the six known Fermi -LAT-detected radio galaxies included in this sample, and find some evidence for γ-ray emission spatially coincident with four previously undetected radio galaxies. As a large parameter space is searched, we calculate a probability distribution to compute the look-elsewhere effect. We find that these four spatially coincident sub-threshold γ-ray excesses are most likely a chance association, and are unlikely to be emission from the radio galaxies. Upper limits on flux are calculated for the radio galaxies from which no γ-ray emission is observed. [ABSTRACT FROM AUTHOR]

This mini-review starts with a summary of the crucial contributions Ricardo Miledi made to our understanding of how the action potential triggers fast, synchronous transmitter release. It then transitions to the discovery of synaptotagmin and its role as the exocytotic Ca2+ sensor at nerve terminals. The final section confronts the array of unique models that have been proposed to explain the membrane fusion step of exocytosis. More than a dozen different hypotheses seek to explain the terminal steps of the exocytotic cascade. It will be an interesting challenge for the field to distinguish among these possibilities. Nevertheless, with ongoing technological advances, perhaps we will have a better picture of this process by the end of the coming decade. This article is part of a Special Issue entitled: Honoring Ricardo Miledi - outstanding neuroscientist of XX-XXI centuries. • This commentary focuses on the molecular machinery underlying fast, synchronous transmitter release at nerve terminals. • It begins with the contributions Ricardo Miledi and his colleagues made to understanding Ca ion entry at nerve endings. • The remainder of the discussion concerns the molecular cascade of events downstream of Ca2+ entry. • In particular, this paper reviews the roles proposed for SNARE proteins and synaptotagmin in the release process. [ABSTRACT FROM AUTHOR]

Monetary incentives are frequently used to improve survey response rates. While it is common to use a single incentive amount for an entire sample, allowing the incentive to vary inversely with the expected probability of response may help to mitigate nonresponse and/or nonresponse bias. Using data from the 2016 National Household Education Survey (NHES:2016), an address-based sample (ABS) of US households, this article evaluates an experiment in which the noncontingent incentive amount was determined by a household's predicted response propensity (RP). Households with the lowest RP received $10, those with the highest received $2 or $0, and those in between received the standard NHES incentive of $5. Relative to a uniform $5 protocol, this "tailored" incentive protocol slightly reduced the response rate and had no impact on observable nonresponse bias. These results serve as an important caution to researchers considering the targeting of incentives or other interventions based on predicted RP. While preferable in theory to "one-size-fits-all" approaches, such differential designs may not improve recruitment outcomes without a dramatic increase in the resources devoted to low RP cases. If budget and/or ethical concerns limit the resources that can be devoted to such cases, RP-based targeting could have little practical benefit. [ABSTRACT FROM AUTHOR]

Motivated by the detection of a hardening in the γ-ray spectrum of the radio galaxy Centaurus A, we have analysed |$\mathord {\sim }10$|  yr of Fermi -Large Area Telescope (LAT) observations of 26 radio galaxies to search for similar spectral features. We find that the majority of the radio galaxies' γ-ray spectral energy distributions are best fitted with a simple power-law model, and no spectral hardening similar to that found in Centaurus A was detected. We show that, had there been any such spectral features present in our sample of radio galaxies, they would have been seen, but note that seven of the radio galaxies (3C 111, 3C 120, 3C 264, IC 4516, NGC 1218, NGC 2892, and PKS 0625−35) show evidence for flux variability on 6-month time-scales, which makes the detection of any steady spectral features difficult. We find a strong positive correlation (r = 0.9) between the core radio power at 5 GHz and the γ-ray luminosity and, using a simple extrapolation to TeV energies, we expect around half of the radio galaxies studied will be detectable with the forthcoming Cherenkov Telescope Array. [ABSTRACT FROM AUTHOR]

This essay focuses on the history of psychometry, the science of soul measuring. For its founder, Dr Joseph Rodes Buchanan, the soul was simultaneously an object for anthropological research and a measuring instrument capable of revealing human character, interpreting natural history, and demonstrating the reality of an immortal soul. Psychometry taught that human souls, especially those of women, were capable of acting as instruments because they could feel the mysterious energies that people and objects radiated. Although orthodox male scientists rejected the visions of sensitive women as the antithesis of reliable data, psychometric researchers believed that the feelings of women were both the instruments and information that made their science possible. Psychometry promised to revolutionize science by insisting that sympathy and subjectivity, not detachment and objectivity, ought to undergird research. Yet as male experimenters worked to prove psychometry's effectiveness, they almost invariably cast themselves as detached observers accurately recording the data provided by their female instruments. Thus, despite pushing for scientific reform, the methods and discourse of male psychometric experimenters eroded their field's core arguments about connectedness and subjectivity and, instead, reinforced the notion that detachment and objectivity were essential to legitimate science. Challenges to objectivity could prove just how thoroughly it dominated scientific discourse and practice. Still, some psychometers, particularly women who practiced at home, were untroubled by the fact that their research was predicated on subjective feelings, and psychometry remained a viable pursuit among spiritualists even as it faded from the realm of science. Psychometry emerged and, ultimately, fractured amid tensions between widespread enthusiasm for sciences that emphasized spiritual connectedness and the mounting pressure to legitimize scientific knowledge through the language and practices of objectivity. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) severity, reflecting both disease intensity and duration, is heterogeneous making it challenging to study in administrative databases where severity may confound or mediate associations with outcomes. Garris et al. developed an administrative claims-based algorithm employing claims over a 1-year period to classify SLE severity as mild, moderate or severe. We sought to compare this administrative algorithm to a measure of SLE activity, the SLE Disease Activity Index-2000 (SLEDAI-2K) score at clinical visits. We identified 100 SLE patients followed in the Brigham and Women's Hospital (BWH) Lupus Center (in 2008–2010) with SLEDAI-2K scores at each visit over a 1-year period per person. We obtained data for the Garris algorithm for the same year per subject. We compared Garris SLE severity to the highest SLEDAI-2K in that year, with SLEDAI-2K categories of mild < 3, moderate 3–6, and severe > 6. We compared classification using weighted kappa statistics, and positive and negative predictive values (PPV, NPV). We also assessed the binary comparison of mild vs. moderate/severe. We calculated sensitivity, specificity, and McNemar's test. We analyzed 377 SLEDAI-2K assessments (mean 3.8 [SD 2.6] per subject/year). For classifying moderate/severe vs. mild SLE severity, the sensitivity was 85.7%, specificity 67.6%, PPV 81.8% and NPV 73.5%. The Garris algorithm for classifying SLE severity in administrative datasets had moderate agreement for classification of mild vs. moderate/severe SLE activity assessed by SLEDAI-2K assessments in an academic lupus center. It may be a useful tool for classifying SLE severity in administrative database studies. [ABSTRACT FROM AUTHOR]

Introduction: Interest in moral injury has burgeoned over the last decade as an increasing number of professionals recognize that current conceptualizations of trauma are not sufficient to explain some of the challenges that military service members face. The Moral Injury Events Scale (MIES) was the first instrument developed to measure exposure to military events that could produce moral injury (Nash et al., 2013). Two previously published validation studies that focused on service members still in uniform reveal some discrepancies regarding the scale's factor structure. Bryan and colleagues (2016) documented a three-factor solution (i.e., transgressions-others, transgressions-self, and betrayal), while Nash and colleagues (2013) noted a two-factor solution (i.e., perceived transgressions and perceived betrayals).Materials and Methods: With an interest in further scale validation, the present study utilized survey data from a group of veterans recently separated from service, to test the fitness of the two- or three-factor model and to examine the invariance of the scale across gender and branch. The investigators followed the policies governing the protection of human subjects as prescribed by ICF Institutional Review Board.Results: Findings revealed a two-factor structure that differed from previous factor solutions (transgressions-self and transgressions-others) and was invariant across gender and branch. High intercorrelations among the MIES items that addressed exposure and reaction to events suggested that these experiences tend to co-occur. Removal of the event items did not significantly impact model fit.Conclusions: The factor structure identified in the present study aligns with current theoretical conceptualizations of moral injury. The inability to distinguish between event and reaction items and the lack of impact on the factor structure when event items were removed from the model suggest the MIES is more accurately described as a measure of moral pain as compared to a measure of potentially morally injurious experiences (PMIEs). Given that all events associated with moral injury have impinged upon welfare, justice, rights, and fairness considerations, one could argue that little would be gained by focusing attention on the development of a measure of PMIEs. Given the lack of convergence in factor structure across samples, future directions may profit from a focus on further clarifying the temporal stability of the MIES factor structure. [ABSTRACT FROM AUTHOR]

Tympanostomy tube (TT) placement is a common surgical procedure for treating pediatric patients with chronic otitis media with effusion (COME) with or without recurrent acute otitis media (rAOM). Prior work suggests children from low-income families face significant disparities in access to care for rAOM or COME. The impact of these health disparities in the care of children with rAOM or COME has yet to be investigated in a state with an expanded public health insurance model. We seek to examine differences in care for patients with rAOM and COME based on insurance status and socioeconomic status (SES) in Massachusetts. Retrospective review of 560 pediatric patients referred for TT insertion at a tertiary academic medical center between 2017 and 2019. Demographic data collected included age, ethnicity, insurance type (public, private, none) and zip code. Otologic history collected included prior AOM episodes, time to postoperative follow-up, postoperative "no-show" appointments, and number of postoperative audiograms. Multinomial logistic regression was used to isolate the effects of race and ethnicity. We found no major differences in preoperative outcome measures between cohorts. Postoperatively, public insurance was independently associated with decreased odds of undergoing an audiogram (OR 0.35, 95% Cl 0.16–0.76) and increased odds of "no-showing" for an appointment (OR 3.1, 95% CI 1.8–5.3). SES was not independently associated with differences in postoperative outcomes. In a state with an early expanded public health insurance model, access to care for rAOM and COME is comparable despite differences in insurance type and SES. However, enrollment in public health insurance is associated with worse measures of follow up care. Despite improvements in access to care with expanded health insurance models, retention continues to be a challenge for vulnerable populations. • MassHealth patients are more likely to "no show" after TT placement. • Access to care for AOM/COME is similar for MassHealth patients vs privately insured. • Vulnerable populations may greatly benefit from methods to improve retention. [ABSTRACT FROM AUTHOR]

Supplemental digital content is available in the text. Background: Multiple cell signaling pathways are implicated in the development, progression, and persistence of cisplatin-induced peripheral neuropathy. Although advances have been made in terms of understanding specific neurotoxic mechanisms, there are few predictive factors identified that can help inform the clinician approach to symptom prevention or management. Objective: We investigate the differential sensitivity to cisplatin-induced peripheral neuropathy and examine the contribution of dorsal root ganglion (DRG) transcriptional profiles across two inbred strains of mice. Methods: Cisplatin (4 mg/kg intraperitoneal or vehicle control) was administered twice a week for 4 weeks to adult female C57BL/6J and A/J mice—the C57BL/6J strain of mice characterized by a robust mechanical allodynia and the A/J with a mild largely resistant allodynia phenotype. Peripheral nerve conduction velocities (NCVs), electrophysiological evaluation of wide dynamic range (WDR) neurons, morphological examination of DRG neurons, and microarray analysis of spinal cord tissues were compared across the 4 weeks. Results: The A/J strain presents with an early, mild nocifensive response to cisplatin with reduced neuronal activity in WDR neurons and small changes in cross-sectional nucleus size in DRG neurons at 4 weeks. The more nocifensive-sensitive C57BL/6J strain presents with no early changes in WDR neuron responsiveness; however, there were significant changes in DRG size. Both strains demonstrate a drop in NCV after 4 weeks of treatment, with the greatest reduction present in the A/J strain. Transcriptome data implicate neuroimmune modulation in the differential response to cisplatin in the DRGs of A/J and C57BL/6J mice. Discussion: Nocifensive responses in both strains implicate involvement of small myelinated and unmyelinated fibers in neurotoxic cisplatin response, whereas reductions in NCV reflect involvement of the largest myelinated fibers in the peripheral nerves. Microarray data analysis identifies neuropathy-relevant gene sets with differential activation of pathways, suggesting a role for antigen presentation in the differential neurotoxic response to cisplatin across strains. Further research is indicated to determine the relative contributions of each of these potential pathological mechanisms to both the neurotoxic response to cisplatin and to the potential for targeted therapy. [ABSTRACT FROM AUTHOR]

Subsurface drip irrigation (SDI) is a micro-irrigation system that could be adopted by producers in the semi-arid regions around the world for efficient use of water. Yet, several crop management issues related to SDI system need to be addressed to assess the feasibility of SDI. One such issue is the impact of crop row placement on crop performance, irrigation water use efficiency and yield under SDI. A study was conducted in the Southern U.S. Great Plains, in which drip tape laterals were buried 30 cm deep at 153 cm spacing, with two crop rows planted at 76 cm spacing, and irrigated with one tape. Corn ( Zea mays L.) and grain sorghum ( Sorghum bicolor L.) rows were offset from equidistance from the drip tape by 0, 8, 15, 23, and 38 cm using high precision guidance system (real time kinematics). This resulted in 5 treatments and 4 replications. This treatment structure was imposed on three irrigation (high, medium and low) regimes. Analysis of Variance showed no interaction between offset treatments and irrigation or year in corn and grain sorghum yields. The row offset did not impact the overall yield as the yield loss in row farther from the tape was compensated by the increased yield in row moved closer to the tape. The yield distribution ranged from 50% in both rows for 0 cm offset to 59% in row closer to the tape for 38 cm offset. The findings of this study suggests that while driver accuracy is important to maintain equal yields in neighboring crop rows, the overall yields are affected more by irrigation and climatic conditions and not by the row offsets with respect to SDI tape. This data suggests that SDI can be successful regardless of access to high precision guidance systems. [ABSTRACT FROM AUTHOR]

Intellectual historians and historians of science have typically portrayed the pursuit of natural knowledge between the Revolution and the Civil War as something that took place in an essentially peaceful context. But warfare was constant in the early United States, and it was neither tangential to, nor even clearly divisible from, how any group produced and circulated knowledge about the natural world. This essay argues that warfare enabled, circumscribed, and conditioned the pursuit of natural knowledge among the diverse peoples who populated the United States. More importantly, warfare provides a lens for reframing the history of natural knowledge in America in a way that is both more comprehensive and less skewed by the legacy of American exceptionalism. This history spans the colonial and national eras, encompasses diverse individuals in diverse places, decenters the eastern Anglos who have too often characterized natural knowledge in the United States on the whole, and situates natural knowledge in the United States as part of a global story. In short, focusing on warfare helps make Anglo-Americans part of a shared intellectual history, not its exclusive protagonists. [ABSTRACT FROM AUTHOR]

Concrete-filled Rectangular Hollow Sections have been tested under large-scale, far-field, air-blast loading for the first time. The concrete-filled, cold-formed steel tubes performed well under the blast loads, with a significant reduction in the global and local displacements compared to unfilled RHS members. The heavily instrumented tests provided a large quantity of response data that was used for the validation of numerical models. Numerical models of the concrete-filled steel tubes were first developed using explicit finite element methodologies. A parametric study was conducted with the validated finite element model to further characterize the response of the concrete-filled steel tubes under air-blast loading. The influence of several key variables on the response of the tubular members was determined and preliminary design guidance is provided. Finally, the test and finite element results were used to develop an idealized single-degree-of-freedom numerical model that is well-suited to future use in design problems. [ABSTRACT FROM AUTHOR]

The independence polynomial i ( G , x ) of a graph G is the generating function of the numbers of independent sets of each size. A graph of order n is very well-covered if every maximal independent set has size n ∕ 2 . Levit and Mandrescu conjectured that the independence polynomial of every very well-covered graph is unimodal (that is, the sequence of coefficients is nondecreasing, then nonincreasing). In this article we show that every graph is embeddable as an induced subgraph of a very well-covered graph whose independence polynomial is unimodal, by considering the location of the roots of such polynomials. [ABSTRACT FROM AUTHOR]

In tall trees, the mechanisms by which foliage maintains sufficient turgor pressure and water content against height-related constraints remain poorly understood. Pressure-volume curves generated from leafy shoots collected crown-wide from 12 large Sequoiadendron giganteum (Lindley) J. Buchholz (giant sequoia) trees provided mechanistic insights into how the components of water potential vary with height in tree and over time. The turgor loss point (TLP) decreased with height at a rate indistinguishable from the gravitational potential gradient and was controlled by changes in tissue osmotica. For all measured shoots, total relative water content at the TLP remained above 75%. This high value has been suggested to help leaves avoid precipitous declines in leaf-level physiological function, and in giant sequoia was controlled by both tissue elasticity and the balance of water between apoplasm and symplasm. Hydraulic capacitance decreased only slightly with height, but importantly this parameter was nearly double in value to that reported for other tree species. Total water storage capacity also decreased with height, but this trend essentially disappeared when considering only water available within the typical range of water potentials experienced by giant sequoia. From summer to fall measurement periods we did not observe osmotic adjustment that would depress the TLP. Instead we observed a proportional shift of water into less mobile apoplastic compartments leading to a reduction in hydraulic capacitance. This collection of foliar traits allows giant sequoia to routinely, but safely, operate close to its TLP, and suggests that gravity plays a major role in the water relations of Earth's largest tree species. [ABSTRACT FROM AUTHOR]

Airway mucociliary clearance (MCC) is required for host defense and is often diminished in chronic lung diseases. Effective clearance depends upon coordinated actions of the airway epithelium and a mobile mucus layer. Dysregulation of the primary secreted airway mucin proteins, MUC5B and MUC5AC, is associated with a reduction in the rate of MCC; however, how other secreted proteins impact the integrity of the mucus layer and MCC remains unclear. We previously identified the gene Bpifb1/Lplunc1 as a regulator of airway MUC5B protein levels using genetic approaches. Here, we show that BPIFB1 is required for effective MCC in vivo using Bpifb1 knockout (KO) mice. Reduced MCC in Bpifb1 KO mice occurred in the absence of defects in epithelial ion transport or reduced ciliary beat frequency. Loss of BPIFB1 in vivo and in vitro altered biophysical and biochemical properties of mucus that have been previously linked to impaired MCC. Finally, we detected colocalization of BPIFB1 and MUC5B in secretory granules in mice and the protein mesh of secreted mucus in human airway epithelia cultures. Collectively, our findings demonstrate that BPIFB1 is an important component of the mucociliary apparatus in mice and a key component of the mucus protein network. NEW & NOTEWORTHY BPIFB1, also known as LPLUNC1, was found to regulate mucociliary clearance (MCC), a key aspect of host defense in the airway. Loss of this protein was also associated with altered biophysical and biochemical properties of mucus that have been previously linked to impaired MCC. [ABSTRACT FROM AUTHOR]

Parallel zippering of the SNARE domains of syntaxin 1A/B, SNAP-25, and VAMP/synaptobrevin 2 is widely regarded as supplying the driving force for exocytotic events at nerve terminals and elsewhere. However, in spite of intensive research, no consensus has been reached concerning the molecular mechanism by which these SNARE proteins catalyze membrane fusion. As an alternative to SNARE-based models, a scenario was developed in which synaptotagmin 1 (or, 2) can serve as a template to guide lipid movements that underlie fast, synchronous exocytosis at nerve terminals. This "dyad model" advanced a novel proposal concerning the membrane disposition of the palmitoylated, cysteine-rich region of these synaptotagmins. Unexpectedly, it now emerges that a similar principle can be exploited to reveal how the hydrophobic, carboxyl-terminal domains of syntaxin 1A and synaptobrevin 2 can perturb membrane structure at the interface between a docked synaptic vesicle and the plasma membrane. These "β-to-α transition" models will be compared and contrasted with other proposals for how macromolecules are thought to intervene to drive membrane fusion. [ABSTRACT FROM AUTHOR]

We have previously shown that the transcription factor HNF4A is required for the formation of hepatic progenitor cells from endoderm that has been derived from human induced pluripotent stem cells (iPSCs). We reasoned that we could uncover regulatory pathways with new roles in hepatocyte differentiation by identifying cellular processes that regulate HNF4A. We therefore performed a screen of 1120 small molecules with well-characterized mechanisms of action to detect those that affect the abundance of HNF4A in iPSC-derived hepatic progenitor cells. This approach uncovered several small molecules that depleted HNF4A. Of those, we chose to focus on an inhibitor of heat shock protein 90 beta (HSP90β). We show that mutation of the gene encoding HSP90β represses hepatocyte differentiation during the formation of hepatocytes from iPSCs. We reveal that HSP90β, although dispensable for expression of HNF4A mRNA, directly interacts with HNF4A protein to regulate its half-life. Our results demonstrate that HSP90β has an unappreciated role in controlling hepatic progenitor cell formation and highlight the efficiency of using small-molecule screens during the differentiation of iPSCs to reveal new molecular mechanisms that control hepatocyte formation. [ABSTRACT FROM AUTHOR]

ABSTRACT Despite extensive investigations of the neocortex in the domestic cat, little is known about neuronal morphology in larger felids. To this end, the present study characterized and quantified the somatodendritic morphology of neocortical neurons in prefrontal, motor, and visual cortices of the Siberian tiger ( Panthera tigris altaica) and clouded leopard ( Neofelis nebulosa). After neurons were stained with a modified Golgi technique ( N = 194), dendritic branching and spine distributions were analyzed using computer-assisted morphometry. Qualitatively, aspiny and spiny neurons in both species appeared morphologically similar to those observed in the domestic cat. Although the morphology of spiny neurons was diverse, with the presence of extraverted, inverted, horizontal, and multiapical pyramidal neurons, the most common variant was the typical pyramidal neuron. Gigantopyramidal neurons in the motor cortex were extremely large, confirming the observation of Brodmann ([1909] Vergleichende Lokalisationlehre der Grosshirnrinde in ihren Prinzipien dargestellt auf Grund des Zellenbaues. Leipzig, Germany: J.A. Barth), who found large somata for these neurons in carnivores in general, and felids in particular. Quantitatively, a MARSplines analysis of dendritic measures differentiated typical pyramidal neurons between the Siberian tiger and the clouded leopard with 93% accuracy. In general, the dendrites of typical pyramidal neurons were more complex in the tiger than in the leopards. Moreover, dendritic measures in tiger pyramidal neurons were disproportionally large relative to body/brain size insofar as they were nearly as extensive as those observed in much larger mammals (e.g., African elephant). Comparison of neuronal morphology in a more diverse collection of larger felids may elucidate the comparative context for the relatively large size of the pyramidal neurons observed in the present study. J. Comp. Neurol. 524:3641-3665, 2016. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background: A detailed description of the natural history of acute Q fever, caused by infection with Coxiella burnetii. Aim: To significantly increase understanding of the illness. Design: Subjects with provisional acute Q fever (n=115) were recruited from primary care in rural Australia, and followed prospectively by interview and blood collection including for serological confirmation. A nested series of subjects with prolonged illness (cases), and those without (controls), were investigated in detail. Methods: Total phase I and phase II anti-C. burnetii antibodies were detected by complement fixation test; and IgG, IgM and IgA phase I and phase II titres by immunofluorescence. Flow cytometric analysis was conducted to enumerate circulating T cells subsets, B cells, monocytes and natural killer cells. Results: Serological testing confirmed acute Q fever in 73 subjects (63%). The acute illness featured fever, headache, sweats, fatigue and anorexia; and varied widely in severity, causing an average of 8 days in bed and 15 days out of work or other role in the first month of illness. The illness course varied from 2 days to greater than a year. No cases of chronic, localized Q fever infection, such as endocarditis, were identified. Neither severe nor prolonged illness were associated with persistence of C. burnetii DNA, altered patterns of C. burnetii-specific IgG, IgM or IgA antibody production, or altered leucocyte subsets. Conclusions: The severity of acute Q fever alone predicted prolonged duration. Further studies are warranted to better understand the pathophysiology of prolonged illness after acute Q fever. [ABSTRACT FROM AUTHOR]

Injecting drug use remains the major risk factor for hepatitis C ( HCV) transmission. A minority of long-term injecting drug users remain seronegative and aviraemic, despite prolonged exposure to HCV - termed highly exposed seronegative subjects. Natural killer (NK) cells have been implicated in this apparent protection. A longitudinal nested, three group case-control series of subjects was selected from a prospective cohort of seronegative injecting drug users who became incident cases ( n = 11), remained seronegative ( n = 11) or reported transient high-risk behaviour and remained uninfected ( n = 11). The groups were matched by age, sex and initial risk behaviour characteristics. Stored peripheral blood mononuclear cells were assayed in multicolour flow cytometry to enumerate natural killer cell subpopulations and to assess functional activity using Toll-like receptor ligands before measurement of activation, cytokine production and natural cytotoxicity receptor expression. Principal components were derived to describe the detailed phenotypic characteristics of the major NK subpopulations (based on CD56 and CD16 co-expression), before logistic regression analysis to identify associations with exposed, seronegative individuals. The CD56dim CD16+ ( P = 0.05, OR 6.92) and CD56dim CD16− ( P = 0.05, OR 6.07) principal components differed between exposed, seronegative individuals and pre-infection samples of the other two groups. These included CD56dim CD16+ and CD56dim CD16− subsets with CD56dim CD16+ IFN- γ and TNF- α on unstimulated cells, and CD56dim CD16− CD69+, CD107a+, IFN- γ and TNF- α following TLR stimulation. The cytotoxic CD56dim NK subset thus distinguished highly exposed, seronegative subjects, suggesting NK cytotoxicity may contribute to protection from HCV acquisition. Further investigation of the determinants of this association and prospective assessment of protection against HCV infection are warranted. [ABSTRACT FROM AUTHOR]

Particulate matter was measured in Conroe, Texas (~60 km north of downtown Houston, Texas) during the September 2013 DISCOVER-AQ campaign to determine the sources of particulate matter in the region. The measurement site is influenced by high biogenic emission rates as well as transport of anthropogenic pollutants from the Houston metropolitan area and is therefore an ideal location to study anthropogenic-biogenic interactions. Data from an Aerosol Chemical Speciation Monitor (ACSM) suggest that on average 64 percent of non-refractory PM1 was organic material, including a high fraction (27%-41%) of organic nitrates. There was little diurnal variation in the concentrations of ammonium sulfate; however, concentrations of organic and organic nitrate aerosol were consistently higher at night than during the day. Potential explanations for the higher organic aerosol loadings at night include changing boundary layer height, increased partitioning to the particle phase at lower temperatures, and differences between daytime and nighttime chemical processes such as nitrate radical chemistry. Positive matrix factorization was applied to the organic aerosol mass spectra measured by the ACSM and three factors were resolved--two factors representing oxygenated organic aerosol and one factor representing hydrocarbon-like organic aerosol. The factors suggest that the measured aerosol was well mixed and highly processed, consistent with the distance from the site to major aerosol sources, as well as the high photochemical activity. [ABSTRACT FROM AUTHOR]