bluuebunny/crossref_metadata_2025 huggingface dataset:
4196 MICROBIAL COMPOSITION DEFINES PELVIC PAIN PHENOTYPES IN REPRODUCTIVE-AGE WOMEN
Authors: Ackerman A. Lenore , Khalique Muhammed Umair , Ackerman James E. , Cheng Zhi , Eilber Karyn S. , Anger Jennifer T. , Underhill David M.
Published: July 2020

OBJECTIVES/GOALS: In young women, there is significant symptomatic overlap among lower urinary tract conditions, including bladder and pelvic pain, leading to misdiagnosis and delayed care. The epidemiology of pelvic pain suggests a microbial involvement, but previous studies have not definitively identified specific bacteria associated with pain diagnoses. METHODS/STUDY POPULATION: We examined urinary bacterial associations with specific symptom clusters, not diagnoses. Catheterized urinary samples were obtained from 78 pre-menopausal controls and cases with bladder and pelvic pain. 16S next-generation sequencing (NGS) characterized urinary microbial populations; validated questionnaires quantified symptom type and severity. K means unsupervised clustering analysis of NGS data assigned subjects to urotypes based on the urinary bacterial community state types. Quantitative PCR (qPCR) confirmed the NGS results and provided objective concentrations for critical taxa. Linear regression analysis confirmed the associations of bacterial concentrations and specific symptoms. RESULTS/ANTICIPATED RESULTS: In a pilot study of 35 reproductive-age women with a variety of complaints NGS revealed four urotypes that correlated with symptomatology. Isolated urgency incontinence was rare; the majority of subjects with symptoms complained of genitourinary pain. Bladder-specific pain (worse with filling, relieved by voiding) was associated with Lactobacillus iners. Asymptomatic patients almost universally had a non-iners, Lactobacillus-predominant microbiota. Vaginal and urethral pain unrelated to voiding correlated with increasing Enterobacteriaceae, primarily Escherichia coli. Detection of these species by qPCR in a validation population (n = 43) was highly predictive of each phenotype (P < 0.00001). Pathologic bacteria were associated with the severity of specific pain symptoms. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results implicate a microbial role in genitourinary pain. We describe clinically-useful bacterial biomarkers for specific pelvic and bladder pain phenotypes. This objective, rapid, and inexpensive testing to classify bladder and pelvic pain would allow more accurate diagnosis and improve treatment. CONFLICT OF INTEREST DESCRIPTION: Dr. Anger is an expert witness for Boston Scientific. Dr. Eilber is an investigator and expert witness for Boston Scientific, an investigator for Aquinox, and a consultant for Boston Scientific and Allergan. Dr. Ackerman is an expert witness for Cynosure.
4582 NICOTINAMIDE ADENINE DINUCLEOTIDE (NAD) DEPLETION MUST BE SEVERE TO INDUCE CARDIAC DYSFUNCTION AND EVENTUAL FAILURE
Authors: Luongo Timothy , Wang Lin , Chellappa Karthikeyani , McReynolds Melanie R. , Kelly Daniel P. , Rabinowitz Joshua D. , Baur Joseph A.
Published: July 2020

OBJECTIVES/GOALS: Nicotinamide adenine dinucleotide (NAD) plays essential roles in energy metabolism and cell signaling pathways. NAD functions as a coenzyme by accepting electrons during glycolysis and the TCA cycle and subsequently donates them to complex I of the electron transport chain providing the driving force for ATP production. NAD also acts as a co-substrate for several classes of enzymes, including sirtuin deacetylases. Both NAD and the enzyme that is rate limiting for synthesis, Nicotinamide phosphoribosyltransferase (Nampt), are depleted in the failing heart, concurrent with hyperacetylation and mitochondrial dysfunction. Moreover, treatment with NAD precursors reduced cardiac injury in several heart failure models. However, NAD precursors may have systemic effects, and it remains unproven whether depletion of myocardial NAD is causative or merely correlative for the onset and progression of heart failure. METHODS/STUDY POPULATION: To test this, we generated a cardiac-specific tamoxifen-inducible (αMHC-MerCreMer) model for deletion of Nampt (Nampt cKO) in cardiomyocytes. Adult mice were administered tamoxifen for 5 days leading to deletion of Nampt, resulting in a 72% reduction in myocardial NAD after two-weeks. RESULTS/ANTICIPATED RESULTS: Echocardiography revealed that Nampt cKO mice displayed a significant reduction in left ventricular (LV) contractility as well as cardiac hypertrophy. Despite the further loss of NAD, the majority of animals survived to 8 weeks of age before experiencing sudden deaths resulting in significant mortality over the next several weeks. Remarkably, we observed only a slight increase in acetylation of mitochondrial proteins, and cardiac mitochondria isolated from Nampt-null mice even at 8 weeks displayed a normal or higher oxygen consumption rate. We found that mitochondrial NAD levels were preferentially maintained and depleted at a slower rate compared to those in bulk tissue. DISCUSSION/SIGNIFICANCE OF IMPACT: While mild depletion of cardiac NAD has been reported in heart failure, our data indicate that the heart can adapt to much more severe loss of NAD prior to the loss of viability.
4081 Quantifying pH buffering capacity and kinetics of tumor and healthy tissue to understand and exploit differences in biology
Authors: Crouch A. Colleen , Thompson Emily A. , Pagel Mark D. , Cressman Erik N.K.
Published: July 2020

OBJECTIVES/GOALS: The purpose of this work is to investigate natural buffering capacity of liver tissue and tumors, to understand and exploit differences for therapy. Using this work, we will determine the concentrations of reagents (acids or bases) used in ablation treatment to optimize treatment by increasing tumor toxicity and minimizing healthy tissue toxicity. METHODS/STUDY POPULATION: For this preliminary study, two methods will be used: benchtop pH experiments ex vivo and non-invasive imaging using acidoCEST MRI in vivo. For ex vivo, two types of tissues will be tested: non-cancerous liver and tumor tissue from HepG2 inoculated mice (n = 10). After mice are euthanized, pH will be measured in tissue homogenates at baseline and then the homogenates will be placed in either acidic (acetic acid) or basic (sodium hydroxide) solutions with varied concentrations (0.5–10M) and time recorded until pH returns to baseline. For in vivo imaging, Mia PaCA-2 flank model mice (n = 10) will be imaged with acidoCEST MRI to quantify pH at baseline. Mice will then be injected intratumorally with (up to 100 μL of) acid or base at increasing concentrations and imaged to quantify pH changes in the tumor. RESULTS/ANTICIPATED RESULTS: For this study, buffering capacity is defined as the concentration threshold for which tissue can buffer pH back to within normal range. Non-cancerous tissue is likely to buffer a wider range of concentrations compared to tumor tissue. From the benchtop experiment, comparison of time-to-buffer will be made for each concentration of acid/base for the two tissue types. AcidoCEST MRI will provide in vivo buffering capacity and potentially demonstrate tumor heterogeneity of buffering capacity. For both experiments, a pH vs. concentration curve for the two tissue types will allow for comparison of ex vivo to in vivo experiments, which will differentiate contributions of local tissue buffering capacity from the full body’s natural bicarbonate buffer system that depends on respiration and blood flow. DISCUSSION/SIGNIFICANCE OF IMPACT: The pH of the body must be maintained within a narrow range. With cancer, impairment in regulation of tumor metabolism causes acidosis, lowering extracellular pH in tumors. It remains unclear if pH plays a role in local recurrence or tumor toxicity. This work will determine if acidoCEST MRI can measure deliberate alteration of pH and how this change affects biology.
4094 Structural Determinants of Immunogenicity for Peptide-Based Immunotherapy
Authors: Devlin Jason , Alonso Jesus , Keller Grant , Bobisse Sara , Harari Alexandre , Baker Brian
Published: July 2020

OBJECTIVES/GOALS: Neoantigen vaccine immunotherapies have shown promise in clinical trials, but identifying which peptides to include in a vaccine remains a challenge. We aim to establish that molecular structural features can help predict which neoantigens to target to achieve tumor regression. METHODS/STUDY POPULATION: Proteins were prepared by recombinant expression in E. coli followed by in vitro refolding. Correctly folded proteins were purified by chromatography. Affinities of protein-protein interactions were measured by surface plasmon resonance (SPR) and thermal stabilities of proteins were determined by differential scanning fluorimetry. All experiments were performed at least in triplicate. Protein crystals were obtained by hanging drop vapor diffusion. The protein crystal structures were solved by molecular replacement and underwent several rounds of automated refinement. Molecular dynamics simulations were performed using the AMBER molecular dynamics package. RESULTS/ANTICIPATED RESULTS: A T cell receptor (TCR) expressed by tumor-infiltrating T cells exhibited a 20-fold stronger binding affinity to the neoantigen peptide compared to the self-peptide. X-ray crystal structures of the peptides with the major histocompatibility complex (MHC) protein demonstrated that a non-mutated residue in the peptide samples different positions with the mutation. The difference in conformations of the non-mutated residue was supported by molecular dynamics simulations. Crystal structures of the TCR engaging both peptide/MHCs suggested that the conformation favored by the mutant peptide was crucial for TCR binding. The TCR bound the neoantigen/MHC with faster binding kinetics. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results suggest that the mutation impacts the conformation of another residue in the peptide, and this alteration allows for more favorable T cell receptor binding to the neoantigen. This highlights the potential of non-mutated residues in contributing to neoantigen recognition.
I Don’t Know
Authors: BACKUS MATTHEW , LITTLE ANDREW T.
Published: July 2020

Political decision makers make choices in a complex and uncertain world, where even the most qualified experts may not know what policies will succeed. Worse, if these experts care about their reputation for competence, they may be averse to admitting what they don’t know. We model the strategic communication of uncertainty, allowing for the salient reality that sometimes the effects of proposed policies are impossible to know. Our model highlights the challenge of getting experts to admit uncertainty, even when it is possible to check predictive success. Moreover, we identify a novel solution: checking features of the question that only good experts will infer—in particular, whether the effect of policies is knowable—can induce uninformed experts do say “I Don’t Know.”
THE CYRUS ANECDOTE IN HERODOTUS 9.122
Authors: Xian Ruobing
Published: July 2020

The Cyrus anecdote recounted in the final chapter of Herodotus’Histories(9.122) has received the frequent notice of critics, with particular attention paid to the anecdote's relation to the work as a whole. Scholars have long since noted that the episode involves ‘the intersection of two basic narrative modes on which Herodotus has relied throughout theHistories: ethnographic description and detailed accounts of political activity and decision-making’. Thus scholars have illuminated the significance of the anecdote by comparing it to other thematically related passages in theHistories. Reading the closure of theHistoriesin terms of didactic enterprise, recent treatments of the anecdote tend to view Herodotus’ use of it as a moral lesson to his contemporary Athenians.
FRATERNAL FRIENDS: SOUTH AFRICAN COMMUNISTS AND CZECHOSLOVAKIA, 1945–89
Authors: Lodge Tom , Oralek Milan
Published: July 2020

Czechoslovak ‘people's democracy’ supplied a model for the development of a South African notion of a ‘national democratic’ revolution as well as providing key skills and resources. Czechoslovak support for this project in the 1960s and 1970s was both a source of confidence and fragility for South African Communists, boosting morale but confirming their subordinate status in their partnership with African nationalism. Drawing upon Czech archival materials as well as memoirs and interviews, this paper explores encounters and connections between South African Communists and the Czechs against the backdrop of the broader strategic concerns that shaped Soviet and Eastern European support for South African liberatory politics.
The cow–calf relationship: from maternal responsiveness to the maternal bond and the possibilities for fostering
Authors: Kent John P.
Published: July 2020

The relationship between the cow and calf develops over time after birth. The behavioural mechanisms underlying its development are important and comparisons with other species may increase our understanding. In nature the cow will separate herself from the herd to give birth and then the cow–calf relationship will develop with the ability to recognise each other. While twinning levels are low in cows, they do rear their twin calves. If the calf is lost at or after birth the cow can be responsive towards other calves and in specific circumstances the cow can develop a maternal bond with an alien calf, i.e. foster. In this Research Reflection a distinction is made between the development of, on the one hand, maternal responsiveness (the tendency of the cow to care for a calf which occurs before birth) and, on the other hand, the development of the maternal–filial bond or relationship which is reciprocal, occurs after birth and is characterised by the ability to discriminate the mother's own calf from alien calves. These processes can overlap and the relationship between cow and calf in this ‘hider’ species is more plastic than in some other mammals. For example, a cow might form an attachment with an alien calf before she gives birth. After the cow has given birth the loss of her own calf may result in the state of maternal responsiveness being maintained, such that developing a maternal bond with one or several appropriate alien calves is possible. Viable fostering techniques are possible. If a maternal relationship to the mother's own calf has developed then fostering will be more difficult. If the cow's relationship with her own calf is not exclusive, and she is in a state of maternal responsiveness then fostering of calves of an appropriate age and status can be achieved.
Exosome cargo in milk as a potential marker of cow health
Authors: Colitti Monica , Sgorlon Sandy , Stefanon Bruno
Published: July 2020

Recent advances on milk exosomes (EXO), cargoes in cell−cell communication, explored their role within and between individuals, including in dairy species. The potential use of EXO as biomarkers of disease and metabolic conditions adds significant interest to the study of EXO in milk. Although several researches have been carried out on circulating miRNA in the milk, less information is available about milk-derived exosomal miRNAs, which are stable over time and resistant to digestion and milk processing. EXO are taken up by recipient cells through specific mechanisms, which enable the selective delivery of cargoes. This suggests that EXO cargoes can be used as biomarkers of health. Nevertheless, methodological limitations and potential applications of milk EXO in dairy ruminants must be considered. The paucity of studies that associate the EXO cargo to specific challenges deserves further investigations to unravel the variation of miRNA and proteins cargo in relation to metabolic imbalance and infectious disease of the mammary gland.
Spirit mediumship and the state in mainland Southeast Asia: A comparative perspective
Authors: Cohen Erik
Published: July 2020

This comparative study examines the complex, changing configurations of the relationships between the state and mediumship cults, under different regimes and histories in three Southeast Asian states and China. Spirit mediums are endowed with charismatic authority, owing to their access to the supernatural sphere, which stands in implicit tension with the authority of the state. This tension underlies state–mediumship relationships in Southeast Asia, but leads to diverse dynamics, according to the place of religion in each state. In the atheist, communist/post-communist states (China and Vietnam) mediumship is primarily approached as a political issue; in Buddhist Thailand as a religious issue, and in multicultural Malaysia, where Islam is the official religion, as a legal issue. Tensions prevail particularly in the communist/post-communist states, where there has been a resurgence of mediumship cults, even as these are officially proscribed as ‘superstitions’. In Thailand tensions have been ameliorated by a gradual amalgamation of the cults and popular Buddhism, while in Malaysia tensions are prevented by controls over religious practices. Further research on the relatively neglected issue of the relationship between the state and mediumship cults in the emergent regions of the world is suggested.
Validation of a Belgian Prediction Model for Patient Encounters at Music Mass Gatherings
Authors: Spaepen Kris , Haenen Winne AP , Kaufman Leonard , Beens Kevin , Vandekerckhove Philippe , Hubloue Ives
Published: July 2020

Introduction:

A Belgian predictive medical resource tool, Plan Risk Manifestations (PRIMA), for the prediction of the number of patient encounters at mass gatherings (MGs) has recently been developed, in addition to the existing models of Arbon and Hartman. This study presents the results of the validation process for the PRIMA model for music MGs.

Methods:

A retrospective study was conducted using data gathered from music MGs in the province of Antwerp (Belgium) during the period of 2012-2016. Data from 87 music MGs were used for the study. The forecast of medical resources for these events was determined by entering the characteristics of individual events into the Arbon, Hartman, and PRIMA models. In order to determine if the PRIMA model is under- or over-predictive, the data gathered were retrospectively compared to the predicted number of resources needed using the aforementioned models. Statistical analysis included means, medians, and interquartile ranges (IQRs). Nonparametric related samples test (Wilcoxon Samples Signed Rank Test) for comparison of the median in deviations in predictions of patient presentation rates (PPRs) was performed using SPSS version 23 (IBM Corp.; Armonk, New York USA). Confidence interval levels were set at 95% and results were deemed statistically significant at P <.05. This triple comparison was used to determine the overall performance of all three models.

Results:

All three models had an acceptable rate of over-prediction of number of patient encounters ([Arbon 25.29%; 95% CI, 30.91-43.74]; [Hartman 29.89%; 95% CI, 57.10-68.90]; and [PRIMA 19.54%; 95% CI, 57.80-76.20]). But all models also had a high rate of under-prediction of number of patient encounters ([Arbon 74.71%; 95% CI, 453.31-752.52]; [Hartman 70.11%; 95% CI, 546.90-873.77]; and [PRIMA 78.16%; 95% CI, 288.91-464.89]). Only the PRIMA model succeeded in the correct prediction of the number of patient encounters on two occasions (2.3%).

Conclusion:

Results of this study are in-line with existing literature. When comparing the predicted patient encounters, all three models had high rates of under-prediction and moderate rates of over-prediction. When comparing mean deviations, the PRIMA model had the lowest mean deviation of all predicted PPRs. Belgian events of the types included in the presented data may use the PRIMA model with confidence to predict PPRs and estimate the in-event health services (IEHS) requirements.
Prevalence of stunting and obesity in Ecuador: a systematic review
Authors: Hajri Tahar , Angamarca-Armijos Viviana , Caceres Luis
Published: July 2020

Objective:

In low- and middle-income countries, undernutrition remains a major risk factor for child growth retardation. In addition, the emergence of obesity in recent years is adding another public health concern in that both stunting and obesity are associated with serious adverse health consequences. This review was designed to evaluate the prevalence of stunting and obesity in Ecuador.

Design:

Electronic databases were searched for articles published through February 2018 reporting the prevalence of stunting and/or obesity. Selected data were subjected to meta-analysis and pooled prevalence and their 95 percentiles (95 % CI) were calculated.

Setting:

Studies were identified in Medline, Web of Science, CINAHL, Cochrane Database and Ibero-America databases.

Participants:

Population of Ecuador.

Results:

Twenty-three articles were selected according to the inclusion/exclusion criteria of the study. The estimate of pooled prevalence of stunting was 23·2 % (95 % CI 23·3, 23·5) in preschoolers (age < 5 years), but was markedly higher in indigenous and rural communities. Pooled prevalence of obesity was 8·1 % (95 % CI 6·9, 9·3), 10·7 % (95 % CI 9·6, 11·7) and 10·5 % (95 % CI 9·2, 11·8) in preschoolers, school-age children (age: 5–11 years) and adolescent (age: 12–18 years), respectively. In adults (age ≥ 19 years), the rate of obesity was remarkably high as indicated by an overall estimate equal to 44·2 % (95 % CI 43·1, 45·4).

Conclusions:

This study underlines high levels of stunting among children and obesity among adults in Ecuador, both of which are not equally distributed among the population. The magnitude of this double burden emphasises the need for sustained and targeted interventions.
The course of depression in late life: a longitudinal perspective
Authors: de la Torre-Luque Alejandro , Ayuso-Mateos Jose Luis
Published: July 2020

Depression in old age deserves special attention in view of the fact of progressive population ageing, because of the way in which depression and risk factors interact in this period of life and the particularly negative impact of late-life depression on health and quality of life. This editorial aims to provide some insight into longitudinal aspects of depression in old age. Depression may follow varying trajectories (e.g. episode emergence, recurrence) across the lifespan. Late-life depression is not an exception. A symptom-based approach is presented as an appropriate research method to study the predictors and course of affective syndromes in old age. Findings from our studies on depressive symptom trajectories in old age revealed that participants with a course of unremitting elevated symptoms showed the highest levels of loneliness across the trajectory groups and that participants with subclinical symptoms also showed higher levels of loneliness than their counterparts with a minimal-symptom course trajectory. This highlights the need to address loneliness as a way of dealing with depression in old age.
Geomagnetic Field Model Indicates Shrinking Northern Auroral Oval
Authors: Zossi Bruno , Fagre Mariano , Amit Hagay , Elias Ana G.
Published: July 2020

Polar cap and auroral oval areas are presented for the period 1900–2015 using a model of the magnetosphere and the International Geomagnetic Reference Field Version 12 (IGRF‐12) model for the geomagnetic field. The effect of the main field long‐term changes is addressed considering steady interplanetary conditions. Until ~1940 both northern and southern polar cap areas increased with time, consistent with the geomagnetic dipole moment decrease during this period. Thereafter, while the southern polar cap area continued to increase steadily, the northern polar cap area has been decreasing rapidly. This hemispherical dichotomy is related to asymmetry in the core field and its secular variation. In the southern polar region the surface field intensity has been decreasing throughout the entire period, whereas in the northern polar region an intensity decrease turned to an increase from 1940 to present day. This recent surface intensity increase stems from intensification of the flux patch below Siberia and cessation of weakening of the flux patch below North America, both on the core‐mantle boundary. The surprising temporal decrease in the area of the northern polar cap has important implications for space weather and communication systems. While the decreasing dipole intensity allows more particles to penetrate the atmosphere, a shrinking northern auroral oval implies an increase in particle precipitation density, resulting in more severe damage to airplanes and ships positioning systems, spacecraft electronic systems and airline passengers when passing above this region. Further study is needed to observationally establish that the northern auroral oval, as defined by optical occurrences of aurora, is indeed shrinking.
Earth System Modeling Must Become More Energy Efficient
Authors: Loft Richard
Published: July 2020

As weather and climate models grow larger and more data intensive, the amount of energy needed to run them continues to increase. Are researchers doing enough to minimize the carbon footprint of their computing?
The Rise of Machine Learning
Authors: Goss Heather
Published: July 2020

Our August issue explores the way we process, analyze, and clearly present the massive amounts of information collected by scientists today.
First Global Images of Ion Energization in the Terrestrial Foreshock by the Interstellar Boundary Explorer
Authors: Dayeh M. A. , Szalay J. R. , Ogasawara K. , Fuselier S. A. , McComas D. J. , Funsten H. O. , Petrinec S. M. , Schwadron N. A. , Zirnstein E. J.
Published: July 2020

The Interstellar Boundary Explorer (IBEX) mission provides global energetic neutral atom (ENA) observations from the heliosphere and the Earth's magnetosphere, including spatial, temporal, and energy information. IBEX views the magnetosphere from the sides and almost always perpendicular to noon‐midnight plane. We report the first ENA images of the energization process in the Earth's ion foreshock and magnetosheath regions. We show ENA flux and spectral images of the dayside magnetosphere with significant energization of ENA plasma sources (above ~2.7 keV) in the region magnetically connected to the Earth's bow shock (BS) in its quasi‐parallel configuration of the interplanetary magnetic field (IMF). We also show that the ion energization increases gradually with decreasing IMF‐BS angle, suggesting more efficient suprathermal ion acceleration deeper in the quasi‐parallel foreshock.
Precipitation‐Induced Reduction in Surface Ocean pCO2: Observations From the Eastern Tropical Pacific Ocean
Authors: Ho David T. , Schanze Julian J.
Published: July 2020

Determining air‐sea CO2 fluxes using pCO2 disequilibrium requires knowing the gas transfer velocity and air‐sea pCO2 difference. Most pCO2 measurements are made from ships, whose uncontaminated seawater intakes are located at >5‐m depth to prevent ingestion of air. However, there could be bias in determinations of CO2 fluxes if there is disagreement between pCO2 measurements at the surface and 5 m. Seawater measurements made at the near surface and 5 m in the eastern Equatorial Pacific Ocean show that precipitation can dilute surface seawater salinity and lower the pCO2 and dissolved inorganic carbon and raise pH of the same water, and that these changes in ocean chemistry are largely missed by measurements at 5 m. This finding implies that estimates of ocean CO2 uptake might be underestimated, since rain will lower surface ocean pCO2 in both source and sink regions and, hence, increase uptake in sink regions and decrease outgassing in source regions.
Surface Wetness as an Unexpected Control on Forest Exchange of Volatile Organic Acids
Authors: Fulgham S. R. , Millet D. B. , Alwe H. D. , Goldstein A. H. , Schobesberger S. , Farmer D. K.
Published: July 2020

We report bidirectional exchange of volatile acids, including isocyanic and alkanoic acids, over a pine forest across multiple seasons. The exchange velocity of these acids is well correlated with dew point depression, suggesting an equilibrium‐driven continuum of flux. Wetness on forest surfaces impacts the vertical exchange of gases, and we suggest that water films and droplets drive equilibrium partitioning, with acids being solvated in surface wetness and released through evaporation. Despite their volatility, these acids partition into neutral‐to‐alkaline aqueous films, consistent with reported dew pH. This relationship between exchange velocity and dew point depression holds for a wetter mixed forest, but not a very dry orchard. Dew point depression is an excellent indicator of acid fluxes so long as the canopy is occasionally wetted.
Submicrosecond Spectroscopy of Lightning‐Like Discharges: Exploring New Time Regimes
Authors: Kieu N. , Gordillo‐Vázquez F. J. , Passas M. , Sánchez J. , Pérez‐Invernón F. J. , Luque A. , Montanyá J. , Christian H.
Published: July 2020

Submicrosecond (0.476 μs per frame with an exposure time of 160 ns) high‐resolution (0.38 nm) time‐resolved spectra of laboratory‐produced lightning‐like electrical discharges have been recorded for the first time within the visible spectral range (645–665 nm). The spectra were recorded with the GrAnada LIghtning Ultrafast Spectrograph (GALIUS), a high‐speed imaging spectrograph recently developed for lightning research in the IAA‐CSIC. Unprecedented spectral time dynamics are explored for meter long laboratory electrical discharges produced with a 2.0 MV Marx generator. The maximum electron density and gas temperature measured in a timescale of ≤0.50 μs (160 ns) were, respectively, ≃1018 cm−3 and ≃32,000 K. Overpressure in the lightning‐like plasma channel, black‐body dynamics, and self‐absorption in spectral lines were investigated.
Strength Evolution of Ice Plume Deposit Analogs of Enceladus and Europa
Authors: Choukroun M. , Molaro J. L. , Hodyss R. , Marteau E. , Backes P. , Carey E. M. , Dhaouadi W. , Moreland S. , Schulson E. M.
Published: July 2020

Enceladus and possibly Europa spew materials from their internal ocean into their exosphere, some of which are deposited back onto the surface of those Ocean Worlds. This setting provides a unique opportunity to seek traces of past or extant life in ice plume deposits on their surfaces. However, the design of lander missions and surface sampling techniques and the choice of sampling locations rely heavily on strength expectations. Here we present an experimental investigation of the evolution in strength of ice plume deposit analogs at several temperatures, as well as a model that predicts first‐order estimates of the strength of evolved ice plume deposits under geologic timescales relevant to Enceladus and Europa. These results suggest that plume deposits remain weak and poorly consolidated on Enceladus, while they may develop substantial strength (comparable to solid ice) within <100 Myr on Europa.
Hydrate is a Nonwetting Phase in Porous Media
Authors: Murphy Zachary W. , DiCarlo David A. , Flemings Peter B. , Daigle Hugh
Published: July 2020

In porous media containing gas hydrate, the hydrate morphology impacts the flow behavior of the fluid phases. We hypothesize that hydrate emplaces itself as a nonwetting phase and use this idea to describe relative permeability of water in a hydrate/water system. We perform steady‐state relative permeability measurements in hydrate‐bearing samples with a range of hydrate saturation. We measure and compare water relative permeability in the presence of gas and in the presence of hydrate and find that the water relative permeability is the same in both cases. This suggests that (1) relative permeability for hydrate systems can be obtained without performing difficult experiments on hydrate bearing sediments, (2) flow properties are porous‐media dependent, and (3) models that assume a fixed pore or tube geometry are inadequate.
The Transition Zone Beneath West Argentina‐Central Chile Using P‐to‐S Converted Waves
Authors: Bonatto Luciana , Piromallo Claudia , Cottaar Sanne
Published: July 2020

We investigate the mantle transition zone beneath the Chile‐Argentina flat subduction region by means of P‐to‐S conversions at mantle discontinuities from teleseismic events recorded at 103 seismic stations. From the analysis of receiver functions, we obtain clear converted phases from the 410 and 660 discontinuities, and we identify a robust precursory signal to P660s, of negative amplitude, that we name P590s. We observe little frequency dependence in the amplitude of the P410s converted phase, while the P660s is less visible toward higher frequencies. The 410 is on average deeper than 410 km by 10 ± 1 km in the higher‐frequency bands, and it is relatively sharp, being consistent with a 10% velocity jump over less than 20 km. The observed 660 depth varies with frequency; it is deeper by up to 18 ± 2 km for lower frequencies and close to reference at higher frequencies, being consistent with a 13% broad velocity gradient over 30–40 km, probably caused by a composite of multiple phase transitions. The transition zone thickness is controlled by the frequency‐dependent depth variability of the 660. Our findings of relative depth, width, and velocity jump of the detected discontinuities, combined with tomographic images of the mantle transition zone, cannot be explained by thermal variations alone. Compositional constraints from mineral physics show that a near pyrolitic mantle is consistent with the ratio of the estimated velocity jumps. However, the negative P590s phase in this region could be signal from the velocity reduction due to basalt accumulation at the base of the transition zone.
Transcriptional activity and strain-specific history of mouse pseudogenes
Authors: Sisu Cristina , Muir Paul , Frankish Adam , Fiddes Ian , Diekhans Mark , Thybert David , Odom Duncan T. , Flicek Paul , Keane Thomas M. , Hubbard Tim , Harrow Jennifer , Gerstein Mark
Published: July 2020

Pseudogenes are ideal markers of genome remodelling. In turn, the mouse is an ideal platform for studying them, particularly with the recent availability of strain-sequencing and transcriptional data. Here, combining both manual curation and automatic pipelines, we present a genome-wide annotation of the pseudogenes in the mouse reference genome and 18 inbred mouse strains (available via the mouse.pseudogene.org resource). We also annotate 165 unitary pseudogenes in mouse, and 303, in human. The overall pseudogene repertoire in mouse is similar to that in human in terms of size, biotype distribution, and family composition (e.g. with GAPDH and ribosomal proteins being the largest families). Notable differences arise in the pseudogene age distribution, with multiple retro-transpositional bursts in mouse evolutionary history and only one in human. Furthermore, in each strain about a fifth of all pseudogenes are unique, reflecting strain-specific evolution. Finally, we find that ~15% of the mouse pseudogenes are transcribed, and that highly transcribed parent genes tend to give rise to many processed pseudogenes.
Gas hydrate dissociation linked to contemporary ocean warming in the southern hemisphere
Authors: Ketzer Marcelo , Praeg Daniel , Rodrigues Luiz F. , Augustin Adolpho , Pivel Maria A. G. , Rahmati-Abkenar Mahboubeh , Miller Dennis J. , Viana Adriano R. , Cupertino José A.
Published: July 2020

Ocean warming related to climate change has been proposed to cause the dissociation of gas hydrate deposits and methane leakage on the seafloor. This process occurs in places where the edge of the gas hydrate stability zone in sediments meets the overlying warmer oceans in upper slope settings. Here we present new evidence based on the analysis of a large multi-disciplinary and multi-scale dataset from such a location in the western South Atlantic, which records massive gas release to the ocean. The results provide a unique opportunity to examine ocean-hydrate interactions over millennial and decadal scales, and the first evidence from the southern hemisphere for the effects of contemporary ocean warming on gas hydrate stability. Widespread hydrate dissociation results in a highly focused advective methane flux that is not fully accessible to anaerobic oxidation, challenging the assumption that it is mostly consumed by sulfate reduction before reaching the seafloor.
Detecting sample swaps in diverse NGS data types using linkage disequilibrium
Authors: Javed Nauman , Farjoun Yossi , Fennell Tim J. , Epstein Charles B. , Bernstein Bradley E. , Shoresh Noam
Published: July 2020

As the number of genomics datasets grows rapidly, sample mislabeling has become a high stakes issue. We present CrosscheckFingerprints (Crosscheck), a tool for quantifying sample-relatedness and detecting incorrectly paired sequencing datasets from different donors. Crosscheck outperforms similar methods and is effective even when data are sparse or from different assays. Application of Crosscheck to 8851 ENCODE ChIP-, RNA-, and DNase-seq datasets enabled us to identify and correct dozens of mislabeled samples and ambiguous metadata annotations, representing ~1% of ENCODE datasets.
Microbiota assembly, structure, and dynamics among Tsimane horticulturalists of the Bolivian Amazon
Authors: Sprockett Daniel D. , Martin Melanie , Costello Elizabeth K. , Burns Adam R. , Holmes Susan P. , Gurven Michael D. , Relman David A.
Published: July 2020

Selective and neutral forces shape human microbiota assembly in early life. The Tsimane are an indigenous Bolivian population with infant care-associated behaviors predicted to increase mother-infant microbial dispersal. Here, we characterize microbial community assembly in 47 infant-mother pairs from six Tsimane villages, using 16S rRNA gene amplicon sequencing of longitudinal stool and tongue swab samples. We find that infant consumption of dairy products, vegetables, and chicha (a fermented drink inoculated with oral microbes) is associated with stool microbiota composition. In stool and tongue samples, microbes shared between mothers and infants are more abundant than non-shared microbes. Using a neutral model of community assembly, we find that neutral processes alone explain the prevalence of 79% of infant-colonizing microbes, but explain microbial prevalence less well in adults from river villages with more regular access to markets. Our results underscore the importance of neutral forces during microbiota assembly. Changing lifestyle factors may alter traditional modes of microbiota assembly by decreasing the role of neutral processes.
The sponge effect and carbon emission mitigation potentials of the global cement cycle
Authors: Cao Zhi , Myers Rupert J. , Lupton Richard C. , Duan Huabo , Sacchi Romain , Zhou Nan , Reed Miller T. , Cullen Jonathan M. , Ge Quansheng , Liu Gang
Published: July 2020

Cement plays a dual role in the global carbon cycle like a sponge: its massive production contributes significantly to present-day global anthropogenic CO2 emissions, yet its hydrated products gradually reabsorb substantial amounts of atmospheric CO2 (carbonation) in the future. The role of this sponge effect along the cement cycle (including production, use, and demolition) in carbon emissions mitigation, however, remains hitherto unexplored. Here, we quantify the effects of demand- and supply-side mitigation measures considering this material-energy-emissions-uptake nexus, finding that climate goals would be imperiled if the growth of cement stocks continues. Future reabsorption of CO2 will be significant (~30% of cumulative CO2 emissions from 2015 to 2100), but climate goal compliant net CO2 emissions reduction along the global cement cycle will require both radical technology advancements (e.g., carbon capture and storage) and widespread deployment of material efficiency measures, which go beyond those envisaged in current technology roadmaps.
Optomechanical mass spectrometry
Authors: Sansa Marc , Defoort Martial , Brenac Ariel , Hermouet Maxime , Banniard Louise , Fafin Alexandre , Gely Marc , Masselon Christophe , Favero Ivan , Jourdan Guillaume , Hentz Sébastien
Published: July 2020

Nanomechanical mass spectrometry has proven to be well suited for the analysis of high mass species such as viruses. Still, the use of one-dimensional devices such as vibrating beams forces a trade-off between analysis time and mass resolution. Complex readout schemes are also required to simultaneously monitor multiple resonance modes, which degrades resolution. These issues restrict nanomechanical MS to specific species. We demonstrate here single-particle mass spectrometry with nano-optomechanical resonators fabricated with a Very Large Scale Integration process. The unique motion sensitivity of optomechanics allows designs that are impervious to particle position, stiffness or shape, opening the way to the analysis of large aspect ratio biological objects of great significance such as viruses with a tail or fibrils. Compared to top-down beam resonators with electrical read-out and state-of-the-art mass resolution, we show a three-fold improvement in capture area with no resolution degradation, despite the use of a single resonance mode.
Alkaline thermal treatment of seaweed for high-purity hydrogen production with carbon capture and storage potential
Authors: Zhang Kang , Kim Woo-Jae , Park Ah-Hyung Alissa
Published: July 2020

Current thermochemical methods to generate H2 include gasification and steam reforming of coal and natural gas, in which anthropogenic CO2 emission is inevitable. If biomass is used as a source of H2, the process can be considered carbon-neutral. Seaweeds are among the less studied types of biomass with great potential because they do not require freshwater. Unfortunately, reaction pathways to thermochemically convert salty and wet biomass into H2 are limited. In this study, a catalytic alkaline thermal treatment of brown seaweed is investigated to produce high purity H2 with substantially suppressed CO2 formation making the overall biomass conversion not only carbon-neutral but also potentially carbon-negative. High-purity 69.69 mmol-H2/(dry-ash-free)g-brown seaweed is produced with a conversion as high as 71%. The hydroxide is involved in both H2 production and in situ CO2 capture, while the Ni/ZrO2 catalyst enhanced the secondary H2 formation via steam methane reforming and water-gas shift reactions.
Understanding important features of deep learning models for segmentation of high-resolution transmission electron microscopy images
Authors: Horwath James P. , Zakharov Dmitri N. , Mégret Rémi , Stach Eric A.
Published: July 2020

Cutting edge deep learning techniques allow for image segmentation with great speed and accuracy. However, application to problems in materials science is often difficult since these complex models may have difficultly learning meaningful image features that would enable extension to new datasets. In situ electron microscopy provides a clear platform for utilizing automated image analysis. In this work, we consider the case of studying coarsening dynamics in supported nanoparticles, which is important for understanding, for example, the degradation of industrial catalysts. By systematically studying dataset preparation, neural network architecture, and accuracy evaluation, we describe important considerations in applying deep learning to physical applications, where generalizable and convincing models are required. With a focus on unique challenges that arise in high-resolution images, we propose methods for optimizing performance of image segmentation using convolutional neural networks, critically examining the application of complex deep learning models in favor of motivating intentional process design.
Global reference mapping of human transcription factor footprints
Authors: Vierstra Jeff , Lazar John , Sandstrom Richard , Halow Jessica , Lee Kristen , Bates Daniel , Diegel Morgan , Dunn Douglas , Neri Fidencio , Haugen Eric , Rynes Eric , Reynolds Alex , Nelson Jemma , Johnson Audra , Frerker Mark , Buckley Michael , Kaul Rajinder , Meuleman Wouter , Stamatoyannopoulos John A.
Published: July 2020

Combinatorial binding of transcription factors to regulatory DNA underpins gene regulation in all organisms. Genetic variation in regulatory regions has been connected with diseases and diverse phenotypic traits1, but it remains challenging to distinguish variants that affect regulatory function2. Genomic DNase I footprinting enables the quantitative, nucleotide-resolution delineation of sites of transcription factor occupancy within native chromatin3–6. However, only a small fraction of such sites have been precisely resolved on the human genome sequence6. Here, to enable comprehensive mapping of transcription factor footprints, we produced high-density DNase I cleavage maps from 243 human cell and tissue types and states and integrated these data to delineate about 4.5 million compact genomic elements that encode transcription factor occupancy at nucleotide resolution. We map the fine-scale structure within about 1.6 million DNase I-hypersensitive sites and show that the overwhelming majority are populated by well-spaced sites of single transcription factor–DNA interaction. Cell-context-dependent cis-regulation is chiefly executed by wholesale modulation of accessibility at regulatory DNA rather than by differential transcription factor occupancy within accessible elements. We also show that the enrichment of genetic variants associated with diseases or phenotypic traits in regulatory regions1,7 is almost entirely attributable to variants within footprints, and that functional variants that affect transcription factor occupancy are nearly evenly partitioned between loss- and gain-of-function alleles. Unexpectedly, we find increased density of human genetic variation within transcription factor footprints, revealing an unappreciated driver of cis-regulatory evolution. Our results provide a framework for both global and nucleotide-precision analyses of gene regulatory mechanisms and functional genetic variation.
The changing mouse embryo transcriptome at whole tissue and single-cell resolution
Authors: He Peng , Williams Brian A. , Trout Diane , Marinov Georgi K. , Amrhein Henry , Berghella Libera , Goh Say-Tar , Plajzer-Frick Ingrid , Afzal Veena , Pennacchio Len A. , Dickel Diane E. , Visel Axel , Ren Bing , Hardison Ross C. , Zhang Yu , Wold Barbara J.
Published: July 2020

During mammalian embryogenesis, differential gene expression gradually builds the identity and complexity of each tissue and organ system1. Here we systematically quantified mouse polyA-RNA from day 10.5 of embryonic development to birth, sampling 17 tissues and organs. The resulting developmental transcriptome is globally structured by dynamic cytodifferentiation, body-axis and cell-proliferation gene sets that were further characterized by the transcription factor motif codes of their promoters. We decomposed the tissue-level transcriptome using single-cell RNA-seq (sequencing of RNA reverse transcribed into cDNA) and found that neurogenesis and haematopoiesis dominate at both the gene and cellular levels, jointly accounting for one-third of differential gene expression and more than 40% of identified cell types. By integrating promoter sequence motifs with companion ENCODE epigenomic profiles, we identified a prominent promoter de-repression mechanism in neuronal expression clusters that was attributable to known and novel repressors. Focusing on the developing limb, single-cell RNA data identified 25 candidate cell types that included progenitor and differentiating states with computationally inferred lineage relationships. We extracted cell-type transcription factor networks and complementary sets of candidate enhancer elements by using single-cell RNA-seq to decompose integrative cis-element (IDEAS) models that were derived from whole-tissue epigenome chromatin data. These ENCODE reference data, computed network components and IDEAS chromatin segmentations are companion resources to the matching epigenomic developmental matrix, and are available for researchers to further mine and integrate.