85 research outputs found
Observations of the Askaryan Effect in Ice
We report on the first observations of the Askaryan effect in ice: coherent impulsive radio Cherenkov radiation from the charge asymmetry in an electromagnetic (EM) shower. Such radiation has been observed in silica sand and rock salt, but this is the first direct observation from an EM shower in ice. These measurements are important since the majority of experiments to date that rely on the effect for ultra-high energy neutrino detection are being performed using ice as the target medium. As part of the complete validation process for the Antarctic Impulsive Transient Antenna (ANITA) experiment, we performed an experiment at the Stanford Linear Accelerator Center (SLAC) in June 2006 using a 7.5 metric ton ice target, yielding results fully consistent with theoretical expectations
New Limits on the Ultra-high Energy Cosmic Neutrino Flux from the ANITA Experiment
We report initial results of the first flight of the Antarctic Impulsive
Transient Antenna (ANITA-1) 2006-2007 Long Duration Balloon flight, which
searched for evidence of a diffuse flux of cosmic neutrinos above energies of 3
EeV. ANITA-1 flew for 35 days looking for radio impulses due to the Askaryan
effect in neutrino-induced electromagnetic showers within the Antarctic ice
sheets. We report here on our initial analysis, which was performed as a blind
search of the data. No neutrino candidates are seen, with no detected physics
background. We set model-independent limits based on this result. Upper limits
derived from our analysis rule out the highest cosmogenic neutrino models. In a
background horizontal-polarization channel, we also detect six events
consistent with radio impulses from ultra-high energy extensive air showers.Comment: 4 pages, 2 table
Characteristics of Four Upward-Pointing Cosmic-Ray-like Events Observed with ANITA
We report on four radio-detected cosmic-ray (CR) or CR-like events observed with the Antarctic Impulsive Transient Antenna (ANITA), a NASA-sponsored long-duration balloon payload. Two of the four were previously identified as stratospheric CR air showers during the ANITA-I flight. A third stratospheric CR was detected during the ANITA-II flight. Here, we report on characteristics of these three unusual CR events, which develop nearly horizontally, 20-30 km above the surface of Earth. In addition, we report on a fourth steeply upward-pointing ANITA-I CR-like radio event which has characteristics consistent with a primary that emerged from the surface of the ice. This suggests a possible τ-lepton decay as the origin of this event, but such an interpretation would require significant suppression of the standard model τ-neutrino cross section
Identifying RNA editing sites using RNA sequencing data alone
We show that RNA editing sites can be called with high confidence using RNA sequencing data from multiple samples across either individuals or species, without the need for matched genomic DNA sequence. We identified many previously unidentified editing sites in both humans and Drosophila; our results nearly double the known number of human protein recoding events. We also found that human genes harboring conserved editing sites within Alu repeats are enriched for neuronal functions
Upward-pointing cosmic-ray-like events observed with ANITA
These proceedings address a recent publication by the ANITA collaboration of four upward-pointing cosmic-ray-like events observed in the first flight of ANITA. Three of these events were consistent with stratospheric cosmic-ray air showers where the axis of propagation does not intersect the surface of the Earth. The fourth event was consistent with a primary particle that emerges from the surface of the ice suggesting a possible τ-lepton decay as the origin of this event. These proceedings follow-up on the modeling and testing of the hypothesis that this event was of τ neutrino origin
Thermodynamic Additivity of Sequence Variations: An Algorithm for Creating High Affinity Peptides Without Large Libraries or Structural Information
BACKGROUND: There is a significant need for affinity reagents with high target affinity/specificity that can be developed rapidly and inexpensively. Existing affinity reagent development approaches, including protein mutagenesis, directed evolution, and fragment-based design utilize large libraries and/or require structural information thereby adding time and expense. Until now, no systematic approach to affinity reagent development existed that could produce nanomolar affinity from small chemically synthesized peptide libraries without the aid of structural information. METHODOLOGY/PRINCIPAL FINDINGS: Based on the principle of additivity, we have developed an algorithm for generating high affinity peptide ligands. In this algorithm, point-variations in a lead sequence are screened and combined in a systematic manner to achieve additive binding energies. To demonstrate this approach, low-affinity lead peptides for multiple protein targets were identified from sparse random sequence space and optimized to high affinity in just two chemical steps. In one example, a TNF-α binding peptide with K(d) = 90 nM and high target specificity was generated. The changes in binding energy associated with each variation were generally additive upon combining variations, validating the basis of the algorithm. Interestingly, cooperativity between point-variations was not observed, and in a few specific cases, combinations were less than energetically additive. CONCLUSIONS/SIGNIFICANCE: By using this additivity algorithm, peptide ligands with high affinity for protein targets were generated. With this algorithm, one of the highest affinity TNF-α binding peptides reported to date was produced. Most importantly, high affinity was achieved from small, chemically-synthesized libraries without the need for structural information at any time during the process. This is significantly different than protein mutagenesis, directed evolution, or fragment-based design approaches, which rely on large libraries and/or structural guidance. With this algorithm, high affinity/specificity peptide ligands can be developed rapidly, inexpensively, and in an entirely chemical manner
Health sector spending and spending on HIV/AIDS, tuberculosis, and malaria, and development assistance for health: progress towards Sustainable Development Goal 3
Background: Sustainable Development Goal (SDG) 3 aims to “ensure healthy lives and promote well-being for all at all
ages”. While a substantial effort has been made to quantify progress towards SDG3, less research has focused on
tracking spending towards this goal. We used spending estimates to measure progress in financing the priority areas
of SDG3, examine the association between outcomes and financing, and identify where resource gains are most
needed to achieve the SDG3 indicators for which data are available.
Methods: We estimated domestic health spending, disaggregated by source (government, out-of-pocket, and prepaid
private) from 1995 to 2017 for 195 countries and territories. For disease-specific health spending, we estimated
spending for HIV/AIDS and tuberculosis for 135 low-income and middle-income countries, and malaria in
106 malaria-endemic countries, from 2000 to 2017. We also estimated development assistance for health (DAH) from
1990 to 2019, by source, disbursing development agency, recipient, and health focus area, including DAH for
pandemic preparedness. Finally, we estimated future health spending for 195 countries and territories from 2018 until
2030. We report all spending estimates in inflation-adjusted 2019 US7·9 trillion (95% uncertainty interval 7·8–8·0) in 2017 and is expected to increase to 20·2 billion
(17·0–25·0) and on tuberculosis it was 5·1 billion (4·9–5·4). Development assistance for health was 374 million of DAH was provided
for pandemic preparedness, less than 1% of DAH. Although spending has increased across HIV/AIDS, tuberculosis,
and malaria since 2015, spending has not increased in all countries, and outcomes in terms of prevalence, incidence,
and per-capita spending have been mixed. The proportion of health spending from pooled sources is expected to
increase from 81·6% (81·6–81·7) in 2015 to 83·1% (82·8–83·3) in 2030.
Interpretation: Health spending on SDG3 priority areas has increased, but not in all countries, and progress towards
meeting the SDG3 targets has been mixed and has varied by country and by target. The evidence on the scale-up of
spending and improvements in health outcomes suggest a nuanced relationship, such that increases in spending do
not always results in improvements in outcomes. Although countries will probably need more resources to achieve
SDG3, other constraints in the broader health system such as inefficient allocation of resources across interventions
and populations, weak governance systems, human resource shortages, and drug shortages, will also need to be
addressed.
Funding: The Bill & Melinda Gates Foundatio
Advancing brain barriers RNA sequencing: guidelines from experimental design to publication
Background: RNA sequencing (RNA-Seq) in its varied forms has become an indispensable tool for analyzing differential gene expression and thus characterization of specific tissues. Aiming to understand the brain barriers genetic signature, RNA seq has also been introduced in brain barriers research. This has led to availability of both, bulk and single-cell RNA-Seq datasets over the last few years. If appropriately performed, the RNA-Seq studies provide powerful datasets that allow for significant deepening of knowledge on the molecular mechanisms that establish the brain barriers. However, RNA-Seq studies comprise complex workflows that require to consider many options and variables before, during and after the proper sequencing process.Main body: In the current manuscript, we build on the interdisciplinary experience of the European PhD Training Network BtRAIN (https://www.btrain-2020.eu/) where bioinformaticians and brain barriers researchers collaborated to analyze and establish RNA-Seq datasets on vertebrate brain barriers. The obstacles BtRAIN has identified in this process have been integrated into the present manuscript. It provides guidelines along the entire workflow of brain barriers RNA-Seq studies starting from the overall experimental design to interpretation of results. Focusing on the vertebrate endothelial blood–brain barrier (BBB) and epithelial blood-cerebrospinal-fluid barrier (BCSFB) of the choroid plexus, we provide a step-by-step description of the workflow, highlighting the decisions to be made at each step of the workflow and explaining the strengths and weaknesses of individual choices made. Finally, we propose recommendations for accurate data interpretation and on the information to be included into a publication to ensure appropriate accessibility of the data and reproducibility of the observations by the scientific community.Conclusion: Next generation transcriptomic profiling of the brain barriers provides a novel resource for understanding the development, function and pathology of these barrier cells, which is essential for understanding CNS homeostasis and disease. Continuous advancement and sophistication of RNA-Seq will require interdisciplinary approaches between brain barrier researchers and bioinformaticians as successfully performed in BtRAIN. The present guidelines are built on the BtRAIN interdisciplinary experience and aim to facilitate collaboration of brain barriers researchers with bioinformaticians to advance RNA-Seq study design in the brain barriers community
Diabetes mortality and trends before 25 years of age: an analysis of the Global Burden of Disease Study 2019
Background Diabetes, particularly type 1 diabetes, at younger ages can be a largely preventable cause of death with the correct health care and services. We aimed to evaluate diabetes mortality and trends at ages younger than 25 years globally using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Methods We used estimates of GBD 2019 to calculate international diabetes mortality at ages younger than 25 years in 1990 and 2019. Data sources for causes of death were obtained from vital registration systems, verbal autopsies, and other surveillance systems for 1990–2019. We estimated death rates for each location using the GBD Cause of Death Ensemble model. We analysed the association of age-standardised death rates per 100 000 population with the Socio-demographic Index (SDI) and a measure of universal health coverage (UHC) and described the variability within SDI quintiles. We present estimates with their 95% uncertainty intervals. Findings In 2019, 16 300 (95% uncertainty interval 14 200 to 18 900) global deaths due to diabetes (type 1 and 2 combined) occurred in people younger than 25 years and 73·7% (68·3 to 77·4) were classified as due to type 1 diabetes. The age-standardised death rate was 0·50 (0·44 to 0·58) per 100 000 population, and 15 900 (97·5%) of these deaths occurred in low to high-middle SDI countries. The rate was 0·13 (0·12 to 0·14) per 100 000 population in the high SDI quintile, 0·60 (0·51 to 0·70) per 100 000 population in the low-middle SDI quintile, and 0·71 (0·60 to 0·86) per 100 000 population in the low SDI quintile. Within SDI quintiles, we observed large variability in rates across countries, in part explained by the extent of UHC (r2=0·62). From 1990 to 2019, age-standardised death rates decreased globally by 17·0% (−28·4 to −2·9) for all diabetes, and by 21·0% (–33·0 to −5·9) when considering only type 1 diabetes. However, the low SDI quintile had the lowest decline for both all diabetes (−13·6% [–28·4 to 3·4]) and for type 1 diabetes (−13·6% [–29·3 to 8·9]). Interpretation Decreasing diabetes mortality at ages younger than 25 years remains an important challenge, especially in low and low-middle SDI countries. Inadequate diagnosis and treatment of diabetes is likely to be major contributor to these early deaths, highlighting the urgent need to provide better access to insulin and basic diabetes education and care. This mortality metric, derived from readily available and frequently updated GBD data, can help to monitor preventable diabetes-related deaths over time globally, aligned with the UN's Sustainable Development Targets, and serve as an indicator of the adequacy of basic diabetes care for type 1 and type 2 diabetes across nations.publishedVersio
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