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Geographic source estimation using airborne plant environmental DNA in dust

Summary

Information obtained from the analysis of dust, particularly biological particles such as pollen, plant parts, and fungal spores, has great utility in forensic geolocation. As an alternative to manual microscopic analysis, we developed a pipeline that utilizes the environmental DNA (eDNA) from plants in dust samples to estimate previous sample location(s). The species of plant-derived eDNA within dust samples were identified using metabarcoding and their geographic distributions were then derived from occurrence records in the USGS Biodiversity in Service of Our Nation (BISON) database. The distributions for all plant species identified in a sample were used to generate a probabilistic estimate of the sample source. With settled dust collected at four U.S. sites over a 15-month period, we demonstrated positive regional geolocation (within 600 km2 of the collection point) with 47.6% (20 of 42) of the samples analyzed. Attribution accuracy and resolution was dependent on the number of plant species identified in a dust sample, which was greatly affected by the season of collection. In dust samples that yielded a minimum of 20 identified plant species, positive regional attribution improved to 66.7% (16 of 24 samples). Using dust samples collected from 31 different U.S. sites, trace plant eDNA provided relevant regional attribution information on provenance in 32.2%. This demonstrated that analysis of plant eDNA in dust can provide an accurate estimate regional provenance within the U.S., and relevant forensic information, for a substantial fraction of samples analyzed.
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Summary

Information obtained from the analysis of dust, particularly biological particles such as pollen, plant parts, and fungal spores, has great utility in forensic geolocation. As an alternative to manual microscopic analysis, we developed a pipeline that utilizes the environmental DNA (eDNA) from plants in dust samples to estimate previous sample...

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COVID-19: famotidine, histamine, mast cells, and mechanisms [eprint]

Summary

SARS-CoV-2 infection is required for COVID-19, but many signs and symptoms of COVID-19 differ from common acute viral diseases. Currently, there are no pre- or post-exposure prophylactic COVID-19 medical countermeasures. Clinical data suggest that famotidine may mitigate COVID-19 disease, but both mechanism of action and rationale for dose selection remain obscure. We explore several plausible avenues of activity including antiviral and host-mediated actions. We propose that the principal famotidine mechanism of action for COVID-19 involves on-target histamine receptor H2 activity, and that development of clinical COVID-19 involves dysfunctional mast cell activation and histamine release.
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Summary

SARS-CoV-2 infection is required for COVID-19, but many signs and symptoms of COVID-19 differ from common acute viral diseases. Currently, there are no pre- or post-exposure prophylactic COVID-19 medical countermeasures. Clinical data suggest that famotidine may mitigate COVID-19 disease, but both mechanism of action and rationale for dose selection remain...

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Kawasaki disease, multisystem inflammatory syndrome in children: antibody-induced mast cell activation hypothesis

Published in:
J Pediatrics & Pediatr Med. 2020; 4(2): 1-7

Summary

Multisystem Inflammatory Syndrome in Children (MIS-C) is appearing in infants, children, and young adults in association with COVID-19 (coronavirus disease 2019) infections of SARS-CoV-2. Kawasaki Disease (KD) is one of the most common vasculitides of childhood. KD presents with similar symptoms to MIS-C especially in severe forms such as Kawasaki Disease Shock Syndrome (KDSS). The observed symptoms for MIS-C and KD are consistent with Mast Cell Activation Syndrome (MCAS) characterized by inflammatory molecules released from activated mast cells. Based on the associations of KD with multiple viral and bacterial pathogens, we put forward the hypothesis that KD and MIS-C result from antibody activation of mast cells by Fc receptor-bound pathogen antibodies causing a hyperinflammatory response upon second pathogen exposure. Within this hypothesis, MIS-C may be atypical KD or a KD-like disease associated with SARS-CoV-2. We extend the mast cell hypothesis that increased histamine levels are inducing contraction of effector cells with impeded blood flow through cardiac capillaries. In some patients, pressure from impeded blood flow, within cardiac capillaries, may result in increased coronary artery blood pressure leading to aneurysms, a well-known complication in KD.
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Summary

Multisystem Inflammatory Syndrome in Children (MIS-C) is appearing in infants, children, and young adults in association with COVID-19 (coronavirus disease 2019) infections of SARS-CoV-2. Kawasaki Disease (KD) is one of the most common vasculitides of childhood. KD presents with similar symptoms to MIS-C especially in severe forms such as Kawasaki...

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Medical countermeasures analysis of 2019-nCoV and vaccine risks for antibody-dependent enhancement (ADE)

Published in:
https://www.preprints.org/manuscript/202003.0138/v1

Summary

Background: In 80% of patients, COVID-19 presents as mild disease. 20% of cases develop severe (13%) or critical (6%) illness. More severe forms of COVID-19 present as clinical severe acute respiratory syndrome, but include a T-predominant lymphopenia, high circulating levels of proinflammatory cytokines and chemokines, accumulation of neutrophils and macrophages in lungs, and immune dysregulation including immunosuppression. Methods: All major SARS-CoV-2 proteins were characterized using an amino acid residue variation analysis method. Results predict that most SARS-CoV-2 proteins are evolutionary constrained, with the exception of the spike (S) protein extended outer surface. Results were interpreted based on known SARS-like coronavirus virology and pathophysiology, with a focus on medical countermeasure development implications. Findings: Non-neutralizing antibodies to variable S domains may enable an alternative infection pathway via Fc receptor-mediated uptake. This may be a gating event for the immune response dysregulation observed in more severe COVID-19 disease. Prior studies involving vaccine candidates for FCoV SARS-CoV-1 and Middle East Respiratory Syndrome coronavirus (MERS-CoV) demonstrate vaccination-induced antibody-dependent enhancement of disease (ADE), including infection of phagocytic antigen presenting cells (APC). T effector cells are believed to play an important role in controlling coronavirus infection; pan-T depletion is present in severe COVID-19 disease and may be accelerated by APC infection. Sequence and structural conservation of S motifs suggests that SARS and MERS vaccine ADE risks may foreshadow SARS-CoV-2 S-based vaccine risks. Autophagy inhibitors may reduce APC infection and T-cell depletion. Amino acid residue variation analysis identifies multiple constrained domains suitable as T cell vaccine targets. Evolutionary constraints on proven antiviral drug targets present in SARS-CoV-1 and SARS-CoV-2 may reduce risk of developing antiviral drug escape mutants. Interpretation: Safety testing of COVID-19 S protein-based B cell vaccines in animal models is strongly encouraged prior to clinical trials to reduce risk of ADE upon virus exposure.
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Summary

Background: In 80% of patients, COVID-19 presents as mild disease. 20% of cases develop severe (13%) or critical (6%) illness. More severe forms of COVID-19 present as clinical severe acute respiratory syndrome, but include a T-predominant lymphopenia, high circulating levels of proinflammatory cytokines and chemokines, accumulation of neutrophils and macrophages...

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The Human Trafficking Technology Roadmap: a targeted development strategy for the Department of Homeland Security

Summary

Human trafficking is a form of modern-day slavery that involves the use of force, fraud, or coercion for the purposes of involuntary labor and sexual exploitation. It affects tens of million of victims worldwide and generates tens of billions of dollars in illicit profits annually. While agencies across the U.S. Government employ a diverse range of resources to combat human trafficking in the U.S. and abroad, trafficking operations remain challenging to measure, investigate, and interdict. Within the Department of Homeland Security, the Science and Technology Directorate is addressing these challenges by incorporating computational social science research into their counter-human trafficking approach. As part of this approach, the Directorate tasked an interdisciplinary team of national security researchers at the Massachusetts Institute of Technology's Lincoln Laboratory, a federally funded research and development center, to undertake a detailed examination of the human trafficking response across the Homeland Security Enterprise. The first phase of this effort was a government-wide systems analysis of major counter-trafficking thrust areas, including law enforcement and prosecution; public health and emergency medicine; victim services; and policy and legislation. The second phase built on this systems analysis to develop a human trafficking technology roadmap and implementation strategy for the Science and Technology Directorate, which is presented in this document.
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Summary

Human trafficking is a form of modern-day slavery that involves the use of force, fraud, or coercion for the purposes of involuntary labor and sexual exploitation. It affects tens of million of victims worldwide and generates tens of billions of dollars in illicit profits annually. While agencies across the U.S...

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Detection and characterization of human trafficking networks using unsupervised scalable text template matching

Summary

Human trafficking is a form of modern-day slavery affecting an estimated 40 million victims worldwide, primarily through the commercial sexual exploitation of women and children. In the last decade, the advertising of victims has moved from the streets to websites on the Internet, providing greater efficiency and anonymity for sex traffickers. This shift has allowed traffickers to list their victims in multiple geographic areas simultaneously, while also improving operational security by using multiple methods of electronic communication with buyers; complicating the ability of law enforcement to disrupt these illicit organizations. In this paper, we address this issue and present a novel unsupervised and scalable template matching algorithm for analyzing and detecting complex organizations operating on adult service websites. The algorithm uses only the advertisement content to uncover signature patterns in text that are indicative of organized activities and organizational structure. We apply this method to a large corpus of adult service advertisements retrieved from backpage.com, and show that the networks identified through the algorithm match well with surrogate truth data derived from phone number networks in the same corpus. Further exploration of the results show that the proposed method provides deeper insights into the complex structures of sex trafficking organizations, not possible through networks derived from phone numbers alone. This method provides a powerful new capability for law enforcement to more completely identify and gather evidence about trafficking networks and their operations.
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Summary

Human trafficking is a form of modern-day slavery affecting an estimated 40 million victims worldwide, primarily through the commercial sexual exploitation of women and children. In the last decade, the advertising of victims has moved from the streets to websites on the Internet, providing greater efficiency and anonymity for sex...

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Large-scale Bayesian kinship analysis

Summary

Kinship prediction in forensics is limited to first degree relatives due to the small number of short tandem repeat loci characterized. The Genetic Chain Rule for Probabilistic Kinship Estimation can leverage large panels of single nucleotide polymorphisms (SNPs) or sets of sequence linked SNPs, called haploblocks, to estimate more distant relationships between individuals. This method uses allele frequencies and Markov Chain Monte Carlo methods to determine kinship probabilities. Allele frequencies are a crucial input to this method. Since these frequencies are estimated from finite populations and many alleles are rare, a Bayesian extension to the algorithm has been developed to determine credible intervals for kinship estimates as a function of the certainty in allele frequency estimates. Generation of sufficiently large samples to accurately estimate credible intervals can take significant computational resources. In this paper, we leverage hundreds of compute cores to generate large numbers of Dirichlet random samples for Bayesian kinship prediction. We show that it is possible to generate 2,097,152 random samples on 32,768 cores at a rate of 29.68 samples per second. The ability to generate extremely large number of samples enables the computation of more statistically significant results from a Bayesian approach to kinship analysis.
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Summary

Kinship prediction in forensics is limited to first degree relatives due to the small number of short tandem repeat loci characterized. The Genetic Chain Rule for Probabilistic Kinship Estimation can leverage large panels of single nucleotide polymorphisms (SNPs) or sets of sequence linked SNPs, called haploblocks, to estimate more distant...

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Detecting pathogen exposure during the non-symptomatic incubation period using physiological data

Summary

Early pathogen exposure detection allows better patient care and faster implementation of public health measures (patient isolation, contact tracing). Existing exposure detection most frequently relies on overt clinical symptoms, namely fever, during the infectious prodromal period. We have developed a robust machine learning based method to better detect asymptomatic states during the incubation period using subtle, sub-clinical physiological markers. Starting with highresolution physiological waveform data from non-human primate studies of viral (Ebola, Marburg, Lassa, and Nipah viruses) and bacterial (Y. pestis) exposure, we processed the data to reduce short-term variability and normalize diurnal variations, then provided these to a supervised random forest classification algorithm and post-classifier declaration logic step to reduce false alarms. In most subjects detection is achieved well before the onset of fever; subject cross-validation across exposure studies (varying viruses, exposure routes, animal species, and target dose) lead to 51h mean early detection (at 0.93 area under the receiver-operating characteristic curve [AUCROC]). Evaluating the algorithm against entirely independent datasets for Lassa, Nipah, and Y. pestis exposures un-used in algorithm training and development yields a mean 51h early warning time (at AUCROC=0.95). We discuss which physiological indicators are most informative for early detection and options for extending this capability to limited datasets such as those available from wearable, non-invasive, ECG-based sensors.
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Summary

Early pathogen exposure detection allows better patient care and faster implementation of public health measures (patient isolation, contact tracing). Existing exposure detection most frequently relies on overt clinical symptoms, namely fever, during the infectious prodromal period. We have developed a robust machine learning based method to better detect asymptomatic states...

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Cloud computing in tactical environments

Summary

Ground personnel at the tactical edge often lack data and analytics that would increase their effectiveness. To address this problem, this work investigates methods to deploy cloud computing capabilities in tactical environments. Our approach is to identify representative applications and to design a system that spans the software/hardware stack to support such applications while optimizing the use of scarce resources. This paper presents our high-level design and the results of initial experiments that indicate the validity of our approach.
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Summary

Ground personnel at the tactical edge often lack data and analytics that would increase their effectiveness. To address this problem, this work investigates methods to deploy cloud computing capabilities in tactical environments. Our approach is to identify representative applications and to design a system that spans the software/hardware stack to...

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A cloud-based brain connectivity analysis tool

Summary

With advances in high throughput brain imaging at the cellular and sub-cellular level, there is growing demand for platforms that can support high performance, large-scale brain data processing and analysis. In this paper, we present a novel pipeline that combines Accumulo, D4M, geohashing, and parallel programming to manage large-scale neuron connectivity graphs in a cloud environment. Our brain connectivity graph is represented using vertices (fiber start/end nodes), edges (fiber tracks), and the 3D coordinates of the fiber tracks. For optimal performance, we take the hybrid approach of storing vertices and edges in Accumulo and saving the fiber track 3D coordinates in flat files. Accumulo database operations offer low latency on sparse queries while flat files offer high throughput for storing, querying, and analyzing bulk data. We evaluated our pipeline by using 250 gigabytes of mouse neuron connectivity data. Benchmarking experiments on retrieving vertices and edges from Accumulo demonstrate that we can achieve 1-2 orders of magnitude speedup in retrieval time when compared to the same operation from traditional flat files. The implementation of graph analytics such as Breadth First Search using Accumulo and D4M offers consistent good performance regardless of data size and density, thus is scalable to very large dataset. Indexing of neuron subvolumes is simple and logical with geohashing-based binary tree encoding. This hybrid data management backend is used to drive an interactive web-based 3D graphical user interface, where users can examine the 3D connectivity map in a Google Map-like viewer. Our pipeline is scalable and extensible to other data modalities.
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Summary

With advances in high throughput brain imaging at the cellular and sub-cellular level, there is growing demand for platforms that can support high performance, large-scale brain data processing and analysis. In this paper, we present a novel pipeline that combines Accumulo, D4M, geohashing, and parallel programming to manage large-scale neuron...

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