Conducting Efficient Remote Science and Planning Operations for Ocean Exploration Using Exploration Ground Data Systems (xGDS)

NASA Ames Exploration Ground Data Systems (xGDS) supports rapid scientific decision making by synchronizing information in time and space, including video and still images, scientific instrument data, and science and operations notes in geographic and temporal context. We have deployed xGDS at multiple NASA field analog missions over the past decade. In the last two years, we have participated in SUBSEA, a multi-institution collaborative project*. SUBSEA used the research ship E/V Nautilus along with its two remotely operated vehicles (ROVs), Hercules and Argus, to explore deep ocean volcanic vents as an analog for ocean worlds (e.g. Enceladus). This work allowed us to compare the existing oceanographic operations methods and technologies used for ocean exploration with corresponding tools and approaches developed and used at NASA. In the first year of SUBSEA we observed existing remote science operations from the Inner Space Center (ISC)**. In the second year, we deployed xGDS at ISC to complement existing capabilities with xGDS tools designed to support remote Nautilus science operations from the ISC. During operations, video, ROV position and instrument telemetry were streamed from the ship to the ISC. As the science team watched dive operations, they could annotate the data with observations that were relevant to their work domain. Later, the team members could review the data at their own pace to collaboratively develop a dive plan for the next day, which had to be delivered on a fixed daily schedule. The opportunity to compare operations under different conditions enabled us to make several key observations about conducting remote science and planning operations efficiently: (i) Reviewing data collaboratively and interactively with temporal and spatial context was critical for the remote science teams ability to plan dive operations on the Nautilus. (ii) Science team members were actively engaged with the remote dive operations because they could interact with the collected data and visualize it as they desired. (iii) Being able to replay past events at accelerated speeds, and jump to points in time and spaced based on search results, provided efficient access to critical points of interest in a massive volume of data, so the remote science team could deliver plans on time. * SUBSEA (Systematic Underwater Biogeochemical Science and Exploration Analog) is a multi-institution collaboration supported by NASA, NOAAs Office of Exploration Research (OER), the Ocean Exploration Trust (OET) and the University of Rhode Islands Graduate School of Oceanography (GSO)

Radiocarbon dating and cultural dynamics across Mongolia’s early pastoral transition

All necessary permits were obtained for the described study, which complied with all relevant regulations. Collaboration contract between the Max Planck Institute for the Science of Human HIstory and the National University of Mongolia began on the 10th November, 2016. Export number 10/413 (7b/52) was received on the 2nd Feb, 2017 (#A0109258, MN DE 7 643). This research was supported by the Max Planck Institute for the Science of Human History. Special thanks to Dr. Katerina Douka and the Oxford Radiocarbon Accelerator Laboratory for conducting 14C analysis, and to all of the original excavators and authors who published the radiocarbon dates cited in this study.Peer reviewedPublisher PD

Atlas of group A streptococcal vaccine candidates compiled using large-scale comparative genomics.

Group A Streptococcus (GAS; Streptococcus pyogenes) is a bacterial pathogen for which a commercial vaccine for humans is not available. Employing the advantages of high-throughput DNA sequencing technology to vaccine design, we have analyzed 2,083 globally sampled GAS genomes. The global GAS population structure reveals extensive genomic heterogeneity driven by homologous recombination and overlaid with high levels of accessory gene plasticity. We identified the existence of more than 290 clinically associated genomic phylogroups across 22 countries, highlighting challenges in designing vaccines of global utility. To determine vaccine candidate coverage, we investigated all of the previously described GAS candidate antigens for gene carriage and gene sequence heterogeneity. Only 15 of 28 vaccine antigen candidates were found to have both low naturally occurring sequence variation and high (>99%) coverage across this diverse GAS population. This technological platform for vaccine coverage determination is equally applicable to prospective GAS vaccine antigens identified in future studies

Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by heterozygous point mutations or genomic deletion copy-number variants (CNVs) of FOXF1 or its upstream enhancer involving fetal lung-expressed long noncoding RNA genes LINC01081 and LINC01082. Using custom-designed array comparative genomic hybridization, Sanger sequencing, whole exome sequencing (WES), and bioinformatic analyses, we studied 22 new unrelated families (20 postnatal and two prenatal) with clinically diagnosed ACDMPV. We describe novel deletion CNVs at the FOXF1 locus in 13 unrelated ACDMPV patients. Together with the previously reported cases, all 31 genomic deletions in 16q24.1, pathogenic for ACDMPV, for which parental origin was determined, arose de novo with 30 of them occurring on the maternally inherited chromosome 16, strongly implicating genomic imprinting of the FOXF1 locus in human lungs. Surprisingly, we have also identified four ACDMPV families with the pathogenic variants in the FOXF1 locus that arose on paternal chromosome 16. Interestingly, a combination of the severe cardiac defects, including hypoplastic left heart, and single umbilical artery were observed only in children with deletion CNVs involving FOXF1 and its upstream enhancer. Our data demonstrate that genomic imprinting at 16q24.1 plays an important role in variable ACDMPV manifestation likely through long-range regulation of FOXF1 expression, and may be also responsible for key phenotypic features of maternal uniparental disomy 16. Moreover, in one family, WES revealed a de novo missense variant in ESRP1, potentially implicating FGF signaling in the etiology of ACDMPV

The Public Repository of Xenografts enables discovery and randomized phase II-like trials in mice

More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional, and proteomic biomarkers in both treatment-naive and relapsed/refractory disease

A protein-truncating R179X variant in RNF186 confers protection against ulcerative colitis

Protein-truncating variants protective against human disease provide in vivo validation of therapeutic targets. Here we used targeted sequencing to conduct a search for protein-truncating variants conferring protection against inflammatory bowel disease exploiting knowledge of common variants associated with the same disease. Through replication genotyping and imputation we found that a predicted protein-truncating variant (rs36095412, p.R179X, genotyped in 11,148 ulcerative colitis patients and 295,446 controls, MAF = up to 0.78%) in RNF186, a single-exon ring finger E3 ligase with strong colonic expression, protects against ulcerative colitis (overall P = 6.89 x 10(-7), odds ratio = 0.30). We further demonstrate that the truncated protein exhibits reduced expression and altered subcellular localization, suggesting the protective mechanism may reside in the loss of an interaction or function via mislocalization and/or loss of an essential transmembrane domain.Peer reviewe

Geographical migration and fitness dynamics of Streptococcus pneumoniae

Streptococcus pneumoniae is a leading cause of pneumonia and meningitis worldwide. Many different serotypes co-circulate endemically in any one location1,2. The extent and mechanisms of spread and vaccine-driven changes in fitness and antimicrobial resistance remain largely unquantified. Here using geolocated genome sequences from South Africa (n = 6,910, collected from 2000 to 2014), we developed models to reconstruct spread, pairing detailed human mobility data and genomic data. Separately, we estimated the population-level changes in fitness of strains that are included (vaccine type (VT)) and not included (non-vaccine type (NVT)) in pneumococcal conjugate vaccines, first implemented in South Africa in 2009. Differences in strain fitness between those that are and are not resistant to penicillin were also evaluated. We found that pneumococci only become homogenously mixed across South Africa after 50 years of transmission, with the slow spread driven by the focal nature of human mobility. Furthermore, in the years following vaccine implementation, the relative fitness of NVT compared with VT strains increased (relative risk of 1.68; 95% confidence interval of 1.59–1.77), with an increasing proportion of these NVT strains becoming resistant to penicillin. Our findings point to highly entrenched, slow transmission and indicate that initial vaccine-linked decreases in antimicrobial resistance may be transient

Vocalisations with a better view : hyperarticulation augments the auditory-visual advantage for the detection of speech in noise

Recent studies have shown that there is a visual influence early in speech processing - visual speech enhances the ability to detect auditory speech in noise. However, identifying exactly how visual speech interacts with auditory processing at such an early stage has been challenging, because this so-called AV speech detection advantage is both highly related to a specific lower-order, signal-based, optic-acoustic relationship between the second formant amplitude and the area of the mouth (F2/Mouth-area), and mediated by higher-order, information-based factors. Previous investigations either have maximised or minimised information-based factors, or have minimised signal-based factors, in order to try to tease out the relative importance of these sources of the advantage, but they have not yet been successful in this endeavour. Maximising signal-based factors has not previously been explored. This avenue was explored in this thesis by manipulating speaking style, hyperarticulated speech was used to maximise signal-based factors, and hypoarticulated speech to minimise signal-based factors - to examine whether the AV speech detection advantage is modified by these means, and to provide a clearer idea of the primary source of visual influence in the AV detection advantage. Two sets of six studies were conducted. In the first set, three recorded speech styles, hyperarticulated, normal, and hypoarticulated, were extensively analysed in physical (optic and acoustic) and perceptual (visual and auditory) dimensions ahead of stimulus selection for the second set of studies. The analyses indicated that the three styles comprise distinctive categories on the Hyper-Hypo continuum of articulatory effort (Lindblom, 1990). Most relevantly, both optically and visually hyperarticulated speech was more informative, and hypoarticulated less informative, than normal speech with regard to signal-based movement factors. However, the F2/Mouth-area correlation was similarly strong for all speaking styles, thus allowing examination of signal-based, visual informativeness on AV speech detection with optic-acoustic association controlled. In the second set of studies, six Detection Experiments incorporating the three speaking styles were designed to examine whether, and if so why, more visually-informative (hyperarticulated) speech augmented, and less visually informative (hypoarticulated) speech attenuated, the AV detection advantage relative to normal speech, and to examine visual influence when auditory speech was absent. Detection Experiment 1 used a two-interval, two-alternative (first or second interval, 2I2AFC) detection task, and indicated that hyperarticulation provided an AV detection advantage greater than for normal and hypoarticulated speech, with less of an advantage for hypoarticulated than for normal speech. Detection Experiment 2 used a single-interval, yes-no detection task to assess responses in signal-absent independent of signal-present conditions as a means of addressing participants’ reports that speech was heard when it was not presented in the 2I2AFC task. Hyperarticulation resulted in an AV detection advantage, and for all speaking styles there was a consistent response bias to indicate speech was present in signal-absent conditions. To examine whether the AV detection advantage for hyperarticulation was due to visual, auditory or auditory-visual factors, Detection Experiments 3 and 4 used mismatching AV speaking style combinations (AnormVhyper, AnormVhypo, AhyperVnorm, AhypoVnorm) that were onset-matched or time-aligned, respectively. The results indicated that higher rates of mouth movement can be sufficient for the detection advantage with weak optic-acoustic associations, but, in circumstances where these associations are low, even high rates of movement have little impact on augmenting detection in noise. Furthermore, in Detection Experiment 5, in which visual stimuli consisted only of the mouth movements extracted from the three styles, there was no AV detection advantage, and it seems that this is so because extra-oral information is required, perhaps to provide a frame of reference that improves the availability of mouth movement to the perceiver. Detection Experiment 6 used a new 2I-4AFC task and the measures of false detections and response bias to identify whether visual influence in signal absent conditions is due to response bias or an illusion of hearing speech in noise (termed here the Speech in Noise, SiN, Illusion). In the event, the SiN illusion occurred for both the hyperarticulated and the normal styles – styles with reasonable amounts of movement change. For normal speech, the responses in signal-absent conditions were due only to the illusion of hearing speech in noise, whereas for hypoarticulated speech such responses were due only to response bias. For hyperarticulated speech there is evidence for the presence of both types of visual influence in signal-absent conditions. It seems to be the case that there is more doubt with regard to the presence of auditory speech for non-normal speech styles. An explanation of past and present results is offered within a new framework -the Dynamic Bimodal Accumulation Theory (DBAT). This is developed in this thesis to address the limitations of, and conflicts between, previous theoretical positions. DBAT suggests a bottom-up influence of visual speech on the processing of auditory speech; specifically, it is proposed that the rate of change of visual movements guides auditory attention rhythms ‘on-line’ at corresponding rates, which allows selected samples of the auditory stream to be given prominence. Any patterns contained within these samples then emerge from the course of auditory integration processes. By this account, there are three important elements of visual speech necessary for enhanced detection of speech in noise. First and foremost, when speech is present, visual movement information must be available (as opposed to hypoarticulated and synthetic speech) Then the rate of change, and opticacoustic relatedness also have an impact (as in Detection Experiments 3 and 4). When speech is absent, visual information has an influence; and the SiN illusion (Detection Experiment 6) can be explained as a perceptual modulation of a noise stimulus by visually-driven rhythmic attention. In sum, hyperarticulation augments the AV speech detection advantage, and, whenever speech is perceived in noisy conditions, there is either response bias to perceive speech or a SiN illusion, or both. DBAT provides a detailed description of these results, with wider-ranging explanatory power than previous theoretical accounts. Predictions are put forward for examination of the predictive power of DBAT in future studies

On-line experimental methods to evaluate text-to-speech (TTS) synthesis : effects of voice gender and signal quality on intelligibility, naturalness and preference

Three experiments are reported that use new experimental methods for the evaluation of text-to-speech (TTS) synthesis from the user's perspective. Experiment 1, using sentence stimuli, and Experiment 2, using discrete “call centre” word stimuli, investigated the effect of voice gender and signal quality on the intelligibility of three concatenative TTS synthesis systems. Accuracy and search time were recorded as on-line, implicit indices of intelligibility during phoneme detection tasks. It was found that both voice gender and noise affect intelligibility. Results also indicate interactions of voice gender, signal quality, and TTS synthesis system on accuracy and search time. In Experiment 3 the method of paired comparisons was used to yield ranks of naturalness and preference. As hypothesized, preference and naturalness ranks were influenced by TTS system, signal quality and voice, in isolation and in combination. The pattern of results across the four dependent variables – accuracy, search time, naturalness, preference – was consistent. Natural speech surpassed synthetic speech, and TTS system C elicited relatively high scores across all measures. Intelligibility, judged naturalness and preference are modulated by several factors and there is a need to tailor systems to particular commercial applications and environmental conditions