DeepGauge: Multi-Granularity Testing Criteria for Deep Learning Systems

Deep learning (DL) defines a new data-driven programming paradigm that constructs the internal system logic of a crafted neuron network through a set of training data. We have seen wide adoption of DL in many safety-critical scenarios. However, a plethora of studies have shown that the state-of-the-art DL systems suffer from various vulnerabilities which can lead to severe consequences when applied to real-world applications. Currently, the testing adequacy of a DL system is usually measured by the accuracy of test data. Considering the limitation of accessible high quality test data, good accuracy performance on test data can hardly provide confidence to the testing adequacy and generality of DL systems. Unlike traditional software systems that have clear and controllable logic and functionality, the lack of interpretability in a DL system makes system analysis and defect detection difficult, which could potentially hinder its real-world deployment. In this paper, we propose DeepGauge, a set of multi-granularity testing criteria for DL systems, which aims at rendering a multi-faceted portrayal of the testbed. The in-depth evaluation of our proposed testing criteria is demonstrated on two well-known datasets, five DL systems, and with four state-of-the-art adversarial attack techniques against DL. The potential usefulness of DeepGauge sheds light on the construction of more generic and robust DL systems.Comment: The 33rd IEEE/ACM International Conference on Automated Software Engineering (ASE 2018

The Comet Interceptor Mission

Here we describe the novel, multi-point Comet Interceptor mission. It is dedicated to the exploration of a little-processed long-period comet, possibly entering the inner Solar System for the first time, or to encounter an interstellar object originating at another star. The objectives of the mission are to address the following questions: What are the surface composition, shape, morphology, and structure of the target object? What is the composition of the gas and dust in the coma, its connection to the nucleus, and the nature of its interaction with the solar wind? The mission was proposed to the European Space Agency in 2018, and formally adopted by the agency in June 2022, for launch in 2029 together with the Ariel mission. Comet Interceptor will take advantage of the opportunity presented by ESA's F-Class call for fast, flexible, low-cost missions to which it was proposed. The call required a launch to a halo orbit around the Sun-Earth L2 point. The mission can take advantage of this placement to wait for the discovery of a suitable comet reachable with its minimum Delta V capability of 600 ms(-1). Comet Interceptor will be unique in encountering and studying, at a nominal closest approach distance of 1000 km, a comet that represents a near-pristine sample of material from the formation of the Solar System. It will also add a capability that no previous cometary mission has had, which is to deploy two sub-probes - B1, provided by the Japanese space agency, JAXA, and B2 - that will follow different trajectories through the coma. While the main probe passes at a nominal 1000 km distance, probes B1 and B2 will follow different chords through the coma at distances of 850 km and 400 km, respectively. The result will be unique, simultaneous, spatially resolved information of the 3-dimensional properties of the target comet and its interaction with the space environment. We present the mission's science background leading to these objectives, as well as an overview of the scientific instruments, mission design, and schedule

Probing the Circumgalactic Medium at High-Redshift Using Composite BOSS Spectra of Strong Lyman-alpha Forest Absorbers

We present composite spectra constructed from a sample of 242,150 Lyman-alpha (Lya) forest absorbers at redshifts 2.4<z<3.1 identified in quasar spectra from the Baryon Oscillation Spectroscopic Survey (BOSS) as part of Data Release 9 of the Sloan Digital Sky Survey III. We select forest absorbers by their flux in bins 138 km/s wide (approximately the size of the BOSS resolution element). We split these absorbers into five samples spanning the range of flux -0.05 < F<0.45. Tests on a smaller sample of high-resolution spectra show that our three strongest absorption bins would probe circumgalactic regions (projected separation < 300 proper kpc and |Delta v| < 300km/s) in about 60% of cases for very high signal-to-noise ratio. Within this subset, weakening Lya absorption is associated with decreasing purity of circumgalactic selection once BOSS noise is included. Our weaker two Lya absorption samples are dominated by the intergalactic medium. We present composite spectra of these samples and a catalogue of measured absorption features from HI and 13 metal ionization species, all of which we make available to the community. We compare measurements of seven Lyman series transitions in our composite spectra to single line models and obtain further constraints from their associated excess Lyman limit opacity. This analysis provides results consistent with column densities over the range 14.4 <~ Log (N_HI) <~ 16.45. We compare our measurements of metal absorption to a variety of simple single-line, single-phase models for a preliminary interpretation. Our results imply clumping on scales down to ~30 pc and near-solar metallicities in the circumgalactic samples, while high-ionization metal absorption consistent with typical IGM densities and metallicities is visible in all samples.Comment: 23 pages, 15 figures, 5 tables, link to downloadable data included. Accepted by MNRAS 2014 March 20. New sections 3.4 and 6.1 limiting the occurrence and impact of Lyman limit system

hSSB1 (NABP2/OBFC2B) is regulated by oxidative stress

The maintenance of genome stability is an essential cellular process to prevent the development of diseases including cancer. hSSB1 (NABP2/ OBFC2A) is a critical component of the DNA damage response where it participates in the repair of double-strand DNA breaks and in base excision repair of oxidized guanine residues (8-oxoguanine) by aiding the localization of the human 8-oxoguanine glycosylase (hOGG1) to damaged DNA. Here we demonstrate that following oxidative stress, hSSB1 is stabilized as an oligomer which is required for hSSB1 to function in the removal of 8-oxoguanine. Monomeric hSSB1 shows a decreased affinity for oxidized DNA resulting in a cellular 8-oxoguanine-repair defect and in the absence of ATM signaling initiation. While hSSB1 oligomerization is important for the removal of 8-oxoguanine from the genome, it is not required for the repair of double-strand DNA-breaks by homologous recombination. These findings demonstrate a novel hSSB1 regulatory mechanism for the repair of damaged DNA.Publisher PDFPeer reviewe

An integrated multicomponent care model for men affected by prostate cancer: A feasibility study of TrueNTH Australia

Objective: To evaluate the feasibility of implementing an integrated multicomponent survivorship care model for men affected by prostate cancer. Methods: Using a single arm prospective cohort study design, men with prostate cancer were recruited from two regional public hospitals in Australia for a 6-months program that provided information and decision support, exercise and nutrition management, specialised clinical support, and practical support through localised and central care coordination. Carers of the men were also invited to the program. Data were collected from multiple sources to evaluate: (1) recruitment capability and participant characteristics; (2) appropriateness and feasibility of delivering the specific intervention components using an electronic care management tool; and (3) suitability of data collection procedures and proposed outcome measures. Results: Of the 105 eligible men, 51 (consent rate 49%) participated in the program. Of the 31 carers nominated by the men, 13 consented (consent rate 42%). All carers and 50 (98%) men completed the program. Most (92%) men were newly diagnosed with localised prostate cancer. All men attended initial screening and assessment for supportive care needs; a total of 838 episodes of contact/consultation were made by the intervention team either in person (9%) or remotely (91%). The intervention was implemented as proposed with no adverse events. The proposed outcome measures and evaluation procedures were found to be appropriate. Conclusions: Our results support the feasibility of implementing this integrated multicomponent care model for men affected by prostate cancer

Clinical, radiologic, pathologic, and molecular characteristics of long-term survivors of diffuse intrinsic pontine glioma (DIPG): a collaborative report from the International and European Society for Pediatric Oncology DIPG registries

Purpose Diffuse intrinsic pontine glioma (DIPG) is a brainstem malignancy with a median survival of &lt; 1 year. The International and European Society for Pediatric Oncology DIPG Registries collaborated to compare clinical, radiologic, and histomolecular characteristics between short-term survivors (STSs) and long-term survivors (LTSs). Materials and Methods Data abstracted from registry databases included patients from North America, Australia, Germany, Austria, Switzerland, the Netherlands, Italy, France, the United Kingdom, and Croatia. Results Among 1,130 pediatric and young adults with radiographically confirmed DIPG, 122 (11%) were excluded. Of the 1,008 remaining patients, 101 (10%) were LTSs (survival ≥ 2 years). Median survival time was 11 months (interquartile range, 7.5 to 16 months), and 1-, 2-, 3-, 4-, and 5-year survival rates were 42.3% (95% CI, 38.1% to 44.1%), 9.6% (95% CI, 7.8% to 11.3%), 4.3% (95% CI, 3.2% to 5.8%), 3.2% (95% CI, 2.4% to 4.6%), and 2.2% (95% CI, 1.4% to 3.4%), respectively. LTSs, compared with STSs, more commonly presented at age &lt; 3 or &gt; 10 years (11% v 3% and 33% v 23%, respectively; P &lt; .001) and with longer symptom duration ( P &lt; .001). STSs, compared with LTSs, more commonly presented with cranial nerve palsy (83% v 73%, respectively; P = .008), ring enhancement (38% v 23%, respectively; P = .007), necrosis (42% v 26%, respectively; P = .009), and extrapontine extension (92% v 86%, respectively; P = .04). LTSs more commonly received systemic therapy at diagnosis (88% v 75% for STSs; P = .005). Biopsies and autopsies were performed in 299 patients (30%) and 77 patients (10%), respectively; 181 tumors (48%) were molecularly characterized. LTSs were more likely to harbor a HIST1H3B mutation (odds ratio, 1.28; 95% CI, 1.1 to 1.5; P = .002). Conclusion We report clinical, radiologic, and molecular factors that correlate with survival in children and young adults with DIPG, which are important for risk stratification in future clinical trials

Complex exon-intron marking by histone modifications is not determined solely by nucleosome distribution

It has recently been shown that nucleosome distribution, histone modifications and RNA polymerase II (Pol II) occupancy show preferential association with exons (“exon-intron marking”), linking chromatin structure and function to co-transcriptional splicing in a variety of eukaryotes. Previous ChIP-sequencing studies suggested that these marking patterns reflect the nucleosomal landscape. By analyzing ChIP-chip datasets across the human genome in three cell types, we have found that this marking system is far more complex than previously observed. We show here that a range of histone modifications and Pol II are preferentially associated with exons. However, there is noticeable cell-type specificity in the degree of exon marking by histone modifications and, surprisingly, this is also reflected in some histone modifications patterns showing biases towards introns. Exon-intron marking is laid down in the absence of transcription on silent genes, with some marking biases changing or becoming reversed for genes expressed at different levels. Furthermore, the relationship of this marking system with splicing is not simple, with only some histone modifications reflecting exon usage/inclusion, while others mirror patterns of exon exclusion. By examining nucleosomal distributions in all three cell types, we demonstrate that these histone modification patterns cannot solely be accounted for by differences in nucleosome levels between exons and introns. In addition, because of inherent differences between ChIP-chip array and ChIP-sequencing approaches, these platforms report different nucleosome distribution patterns across the human genome. Our findings confound existing views and point to active cellular mechanisms which dynamically regulate histone modification levels and account for exon-intron marking. We believe that these histone modification patterns provide links between chromatin accessibility, Pol II movement and co-transcriptional splicing

An assessment of particulate organic carbon to thorium-234 ratios in the ocean and their impact on the application of 234Th as a POC flux proxy

Author Posting. © The Authors, 2006. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Marine Chemistry 100 (2006): 213-233, doi:10.1016/j.marchem.2005.10.013.Thorium-234 is increasingly used as a tracer of ocean particle flux, primarily as a means to estimate particulate organic carbon export from the surface ocean. This requires determination of both the 234Th activity distribution (in order to calculate 234Th fluxes) and an estimate of the C/234Th ratio on sinking particles, to empirically derive C fluxes. In reviewing C/234Th variability, results obtained using a single sampling method show the most predictable behavior. For example, in most studies that employ in situ pumps to collect size fractionated particles, C/234Th either increases or is relatively invariant with increasing particle size (size classes >1 to 100’s μm). Observations also suggest that C/234Th decreases with depth and can vary significantly between regions (highest in blooms of large diatoms and highly productive coastal settings). Comparisons of C fluxes derived from 234Th show good agreement with independent estimates of C flux, including mass balances of C and nutrients over appropriate space and time scales (within factors of 2-3). We recommend sampling for C/234Th from a standard depth of 100 m, or at least one depth below the mixed layer using either large volume size fractionated filtration to capture the rarer large particles, or a sediment trap or other device to collect sinking particles. We also recommend collection of multiple 234Th profiles and C/234Th samples during the course of longer observation periods to better sample temporal variations in both 234Th flux and the characteristic of sinking particles. We are encouraged by new technologies which are optimized to more reliably sample truly settling particles, and expect the utility of this tracer to increase, not just for upper ocean C fluxes but for other elements and processes deeper in the water column.Individuals and science efforts discussed herein were supported by many national science programs, including the U.S. National Science Foundation and U.S. Department of Energy. S.F. and J.C.M. acknowledge the support provided to the International Atomic Energy Agency (IAEA) Marine Environment Laboratory by the Government of the Principality of Monaco. T.T. acknowledges support from the Australian Antarctic Science Program. K.B. was supported in part by a WHOI Ocean Life Institute Fellowship

A new valuation school: Integrating diverse values of nature in resource and land use decisions

We are increasingly confronted with severe social and economic impacts of environmental degradation all over the world. From a valuation perspective, environmental problems and conflicts originate from trade-offs between values. The urgency and importance to integrate nature\u27s diverse values in decisions and actions stand out more than ever. Valuation, in its broad sense of ‘assigning importance’, is inherently part of most decisions on natural resource and land use. Scholars from different traditions -while moving from heuristic interdisciplinary debate to applied transdisciplinary science- now acknowledge the need for combining multiple disciplines and methods to represent the diverse set of values of nature. This growing group of scientists and practitioners share the ambition to explore how combinations of ecological, socio-cultural and economic valuation tools can support real-life resource and land use decision-making. The current sustainability challenges and the ineffectiveness of single-value approaches to offer relief demonstrate that continuing along a single path is no option. We advocate for the adherence of a plural valuation culture and its establishment as a common practice, by contesting and complementing ineffective and discriminatory single-value approaches. In policy and decision contexts with a willingness to improve sustainability, integrated valuation approaches can be blended in existing processes, whereas in contexts of power asymmetries or environmental conflicts, integrated valuation can promote the inclusion of diverse values through action research and support the struggle for social and environmental justice. The special issue and this editorial synthesis paper bring together lessons from pioneer case studies and research papers, synthesizing main challenges and setting out priorities for the years to come for the field of integrated valuation

A new valuation school : Integrating diverse values of nature in resource and land use decisions

We are increasingly confronted with severe social and economic impacts of environmental degradation all over the world. From a valuation perspective, environmental problems and conflicts originate from trade-offs between values. The urgency and importance to integrate nature's diverse values in decisions and actions stand out more than ever. Valuation, in its broad sense of 'assigning importance', is inherently part of most decisions on natural resource and land use. Scholars from different traditions -while moving from heuristic interdisciplinary debate to applied transdisciplinary science- now acknowledge the need for combining multiple disciplines and methods to represent the diverse set of values of nature. This growing group of scientists and practitioners share the ambition to explore how combinations of ecological, socio-cultural and economic valuation tools can support real-life resource and land use decision-making. The current sustainability challenges and the ineffectiveness of single-value approaches to offer relief demonstrate that continuing along a single path is no option. We advocate for the adherence of a plural valuation culture and its establishment as a common practice, by contesting and complementing ineffective and discriminatory single-value approaches. In policy and decision contexts with a willingness to improve sustainability, integrated valuation approaches can be blended in existing processes, whereas in contexts of power asymmetries or environmental conflicts, integrated valuation can promote the inclusion of diverse values through action research and support the struggle for social and environmental justice. The special issue and this editorial synthesis paper bring together lessons from pioneer case studies and research papers, synthesizing main challenges and setting out priorities for the years to come for the field of integrated valuation.Peer reviewe