Visualizing the Feature Importance for Black Box Models

In recent years, a large amount of model-agnostic methods to improve the transparency, trustability and interpretability of machine learning models have been developed. We introduce local feature importance as a local version of a recent model-agnostic global feature importance method. Based on local feature importance, we propose two visual tools: partial importance (PI) and individual conditional importance (ICI) plots which visualize how changes in a feature affect the model performance on average, as well as for individual observations. Our proposed methods are related to partial dependence (PD) and individual conditional expectation (ICE) plots, but visualize the expected (conditional) feature importance instead of the expected (conditional) prediction. Furthermore, we show that averaging ICI curves across observations yields a PI curve, and integrating the PI curve with respect to the distribution of the considered feature results in the global feature importance. Another contribution of our paper is the Shapley feature importance, which fairly distributes the overall performance of a model among the features according to the marginal contributions and which can be used to compare the feature importance across different models.Comment: To Appear in Machine Learning and Knowledge Discovery in Databases: European Conference, ECML PKDD 2018, Dublin, Ireland, September 10 to 14, 2018, Proceedings, Part

Regulation of Anthrax Toxin-Specific Antibody Titers by Natural Killer T Cell-Derived IL-4 and IFNγ

Activation of Natural Killer-like T cells (NKT) with the CD1d ligand α-GC leads to enhanced production of anthrax toxin protective Ag (PA)-neutralizing Abs, yet the underlying mechanism for this adjuvant effect is not known. In the current study we examined the role of Th1 and Th2 type responses in NKT-mediated enhancement of antibody responses to PA. First, the contribution of IL-4 and IFNγ to the production of PA-specific toxin-neutralizing Abs was examined. By immunizing C57Bl/6 controls IL-4−/− mice and IFNγ−/− mice and performing passive serum transfer experiments, it was observed that sera containing PA-specific IgG1, IgG2b and IgG2c neutralized toxin in vitro and conferred protection in vivo. Sera containing IgG2b and IgG2c neutralized toxin in vitro but were not sufficient for protection in vivo. Sera containing IgG1 and IgG2b neutralized toxin in vitro and conferred protection in vivo. IgG1 therefore emerged as a good correlate of protection. Next, C57Bl/6 mice were immunized with PA alone or PA plus a Th2-skewing α-GC derivative known as OCH. Neutralizing PA-specific IgG1 responses were modestly enhanced by OCH in C57Bl/6 mice. Conversely, IgG2b and IgG2c were considerably enhanced in PA/OCH-immunized IL-4−/− mice but did not confer protection. Finally, bone marrow chimeras were generated such that NKT cells were unable to express IL-4 or IFNγ. NKT-derived IL-4 was required for OCH-enhanced primary IgG1 responses but not recall responses. NKT-derived IL-4 and IFNγ also influenced primary and recall IgG2b and IgG2c titers. These data suggest targeted skewing of the Th2 response by α-GC derivatives can be exploited to optimize anthrax vaccination

Quantum phase transitions of light

Recently, condensed matter and atomic experiments have reached a length-scale and temperature regime where new quantum collective phenomena emerge. Finding such physics in systems of photons, however, is problematic, as photons typically do not interact with each other and can be created or destroyed at will. Here, we introduce a physical system of photons that exhibits strongly correlated dynamics on a meso-scale. By adding photons to a two-dimensional array of coupled optical cavities each containing a single two-level atom in the photon-blockade regime, we form dressed states, or polaritons, that are both long-lived and strongly interacting. Our zero temperature results predict that this photonic system will undergo a characteristic Mott insulator (excitations localised on each site) to superfluid (excitations delocalised across the lattice) quantum phase transition. Each cavity's impressive photon out-coupling potential may lead to actual devices based on these quantum many-body effects, as well as observable, tunable quantum simulators. We explicitly show that such phenomena may be observable in micro-machined diamond containing nitrogen-vacancy colour centres and superconducting microwave strip-line resonators.Comment: 11 pages, 5 figures (2 in colour

Role of the mesoamygdaloid dopamine projection in emotional learning

Amygdala dopamine is crucially involved in the acquisition of Pavlovian associations, as measured via conditioned approach to the location of the unconditioned stimulus (US). However, learning begins before skeletomotor output, so this study assessed whether amygdala dopamine is also involved in earlier 'emotional' learning. A variant of the conditioned reinforcement (CR) procedure was validated where training was restricted to curtail the development of selective conditioned approach to the US location, and effects of amygdala dopamine manipulations before training or later CR testing assessed. Experiment 1a presented a light paired (CS+ group) or unpaired (CS- group) with a US. There were 1, 2 or 10 sessions, 4 trials per session. Then, the US was removed, and two novel levers presented. One lever (CR+) presented the light, and lever pressing was recorded. Experiment 1b also included a tone stimulus. Experiment 2 applied intra-amygdala R(+) 7-OH-DPAT (10 nmol/1.0 A mu l/side) before two training sessions (Experiment 2a) or a CR session (Experiment 2b). For Experiments 1a and 1b, the CS+ group preferred the CR+ lever across all sessions. Conditioned alcove approach during 1 or 2 training sessions or associated CR tests was low and nonspecific. In Experiment 2a, R(+) 7-OH-DPAT before training greatly diminished lever pressing during a subsequent CR test, preferentially on the CR+ lever. For Experiment 2b, R(+) 7-OH-DPAT infusions before the CR test also reduced lever pressing. Manipulations of amygdala dopamine impact the earliest stage of learning in which emotional reactions may be most prevalent

Incidental Thyroid Carcinoma by FDG-PET/CT: A Study of Clinicopathological Characteristics

BACKGROUND: The rising incidence of incidental thyroid carcinoma (ITC) detected during fluoro-2-deoxy-D: -glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) scanning poses a challenge to clinicians. The present study aims to critically evaluate the clinicopathological characteristics of ITC detected by FDG-PET/CT. METHODS: Among the 557 patients managed at our institution, 40 (7.2%) patients were identified as having ITC. Of these, 22 patients had their tumor detected by FDG-PET/CT (PET group) and 11 by ultrasonography (USG group). Additional bedside ultrasonography +/- fine-needle aspiration (FNA) was done in all patients at their clinic visit. The clinicopathological characteristics were compared between the PET and USG groups. RESULTS: The PET group had significantly more patients with history of nonthyroidal malignancy (P < 0.001). Papillary carcinoma was the most common histological type in both groups. Despite having similar histological and prognostic features including tumor size, tumor multifocality, capsular invasion, extrathyroidal extension, and lymph node metastases, tumor bilaterality (or presence of contralateral tumor focus) was significantly more frequent in the PET than the USG group (P = 0.04). The tumors were also more advanced by the tumor-node-metastasis (TNM) staging system in the PET group (P = 0.021). None of the contralateral tumor foci were evident preoperatively. One patient in the USG group developed metastatic thyroid carcinoma in neck lymph nodes 28 months after thyroid resection. CONCLUSION: ITC by FDG-PET/CT had higher incidence of tumor bilaterality than those detected by ultrasonography. Total thyroidectomy should be considered for ITC detected by FDG-PET/CT even for tumor size <10 mm.published_or_final_versionSpringer Open Choice, 31 May 201

IUPAC specification for the FAIR management of spectroscopic data in chemistry (IUPAC FAIRSpec) - guiding principles

set of guiding principles for the development of a standard for FAIR management of spectroscopic data are outlined and discussed. The principles form the basis for future recommendations of IUPAC Project 2019-031-1-024 specifying a detailed data model and metadata schema for describing the contents of an “IUPAC FAIRData Collection” and the organization of digital objects within that collection. Foremost among the recommendations will be a specification for an “IUPAC FAIRData Finding Aid” that describes the collection in such a way as to optimize the findability, accessibility, interoperability, and reusability of its contents. Results of an analysis of data provided by an American Chemical Society Publications pilot study are discussed in relation to potential workflows that might be used in implementing the “IUPAC FAIRSpec” standard based on these principles

Transmission Shifts Underlie Variability in Population Responses to Yersinia pestis Infection

Host populations for the plague bacterium, Yersinia pestis, are highly variable in their response to plague ranging from near deterministic extinction (i.e., epizootic dynamics) to a low probability of extinction despite persistent infection (i.e., enzootic dynamics). Much of the work to understand this variability has focused on specific host characteristics, such as population size and resistance, and their role in determining plague dynamics. Here, however, we advance the idea that the relative importance of alternative transmission routes may vary causing shifts from epizootic to enzootic dynamics. We present a model that incorporates host and flea ecology with multiple transmission hypotheses to study how transmission shifts determine population responses to plague. Our results suggest enzootic persistence relies on infection of an off-host flea reservoir and epizootics rely on transiently maintained flea infection loads through repeated infectious feeds by fleas. In either case, early-phase transmission by fleas (i.e., transmission immediately following an infected blood meal) has been observed in laboratory studies, and we show that it is capable of driving plague dynamics at the population level. Sensitivity analysis of model parameters revealed that host characteristics (e.g., population size and resistance) vary in importance depending on transmission dynamics, suggesting that host ecology may scale differently through different transmission routes enabling prediction of population responses in a more robust way than using either host characteristics or transmission shifts alone