Learning Interpretable Models Through Multi-Objective Neural Architecture Search

Monumental advances in deep learning have led to unprecedented achievements across a multitude of domains. While the performance of deep neural networks is indubitable, the architectural design and interpretability of such models are nontrivial. Research has been introduced to automate the design of neural network architectures through neural architecture search (NAS). Recent progress has made these methods more pragmatic by exploiting distributed computation and novel optimization algorithms. However, there is little work in optimizing architectures for interpretability. To this end, we propose a multi-objective distributed NAS framework that optimizes for both task performance and introspection. We leverage the non-dominated sorting genetic algorithm (NSGA-II) and explainable AI (XAI) techniques to reward architectures that can be better comprehended by humans. The framework is evaluated on several image classification datasets. We demonstrate that jointly optimizing for introspection ability and task error leads to more disentangled architectures that perform within tolerable error.Comment: 14 pages main text, 5 pages references, 17 pages supplementa

Protein SUMOylation regulates insulin secretion at multiple stages

Type-II Diabetes Mellitus (T2DM) is one of the fastest growing public health issues of modern times, consuming 12% of worldwide health budgets and affecting an estimated 400 million people. A key pathological trait associated with this disease is the failure of normal glucose-stimulated insulin secretion (GSIS) from pancreatic beta cells. Several lines of evidence suggest that vesicle trafficking events such as insulin secretion are regulated by the post-translational modification, SUMOylation, and indeed SUMOylation has been proposed to act as a ‘brake’ on insulin exocytosis. Here, we show that diabetic stimuli which inhibit GSIS are correlated with an increase in cellular protein SUMOylation, and that inhibition of deSUMOylation reduces GSIS. We demonstrate that manipulation of cellular protein SUMOylation levels, by overexpression of several different components of the SUMOylation pathway, have varied and complex effects on GSIS, indicating that SUMOylation regulates this process at multiple stages. We further demonstrate that inhibition of syntaxin1A SUMOylation, via a knockdown-rescue strategy, greatly enhances GSIS. Our data are therefore consistent with the model that SUMOylation acts as a brake on GSIS, and we have identified SUMOylation of syntaxin 1A as a potential component of this brake. However, our data also demonstrates that the role of SUMOylation in GSIS is complex and may involve many substrates

Insulin-dependent GLUT4 trafficking is not regulated by protein SUMOylation in L6 myocytes

Type-II Diabetes Mellitus (T2DM) is one of the fastest growing public health issues today, consuming 12% of worldwide health budgets and affecting an estimated 400 million people. One of the key pathological traits of this disease is insulin resistance at ‘glucose sink’ tissues (mostly skeletal muscle), and this remains one of the features of this disease most intractable to therapeutic intervention. Several lines of evidence have implicated the post-translational modification,SUMOylation, in insulin signalling and insulin resistance in skeletal muscle. In this study, we examined this possibility by manipulation of cellular SUMOylation levels using multiple different tools, and assaying the effect on insulin-stimulated GLUT4 surface expression in differentiated L6 rat myocytes. Although insulin stimulation of L6 myocytes produced a robust decrease in total cellular SUMO1-ylation levels, manipulating cellular SUMOylation had no effect on insulin-responsive GLUT4 surface trafficking using any of the tools we employed. Whilst we cannot totally exclude the possibility that SUMOylation plays a role in the insulin signalling pathway in human health and disease, our data strongly argue that GLUT4 trafficking in response to insulin is not regulated by protein SUMOylation, and that SUMOylation does not therefore represent a viable therapeutic target for the treatment of insulin resistance

Evidence base for health and planning – lessons from an ESRC seminar series

The article looks at the lessons on the health and planning evidence base, evidence-sharing and integration that have been emerging from an ESRC seminar series on reuniting health and planning bringing together academics and planning and public health professionals

Urban planning as an enabler of urban health: Challenges and good practice in England following the 2012 planning and public health reforms

© 2019 The Authors This article synthesises the challenges faced by the English (urban) spatial planning system to become an enabler of urban health and explores some keys features of the evidence base, policy tools and policy implementation issues that urban planners need to be aware of to become health enablers. It draws on good practice identified in an Economic and Social Research Council (ESRC) seminar series involving over 500 academic researchers and practitioners between 2015 and 2017. A number of key recommendations emerged out of the project. First, planning and health agendas must align at the local level. Second, the evidence base of health priorities must be locally relevant. Third, robust tools can support the creation of frameworks for delivering health outcomes through planning. And finally, adequate resources are necessary to develop the capacity of key place-making stakeholders

Extending the validity range of quantum optical master equations

This paper derives master equations for an atomic two-level system for a large set of unitarily equivalent Hamiltonians without employing the rotating wave and certain Markovian approximations. Each Hamiltonian refers to physically different components as representing the "atom" and as representing the "field" and hence results in a different master equation, when assuming a photon-absorbing environment. It is shown that the master equations associated with the minimal coupling and the multipolar Hamiltonians predict enormous stationary state narrowband photon emission rates, even in the absence of external driving, for current experiments with single quantum dots and colour centers in diamond. These seem to confirm that the rotating wave Hamiltonian identifies the components of the atom-field system most accurately.Comment: substantially revised version, 15 pages, 6 figures, 1 tabl

Integrative analysis of RUNX1 downstream pathways and target genes

Background: The RUNX1 transcription factor gene is frequently mutated in sporadic myeloid and lymphoid leukemia through translocation, point mutation or amplification. It is also responsible for a familial platelet disorder with predisposition to acute myeloid leukemia (FPD-AML). The disruption of the largely unknown biological pathways controlled by RUNX1 is likely to be responsible for the development of leukemia. We have used multiple microarray platforms and bioinformatic techniques to help identify these biological pathways to aid in the understanding of why RUNX1 mutations lead to leukemia. Results: Here we report genes regulated either directly or indirectly by RUNX1 based on the study of gene expression profiles generated from 3 different human and mouse platforms. The platforms used were global gene expression profiling of: 1) cell lines with RUNX1 mutations from FPD-AML patients, 2) over-expression of RUNX1 and CBF[Beta], and 3) Runx1 knockout mouse embryos using either cDNA or Affymetrix microarrays. We observe that our datasets (lists of differentially expressed genes) significantly correlate with published microarray data from sporadic AML patients with mutations in either RUNX1 or its cofactor, CBF[Beta]. A number of biological processes were identified among the differentially expressed genes and functional assays suggest that heterozygous RUNX1 point mutations in patients with FPD-AML impair cell proliferation, microtubule dynamics and possibly genetic stability. In addition, analysis of the regulatory regions of the differentially expressed genes has for the first time systematically identified numerous potential novel RUNX1 target genes. Conclusion: This work is the first large-scale study attempting to identify the genetic networks regulated by RUNX1, a master regulator in the development of the hematopoietic system and leukemia. The biological pathways and target genes controlled by RUNX1 will have considerable importance in disease progression in both familial and sporadic leukemia as well as therapeutic implications

HSRL-2 Observations of Aerosol Variability During an Aerosol Build-up Event in Houston and Comparisons With WRF-Chem

The NASA Langley airborne multi-wavelength High Spectral Resolution Lidar (HSRL-2) provides vertical distribution of aerosol optical properties as curtains of aerosol extinction, backscatter and depolarization along the flight track, plus intensive properties that are used to infer aerosol type and external mixing of types. Deployed aboard the NASA Langley King Air on the DISCOVER-AQ field mission in Houston in September 2013, HSRL-2 flew a pattern that included 18 ground sites, repeated four times a day, coordinated with a suite of airborne in situ measurements. The horizontally and vertically resolved curtains of HSRL-2 measurements give an unparalleled view of the spatial and temporal variability of aerosol, which provide broad context for interpreting other measurements and models. Detailed comparisons of aerosol extinction are made with the WRF-Chem chemical transport model along the HSRL-2 flight path. The period from Sept. 11-14 is notable for a large aerosol build-up and persistent smoke layers. We investigate the aerosol properties using the vertically resolved HSRL-2 measurements and aerosol typing analysis plus WRFChem model tracers and back trajectories, and modeling of humidification effects

Phosphorylation of Syntaxin‐1a by casein kinase 2α (CK2α) regulates presynaptic vesicle exocytosis from the reserve pool

The t-soluble NSF-attachment protein receptor protein Syntaxin-1a (Stx-1a) is abundantly expressed at pre-synaptic terminals where it plays a critical role in the exocytosis of neurotransmitter-containing synaptic vesicles. Stx-1a is phosphorylated by Casein kinase 2α (CK2α) at Ser14, which has been proposed to regulate the interaction of Stx-1a and Munc-18 to control of synaptic vesicle priming. However, the role of CK2α in synaptic vesicle dynamics remains unclear. Here, we show that CK2α over-expression reduces evoked synaptic vesicle release. Furthermore, shRNA-mediated knockdown of CK2α in primary hippocampal neurons strongly enhanced vesicle exocytosis from the reserve pool, with no effect on the readily releasable pool of primed vesicles. In neurons in which endogenous Stx-1a was knocked down and replaced with a CK2α phosphorylation-deficient mutant, Stx-1a(D17A), vesicle exocytosis was also increased. These results reveal a previously unsuspected role of CK2α phosphorylation in specifically regulating the reserve synaptic vesicle pool, without changing the kinetics of release from the readily releasable pool