EEF: Exponentially Embedded Families with Class-Specific Features for Classification

In this letter, we present a novel exponentially embedded families (EEF) based classification method, in which the probability density function (PDF) on raw data is estimated from the PDF on features. With the PDF construction, we show that class-specific features can be used in the proposed classification method, instead of a common feature subset for all classes as used in conventional approaches. We apply the proposed EEF classifier for text categorization as a case study and derive an optimal Bayesian classification rule with class-specific feature selection based on the Information Gain (IG) score. The promising performance on real-life data sets demonstrates the effectiveness of the proposed approach and indicates its wide potential applications.Comment: 9 pages, 3 figures, to be published in IEEE Signal Processing Letter. IEEE Signal Processing Letter, 201

Source Detection in Interferometric Visibility Data. I. Fundamental Estimation Limits

Transient radio signals of astrophysical origin present an avenue for studying the dynamic universe. With the next generation of radio interferometers being planned and built, there is great potential for detecting and studying large samples of radio transients. Currently used image-based techniques for detecting radio sources have not been demonstrated to be optimal, and there is a need for development of more sophisticated algorithms and methodology for comparing different detection techniques. A visibility-space detector benefits from our good understanding of visibility-space noise properties and does not suffer from the image artifacts and need for deconvolution in image-space detectors. In this paper, we propose a method for designing optimal source detectors using visibility data, building on statistical decision theory. The approach is substantially different to conventional radio astronomy source detection. Optimal detection requires an accurate model for the data, and we present a realistic model for the likelihood function of radio interferometric data, including the effects of calibration, signal confusion, and atmospheric phase fluctuations. As part of this process, we derive fundamental limits on the calibration of an interferometric array, including the case where many relatively weak “in-beam” calibrators are used. These limits are then applied, along with a model for atmospheric phase fluctuations, to determine the limits on measuring source position, flux density, and spectral index, in the general case. We then present an optimal visibility-space detector using realistic models for an interferometer

Rare and common epilepsies converge on a shared gene regulatory network providing opportunities for novel antiepileptic drug discovery

Background The relationship between monogenic and polygenic forms of epilepsy is poorly understood, and the extent to which the genetic and acquired epilepsies share common pathways is unclear. Here, we use an integrated systems-level analysis of brain gene expression data to identify molecular networks disrupted in epilepsy. Results We identify a co-expression network of 320 genes (M30), which is significantly enriched for non-synonymous de novo mutations ascertained from patients with monogenic epilepsy, and for common variants associated with polygenic epilepsy. The genes in M30 network are expressed widely in the human brain under tight developmental control, and encode physically interacting proteins involved in synaptic processes. The most highly connected proteins within M30 network are preferentially disrupted by deleterious de novo mutations for monogenic epilepsy, in line with the centrality-lethality hypothesis. Analysis of M30 expression revealed consistent down-regulation in the epileptic brain in heterogeneous forms of epilepsy including human temporal lobe epilepsy, a mouse model of acquired temporal lobe epilepsy, and a mouse model of monogenic Dravet (SCN1A) disease. These results suggest functional disruption of M30 via gene mutation or altered expression as a convergent mechanism regulating susceptibility to epilepsy broadly. Using the large collection of drug-induced gene expression data from Connectivity Map, several drugs were predicted to preferentially restore the down-regulation of M30 in epilepsy toward health, most notably valproic acid, whose effect on M30 expression was replicated in neurons. Conclusions Taken together, our results suggest targeting the expression of M30 as a potential new therapeutic strategy in epilepsy

Toward a Noninvasive Automatic Seizure Control System in Rats With Transcranial Focal Stimulations via Tripolar Concentric Ring Electrodes

Epilepsy affects approximately 1% of the world population. Antiepileptic drugs are ineffective in approximately 30% of patients and have side effects. We are developing a noninvasive, or minimally invasive, transcranial focal electrical stimulation system through our novel tripolar concentric ring electrodes to control seizures. In this study, we demonstrate feasibility of an automatic seizure control system in rats with pentylenetetrazole-induced seizures through single and multiple stimulations. These stimulations are automatically triggered by a real-time electrographic seizure activity detector based on a disjunctive combination of detections from a cumulative sum algorithm and a generalized likelihood ratio test. An average seizure onset detection accuracy of 76.14% was obtained for the test set (n = 13). Detection of electrographic seizure activity was accomplished in advance of the early behavioral seizure activity in 76.92% of the cases. Automatically triggered stimulation significantly (p = 0.001) reduced the electrographic seizure activity power in the once stimulated group compared to controls in 70% of the cases. To the best of our knowledge this is the first closed-loop automatic seizure control system based on noninvasive electrical brain stimulation using tripolar concentric ring electrode electrographic seizure activity as feedback

Identification of Evening Complex Associated Proteins in Arabidopsis by Affinity Purification and Mass Spectrometry

Many species possess an endogenous circadian clock to synchronize internal physiology with an oscillating external environment. In plants, the circadian clock coordinates growth, metabolism and development over daily and seasonal time scales. Many proteins in the circadian network form oscillating complexes that temporally regulate myriad processes, including signal transduction, transcription, protein degradation and post-translational modification. In Arabidopsis thaliana, a tripartite complex composed of EARLY FLOWERING 4 (ELF4), EARLY FLOWERING 3 (ELF3), and LUX ARRHYTHMO (LUX), named the evening complex, modulates daily rhythms in gene expression and growth through transcriptional regulation. However, little is known about the physical interactions that connect the circadian system to other pathways. We used affinity purification and mass spectrometry (AP-MS) methods to identify proteins that associate with the evening complex in A. thaliana. New connections within the circadian network as well as to light signaling pathways were identified, including linkages between the evening complex, TIMING OF CAB EXPRESSION1 (TOC1), TIME FOR COFFEE (TIC), all phytochromes and TANDEM ZINC KNUCKLE/PLUS3 (TZP). Coupling genetic mutation with affinity purifications tested the roles of phytochrome B (phyB), EARLY FLOWERING 4, and EARLY FLOWERING 3 as nodes connecting the evening complex to clock and light signaling pathways. These experiments establish a hierarchical association between pathways and indicate direct and indirect interactions. Specifically, the results suggested that EARLY FLOWERING 3 and phytochrome B act as hubs connecting the clock and red light signaling pathways. Finally, we characterized a clade of associated nuclear kinases that regulate circadian rhythms, growth, and flowering in A. thaliana. Coupling mass spectrometry and genetics is a powerful method to rapidly and directly identify novel components and connections within and between complex signaling pathways

The impact of point source subtraction residuals on 21 cm Epoch of Reionization estimation

Precise subtraction of foreground sources is crucial for detecting and estimating 21cm HI signals from the Epoch of Reionization (EoR). We quantify how imperfect point source subtraction due to limitations of the measurement dataset yields structured residual signal in the dataset. We use the Cramer-Rao lower bound, as a metric for quantifying the precision with which a parameter may be measured, to estimate the residual signal in a visibility dataset due to imperfect point source subtraction. We then propagate these residuals into two metrics of interest for 21cm EoR experiments - the angular and two-dimensional power spectrum - using a combination of full analytic covariant derivation, analytic variant derivation, and covariant Monte Carlo simulations. This methodology differs from previous work in two ways: (1) it uses information theory to set the point source position error, rather than assuming a global root-mean-square error, and (2) it describes a method for propagating the errors analytically, thereby obtaining the full correlation structure of the power spectra. The methods are applied to two upcoming low-frequency instruments: the Murchison Widefield Array and the Precision Array for Probing the Epoch of Reionization. In addition to the actual antenna configurations, we apply the methods to minimally-redundant and maximally-redundant configurations. We find that for peeling sources above 1 Jy, the amplitude of the residual signal, and its variance, will be smaller than the contribution from thermal noise for the observing parameters proposed for upcoming EoR experiments, and that optimal subtraction of bright point sources will not be a limiting factor for EoR parameter estimation. We then use the formalism to provide an ab initio analytic derivation motivating the 'wedge' feature in the two-dimensional power spectrum, complementing previous discussion in the literature.Comment: 39 pages, 9 figures, accepted for publication in Ap

Safety, Immunogenicity, and Transmissibility of Single-Dose Live Oral Cholera Vaccine Strain CVD l03-HgR in 24- to 59-Month-Old Indonesian Children

Recombinant A-B+ Vibrio cholerae O1 strain CVD 103-HgR is a safe, highly immunogenic, single-dose live oral vaccine in adults in industrialized countries, Safety, excretion, immunogenicity, vaccine transmissibility, and environmental introduction ofCVD 103-HgR were investigated among 24- to 59-month-old children in Jakarta. In 81 households, 1 child was randomly allocated a single dose of vaccine (5 x 109 cfu) and another, placebo. Additionally, 139 unpaired children were randomly allocated vaccine or placebo. During 9 days of follow-up, diarrhea or vomiting did not occur more often among vaccinees than controls. Vaccine was minimally excreted and was isolated from no controls and from 1 (0.6%) of 177 unvaccinated family contacts. A 4-fold or higher rise in serum vibriocidal antibody was observed in 75% of vaccinees (10-fold rise in geometric mean titer over baseline). Of 135 paired placebo recipients or household contacts, 5 had vibriocidal seroconversions. Moore swabs placed in sewers and latrines near 97 households failed to detect vaccine. These observations pave the way for a large-scale field trial of efficac

The structure of Herpesvirus Fusion Glycoprotein B-Bilayer Complex reveals the protein-membrane and lateral protein-protein interaction

Glycoprotein B (gB) is a key component of the complex herpesvirus fusion machinery. We studied membrane interaction of two gB ectodomain forms and present an electron cryotomography structure of the gB-bilayer complex. The two forms differed in presence or absence of the membrane proximal region (MPR) but showed an overall similar trimeric shape. The presence of the MPR impeded interaction with liposomes. In contrast, the MPR-lacking form interacted efficiently with liposomes. Lateral interaction resulted in coat formation on the membranes. The structure revealed that interaction of gB with membranes was mediated by the fusion loops and limited to the outer membrane leaflet. The observed intrinsic propensity of gB to cluster on membranes indicates an additional role of gB in driving the fusion process forward beyond the transient fusion pore opening and subsequently leading to fusion pore expansion

Constitutive Activation of the Src Family Kinase Hck Results in Spontaneous Pulmonary Inflammation and an Enhanced Innate Immune Response

To identify the physiological role of Hck, a functionally redundant member of the Src family of tyrosine kinases expressed in myelomonocytic cells, we generated HckF/F “knock-in” mice which carry a targeted tyrosine (Y) to phenylalanine (F) substitution of the COOH-terminal, negative regulatory Y499-residue in the Hck protein. Unlike their Hck−/− “loss-of-function” counterparts, HckF/F “gain-of-function” mice spontaneously acquired a lung pathology characterized by extensive eosinophilic and mononuclear cell infiltration within the lung parenchyma, alveolar airspaces, and around blood vessels, as well as marked epithelial mucus metaplasia in conducting airways. Lungs from HckF/F mice showed areas of mild emphysema and pulmonary fibrosis, which together with inflammation resulted in altered lung function and respiratory distress in aging mice. When challenged transnasally with lipopolysaccharide (LPS), HckF/F mice displayed an exaggerated pulmonary innate immune response, characterized by excessive release of matrix metalloproteinases and tumor necrosis factor (TNF)α. Similarly, HckF/F mice were highly sensitive to endotoxemia after systemic administration of LPS, and macrophages and neutrophils derived from HckF/F mice exhibited enhanced effector functions in vitro (e.g., nitric oxide and TNFα production, chemotaxis, and degranulation). Based on the demonstrated functional association of Hck with leukocyte integrins, we propose that constitutive activation of Hck may mimic adhesion-dependent priming of leukocytes. Thus, our observations collectively suggest an enhanced innate immune response in HckF/F mice thereby skewing innate immunity from a reversible physiological host defense response to one causing irreversible tissue damage