Linearly bounded infinite graphs

Linearly bounded Turing machines have been mainly studied as acceptors for context-sensitive languages. We define a natural class of infinite automata representing their observable computational behavior, called linearly bounded graphs. These automata naturally accept the same languages as the linearly bounded machines defining them. We present some of their structural properties as well as alternative characterizations in terms of rewriting systems and context-sensitive transductions. Finally, we compare these graphs to rational graphs, which are another class of automata accepting the context-sensitive languages, and prove that in the bounded-degree case, rational graphs are a strict sub-class of linearly bounded graphs

TD-CARMA: Painless, accurate, and scalable estimates of gravitational-lens time delays with flexible CARMA processes

Cosmological parameters encoding our current understanding of the expansion history of the Universe can be constrained by the accurate estimation of time delays arising in gravitationally lensed systems. We propose TD-CARMA, a Bayesian method to estimate cosmological time delays by modelling the observed and irregularly sampled light curves as realizations of a Continuous Auto-Regressive Moving Average (CARMA) process. Our model accounts for heteroskedastic measurement errors and microlensing, an additional source of independent extrinsic long-term variability in the source brightness. The CARMA formulation admits a linear state-space representation, that allows for efficient and scalable likelihood computation using the Kalman Filter. We obtain a sample from the joint posterior distribution of the model parameters using a nested sampling approach. This allows for "painless" Bayesian Computation, dealing with the expected multi-modality of the posterior distribution in a straightforward manner and not requiring the specification of starting values or an initial guess for the time delay, unlike existing methods. In addition, the proposed sampling procedure automatically evaluates the Bayesian evidence, allowing us to perform principled Bayesian model selection. TD-CARMA is parsimonious, and typically includes no more than a dozen unknown parameters. We apply TD-CARMA to three doubly lensed quasars HS 2209+1914, SDSS J1001+5027 and SDSS J1206+4332, estimating their time delays as $-21.96 \pm 1.448$ (6.6$\%$ precision), $120.93 \pm 1.015$ (0.8$\%$), and $111.51 \pm 1.452$ (1.3$\%$), respectively. A python package, TD-CARMA, is publicly available to implement the proposed method

Scattering in flatland: Efficient representations via wave atoms

This paper presents a numerical compression strategy for the boundary integral equation of acoustic scattering in two dimensions. These equations have oscillatory kernels that we represent in a basis of wave atoms, and compress by thresholding the small coefficients to zero. This phenomenon was perhaps first observed in 1993 by Bradie, Coifman, and Grossman, in the context of local Fourier bases \cite{BCG}. Their results have since then been extended in various ways. The purpose of this paper is to bridge a theoretical gap and prove that a well-chosen fixed expansion, the nonstandard wave atom form, provides a compression of the acoustic single and double layer potentials with wave number $k$ as $O(k)$-by-$O(k)$ matrices with $O(k^{1+1/\infty})$ nonnegligible entries, with a constant that depends on the relative $\ell_2$ accuracy \eps in an acceptable way. The argument assumes smooth, separated, and not necessarily convex scatterers in two dimensions. The essential features of wave atoms that enable to write this result as a theorem is a sharp time-frequency localization that wavelet packets do not obey, and a parabolic scaling wavelength $\sim$ (essential diameter)${}^2$. Numerical experiments support the estimate and show that this wave atom representation may be of interest for applications where the same scattering problem needs to be solved for many boundary conditions, for example, the computation of radar cross sections.Comment: 39 page

Inflammatory Disease Processes and Interactions with Nutrition

Inflammation is a stereotypical physiological response to infections and tissue injury; it initiates pathogen killing as well as tissue repair processes and helps to restore homeostasis at infected or damaged sites. Acute inflammatory reactions are usually self-limiting and resolve rapidly, due to the involvement of negative feedback mechanisms. Thus, regulated inflammatory responses are essential to remain healthy and maintain homeostasis. However, inflammatory responses that fail to regulate themselves can become chronic and contribute to the perpetuation and progression of disease. Characteristics typical of chronic inflammatory responses underlying the pathophysiology of several disorders include loss of barrier function, responsiveness to a normally benign stimulus, infiltration of inflammatory cells into compartments where they are not normally found in such high numbers, and overproduction of oxidants, cytokines, chemokines, eicosanoids and matrix metalloproteinases. The levels of these mediators amplify the inflammatory response, are destructive and contribute to the clinical symptoms. Various dietary components including long chain ω-3 fatty acids, antioxidant vitamins, plant flavonoids, prebiotics and probiotics have the potential to modulate predisposition to chronic inflammatory conditions and may have a role in their therapy. These components act through a variety of mechanisms including decreasing inflammatory mediator production through effects on cell signaling and gene expression (ω-3 fatty acids, vitamin E, plant flavonoids), reducing the production of damaging oxidants (vitamin E and other antioxidants), and promoting gut barrier function and anti-inflammatory responses (prebiotics and probiotics). However, in general really strong evidence of benefit to human health through anti-inflammatory actions is lacking for most of these dietary components. Thus, further studies addressing efficacy in humans linked to studies providing greater understanding of the mechanisms of action involved are require

Phosphorylation of the Leukemic Oncoprotein EVI1 on Serine 196 Modulates DNA Binding, Transcriptional Repression and Transforming Ability

The EVI1 (ecotropic viral integration site 1) gene at 3q26 codes for a transcriptional regulator with an essential role in haematopoiesis. Overexpression of EVI1 in acute myeloid leukaemia (AML) is frequently associated with 3q26 rearrangements and confers extremely poor prognosis. EVI1 mediates transcriptional regulation, signalling, and epigenetic modifications by interacting with DNA, proteins and protein complexes. To explore to what extent protein phosphorylation impacts on EVI1 functions, we analysed endogenous EVI1 protein from a high EVI1 expressing Fanconi anaemia (FA) derived AML cell line. Mass spectrometric analysis of immunoprecipitated EVI1 revealed phosphorylation at serine 196 (S196) in the sixth zinc finger of the N-terminal zinc finger domain. Mutated EVI1 with an aspartate substitution at serine 196 (S196D), which mimics serine phosphorylation of this site, exhibited reduced DNA-binding and transcriptional repression from a gene promotor selectively targeted by the N-terminal zinc finger domain. Forced expression of the S196D mutant significantly reduced EVI1 mediated transformation of Rat1 fibroblasts. While EVI1-mediated serial replating of murine haematopoietic progenitors was maintained by EVI1-S196D, this was associated with significantly higher Evi1-trancript levels compared with WT-EVI1 or EVI1-S196A, mimicking S196 non-phosphorylated EVI1. These data suggest that EVI1 function is modulated by phosphorylation of the first zinc finger domain

The Near Infrared Imager and Slitless Spectrograph for JWST -- V. Kernel Phase Imaging and Data Analysis

Kernel phase imaging (KPI) enables the direct detection of substellar companions and circumstellar dust close to and below the classical (Rayleigh) diffraction limit. We present a kernel phase analysis of JWST NIRISS full pupil images taken during the instrument commissioning and compare the performance to closely related NIRISS aperture masking interferometry (AMI) observations. For this purpose, we develop and make publicly available the custom "Kpi3Pipeline" enabling the extraction of kernel phase observables from JWST images. The extracted observables are saved into a new and versatile kernel phase FITS file (KPFITS) data exchange format. Furthermore, we present our new and publicly available "fouriever" toolkit which can be used to search for companions and derive detection limits from KPI, AMI, and long-baseline interferometry observations while accounting for correlated uncertainties in the model fitting process. Among the four KPI targets that were observed during NIRISS instrument commissioning, we discover a low-contrast (~1:5) close-in (~1 $\lambda/D$) companion candidate around CPD-66~562 and a new high-contrast (~1:170) detection separated by ~1.5 $\lambda/D$ from 2MASS~J062802.01-663738.0. The 5-$\sigma$ companion detection limits around the other two targets reach ~6.5 mag at ~200 mas and ~7 mag at ~400 mas. Comparing these limits to those obtained from the NIRISS AMI commissioning observations, we find that KPI and AMI perform similar in the same amount of observing time. Due to its 5.6 times higher throughput if compared to AMI, KPI is beneficial for observing faint targets and superior to AMI at separations >325 mas. At very small separations (<100 mas) and between ~250-325 mas, AMI slightly outperforms KPI which suffers from increased photon noise from the core and the first Airy ring of the point-spread function.Comment: 34 pages, 17 figures, accepted for publication in PAS

Modified Vaccinia Virus Ankara Exerts Potent Immune Modulatory Activities in a Murine Model

Background: Modified vaccinia virus Ankara (MVA), a highly attenuated strain of vaccinia virus, has been used as vaccine delivery vector in preclinical and clinical studies against infectious diseases and malignancies. Here, we investigated whether an MVA which does not encode any antigen (Ag) could be exploited as adjuvant per se. Methodology/Principal Findings: We showed that dendritic cells infected in vitro with non-recombinant (nr) MVA expressed maturation and activation markers and were able to efficiently present exogenously pulsed Ag to T cells. In contrast to the dominant T helper (Th) 1 biased responses elicited against Ags produced by recombinant MVA vectors, the use of nrMVA as adjuvant for the co-administered soluble Ags resulted in a long lasting mixed Th1/Th2 responses. Conclusions/Significance: These findings open new ways to potentiate and modulate the immune responses to vaccin

Detection of small RNAs in Bordetella pertussis and identification of a novel repeated genetic element

Background: Small bacterial RNAs (sRNAs) have been shown to participate in the regulation of gene expression and have been identified in numerous prokaryotic species. Some of them are involved in the regulation of virulence in pathogenic bacteria. So far, little is known about sRNAs in Bordetella, and only very few sRNAs have been identified in the genome of Bordetella pertussis, the causative agent of whooping cough. Results: An in silico approach was used to predict sRNAs genes in intergenic regions of the B. pertussis genome. The genome sequences of B. pertussis, Bordetella parapertussis, Bordetella bronchiseptica and Bordetella avium were compared using a Blast, and significant hits were analyzed using RNAz. Twenty-three candidate regions were obtained, including regions encoding the already documented 6S RNA, and the GCVT and FMN riboswitches. The existence of sRNAs was verified by Northern blot analyses, and transcripts were detected for 13 out of the 20 additional candidates. These new sRNAs were named Bordetella pertussis RNAs, bpr. The expression of 4 of them differed between the early, exponential and late growth phases, and one of them, bprJ2, was found to be under the control of BvgA/BvgS two-component regulatory system of Bordetella virulence. A phylogenetic study of the bprJ sequence revealed a novel, so far undocumented repeat of ~90 bp, found in numerous copies in the Bordetella genomes and in that of other Betaproteobacteria. This repeat exhibits certain features of mobil

The N-Terminal Domain of the Arenavirus L Protein Is an RNA Endonuclease Essential in mRNA Transcription

Arenaviridae synthesize viral mRNAs using short capped primers presumably acquired from cellular transcripts by a ‘cap-snatching’ mechanism. Here, we report the crystal structure and functional characterization of the N-terminal 196 residues (NL1) of the L protein from the prototypic arenavirus: lymphocytic choriomeningitis virus. The NL1 domain is able to bind and cleave RNA. The 2.13 Å resolution crystal structure of NL1 reveals a type II endonuclease α/β architecture similar to the N-terminal end of the influenza virus PA protein. Superimposition of both structures, mutagenesis and reverse genetics studies reveal a unique spatial arrangement of key active site residues related to the PD…(D/E)XK type II endonuclease signature sequence. We show that this endonuclease domain is conserved and active across the virus families Arenaviridae, Bunyaviridae and Orthomyxoviridae and propose that the arenavirus NL1 domain is the Arenaviridae cap-snatching endonuclease

Single-nanoparticle phase transitions visualized by four-dimensional electron microscopy

The advancement of techniques that can probe the behaviour of individual nanoscopic objects is of paramount importance in various disciplines, including photonics and electronics. As it provides images with a spatiotemporal resolution, four-dimensional electron microscopy, in principle, should enable the visualization of single-nanoparticle structural dynamics in real and reciprocal space. Here, we demonstrate the selectivity and sensitivity of the technique by visualizing the spin crossover dynamics of single, isolated metal–organic framework nanocrystals. By introducing a small aperture in the microscope, it was possible to follow the phase transition and the associated structural dynamics within a single particle. Its behaviour was observed to be distinct from that imaged by averaging over ensembles of heterogeneous nanoparticles. The approach reported here has potential applications in other nanosystems and those that undergo (bio)chemical transformations