SATURN'S INNER SATELLITES: ORBITS, MASSES, AND THE CHAOTIC MOTION OF ATLAS FROM NEW CASSINI IMAGING OBSERVATIONS

We present numerically-derived orbits and mass estimates for the inner Saturnian satellites, Atlas, Prometheus, Pandora, Janus and Epimetheus from a fit to 2580 new Cassini ISS astrometric observations spanning February 2004 to August 2013. The observations are provided in a supplementary table. We estimate GM_ Atlas=0.384+/-0.001 x 10^(-3)km^3s^(-2), a value 13% smaller than the previously published estimate but with an order of magnitude reduction in the uncertainty. We also find GM_ Prometheus=10.677+/-0.006x10(-3)km^3s^(-2), GM_Pandora=9.133+/-0.009x10^(-3)km^3s^(-2), GM_Janus=126.51+/-0.03x10^(-3)km^3s^(-2) and GM_Epimetheus=35.110+/-0.009x10^(-3)km^3s^(-2), consistent with previously published values, but also with significant reductions in uncertainties. We show that Atlas is currently librating in both the 54:53 co-rotation-eccentricity resonance (CER) and the 54:53 inner Lindblad (ILR) resonance with Prometheus, making it the latest example of a coupled CER-ILR system, in common with the Saturnian satellites Anthe, Aegaeon and Methone, and possibly Neptune's ring arcs. We further demonstrate that Atlas's orbit is chaotic, with a Lyapunov time of ~10 years, and show that its chaotic behaviour is a direct consequence of the coupled resonant interaction with Prometheus, rather than being an indirect effect of the known chaotic interaction between Prometheus and Pandora. We provide an updated analysis of the second-order resonant perturbations involving Prometheus, Pandora and Epimetheus based on the new observations, showing that these resonant arguments are librating only when Epimetheus is the innermost of the co-orbital pair, Janus and Epimetheus. We also find evidence that the known chaotic changes in the orbits of Prometheus and Pandora are not confined to times of apse anti-alignement.Comment: 23 pages, 16 figures. Accepted for publication in The Astronomical Journal 23 September 2014 (corrected Fig. 11

Solution structure of a repeated unit of the ABA-1 nematode polyprotein allergen of ascaris reveals a novel fold and two discrete lipid-binding sites

Parasitic nematode worms cause serious health problems in humans and other animals. They can induce allergic-type immune responses, which can be harmful but may at the same time protect against the infections. Allergens are proteins that trigger allergic reactions and these parasites produce a type that is confined to nematodes, the nematode polyprotein allergens (NPAs). These are synthesized as large precursor proteins comprising repeating units of similar amino acid sequence that are subsequently cleaved into multiple copies of the allergen protein. NPAs bind small lipids such as fatty acids and retinol (Vitamin A) and probably transport these sensitive and insoluble compounds between the tissues of the worms. Nematodes cannot synthesize these lipids, so NPAs may also be crucial for extracting nutrients from their hosts. They may also be involved in altering immune responses by controlling the lipids by which the immune and inflammatory cells communicate. We describe the molecular structure of one unit of an NPA, the well-known ABA-1 allergen of Ascaris and find its structure to be of a type not previously found for lipid-binding proteins, and we describe the unusual sites where lipids bind within this structur

Azacitidine for treating acute myeloid leukaemia with more than 30% bone marrow blasts: A Single Technology Appraisal

Report commissioned by the NIHR HTA ProgrammeThis report was commissioned by the NIHR HTA Programme as project number 15/64/10

Topoisomer Differentiation of Molecular Knots by FTICR MS: Lessons from Class II Lasso Peptides

Lasso peptides constitute a class of bioactive peptides sharing a knotted structure where the C-terminal tail of the peptide is threaded through and trapped within an N-terminalmacrolactamring. The structural characterization of lasso structures and differentiation from their unthreaded topoisomers is not trivial and generally requires the use of complementary biochemical and spectroscopic methods. Here we investigated two antimicrobial peptides belonging to the class II lasso peptide family and their corresponding unthreaded topoisomers: microcin J25 (MccJ25), which is known to yield two-peptide product ions specific of the lasso structure under collisioninduced dissociation (CID), and capistruin, for which CID does not permit to unambiguously assign the lasso structure. The two pairs of topoisomers were analyzed by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR MS) upon CID, infrared multiple photon dissociation (IRMPD), and electron capture dissociation (ECD). CID and ECDspectra clearly permitted to differentiate MccJ25 from its non-lasso topoisomer MccJ25-Icm, while for capistruin, only ECD was informative and showed different extent of hydrogen migration (formation of c\bullet/z from c/z\bullet) for the threaded and unthreaded topoisomers. The ECD spectra of the triply-charged MccJ25 and MccJ25-lcm showed a series of radical b-type product ions {\eth}b0In{\TH}. We proposed that these ions are specific of cyclic-branched peptides and result from a dual c/z\bullet and y/b dissociation, in the ring and in the tail, respectively. This work shows the potentiality of ECD for structural characterization of peptide topoisomers, as well as the effect of conformation on hydrogen migration subsequent to electron capture

The Caviar software package for the astrometric reduction of Cassini ISS images: description and examples

N.J.C. is grateful to the Paris Observatory for funding as an invited researcher at the IMCCE. We thank the FP7-ESPaCE European program for funding under the agreement No. 263466. N.J.C. and C.D.M. thank the Science and Technology Facilities Council (Grant No. ST/P000622/1) for financial support. This work was also supported by the International Space Science Institute (ISSI)

Molecular Genetics of T Cell Development

T cell development is guided by a complex set of transcription factors that act recursively, in different combinations, at each of the developmental choice points from T-lineage specification to peripheral T cell specialization. This review describes the modes of action of the major T-lineage-defining transcription factors and the signal pathways that activate them during intrathymic differentiation from pluripotent precursors. Roles of Notch and its effector RBPSuh (CSL), GATA-3, E2A/HEB and Id proteins, c-Myb, TCF-1, and members of the Runx, Ets, and Ikaros families are critical. Less known transcription factors that are newly recognized as being required for T cell development at particular checkpoints are also described. The transcriptional regulation of T cell development is contrasted with that of B cell development, in terms of their different degrees of overlap with the stem-cell program and the different roles of key transcription factors in gene regulatory networks leading to lineage commitment

Citrulline as a marker of intestinal function and absorption in clinical settings: A systematic review and meta-analysis

Background: Citrulline has been described as a marker of intestinal function or absorption but evidence varies according to clinical settings. Objective: The objective of this article is to examine the evidence of plasma citrulline as a marker of intestinal function and absorption in various clinical settings. Methods: Studies were examined for p values, means and standard deviations, correlation coefficients or other metrics depicting the association of citrulline with intestinal function. A random effects model was used to produce a pooled estimate. A hierarchical summary receiver operating curve model was fitted for diagnostic accuracy measures. Results: Citrulline levels are correlated strongly with small bowel length in short bowel syndrome patients (r = 0.67). Citrulline is strongly negatively correlated (r = –0.56) with intestinal disease severity with regards to enteropathies (coeliac disease, tropical enteropathy, Crohn’s disease, mucositis, acute rejection in intestinal transplantation). Citrulline cut-off levels have an overall sensitivity and specificity of 80% and 84% respectively. Citrulline levels in untreated coeliac patients compared to controls were reduced by 10 µmol/l. Citrulline levels increase with gluten-free diet and with improvement of enteropathy. Citrulline is decreased in critical illness and sepsis. Conclusion: These findings allow us to advocate quite reasonably that citrulline is a marker of acute and chronic intestinal insufficiency

Potentiation of photodynamic therapy of cancer by complement: the effect of γ-inulin

Host response elicited by photodynamic therapy (PDT) of cancerous lesions is a critical contributor to the clinical outcome, and complement system has emerged as its important element. Amplification of complement action was shown to improve tumour PDT response. In search of a clinically relevant complement activator for use as a PDT adjuvant, this study focused on γ-inulin and examined its effects on PDT response of mouse tumours. Intralesional γ-inulin (0.1 mg mouse−1) delivered immediately after PDT rivaled zymosan (potent classical complement activator) in delaying the recurrence of B16BL6 melanomas. This effect of γ-inulin was further enhanced by IFN-γ pretreatment. Tumour C3 protein levels, already elevated after individual PDT or γ-inulin treatments, increased much higher after their combination. With fibrosarcomas MCA205 and FsaR, adjuvant γ-inulin proved highly effective in reducing recurrence rates following PDT using four different photosensitisers (BPD, ce6, Photofrin, and mTHPC). At 3 days after PDT plus γ-inulin treatment, over 50% of cells found at the tumour site were CTLs engaged in killing specific targets via perforin–granzyme pathway. This study demonstrates that γ-inulin is highly effective PDT adjuvant and suggests that by amplifying the activation of complement system, this agent potentiates the development of CTL-mediated immunity against PDT-treated tumours

Three-body interactions with cold polar molecules

We show that polar molecules driven by microwave fields give naturally rise to strong three-body interactions, while the two-particle interaction can be independently controlled and even switched off. The derivation of these effective interaction potentials is based on a microscopic understanding of the underlying molecular physics, and follows from a well controlled and systematic expansion into many-body interaction terms. For molecules trapped in an optical lattice, we show that these interaction potentials give rise to Hubbard models with strong nearest-neighbor two-body and three-body interaction. As an illustration, we study the one-dimensional Bose-Hubbard model with dominant three-body interaction and derive its phase diagram.Comment: 8 pages, 4 figure

Constrictive pericarditis is an easily overlooked cause of right heart failure: a case report

We describe a patient who suffered progressive right heart failure of unknown aetiology, despite a lengthy series of hospital investigations. Constrictive pericarditis had not been suspected during life, and was ultimately diagnosed as an autopsy finding. The salient clinical features and confirmatory investigations for this unusual disorder are reviewed. The case reminds us to consider the possibility of constrictive pericarditis in patients with unexplained chronic right heart failure, so that prompt investigation and treatment can be instigated