Evolutionary transition from degenerate to nonredundant cytokine signaling networks supporting intrathymic T cell development

In mammals, T cell development critically depends on the IL-7 cytokine signaling pathway. Here we describe the identification of the zebrafish ortholog of mammalian IL-7 based on chromosomal localization, deduced protein sequence, and expression patterns. To examine the biological role of il7 in teleosts, we generated an il7 allele lacking most of its coding exons using CRISPR/Cas9-based mutagenesis. il7-deficient animals are viable and exhibit no obvious signs of immune disorder. With respect to intrathymic T cell development, il7 deficiency is associated with only a mild reduction of thymocyte numbers, contrasting with a more pronounced impairment of T cell development in il7r-deficient fish. Genetic interaction studies between il7 and il7r mutants, and il7 and crlf2(tslpr) mutants suggest the contribution of additional, as-yet unidentified cytokines to intrathymic T cell development. Such activities were also ascertained for other cytokines, such as il2 and il15, collectively indicating that in contrast to the situation in mammals, T cell development in the thymus of teleosts is driven by a degenerate multicomponent network of γc cytokines; this explains why deficiencies of single components have little detrimental effect. In contrast, the dependence on a single cytokine in the mammalian thymus has catastrophic consequences in cases of congenital deficiencies in genes affecting the IL-7 signaling pathway. We speculate that the transition from a degenerate to a nonredundant cytokine network supporting intrathymic T cell development emerged as a consequence of repurposing evolutionarily ancient constitutive cytokine pathways for regulatory functions in the mammalian peripheral immune system

Medical data processing and analysis for remote health and activities monitoring

Recent developments in sensor technology, wearable computing, Internet of Things (IoT), and wireless communication have given rise to research in ubiquitous healthcare and remote monitoring of human\u2019s health and activities. Health monitoring systems involve processing and analysis of data retrieved from smartphones, smart watches, smart bracelets, as well as various sensors and wearable devices. Such systems enable continuous monitoring of patients psychological and health conditions by sensing and transmitting measurements such as heart rate, electrocardiogram, body temperature, respiratory rate, chest sounds, or blood pressure. Pervasive healthcare, as a relevant application domain in this context, aims at revolutionizing the delivery of medical services through a medical assistive environment and facilitates the independent living of patients. In this chapter, we discuss (1) data collection, fusion, ownership and privacy issues; (2) models, technologies and solutions for medical data processing and analysis; (3) big medical data analytics for remote health monitoring; (4) research challenges and opportunities in medical data analytics; (5) examples of case studies and practical solutions

TUMOUR NECROSIS FACTOR alpha IN RHEUMATOID ARTHRITIS AND OSTEOARTHRITIS PATIENTS IN BLOOD SERUM AND SYNOVIAL FLUID

publishersversionPeer reviewe

Maximally localized Wannier functions in LaMnO3 within PBE+U, hybrid functionals, and partially self-consistent GW: an efficient route to construct ab-initio tight-binding parameters for e_g perovskites

Using the newly developed VASP2WANNIER90 interface we have constructed maximally localized Wannier functions (MLWFs) for the e_g states of the prototypical Jahn-Teller magnetic perovskite LaMnO3 at different levels of approximation for the exchange-correlation kernel. These include conventional density functional theory (DFT) with and without additional on-site Hubbard U term, hybrid-DFT, and partially self-consistent GW. By suitably mapping the MLWFs onto an effective e_g tight-binding (TB) Hamiltonian we have computed a complete set of TB parameters which should serve as guidance for more elaborate treatments of correlation effects in effective Hamiltonian-based approaches. The method-dependent changes of the calculated TB parameters and their interplay with the electron-electron (el-el) interaction term are discussed and interpreted. We discuss two alternative model parameterizations: one in which the effects of the el-el interaction are implicitly incorporated in the otherwise "noninteracting" TB parameters, and a second where we include an explicit mean-field el-el interaction term in the TB Hamiltonian. Both models yield a set of tabulated TB parameters which provide the band dispersion in excellent agreement with the underlying ab initio and MLWF bands.Comment: 30 pages, 7 figure

High Energy gamma-rays From FR I Jets

Thanks to Hubble and Chandra telescopes, some of the large scale jets in extragalactic radio sources are now being observed at optical and X-ray frequencies. For the FR I objects the synchrotron nature of this emission is surely established, although a lot of uncertainties - connected for example with the particle acceleration processes involved - remain. In this paper we study production of high energy gamma-rays in FR I kiloparsec-scale jets by inverse-Compton emission of the synchrotron-emitting electrons. We consider different origin of seed photons contributing to the inverse-Compton scattering, including nuclear jet radiation as well as ambient, stellar and circumstellar emission of the host galaxies. We discuss how future detections or non-detections of the evaluated gamma-ray fluxes can provide constraints on the unknown large scale jet parameters, i.e. the magnetic field intensity and the jet Doppler factor. For the nearby sources Centaurus A and M 87, we find measurable fluxes of TeV photons resulting from synchrotron self-Compton process and from comptonisation of the galactic photon fields, respectively. In the case of Centaurus A, we also find a relatively strong emission component due to comptonisation of the nuclear blazar photons, which could be easily observed by GLAST at energy ~10 GeV, providing important test for the unification of FR I sources with BL Lac objects.Comment: 39 pages, 6 figures included. Modified version, accepted for publication in Astrophysical Journa

Monoclonal antibodies against human astrocytomas and their reactivity pattern

The establishment of hybridomas after fusion of X63-Ag8.653 mouse myeloma cells and splenocytes from mice hyperimmunized against human astrocytomas is presented. The animals were primed with 5 × 106 chemically modified uncultured or cultured glioma cells. Six weeks after the last immunization step an intrasplenal booster injection was administrated and 3 days later the spleen cells were prepared for fusion experiments. According to the specificity analysis of the generated antibodies 7 hybridoma products (MUC 7-22, MUC 8-22, MUC 10-22, MUC 11-22, MUC 14-22, MUC 15-22 and MUC 2-63) react with gliomas, neuroblastomas and melanomas as well as with embryonic and fetal cells but do not recognize non-neurogenic tumors. The selected monoclonal antibodies (McAbs) of IgG1 and IgG2a isotypes are not extensively characterized but these antibodies have been demonstrated to be reactive with a panel of glioma cell lines with varying patterns of antigen distribution. Using the McAbs described above and a series of cryosections of glioma biopsies and paraffin sections of the same material as well as glioma cultures established from these, variable antigenic profiles among glioma cell populations could be demonstrated. From these results it is evident that there is not only a distinct degree of antigenic heterogeneity among and within brain tumors, but also that the pattern of antigenic expression can change continuously. Some of the glioma associated antigens recognized by the selected antibodies persist after fixation with methanol/acetone and Karnovsky's fixative and probably are oncoembryonic/oncofetal antigen(s). The data suggest that the use of McAbs recognizing tumor associated oncofetal antigens in immunohistochemistry facilitates objective typing of intracranial malignancies and precise analysis of fine needle brain/tumor biopsies in a sensitive and reproducible manner

The attitudes of European consumers toward innovation in bread; interest of the consumers toward selected quality attributes

16 pages, 7 tables, 4 figures.-- The definitive version is available at www3.interscience.wiley.comThe present survey is integrated in the European project entitled EU-FRESHBAKE. This three years project started in October 2006. It aims at developing innovative processes and innovative formulations for the Bake Off technology taking into consideration, energy demand of the process, nutrition parameters and overall quality of the bread. To help and to advise the project on the expectations of the European consumers toward innovation, a consumer survey has been carried out taking into consideration 1050 consumers from 5 countries (Belgium, Croatia, Spain, France and Poland). The global objectives are (i) to better understand the attitudes of the European innovations in bread and (ii) to understand the main determinants of it. Globally the key points that arose from the survey were the environmental concern and the concern regarding health; these two aspects seem to steer the attitudes of the consumer. Basically, two categories of consumers were observed; (i) frequent (daily) buyers with a focus on quality and pleasure and (ii) less frequent buyers (once a week) with a more pronounced interest in nutrition and energy (process). The first group was named the crust group and the second one the crumb group. The crumb family seems to be the one that is the most interested in the outcomes of the EU-FRESHBAKE project. This group is concerned by nutrition quality and would prefer a bread which has been done with a less energy demanding process. The “crust” group is schematically less interested in the nutrition, in the shelf life and in the energy demand of the process used to prepare the bread. The results from this survey should be handled with care due to the relative small size of the sample and to the fact that the average age of the sample was rather young.This study (report, paper, workshop…) has been carried out with financial support from the Commission of the European Communities, FP6, Thematic Area “Food quality and safety”, FOOD-2006-36302 EU-FRESH BAKE.Peer reviewe

K+ΛK^+\Lambda and K+Σ0K^+\Sigma^0 photoproduction with fine center-of-mass energy resolution

Measurements of $\gamma p \rightarrow K^{+} \Lambda$ and $\gamma p \rightarrow K^{+} \Sigma^0$ cross-sections have been obtained with the photon tagging facility and the Crystal Ball calorimeter at MAMI-C. The measurement uses a novel $K^+$ meson identification technique in which the weak decay products are characterized using the energy and timing characteristics of the energy deposit in the calorimeter, a method that has the potential to be applied at many other facilities. The fine center-of-mass energy ($W$) resolution and statistical accuracy of the new data results in a significant impact on partial wave analyses aiming to better establish the excitation spectrum of the nucleon. The new analyses disfavor a strong role for quark-diquark dynamics in the nucleon.Comment: 7 pages, 8 figure

The isospin structure of photoproduction of pi-eta pairs from the nucleon in the threshold region

Photoproduction of $\pi\eta$-pairs from nucleons has been investigated from threshold up to incident photon energies of $\approx$~1.4~GeV. The quasi-free reactions $\gamma p\rightarrow p\pi^0\eta$, $\gamma n\rightarrow n\pi^0\eta$, $\gamma p\rightarrow n\pi^+\eta$, and $\gamma n\rightarrow p\pi^-\eta$ were for the first time measured from nucleons bound in the deuteron. The corresponding reactions from a free-proton target were also studied to investigate final-state interaction effects (for neutral pions the free-proton results could be compared to previous measurements; the $\gamma p\rightarrow n\pi^+\eta$ reaction was measured for the first time). For the $\pi^0\eta$ final state coherent production via the $\gamma d\rightarrow d\pi^0\eta$ reaction was also investigated. The experiments were performed at the tagged photon beam of the Mainz MAMI accelerator using an almost $4\pi$ coverage electromagnetic calorimeter composed of the Crystal Ball and TAPS detectors. The total cross sections for the four different final states obey the relation $\sigma(p\pi^0\eta)$ $\approx$ $\sigma(n\pi^0\eta)$ $\approx$ $2\sigma(p\pi^-\eta)$ $\approx$ $2\sigma(n\pi^+\eta)$ as expected for a dominant contribution from a $\Delta^{\star}\rightarrow\eta\Delta(1232)\rightarrow\pi\eta N$ reaction chain, which is also supported by the shapes of the invariant-mass distributions of nucleon-meson and $\pi$-$\eta$ pairs. The experimental results are compared to the predictions from an isobar reaction model.Comment: accepted for publication in Phys. Lett.