Tight WCRT Analysis for Synchronous C Programs

Accurate estimation of the tick length of a synchronous program is essential for efficient and predictable implementations that are devoid of timing faults. The techniques to determine the tick length statically are classified as worst case reaction time (WCRT) analysis. While a plethora of techniques exist for worst case execution time (WCET) analysis of procedural programs, there are only a handful of techniques for determining the WCRT value of synchronous programs. Most of these techniques produce overestimates and hence are unsuitable for the design of systems that are predictable while being also efficient. In this paper, we present an approach for the accurate estimation of the exact WCRT value of a synchronous program, called its tight WCRT value, using model checking. For our input specifications we have selected a synchronous C based language called PRET-C that is designed for programming Precision Timed (PRET) architectures. We then present an approach for static WCRT analysis of these programs via an intermediate format called TCCFG. This intermediate representation is then compiled to produce the input for the model checker. Experimental results that compare our approach to existing approaches demonstrate the benefits of the proposed approach. The proposed approach, while presented for PRET-C is also applicable for WCRT analysis of Esterel using simple adjustments to the generated model. The proposed approach thus paves the way for a generic approach for determining the tight WCRT value of synchronous programs at compile time

Human Complement Regulators C4b-Binding Protein and C1 Esterase Inhibitor Interact with a Novel Outer Surface Protein of Borrelia recurrentis

The spirochete Borrelia recurrentis is the causal agent of louse-borne relapsing fever and is transmitted to humans by the infected body louse Pediculus humanus. We have recently demonstrated that the B. recurrentis surface receptor, HcpA, specifically binds factor H, the regulator of the alternative pathway of complement activation, thereby inhibiting complement mediated bacteriolysis. Here, we show that B. recurrentis spirochetes express another potential outer membrane lipoprotein, termed CihC, and acquire C4b-binding protein (C4bp) and human C1 esterase inhibitor (C1-Inh), the major inhibitors of the classical and lectin pathway of complement activation. A highly homologous receptor for C4bp was also found in the African tick-borne relapsing fever spirochete B. duttonii. Upon its binding to B. recurrentis or recombinant CihC, C4bp retains its functional potential, i.e. facilitating the factor I-mediated degradation of C4b. The additional finding that ectopic expression of CihC in serum sensitive B. burgdorferi significantly increased spirochetal resistance against human complement suggests this receptor to substantially contribute, together with other known strategies, to immune evasion of B. recurrentis

Kinematically complete experimental study of Compton scattering at helium atoms near the ionization threshold

Compton scattering is one of the fundamental interaction processes of light with matter. Already upon its discovery [1] it was described as a billiard-type collision of a photon kicking a quasi-free electron. With decreasing photon energy, the maximum possible momentum transfer becomes so small that the corresponding energy falls below the binding energy of the electron. Then ionization by Compton scattering becomes an intriguing quantum phenomenon. Here we report a kinematically complete experiment on Compton scattering at helium atoms below that threshold. We determine the momentum correlations of the electron, the recoiling ion, and the scattered photon in a coincidence experiment finding that electrons are not only emitted in the direction of the momentum transfer, but that there is a second peak of ejection to the backward direction. This finding links Compton scattering to processes as ionization by ultrashort optical pulses [2], electron impact ionization [3,4], ion impact ionization [5,6], and neutron scattering [7] where similar momentum patterns occur.Comment: 7 pages, 4 figure

The SINS Survey: Broad Emission Lines in High-Redshift Star-Forming Galaxies

High signal-to-noise, representative spectra of star-forming galaxies at z~2, obtained via stacking, reveal a high-velocity component underneath the narrow H-alpha and [NII] emission lines. When modeled as a single Gaussian, this broad component has FWHM > 1500 km/s; when modeled as broad wings on the H-alpha and [NII] features, it has FWHM > 500 km/s. This feature is preferentially found in the more massive and more rapidly star-forming systems, which also tend to be older and larger galaxies. We interpret this emission as evidence of either powerful starburst-driven galactic winds or active supermassive black holes. If galactic winds are responsible for the broad emission, the observed luminosity and velocity of this gas imply mass outflow rates comparable to the star formation rate. On the other hand, if the broad line regions of active black holes account for the broad feature, the corresponding black holes masses are estimated to be an order of magnitude lower than those predicted by local scaling relations, suggesting a delayed assembly of supermassive black holes with respect to their host bulges.Comment: 11 pages, 5 figures. Accepted version, incorporating referee comments, including changes to title, abstract, figures, and discussion sectio

Angular dependence of the Wigner time delay upon tunnel ionization of H2H_{2}

More than 100 years after its discovery and its explanation in the energy domain, the duration of the photoelectric effect is still heavily studied. The emission time of a photoelectron can be quantified by the Wigner time delay. Experiments addressing this time delay for single-photon ionization became feasible during the last 10 years. A missing piece, which has not been studied, so far, is the Wigner time delay for strong-field ionization of molecules. Here we show experimental data on the Wigner time delay for tunnel ionization of $H_{2}$ molecules and demonstrate its dependence on the emission direction of the electron with respect to the molecular axis. We find, that the observed changes in the Wigner time delay can be quantitatively explained by elongated/shortened travel paths of the electrons that are due to spatial shifts of the electron's birth position after tunneling. This introduces an intuitive perspective towards the Wigner time delay in strong-field ionization.Comment: 17 pages, 6 figure

Borrelia recurrentis Employs a Novel Multifunctional Surface Protein with Anti-Complement, Anti-Opsonic and Invasive Potential to Escape Innate Immunity

Borrelia recurrentis, the etiologic agent of louse-borne relapsing fever in humans, has evolved strategies, including antigenic variation, to evade immune defence, thereby causing severe diseases with high mortality rates. Here we identify for the first time a multifunctional surface lipoprotein of B. recurrentis, termed HcpA, and demonstrate that it binds human complement regulators, Factor H, CFHR-1, and simultaneously, the host protease plasminogen. Cell surface bound factor H was found to retain its activity and to confer resistance to complement attack. Moreover, ectopic expression of HcpA in a B. burgdorferi B313 strain, deficient in Factor H binding proteins, protected the transformed spirochetes from complement-mediated killing. Furthermore, HcpA-bound plasminogen/plasmin endows B. recurrentis with the potential to resist opsonization and to degrade extracellular matrix components. Together, the present study underscores the high virulence potential of B. recurrentis. The elucidation of the molecular basis underlying the versatile strategies of B. recurrentis to escape innate immunity and to persist in human tissues, including the brain, may help to understand the pathological processes underlying louse-borne relapsing fever

Nuclear Skins and Halos in the Mean-Field Theory

Nuclei with large neutron-to-proton ratios have neutron skins, which manifest themselves in an excess of neutrons at distances greater than the radius of the proton distribution. In addition, some drip-line nuclei develop very extended halo structures. The neutron halo is a threshold effect; it appears when the valence neutrons occupy weakly bound orbits. In this study, nuclear skins and halos are analyzed within the self-consistent Skyrme-Hartree-Fock-Bogoliubov and relativistic Hartree-Bogoliubov theories for spherical shapes. It is demonstrated that skins, halos, and surface thickness can be analyzed in a model-independent way in terms of nucleonic density form factors. Such an analysis allows for defining a quantitative measure of the halo size. The systematic behavior of skins, halos, and surface thickness in even-even nuclei is discussed.Comment: 22 RevTeX pages, 22 EPS figures included, submitted to Physical Review

PET/CT radiomics for prediction of hyperprogression in metastatic melanoma patients treated with immune checkpoint inhibitors

PurposeThis study evaluated pretreatment 2[18F]fluoro-2-deoxy-D-glucose (FDG)-PET/CT-based radiomic signatures for prediction of hyperprogression in metastatic melanoma patients treated with immune checkpoint inhibition (ICI).Material and methodFifty-six consecutive metastatic melanoma patients treated with ICI and available imaging were included in the study and 330 metastatic lesions were individually, fully segmented on pre-treatment CT and FDG-PET imaging. Lesion hyperprogression (HPL) was defined as lesion progression according to RECIST 1.1 and doubling of tumor growth rate. Patient hyperprogression (PD-HPD) was defined as progressive disease (PD) according to RECIST 1.1 and presence of at least one HPL. Patient survival was evaluated with Kaplan-Meier curves. Mortality risk of PD-HPD status was assessed by estimation of hazard ratio (HR). Furthermore, we assessed with Fisher test and Mann-Whitney U test if demographic or treatment parameters were different between PD-HPD and the remaining patients. Pre-treatment PET/CT-based radiomic signatures were used to build models predicting HPL at three months after start of treatment. The models were internally validated with nested cross-validation. The performance metric was the area under receiver operating characteristic curve (AUC).ResultsPD-HPD patients constituted 57.1% of all PD patients. PD-HPD was negatively related to patient overall survival with HR=8.52 (95%CI 3.47-20.94). Sixty-nine lesions (20.9%) were identified as progressing at 3 months. Twenty-nine of these lesions were classified as hyperprogressive, thereby showing a HPL rate of 8.8%. CT-based, PET-based, and PET/CT-based models predicting HPL at three months after the start of treatment achieved testing AUC of 0.703 +/- 0.054, 0.516 +/- 0.061, and 0.704 +/- 0.070, respectively. The best performing models relied mostly on CT-based histogram features.ConclusionsFDG-PET/CT-based radiomic signatures yield potential for pretreatment prediction of lesion hyperprogression, which may contribute to reducing the risk of delayed treatment adaptation in metastatic melanoma patients treated with ICI