Differential K-theory. A survey

Generalized differential cohomology theories, in particular differential K-theory (often called "smooth K-theory"), are becoming an important tool in differential geometry and in mathematical physics. In this survey, we describe the developments of the recent decades in this area. In particular, we discuss axiomatic characterizations of differential K-theory (and that these uniquely characterize differential K-theory). We describe several explicit constructions, based on vector bundles, on families of differential operators, or using homotopy theory and classifying spaces. We explain the most important properties, in particular about the multiplicative structure and push-forward maps and will state versions of the Riemann-Roch theorem and of Atiyah-Singer family index theorem for differential K-theory.Comment: 50 pages, report based in particular on work done sponsored the DFG SSP "Globale Differentialgeometrie". v2: final version (only typos corrected), to appear in C. B\"ar et al. (eds.), Global Differential Geometry, Springer Proceedings in Mathematics 17, Springer-Verlag Berlin Heidelberg 201

Optimizing the spin sensitivity of grain boundary junction nanoSQUIDs -- towards detection of small spin systems with single-spin resolution

We present an optimization study of the spin sensitivity of nanoSQUIDs based on resistively shunted grain boundary Josephson junctions. In addition the dc SQUIDs contain a narrow constriction onto which a small magnetic particle can be placed (with its magnetic moment in the plane of the SQUID loop and perpendicular to the grain boundary) for efficient coupling of its stray magnetic field to the SQUID loop. The separation of the location of optimum coupling from the junctions allows for an independent optimization of the coupling factor $\phi_\mu$ and junction properties. We present different methods for calculating $\phi_\mu$ (for a magnetic nanoparticle placed 10\,nm above the constriction) as a function of device geometry and show that those yield consistent results. Furthermore, by numerical simulations we obtain a general expression for the dependence of the SQUID inductance on geometrical parameters of our devices, which allows to estimate their impact on the spectral density of flux noise $S_\Phi$ of the SQUIDs in the thermal white noise regime. Our analysis of the dependence of $S_\Phi$ and $\phi_\mu$ on the geometric parameters of the SQUID layout yields a spin sensitivity $S_\mu^{1/2}=S_\Phi^{1/2}/\phi_\mu$ of a few $\mu_{\rm{B}}/\rm{Hz^{1/2}}$ ($\mu_B$ is the Bohr magneton) for optimized parameters, respecting technological constraints. However, by comparison with experimentally realized devices we find significantly larger values for the measured white flux noise, as compared to our theoretical predictions. Still, a spin sensitivity on the order of $10\,\mu_{\rm B}/\rm{Hz^{1/2}}$ for optimized devices seems to be realistic.Comment: 10 pages, 5 figures, Superconductor Science and Technology (submitted

Modulation of the Major Paths of Carbon in Photorespiratory Mutants of Synechocystis

Background: Recent studies using transcript and metabolite profiles of wild-type and gene deletion mutants revealed that photorespiratory pathways are essential for the growth of Synechocystis sp. PCC 6803 under atmospheric conditions. Pool size changes of primary metabolites, such as glycine and glycolate, indicated a link to photorespiration. Methodology/Principal Findings: The C-13 labelling kinetics of primary metabolites were analysed in photoautotrophically grown cultures of Synechocystis sp. PCC 6803 by gas chromatography-mass spectrometry (GC-MS) to demonstrate the link with photorespiration. Cells pre-acclimated to high CO2 (5%, HC) or limited CO2 (0.035%, LC) conditions were pulse-labelled under very high (2% w/w) C-13-NaHCO3 (VHC) conditions followed by treatment with ambient C-12 at HC and LC conditions, respectively. The C-13 enrichment, relative changes in pool size, and C-13 flux of selected metabolites were evaluated. We demonstrate two major paths of CO2 assimilation via Rubisco in Synechocystis, i.e., from 3PGA via PEP to aspartate, malate and citrate or, to a lesser extent, from 3PGA via glucose-6-phosphate to sucrose. The results reveal evidence of carbon channelling from 3PGA to the PEP pool. Furthermore, C-13 labelling of glycolate was observed under conditions thought to suppress photorespiration. Using the glycolate-accumulating Delta glcD1 mutant, we demonstrate enhanced C-13 partitioning into the glycolate pool under conditions favouring photorespiration and enhanced C-13 partitioning into the glycine pool of the glycine-accumulating Delta gcvT mutant. Under LC conditions, the photorespiratory mutants Delta glcD1 and Delta gcvT showed enhanced activity of the additional carbon-fixing PEP carboxylase pathway. Conclusions/Significance: With our approach of non-steady-state C-13 labelling and analysis of metabolite pool sizes with respective C-13 enrichments, we identify the use and modulation of major pathways of carbon assimilation in Synechocystis in the presence of high and low inorganic carbon supplies

MRSA Infection in the Thigh Muscle Leads to Systemic Disease, Strong Inflammation, and Loss of Human Monocytes in Humanized Mice

MRSA (Methicillin-resistant Staphylococcus aureus) is the second-leading cause of deaths by antibiotic-resistant bacteria globally, with more than 100,000 attributable deaths annually. Despite the high urgency to develop a vaccine to control this pathogen, all clinical trials with pre-clinically effective candidates failed so far. The recent development of “humanized” mice might help to edge the pre-clinical evaluation closer to the clinical situation and thus close this gap. We infected humanized NSG mice (huNSG: (NOD)-scid IL2Rγnull mice engrafted with human CD34+ hematopoietic stem cells) locally with S. aureus USA300 LAC* lux into the thigh muscle in order to investigate the human immune response to acute and chronic infection. These mice proved not only to be more susceptible to MRSA infection than wild-type or “murinized” mice, but displayed furthermore inferior survival and signs of systemic infection in an otherwise localized infection model. The rate of humanization correlated directly with the severity of disease and survival of the mice. Human and murine cytokine levels in blood and at the primary site of infection were strongly elevated in huNSG mice compared to all control groups. And importantly, differences in human and murine immune cell lineages surfaced during the infection, with human monocyte and B cell numbers in blood and bone marrow being significantly reduced at the later time point of infection. Murine monocytes in contrast behaved conversely by increasing cell numbers. This study demonstrates significant differences in the in vivo behavior of human and murine cells towards S. aureus infection, which might help to sharpen the translational potential of pre-clinical models for future therapeutic approaches

Towards a Standardized Antimicrobial Susceptibility Testing Method for Mycoplasma hyorhinis

Conducting antimicrobial susceptibility testing (AST) in a comparable manner requires the availability of a standardized method. Organizations, such as the Clinical and Laboratory Standards Institute (CLSI) or the European Committee on Antimicrobial Susceptibility Testing (EUCAST), provide standardized protocols for a range of fastidious bacteria but not for Mycoplasma hyorhinis. We developed a broth microdilution method for testing M. hyorhinis in a standardized and harmonized way using a modified Friis broth devoid of antimicrobial or otherwise bacterial growth-inhibiting agents. The type strain M. hyorhinis DSM 25591 was chosen to establish the methodology. The antimicrobial agents of interest were doxycycline, enrofloxacin, erythromycin, florfenicol, gentamicin, marbofloxacin, tetracycline, tiamulin, tilmicosin, tulathromycin, and tylosin, tested by using commercial SensititreTM microtiter plates. In addition, the suitability of the methodology was evaluated via variation of the individual ingredients of the modified Friis broth by either using different batches or choosing other distributors. Despite these alterations, the method provided reliable results. We obtained repeatable minimal inhibitory concentrations for all six tested field isolates and the M. hyorhinis type strain. With this newly proposed method, we aim to provide an improved AST method for diagnostic laboratories and monitoring purposes with better comparability between times and countries. In addition, this new method will allow for an improvement of targeted treatments using antimicrobial agents and thereby reduce the options for resistance development