A phantom for the quantitative determination and improvement of the spatial resolution in slice-selective 2D-FT magnetic resonance micro-imaging and -microscopy based on Deep X-ray Lithography (DXRL)

Introduction: The most important assessed quality-control (QC) criteria for improvements in high-resolution imaging are represented by the contrast-to-noise-ratio and spatial resolution. Ultra-High-Field (UHF) Magnetic-Resonance-scanners (B ≥ 7 T) for medical research allowed for the improvement in spatial resolution up to the microimaging and nominal microscopy range [pixel-size: ps < (100 μm)2], even in-vivo on humans just recently. Preclinical MRI- and dedicated MR-microscopy (MRM) scanners already allow for microimaging and MRM (1-256 μm) but lack a sensible spatial resolution phantom for QC and performance improvements in hardware, pulse-sequencing and MRprotocols. In most scientific MRI articles, the spatial resolution is characterized by the ps, though this measurement parameter only limits the actual resolution. Methods: Here the Modulation-Transfer-Function (MTF) is used as evaluation concept for the determination of the spatial resolution in MRM using simple intensity profiles. The resolution limit is defined using a critical modulation-level. In approaching visual impressions on spatial resolution an additional criterion derived from the Modulation-depth-to-Noise-Ratio (MNR) is proposed. A practical method for assessment based on a concrete phantom design and its realization is shown. Results: The phantom design consists of several sets of fine grids, specifically featuring high structural anisotropy for optimum SNR and CNR, with different spatial periods ranging from a1 = 256 μm down to a8 = 2 μm, not only for a quick visual qualitative check, but also for quantification of resolution using the MTF for two different spatial encodings in two orthogonal in-plane directions. The challenging demands on the manufacturing technology especially with regard to the aspect-ratio are approached using Deep-X-Ray-Lithography (DXRL) relying on the high brilliance of Synchroton-radiation. Smallest grid plates with width of 4 μm corresponding to 125 line pairs/mm at a plate depth of 100 μm were achieved. Discussion: MR-microscopic images, originating from a microscopy insert on a human UHF-MR-scanner, were used for demonstration of the evaluation process with two independent resolution-criteria. The developed prototype offers unique possibilities for quantitative resolution QC on UHF human and preclinical MR-scanners. Such a resolution-phantom might be very important for the improvement of MR-pulse-sequences, MR-protocols and even hardware. In principle the phantom can also be used for other microscopic imaging-modalities as for instance μCT and Optical-Coherence-Tomography (OCT)

Equivalence of Additive and Multiplicative Coupling in Spiking Neural Networks

Spiking neural network models characterize the emergent collective dynamics of circuits of biological neurons and help engineer neuro-inspired solutions across fields. Most dynamical systems' models of spiking neural networks typically exhibit one of two major types of interactions: First, the response of a neuron's state variable to incoming pulse signals (spikes) may be additive and independent of its current state. Second, the response may depend on the current neuron's state and multiply a function of the state variable. Here we reveal that spiking neural network models with additive coupling are equivalent to models with multiplicative coupling for simultaneously modified intrinsic neuron time evolution. As a consequence, the same collective dynamics can be attained by state-dependent multiplicative and constant (state-independent) additive coupling. Such a mapping enables the transfer of theoretical insights between spiking neural network models with different types of interaction mechanisms as well as simpler and more effective engineering applications

A phantom for the quantitative determination and improvement of the spatial resolution in slice-selective 2D-FT magnetic resonance micro-imaging and -microscopy based on Deep X-ray Lithography (DXRL)

Introduction: The most important assessed quality-control (QC) criteria for improvements in high-resolution imaging are represented by the contrast-to-noise-ratio and spatial resolution. Ultra-High-Field (UHF) Magnetic-Resonance-scanners (B ≥ 7 T) for medical research allowed for the improvement in spatial resolution up to the microimaging and nominal microscopy range [pixel-size: ps &lt; (100 μm)2], even in-vivo on humans just recently. Preclinical MRI- and dedicated MR-microscopy (MRM) scanners already allow for microimaging and MRM (1-256 μm) but lack a sensible spatial resolution phantom for QC and performance improvements in hardware, pulse-sequencing and MRprotocols. In most scientific MRI articles, the spatial resolution is characterized by the ps, though this measurement parameter only limits the actual resolution.Methods: Here the Modulation-Transfer-Function (MTF) is used as evaluation concept for the determination of the spatial resolution in MRM using simple intensity profiles. The resolution limit is defined using a critical modulation-level. In approaching visual impressions on spatial resolution an additional criterion derived from the Modulation-depth-to-Noise-Ratio (MNR) is proposed. A practical method for assessment based on a concrete phantom design and its realization is shown.Results: The phantom design consists of several sets of fine grids, specifically featuring high structural anisotropy for optimum SNR and CNR, with different spatial periods ranging from a1 = 256 μm down to a8 = 2 μm, not only for a quick visual qualitative check, but also for quantification of resolution using the MTF for two different spatial encodings in two orthogonal in-plane directions. The challenging demands on the manufacturing technology especially with regard to the aspect-ratio are approached using Deep-X-Ray-Lithography (DXRL) relying on the high brilliance of Synchroton-radiation. Smallest grid plates with width of 4 μm corresponding to 125 line pairs/mm at a plate depth of 100 μm were achieved.Discussion: MR-microscopic images, originating from a microscopy insert on a human UHF-MR-scanner, were used for demonstration of the evaluation process with two independent resolution-criteria. The developed prototype offers unique possibilities for quantitative resolution QC on UHF human and preclinical MR-scanners. Such a resolution-phantom might be very important for the improvement of MR-pulse-sequences, MR-protocols and even hardware. In principle the phantom can also be used for other microscopic imaging-modalities as for instance μCT and Optical-Coherence-Tomography (OCT)

Untersuchungen zur Beäsung von Futterhecken mit Ziegenlämmern

In der Untersuchung zur Beäsung von Futterhecken mit Ziegenlämmern wurden in drei Futterhecken, die in den Jahren zuvor unterschiedlich gepflegt wurden, Fraßhorizont, Biomassevolumen, Blatt- und Rindenverbiss bestimmt

Explosive Transitions in Epidemic Dynamics

Standard epidemic models exhibit one continuous, second order phase transition to macroscopic outbreaks. However, interventions to control outbreaks may fundamentally alter epidemic dynamics. Here we reveal how such interventions modify the type of phase transition. In particular, we uncover three distinct types of explosive phase transitions for epidemic dynamics with capacity-limited interventions. Depending on the capacity limit, interventions may (i) leave the standard second order phase transition unchanged but exponentially suppress the probability of large outbreaks, (ii) induce a first-order discontinuous transition to macroscopic outbreaks, or (iii) cause a secondary explosive yet continuous third-order transition. These insights highlight inherent limitations in predicting and containing epidemic outbreaks. More generally our study offers a cornerstone example of a third order explosive phase transition in complex systems.Comment: Main manuscript: 5 pages, 3 figures; Supplemental material: 27 pages, 13 figure

Proteome analysis of the HIV-1 Gag interactome

AbstractHuman immunodeficiency virus Gag drives assembly of virions in infected cells and interacts with host factors which facilitate or restrict viral replication. Although several Gag-binding proteins have been characterized, understanding of virus–host interactions remains incomplete. In a series of six affinity purification screens, we have identified protein candidates for interaction with HIV-1 Gag. Proteins previously found in virions or identified in siRNA screens for host factors influencing HIV-1 replication were recovered. Helicases, translation factors, cytoskeletal and motor proteins, factors involved in RNA degradation and RNA interference were enriched in the interaction data. Cellular networks of cytoskeleton, SR proteins and tRNA synthetases were identified. Most prominently, components of cytoplasmic RNA transport granules were co-purified with Gag. This study provides a survey of known Gag–host interactions and identifies novel Gag binding candidates. These factors are associated with distinct molecular functions and cellular pathways relevant in host–pathogen interactions

Transcriptomic response to prolonged ethanol production in the cyanobacterium Synechocystis sp. PCC6803

BACKGROUND: The production of biofuels in photosynthetic microalgae and cyanobacteria is a promising alternative to the generation of fuels from fossil resources. To be economically competitive, producer strains need to be established that synthesize the targeted product at high yield and over a long time. Engineering cyanobacteria into forced fuel producers should considerably interfere with overall cell homeostasis, which in turn might counteract productivity and sustainability of the process. Therefore, in-depth characterization of the cellular response upon long-term production is of high interest for the targeted improvement of a desired strain. RESULTS: The transcriptome-wide response to continuous ethanol production was examined in Synechocystis sp. PCC6803 using high resolution microarrays. In two independent experiments, ethanol production rates of 0.0338% (v/v) ethanol d(-1) and 0.0303% (v/v) ethanol d(-1) were obtained over 18 consecutive days, measuring two sets of biological triplicates in fully automated photobioreactors. Ethanol production caused a significant (~40%) delay in biomass accumulation, the development of a bleaching phenotype and a down-regulation of light harvesting capacity. However, microarray analyses performed at day 4, 7, 11 and 18 of the experiment revealed only three mRNAs with a strongly modified accumulation level throughout the course of the experiment. In addition to the overexpressed adhA (slr1192) gene, this was an approximately 4 fold reduction in cpcB (sll1577) and 3 to 6 fold increase in rps8 (sll1809) mRNA levels. Much weaker modifications of expression level or modifications restricted to day 18 of the experiment were observed for genes involved in carbon assimilation (Ribulose bisphosphate carboxylase and Glutamate decarboxylase). Molecular analysis of the reduced cpcB levels revealed a post-transcriptional processing of the cpcBA operon mRNA leaving a truncated mRNA cpcA* likely not competent for translation. Moreover, western blots and zinc-enhanced bilin fluorescence blots confirmed a severe reduction in the amounts of both phycocyanin subunits, explaining the cause of the bleaching phenotype. CONCLUSIONS: Changes in gene expression upon induction of long-term ethanol production in Synechocystis sp. PCC6803 are highly specific. In particular, we did not observe a comprehensive stress response as might have been expected

Lipidomimetic Compounds Act as HIV-1 Entry Inhibitors by Altering Viral Membrane Structure

The envelope of Human Immunodeficiency Virus type 1 (HIV-1) consists of a liquid-ordered membrane enriched in raft lipids and containing the viral glycoproteins. Previous studies demonstrated that changes in viral membrane lipid composition affecting membrane structure or curvature can impair infectivity. Here, we describe novel antiviral compounds that were identified by screening compound libraries based on raft lipid-like scaffolds. Three distinct molecular structures were chosen for mode-of-action studies, a sterol derivative (J391B), a sphingosine derivative (J582C) and a long aliphatic chain derivative (IBS70). All three target the viral membrane and inhibit virus infectivity at the stage of fusion without perturbing virus stability or affecting virion-associated envelope glycoproteins. Their effect did not depend on the expressed envelope glycoproteins or a specific entry route, being equally strong in HIV pseudotypes carrying VSV-G or MLV-Env glycoproteins. Labeling with laurdan, a reporter of membrane order, revealed different membrane structure alterations upon compound treatment of HIV-1, which correlated with loss of infectivity. J582C and IBS70 decreased membrane order in distinctive ways, whereas J391B increased membrane order. The compounds' effects on membrane order were reproduced in liposomes generated from extracted HIV lipids and thus independent both of virion proteins and of membrane leaflet asymmetry. Remarkably, increase of membrane order by J391B required phosphatidylserine, a lipid enriched in the HIV envelope. Counterintuitively, mixtures of two compounds with opposite effects on membrane order, J582C and J391B, did not neutralize each other but synergistically inhibited HIV infection. Thus, altering membrane order, which can occur by different mechanisms, constitutes a novel antiviral mode of action that may be of general relevance for enveloped viruses and difficult to overcome by resistance development