Balancing and model reduction for discrete-time nonlinear systems based on Hankel singular value analysis

This paper is concerned with balanced realization and model reduction for discrete-time nonlinear systems. Singular perturbation type balanced truncation method is proposed. In this procedure, the Hankel singular values and the related controllability and observability properties are preserved, which is a natural generalization of both the linear discrete-time case and the nonlinear continuous-time case.

Shp2/MAPK signaling controls goblet/paneth cell fate decisions in the intestine

In the development of the mammalian intestine, Notch and Wnt/{beta}-catenin signals control stem cell maintenance and their differentiation into absorptive and secretory cells. Mechanisms that regulate differentiation of progenitors into the three secretory lineages, goblet, paneth, or enteroendocrine cells, are not fully understood. Using conditional mutagenesis in mice, we observed that Shp2-mediated MAPK signaling determines the choice between paneth and goblet cell fates and also affects stem cells, which express the leucine-rich repeat-containing receptor 5 (Lgr5). Ablation of the tyrosine phosphatase Shp2 in the intestinal epithelium reduced MAPK signaling and led to a reduction of goblet cells while promoting paneth cell development. Conversely, conditional mitogen-activated protein kinase kinase 1 (Mek1) activation rescued the Shp2 phenotype, promoted goblet cell and inhibited paneth cell generation. The Shp2 mutation also expanded Lgr5+ stem cell niches, which could be restricted by activated Mek1 signaling. Changes of Lgr5+ stem cell quantities were accompanied by alterations of paneth cells, indicating that Shp2/MAPK signaling might affect stem cell niches directly or via paneth cells. Remarkably, inhibition of MAPK signaling in intestinal organoids and cultured cells changed the relative abundance of Tcf4 isoforms and by this, promoted Wnt/{beta}-catenin activity. The data thus show that Shp2-mediated MAPK signaling controls the choice between goblet and paneth cell fates by regulating Wnt/{beta}-catenin activity

An MILP modeling approach to systemic energy technology valuation in the 21st Century energy system

New cannot be measured with old. The transformation of the electricity system from a network of fossil-based dispatchable power plants to one with large amounts of intermittent renewable power generation, flexible loads and markets, requires a concurrent development of new evaluation tools and metrics. The focus of this research is to investigate the value of power technologies in order to support decision making on optimal power system design and operation. Technology valuation metrics need to consider the complexity and interdependency of environmental and security objectives, rather than focusing on individual cost-competitiveness of technologies outside of the power system. We present the System Value as a new technology valuation metric, based on a mixed-integer linear program (MILP) formulation of a national-scale electricity system. The Electricity System Optimization model is able to capture detailed technical operation of the individual power plants as well as environmental and security requirements on the system level. We present a case study on the System Value of onshore wind power plants in comparison with Carbon Capture and Storage (CCS) equipped gas-fired power plants in a 2035 UK electricity system. Under the given emission constraints, the deployment of both technologies reduce total system cost of electricity generation. In the case of CCS-equipped power plants the reductions in total system cost are 2 to 5 times higher than for the deployment of onshore wind capacity

Bacterial protein microarrays for identification of new potential diagnostic markers for Neisseria meningitidis infections

Neisseria meningitidis is the most common cause of meningitis and causes epidemic outbreaks. One trait of N. meningitidis, which is associated with most of the currently recognized virulence determinants, is the presence of phase-variable genes that are suspected to enhance its ability to cause an invasive disease. To detect the immune responses to phase-variable expressed proteins, we applied protein microarray technology for the screening of meningitis patient sera. We amplified all 102 known phase-variable genes from N. meningitidis serogroup B strain MC58 by polymerase chain reaction and subcloned them for expression in Escherichia coli. With this approach, we were able to express and purify 67 recombinant proteins representing 66% of the annotated genes. These were spotted robotically onto coated glass slides to generate protein microarrays, which were screened using 20 sera of patients suffering from meningitis, as well as healthy controls. From these screening experiments, 47 proteins emerged as immunogenic, exhibiting a variable degree of seroreactivity with some of the patient sera. Nine proteins elicited an immune response in more than three patients, with one of them, the phase-variable opacity protein OpaV (NMB0442), showing responses in 11 patient sera. This is the first time that protein microarray technology has been applied for the investigation of genetic phase variation in pathogens. The identification of disease-specific proteins is a significant target in biomedical research, as such proteins may have medical, diagnostic, and commercial potential as disease markers

High magnitude and rapid incision from river capture: Rhine River, Switzerland

Landscape evolution is controlled by the development and organization of drainage basins. As a landscape evolves, drainage reorganization events can occur via river capture or piracy, whereby one river basin grows at the expense of another. The river downstream of a capture location will generate a transient topographic response as the added water discharge increases sediment transport and erosion efficiency. This erosional response will propagate upstream through both the captured and original river basins. Here we focus on quantifying the impact of drainage reorganization along the Rhine/Aare River system (~45,000 km 2 ) during the late Pliocene/early Pleistocene, where gravel remnants indicate total incision of ~650 m during the last ~4.2 Myr in the region of the recent Aare‐Rhine confluence. We develop a numerical model of drainage capture to quantify the range of possible magnitudes of erosion and the transient river response resulting from the reorganization of the Rhine River. The model accounts for both fluvial incision and sediment transport. Our model estimates 400–800 m of river elevation change (lowering profiles) during the last ~4 Myr due to river capture events, providing an important component to the recent exhumation budget of the Swiss Alpine Foreland. The model indicates a rapid response to capture events (re‐equilibration timescale of ~1 Myr). The predicted incision magnitudes are consistent with incision measured from the elevation of Pliocene and early Pleistocene river gravels, suggesting that across northern Switzerland, a significant amount of incision can be explained by drainage reorganization. Key Points Drainage capture has caused significant erosion along the Rhine River The transient erosional wave propagates quickly through the landscape The incision is a significant fraction of Plio‐Pleistocene erosion in the regionPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99064/1/jgrf20056.pd

Cognitive facilitation following intentional odor exposure

This paper reviews evidence that, in addition to incidental olfactory pollutants, intentional odor delivery can impact cognitive operations both positively and negatively. Evidence for cognitive facilitation/interference is reviewed alongside four potential explanations for odor-induced effects. It is concluded that the pharmacological properties of odors can induce changes in cognition. However, these effects can be accentuated/attenuated by the shift in mood following odor exposure, expectancy of cognitive effects, and cues to behavior via the contextual association with the odor. It is proposed that greater consideration is required in the intentional utilization of odors within both industrial and private locations, since differential effects are observed for odors with positive hedonic qualities

Transverse thermal depinning and nonlinear sliding friction of an adsorbed monolayer

We study the response of an adsorbed monolayer under a driving force as a model of sliding friction phenomena between two crystalline surfaces with a boundary lubrication layer. Using Langevin-dynamics simulation, we determine the nonlinear response in the direction transverse to a high symmetry direction along which the layer is already sliding. We find that below a finite transition temperature, there exist a critical depinning force and hysteresis effects in the transverse response in the dynamical state when the adlayer is sliding smoothly along the longitudinal direction.Comment: 4 pages, 4 figures, to appear in Phys. Rev. Let