Family of solvable generalized random-matrix ensembles with unitary symmetry

We construct a very general family of characteristic functions describing Random Matrix Ensembles (RME) having a global unitary invariance, and containing an arbitrary, one-variable probability measure which we characterize by a `spread function'. Various choices of the spread function lead to a variety of possible generalized RMEs, which show deviations from the well-known Gaussian RME originally proposed by Wigner. We obtain the correlation functions of such generalized ensembles exactly, and show examples of how particular choices of the spread function can describe ensembles with arbitrary eigenvalue densities as well as critical ensembles with multifractality.Comment: 4 pages, to be published in Phys. Rev. E, Rapid Com

Statistics of work performed on a forced quantum oscillator

Various aspects of the statistics of work performed by an external classical force on a quantum mechanical system are elucidated for a driven harmonic oscillator. In this special case two parameters are introduced that are sufficient to completely characterize the force protocol. Explicit results for the characteristic function of work and the respective probability distribution are provided and discussed for three different types of initial states of the oscillator: microcanonical, canonical and coherent states. Depending on the choice of the initial state the probability distributions of the performed work may grossly differ. This result in particular holds also true for identical force protocols. General fluctuation and work theorems holding for microcanonical and canonical initial states are confirmed

Scale and sense of place among urban dwellers

Place connections are core to being human: Every person lives in, and thus has direct experience of, at least one place and likely of numerous places throughout a lifetime. Sense of place—or the meanings, knowledge, and bonds that arise from the biophysical, social, and political–economic aspects of places—in turn influences people\u27s interactions with those places. Of particular interest to researchers, practitioners, and policymakers, such interactions can impact place-protective, stewardship, or conservation behaviors. However, how sense of place develops and what it represents is shifting in today\u27s rapidly urbanizing, globalizing world. Especially when considering the integrated social–ecological context, questions related to how sense of place forms and is enacted in urban settings and at a range of geographic scales are challenging to study. Our study addresses this dynamic space: We examined how people\u27s place connections intersect with their notions of geographic scale and levels of urbanity. Specifically, we conducted a 1201-person randomized telephone survey in the San Francisco Bay Area ecoregion of California, USA, to explore how sense of place varies by (1) the scale of what people consider to be their place, and (2) the urbanity of where people live. In comparison with respondents who perceived their place as the larger-scale ecoregion, we found that respondents who perceived their place as primarily focused on the urban area rated their connection to the biophysical aspects of place (the plants, animals, and landscape-related elements) lower. Similarly, overall, respondents who lived in urban areas rated their connections to the biophysical aspects of place lower than did respondents who lived in non-urban areas. Our findings suggest the importance of encouraging conceptualizations of place at broader geographic scales and, particularly, of supporting notions of urban spaces that stretch beyond urban boundaries. We also call for supporting increased engagement with urban nature, especially among residents of urban areas

BLUF Domain Function Does Not Require a Metastable Radical Intermediate State

BLUF (blue light using flavin) domain proteins are an important family of blue light-sensing proteins which control a wide variety of functions in cells. The primary light-activated step in the BLUF domain is not yet established. A number of experimental and theoretical studies points to a role for photoinduced electron transfer (PET) between a highly conserved tyrosine and the flavin chromophore to form a radical intermediate state. Here we investigate the role of PET in three different BLUF proteins, using ultrafast broadband transient infrared spectroscopy. We characterize and identify infrared active marker modes for excited and ground state species and use them to record photochemical dynamics in the proteins. We also generate mutants which unambiguously show PET and, through isotope labeling of the protein and the chromophore, are able to assign modes characteristic of both flavin and protein radical states. We find that these radical intermediates are not observed in two of the three BLUF domains studied, casting doubt on the importance of the formation of a population of radical intermediates in the BLUF photocycle. Further, unnatural amino acid mutagenesis is used to replace the conserved tyrosine with fluorotyrosines, thus modifying the driving force for the proposed electron transfer reaction; the rate changes observed are also not consistent with a PET mechanism. Thus, while intermediates of PET reactions can be observed in BLUF proteins they are not correlated with photoactivity, suggesting that radical intermediates are not central to their operation. Alternative nonradical pathways including a keto–enol tautomerization induced by electronic excitation of the flavin ring are considered

Differential regulation of C-C chemokines during fibroblast-monocyte interactions: adhesion vs. inflammatory cytokine pathways.

The cell-to-cell interactions during chronic inflammatory diseases likely contribute to leukocyte accumulation leading to increased pathology and organ dysfunction. In particular, there is a paucity of information relating to the maintenance of chronic fibrotic diseases. Using a lung fibroblast line and enriched monocyte populations, we have investigated the activational events which contribute to the production of two C-C chemokines, macrophage inflammatory protein-1 alpha (MIP-1alpha) and monocyte chemoattractant protein-1 (MCP-1), during fibroblast-monocyte interactions. Neither the fibroblast cell line (16lu) nor isolated monocytes alone produced significant levels of MIP-1alpha or MCP-1. However, when isolated monocytes were layered onto 16 lu fibroblast monolayers a significant increase in MIP-1alpha and MCP-1 production was observed. The use of fixed cell populations indicated that the MIP-1alpha was derived from monocytes and MCP-1 from both cell populations. To examine the molecules which were required for chemokine production during the interaction, specific antibodies were used in the co-cultures. Blocking beta3-integrin interactions significantly inhibited MIP-1alpha production. In contrast, beta-integrin interactions had no effect on the MCP-1 production, while, neutralization of TNF significantly decreased MCP-1 production during the co-culture. These data indicate that fibroblast-monocyte interactions induce chemokine production through different mechanisms and a combination of these responses may contribute to the maintenance of the mononuclear cell accumulation during disease progression

Inhibition of uric acid or IL- 1β ameliorates respiratory syncytial virus immunopathology and development of asthma

BackgroundRespiratory syncytial virus (RSV) affects most infants early in life and is associated with increased asthma risk. The specific mechanism remains unknown.ObjectiveTo investigate the role of uric acid (UA) and IL- 1β in RSV immunopathology and asthma predisposition.MethodsTracheal aspirates from human infants with and without RSV were collected and analyzed for pro- IL- 1β mRNA and protein to establish a correlation in human disease. Neonatal mouse models of RSV were employed, wherein mice infected at 6- 7 days of life were analyzed at 8 days postinfection, 5 weeks postinfection, or after a chronic cockroach allergen asthma model. A xanthine oxidase inhibitor or IL- 1 receptor antagonist was administered during RSV infection.ResultsHuman tracheal aspirates from RSV- infected infants showed elevated pro- IL- 1β mRNA and protein. Inhibition of UA or IL- 1β during neonatal murine RSV infection decreased mucus production, reduced cellular infiltrates to the lung (especially ILC2s), and decreased type 2 immune responses. Inhibition of either UA or IL- 1β during RSV infection led to chronic reductions in pulmonary immune cell composition and reduced type 2 immune responses and reduced similar responses after challenge with cockroach antigen.ConclusionsInhibiting UA and IL- 1β during RSV infection ameliorates RSV immunopathology, reduces the consequences of allergen- induced asthma, and presents new therapeutic targets to reduce early- life viral- induced asthma development.Neonatal RSV infection is associated with increases in pulmonary uric acid and IL- 1β and lung immunopathology. XOI or IL- 1RA administration during neonatal RSV infection leads to reduced RSV immunopathology. XOI or IL- 1RA administration during neonatal RSV infection leads to reduced type 2 immune responses during a subsequent model of asthma.Abbreviations: IL- 1RA, IL- 1 receptor antagonist; RSV: Respiratory syncytial virus; XOI, xanthine oxidase inhibitor.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162774/3/all14310.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162774/2/all14310_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162774/1/all14310-sup-0005-TableS1.pd

Ultrafast Structural Dynamics of BlsA, a Photoreceptor from the Pathogenic Bacterium Acinetobacter baumannii

Acinetobacter baumannii is an important human pathogen that can form biofilms and persist under harsh environmental conditions. Biofilm formation and virulence are modulated by blue light, which is thought to be regulated by a BLUF protein, BlsA. To understand the molecular mechanism of light sensing, we have used steady-state and ultrafast vibrational spectroscopy to compare the photoactivation mechanism of BlsA to the BLUF photosensor AppA from Rhodobacter sphaeroides. Although similar photocycles are observed, vibrational data together with homology modeling identify significant differences in the β5 strand in BlsA caused by photoactivation, which are proposed to be directly linked to downstream signaling

Development and characterization of synthetic antibodies binding to the cystic fibrosis conductance regulator

Cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel in the apical surface of epithelial cells in the airway and gastrointestinal tract, and mutation of CFTR is the underlying cause of cystic fibrosis. However, the precise molecular details of the structure and function of CFTR in native and disease states remains elusive and cystic fibrosis researchers are hindered by a lack of high specificity, high affinity binding reagents for use in structural and biological studies. Here, we describe a panel of synthetic antigen-binding fragments (Fabs) isolated from a phage-displayed library that are specific for intracellular domains of CFTR that include the nucleotide-binding domains (NBD1 and NBD2), the R-region, and the regulatory insertion loop of NBD1. Binding assays performed under conditions that promote the native fold of the protein demonstrated that all Fabs recognized full-length CFTR. However, only the NBD1-specific Fab recognized denatured CFTR by western blot, suggesting a conformational epitope requirement for the other Fabs. Surface plasmon resonance experiments showed that the R-region Fab binds with high affinity to both the phosphorylated and unphosphorylated R-region. In addition, NMR analysis of bound versus unbound R-region revealed a distinct conformational effect upon Fab binding. We further defined residues involved with antibody recognition using an overlapping peptide array. In summary, we describe methodology complementary to previous hybridoma-based efforts to develop antibody reagents to CFTR, and introduce a synthetic antibody panel to aid structural and biological studies