Applications of Commutator-Type Operators to pp-Groups

For a p-group G admitting an automorphism $\phi$ of order $p^n$ with exactly $p^m$ fixed points such that $\phi^{p^{n-1}}$ has exactly $p^k$ fixed points, we prove that G has a fully-invariant subgroup of m-bounded nilpotency class with $(p,n,m,k)$-bounded index in G. We also establish its analogue for Lie p-rings. The proofs make use of the theory of commutator-type operators.Comment: 11 page

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

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

Eosinophil recruitment into sites of delayed‐type hypersensitivity reactions in mice

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142239/1/jlb0353.pd

C‐C chemokine‐induced eosinophil chemotaxis during allergic airway inflammation

The production of eosinophil‐specific chemotactic factors during allergic airway responses may be a pivotal event resulting in eosinophil accumulation, activation, and airway damage. Recent studies have identified specific chemokines that may play crucial roles in recruitment of eosinophils to the site of allergic reactions. In this study we have utilized an established model of schistosome egg antigen (SEA)‐mediated allergic responses to examine the role of specific C‐C chemokines [macrophage inflammatory protein‐1α (MIP‐1α), RANTES, and monocyte chemoattractant protein‐1 (MCP‐1)] in eosinophil recruitment. We have previously identified a role for MIP‐1α in eosinophil accumulation in the lung and airway during allergic airway inflammation. We extend those studies using in vitro eosinophil chemotaxis to establish that both MIP‐1α and RANTES are potent eosinophil chemotactic factors in lungs during allergic airway responses. Morphometric analysis demonstrated a peribronchial accumulation of eosinophils within the lungs beginning at 8 h, peaking at 24 h, and plateauing at 48–96 h after allergen (SEA) challenge. Utilizing whole‐lung homogenates from allergen‐challenged mice, in vitro eosinophil chemotactic assays demonstrated significant increases in eosinophil chemotactic activity with 8‐h lung homogenates and peak activity with samples from 24‐h lung homogenates. These data correlated with the morphometric analysis of peribronchial eosinophil accumulation in situ. When lung homogenates from allergen‐challenged mice were preincubated in vitro with antibodies specific for MIP‐1α, RANTES, or MCP‐1, a significant reduction in eosinophil chemotaxis was observed with only MIP‐1α and RANTES neutralization. Altogether, these studies indicate that RANTES and MIP‐1α are major eosinophil chemotactic factors produced during allergic airway responses. J. Leukoc. Biol. 60:573–578; 1996.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141543/1/jlb0573.pd

A Grassmann integral equation

The present study introduces and investigates a new type of equation which is called Grassmann integral equation in analogy to integral equations studied in real analysis. A Grassmann integral equation is an equation which involves Grassmann integrations and which is to be obeyed by an unknown function over a (finite-dimensional) Grassmann algebra G_m. A particular type of Grassmann integral equations is explicitly studied for certain low-dimensional Grassmann algebras. The choice of the equation under investigation is motivated by the effective action formalism of (lattice) quantum field theory. In a very general setting, for the Grassmann algebras G_2n, n = 2,3,4, the finite-dimensional analogues of the generating functionals of the Green functions are worked out explicitly by solving a coupled system of nonlinear matrix equations. Finally, by imposing the condition G[{\bar\Psi},{\Psi}] = G_0[{\lambda\bar\Psi}, {\lambda\Psi}] + const., 0<\lambda\in R (\bar\Psi_k, \Psi_k, k=1,...,n, are the generators of the Grassmann algebra G_2n), between the finite-dimensional analogues G_0 and G of the (``classical'') action and effective action functionals, respectively, a special Grassmann integral equation is being established and solved which also is equivalent to a coupled system of nonlinear matrix equations. If \lambda \not= 1, solutions to this Grassmann integral equation exist for n=2 (and consequently, also for any even value of n, specifically, for n=4) but not for n=3. If \lambda=1, the considered Grassmann integral equation has always a solution which corresponds to a Gaussian integral, but remarkably in the case n=4 a further solution is found which corresponds to a non-Gaussian integral. The investigation sheds light on the structures to be met for Grassmann algebras G_2n with arbitrarily chosen n.Comment: 58 pages LaTeX (v2: mainly, minor updates and corrections to the reference section; v3: references [4], [17]-[21], [39], [46], [49]-[54], [61], [64], [139] added

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

Quantum Zeno Effect and Light-Dark Periods for a Single Atom

The quantum Zeno effect (QZE) predicts a slow-down of the time development of a system under rapidly repeated ideal measurements, and experimentally this was tested for an ensemble of atoms using short laser pulses for non-selective state measurements. Here we consider such pulses for selective measurements on a single system. Each probe pulse will cause a burst of fluorescence or no fluorescence. If the probe pulses were strictly ideal measurements, the QZE would predict periods of fluorescence bursts alternating with periods of no fluorescence (light and dark periods) which would become longer and longer with increasing frequency of the measurements. The non-ideal character of the measurements is taken into account by incorporating the laser pulses in the interaction, and this is used to determine the corrections to the ideal case. In the limit, when the time between the laser pulses goes to zero, no freezing occurs but instead we show convergence to the familiar macroscopic light and dark periods of the continuously driven Dehmelt system. An experiment of this type should be feasible for a single atom or ion in a trapComment: 16 pages, LaTeX, a4.sty; to appear in J. Phys.

Misfolding diverts CFTR from recycling to degradation: quality control at early endosomes

To investigate the degradation mechanism of misfolded membrane proteins from the cell surface, we used mutant cystic fibrosis transmembrane conductance regulators (CFTRs) exhibiting conformational defects in post-Golgi compartments. Here, we show that the folding state of CFTR determines the post-endocytic trafficking of the channel. Although native CFTR recycled from early endosomes back to the cell surface, misfolding prevented recycling and facilitated lysosomal targeting by promoting the ubiquitination of the channel. Rescuing the folding defect or down-regulating the E1 ubiquitin (Ub)-activating enzyme stabilized the mutant CFTR without interfering with its internalization. These observations with the preferential association of mutant CFTRs with Hrs, STAM-2, TSG101, hVps25, and hVps32, components of the Ub-dependent endosomal sorting machinery, establish a functional link between Ub modification and lysosomal degradation of misfolded CFTR from the cell surface. Our data provide evidence for a novel cellular mechanism of CF pathogenesis and suggest a paradigm for the quality control of plasma membrane proteins involving the coordinated function of ubiquitination and the Ub-dependent endosomal sorting machinery

Some gating potentiators, including VX-770, diminish ΔF508-CFTR functional expression.

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane regulator (CFTR) that result in reduced anion conductance at the apical membrane of secretory epithelia. Treatment of CF patients carrying the G551D gating mutation with the potentiator VX-770 (ivacaftor) largely restores channel activity and has shown substantial clinical benefit. However, most CF patients carry the ΔF508 mutation, which impairs CFTR folding, processing, function, and stability. Studies in homozygous ΔF508 CF patients indicated little clinical benefit of monotherapy with the investigational corrector VX-809 (lumacaftor) or VX-770, whereas combination clinical trials show limited but significant improvements in lung function. We show that VX-770, as well as most other potentiators, reduces the correction efficacy of VX-809 and another investigational corrector, VX-661. To mimic the administration of VX-770 alone or in combination with VX-809, we examined its long-term effect in immortalized and primary human respiratory epithelia. VX-770 diminished the folding efficiency and the metabolic stability of ΔF508-CFTR at the endoplasmic reticulum (ER) and post-ER compartments, respectively, causing reduced cell surface ΔF508-CFTR density and function. VX-770-induced destabilization of ΔF508-CFTR was influenced by second-site suppressor mutations of the folding defect and was prevented by stabilization of the nucleotide-binding domain 1 (NBD1)-NBD2 interface. The reduced correction efficiency of ΔF508-CFTR, as well as of two other processing mutations in the presence of VX-770, suggests the need for further optimization of potentiators to maximize the clinical benefit of corrector-potentiator combination therapy in CF