Ion channels and neuronal excitability in polyglutamine neurodegenerative diseases

Abstract Polyglutamine (polyQ) diseases are a family composed of nine neurodegenerative inherited disorders (NDDs) caused by pathological expansions of cytosine-adenine-guanine (CAG) trinucleotide repeats which encode a polyQ tract in the corresponding proteins. CAG polyQ repeat expansions produce neurodegeneration via multiple downstream mechanisms; among those the neuronal activity underlying the ion channels is affected directly by specific channelopathies or indirectly by secondary dysregulation. In both cases, the altered excitability underlies to gain- or loss-of-function pathological effects. Here we summarize the repertoire of ion channels in polyQ NDDs emphasizing the biophysical features of neuronal excitability and their pathogenic role. The aim of this review is to point out the value of a deeper understanding of those functional mechanisms and processes as crucial elements for the designing and targeting of novel therapeutic avenues

On representation of the t-J model via spin-charge variables

We show that the t-J Hamiltonian is not in general reduced to H(S,f), where S and f stand for independent ([S,f]=0) SU(2) (spin) generators and spinless fermionic (hole) field, respectively. The proof is based upon an identification of the Hubbard operators with the generators of the su(2|1) superalgebra in the degenerate fundamental representation and ensuing SU(2|1) path integral representation of the partition function.Comment: 15 pages, latex, no figure

Essential spectra and exponential estimates of eigenfunctions of lattice operators of quantum mechanics

This paper is devoted to estimates of the exponential decay of eigenfunctions of difference operators on the lattice Z^n which are discrete analogs of the Schr\"{o}dinger, Dirac and square-root Klein-Gordon operators. Our investigation of the essential spectra and the exponential decay of eigenfunctions of the discrete spectra is based on the calculus of so-called pseudodifference operators (i.e., pseudodifferential operators on the group Z^n) with analytic symbols and on the limit operators method. We obtain a description of the location of the essential spectra and estimates of the eigenfunctions of the discrete spectra of the main lattice operators of quantum mechanics, namely: matrix Schr\"{o}dinger operators on Z^n, Dirac operators on Z^3, and square root Klein-Gordon operators on Z^n

New evidence of dominant processing effects in standard and oxygenated silicon diodes after neutron irradiation

Abstract Silicon diodes processed on standard and oxygenated silicon substrates by three different manufacturers have been irradiated by neutrons in a nuclear reactor. The leakage current density ( J D ) increase is linear with the neutron fluence. J D and its annealing curve at 80°C do not present any sizeable dependence on substrate oxygenation and/or manufacturing process. The acceptor introduction rate ( β ) of the effective substrate doping concentration ( N eff ) is independent from the oxygen concentration when standard and oxygenated devices from the same manufacturer are considered. On the contrary, β significantly varies from one manufacturer to another showing that the β dependence on the particular process can be important, overtaking the small substrate oxygenation effect. Finally, the average saturation value of the N eff reverse annealing is slightly lower for the oxygenated samples, pointing out a positive effect of the substrate oxygenation even for devices irradiated by neutrons

Spectral properties of the t-J model in the presence of hole-phonon interaction

We examine the effects of electron-phonon interaction on the dynamics of the charge carriers doped in two-dimensional (2D) Heisenberg antiferromagnet. The $t$-$J$ model Hamiltonian with a Fr\"ohlich term which couples the holes to a dispersionless (optical) phonon mode is considered for low doping concentration. The evolution of the spectral density function, the density of states, and the momentum distribution function of the holes with an increase of the hole-phonon coupling constant $g$ is studied numerically. As the coupling to a phonon mode increases the quasiparticle spectral weight decreases and a ``phonon satellite'' feature close to the quasi-particle peak becomes more pronounced. Furthermore, strong electron-phonon coupling smears the multi-magnon resonances (``string states'') in the incoherent part of the spectral function. The jump in the momentum distribution function at the Fermi surface is reduced without changing the hole pocket volume, thereby providing a numerical verification of Luttinger theorem for this strongly interacting system. The vertex corrections due to electron- phonon interaction are negligible in spite of the fact that the ratio of the phonon frequency to the effective bandwidth is not small.Comment: REVTeX, 20 pages, 9 figures, to be published in Phys. Rev. B (Nov. 1, 1996

Multi-store Competition: Market Segmentation or Interlacing

This paper develops a model for multi-store competition between firms. Using the fact that different firms have different outlets and produce horizontally differentiated goods, we obtain a pure strategy equilibrium where firms choose a different location for each outlet and firms' locations are interlaced. The location decisions of multi-store firms are completely independent of each other. Firms choose locations that minimize transportation costs of consumers. Moreover, generically, the subgame perfect equilibrium is unique and when the firms have an equal number of outlets, prices are independent of the number of outlets

Clinical Outcomes in Patients Undergoing Percutaneous Closure of Periprosthetic Paravalvular Leaks

ObjectivesThe purpose of this study was to evaluate the feasibility and efficacy of the percutaneous device closure of a consecutive series of patients with periprosthetic paravalvular leaks referred to our structural heart disease center with congestive heart failure and hemolytic anemia.BackgroundClinically significant periprosthetic paravalvular leak is an uncommon but serious complication after surgical valve replacement. Percutaneous closure has been utilized as an alternative to surgical repair of this defect in high-risk surgical patients.MethodsThis is a retrospective review of 57 percutaneous paravalvular leak closures that were performed in 43 patients (67% male, mean age 69.4 ± 11.7 years) between April 2006 and September 2010. Integrated imaging modalities were used for the evaluation, planning, and guidance of the interventions.ResultsClosure was successful in 86% of leaks and in 86% of patients. Twenty-eight of 35 patients improved by at least 1 New York Heart Association functional class. The percentage of patients requiring blood transfusions and/or erythropoietin injections post-procedure decreased from 56% to 5%. Clinical success was achieved in 89% of the patients in whom procedure was successful. The survival rates for patients at 6, 12, and 18 months after paravalvular leak closures were 91.9%, 89.2%, and 86.5%, respectively. Freedom from cardiac-related death at 42 months post-procedure was 91.9%.ConclusionsPercutaneous closure of symptomatic paravalvular leaks, facilitated by integrated imaging modalities has a high rate of acute and long-term success and appears to be effective in managing symptoms of heart failure and hemolytic anemia

Competition-based model of pheromone component ratio detection in the moth

For some moth species, especially those closely interrelated and sympatric, recognizing a specific pheromone component concentration ratio is essential for males to successfully locate conspecific females. We propose and determine the properties of a minimalist competition-based feed-forward neuronal model capable of detecting a certain ratio of pheromone components independently of overall concentration. This model represents an elementary recognition unit for the ratio of binary mixtures which we propose is entirely contained in the macroglomerular complex (MGC) of the male moth. A set of such units, along with projection neurons (PNs), can provide the input to higher brain centres. We found that (1) accuracy is mainly achieved by maintaining a certain ratio of connection strengths between olfactory receptor neurons (ORN) and local neurons (LN), much less by properties of the interconnections between the competing LNs proper. An exception to this rule is that it is beneficial if connections between generalist LNs (i.e. excited by either pheromone component) and specialist LNs (i.e. excited by one component only) have the same strength as the reciprocal specialist to generalist connections. (2) successful ratio recognition is achieved using latency-to-first-spike in the LN populations which, in contrast to expectations with a population rate code, leads to a broadening of responses for higher overall concentrations consistent with experimental observations. (3) when longer durations of the competition between LNs were observed it did not lead to higher recognition accuracy

Interplay of thermal and non-thermal effects in x-ray-induced ultrafast melting

X-ray laser-induced structural changes in silicon undergoing femtosecond melting have been investigated by using an x-ray pump-x-ray probe technique. The experimental results for different initial sample temperatures reveal that the onset time and the speed of the atomic disordering are independent of the initial temperature, suggesting that equilibrium atomic motion in the initial state does not play a pivotal role in the x-ray-induced ultrafast melting. By comparing the observed time-dependence of the atomic disordering and the dedicated theoretical simulations, we interpret that the energy transfer from the excited electrons to ions via electron-ion coupling (thermal effect) as well as a strong modification of the interatomic potential due to electron excitations (non-thermal effect) trigger the ultrafast atomic disordering. Our finding of the interplay of thermal and non-thermal effects in the x-ray-induced melting demonstrates that accurate modeling of intense x-ray interactions with matter is essential to ensure a correct interpretation of experiments using intense x-ray laser pulses