Current developments in gene therapy for amyotrophic lateral sclerosis.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a devastating adult neurodegenerative disorder characterized by motor neuron degeneration and death around 3 years from onset. So far, riluzole is the only treatment available, although it only offers a slight increase in survival. The complex etiology of ALS, with several genes able to trigger the disease, makes its study difficult. Areas covered: RNA-mediated or protein-mediated toxic gain-of-function leading to motor neuron degeneration appears to be likely common pathogenic mechanisms in ALS. Consequently, gene therapy technologies to reduce toxic RNA and/or proteins and to protect motor neurons by modulating gene expression are at the forefront of the field. Here, we review the most promising scientific advances, paying special attention to the successful treatments tested in animal models as well as analyzing relevant gene therapy clinical trials. Expert opinion: Despite broad advances in target gene identification in ALS and advances in gene therapy technologies, a successful gene therapy for ALS continues to elude researchers. Multiple hurdles encompassing technical, biological, economical and clinical challenges must be overcome before a therapy for patients becomes available. Optimism remains due to positive results obtained in several in vivo studies demonstrating significant disease amelioration in animal models of ALS

Pilot plant for the capture of ammonia from the atmosphere of pig and poultry farms using gas-permeable membrane technology

Gas-permeable membrane (GPM) technology is a possible solution to reduce ammonia (NH3) emissions from livestock housing. This paper presents the results obtained with an NH3-capture prototype based on the use of expanded polytetrafluoroethylene (ePTFE) membranes in real conditions in a gestating sow house and a free-range laying hen house, comparing them with the results obtained in controlled laboratory conditions for the same type of waste. The NH3 present in the air of the livestock housing was captured by reaction with an acidic solution flowing inside the membranes. The periods of continuous operation of the pilot plant were 232 days at the pig farm and 256 days at the poultry farm. The NH3 recovery rate at the end of those periods was 2.3 and 0.4 g TAN·m−2·d−1 in the pig and the poultry farms, respectively. The limiting factor for the capture process was the NH3 concentration in the air, with the highest recovery occurring in the most concentrated atmosphere. Differences in NH3 capture were observed between seasons and farms, with capture efficiencies of 1.62 and 0.33 g·m−2·d−1 in summer and 3.85 and 1.20 g·m−2·d−1 in winter for pig and poultry farms, respectively. The observed differences were mainly due to the higher ventilation frequency in the summer months, which resulted in a lower NH3 concentration inside the houses compared to the winter months. This is especially important when considering the real applicability of this technology. The results obtained suggest that GPM technology holds promise for limiting NH3 emissions from livestock housing with NH3 ambient concentrations close to 20 ppm or as part of manure storage facilities, given that it allows for recovery of nitrogen in a stable and concentrated solution, which can be used as a fertilizer

Contractions, deformations and curvature

The role of curvature in relation with Lie algebra contractions of the pseudo-ortogonal algebras so(p,q) is fully described by considering some associated symmetrical homogeneous spaces of constant curvature within a Cayley-Klein framework. We show that a given Lie algebra contraction can be interpreted geometrically as the zero-curvature limit of some underlying homogeneous space with constant curvature. In particular, we study in detail the contraction process for the three classical Riemannian spaces (spherical, Euclidean, hyperbolic), three non-relativistic (Newtonian) spacetimes and three relativistic ((anti-)de Sitter and Minkowskian) spacetimes. Next, from a different perspective, we make use of quantum deformations of Lie algebras in order to construct a family of spaces of non-constant curvature that can be interpreted as deformations of the above nine spaces. In this framework, the quantum deformation parameter is identified as the parameter that controls the curvature of such "quantum" spaces.Comment: 17 pages. Based on the talk given in the Oberwolfach workshop: Deformations and Contractions in Mathematics and Physics (Germany, january 2006) organized by M. de Montigny, A. Fialowski, S. Novikov and M. Schlichenmaie

Improved dead-time correction for PET scanners: Application to small-animal PET

Pile-up and dead-time are two main causes of nonlinearity in the response of a PET scanner as a function of activity in the field of view (FOV). For a given scanner and acquisition system, pile-up effects depend on the material and size of the object being imaged and on the distribution of activity inside and outside the FOV, because these factors change the singles-to-coincidences ratio (SCR). Thus, it is difficult to devise an accurate correction that would be valid for any acquisition. In this work, we demonstrate a linear relationship between SCR and effective dead-time, which measures the effects of both dead-time (losses) and pile-up (gains and losses). This relationship allows us to propose a simple method to accurately estimate dead-time and pile-up corrections using only two calibration acquisitions with, respectively, a high and low SCR. The method has been tested with simulations and experimental data for two different scanner geometries: a scanner with large area detectors and no pile-up rejection, and a scanner composed of two full rings of smaller detectors. Our results show that the SCR correction method is accurate within 7%, even for high activities in the FOV, and avoids the bias of the standard single-parameter method. © 2013 Institute of Physics and Engineering in Medicine.This work was partially funded by AMIT project (CEN-20101014) from the CDTICENIT program, CIBERsam (CB07/09/0031), projects TEC2010-21619-C04-01 and TEC2011-28972-C02-01 from Spanish Ministerio de Ciencia e Innovación, Spanish Government (ENTEPRASE Grant, PSE-300000-2009-5), PRECISION grant IPT-300000- 2010-3, CPAN (CSD-2007-00042@Ingenio2010), MEC (FPA2010-17142) and ARTEMIS program (S2009/DPI-1802) from Spanish Comunidad de Madrid and EU-ERDF program.Peer Reviewe

Highly efficient t2 cobalt ferrite nanoparticles vectorized for internalization in cancer cells

Uniform cobalt ferrite nanoparticles have been synthesized using an electrochemical synthesis method in aqueous media. Their colloidal, magnetic, and relaxometric properties have been analyzed. The novelty of this synthesis relies on the use of iron and cobalt foils as precursors, which assures the reproducibility of the iron and cobalt ratio in the structure. A stable and biocompatible targeting conjugate nanoparticle-folic acid (NP-FA) was developed that was capable of targeting FA receptor positivity in HeLa (human cervical cancer) cancer cells. The biocompatibility of NP-FA was assessed in vitro in HeLa cells using the MTT assay, and morphological analysis of the cytoskeleton was performed. A high level of NP-FA binding to HeLa cells was confirmed through qualitative in vitro targeting studies. A value of 479 Fe+Co mM-1s-1 of transverse relaxivity (r2 ) was obtained in colloidal suspension. In addition, in vitro analysis in HeLa cells also showed an important effect in negative T2 contrast. Therefore, the results show that NP-FA can be a potential biomaterial for use in bio medical trials, especially as a contrast agent in magnetic resonance imaging (MRI)

Populism in the Communication Strategy of Lula and Bolsonaro: An Analysis of the Television Debates in Brazil’s 2022 General Election

The 2022 presidential election in Brazil involved two radically different candidates but with broad similarities in their populist discourse and communication strategies. The electoral campaign and the results polarized the country between the supporters of the outgoing president, Jair Bolsonaro, and the incoming one, Lula da Silva. This article analyzes the two television debates that took place in the second round of the presidential election in October. The interventions of the candidates have been studied using the methodology of critical discourse analysis applied by Hawkins (2010). The goal is to discover the degree of populism present in the candidates’ discourse in the two debates studied. The results show evidence of the highly populist nature of the discourse of the two leaders in both television events. This characteristic, as well as other important aspects of the campaigns and the narrow margin of Lula’s eventual victory, may explain the level of polarization evident in the country. It may also be the reason behind the rejection of the election results by the followers of Bolsonaro and their protest against the change in president

A Chern-Simons approach to Galilean quantum gravity in 2+1 dimensions

We define and discuss classical and quantum gravity in 2+1 dimensions in the Galilean limit. Although there are no Newtonian forces between massive objects in (2+1)-dimensional gravity, the Galilean limit is not trivial. Depending on the topology of spacetime there are typically finitely many topological degrees of freedom as well as topological interactions of Aharonov-Bohm type between massive objects. In order to capture these topological aspects we consider a two-fold central extension of the Galilei group whose Lie algebra possesses an invariant and non-degenerate inner product. Using this inner product we define Galilean gravity as a Chern-Simons theory of the doubly-extended Galilei group. The particular extension of the Galilei group we consider is the classical double of a much studied group, the extended homogeneous Galilei group, which is also often called Nappi-Witten group. We exhibit the Poisson-Lie structure of the doubly extended Galilei group, and quantise the Chern-Simons theory using a Hamiltonian approach. Many aspects of the quantum theory are determined by the quantum double of the extended homogenous Galilei group, or Galilei double for short. We study the representation theory of the Galilei double, explain how associated braid group representations account for the topological interactions in the theory, and briefly comment on an associated non-commutative Galilean spacetime.Comment: 38 pages, 1 figure, references update

Peculiarities of the stochastic motion in antiferromagnetic nanoparticles

Antiferromagnetic (AFM) materials are widely used in spintronic devices as passive elements (for stabilization of ferromangetic layers) and as active elements (for information coding). In both cases switching between the different AFM states depends in a great extent from the environmental noise. In the present paper we derive the stochastic Langevin equations for an AFM vector and corresponding Fokker-Planck equation for distribution function in the phase space of generalised coordinate and momentum. Thermal noise is modeled by a random delta-correlated magnetic field that interacts with the dynamic magnetisation of AFM particle. We analyse in details a particular case of the collinear compensated AFM in the presence of spin-polarised current. The energy distribution function for normal modes in the vicinity of two equilibrium states (static and stationary) in sub- and super-critical regimes is found. It is shown that the noise-induced dynamics of AFM vector has pecuilarities compared to that of magnetisation vector in ferromagnets.Comment: Submitted to EPJ ST, presented at the 4-th Conference on Statistical Physics, Lviv, Ukraine, 201