Botulinum Toxin: From Poison to Possible Treatment for Spasticity in Spinal Cord Injury

Botulism has been known for about three centuries, and since its discovery, botulinum toxin has been considered one of the most powerful toxins. However, throughout the 20th century, several medical applications have been discovered, among which the treatment of spasticity stands out. Botulinum toxin is the only pharmacological treatment recommended for spasticity of strokes and cerebral palsy. Although its use as an adjuvant treatment against spasticity in spinal cord injuries is not even approved, botulinum toxin is being used against such injuries. This article describes the advances that have been made throughout history leading to the therapeutic use of botulinum toxin and, in particular, its application to the treatment of spasticity in spinal cord injury.     

Barocalorimetric technique for monitoring pressurized copolymer reactors

The problem of on‐line estimation of the conversion and composition evolutions in a pressurized batch copolymer reactor with temperature and pressure measurements was addressed. The estimation model consisted of mass and energy balances with a pressure equation built from phase‐equilibrium considerations. The application of a nonlinear geometric estimation approach yielded the underlying solvability condition with physical meaning, a straightforward estimator construction, and a conventional‐like tuning procedure. The resulting barocalorimetric estimator was an on‐line dynamic measurement processor with a model‐based predictor and a measurement‐driven corrector, and whose implementation did not require the polymerization rates and heat‐transfer coefficient function dependencies. The technique was tested with a representative laboratory styrene–butadiene system. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 475–482, 2005     

A genetic algorithm for job-shop scheduling with operators enhanced by weak Lamarckian evolution and search space narrowing

The job-shop scheduling problem with operators is a very interesting problem that generalizes the classic job-shop problem in such a way that an operation must be algorithm to solve this problem considering makespan minimization. The genetic algorithm uses permutations with repetition to encode chromosomes and a schedule generation scheme, termed OG&T, as decoding algorithm. This combination guaranties that at least one of the chromosomes represents and optimal schedule and, at the samhat machines and operators are idle while an operation is available to be processed. To improve the quality of the schedules for large instances, we use Lamarckian evolution and modify the OG&T algorithm to further reduce the idle time of the machines and operators, in this case at the risk of leaving all optimal schedules out of the search space. We conducted a large experimental study showing that these improvements allow the genetic algorithm to reach high quality solutions in very short time, and so it is quite competitive with the current state-of-the-art methods.     

Line planning on tree networks with applications to the Quito Trolebús system

We discuss an optimization model for the line planning problem in public transport in order to minimize operation costs while guaranteeing a certain level of quality of service, in terms of available transport capacity. We analyze the computational complexity of this problem for tree network topologies as well as several categories of line operations that are important for the Quito Trolebús system. In practice, these instances can be solved quite well, and significant optimization potentials can be demonstrated.     

Study of the Electrochemical Behavior of N-Substituted-4-Piperidones Curcumin Analogs: A Combined Experimental and Theoretical Approach

The electrochemical behavior of N-methyl- and N-benzyl-4-piperidone curcumin analogs were studied experimentally and theoretically. The studied compounds present different substituents at the para position in the phenyl rings (-H, -Br, -Cl, -CF₃, and -OCH₃). We assessed their electrochemical behavior by differential pulse and cyclic voltammetry, while we employed density functional theory (DFT) M06 and M06-2x functionals along with 6-311+G(d,p) basis set calculations to study them theoretically. The results showed that compounds suffer a two-electron irreversible oxidation in the range of 0.72 to 0.86 V, with surface concentrations ranging from 1.72 × 10⁻⁷ to 5.01 × 10⁻⁷ mol/cm². The results also suggested that the process is diffusion-controlled for all compounds. M06 DFT calculations showed a better performance than M06-2x to obtain oxidation potentials. We found a good correlation between the experimental and theoretical oxidation potential for N-benzyl-4-piperidones (R² = 0.9846), while the correlation was poor for N-methyl-4-piperidones (R² = 0.3786), suggesting that the latter suffer a more complex oxidation process. Calculations of the BDEs for labile C-H bonds in the compounds suggested that neither of the two series of compounds has a different tendency for a proton-coupled electron transfer (PCET) oxidation process. It is proposed that irreversible behavior is due to possible dimerization of the compounds by Shono-type oxidation.     

Evaluation and Characterization of Post-Stroke Lung Damage in a Murine Model of Cerebral Ischemia

After stroke and other brain injuries, there is a high incidence of respiratory complications such as pneumonia or acute lung injury. The molecular mechanisms that drive the brain-lung interaction post-stroke have not yet been elucidated. We performed transient middle cerebral artery occlusion (MCAO) and sham surgery on C57BL/6J mice and collected bronchoalveolar lavage fluid (BALF), serum, brain, and lung homogenate samples 24 h after surgery. A 92 proteins-panel developed by Olink Proteomics^® was used to analyze the content in BALF and lung homogenates. MCAO animals had higher protein concentration levels in BALF than sham-controls, but these levels did not correlate with the infarct volume. No alteration in alveolar-capillary barrier permeability was observed. A total of 12 and 14 proteins were differentially expressed between the groups (FDR < 0.1) in BALF and lung tissue homogenates, respectively. Of those, HGF, TGF-α, and CCL2 were identified as the most relevant to this study. Their protein expression patterns were verified by ELISA. This study confirmed that post-stroke lung damage was not associated with increased lung permeability or cerebral ischemia severity. Furthermore, the dysregulation of HGF, TGF-α, and CCL2 in BALF and lung tissue after ischemia could play an important role in the molecular mechanisms underlying stroke-induced lung damage.     

Quantitative Prediction of Steatosis in Patients with Non-Alcoholic Fatty Liver by Means of Hepatic MicroRNAs Present in Serum and Correlating with Hepatic Fat

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease worldwide, but a reliable non-invasive method to quantify liver steatosis in primary healthcare is not available. Circulating microRNAs have been proposed as biomarkers of severe/advanced NAFLD (steatohepatitis and fibrosis). However, the use of circulating miRNAs to quantitatively assess the % of liver fat in suspected NAFLD patients has not been investigated. We performed global miRNA sequencing in two sets of samples: human livers from organ donors (n = 20), and human sera from biopsy-proven NAFLD patients (n = 23), both with a wide range of steatosis quantified in their liver biopsies. Partial least squares (PLS) regression combined with recursive feature elimination (RFE) was used to select miRNAs associated with steatosis. Moreover, regression models with only 2 or 3 miRNAs, with high biological relevance, were built. Comprehensive microRNA sequencing of liver and serum samples resulted in two sets of abundantly expressed miRNAs (418 in liver and 351 in serum). Pearson correlation analyses indicated that 18% of miRNAs in liver and 14.5% in serum were significantly associated with the amount of liver fat. PLS-RFE models demonstrated that 50 was the number of miRNAs providing the lowest error in both liver and serum models predicting steatosis. Comparison of the two miRNA subsets showed 19 coincident miRNAs that were ranked according to biological significance (guide/passenger strand, relative abundance in liver and serum, number of predicted lipid metabolism target genes, correlation significance, etc.). Among them, miR-10a-5p, miR-98-5p, miR-19a-3p, miR-30e-5p, miR-32-5p and miR-145-5p showed the highest biological relevance. PLS regression models with serum levels of 2–3 of these miRNAs predicted the % of liver fat with errors <5%.     

Genomic and Immunological Characterization of Hypermucoviscous Carbapenem-Resistant Klebsiella pneumoniae ST25 Isolates from Northwest Argentina

In recent years, an increase in the prevalence hypermucoviscous carbapenem-resistant Klebsiella pneumoniae with sequence type 25 (ST25) was detected in hospitals of Tucuman (Northwest Argentina). In this work, the virulence and the innate immune response to two K. pneumoniae ST25 strains (LABACER 01 and LABACER 27) were evaluated in a murine model after a respiratory challenge. In addition, comparative genomics was performed with K. pneumoniae LABACER01 and LABACER27 to analyze genes associated with virulence. Both LABACER01 and LABACER27 were detected in the lungs of infected mice two days after the nasal challenge, with LABACER01 counts significantly higher than those of LABACER27. Only LABACER01 was detected in hemocultures. Lactate dehydrogenase (LDH) and albumin levels in bronchoalveolar lavage (BAL) samples were significantly higher in mice challenged with LABACER01 than in LABACER27-infected animals, indicating greater lung tissue damage. Both strains increased the levels of neutrophils, macrophages, TNF-α, IL-1β, IL-6, KC, MCP-1, IFN-γ, and IL-17 in the respiratory tract and blood, with the effect of LABACER01 more marked than that of LABACER27. In contrast, LABACER27 induced higher levels of IL-10 in the respiratory tract than LABACER01. Genomic analysis revealed that K. pneumoniae LABACER01 and LABACER27 possess virulence factors found in other strains that have been shown to be hypervirulent, including genes required for enterobactin (entABCDEF) and salmochelin (iroDE) biosynthesis. In both strains, the genes of toxin–antitoxin systems, as well as regulators of the expression of virulence factors and adhesion genes were also detected. Studies on the genetic potential of multiresistant K. pneumoniae strains as well as their cellular and molecular interactions with the host are of fundamental importance to assess the association of certain virulence factors with the intensity of the inflammatory response. In this sense, this work explored the virulence profile based on genomic and in vivo studies of hypermucoviscous carbapenem-resistant K. pneumoniae ST25 strains, expanding the knowledge of the biology of the emerging ST25 clone in Argentina.     

Passive elastic mechanism to mimic fish-muscle action in anguilliform swimming

Swimmers in nature use body undulations to generate propulsive and manoeuvring forces. The anguilliform kinematics is driven by muscular actions all along the body, involving a complex temporal and spatial coordination of all the local actuations. Such swimming kinematics can be reproduced artificially, in a simpler way, by using the elasticity of the body passively. Here, we present experiments on self-propelled elastic swimmers at a free surface in the inertial regime. By addressing the fluid–structure interaction problem of anguilliform swimming, we show that our artificial swimmers are well described by coupling a beam theory with the potential flow model of Lighthill. In particular, we show that the propagative nature of the elastic wave producing the propulsive force is strongly dependent on the dissipation of energy along the body of the swimmer.     

Estimation of the state-of-charge of gel lead-acid batteries and application to the control of a stand-alone wind-solar test-bed with hydrogen support

In hybrid renewable energy systems, batteries act as a DC bus to provide constant voltage and to smooth out commutations between the generating devices. These batteries are usually of a lead-acid type and operate under harsh variable conditions due to fluctuations of both solar radiation and wind speed. Precise knowledge of the state-of-charge of the batteries, and hence of their available energy, play a key role in effecting efficient control and energy management of the installation. The present study had a twofold aim. One objective was to adjust and validate a method based on coulomb counting to estimate the state-of-charge (SOC) of a gelled lead-acid battery which is the DC bus of a hybrid wind-solar system with hydrogen storage. Other works evaluate SOC models based on several parameters, however, the present proposal based on experimental measurements involves only a few parameters. The second objective was to modify the installation's control algorithm to use the battery's calculated SOC as control parameter instead of its voltage. The results of a test-bed system, showing how the system evolved under real operating conditions, constitute a proof-of-concept of the validity of the method.