Effect of voluntary repetitive long-lasting muscle contraction activity on the BOLD signal as assessed by optimal hemodynamic response function

Objective

Among other neuroimaging techniques, functional magnetic resonance imaging (fMRI) can be useful for studying the development of motor fatigue. The aim of this study was to identify differences in cortical neuronal activation in nine subjects on three motor tasks: right-hand movement with minimum, maximum, and post-fatigue maximum finger flexion.

Materials and methods

fMRI activation maps for each subject and during each condition were obtained by estimating the optimal model of the hemodynamic response function (HRF) out of four standard HRF models and an individual-based HRF model (ibHRF).

Results

ibHRF was selected as the optimal model in six out of nine subjects for minimum movement, in five out of nine for maximum movement, and in eight out of nine for post-fatigue maximum movement. As compared to maximum movement, a large reduction in the total number of active voxels (primary sensorimotor area, supplementary motor area and cerebellum) was observed in post-fatigue maximum movement.

Conclusion

This is the first approach to the evaluation of long-lasting contraction effort in healthy subjects by means of the fMRI paradigm with the use of an individual-based hemodynamic response. The results may be relevant for defining a baseline in future studies on central fatigue in patients with neuropathological disorders.     

A Beckwith–Wiedemann-Associated CDKN1C Mutation Allows the Identification of a Novel Nuclear Localization Signal in Human p57Kip2

p57^Kip2 protein is a member of the CIP/Kip family, mainly localized in the nucleus where it exerts its Cyclin/CDKs inhibitory function. In addition, the protein plays key roles in embryogenesis, differentiation, and carcinogenesis depending on its cellular localization and interactors. Mutations of CDKN1C, the gene encoding human p57^Kip2, result in the development of different genetic diseases, including Beckwith–Wiedemann, IMAGe and Silver–Russell syndromes. We investigated a specific Beckwith–Wiedemann associated CDKN1C change (c.946 C>T) that results in the substitution of the C-terminal amino acid (arginine 316) with a tryptophan (R316W-p57^Kip2). We found a clear redistribution of R316W-p57^Kip2, in that while the wild-type p57^Kip2 mostly occurs in the nucleus, the mutant form is also distributed in the cytoplasm. Transfection of two expression constructs encoding the p57^Kip2 N- and C-terminal domain, respectively, allows the mapping of the nuclear localization signal(s) (NLSs) between residues 220–316. Moreover, by removing the basic RKRLR sequence at the protein C-terminus (from 312 to 316 residue), p57^Kip2 was confined in the cytosol, implying that this sequence is absolutely required for nuclear entry. In conclusion, we identified an unreported p57^Kip2 NLS and suggest that its absence or mutation might be of relevance in CDKN1C-associated human diseases determining significant changes of p57^Kip2 localization/regulatory roles.     

Nitrous oxide emission and ammonia volatilization induced by vinasse and N fertilizer application in a sugarcane crop at Rio de Janeiro,Brazil

In Brazilian sugarcane plantations, fertilization with vinasse, supplemented or not with mineral fertilizer, is a common practice. But little is known about the effects of this application on N losses, especially those forms of N which give rise to greenhouse gas emissions. The aim of this study was to quantify N₂O and NH₃ emissions from soil after vinasse application and urea fertilizer addition and to examine the possible impact adding vinasse before or after urea. Two experiments were conducted under greenhouse conditions and one in the field with treatments of vinasse and urea fertilizer, either alone, or in sequence. The highest proportions of N emitted as N₂O were registered in the vinasse treatment, which amounted to 15 % of the N applied in the first greenhouse experiment, and 2.5 % in the field experiment. With respect to the losses by NH₃ volatilization, urea was the only treatment where this process was significant. N₂O emission from vinasse was 2.5 %, somewhat above the default emission factor of 1 % of the IPCC. N₂O emissions from urea were also variable, but emission factors registered were still well below the default IPCC factor for organic residues. The order of addition of urea and vinasse had little effect on NH₃ volatilization in the field, but there were evidences it was important for N₂O.     

Targeting Serotonin 2A and Adrenergic α1 Receptors for Ocular Antihypertensive Agents: Discovery of 3,4‐Dihydropyrazino[1,2‐b]indazol‐1(2H)‐one Derivatives

Glaucoma affects millions of people worldwide and causes optic nerve damage and blindness. The elevation of the intraocular pressure (IOP) is the main risk factor associated with this pathology, and decreasing IOP is the key therapeutic target of current pharmacological treatments. As potential ocular hypotensive agents, we studied compounds that act on two receptors (serotonin 2A and adrenergic α₁) linked to the regulation of aqueous humour dynamics. Herein we describe the design, synthesis, and pharmacological profiling of a series of novel bicyclic and tricyclic N2‐alkyl‐indazole‐amide derivatives. This study identified a 3,4‐dihydropyrazino[1,2‐b]indazol‐1(2H)‐one derivative with potent serotonin 2A receptor antagonism, >100‐fold selectivity over other serotonin subtype receptors, and high affinity for the α₁ receptor. Moreover, upon local administration, this compound showed superior ocular hypotensive action in vivo relative to the clinically used reference compound timolol.     

Ergonomics, gerontechnology, and design for the home-environment

An ergonomic approach could improve the quality of life and activities in daily living. Gerontechnology reduces the effects of age-related impairments with technological devices and particular design for the home-environment. Physiological decline with increasing age renders the daily activities at home more difficult. This paper highlights some "common sense" and specific design suggestions in the entrance and kitchen, aimed to increase the self-sufficiency of elderly people. We suggest that gerontechnology may have a particular role in the improvement of comfort and safety for aged people.     

Algorithm based on simulated annealing for land-use allocation

This article describes the use of simulated annealing for allocation of land units to a set of possible uses on, the basis of their suitability for those uses, and the compactness of the total areas allotted to the same use or kind of use, which are fixed a priori. The results obtained for the Terra Chá district of Galicia (N.W. Spain) using different objective weighting schemes are compared with each other and with those obtained for this district under the same area constraints, using hierarchical optimization, ideal point analysis, and multi-objective land allocation (MOLA) to maximize average use suitability. Inclusion of compactness in the simulated annealing objective function avoids the highly disperse allocations typical of optimizations that ignore this sub-objective.     

Ejection chain moves for automatic neighborhood synthesis in constrained cardinality‐minimization problems

In this paper, we deal with the problem of automatically synthesizing “good” neighborhoods for a specific class of problems, namely constrained cardinality‐minimization problems. Exploiting the peculiarity of the objective function of such problems, we develop automatic ejection chain moves that define neighborhood structures to be explored with a black‐box solver. In particular, starting from a formulation of a cardinality‐minimization problem and a feasible solution, our procedure automatically detects the “entities” involved in the problem and learns the strength of the relationships among them. This information is then used to define the characteristics of our moves that consist in ejecting one entity at a time from the solution. If one of such moves results in an infeasible solution, then feasibility is recovered by performing an additional step based on the solution of an auxiliary problem. The computational results show that, when assessed on four well‐known constrained cardinality‐minimization problems, our approach outperforms both a black‐box mixed integer programming solver and a state‐of‐the‐art model‐based neighborhood search procedure with respect to both solution quality and computing times.     

Beta control charts for monitoring fraction data

p-Charts and np-Charts are commonly used in monitoring variables of the fraction type and these charts assume that the monitored variables are binomially distributed. In this paper we propose a new control chart called Beta Charts, for monitoring fraction data (p). The Beta Chart presents the control limits based on the Beta probability distribution. It was applied for monitoring the variables in three real studies, and it was compared to the control limits with three schemes. The comparative analysis showed that: (i) Beta approximation to the Binomial distribution was more appropriate with values confined in the [0, 1]-interval; and (ii) the charts proposed were more sensitive to the average run length (ARL), in both in-control and out-of-control processes monitoring. The Beta Charts outperform the control charts analyzed for monitoring fraction data.     

Reliability of RF MEMS switches due to charging effects and their circuital modelling

The reliability of RF MEMS switches is typically reduced by charging effects occurring in the dielectrics. The aim of this paper is to discuss these effects, and to propose analytical and equivalent circuit models which account for most of the physical contributions present in the structure.