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Differential evolution (DE) is one of the most popular and widely used optimizers among the community of evolutionary computation. Despite numerous works having been conducted on the improvement of DE performance, there are still some defects, such as premature convergence and stagnation. In order to alleviate them, this paper presents a novel DE variant by designing a new mutation operator (named "DE/current-to-pbest_id/1") and a new control parameter setting. In the new operator, the fitness value of the individual is adopted to determine the chosen scope of its guider among the population. Meanwhile, a group-based competitive control parameter setting is presented to ensure the various search potentials of the population and the adaptivity of the algorithm. In this setting, the whole population is randomly divided into multiple equivalent groups, the control parameters for each group are independently generated based on its location information, and the worst location information among all groups is competitively updated with the current successful parameters. Moreover, a piecewise population size reduction mechanism is further devised to enhance the exploration and exploitation of the algorithm at the early and later evolution stages, respectively. Differing from the previous DE versions, the proposed method adaptively adjusts the search capability of each individual, simultaneously utilizes multiple pieces of successful parameter information to generate the control parameters, and has different speeds to reduce the population size at different search stages. Then it could achieve the well trade-off of exploration and exploitation. Finally, the performance of the proposed algorithm is measured by comparing with five well-known DE variants and five typical non-DE algorithms on the IEEE CEC 2017 test suite. Numerical results show that the proposed method is a more promising optimizer. [ABSTRACT FROM AUTHOR]

In this paper, a novel water cycle algorithm is presented by dynamically assigning sea and rivers and devising an enhanced position updating strategy. To effectively maintain the diversity of solutions and ensure the convergence of algorithm, an adaptive distance-based assignment mechanism is first developed to set sea, rivers and their corresponding streams. In this mechanism, the fitness values and position information of solutions are simultaneously considered, and the total number of sea and rivers is nonlinearly reduced during the search process. Meanwhile, an enhanced position updating strategy is designed to update the solutions by incorporating both the gravitational search and greedy strategy. Moreover, a modified evaporation operation is further proposed to dynamically refresh the search capability of algorithm by properly making full use of the promising information of solutions. Differing from the existing WCA variants, the proposed algorithm dynamically assigns sea, rivers and their streams, additionally incorporates the gravitational search and greedy strategy, and fully exploits the obtained promising information in the raining process. Then it could availably strengthen the search effectiveness and balance the exploration and exploitation. Finally, the performance of the proposed algorithm is evaluated by comparing with 12 typical algorithms on 30 CEC2017 benchmark functions. Numerical results show that the proposed algorithm has better performance. [ABSTRACT FROM AUTHOR]

This paper presents a novel composite heuristic algorithm for global optimization by organically integrating the merits of a water cycle algorithm (WCA) and gravitational search algorithm (GSA). To effectively reinforce the exploration and exploitation of algorithms and reasonably achieve their balance, a modified WCA is first put forward to strengthen its search performance by introducing the concept of the basin, where the position of the solution is also considered into the assignment of the sea or river and its streams, and the number of the guider solutions is adaptively reduced during the search process. Furthermore, the enhanced WCA is adaptively cooperated with the gravitational search to search for new solutions based on their historical performance within a certain stage. Moreover, the binomial crossover operation is also incorporated after the water cycle search or the gravitational search to further improve the search capability of the algorithm. Finally, the performance of the proposed algorithm is evaluated by comparing with six excellent meta-heuristic algorithms on the IEEE CEC2014 test suite, and the numerical results indicate that the proposed algorithm is very competitive. [ABSTRACT FROM AUTHOR]

This paper presents a novel differential evolution algorithm by designing two prediction-based mutation operators and a two-level adaptive mechanism. To accelerate the search efficiency of algorithm and enhance the suitability of integrating multiple mutation operators with different characteristics, two new mutation operators are first developed to strengthen the local search ability by making full use of the neighborhood information of each individual to predict its promising region and guide the search process. Meanwhile, a two-level adaptive mechanism is designed to meet the search requirements of both individual and population by utilizing the history search information of its neighbors and that of the whole population simultaneously to assign a more suitable mutation operator for it. Moreover, an enhanced restart operation is further adopted to avoid the invalid search during the evolutionary process. Differing from the existing DE variants, the proposed algorithm incorporates the prediction process in mutation to enhance the exploitation, and simultaneously uses the local information of each individual and the global information of population to adaptively adjust the search capability. Then it could effectively improve the search efficiency and balance the exploration and exploitation. Compared with 21 typical algorithms, the numerical results on the benchmark functions from both IEEE CEC2014 and CEC2017 show that the proposed algorithm has better performance. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of the study was to explore the pathogenic mechanisms underlying generalized epilepsy and febrile seizures plus (GEFS+) in a family with a novel γ2 subunit gene (GABRG2) frameshift mutation. Four affected and one unaffected individuals carried a c.1329delC GABRG2 mutation resulting in a subunit [γ2S(S443delC)] with a modified and elongated carboxy-terminus that is different from that of the wildtype γ2S subunit. We expressed the wildtype γ2S subunit and the predicted mutant γ2S(S443delC) subunit cDNAs in HEK293T cells and performed immunoblotting, flow cytometry and electrophysiology studies. The mutant subunit was translated as a stable protein that was larger than the wildtype γ2S subunit and was retained in the ER and not expressed on the cell surface membrane, suggesting GABRG2 haploinsufficiency. Peak GABA-evoked currents recorded from cells cotransfected with wildtype α1 and β2 subunits and mutant γ2S subunits were significantly decreased and were comparable to α1β2 receptor currents. S443delC is the first GABR epilepsy mutation predicted to abolish the natural stop codon and produce a stop codon in the 3′ UTR that leads to translation of an extended peptide. The GEFS+ phenotype observed in this family is likely caused by γ2S subunit loss-of-function and possibly to dominant-negative suppression of α1β2γ2 receptors. Many GABRG2 truncation mutations result in GEFS+, but the spectrum of phenotypic severity is wider, ranging from asymptomatic individuals to the Dravet syndrome. Mechanisms influencing the severity of the phenotype are therefore complex and difficult to correlate with its demonstrable functional effects. [Copyright &y& Elsevier]

Abstract: The GABRG2 nonsense mutation, Q40X, is associated with the severe epilepsy syndrome, Dravet syndrome, and is predicted to generate a premature translation–termination codon (PTC) in the GABAA receptor γ2 subunit mRNA in a position that codes for the first amino acid of the mutant subunit. We determined the effects of the mutation on γ2 subunit mRNA and protein synthesis and degradation, as well as on α1β2γ2 GABAA receptor assembly, trafficking and surface expression in HEK cells. Using bacterial artificial chromosome (BAC) constructs, we found that γ2(Q40X) subunit mRNA was degraded by nonsense mediated mRNA decay (NMD). Undegraded mutant mRNA was translated to a truncated peptide, likely the signal peptide, which was cleaved further. We also found that mutant γ2(Q40X) subunits did not assemble into functional receptors, thus decreasing GABA-evoked current amplitudes. The GABRG2(Q40X) mutation is one of several epilepsy-associated nonsense mutations that have the potential to be rescued by reading through the PTC, thus restoring full-length protein translation. As a first approach, we investigated the use of the aminoglycoside, gentamicin, to rescue translation of intact mutant subunits by inducing mRNA read-through. In the presence of gentamicin, synthesis of full length γ2 subunits was partially restored, and surface biotinylation and whole cell recording experiments suggested that rescued γ2 subunits could corporate into functional, surface GABAA receptors, indicating a possible direction for future therapy. [Copyright &y& Elsevier]

The intronic GABRG2 mutation, IVS6+2T3→G, was identified in an Australian family with childhood absence epilepsy and febrile seizures (Kananura et al., 2002). The GABRG2 intron 6 splice donor site was found to be mutated from GT to GG. We generated wild-type and mutant γ2 subunit bacterial artificial chromosomes (BACs) driven by a CMV promoter and expressed them in HEK293T cells and expressed wild-type and mutant γ2 subunit BACs containing the endogenous hGABRG2 promoter in transgenic mice. Wild-type and mutant GABRG2 mRNA splicing patterns were determined in both BAC-transfected HEK293T cells and transgenic mouse brain, and in both, the mutation abolished intron 6 splicing at the donor site, activated a cryptic splice site, generated partial intron 6 retention, and produced a frameshift in exon 7 that created a premature translation termination codon (PTC). The resultant mutant mRNA was either degraded partially by nonsense-mediated mRNA decay or translated to a stable, truncated subunit (the γ2-PTC subunit) containing the first six GABRG2 exons and a novel frameshifted 29 aa C-terminal tail. The γ2-PTC subunit was homologous to the mollusk AChBP (acetylcholine binding protein) but was not secreted from cells. It was retained in the ER and not expressed on the surface membrane, but it did oligomerize with α1 and &bete;2 subunits. These results suggested that the GABRG2 mutation, IVS6+2T3→G, reduced surface α&bete;γ2 receptor levels, thus reducing GABAergic inhibition, by reducing GABRG2 transcript level and producing a stable, nonfunctional truncated subunit that had a dominant-negative effect on α&bete;γ2 receptor assembly. [ABSTRACT FROM AUTHOR]

This paper presents a novel differential evolution algorithm for numerical optimization by making full use of the neighborhood information to balance exploration and exploitation. To effectively meet the search requirement of each individual, a neighborhood-based adaptive mutation strategy is developed by using the ring topology to construct an elite individual set and adaptively choosing a suitable elite individual to guide its search according to its neighborhood performance. Then, a neighborhood-based adaptive parameter setting is designed to improve the suitability of parameters for each individual by utilizing the feedback information of population and its neighbors simultaneously. Furthermore, a restart mechanism is proposed to further enhance the performance of algorithm by adaptively strengthening the search abilities of unpromising individuals, removing the worse individuals and randomly replacing some individuals with Gaussian Walks. Differing from the existing DE variants, the proposed algorithm adaptively guides the search and suitably adjusts the parameters for each individual by using its neighborhood performance, and strengthens the exploitation and exploration by removing the worse individuals and randomly replacing some individuals. Then it could properly adjust the search ability of each individual, and effectively balance diversity and convergence. Compared with 16 typical algorithms, the numerical results on 30 IEEE CEC2014 benchmark functions show that the proposed algorithm has better performance. [ABSTRACT FROM AUTHOR]

Objective The mutant γ-aminobutyric acid type A ( GABAA) receptor γ2(Q390X) subunit (Q351X in the mature peptide) has been associated with the epileptic encephalopathy, Dravet syndrome, and the epilepsy syndrome genetic epilepsy with febrile seizures plus ( GEFS+). The mutation generates a premature stop codon that results in translation of a stable truncated and misfolded γ2 subunit that accumulates in neurons, forms intracellular aggregates, disrupts incorporation of γ2 subunits into GABAA receptors, and affects trafficking of partnering α and β subunits. Heterozygous Gabrg2 +/Q390X knock-in ( KI) mice had reduced cortical inhibition, spike wave discharges on electroencephalography (EEG), a lower seizure threshold to the convulsant drug pentylenetetrazol ( PTZ), and spontaneous generalized tonic-clonic seizures. In this proof-of-principal study, we attempted to rescue these deficits in KI mice using a γ2 subunit gene ( GABRG2) replacement therapy. Methods We introduced the GABRG2 allele by crossing Gabrg2 +/Q390X KI mice with bacterial artificial chromosome ( BAC) transgenic mice overexpressing HA (hemagglutinin)-tagged human γ2 HA subunits, and compared GABAA receptor subunit expression by Western blot and immunohistochemical staining, seizure threshold by monitoring mouse behavior after PTZ-injection, and thalamocortical inhibition and network oscillation by slice recording. Results Compared to KI mice, adult mice carrying both mutant allele and transgene had increased wild-type γ2 and partnering α1 and β2/3 subunits, increased miniature inhibitory postsynaptic current ( mIPSC) amplitudes recorded from layer VI cortical neurons, reduced thalamocortical network oscillations, and higher PTZ seizure threshold. Significance Based on these results we suggest that seizures in a genetic epilepsy syndrome caused by epilepsy mutant γ2(Q390X) subunits with dominant negative effects could be rescued potentially by overexpression of wild-type γ2 subunits. [ABSTRACT FROM AUTHOR]

We describe a dual-axis atomic spin comagnetometer for rotation sensing using a single laser beam. A circularly polarized laser is used to pump the co-located atomic ensembles of alkali metal and noble gas and probe their gyroscopic precession at the same time, which is different from the traditional two-beam orthogonal pump-probe configuration. Combined with magnetic field modulations perpendicular to the laser propagating direction, the comagnetometer could measure dual-axis rotation rates simultaneously. This system is demonstrated theoretically and experimentally. A rotation sensitivity of 5.1 × 10–7 rad s−1 Hz−1∕2 and a bias instability of 0.016 °/h have been achieved. The theory and method presented here shed light on the way to miniaturize the comagnetometer with high precision for practical applications. [ABSTRACT FROM AUTHOR]

This study investigates the effects of power broadening on nonlinear magneto-optical rotation (NMOR) magnetometers. As the laser power increases, the interference between two partially resolved transitions of 87Rb induced by velocity-changing collisions can be exacerbated by power broadening, resulting in a reduction of the rotation rate, and the shift of the optimal laser frequency corresponding to the maximum rotation rate. The theoretical model of NMOR is established using a four-level double Λ scheme, which takes into account power broadening effects, and experimentally studied in a single-beam NMOR magnetometer with a buffer-gas filled cell. The results indicate that the significant enhancement in rotation rate can be achieved by tuning the laser frequency to the optimal detuning based on our model. This study holds considerable importance for the improvement of magnetic field sensitivity in NMOR magnetometers. [Display omitted] • Introducing the power broadening into the four-level double Λ system for modeling NMOR. • Revealing that power broadening exacerbating the interference between two partially resolved transitions. • The dependence of the laser frequency in NMOR on laser power was reported for the first time. [ABSTRACT FROM AUTHOR]

Schizophrenia (SZ) and bipolar disorder (BP) are highly heritable major psychiatric disorders that share a substantial portion of genetic risk as well as their clinical manifestations. This raises a fundamental question of whether, and how, common neurobiological pathways translate their shared polygenic risks into shared clinical manifestations. This study shows the miR-124-3p-AMPAR pathway as a key common neurobiological mediator that connects polygenic risks with behavioral changes shared between these two psychotic disorders. We discovered the upregulation of miR-124-3p in neuronal cells and the postmortem prefrontal cortex from both SZ and BP patients. Intriguingly, the upregulation is associated with the polygenic risks shared between these two disorders. Seeking mechanistic dissection, we generated a mouse model that upregulates miR-124-3p in the medial prefrontal cortex. We demonstrated that the upregulation of miR-124-3p increases GRIA2-lacking calcium-permeable AMPARs and perturbs AMPAR-mediated excitatory synaptic transmission, leading to deficits in the behavioral dimensions shared between SZ and BP. • Schizophrenia (SZ) and bipolar disorder (BP) share genetic risks/clinical features • MiR-124 is upregulated in biopsied neuronal cells from SZ and BP patients • The upregulation of miR-124 is associated with polygenic risks shared by SZ and BP • MiR-124-AMPAR pathway connects their shared genetic risk with behavioral changes Schizophrenia and bipolar disorder share genetic risks as well as clinical manifestations. Nevertheless, it remains unknown whether, and how, common neurobiological pathways translate their shared polygenic risks into shared clinical manifestations. We present the miR-124-AMPAR pathway as a key neurobiological pathway that connects their shared polygenic risks with behavioral changes. [ABSTRACT FROM AUTHOR]

An abstract of the article "Canine Mini-Dystrophin Gene Transfer by AAV1 in mdx Mice Ameliorates Dystrophic Pathology and Protects Membrane Integrity," by Bing Wang, Juan Li, Liqiao Zhou, Chunping Qiao, Mengnan Tian, Tong Zh Janet Bogan, Joseph Kornegay, and Xiao Xiao is presented.