FReLU: Flexible Rectified Linear Units for Improving Convolutional Neural Networks

Rectified linear unit (ReLU) is a widely used activation function for deep convolutional neural networks. However, because of the zero-hard rectification, ReLU networks miss the benefits from negative values. In this paper, we propose a novel activation function called \emph{flexible rectified linear unit (FReLU)} to further explore the effects of negative values. By redesigning the rectified point of ReLU as a learnable parameter, FReLU expands the states of the activation output. When the network is successfully trained, FReLU tends to converge to a negative value, which improves the expressiveness and thus the performance. Furthermore, FReLU is designed to be simple and effective without exponential functions to maintain low cost computation. For being able to easily used in various network architectures, FReLU does not rely on strict assumptions by self-adaption. We evaluate FReLU on three standard image classification datasets, including CIFAR-10, CIFAR-100, and ImageNet. Experimental results show that the proposed method achieves fast convergence and higher performances on both plain and residual networks

Tolerability and effectiveness of (S)-amlodipine compared with racemic amlodipine in hypertension: A systematic review and meta-analysis

AbstractBackground: Amlodipine is a calcium channel blocker prescribed for the management of angina and hypertension. As a racemic mixture, amlodipine contains (R)- and (S)-amlodipine isomers, but only (S)-amlodipine as the active moiety possesses therapeutic activity. Based on pharmacologic research, it remains uncertain if (S)-amlodipine alone has similar efficacy and fewer associated adverse events (AEs) compared with the racemic mixtures.Objective: The aim of this systematic review and meta-analysis was to determine the effectiveness and tolerability of (S)-amlodipine compared with that of racemic amlodipine.Methods: A systematic literature search was performed using MEDLINE (1966–2009), EMBASE (1966–2009), the Cochrane Central Register of Controlled Trials (issue 3, 2009), the Chinese Biomedical Database (1978–2009), and the China National Knowledge Internet (1980–2009). All randomized controlled trials (RCTs) comparing (S)-amlodipine 2.5 mg and racemic amlodipine 5.0 mg in the treatment of hypertension were included in the review. The outcome measures to be collected were cardiovascular events, systolic blood pressure (SBP), diastolic BP (DBP), and AEs. Quality assessments of clinical trials were conducted using a modified Jadad Scale, with trials being rated as low quality (score 0–3) or high quality (score 4–7). Meta-analysis of the included studies was performed using RevMan software.Results: Of the 229 references identified, 214 were excluded after screening the titles, abstracts, or full texts. Fifteen RCTs were included, of which 13 were in Chinese and 2 in English. Based on the Jadad Scale score, 3 of the RCTs were classified as high quality (score 5 or 6) and the remaining 12 as low quality (score 1–3). None of the trials evaluated cardiovascular events beyond 40 weeks. Meta-analysis of the 15 trials indicated that (S)-amlodipine was not significantly different from racemic amlodipine in the effect on BP. When only high-quality studies were included, after 4 weeks' treatment, the weighted mean difference (WMD) of SBP and DBP decrease (1 study) was −2.84 (95% CI, −6.42 to 0.74) with (S)-amlodipine and −1.71 (95% CI, −3.48 to 0.06) with racemic amlodipine. After 8 weeks' treatment, the WMD of SBP and DBP decrease (2 studies) was −1.13 (95% CI, −5.29 to 3.03) and −1.34 (95% CI, −2.67 to −0.01), respectively. The risk difference (RD) for the number of patients who experienced AEs with (S)-amlodipine and racemic amlodipine was found to be −0.04 (95% CI, −0.06 to −0.02). When all the trials were included, (S)-amlodipine treatment was associated with significantly less edema than racemic amlodipine (RD, −0.02; 95% CI, −0.03 to 0.00); however, when only high-quality studies (2 studies) were included, no difference was found between the 2 groups (RD, 0.01; 95% CI, −0.02 to 0.03). One high-quality study found significant differences in increases in aspartate and alanine aminotransferase activities in the 2 groups (RD, 0.08; 95% CI, 0.01 to 0.05). No significant differences between the 2 groups were found in the incidence of headache (RD, 0.00; 95% CI, −0.02 to 0.01) or flushing (RD, −0.01; 95% CI, −0.02 to 0.00).Conclusions: The majority of the clinical trials comparing (S)-amlodipine and racemic amlodipine treatment were low quality (12/15 [80%]). According to the limited evidence, there were no significant differences between (S)-amlodipine 2.5 mg and racemic amlodipine 5.0 mg in controlling BP. When all the trials were considered, (S)-amlodipine treatment was associated with significantly less edema than racemic amlodipine; however, when only high-quality trials were included, no significant difference was found. More long-term, high-quality RCTs with cardiovascular events as the primary outcome are needed to compare the safety and efficacy of (S)-amlodipine and racemic amlodipine

Partial sex linkage and linkage disequilibrium on the guppy sex chromosome

The guppy Y chromosome has been considered a model system for the evolution of suppressed recombination between sex chromosomes, and it has been proposed that complete sex‐linkage has evolved across about 3 Mb surrounding this fish's sex‐determining locus, followed by recombination suppression across a further 7 Mb of the 23 Mb XY pair, forming younger “evolutionary strata”. Sequences of the guppy genome show that Y is very similar to the X chromosome. Knowing which parts of the Y are completely nonrecombining, and whether there is indeed a large completely nonrecombining region, are important for understanding its evolution. Here, we describe analyses of PoolSeq data in samples from within multiple natural populations from Trinidad, yielding new results that support previous evidence for occasional recombination between the guppy Y and X. We detected recent demographic changes, notably that downstream populations have higher synonymous site diversity than upstream ones and other expected signals of bottlenecks. We detected evidence of associations between sequence variants and the sex‐determining locus, rather than divergence under a complete lack of recombination. Although recombination is infrequent, it is frequent enough that associations with SNPs can suggest the region in which the sex‐determining locus must be located. Diversity is elevated across a physically large region of the sex chromosome, conforming to predictions for a genome region with infrequent recombination that carries one or more sexually antagonistic polymorphisms. However, no consistently male‐specific variants were found, supporting the suggestion that any completely sex‐linked region may be very small

Has recombination changed during the recent evolution of the guppy Y chromosome?

Genome sequencing and genetic mapping of molecular markers have demonstrated nearly complete Y-linkage across much of the guppy (Poecilia reticulata) XY chromosome pair. Predominant Y-linkage of factors controlling visible male-specific coloration traits also suggested that these polymorphisms are sexually antagonistic (SA). However, occasional exchanges with the X are detected, and recombination patterns also appear to differ between natural guppy populations, suggesting ongoing evolution of recombination suppression under selection created by partially sex-linked SA polymorphisms. We used molecular markers to directly estimate genetic maps in sires from four guppy populations. The maps are very similar, suggesting that their crossover patterns have not recently changed. Our maps are consistent with population genomic results showing that variants within the terminal 5 Mb of the 26.5 Mb sex chromosome, chromosome 12, are most clearly associated with the maleness factor, albeit incompletely. We also confirmed occasional crossovers proximal to the male-determining region, defining a second, rarely recombining, pseudo-autosomal region, PAR2. This fish species may therefore have no completely male-specific region (MSY) more extensive than the male-determining factor. The positions of the few crossover events suggest a location for the male-determining factor within a physically small repetitive region. A sex-reversed XX male had few crossovers in PAR2, suggesting that this region’s low crossover rate depends on the phenotypic, not the genetic, sex. Thus, rare individuals whose phenotypic and genetic sexes differ, and/or occasional PAR2 crossovers in males can explain the failure to detect fully Y-linked variants

Time-Course of the Effects of QSYQ in Promoting Heart Function in Ameroid Constrictor-Induced Myocardial Ischemia Pigs

We aim to investigate the therapeutic effects of QSYQ on a pig myocardial ischemia (MI) model and to determine its mechanism of action. The MI model was induced by Ameroid constriction of the left anterior descending coronary (LAD) in Ba-Ma miniature pigs. Four groups were created: model group, digoxin group, QSYQ group, and sham-operated group. Heart function, Ang II, CGMP, TXB2, BNP, and cTnT were evaluated before (3 weeks after operation: 0 weeks) and at 2, 4, and 8 weeks after drug administration. After 8 weeks of administration, the pigs were sacrificed for cardiac injury measurements. Pigs with MI showed obvious histological changes, including BNP, cTnT, Ang II, CGRP, TXB2, and ET, deregulated heart function, and increased levels of apoptotic cells in myocardial tissue. Treatment with QSYQ improved cardiac remodeling by counteracting those events. The administration of QSYQ was accompanied by a restoration of heart function and of the levels of Ang II, CGRP, TXB2, ET BNP, and cTnT. In addition, QSYQ attenuated administration, reduced the apoptosis, and decreased the level of TNF-α and active caspase-3. In conclusion, administration of QSYQ could attenuate Ameroid constrictor induced myocardial ischemia, and TNF-α and active caspase-3 seemed to be the critical potential target of QSYQ

Identify submitochondria and subchloroplast locations with pseudo amino acid composition: Approach from the strategy of discrete wavelet transform feature extraction

AbstractIt is very challenging and complicated to predict protein locations at the sub-subcellular level. The key to enhancing the prediction quality for protein sub-subcellular locations is to grasp the core features of a protein that can discriminate among proteins with different subcompartment locations. In this study, a different formulation of pseudoamino acid composition by the approach of discrete wavelet transform feature extraction was developed to predict submitochondria and subchloroplast locations. As a result of jackknife cross-validation, with our method, it can efficiently distinguish mitochondrial proteins from chloroplast proteins with total accuracy of 98.8% and obtained a promising total accuracy of 93.38% for predicting submitochondria locations. Especially the predictive accuracy for mitochondrial outer membrane and chloroplast thylakoid lumen were 82.93% and 82.22%, respectively, showing an improvement of 4.88% and 27.22% when other existing methods were compared. The results indicated that the proposed method might be employed as a useful assistant technique for identifying sub-subcellular locations. We have implemented our algorithm as an online service called SubIdent (http://bioinfo.ncu.edu.cn/services.aspx)

Assessment of chemotherapy response in non-Hodgkin lymphoma involving the neck utilizing diffusion kurtosis imaging: a preliminary study

PURPOSE:We aimed to examine the utility of non-Gaussian diffusion kurtosis imaging (DKI) for assessment of chemotherapy response in patients with cervical (neck) non-Hodgkin lymphoma (NHL).METHODS:Patients with cervical NHL underwent 3.0 T magnetic resonance imaging with maximal b value of 2000 s/mm2 at baseline and seven days after chemotherapy onset. Apparent diffusion coefficient (ADC) value and diffusion kurtosis imaging maps for diffusion coefficient (D) and kurtosis (K) were calculated. Based on clinical examination, laboratory screening, and PET/CTs, patients were classified as responders or nonresponders.RESULTS:Twenty-six patients were enrolled. Among them, 24 patients were classified as responders and two as nonresponders. For responders, mean follow-up ADC and D increased significantly compared with baseline (ADC: 0.92±0.11 ×10-3 mm2/s vs. 0.68±0.11 ×10-3 mm2/s; D: 1.47±0.32 ×10-3 mm2/s vs. 0.98±0.21 ×10-3 mm2/s, P < 0.001 for both). Mean follow-up K decreased significantly compared with baseline (1.14±0.10 vs. 1.47±0.19, P < 0.001) for responders. Dratio showed significant positive correlation and high agreement with ADCratio (r = 0.776, P < 0.001). Likewise, Kratio showed significant negative correlation and high agreement with ADCratio (r = -0.658, P < 0.001).CONCLUSION:The new DKI model may serve as a new biomarker for the evaluation of early chemotherapy response in NHL

A simulation study on the measurement of D0-D0bar mixing parameter y at BES-III

We established a method on measuring the \dzdzb mixing parameter $y$ for BESIII experiment at the BEPCII $e^+e^-$ collider. In this method, the doubly tagged $\psi(3770) \to D^0 \overline{D^0}$ events, with one $D$ decays to CP-eigenstates and the other $D$ decays semileptonically, are used to reconstruct the signals. Since this analysis requires good $e/\pi$ separation, a likelihood approach, which combines the $dE/dx$, time of flight and the electromagnetic shower detectors information, is used for particle identification. We estimate the sensitivity of the measurement of $y$ to be 0.007 based on a $20fb^{-1}$ fully simulated MC sample.Comment: 6 pages, 7 figure