An integrated approach with new strategies for QSAR models and lead optimization

Compound testing set for huAChE collected from Guo et al. (PDF 52 kb

Hydrodynamical Simulations of the Barred Spiral Galaxy NGC 1097

NGC 1097 is a nearby barred spiral galaxy believed to be interacting with the elliptical galaxy NGC 1097A located to its northwest. It hosts a Seyfert 1 nucleus surrounded by a circumnuclear starburst ring. Two straight dust lanes connected to the ring extend almost continuously out to the bar. The other ends of the dust lanes attach to two main spiral arms. To provide a physical understanding of its structural and kinematical properties, two-dimensional hydrodynamical simulations have been carried out. Numerical calculations reveal that many features of the gas morphology and kinematics can be reproduced provided that the gas flow is governed by a gravitational potential associated with a slowly rotating strong bar. By including the self-gravity of the gas disk in our calculation, we have found the starburst ring to be gravitationally unstable which is consistent with the observation in \citet{hsieh11}. Our simulations show that the gas inflow rate is 0.17 M_\sun yr$^{-1}$ into the region within the starburst ring even after its formation, leading to the coexistence of both a nuclear ring and a circumnuclear disk.Comment: 32 pages, 14 figures, 1 table, accepted for publication in the Ap

Training Energy-Based Normalizing Flow with Score-Matching Objectives

In this paper, we establish a connection between the parameterization of flow-based and energy-based generative models, and present a new flow-based modeling approach called energy-based normalizing flow (EBFlow). We demonstrate that by optimizing EBFlow with score-matching objectives, the computation of Jacobian determinants for linear transformations can be entirely bypassed. This feature enables the use of arbitrary linear layers in the construction of flow-based models without increasing the computational time complexity of each training iteration from $\mathcal{O}(D^2L)$ to $\mathcal{O}(D^3L)$ for an $L$-layered model that accepts $D$-dimensional inputs. This makes the training of EBFlow more efficient than the commonly-adopted maximum likelihood training method. In addition to the reduction in runtime, we enhance the training stability and empirical performance of EBFlow through a number of techniques developed based on our analysis on the score-matching methods. The experimental results demonstrate that our approach achieves a significant speedup compared to maximum likelihood estimation, while outperforming prior efficient training techniques with a noticeable margin in terms of negative log-likelihood (NLL)

Paper-Based ELISA: A Novel Diagnostic Approach for Monitoring Aqueous Humour VEGF Level in Ocular Diseases

We commonly diagnose ocular diseases via both morphological changes and symptoms. It is necessary to develop biochemically based assays for early or follow-up diagnosis of these diseases with a focus on robustness and ease of handling. To lay out a prospective path toward this goal, we describe and propose the use of ultrahigh sensitive paper-based ELISA (p-ELISA), which uses a treated piece of filter paper to monitor the activity of ocular diseases (i.e., detecting the vascular endothelial growth factor (VEGF) concentration in aqueous humour for proliferative diabetic retinopathy or age-related macular degeneration diagnosis). The advantages of p-ELISA include the following: (1) the capacity to directly measure biomarker concentrations in aqueous humour using only a tiny sample volume (as little as 2 μL); (2) significantly increased sensitivity compared to conventional ELISA (fg/mL levels); and (3) inexpensive materials and a short operation duration. P-ELISA is a novel point-of-care diagnostic tool with the significant potential to advance ophthalmological treatment guidelines by facilitating early detection and routinely monitoring therapeutic response

POWER: PhylOgenetic WEb Repeater—an integrated and user-optimized framework for biomolecular phylogenetic analysis

POWER, the PhylOgenetic WEb Repeater, is a web-based service designed to perform user-friendly pipeline phylogenetic analysis. POWER uses an open-source LAMP structure and infers genetic distances and phylogenetic relationships using well-established algorithms (ClustalW and PHYLIP). POWER incorporates a novel tree builder based on the GD library to generate a high-quality tree topology according to the calculated result. POWER accepts either raw sequences in FASTA format or user-uploaded alignment output files. Through a user-friendly web interface, users can sketch a tree effortlessly in multiple steps. After a tree has been generated, users can freely set and modify parameters, select tree building algorithms, refine sequence alignments or edit the tree topology. All the information related to input sequences and the processing history is logged and downloadable for the user's reference. Furthermore, iterative tree construction can be performed by adding sequences to, or removing them from, a previously submitted job. POWER is accessible at

Does Long-Term Use of Silver Nanoparticles Have Persistent Inhibitory Effect on H. pylori Based on Mongolian Gerbil’s Model?

It is urgent to find alternative agents due to increasing failure rate of Helicobacter pylori (H. pylori) eradication. The study surveyed the long-term effect of silver nanoparticles (AgNP) on H. pylori based on Mongolian gerbil's model

The upper limits of risk ratios and recommendations for reporting risk ratios, odds ratios, and rate ratios

Background Relative measures, including risk ratios (RRs) and odds ratios (ORs), are reported in many epidemiological studies. RRs represent how many times a condition is likely to develop when exposed to a risk factor. The upper limit of RRs is the multiplicative inverse of the baseline incidence. Ignoring the upper limits of RRs can lead to reporting exaggerated relative effect sizes. Objectives This study aims to demonstrate the importance of such upper limits for effect size reporting via equations, examples, and simulations and provide recommendations for the reporting of relative measures. Methods Equations to calculate RRs and their 95% confidence intervals (CIs) were listed. We performed simulations with 10,000 simulated subjects and three population variables: proportions at risk (0.05, 0.1, 0.3, 0.5, and 0.8), baseline incidence (0.05, 0.1, 0.3, 0.5, and 0.8), and RRs (0.5, 1.0, 5.0, 10.0, and 25.0). Subjects were randomly assigned with a risk based on the set of proportions-at-risk values. A disease occurred based on the baseline incidence among those not at risk. The incidence of those at risk was the product of the baseline incidence and the RRs. The 95% CIs of RRs were calculated according to Altman. Results The calculation of RR 95% CIs is not connected to the RR upper limits in equations. The RRs in the simulated populations at risk could reach the upper limits of RRs: multiplicative inverse of the baseline incidence. The upper limits to the derived RRs were around 1.25, 2, 3.3, 10, and 20, when the assumed baseline incidence rates were 0.8, 0.5, 0.3, 0.2, and 0.05, respectively. We demonstrated five scenarios in which the RR 95% CIs might exceed the upper limits. Conclusions Statistical significance does not imply the RR 95% CIs not exceeding the upper limits of RRs. When reporting RRs or ORs, the RR upper limits should be assessed. The rate ratio is also subject to a similar upper limit. In the literature, ORs tend to overestimate effect sizes. It is recommended to correct ORs that aim to approximate RRs assuming outcomes are rare. A reporting guide for relative measures, RRs, ORs, and rate ratios, is provided. Researchers are recommended to report whether the 95% CIs of relative measures, RRs, ORs, and rate ratios, overlap with the range of upper limits and discuss whether the relative measure estimates may exceed the upper limits