Prediction of protein-protein interaction sites using an ensemble method

<p>Abstract</p> <p>Background</p> <p>Prediction of protein-protein interaction sites is one of the most challenging and intriguing problems in the field of computational biology. Although much progress has been achieved by using various machine learning methods and a variety of available features, the problem is still far from being solved.</p> <p>Results</p> <p>In this paper, an ensemble method is proposed, which combines bootstrap resampling technique, SVM-based fusion classifiers and weighted voting strategy, to overcome the imbalanced problem and effectively utilize a wide variety of features. We evaluate the ensemble classifier using a dataset extracted from 99 polypeptide chains with 10-fold cross validation, and get a AUC score of 0.86, with a sensitivity of 0.76 and a specificity of 0.78, which are better than that of the existing methods. To improve the usefulness of the proposed method, two special ensemble classifiers are designed to handle the cases of missing homologues and structural information respectively, and the performance is still encouraging. The robustness of the ensemble method is also evaluated by effectively classifying interaction sites from surface residues as well as from all residues in proteins. Moreover, we demonstrate the applicability of the proposed method to identify interaction sites from the non-structural proteins (NS) of the influenza A virus, which may be utilized as potential drug target sites.</p> <p>Conclusion</p> <p>Our experimental results show that the ensemble classifiers are quite effective in predicting protein interaction sites. The Sub-EnClassifiers with resampling technique can alleviate the imbalanced problem and the combination of Sub-EnClassifiers with a wide variety of feature groups can significantly improve prediction performance.</p

Free from Bellman Completeness: Trajectory Stitching via Model-based Return-conditioned Supervised Learning

Off-policy dynamic programming (DP) techniques such as $Q$-learning have proven to be important in sequential decision-making problems. In the presence of function approximation, however, these techniques often diverge due to the absence of Bellman completeness in the function classes considered, a crucial condition for the success of DP-based methods. In this paper, we show how off-policy learning techniques based on return-conditioned supervised learning (RCSL) are able to circumvent these challenges of Bellman completeness, converging under significantly more relaxed assumptions inherited from supervised learning. We prove there exists a natural environment in which if one uses two-layer multilayer perceptron as the function approximator, the layer width needs to grow linearly with the state space size to satisfy Bellman completeness while a constant layer width is enough for RCSL. These findings take a step towards explaining the superior empirical performance of RCSL methods compared to DP-based methods in environments with near-optimal datasets. Furthermore, in order to learn from sub-optimal datasets, we propose a simple framework called MBRCSL, granting RCSL methods the ability of dynamic programming to stitch together segments from distinct trajectories. MBRCSL leverages learned dynamics models and forward sampling to accomplish trajectory stitching while avoiding the need for Bellman completeness that plagues all dynamic programming algorithms. We propose both theoretical analysis and experimental evaluation to back these claims, outperforming state-of-the-art model-free and model-based offline RL algorithms across several simulated robotics problems

Tungsten Disulphide Based All Fiber Q-Switching Cylindrical-Vector Beam Generation

We proposed and demonstrated an all fiber passively Q-switching laser to generate cylindrical-vectorbeam, a two dimensional material,tungsten disulphide (WS2), was adopted as a saturable absorber inside the laser cavity, while a few-mode fiber Bragg grating was used as a transverse mode-selective output coupler. The repetition rate of the Q-switching output pulses can be varied from 80 kHz to 120 kHz with a shortest duration of 958 ns. Attributed to the high damage threshold and polarization insensitivity of the WS2 based saturable absorber, the radially polarized beam and azimuthally polarized beam can be easily generated in the Q-switchingfiber laser

The fast light of CsI(Na) crystals

The responds of different common alkali halide crystals to alpha-rays and gamma-rays are tested in our research. It is found that only CsI(Na) crystals have significantly different waveforms between alpha and gamma scintillations, while others have not this phenomena. It is suggested that the fast light of CsI(Na) crystals arises from the recombination of free electrons with self-trapped holes of the host crystal CsI. Self-absorption limits the emission of fast light of CsI(Tl) and NaI(Tl) crystals.Comment: 5 pages, 11 figures Submit to Chinese Physics

Active Surveillance of Carbapenemase-Producing Organisms (CPO) Colonization With Xpert Carba-R Assay Plus Positive Patient Isolation Proves to Be Effective in CPO Containment

Background: Rapid screening of patients for colonization with carbapenemase-producing organisms (CPO), coupled with implementation of infection prevention strategies, has the potential to contain the spread of CPO.Methods: We first evaluated the performance of Xpert Carba-R assay (in comparison with other phenotypic methods) for carbapenemase detection using clinical isolates, and then used it to determine the intestinal CPO colonization in hospitalized patients. We then assessed the effectiveness of patient isolation in controlling the spread of CPO in a medical intensive care unit.Results: The Xpert Carba-R assay required the least processing time to reveal results and showed a 94.5% sensitivity and specificity in carbapenemase detection, except for IMP-8 (n = 4). During a 6-month study period, 134 patients in one ward were studied for CPO colonization and infection. Fifteen patients (11.2%) were colonized by CPO as detected by Xpert Carba-R assay, including three NDM, three IMP, and nine KPC possessing strains. The overall colonization and CPO infection rates were both 11.2% each. Isolation of patients with CPO led to a reduction in both colonization (from 28.6 to 5.6%) and infection rates (from 35.7 to 2.8%) during the study period (p &lt; 0.05).Conclusion: Active surveillance of CPO utilizing the Xpert Carba-R assay supplemented with immediate patient isolation, proved to be an effective strategy to limit the spread of CPO in a health care setting

Antidepressant Effects of Repetitive Transcranial Magnetic Stimulation Over Prefrontal Cortex of Parkinson's Disease Patients With Depression: A Meta-Analysis

Objective: The purpose of this meta-analysis was to investigate the antidepressant effects of repetitive transcranial magnetic stimulation (rTMS) over the prefrontal cortex (PFC) of patients with Parkinson's disease (PD) and to determine the optimal rTMS parameters, such as the intensity, frequency and the delivered pattern of rTMS stimulation.Methods: EMBASE, PubMed, Web of Science, MEDLINE, and Cochrane data bases were researched for papers published before March 12, 2018. Studies investigating the anti-depression effects of rTMS over PFC in patients with PD were considered. The main outcomes of pre- and post-rTMS treatment as well as score changes were all extracted. The mean effect size was estimated by calculating the standardized mean difference (SMD) with 95% confidence interval (CI) by using fixed or random effect models as appropriate.Results: Nine studies containing 137 PD patients with depression were included. The pooled results showed significant pre-post anti-depressive effects of rTMS over PFC in PD patients with depression (SMD = −0.80, P &lt; 0.00001). The subgroup analyses of stimulation intensity, frequencies, and models also revealed significant effects (Intensities: 90% RMT: SMD = −1.16, P = 0.0006; &gt;100% RMT: SMD = −0.82, P &lt; 0.0001. Frequencies: &lt; 1.0 Hz: SMD = −0.83, P = 0.03; 5.0 Hz: SMD = −1.10, P &lt; 0.0001; ≥10.0 Hz: SMD = −0.55, P = 0.02. Models: Continuous: SMD = −0.79, P &lt; 0.0001; Discontinuous: SMD = −0.84, P = 0.02). But the results of the studies with place-controlled designs were not significant (Overall: SMD = −0.27, P = 0.54. Intensities: 90% RMT: SMD = 0.27, P = 0.68; 100% RMT: SMD = −0.32, P = 0.33. Frequencies: 5.0 Hz: SMD = −0.87, P = 0.10; ≥10.0 Hz: SMD = 0.27, P = 0.66. Models: Continuous: SMD = −0.28, P = 0.68; Discontinuous: SMD = −0.32, P = 0.33). The greater effect sizes of rTMS with 90% RMT, 5.0 Hz in discontinuous days can be observed rather than the other parameters in both kinds of analyses across study design.Conclusions: rTMS may have a significant positive pre-post anti-depressive effect over PFC on patients with depression, especially by using 5.0 Hz frequency with 90% RMT intensity in discontinuous days, which may produce better effects than other parameters. The real effect, though, was not different from that of the placebo. Future studies with larger sample sizes and high-quality studies are needed to further corroborate our results and to identify the optimal rTMS protocols

Percutaneous angioplasty and/or stenting versus aggressive medical therapy in patients with symptomatic intracranial atherosclerotic stenosis: a 1-year follow-up study

BackgroundSymptomatic intracranial atherosclerotic stenosis (sICAS) is one of the common causes of ischemic stroke. However, the treatment of sICAS remains a challenge in the past with unfavorable findings. The purpose of this study was to explore the effect of stenting versus aggressive medical management on preventing recurrent stroke in patients with sICAS.MethodsWe prospectively collected the clinical information of patients with sICAS who underwent percutaneous angioplasty and/or stenting (PTAS) or aggressive medical therapy from March 2020 to February 2022. Propensity score matching (PSM) was employed to ensure well-balanced characteristics of two groups. The primary outcome endpoint was defined as recurrent stroke or transient ischemic attack (TIA) within 1 year.ResultsWe enrolled 207 patients (51 in the PTAS and 156 in the aggressive medical groups) with sICAS. No significant difference was found between PTAS group and aggressive medical group for the risk of stroke or TIA in the same territory beyond 30 days through 6 months (P = 0.570) and beyond 30 days through 1 year (P = 0.739) except for within 30 days (P = 0.003). Furthermore, none showed a significant difference for disabling stroke, death and intracranial hemorrhage within 1 year. These results remain stable after adjustment. After PSM, all the outcomes have no significant difference between these two groups.ConclusionThe PTAS has similar treatment outcomes compared with aggressive medical therapy in patients with sICAS across 1-year follow-up

A Novel Non-Volatile Inverter-based CiM: Continuous Sign Weight Transition and Low Power on-Chip Training

In this work, we report a novel design, one-transistor-one-inverter (1T1I), to satisfy high speed and low power on-chip training requirements. By leveraging doped HfO2 with ferroelectricity, a non-volatile inverter is successfully demonstrated, enabling desired continuous weight transition between negative and positive via the programmable threshold voltage (VTH) of ferroelectric field-effect transistors (FeFETs). Compared with commonly used designs with the similar function, 1T1I uniquely achieves pure on-chip-based weight transition at an optimized working current without relying on assistance from off-chip calculation units for signed-weight comparison, facilitating high-speed training at low power consumption. Further improvements in linearity and training speed can be obtained via a two-transistor-one-inverter (2T1I) design. Overall, focusing on energy and time efficiencies, this work provides a valuable design strategy for future FeFET-based computing-in-memory (CiM)

An Improved In-house MALDI-TOF MS Protocol for Direct Cost-Effective Identification of Pathogens from Blood Cultures

Background: Bloodstream infection is a major cause of morbidity and mortality in hospitalized patients worldwide. Delays in the identification of microorganisms often leads to a poor prognosis. The application of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) directly to blood culture (BC) broth can potentially identify bloodstream infections earlier, and facilitate timely management.Methods: We developed an “in-house” (IH) protocol for direct MALDI-TOF MS based identification of organisms in positive BCs. The IH protocol was initially evaluated and improved with spiked BC samples, and its performance was compared with the commercial Sepsityper™ kit using both traditional and modified cut-off values. We then studied in parallel the performance of the IH protocol and the colony MS identifications in positive clinical BC samples using only modified cut-off values. All discrepancies were investigated by “gold standard” of gene sequencing.Results: In 54 spiked BC samples, the IH method showed comparable results with Sepsityper™ after applying modified cut-off values. Specifically, accurate species and genus level identification was achieved in 88.7 and 3.9% of all the clinical monomicrobial BCs (284/301, 94.4%), respectively. The IH protocol exhibited superior performance for Gram negative bacteria than for Gram positive bacteria (92.8 vs. 82.4%). For anaerobes and yeasts, accurate species identification was achieved in 80.0 and 90.0% of the cases, respectively. For polymicrobial cultures (17/301, 5.6%), MALDI-TOF MS correctly identified a single species present in all the polymicrobial BCs under the Standard mode, while using the MIXED method, two species were correctly identified in 52.9% of the samples. Comparisons based on BC bottle type, showed that the BACTEC™ Lytic/10 Anaerobic/F culture vials performed the best.Conclusion: Our study provides a novel and effective sample preparation method for MALDI-TOF MS direct identification of pathogens from positive BC vials, with a lower cost ($1.5 vs.$ 7) albeit a slightly more laborious extracting process (an extra 15 min) compared with Sepsityper™ kit

Clinical Performance Evaluation of VersaTrek 528 Blood Culture System in a Chinese Tertiary Hospital

Background: The aim of this study was to evaluate the clinical performance of VersaTrek 528 compared to BACTEC FX 400 blood culture (BC) systems.Materials and Methods: Simulated and clinically obtained BCs were used in the study. Confirmed bacterial species (n = 78), including 43 Gram-positives, 30 Gram-negatives, and 5 Candida albicans strains, were each inoculated into BC bottles. Clinically obtained BCs were subdivided into two groups, A and B. In group A were 72 BC sets (pair: aerobic and anaerobic) in which a set inoculated with 5 ml blood was processed in the VersaTrek BC system, whilst the one inoculated with 10 ml blood was processed in the FX BC system. In group B, 76 BC sets (pairs) corresponding to 152 VersaTrek bottles and 152 FX bottles were inoculated with the same volume (10 ml) of blood, and processed in each system.Results: In the simulated BC study, 90% (63/70) of the VersaTrek aerobic bottles were positive, which was higher than that of FX 400 (59/70, 84%), but was not statistically significant (P = 0.423). In contrast, FX 400 anaerobic bottles had a higher positive rate than the other BC system (84 vs. 77%), although it was statistically insignificant (P = 0.267). Time to detection of organisms in the two BCs was comparable for both aerobic (P = 0.131) and anaerobic bottles (P = 0.104). In clinical BCs of group A, FX BC system had slightly higher positive rates for both aerobic (11.1 vs. 9.7%, P = 0.312) and anaerobic (8.3 vs. 6.9%, P = 0.375) bottles. However, the difference was not statistically significant. In group B, VersaTrek aerobic bottles had a higher positive rate compared to the other BC system (10.5 vs. 5.2%, P = 0.063). In terms of positive rates of sub-studies A and B, VersaTrek and FX BC systems were comparable.Conclusion: There was no significant difference between the two BC systems in the detection of bacteria and fungi in simulated BCs. In clinical BCs, the performance of the VersaTrek BC system, with inoculation of 5 or 10 ml patient’s blood, was comparable to the FX system with inoculation of 10 ml patient’s blood