LC4SV: A Denoising Framework Learning to Compensate for Unseen Speaker Verification Models

The performance of speaker verification (SV) models may drop dramatically in noisy environments. A speech enhancement (SE) module can be used as a front-end strategy. However, existing SE methods may fail to bring performance improvements to downstream SV systems due to artifacts in the predicted signals of SE models. To compensate for artifacts, we propose a generic denoising framework named LC4SV, which can serve as a pre-processor for various unknown downstream SV models. In LC4SV, we employ a learning-based interpolation agent to automatically generate the appropriate coefficients between the enhanced signal and its noisy input to improve SV performance in noisy environments. Our experimental results demonstrate that LC4SV consistently improves the performance of various unseen SV systems. To the best of our knowledge, this work is the first attempt to develop a learning-based interpolation scheme aiming at improving SV performance in noisy environments

A KINEMATIC ANALYSIS OF ELDERLY GAIT WHILE STEPPING OVER OBSTACLES OF VARYING HEIGHT

The purpose of this study was to investigate the kinematics of elderly people who had experienced a fall stepping over obstacles of varying height. Six elderly non-fallers and six elderly fallers stepped over obstacles of height 0, 2.5, 5.1, 15.2cm. The longest stance duration was found in the highest obstacle 15.2cm, which might reflect relatively fast degrading gait function of the faller group. It was found that fallers took a longer time to cross the obstacles, which resulted in slower crossing speeds than when non-fallers stepped over the obstacles. We concluded that elderly persons who had experienced falling tend to step over obstacles conservatively as characterized

The Influence of Type 2 Diabetes and Glucose-Lowering Therapies on Cancer Risk in the Taiwanese

Objective. To investigate the association between type 2 diabetes, glucose-lowering therapies (monotherapy with either metformin, sulphonylurea or insulin) and cancer risk in Taiwan. Methods. Using Taiwan's National Health Research Institutes database of 1,000,000 random subjects from 2000–2008, we found 61777 patients with type 2 diabetes (age ≥20 years) and 677378 enrollees with no record of diabetes. Results. After adjusting for age and sex, we found patients with diabetes to have significantly higher risk of all cancers (OR: 1.176; 95% CI: 1.149–1.204, P < 0.001). Diabetic patients treated with insulin or sulfonylureas had significantly higher risk of all cancers, compared to those treated with metformin (OR: 1.583; 95% CI: 1.389–1.805, P < 0.001 and OR: 1.784; 95% CI: 1.406–2.262, P < 0.001). Metformin treatment was associated with a decreased risk of colon and liver cancer compared to sulphonylureas or insulin treatment. Sulfonylureas treatment was associated with an increased risk of breast and lung cancer compared to metformin therapy. Conclusions. Taiwanese with type 2 diabetes are at a high risk of breast, prostate, colon, lung, liver and pancreatic cancer. Those treated with insulin or sulfonylureas monotherapy are more likely to develop colon and liver cancer than those treated with metformin

The Knotted Protein UCH-L1 Exhibits Partially Unfolded Forms under Native Conditions that Share Common Structural Features with Its Kinetic Folding Intermediates.

The human ubiquitin C-terminal hydrolase, UCH-L1, is an abundant neuronal deubiquitinase that is associated with Parkinson's disease. It contains a complex Gordian knot topology formed by the polypeptide chain alone. Using a combination of fluorescence-based kinetic measurements, we show that UCH-L1 has two distinct kinetic folding intermediates that are transiently populated on parallel pathways between the denatured and native states. NMR hydrogen-deuterium exchange (HDX) experiments indicate the presence of partially unfolded forms (PUFs) of UCH-L1 under native conditions. HDX measurements as a function of urea concentration were used to establish the structure of the PUFs and pulse-labelled HDX NMR was used to show that the PUFs and the folding intermediates are likely the same species. In both cases, a similar stable core encompassing most of the central β-sheet is highly structured and α-helix 3, which is partially formed, packs against it. In contrast to the stable β-sheet core, the peripheral α-helices display significant local fluctuations leading to rapid exchange. The results also suggest that the main difference between the two kinetic intermediates is structure and packing of α-helices 3 and 7 and the degree of structure in β-strand 5. Together, the fluorescence and NMR results establish that UCH-L1 neither folds through a continuum of pathways nor by a single discrete pathway. Its folding is complex, the β-sheet core forms early and is present in both intermediate states, and the rate-limiting step which is likely to involve the threading of the chain to form the 52-knot occurs late on the folding pathway.This work was supported by the National Science Council (99-2911-I-007-034 and 104-2113-M-001-016), National Tsing Hua University and Academia Sinica, Taiwan. S.-T.D.H. was supported by a Career Development Award (CDA- 00025/2010-C) from the International Human Frontier Science Program. The NMR spectra were obtained at the NMR facility of the Department of Chemistry, University of Cambridge and at the Core Facility for Protein Structural Analysis, supported by the National Core Facility Program for Biotechnology, Taiwan.This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.jmb.2016.04.00

Early Detection of Tumor Response by FLT/MicroPET Imaging in a C26 Murine Colon Carcinoma Solid Tumor Animal Model

Fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) imaging demonstrated the change of glucose consumption of tumor cells, but problems with specificity and difficulties in early detection of tumor response to chemotherapy have led to the development of new PET tracers. Fluorine-18-fluorothymidine (18F-FLT) images cellular proliferation by entering the salvage pathway of DNA synthesis. In this study, we evaluate the early response of colon carcinoma to the chemotherapeutic drug, lipo-Dox, in C26 murine colorectal carcinoma-bearing mice by 18F-FDG and 18F-FLT. The male BALB/c mice were bilaterally inoculated with 1 × 105 and 1 × 106 C26 tumor cells per flank. Mice were intravenously treated with 10 mg/kg lipo-Dox at day 8 after 18F-FDG and 18F-FLT imaging. The biodistribution of 18F-FDG and 18F-FLT were followed by the microPET imaging at day 9. For the quantitative measurement of microPET imaging at day 9, 18F-FLT was superior to 18F-FDG for early detection of tumor response to Lipo-DOX at various tumor sizes (P < 0.05). The data of biodistribution showed similar results with those from the quantification of SUV (standard uptake value) by microPET imaging. The study indicates that 18F-FLT/microPET is a useful imaging modality for early detection of chemotherapy in the colorectal mouse model

Evolution of carbapenem resistance in Acinetobacter baumannii: An 18-year longitudinal study from a medical center in northern Taiwan

BackgroundCarbapenem-resistant Acinetobacter baumannii has emerged as an important cause of nosocomial infections with high morbidity and mortality. The carbapenemases, especially class D carbapenem-hydrolyzing oxacillinases (CHDLs), play an important role, but the relationship between their prevalence trend and carbapenem resistance remains unclear.Materials and methodsBetween 1995 and 2012, we collected 667 isolates of A. baumannii from a single medical center in northern Taiwan. Pulsed-field gel electrophoresis (PFGE) was used to determine clonality. Antimicrobial susceptibility was determined. Carbapenemase genes and associated genetic structures were detected by polymerase chain reaction.ResultsIsolates were heterogeneous on PFGE. Susceptibility to carbapenem decreased steadily over the study period from 88.1% (2001–2003) to <25% (2010–2012), whereas the isolates remained susceptible to colistin (nearly 100%) and partially susceptible to tigecycline (80%). Starting in 2001, isolates carrying the ISAba1-blaOXA-51-like allele were consistently identified. Isolates containing the transposons Tn2006 or Tn2008 first appeared in 2007 with increasing carriage rates from 17.5% (2007–2009) to 50.0% (2010–2012). The IS1008-ΔISAba3-blaOXA-58-like, blaOXA-72 and metallo-β-lactamase genes were detected only sporadically. Isolates carrying CHDL genes were resistant to multiple drugs, including carbapenem, but remained susceptible to colistin (100.0%).ConclusionIncreased carbapenem resistance in A. baumannii may be caused by the increased prevalence of isolates containing the ISAba1-blaOXA-51-like allele and the transposons Tn2006 and Tn2008

Foreword

The postsynaptic density protein-95/disks large/zonula occludens-1 (PDZ) protein domain family is one of the most common proteinprotein interaction modules in mammalian cells, with paralogs present in several hundred human proteins. PDZ domains are found in most cell types, but neuronal proteins, for example, are particularly rich in these domains. The general function of PDZ domains is to bring proteins together within the appropriate cellular compartment, thereby facilitating scaffolding, signaling, and trafficking events. The many functions of PDZ domains under normal physiological as well as pathological conditions have been reviewed recently. In this review, we focus on the molecular details of how PDZ domains bind their protein ligands and their potential as drug targets in this context

Isotretinoin Oil-Based Capsule Formulation Optimization

The purpose of this study was to develop and optimize an isotretinoin oil-based capsule with specific dissolution pattern. A three-factor-constrained mixture design was used to prepare the systemic model formulations. The independent factors were the components of oil-based capsule including beeswax (X1), hydrogenated coconut oil (X2), and soybean oil (X3). The drug release percentages at 10, 30, 60, and 90 min were selected as responses. The effect of formulation factors including that on responses was inspected by using response surface methodology (RSM). Multiple-response optimization was performed to search for the appropriate formulation with specific release pattern. It was found that the interaction effect of these formulation factors (X1X2, X1X3, and X2X3) showed more potential influence than that of the main factors (X1, X2, and X3). An optimal predicted formulation with Y10 min, Y30 min, Y60 min, and Y90 min release values of 12.3%, 36.7%, 73.6%, and 92.7% at X1, X2, and X3 of 5.75, 15.37, and 78.88, respectively, was developed. The new formulation was prepared and performed by the dissolution test. The similarity factor f2 was 54.8, indicating that the dissolution pattern of the new optimized formulation showed equivalence to the predicted profile