A sequence-based hybrid predictor for identifying conformationally ambivalent regions in proteins

<p>Abstract</p> <p>Background</p> <p>Proteins are dynamic macromolecules which may undergo conformational transitions upon changes in environment. As it has been observed in laboratories that protein flexibility is correlated to essential biological functions, scientists have been designing various types of predictors for identifying structurally flexible regions in proteins. In this respect, there are two major categories of predictors. One category of predictors attempts to identify conformationally flexible regions through analysis of protein tertiary structures. Another category of predictors works completely based on analysis of the polypeptide sequences. As the availability of protein tertiary structures is generally limited, the design of predictors that work completely based on sequence information is crucial for advances of molecular biology research.</p> <p>Results</p> <p>In this article, we propose a novel approach to design a sequence-based predictor for identifying conformationally ambivalent regions in proteins. The novelty in the design stems from incorporating two classifiers based on two distinctive supervised learning algorithms that provide complementary prediction powers. Experimental results show that the overall performance delivered by the hybrid predictor proposed in this article is superior to the performance delivered by the existing predictors. Furthermore, the case study presented in this article demonstrates that the proposed hybrid predictor is capable of providing the biologists with valuable clues about the functional sites in a protein chain. The proposed hybrid predictor provides the users with two optional modes, namely, the <it>high-sensitivity </it>mode and the <it>high-specificity </it>mode. The experimental results with an independent testing data set show that the proposed hybrid predictor is capable of delivering sensitivity of 0.710 and specificity of 0.608 under the <it>high-sensitivity </it>mode, while delivering sensitivity of 0.451 and specificity of 0.787 under the <it>high-specificity </it>mode.</p> <p>Conclusion</p> <p>Though experimental results show that the hybrid approach designed to exploit the complementary prediction powers of distinctive supervised learning algorithms works more effectively than conventional approaches, there exists a large room for further improvement with respect to the achieved performance. In this respect, it is of interest to investigate the effects of exploiting additional physiochemical properties that are related to conformational ambivalence. Furthermore, it is of interest to investigate the effects of incorporating lately-developed machine learning approaches, e.g. the random forest design and the multi-stage design. As conformational transition plays a key role in carrying out several essential types of biological functions, the design of more advanced predictors for identifying conformationally ambivalent regions in proteins deserves our continuous attention.</p

T Oligo-Primed Polymerase Chain Reaction (TOP-PCR): A Robust Method for the Amplification of Minute DNA Fragments in Body Fluids.

Body fluid DNA sequencing is a powerful noninvasive approach for the diagnosis of genetic defects, infectious agents and diseases. The success relies on the quantity and quality of the DNA samples. However, numerous clinical samples are either at low quantity or of poor quality due to various reasons. To overcome these problems, we have developed T oligo-primed polymerase chain reaction (TOP-PCR) for full-length nonselective amplification of minute quantity of DNA fragments. TOP-PCR adopts homogeneous "half adaptor" (HA), generated by annealing P oligo (carrying a phosphate group at the 5' end) and T oligo (carrying a T-tail at the 3' end), for efficient ligation to target DNA and subsequent PCR amplification primed by the T oligo alone. Using DNA samples from body fluids, we demonstrate that TOP-PCR recovers minute DNA fragments and maintains the DNA size profile, while enhancing the major molecular populations. Our results also showed that TOP-PCR is a superior method for detecting apoptosis and outperforms the method adopted by Illumina for DNA amplification

The incidence of symptomatic venous thromboembolism following hip fractures with or without surgery in Taiwan

AbstractBackgroundInformation on the incidence of venous thromboembolism (VTE) following hip fractures in Asia is rare. This study will investigate the epidemiology of symptomatic VTE in Taiwanese patients experiencing hip fractures.Methods and resultsWe used Taiwan's National Health Insurance Research Database to retrospectively identify patients (≧45years) who experienced hip fractures from 1998 to 2007 and were followed up for 3months after the discharge. Logistic regression analysis determined the independent risk factors of symptomatic VTE after the fractures. We identified 134,034 patients (mean age: 76.2±9.7years; female: 57.8%) who experienced hip fractures, 83.2% of whom underwent hip surgery. The overall pharmacological thromboprophylaxis rate was 2.7%. The mean length of stay was 11.3±7.9days. The 3-month cumulative incidence of symptomatic VTE was 77 events per 10,000 persons. Multivariate analysis showed that previous DVT, previous PE, varicose veins, cancer, heart failure, renal insufficiency, and older age were independent risk factors of developing VTE.ConclusionsThe incidence of symptomatic VTE after hip fractures is low in Taiwan. Patients rarely received pharmacological thromboprophylaxis following hip fractures. Universal thromboprophylaxis for patients experiencing hip fractures was not necessary in Taiwan, but it should be considered in high-risk populations

CCDWT-GAN: Generative Adversarial Networks Based on Color Channel Using Discrete Wavelet Transform for Document Image Binarization

To efficiently extract the textual information from color degraded document images is an important research topic. Long-term imperfect preservation of ancient documents has led to various types of degradation such as page staining, paper yellowing, and ink bleeding; these degradations badly impact the image processing for information extraction. In this paper, we present CCDWT-GAN, a generative adversarial network (GAN) that utilizes the discrete wavelet transform (DWT) on RGB (red, green, blue) channel splited images. The proposed method comprises three stages: image preprocessing, image enhancement, and image binarization. This work conducts comparative experiments in the image preprocessing stage to determine the optimal selection of DWT with normalization. Additionally, we perform an ablation study on the results of the image enhancement stage and the image binarization stage to validate their positive effect on the model performance. This work compares the performance of the proposed method with other state-of-the-art (SOTA) methods on DIBCO and H-DIBCO ((Handwritten) Document Image Binarization Competition) datasets. The experimental results demonstrate that CCDWT-GAN achieves a top two performance on multiple benchmark datasets, and outperforms other SOTA methods

System-Level Biochip for Impedance Sensing and Programmable Manipulation of Bladder Cancer Cells

This paper develops a dielectrophoretic (DEP) chip with multi-layer electrodes and a micro-cavity array for programmable manipulations of cells and impedance measurement. The DEP chip consists of an ITO top electrode, flow chamber, middle electrode on an SU-8 surface, micro-cavity arrays of SU-8 and distributed electrodes at the bottom of the micro-cavity. Impedance sensing of single cells could be performed as follows: firstly, cells were trapped in a micro-cavity array by negative DEP force provided by top and middle electrodes; then, the impedance measurement for discrimination of different stage of bladder cancer cells was accomplished by the middle and bottom electrodes. After impedance sensing, the individual releasing of trapped cells was achieved by negative DEP force using the top and bottom electrodes in order to collect the identified cells once more. Both cell manipulations and impedance measurement had been integrated within a system controlled by a PC-based LabVIEW program. In the experiments, two different stages of bladder cancer cell lines (grade III: T24 and grade II: TSGH8301) were utilized for the demonstration of programmable manipulation and impedance sensing; as the results show, the lower-grade bladder cancer cells (TSGH8301) possess higher impedance than the higher-grade ones (T24). In general, the multi-step manipulations of cells can be easily programmed by controlling the electrical signal in our design, which provides an excellent platform technology for lab-on-a-chip (LOC) or a micro-total-analysis-system (Micro TAS)

Correction of Tetralogy of Fallot with Absent Pulmonary Valve Syndrome in a Young Infant Using a Bicuspid Equine Pericardial Tube

Absent pulmonary valve syndrome (APVS) is an uncommon variant of tetralogy of Fallot (TOF), which manifests morphologically as vestigial pulmonary valve cusps at the right ventricle-pulmonary trunk junction. The aneurysmally dilated pulmonary arteries may compress the tracheobronchial tree and cause severe respiratory distress in the neonatal or infant stage. Early surgical correction in these patients is necessary despite the high operative mortality rate. A 1-day-old male neonate suffered from progressive shortness of breath after birth. Echocardiography confirmed the diagnosis of TOF with APVS. The marked dilatation of pulmonary arteries resulted in airway compression in addition to heart failure. Total surgical correction was performed at 40 days of age, using a homemade bicuspid equine pericardial tube for right ventricular outflow reconstruction. The short-term follow-up echocardiogram demonstrated good motility of the pericardial leaflet. However, patients receiving this type of valved conduit require meticulous long-term follow-up

Urinary Neutrophil Gelatinase-Associated Lipocalin Is a Potential Biomarker for Renal Damage in Patients with Systemic Lupus Erythematosus

Neutrophil gelatinase-associated lipocalin (NGAL) has been demonstrated to be a novel biomarker in acute and chronic kidney disease. We hypothesized that 24-hour urinary NGAL excretion may be a predictor for renal damage in patients with systemic lupus erythematosus (SLE). Thirty-four SLE patients with renal involvement (SLE-renal group), 8 SLE patients without renal involvement (SLE-nonrenal group), 14 patients with non-SLE autoimmune diseases (disease control or DC group), and 12 healthy volunteers (normal control or NC group) were compared for 24-hour urinary excretion of NGAL and different cytokines. We found that the 24-hour urinary NGAL excretion in the SLE-renal group was higher than that in the SLE-non-renal, DC, and NC groups. However, the excretion of interleukin-10, transforming growth factor-β1, and tumor necrosis factor-α was not different between the SLE-renal and SLE-non-renal groups. Furthermore, NGAL excretion in the SLE-renal group was correlated with serum creatinine levels and creatinine clearance, but not with the SLE Disease Activity Index score. Multivariate logistic regression analysis and receiver operating characteristic curve analysis revealed that 24-hour urinary NGAL excretion is a potential biomarker for renal damage in SLE patients, with higher sensitivity and specificity than anti-dsDNA antibody titers

Paeoniae alba Radix Promotes Peripheral Nerve Regeneration

The present study provides in vitro and in vivo evaluation of Paeoniae alba Radix (PR) on peripheral nerve regeneration. In the in vitro study, we found the PR caused a marked enhancement of the nerve growth factor-mediated neurite outgrowth from PC12 cells as well as their expression of growth associated protein 43 and synapsin I. In the in vivo study, silicone rubber chambers filled with the PR water extract were used to bridge a 10-mm sciatic nerve defect in rats. At the conclusion of 8 weeks, regenerated nerves in the PR groups, especially at 1.25 mg ml−1 had a higher rate of successful regeneration across the wide gap, relatively larger mean values of total nerve area, myelinated axon count and blood vessel number, and a significantly larger nerve conductive velocity compared to the control group (P  <  .05). These results suggest that the PR extract can be a potential nerve growth-promoting factor, being salutary in aiding the growth of injured peripheral nerve