MOKPE: drug-target interaction prediction via manifold optimization based kernel preserving embedding.

BACKGROUND: In many applications of bioinformatics, data stem from distinct heterogeneous sources. One of the well-known examples is the identification of drug-target interactions (DTIs), which is of significant importance in drug discovery. In this paper, we propose a novel framework, manifold optimization based kernel preserving embedding (MOKPE), to efficiently solve the problem of modeling heterogeneous data. Our model projects heterogeneous drug and target data into a unified embedding space by preserving drug-target interactions and drug-drug, target-target similarities simultaneously. RESULTS: We performed ten replications of ten-fold cross validation on four different drug-target interaction network data sets for predicting DTIs for previously unseen drugs. The classification evaluation metrics showed better or comparable performance compared to previous similarity-based state-of-the-art methods. We also evaluated MOKPE on predicting unknown DTIs of a given network. Our implementation of the proposed algorithm in R together with the scripts that replicate the reported experiments is publicly available at https://github.com/ocbinatli/mokpe .

Robust Measures of Image-Registration-Derived Lung Biomechanics in SPIROMICS.

Chronic obstructive pulmonary disease (COPD) is an umbrella term used to define a collection of inflammatory lung diseases that cause airflow obstruction and severe damage to the lung parenchyma. This study investigated the robustness of image-registration-based local biomechanical properties of the lung in individuals with COPD as a function of Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage. Image registration was used to estimate the pointwise correspondences between the inspiration (total lung capacity) and expiration (residual volume) computed tomography (CT) images of the lung for each subject. In total, three biomechanical measures were computed from the correspondence map: the Jacobian determinant; the anisotropic deformation index (ADI); and the slab-rod index (SRI). CT scans from 245 subjects with varying GOLD stages were analyzed from the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS). Results show monotonic increasing or decreasing trends in the three biomechanical measures as a function of GOLD stage for the entire lung and on a lobe-by-lobe basis. Furthermore, these trends held across all five image registration algorithms. The consistency of the five image registration algorithms on a per individual basis is shown using Bland-Altman plots.

PLOSL: Population learning followed by one shot learning pulmonary image registration using tissue volume preserving and vesselness constraints.

This paper presents the Population Learning followed by One Shot Learning (PLOSL) pulmonary image registration method. PLOSL is a fast unsupervised learning-based framework for 3D-CT pulmonary image registration algorithm based on combining population learning (PL) and one-shot learning (OSL). The PLOSL image registration has the advantages of the PL and OSL approaches while reducing their respective drawbacks. The advantages of PLOSL include improved performance over PL, substantially reducing OSL training time and reducing the likelihood of OSL getting stuck in local minima. PLOSL pulmonary image registration uses tissue volume preserving and vesselness constraints for registration of inspiration-to-expiration and expiration-to-inspiration pulmonary CT images. A coarse-to-fine convolution encoder-decoder CNN architecture is used to register large and small shape features. During training, the sum of squared tissue volume difference (SSTVD) compensates for intensity differences between inspiration and expiration computed tomography (CT) images and the sum of squared vesselness measure difference (SSVMD) helps match the lung vessel tree. Results show that the PLOSL (SSTVD+SSVMD) algorithm achieved subvoxel landmark error while preserving pulmonary topology on the SPIROMICS data set, the public DIR-LAB COPDGene and 4DCT data sets.

Geodesic density regression for correcting 4DCT pulmonary respiratory motion artifacts.

Pulmonary respiratory motion artifacts are common in four-dimensional computed tomography (4DCT) of lungs and are caused by missing, duplicated, and misaligned image data. This paper presents a geodesic density regression (GDR) algorithm to correct motion artifacts in 4DCT by correcting artifacts in one breathing phase with artifact-free data from corresponding regions of other breathing phases. The GDR algorithm estimates an artifact-free lung template image and a smooth, dense, 4D (space plus time) vector field that deforms the template image to each breathing phase to produce an artifact-free 4DCT scan. Correspondences are estimated by accounting for the local tissue density change associated with air entering and leaving the lungs, and using binary artifact masks to exclude regions with artifacts from image regression. The artifact-free lung template image is generated by mapping the artifact-free regions of each phase volume to a common reference coordinate system using the estimated correspondences and then averaging. This procedure generates a fixed view of the lung with an improved signal-to-noise ratio. The GDR algorithm was evaluated and compared to a state-of-the-art geodesic intensity regression (GIR) algorithm using simulated CT time-series and 4DCT scans with clinically observed motion artifacts. The simulation shows that the GDR algorithm has achieved significantly more accurate Jacobian images and sharper template images, and is less sensitive to data dropout than the GIR algorithm. We also demonstrate that the GDR algorithm is more effective than the GIR algorithm for removing clinically observed motion artifacts in treatment planning 4DCT scans. Our code is freely available at https://github.com/Wei-Shao-Reg/GDR.

N-Phase Local Expansion Ratio for Characterizing Out-of-Phase Lung Ventilation.

Out-of-phase ventilation occurs when local regions of the lung reach their maximum or minimum volumes at breathing phases other than the global end inhalation or exhalation phases. This paper presents the N-phase local expansion ratio (LER N ) as a surrogate for lung ventilation. A common approach to estimate lung ventilation is to use image registration to align the end exhalation and inhalation 3DCT images and then analyze the resulting correspondence map. This 2-phase local expansion ratio (LER2) is limited because it ignores out-of-phase ventilation and thus may underestimate local lung ventilation. To overcome this limitation, LER N measures the maximum ratio of local expansion and contraction over the entire breathing cycle. Comparing LER2 to LER N provides a means for detecting and characterizing locations of the lung that experience out-of-phase ventilation. We present a novel in-phase/out-of-phase ventilation (IOV) function plot to visualize and measure the amount of high-function IOV that occurs during a breathing cycle. Treatment planning 4DCT scans collected during coached breathing from 32 human subjects with lung cancer were analyzed in this study. Results show that out-of-phase breathing occurred in all subjects and that the spatial distribution of out-of-phase ventilation varied from subject to subject. For the 32 subjects analyzed, 50% of the out-of-phase regions on average were mislabeled as low-function by LER2 (high-function threshold of 1.1, IOV threshold of 1.05). 4DCT and Xenon-enhanced CT of four sheep showed that LER8 is more accurate than LER2 for measuring lung ventilation.

Monotonic and Cyclic Bond Behavior of Deformed CFRP Bars in High Strength Concrete.

Composite reinforcing bars (rebars) that are used in concrete members with high performance (strength and durability) properties could have beneficial effects on the behavior of these members. This is especially vital when a building is constructed in an aggressive environment, for instance a corrosive environment. Although tension capacity/weight (or volume) ratios in composite rebars (carbon fiber reinforced polymer (CFRP), glass fiber reinforced polymer (GFRP), etc.) are very high when compared to steel rebars, major weaknesses in concrete members reinforced with these composite rebars may be the potential consequences of relatively poor bonding capacity. This may even be more crucial when the member is subjected to cyclic loading. Although monotonic bond tests are available in the literature, only limited experimental studies exist on bond characteristics under cyclic loading conditions. In order to fill this gap and propose preliminary design recommendations, 10 specimens of 10-mm-diameter ribbed CFRP rebars embedded in specially designed high strength concrete (f'c = 70 MPa) blocks were subjected to monotonic and cyclic pullout tests. The experimental results showed that cyclically loaded CFRP rebars had less bond strength than those companion specimens loaded monotonically.

The effect of trochleoplasty on patellar stability and kinematics: a biomechanical study in vitro.

Objective patellar instability has been correlated with dysplasia of the femoral trochlea. This in vitro study tested the hypothesis that trochleoplasty would increase patellar stability and normalise the kinematics of a knee with a dysplastic trochlea. Six fresh-frozen knees were loaded via the heads of the quadriceps. The patella was displaced 10 mm laterally and the displacing force was measured from 0 degrees to 90 degrees of flexion. Patellar tracking was measured from 0 degrees to 130 degrees of knee flexion using magnetic sensors. These tests were repeated after raising the central anterior trochlea to simulate dysplasia, and repeated again after performing a trochleoplasty on each specimen. The simulated dysplasia significantly reduced stability from that of the normal knee (p < 0.001). Trochleoplasty significantly increased the stability (p < 0.001), so that it did not then differ significantly from the normal knee (p = 0.244). There were small but statistically significant changes in patellar tracking (p< 0.001). This study has provided objective biomechanical data to support the use of trochleoplasty in the treatment of patellar instability associated with femoral trochlear dysplasia.

Disruptions to women's social identity: a comparative study of workplace stress experienced by women in three geographic regions.

Drawing on social identity theory (P. J. Burke, 1991) and the current status of women and equal opportunity legislation, the authors tested several factors associated with distress in working women in the People's Republic of China (PRC), Hong Kong, and the United States. Women in Hong Kong experienced significantly greater levels of life stress than PRC and U.S. women. Reports of negative attitudes toward women, gender evaluation, and avoidance coping were greater for Hong Kong and PRC women than for U.S. women. Hong Kong women reported more use of positive/confrontational coping mechanisms. Negative attitudes toward women had an important influence on life stress across regions. Moderator tests resulted in 2 significant findings: The effect of negative attitudes toward women on life stress was stronger for PRC and Hong Kong women, and the relationship between nervous/self-destructive coping and life stress was stronger for U.S. women.