A spectrally discretized wide-angle parabolic equation model for simulating acoustic propagation in laterally inhomogeneous oceans.

Sound waves can be used to carry out underwater activities. Rapidly and accurately simulating sound propagation is the basis for underwater detection. The wide-angle parabolic model has a good computational speed and accuracy and is currently the main numerical model for mid- and low-frequency sound propagation. The classical wide-angle parabolic equation model is discretized by the finite difference method and a low-order difference scheme is generally adopted. In this paper, a wide-angle parabolic equation model based on a spectral method is proposed. The depth operators of each layer are discretized via the Chebyshev spectral method and then assembled into a global matrix for the forward step. Lateral inhomogeneity is addressed by updating the global depth matrix while stepping forward. In the proposed spectral algorithm, both soft and hard seabeds can be accurately simulated by imposing boundary conditions, and the perfectly matched layer technique is used to truncate the unbounded acoustic half-space. Several representative numerical experiments prove the accuracy and efficiency of the proposed algorithm. However, the spectral method requires that the thickness of the layers does not change during the forward step. Thus, the current spectral algorithm cannot simulate waveguides with terrain undulation, which is its main limitation.

Protein pK a Prediction with Machine Learning.

Protein pK a prediction is essential for the investigation of the pH-associated relationship between protein structure and function. In this work, we introduce a deep learning-based protein pK a predictor DeepKa, which is trained and validated with the pK a values derived from continuous constant-pH molecular dynamics (CpHMD) simulations of 279 soluble proteins. Here, the CpHMD implemented in the Amber molecular dynamics package has been employed (Huang Y.J. Chem. Inf. Model.2018, 58, 1372-1383). Notably, to avoid discontinuities at the boundary, grid charges are proposed to represent protein electrostatics. We show that the prediction accuracy by DeepKa is close to that by CpHMD benchmarking simulations, validating DeepKa as an efficient protein pK a predictor. In addition, the training and validation sets created in this study can be applied to the development of machine learning-based protein pK a predictors in the future. Finally, the grid charge representation is general and applicable to other topics, such as the protein-ligand binding affinity prediction.

A High-Efficiency Spectral Method for Two-Dimensional Ocean Acoustic Propagation Calculations.

The accuracy and efficiency of sound field calculations highly concern issues of hydroacoustics. Recently, one-dimensional spectral methods have shown high-precision characteristics when solving the sound field but can solve only simplified models of underwater acoustic propagation, thus their application range is small. Therefore, it is necessary to directly calculate the two-dimensional Helmholtz equation of ocean acoustic propagation. Here, we use the Chebyshev-Galerkin and Chebyshev collocation methods to solve the two-dimensional Helmholtz model equation. Then, the Chebyshev collocation method is used to model ocean acoustic propagation because, unlike the Galerkin method, the collocation method does not need stringent boundary conditions. Compared with the mature Kraken program, the Chebyshev collocation method exhibits a higher numerical accuracy. However, the shortcoming of the collocation method is that the computational efficiency cannot satisfy the requirements of real-time applications due to the large number of calculations. Then, we implemented the parallel code of the collocation method, which could effectively improve calculation effectiveness.

A three-dimensional finite difference model for ocean acoustic propagation and benchmarking for topographic effects.

A three-dimensional (3D) finite difference (FD) model with formal fourth-order accuracy has been developed for the ocean acoustic Helmholtz equation (HE), which can be used to address arbitrary bathymetry and provide more accurate benchmark solutions for other 3D underwater acoustic approximate models. The derivatives in the acoustic HE are numerically discretized based on regular grids, and the perfectly matched layer is introduced to absorb unphysical reflections from the boundaries where Sommerfeld radiation conditions are deployed. The system of linear equations is solved using a parallel matrix-free geometric multigrid preconditioned biconjugate gradient stabilized iteration method, and the code (named COACH) is run on the Tianhe-2 supercomputer in China. Four 3D topographic benchmark acoustic cases-a wedge waveguide, Gaussian canyon, conical seamount, and corrugated seabed-are simulated to test the present FD model, and the maximum number of grid points reaches 33.15 × 109 in the wedge waveguide case, running in parallel with 988 central processing unit cores. Furthermore, the accuracy and generality of the present model have been verified by solution comparisons with other available 3D acoustic propagation models, and the two-dimensional and 3D transmission loss contours are presented to facilitate the distinguishing among the acoustic field features of these cases.

Two Chebyshev Spectral Methods for Solving Normal Modes in Atmospheric Acoustics.

The normal mode model is important in computational atmospheric acoustics. It is often used to compute the atmospheric acoustic field under a time-independent single-frequency sound source. Its solution consists of a set of discrete modes radiating into the upper atmosphere, usually related to the continuous spectrum. In this article, we present two spectral methods, the Chebyshev-Tau and Chebyshev-Collocation methods, to solve for the atmospheric acoustic normal modes, and corresponding programs are developed. The two spectral methods successfully transform the problem of searching for the modal wavenumbers in the complex plane into a simple dense matrix eigenvalue problem by projecting the governing equation onto a set of orthogonal bases, which can be easily solved through linear algebra methods. After the eigenvalues and eigenvectors are obtained, the horizontal wavenumbers and their corresponding modes can be obtained with simple processing. Numerical experiments were examined for both downwind and upwind conditions to verify the effectiveness of the methods. The running time data indicated that both spectral methods proposed in this article are faster than the Legendre-Galerkin spectral method proposed previously.

Application of hyperspectral imaging for spatial prediction of soluble solid content in sweet potato.

Visible and near infrared (Vis-NIR) hyperspectral imaging was used for fast detection and visualization of soluble solid content (SSC) in 'Beijing 553' and 'Red Banana' sweet potatoes. Hyperspectral images were acquired from 420 ROIs of each cultivar of sliced sweet potatoes. There were 8 and 10 outliers removed from 'Beijing 553' and 'Red Banana' sweet potatoes by Monte Carlo partial least squares (MCPLS). The optimal spectral pretreatments were determined to enhance the performance of the prediction model. Successive projections algorithm (SPA) and competitive adaptive reweighted sampling (CARS) were employed to select characteristic wavelengths. SSC prediction models were developed using partial least squares regression (PLSR), support vector regression (SVR) and multivariate linear regression (MLR). The more effective prediction performances emerged from the SPA-SVR model with R p 2 of 0.8581, RMSEP of 0.2951 and RPDp of 2.56 for 'Beijing 553' sweet potato, and the CARS-MLR model with R p 2 of 0.8153, RMSEP of 0.2744 and RPDp of 2.09 for 'Red Banana' sweet potato. Spatial distribution maps of SSC were obtained in a pixel-wise manner using SPA-SVR and CARS-MLR models for quantifying the SSC level in a simple way. The overall results illustrated that Vis-NIR hyperspectral imaging was a powerful tool for spatial prediction of SSC in sweet potatoes.

Contribution of root uptake to cadmium accumulation in two peanut cultivars: evidence from a split-column soil experiment.

Cadmium (Cd) accumulation and internal Cd translocation in the peanut (Arachis hypogaea L.) are highly related to root uptake, which may largely depend on the cultivar variation and the depth of the Cd-contaminated soil. A split-column soil experiment was conducted using two common Chinese peanut cultivars (Huayu-20 and Huayu-23) known to relocate Cd to different tissues. The growth medium was separated into four layers and Cd solution was solely applied to one layer to determine the key depth affecting the Cd accumulation in a plant via root uptakes. The results showed that the biomass of Huayu-23 was significantly higher biomass (3.28-94.0%) than that of Huayu-20, especially in the aerial parts (stems and leaves) and kernels, implying the dilution of Cd. Following the addition of Cd to the soil, the Cd concentrations in peanut tissues increased on average by 28.9-172 and 28.3-111% in Huayu-20 and Huayu-23, respectively. The largest presence of Cd in a peanut plant was observed in the aerial parts, followed by the kernels. Huayu-20 accumulated more Cd in plant tissues than did Huayu-23 due to the former's high Cd translocation. These findings imply that peanut cultivars vary widely in biomass, Cd accumulation, and the percentage distribution of Cd among various plant tissues, especially kernels. Different Cd treatments in the full depth of the root zone induced significant alterations in Cd accumulation of peanut tissues, especially kernels, for both cultivars. The percentage distribution of Cd accumulation by kernels was significantly higher in the deeper layer than in the top layer of the root zone for both peanut cultivars. This study suggests that soil modifications performed during agronomic activities should take into account the full depth of root exploration as well as the peanut cultivars to manage plant Cd uptake.

2940-nm Er:YAG fractional laser enhanced the effect of topical drug for psoriasis.

We observed the promoting effects of the 2940-nm erbium:YAG (Er:YAG) fractional laser in topical drug delivery for psoriasis. A total of five (four males and one female) recalcitrant psoriasis patients were given laser treatment eight times at 1-week intervals with the following parameters: 5-11% spot density and 100-µm energy depth. The psoriatic skin lesions on the left knee and the corresponding lesions at the right ones of each psoriasis patient were randomly divided into two groups: laser + topical drug group (L) and drug alone group (D). The psoriatic lesions in both groups were treated with the same topical treatment (calcipotriol ointment). The corresponding psoriatic lesions in the L group received extra 2940-nm Er:YAG laser irradiation before topical treatment. The photos of psoriatic lesions were taken before each treatment. The final photos were obtained from the patients at the seventh day after the final treatment. Drug alone or in combination with laser Er:YAG both reduced psoriatic lesions. However, with the increase in the number of treatments, increasing differences were observed between the treatment and the control sides. The therapeutic outcomes in the L groups were better than those in the D groups. Psoriasis area and severity index (PASI) scores for five cases of both groups were decreased. However, the scores in the L groups were lower than those in the D groups. The use of 2940 nm Er:YAG promoted the absorption of topical drugs for psoriasis, improving the therapeutic effect.

The progression of CD56+ myeloid sarcoma: A case report and literature review.

The current study presents a case of cluster of differentiation (CD)56+ myeloid sarcoma in a patient that initially presented with skin lesions, and provides evidence for the clinical and differential diagnosis of myeloid sarcoma. The patient of the present case report was a 65-year-old man who was admitted to hospital with a six-month history of bilateral purple-red papules and nodules, which were present on the upper limbs of the patient and had spread over his whole body one month prior to admission to the hospital. Pathological examination demonstrated a diffuse infusion of primitive round cells at the papillary dermis and subcutaneous tissues. The infiltrated cells were 40-60 µm in diameter and morphologically identical. Immunohistochemical examination revealed that the cells expressed myeloperoxidase, CD56, CD43 and T-cell intracytoplasmic antigen. In addition, several cells expressed CD34, and 90% of the cells expressed Ki67. While the majority of cells in myeloid sarcoma do not express CD56, the present case was a myeloid sarcoma that expressed CD56, which is extremely rare. The sarcoma in the present patient progressed rapidly, and the patient died eight months following the onset of disease. Clinicians should be aware of CD56+ myeloid sarcoma, which is easily misdiagnosed and inappropriately treated. Consequently, myeloid sarcoma may have a high malignancy and poor outcome for patients.

Dermatofibrosarcoma protuberans with pit-like lesions: A case report and literature review.

The present study describes a case of pit-like dermatofibrosarcoma protuberans (DFSP) with the clinical manifestations, histopathological features and criteria for diagnosis. The study also reviews the relevant literature in order to raise awareness among dermatologists with regard to the specific behavior of DFSP. A 27-year-old female presented with subcutaneous nodules on the left side of the neck that had been apparent for 5 years and which had gradually begun caving in during the last year. Histopathological examination revealed that the tumor was composed of a large number of spindle cells arranged in a whirlpool-like pattern. Immunohistochemical studies revealed positive staining for cluster of differentiation 34, vimentin and lysozyme, which could be used as diagnostic markers of DFSP. The patient was finally diagnosed with DFSP by pathological and immunohistochemical analyses. The DFSP was treated with an extended resection followed by adjacent skin repair. The patient responded well and no relapse occurred during the 8-month clinical follow-up. Thus, the current study describes a unique pit-like clinical manifestation of DFSP with typical immunohistochemical and pathological features. In addition, histopathological examination revealed a downward depression in the epidermis. Therefore, histopathological examination should be considered as an essential diagnostic tool for DFSP.

F-18 labeled vasoactive intestinal peptide analogue in the PET imaging of colon carcinoma in nude mice.

As large amount of vasoactive intestinal peptide (VIP) receptors are expressed in various tumors and VIP-related diseases, radiolabeled VIP provides a potential PET imaging agent for VIP receptor. However, structural modification of VIP is required before being radiolabeled and used for VIP receptor imaging due to its poor in vivo stability. As a VIP analogue, [R(8, 15, 21), L(17)]-VIP exhibited improved stability and receptor specificity in preliminary studies. In this study, F-18 labeled [R(8,15,21), L(17)]-VIP was produced with the radiochemical yield being as high as 33.6% ± 3% (decay-for-corrected, n = 5) achieved within 100 min, a specific activity of 255 GBq/ µmol, and a radiochemical purity as high as 99% as characterized by radioactive HPLC, TLC, and SDS-Page radioautography. A biodistribution study in normal mice also demonstrated fast elimination of F-18 labeled [R(8,15,21), L(17)]-VIP in the blood, liver, and gastrointestinal tracts. A further micro-PET imaging study in C26 colon carcinoma bearing mice confirmed the high tumor specificity, with the tumor/muscle radioactivity uptake ratio being as high as 3.03 at 60 min following injection, and no apparent radioactivity concentration in the intestinal tracts. In addition, blocking experiment and Western Blot test further confirmed its potential in PET imaging of VIP receptor-positive tumor.

Synthesis and cell uptake of a novel dualmodality (188)Re-HGRGD (D) F-CdTe QDs probe.

A novel dualmodality probe was prepared by linking (188)Re-HGRGD (D) F with CdTe QDs, which was monitored using radio-thin layer chromatography (TLC) and -high performance liquid chromatography (HPLC). The (188)Re-HGRGD (D) F-CdTe QDs probe possesses a radiochemistry yield of 92.1% and strong photoluminescence (PL) stability. However, the radiochemical purity of (188)Re-HGRGD (D) F-QDs would reduce to 74.8%, which should be further improved, after incubation with newborn calf serum (NCF) for 24h. Human glioblastoma U87MG cells, known to express a high-affinity to RGD, were used to assess the in vitro cell binding of probe. The results showed that the radio-signal was in accord with the change of PL intensity, which meant the successful integration of (188)Re and QDs.

Combined prediction of transmembrane topology and signal peptide of beta-barrel proteins: using a hidden Markov model and genetic algorithms.

BACKGROUND: Hidden Markov models (HMMs) have been extensively used in computational molecular biology, for modelling protein and nucleic acid sequences. The design of the model architecture and the algorithms for parameter estimation and decoding are extremely important for improve the performance of HMM. In topology prediction of transmembrane beta-barrels proteins (TMBs), the Baum-Welch algorithm is widely adapted for HMM training but usually leads to a sub-optimal model in practice. In addition, all the existing HMM-based predictors are only designed to model the transmembrane segment without a submodel to model the signal peptide (SP) for full-length sequences. It is not convenient for users to investigate the structures of full-length TMB sequences. RESULTS: We present here, an HMM that combine a transmembrane barrel submodel and an SP submodel for both topology and SP predictions. A new genetic algorithm (GA) is presented here to training the model, at the same time the Posterior-Viterbi algorithm is adopted for decoding. A dataset including 33 TMBs that is the most so far in literature are collected for model training and testing. Results of self-consistency and jackknife tests shows the GA has better global performance than the Baum-Welch algorithm. Results of jackknife tests show that this method performs better than all well known existing methods for topology predictions. Furthermore, it provides a function to predict SP in full-length TMBs sequences with fairish accuracy. CONCLUSION: We show that our combined HMM-based method is a better choice for TMB topology prediction, which implements topology predictions with higher accuracy and additional SP predictions for full-length TMB sequences.

[Effects of all-trans retinioic acid and tazarotene on MMP-1 and TIMP-1 expression in cultured human fibroblasts after heat shock].

OBJECTIVE: To investigate the molecular mechanism of dermal damage in heat shock-induced skin aging by observing the expressions of metalloproteinase-1 (MMP-1) and tissue inhibitor of MMP-1 (TIMP-1) in retinoic acid-treated cultured human fibroblasts with heat shock. METHODS: Cultured human fibroblasts were treated with tazarotene or all-trans-retinioic acid (at-RA) after heat shock for 30 min in 43 degrees celsius; water bath. Twenty-four hours later, MMP-1 and TIMP-1 contents in the supernatant of the cell culture medium were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: Both tazarotene and at-RA dose-dependently reduced the expression of MMP-1 and increased the expression of TIMP-1 in cultured human fibroblasts exposed to heat shock, and tazarotene produced stronger effect than at-RA. CONCLUSION: Retinoic acid can reduce the expression of MMP-1 and increase the expression of TIMP-1 in cultured human fibroblasts, suggesting its therapeutic potential for heat shock-induced skin aging.

[Prediction of outer membrane proteins using support vector machine with combined features].

Outer membrane proteins (OMPs) are embedded in the outer membrane of Gram-negative bacteria, mitochondria, and chloroplasts. The cellular location and functional diversity of OMPs makes them an important protein class. Researches on prediction of OMPs by bioinformatics methods can bring helpful methodologies for identifying OMPs from genomic sequences and for the successful prediction of their secondary and tertiary structures. In this paper, three feature classes were calculated from protein sequences: amino acid compositions, dipeptide compositions and weighted amino acid index correlation coefficients. Then, three feature classes were combined and inputted into a support vector machine (SVM) based predictor to identify OMPs from other folding types of proteins. The results of discrimination using several combined features including four amino acid index categories were calculated, and the influence on discrimination accuracy using different correlation coefficients with different orders and weights was discussed. In cross-validated tests and independent tests for identifying OMPs from a dataset of 1087 proteins belonging to all different types of globular and membrane proteins, the method using combined features obtains an overall accuracy of 96.96% and 97.33% respectively. And these results outperform that of other methods in the literature. Using this method, high specificities are shown from the results of identifying OMPs in five bacterial genomes, and over 99% OMPs with known three-dimensional structures in the PDB database are correctly discriminated. These results indicate that the method is a powerful tool for OMPs discrimination in genomes.

Preparation and biological evaluation of 2-amino-6-[18F]fluoro-9-(4-hydroxy-3-hydroxy-methylbutyl) purine (6-[18F]FPCV) as a novel PET probe for imaging HSV1-tk reporter gene expression.

INTRODUCTION: 2-Amino-6-[(18)F]fluoro-9-(4-hydroxy-3-hydroxy-methylbutyl) purine (6-[(18)F]FPCV) was prepared via a one-step nucleophilic substitution and evaluated as a novel probe for imaging the expression of herpes simplex virus type 1 thymidine kinase (HSV1-tk) reporter gene. METHODS: Log P of 6-[(18)F]FPCV was calculated in octanol/phosphate-buffered saline (PBS). Stability studies were performed in PBS and bovine serum albumin (BSA). Cell uptake was performed at various time points in wild-type cells and transduced cells. For in vivo studies, tumors were grown in nude mice by inoculation with C6 cells, wild type and tk positive. The radiotracer was intravenously injected to animals, and micro-PET imaging was performed. Biodistribution of 6-[(18)F]FPCV was performed on another group of animals at different time points. RESULTS: Log P of 6-[(18)F]FPCV was -0.517. 6-[(18)F]FPCV was fairly stable in PBS and BSA at 6 h. The tracer uptake in C6-tk cells was 5.5-18.8 times higher than that in wild-type cells. The plasma half-life of 6-[(18)F]FPCV was as follows: alpha t(1/2)=1.2 min and beta t(1/2)=73.7 min. The average ratio of tumor uptake between the transduced tumor and the wild-type tumor was 1.69 at 15 min. CONCLUSION: Biological evaluation showed that 6-[(18)F]FPCV is a potential probe for imaging HSV1-tk gene expression. However, its in vivo defluorination may limit its application in PET imaging of gene expression.

Surface modified superparamagnetic iron oxide nanoparticles: as a new carrier for bio-magnetically targeted therapy.

Amino-functionalized superparamagnetic iron oxide nanoparticles (SPION) were synthesized by coprecipitation method. The particles were characterized by X-ray diffraction (XRD), vibrating sample magnetometer (VSM), scanning electron micrographs (SEM), transmission electron micrographs (TEM) and atomic force micrographs (AFM). The size of the modified particles varied in the range 10-15 nm and did not change significantly after modification. Hepama-1, an excellent humanized monoclonal antibody directed against liver cancer, was conjugated to the SPION to prepare immuno-magnetic nanoparticles (IMN). A direct labeling method was employed to radiolabel IMN with rhenium-188. The radiolabeling efficiency was about 90% with good in vitro stability. (188)Re labeled IMN could markedly kill SMMC-7721 liver cancer cells. Such SPION might be very useful for bio-magnetically targeted radiotherapy in liver cancer treatment.

Radiosynthesis of 18F-(R8,15,21, L17)-vasoactive intestinal peptide and preliminary evaluation in mice bearing C26 colorectal tumours.

BACKGROUND: Radiolabelled vasoactive intestinal peptide (VIP) and its analogues have shown their potential as imaging agents for diagnosing tumours expressing VIP receptor. However, the fast proteolytic degradation in vivo has limited their clinical use. AIM: To prepare the 18F-labelled (R8,15,21, L17)-VIP analogue in a convenient way and to evaluate its potential as an imaging agent for VIP receptor-positive tumours. METHODS: Radiolabelled (R8,15,21, L17)-VIP was obtained by conjugation with N-succinimidyl 4-([18F]fluoromethyl) benzoate and purified by HPLC. Radiochemical purity and specific radioactivity were measured by analytical HPLC. In-vitro stability of the product was carried out in HSA solution and analysed by HPLC. Biodistribution study was carried out in mice bearing C26 colorectal tumours. RESULTS: 18F-(R8,15,21, L17)-VIP was obtained in greater than 99% radiochemical purity within 60 min in decay-for-corrected radiochemical yields of 21.8+/-4.7% (n=5) and a specific activity of 17.76 GBq x mumol(-1) at the end of synthesis (EOS). Results of in-vitro studies demonstrated a high stability in human serum albumin (HSA) solution. Biodistribution data showed a rapid blood clearance and specific binding towards receptor-positive tumours. CONCLUSION: 18F-(R8,15,21, L17)-VIP was prepared by a convenient method. Preliminary biodistribution results showed its potential for imaging tumours over-expressing VIP receptors and encouraged further investigation.