Search

Dual phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), has shown a great prospect in cancer treatment. However, its therapeutic effect is restricted by the depth of light penetration in tissue and tumor hypoxia environment. Herein, inspired by the specific response of nanozymes to the tumor microenvironment (TME), a simple and versatile nanozyme-mediated synergistic dual phototherapy nanoplatform (denoted as FePc/HNCSs) is constructed using hollow nitrogen-doped carbon nanospheres (HNCSs) and iron phthalocyanine (FePc). FePc/HNCSs simultaneously exhibit peroxidase (POD)- and catalase (CAT)-like activities, which not only can convert endogenous hydrogen peroxide (H2 O2 ) into highly toxic hydroxyl radicals (•OH) for catalytic therapy, but also decompose H2 O2 to oxygen (O2 ) to enhance O2 -dependent PDT. In addition, their enzyme-like activities are significantly enhanced under light irradiation. Combining with the excellent photothermal effect, FePc/HNCSs realize a high tumor inhibition rate of 96.3%. This strategy opens a new horizon for exploring a more powerful tumor treatment nanoplatform.

Cultivated grassland can serve as one solution to the degradation of natural grassland. However, less is understood of the response of the microbial communities in cultivated grassland soils to global change factors such as nitrogen (N) deposition and precipitation change, and their linkages with the dynamics of soil organic carbon (SOC). In this study, field experimental plots that simulate different N deposition and precipitation levels were established to investigate the responses of soil microbial communities and their linkages with particulate-sized SOC fractions. Results showed that the activities of hydrolytic enzymes responded significantly to N addition, watering and their combinations, whereas the abundance and composition of microbial communities showed no significant difference among treatments. Addition of N and water generally promoted the activities of N-degrading enzymes such as β-N-acetylglucosaminidase (NAG) and leucine aminopeptidase (LAP), and thus decreased the C- to N-degrading activity (enzyme C/N ratio). This decrease in enzyme C/N ratio was significantly correlated with the accumulation of microbial-accessible particulate organic carbon (POC), indicating that three years of N application did not alleviate microbial N limitation so that microbial communities had invested more in acquisition of N instead of C. In contrast, the content of microbial-inaccessible mineral associated organic carbon (MAOC) was decreased probably as a result of N limitation on the suppressed microbial growth. Collectively, these results highlight that stoichiometric deviation between substrate and microbial demand can be one critical driver for SOC dynamics in cultivated grassland under global change scenarios.

In this study, we propose a strategy of using a 4-element sector array, fundamental and second harmonic pressure superposition, and waveform of hundred-microsecond pulses and two stages. Hopefully, the rapid histotripsy process can be achieved through increasing one-spot lesion volume, enhancing pressure from cavitation reflection and multi boiling bubbles. A custom-designed 4-element sector array operated at 1.2 and 2.4 MHz with 146 mm aperture, 100 mm geometric focal length. In our initial experiments, we used the one focus pattern with acoustic focus dimension of 0.7 mm by 3 mm (lateral by axial length) and the peak negative pressure of each frequency exceeding −10 MPa. The histotripsy waveform scheme of hundred-microsecond pulses and two stages was used: stage 1, pulses with a pulse duration (PD) of 350 μs and pulse repetition frequency (PRF) of 100 Hz; stage 2, same PD and PRF as those in stage 1 and 1 % duty factor. The experiments were implemented in gel-phantom with bovine serum albumin (BSA), ex vivo porcine kidneys, monitored via high speed camera or passive cavitation detection (PCD). As expected, the experiments achieved successfully the disintegrated lesions with typical dimension of 5.5 mm by 7.5 mm (lateral by axial length) in porcine kidneys. The slide of H&E stained shows the lesion region where tissue fractionates into acellular debris with sharp boundary. The filtered-PCD mean square waveform indicates the enhanced inertial cavitation energy. The selected images from high speed imaging show the cavitation cloud structure and cavitation-bubble-layer reflection effects toward to transducer in prefocal region. The large sized lesion with wider 5.5-mm lateral dimension generated in prefocal region can attribute to dual-frequency parallel beams with shock waves, strong cavitation-bubble-layer reflection effects, and the parallel boiling bubbles of two frequencies.

The previous study has demonstrated that pulsed HIFU with tens of microseconds pulse duration and 10kHz pulse repetition frequency is effective for cavitation generation. With the assistance of perfluorocarbon (PFC) nano-droplets, cavitation can be further enhanced. But despite higher efficiency, we also need precisely controlled cavitation for sake of therapeutic safety. In this work, we propose a combinatorial ultrasound wave sequence to realize precisely controlled cavitation in PFC nano-droplets assisted HIFU ablation. The applied combinatorial wave sequence was composed of a preconditioned continuous wave sustained for several seconds, then a pause and eventually the pulsed waves. We employed sonoluminescence (SL) to visualize the cavitation active spots. The luminous area and mean light intensity were measured to represent cavitation area and intensity, respectively. High-speed photography was utilized to record the thermal ablation development process. The results showed that cavitation distribution space became more confined and less stretched when sonicated by the combinatorial sequence. The SL area decreased about 60%. Meanwhile, no obvious change in the mean intensity. Higher efficient and better-controlled cavitation and ablation were achieved through applying the combinatorial ultrasound wave sequence.

A novel hundred-microsecond histotripsy treatment method is proposed. This method utilizes the confocal dual-frequency of second harmonic superimposition control approach. A custom-designed transducer consisting of two confocal spherical-annular element arrays is used. The frequencies of the transducer are 1.1 and 2.2 MHz, and the peak negative pressures are 5 MPa and 12 MPa with shock wave. Due to the dual-frequency superimposition, inertial cavitation threshold can be significantly decreased and inertial cavitation activity can be enhanced. By controlling the ratio of the dual-frequency acoustic power, the superimposition of two frequency pressures results in nine split foci along a beam axis within the confocal region, and the maximal peak intensity of the split foci can reach approximately twice the sum of the two frequency intensities, indicating strong wave interference. Experiments were conducted on BSA gel phantoms and on porcine liver tissues ex vivo. Target tissue could be mechanically disintegrated into long-tear-shape lesion with smooth borders. Lesion inception time, boiling bubble emergence time, and first stage treatment time were decreased to nearly 1/6, 1/7, and 1/2 of the single-frequency monofocal mode. The boiling bubbles occurred frequently at multiple foci in each lesion formation, beneficiating shorten the treatment time. The inertial-cavitation-energy waveform revealed that the energetic inertial cavitation activity dominated the entire histotripsy treatment and the occurrence of boiling activity significantly increased the filtered-PCD signal amplitude in the frequency-domain. These results demonstrated that the hundred-microsecond dual-frequency of second harmonic superimposition had potential value being used in improvement of histotripsy treatment efficiency.

Rapid and effective determination of biomechanical properties is important in examining and diagnosing skin thermal injury. Among the methods used, viscoelasticity quantification is one of the most effective methods in determining such properties. This study aims to rapidly determine skin viscoelasticity by optically tracking the local surface wave. New elastic and viscous coefficients were proposed to indicate skin viscoelasticity based on a single impulse response of the skin. Experiments were performed using fresh porcine skin samples. Surface wave was generated in a single impulse using a vibrator with a ball-tipped device and was detected using a laser Doppler vibrometer. The motions along the depth direction were monitored using an ultrasound system. The ultrasound monitoring results indicated the multi-layered viscoelasticity of the epidermis and dermis. The viscoelastic coefficients from four healthy samples show a potential viscoelasticity variation of porcine skin. In one sample, the two coefficients were evidently higher than those in a healthy area if the skin was slightly burned. These results indicate that the proposed method is sensitive, effective, and quick in determining skin viscoelasticity.

A novel approach combining dual frequency and split focus approaches is proposed to substantially enhance heating in treatment by using a prototype broadband splitfocus transducer. Using a dual-frequency mode in which the higher frequency is twice the lower frequency, the superimposition of two frequency pressures in the confocal region can enhance nucleation cavitation and inertial cavitation activity. Ex vivo liver or gel phantom experiments using the dual frequencies of 1.2 and 2.4 MHz confirmed a lesion size about two times larger than that obtained using a single 1.6 MHz frequency. The mean square indicating inertial cavitation energy from filtered passive cavitation detection (PCD) data demonstrated that the inertial cavitation activity dominated the enhanced heating rate and that the extra frequency components in the dual-frequency case contributed to increasing the lesion size. The dual-frequency, split-focus protocol takes great advantages of temporally and spatially enhanced-cavitation heating. The results revealed that the dual-frequency, split-focus method enhanced the heating rate one order of magnitude more than other methods. The inertial cavitation energy waveform revealed that the strong inertial cavitation action was involved in enhanced heating in the entire 22 s treatment. The greater spatial area of preformed bubble-layer surface reflection (or scatter ultrasound) regime in the dual-frequency, split-focus protocol enhanced the proximal acoustic field and enlarged the enhanced-pressure field toward the transducer about 3 times in the axial original-focal dimension, as well as laterally. This regime supported the sustained inertial cavitation during a 22 s treatment. An increased pulse-repetition frequency (PRF) protocol was formed using dual frequency and split focus, increasing PRF from 1 to 10, 20, and 40 Hz to take advantage of pulse-induced cavitation. The experiments demonstrated that the lesion size with 20 Hz PRF was about 2.5 times that obtained with 1 Hz PRF, and possessed quick 0.2 s lesioninception time. Within the high-frequency band, the inertialcavitation frequency integral was approximately proportional to the lesion size of 1, 10, 20, and 40 Hz PRF respectively, indicating higher frequency contribution to enhanced heating.

In this paper, based on a programmable diagnostic ultrasound scanner, a combined approach was proposed, in which a variable-sized focal region wherein the acoustic pressure is above the ultrasound contrast agents (UCA) fragmentation threshold is synthesized by reasonably matching the excitation voltage and the transmit aperture of the linear array at 5MHz, the UCAs’ temporal and spatial distribution before and after the microbubbles fragmentation is monitored using the plane-wave transmission and reception at 400Hz and, simultaneously, the broadband noise emission during the microbubbles fragmentation is extracted using the backscattering of focused release bursts (destruction pulse) themselves on the linear array. Then, acquired radio frequency (RF) data are processed to draw parameters which can be correlated with the indicator of broadband noise emission level, namely inertial cavitation dose (ICD) and microbubble fragmentation efficiency, namely decay rate of microbubbles.

We proposed that high efficiency high-intensity focused ultrasound (HIFU) could be achieved by using a splitting transducer with various frequencies and focusing patterns, and explored the feasibility of using ultrafast active cavitation imaging (UACI), pulse inversion (PI) sub-harmonic cavitation imaging and bubble wavelet transform imaging for monitoring of cavitation during HIFU, as well as the ultrasonic B-mode images, differential integrated backscatter (IBS) images, Nakagami images and elastography for monitoring HIFU-induced lesion. The use of HIFU splitting transducer had the potential to increase the size of the thermal lesion in a shorter duration and may improve the ablation efficiency of HIFU and would shorten the exposure duration significantly. The spatial-temporal evolution of residual cavitation bubbles at the tissue-water interface was obtained by UACI and the results showed that the UACI had a frame rate high enough to capture the transient behavior of the cavitation bubbles. The experim...

To substantially enhance heating in HIFU treatment, several methods such as split foci, multi foci, and dual-frequency modes are used. The enhanced-cavitation heating protocols are implemented experimentally in BSA gel-phantom using four-element split-focus array. Using dual frequency of 1.2 and 2.4 MHz, the superimposing of two frequency pressures at confocal region can enhance nucleation cavitation and inertial cavitation activity. When using 135° phase shift combined with dual frequency of 1.2 and 2.4 MHz, the peak negative pressure reach maximum due to peak-negative pressures of two frequencies occur at same time, resulting strong cavitation activities. When using dual frequency of 1.2 and 2.4 MHz, 25-Hz pulse-repetition frequency (PRF), both 135° and 180° phase shift protocols, the experiment results show the largest lesion size of 10.5 × 10.5 × 11 mm3, quickest lesion inception time of less than 0.2 s, therefore, both 135° and 180° phase shift protocols are most efficient in enhanced-cavitation heat...

Background There is global health concern that the mass movement of pilgrims to and from Mecca annually could contribute to the international spread of Middle East Respiratory Syndrome Coronavirus (MERS-CoV). In China, about 11,000 Muslim pilgrims participate in the Hajj gathering in Mecca annually. This is the first report of MERS-CoV and respiratory virus molecular screening of returning pilgrims at points of entry in China from 2013 to 2015. Methods and results A total of 847 returning Hajj pilgrims participated in this study. The test results indicated that of the travelers, 34 tested positive for influenza A virus, 14 for influenza B virus, 4 for metapneumo virus, 2 for respiratory syncytial virus, and 3 for human coronavirus. There was a significant difference in the rates of positive and negative influenza virus tests between Hajj pilgrims with symptoms and those without. The detection rates of influenza virus were not significantly different among the three years studied, at 5.3, 6.0 and 6.3% for 2013, 2014 and 2015, respectively. Discussion and conclusion The MERS-CoV and respiratory viruses detection results at points of entry in China from 2013 to 2015 indicated that there were no MERS-CoV infection but a 5.7% positive influenza viruses in returning Chinese pilgrims.

This paper aims to provide researchers with a computational background, a comprehensive discussion on the importance of miRNA (microRNA), the related high-throughput technology and databases, the current development of computational algorithms for elucidating miRNA regulatory functions, and the prospective directions on related topics. Some topics discussed were about miRNA target recognition, silencing, expression profiling, transfection experiments, target predictions, databases, microarray data, biochemical approaches, rule-based algorithms, data-driven algorithms, prediction algorithms, transcription factors, and other computational techniques.

In this article, the construction and functions of ultrasound-guided 256-element phased-array surgery system is described. An image-guided phase array therapy system has been developed. Several flexible multifocus control methods for accurate, highly efficient, and fit-to-shape ultrasound surgery are concentrated. The system experiment results show that the multiple foci are positioned exactly at designed locations. In addition, the experiment results agreed well with the simulations.

A two-stage treatment was performed to explore the feasibility of generating histotripsy using hundred-microsecond pulses. A single-element 1.06-MHz transducer was used at 8 MPa peak negative pressure with shockwaves. Stage 1 was performed to accelerate the rupture of local tissue structure by boiling bubbles. The pulse group had 500-µs/400-µs pulse duration (PD) and 100-Hz pulse repetition frequency (PRF) with 4.9%/3.9% duty cycle (DC). Stage 2 involved the mechanical homogenization of the lesion by inertial cavitation. Several locations in the lesion axial direction were treated simultaneously by the bubble clusters induced by multiple reflection of shocks. The pulse group had 500-µs/400-µs PD with 100-Hz PRF and 200-µs PD with 200-Hz PRF with 1%/0.88% DC. Experiments were conducted on polyacrylamide phantoms with bovine serum albumin and on rabbit liver tissues ex vivo. Final lesions had a cylindrical shape with smooth borders and total homogenate inside. These results demonstrated that hundred-microsecond pulses enabled controllable histotripsy with a lower acoustic pressure.

This study aims at enhancing cavitation heating by using dual-frequency modes of second-harmonic and third-harmonic superimposition for high-efficient focused-ultrasound surgery. By controlling the ratio of dual-frequency acoustic powers, the superimposing of two frequency pressures result in split foci along beam axial within confocal region, and the maximal peak intensity of split focus can reach about 2 times the sum of two frequency intensities, indicating strong wave interference. The 1.1 MHz/3.3 MHz and 1.1 MHz/2.2 MHz experiments implemented in BSA gel-phantom, and lesion inception time is about 0.3 s, which is 10 times shorter than that in single frequency mode. The boiling bubbles occur frequently in each lesion formation, beneficiating increase the lesion size. In 1.1 MHz/3.3 MHz modes, lesions developed in a symmetrical manner in ellipsoid shapes. The 12-s lesion size of 1.1 MHz/3.3 MHz modes is nearly two times as large as the lesion size of 1.1 MHz/2.2 MHz modes. Although in 20% DC case, the acoustic power dose is only a half that used in 80% DC case, the 12-s lesion size with 20% DC is nearly same as that with 80% DC for both 1.1 MHz/3.3 MHz and 1.1 MHz/2.2 MHz conditions. The inertial-cavitation-energy waveforms reveal that the strong inertial-cavitation activities involve in all cases.

The present study aimed to investigate the association between the methylation status of the reversion-inducing cysteine-rich protein with kazal motifs (RECK) gene and its mRNA expression levels in patients with esophageal squamous cell carcinoma (ESCC). The methylation status of RECK was analyzed by methylation-specific polymerase chain reaction (PCR), and RECK mRNA expression levels were analyzed by quantitative PCR, in 310 paired ESCC tissues. The mean RECK methylation index (MI) was 0.65 in ESCCs and 0.49 in non-tumor samples. There was a significant association between RECK methylation and the American Joint Committee on Cancer stage and lymph node metastasis in ESCC (P0.16; mean-∆∆Cq=−2.85) compared with those with hypomethylation of the RECK gene (∆MI ≤0.16; mean-∆∆Ct=−0.83), and there was a significant difference in the mRNA expression levels of RECK between those with N0–1 and N2–3 lymph node metastasis (P

Aims: Expression of gonadotropin-releasing hormone receptor (GnRHR) has been demonstrated in a number of malignancies. The aim is to investigate the expression of GnRHR and prognosis in gastric cancer. Methods and materials: GnRHR mRNA was examined in tumor and non-tumor tissues from 48 gastric cancer patients by Real-time PCR. The GnRHR protein expression was performed by immunohistochemical analysis. Results: The expression of GnRHR mRNA was higher (mean ± SD, -10.06 ± 1.28) in gastric tumor tissues than matched non-tumor tissues (mean ± SD, -12.43 ± 1.33). GnRHR mRNA expression was associated with lymph node metastasis, distant metastasis, and TNM stage. We found the decreased expression of GnRHR mRNA were significantly correlated with poor overall survival (P = 0.003). Immunocytochemical staining of GnRHR in tumor tissues showed mainly weak staining (43.48%, 10/23) and moderate staining (21.74%, 5/23) in high GnRHR mRNA patients, and mainly negative staining in low GnRHR mRNA patients. And the staining of GnRHR was not detection in tumor tissues for more than half of gastric patients (52.08%, 25/48). These results implied that the loss of GnRHR protein could be a main event in gastric cancer. Conclusion: The GnRHR expression is very low in gastric cancer, and the loss of GnRHR expression could be a poor prognostic factor, which implied that GnRHR could play an important role in the development of gastric cancer.

A new strategy is proposed in this study to rapidly generate mechanical homogenized lesions using hundred-microsecond-long pulses. The pulsing scheme was divided into two stages: generating sufficient bubble seed nuclei via acceleration by boiling bubbles and efficiently forming a mechanically homogenized and regularly shaped lesion with a homogenate inside via inertial cavitation. The duty cycle was set at 4.9%/3.9% in stage 1 and 1%/0.88% in stage 2 by changing the pulse duration (PD) and off-time independently. The pulse sequence was 500-μs/400-μs PD with a 100-Hz pulse repetition frequency (PRF) in stage 1, followed by 500-μs/400-μs PD with a 100-Hz PRF and 200-μs PD with a 200-Hz PRF in stage 2. Experiments were conducted on polyacrylamide phantoms with bovine serum albumin and on ex vivo porcine kidney tissues using a single-element 1.06-MHz transducer at an 8-MPa peak negative pressure with shock waves. The lesion evolution and dynamic elastic modulus variation in the phantoms and the histology in the tissue samples were investigated. The results indicate that the two-stage treatment using hundred-microsecond-long pulses can efficiently produce mechanically homogenized lesions with smooth borders, long tear shapes and the total homogenate inside. The time to generate a single mechanically homogenized lesion is shortened from >50 s to 17.1 s.

Volume estimation is particularly important in clinical medicine. Accurate volume estimation can provide quantitative information from which the follow-up therapy can be derived. In this paper, an efficient approach to volume estimation in a sequence of freehand ultrasound images is proposed. By integral of vector areas along the path of centroids of serial cross-sections, 3D volume estimation can be represented as 2D area calculation, where a fast mapping algorithm generating 2D representation is presented so that the position of interpolation points can be calculated with high efficiency. Meanwhile, to improve the accuracy, the cubic spline with second-order continuity is proposed for interpolation of 2D representation. Volume estimation on simulating phantoms for parallel cutting, fan cutting and random cuttings is provided. The experimental results show that the 2D representation generated by the fast mapping algorithm is highly efficient with less than 0.001 ms for 100 cross-sections. Quantitative comparisons show that the proposed interpolation method can approximate the original volume more precisely as compared to the Catmull?Rom (CR) spline, especially in the case of small number of cross-sections. In all cases, our approach can obtain accurate results at an error of less than 2% for ten cross-sections. Additionally, volume estimation on a high intensity focused ultrasound (HIFU) lesion based on linear B-scan and rotational B-scan sequential images are also performed. The experiments show that the proposed approach is promising and may have potential in clinical applications.

This study aims at a sound field calculation for the spherical-section phased array and an optimization algorithm for the focus patterns of phased array ultrasound surgery. An efficient field calculation formula represented as an explicit expression is derived by the strategies of projection and binomial expansion. An optimization algorithm based on genetic algorithm is constructed by the suitable fitness function and the selection strategies. The simulation results of 256-element spherical-section phased array show the capability of controlling focus accurately and effectively with the combined method made up of the explicit expression method and the genetic optimization algorithm. The simulation results of single focus, multiple foci, on-axial focus, and off-axial focus further convince the feasibility of three-dimensional (3-D) focus steering with excellent acoustic performances. A single focus with the focus dimension of 1.25 mm /spl times/ 1.25 mm /spl times/ 7 mm and with the intensity of 6080 W/cm/sup 2/ is formed. The multiple-focus pattern can enlarge the treatment volume 22 times larger than that of single focus with a sonication. In addition, a comparison between the explicit expression approach and the point source approach testifies to the applicability of the explicit expression approach. The experiment and simulation results of 16-element array actually confirm the feasibility of the combined method.

The objective of this study was to investigate the alteration of the protein profile in cells after sonication and to identify the key proteins involved in the process of cell apoptosis. Walker 256 carinosarcoma cells were exposed to focused ultrasound (US) at the intensity of 2.0, 7.0, 10.2, 14.2 and 17.0 W/cm 2 (I spta ) for 10 min in vitro and the morphologic and functional changes of the cells were detected by hematoxylin & eosin staining and flow cytometry, with double staining of fluorescein isothiocyanate (FITC)-labeled Annexin V/propidium iodide (PI). The protein compositions in the cells after sonication were detected by 2-D SDS polyacrylamide gel electrophoresis. Our results showed that apoptosis of Walker 256 carinosarcoma cells could be induced by US. The percentage of early apoptosis and secondary necrosis increased with increasing intensity of US irradiation. Comparing with the protein patterns of cells before sonication, it was found that around 420 new protein spots were present in the gel after sonication. Among them, Hsp60 and Bcl-2 like protein 13 were found to be involved in the process of cell apoptosis and US-induced apoptosis of the cells was probably performed through the pathway of promoting the activation of caspase-3. (E-mail: mxwan@mail.xjtu.edu.cn )

The aim of the present study was to determine the frequency of p27kip1 promoter methylation in esophageal squamous cell carcinoma (ESCC). The methylation status of the p27kip1 promoter was analyzed by methylation‑specific polymerase chain reaction (MSP) in 50 ESCC and matched non‑tumor tissues. Cell lines were treated with the demethylation agent 5‑aza‑2'‑deoxycytidine (5‑Aza‑CdR) and p27kip1 mRNA expression was detected by quantitative polymerase chain reaction. p27kip1 methylation was found in 36% (18/50) of ESCC patients, but only in 12% (6/50) of the corresponding non‑tumor tissues (P=0.005). There were statistically significant associations between the presence of methylation and tumor metastasis (P=0.002). The p27kip1 mRNA was lower in ESCC compared with non‑tumor tissues (mean ± standard deviation, ‑0.886±3.298 vs. 0.988±0.257; P=0.0033). Furthermore, a significant association was identified between the methylation status of the p27kip1 promoter and p27kip1 mRNA expression in the tissue (P

A modified Monte Carlo model of speckle tracking of shear wave propagation in scattering media is proposed. The established Monte Carlo model mainly concerns the variations of optical electric field and speckle. The two-dimensional intensity distribution and the time evolution of speckles in different probe locations are obtained. The fluctuation of speckle intensity tracks the acoustic-radiation-force shear wave propagation, and especially the reduction of speckle intensity implies attenuation of shear wave. Then, the shear wave velocity is estimated quantitatively on the basis of the time-to-peak algorithm and linear regression processing. The results reveal that a smaller sampling interval yields higher estimation precision and the shear wave velocity is estimated more efficiently by using speckle intensity difference than by using speckle contrast difference according to the estimation error. Hence, the shear wave velocity is estimated to be 2.25 m/s with relatively high accuracy for the estimation error reaches the minimum (0.071).

MicroRNAs function as important regulators of gene expression and are commonly linked to development, differentiation, and diseases such as cancer. To better understand their roles in various biological processes, identification of genes targeted by microRNAs is necessary. Although prediction tools have significantly helped with this task, experimental approaches are ultimately required for extensive target search and validation. We employed two independent yet complementary high throughput approaches to map a large set of mRNAs regulated by miR-122, a liver-specific microRNA implicated in regulation of fatty acid and cholesterol metabolism, hepatitis C infection, and hepatocellular carcinoma. The combination of luciferase reporterbased screening and shotgun proteomics resulted in the identification of 260 proteins significantly down-regulated in response to miR-122 in at least one method, 113 of which contain predicted miR-122 target sites. These proteins are enriched for functions associated with the cell cycle, differentiation, proliferation, and apoptosis. Among these miR-122-sensitive proteins, we identified a large group with strong connections to liver metabolism, diseases, and hepatocellular carcinoma. Additional analyses, including examination of consensus binding motifs for both miR-122 and target sequences, provide further insight into miR-122 function., link_to_OA_fulltext

Motivated by overcoming the drawbacks of traditional decision tree and improving the efficiency of large margin learning based multi-stage decision tree when dealing with multi-class classification problems, this paper proposes a novel Multi-stage Decision Tree algorithm based on inter-class and inner class margin of SVM. This new algorithm is well designed for multi-class classification problem based on the maximum margin of SVM and the cohesion and coupling theory of clustering. Considering the multi-class classification problem as a clustering problem, this new algorithm attempts to convert the multi-class classification problem into a two-class classification problem such that the highest cohesion degree within classes while lowest coupling degree between classes, where the margin of SVM is considered as the measurement of the degree. Then for each two-class problem, this paper uses traditional C4.5 algorithm to generate each stage decision tree which splits a dataset into two subsets for the further induction. Recursively, the Multi-stage decision tree is obtained. Numerical simulations and theoretical analysis show this new multi-stage decision tree improves the performance of traditional decision tree and decreases the computational complexity a lot compare with large margin learning based multi-stage decision tree.

To choose an appropriate kernel function is one major task for SVM. Different kernel functions will produce different SVMs and may result in different performances. Combined kernel function shows more stable and higher performance than single kernel function, so there is a need to optimize the combined kernel function to enhance the generalization capability of SVM. This paper proposes to optimize the combined kernel function by Particle Swarm Optimization (PSO) based on large margin learning theory of SVM. The comparison of the performance between GA and PSO algorithm on this optimization problem is provided. The simulation results show that the PSO is another feasible solution for optimization of combined kernel function, which normally leads to SVM with better generalization capability and stability.

The genetic optimal algorithm and sound field calculation approach for the spherical-section phased array are presented in this paper. The in-house manufactured 256-element phased array focused ultrasound surgery system is briefly described. The on-axis single focus and off-axis single focus are simulated along with the axis-symmetric six-focus patter and the axis-asymmetric four-focus pattern using a 256-element phased array and the genetic optimal algorithm and sound field calculation approach. The experimental results of the described 256-element phased array focused ultrasound surgery system acting on organic glass and phantom are also analyzed. The results of the simulations and experiments confirm the applicability of the genetic algorithm and field calculation approaches in accurately steering three dimensional foci and focus.

This paper investigates how we can work towards building net-centric swarms of land, sea and air robots working together to accomplish a common goal. The goal is to bring together swarms of robots from all three sectors to safely benefit mankind without increasing dangers in the process. Several platforms are explored for simulation to investigate swarm robotics within heterogeneous environments.

To assess the features of four types of operation for treating chronic hypertrophy rhinitis and to observe the ultrastructure of inferior turbinate mucosa.Eighty-eight cases of chronic hypertrophic rhinitis (HR) were treated by transnasal endoscopic submucous inferior turbinate resection (group A), thirty cases of HR were treated by partial inferior turbinectomy (group B), thirty six cases of HR were treated by bipolar radiofrequency ablation on inferior turbinate (group C), ten cases of HR were treated by injection of sclerosing agent (group D). The efficacy in the three groups (A,B,C) and the features of four types operation were compared and the ultrastructure of inferior turbinate was observed both preoperatively and postoperatively.Four groups of HR were followed up 4 months to half year after operation, effective rate was 97.4 (group A) 100% (group B) and 93.4% (group C) respectively, while group A, group B and group C effective rate had no significant difference among them. Group A and group C have more advantages compared to the other 2 groups for they remained good ultrastructure of inferior turbinate mucosal cilia after 4 to 6 months postoperatively.The use of transnasal endoscopic submucous inferior turbinate resection and bipolar radiofrequency ablation for treatment of chronic hypertrophy rhinitis are effective modality for the treatment of chronic hypertrophy rhinitis.

Motivated by improving the existing decision tree performance of dealing with multi-class problems, this paper proposes a new algorithm named multi-stage decision tree (MDT). The MDT algorithm is based on the relationship between the margin of SVM hyper-planes and their generalization capability and tries to find the large margin among the clusters. First the MDT algorithm converts the multi-class problem into two-class problem by large margin learning of SVM hyper-planes, and then for each two-class problem, it uses traditional decision tree induction algorithm to generate a decision tree which splits a dataset into two subsets for the further induction. Recursively, the multi-stage decision tree is obtained finally. Numerical simulations show the effectiveness and high accuracy of MDT algorithm. Initial experiments show that the MDT algorithm has the potential application to text classification with many classes.

The fault diagnosis of power transformer is important for safety of the device and reliability of the power system. This paper proposes the large margin learning classifier, which is well designed for multi-class problem based on the large margin learning of SVM hyper-planes theory. Each time it attempts to find the separating hyper-plane with maximum margin to split the clusters. As a novel tool, the large margin learning classifier is applied into the fault diagnosis of power transformer. Due to its extraordinary generalization capability, it has excellent performance on reliability and training speed. The experimental results show the feasibility and effectiveness of this method.

A Monte Carlo method of multiple scattered coherent light with the information of shear wave propagation in scattering media is presented. The established Monte-Carlo algorithm is mainly relative to optical phase variations due to the acoustic-radiation-force shear-wave-induced displacements of light scatterers. Both the distributions and temporal behaviors of optical phase increments in probe locations are obtained. Consequently, shear wave speed is evaluated quantitatively. It is noted that the phase increments exactly track the propagations of shear waves induced by focus-ultrasound radiation force. In addition, attenuations of shear waves are demonstrated in simulation results. By using linear regression processing, the shear wave speed, which is set to 2.1 m/s in simulation, is estimated to be 2.18 m/s and 2.35 m/s at time sampling intervals of 0.2 ms and 0.5 ms, respectively.

We concentrate on the nondissipative mechanism induced shear wave in inhomogenous tissue. The shear wave equation of radiation force in inhomogeneous media is solved numerically with a finite-difference time-domain method. A rarely studied nondissipative mechanism of shear displacement due to a smooth medium inhomogeneity is evaluated. It is noted that unlike the dissipative effect, the nondissipative action on a localized inhomogeneity with its hardness parameter changing smoothly along the beam axis, compresses or stretches the focus area. The shear waves in nondissipative inhomogeneous media remain the property of sharp turn with 100% peak positive displacement and 64% peak negative displacement. This action is useful in discerning the water-like lesion.

Since miRNA plays an important role in post-transcript regulation, many computational approaches have been proposed for miRNA target prediction. Yet, the existing algorithms lack the capability to predict the true target when the perfect seed match presents in mRNA sequences and methods based on seed-match still suffer from a high false positive rate. Therefore, this paper proposes a new prediction method that exploits the data produced by the PAR-CLIP, which is a recent high throughput, high precision technology for genome-wide miRNA targets. This algorithm searches true miRNA targets among the candidates with seed-matches by using machine learning approaches. The target prediction results on top 20 expressed miRNAs in HEK293 cells of AGO1-4 proteins PAR-CLIP data show that given presence of seed pairing, the proposed method greatly outperforms the traditional miRNA target prediction algorithms and improve the precision significantly. Because biologists usually need to mutate the seed region to validation the miRNA targets, and only capable of conducting biological experiments on limited miRNA and mRNA sequences due to the time and cost, the proposed approach will make significant impact on the biology and healthcare fields.

Background Response of cells to changing endogenous or exogenous conditions is governed by intricate molecular interactions, or regulatory networks. To lead to appropriate responses, regulatory network should be 1) context-specific, i.e., its constituents and topology depend on the phonotypical and experimental context including tissue types and cell conditions, such as damage, stress, macroenvironments of cell, etc. and 2) time varying, i.e., network elements and their regulatory roles change actively over time to control the endogenous cell states e.g. different stages in a cell cycle. Results A novel network model PathRNet and a reconstruction approach PATTERN are proposed for reconstructing the context specific time varying regulatory networks by integrating microarray gene expression profiles and existing knowledge of pathways and transcription factors. The nodes of the PathRNet are Transcription Factors (TFs) and pathways, and edges represent the regulation between pathways and TFs. The reconstructed PathRNet for Kaposi's sarcoma-associated herpesvirus infection of human endothelial cells reveals the complicated dynamics of the underlying regulatory mechanisms that govern this intricate process. All the related materials including source code are available at http://compgenomics.utsa.edu/tvnet.html. Conclusions The proposed PathRNet provides a system level landscape of the dynamics of gene regulatory circuitry. The inference approach PATTERN enables robust reconstruction of the temporal dynamics of pathway-centric regulatory networks. The proposed approach for the first time provides a dynamic perspective of pathway, TF regulations, and their interaction related to specific endogenous and exogenous conditions.