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PURPOSE To assess the added value of serial blood biomarkers in liver metastasis stereotactic body radiation therapy (SBRT). MATERIALS AND METHODS Eighty-nine patients were retrospectively included. Pre- and midtreatment blood samples were analyzed for potential biomarkers of the treatment response. Three biomarker classes were studied: gene mutation status, complete blood count, and inflammatory cytokine concentration in plasma. One-year local failure (LF) and 2-year overall survival (OS) were chosen as study end points. Multivariate logistic regression was used for response prediction. Added predictive benefit was assessed by quantifying the difference between the predictive performance of a baseline model (clinicopathologic and dosimetric predictors) and that of the biomarker-enhanced model, using three metrics: (1) likelihood ratio, (2) predictive variance, and (3) area under the receiver operating characteristic curve (AUC). RESULTS The most important predictors of LF were mutation in KRAS gene (hazard ratio [HR] = 2.92, 95% CI, [1.17 to 7.28], P = .02) and baseline and midtreatment concentration of plasma interleukin-6 (HR = 1.15 [1.04 to 1.26] and 1.06 [1.01 to 1.13], P = .01). Absolute lymphocyte count and platelet-to-lymphocyte ratio at baseline as well as neutrophil-to-lymphocyte ratio at baseline and before fraction 3 (HR = 1.33 [1.16 to 1.51] and 1.19 [1.09 to 1.30]) had the most significant association with OS ( P = .0003). Addition of baseline GEN and inflammatory plasma cytokine biomarkers in predicting LF, respectively, increased AUC by 0.06 (from 0.73 to 0.79) and 0.07 (from 0.77 to 0.84). In predicting OS, inclusion of midtreatment complete blood count biomarkers increased AUC from 0.72 to 0.80, along with significant boosts in likelihood ratio and predictive variance. CONCLUSION Inclusion of serial blood biomarkers leads to significant gain in predicting response to liver metastasis stereotactic body radiation therapy and can guide treatment personalization.

Background and purpose Clinical targeted volume (CTV) delineation accounting for the patient-specific microscopic tumor spread can be a difficult step in defining the treatment volume. We developed an intelligent and automated CTV delineation system for locally advanced non-small cell lung carcinoma (NSCLC) to cover the microscopic tumor spread while avoiding organs-at-risk (OAR). Materials and methods A 3D UNet with a customized loss function was used, which takes both the patients’ respiration-correlated (“4D”) CT scan and the physician contoured internal gross target volume (iGTV) as inputs, and outputs the CTV delineation. Among the 84 identified patients, 60 were randomly selected to train the network, and the remaining as testing. The model performance was evaluated and compared with cropped expansions using the shape similarities to the physicians’ contours (the ground-truth) and the avoidance of critical OARs. Results On the testing datasets, all model-predicted CTV contours followed closely to the ground truth, and were acceptable by physicians. The average dice score was 0.86. Our model-generated contours demonstrated better agreement with the ground-truth than the cropped 5 mm/8 mm expansion method (median of median surface distance of 1.0 mm vs 1.9 mm/2.0 mm), with a small overlap volume with OARs (0.4 cm3 for the esophagus and 1.2 cm3 for the heart). Conclusions The CTVs generated by our CTV delineation system agree with the physician's contours. This approach demonstrates the capability of intelligent volumetric expansions with the potential to be used in clinical practice.

Imbalances of soil available nutrients and soilborne diseases have seriously restricted the productivity of crops and jeopardized food security worldwide. Pyrroloquinoline quinone (PQQ), a redox cofactor in some bacteria involved in glucose metabolism and phosphorus mineralization, could be anticipated to alter soil ecosystems to a certain extent. However, there is limited information on PQQ defending soilborne pathogens and regulating soil main nutrients. Here, a pot experiment based on mono-cropping soils of pepper was conducted to examine the effects of PQQ amendment on reconstructing soil microbial communities and soil nutrients under aerobic/anaerobic conditions comprising three treatments, namely, control, PQQ (aerobic), and FL-PQQ (anaerobic). The results revealed that soil microbial community composition and soil nutrients were distinctly altered by PQQ regimes. Compared to control, PQQ treatment significantly increased the content of soil available phosphorus (AP), while FL_PQQ treatment strongly improved the content of soil available nitrogen (AN). In terms of pathogens, relative to control, both PQQ treatments suppressed the abundances of pathogens, of which FL_PQQ treatment significantly decreased the abundance of the pathotrophic fungal by 64% and the abundance of Fusarium oxysporum by 57%, largely attributed to the increase of organic acid generators (O

As an integration of spectrum aggregation (SA) and cognitive radio Ad Hoc networks (CRAHNs), SA-enabled CRAHNs are capable of utilizing non-continuous spectrum components and is promising in improving the network performance. However, existing research on CRAHNs mainly assuming of an ideal spectrum sensing while ignoring the false alarm probability, resulting in an inaccurate capacity characterization. Hence, in this paper, we propose a more accurate capacity characterization while the detection and false alarm probability are considered. Moreover, we propose the joint optimization model for SA-enabled CRAHNs constrained by QoS requirements of primary users and network resource allocation. We propose the prim-dual method to decompose this problem into two sub-problems: a physical (PHY) layer sub-problem on CC assignment and power allocation, and a network layer sub-problem on route selection. Besides, these two sub-problems are coupled on the link capacity constraint. For sub-problem at PHY layer, we propose the genetic algorithm to obtain the optimal CC assignment and successive convex approximation method to the find the optimal power allocation. For sub-problem at network layer, we propose to apply the standard convex method to find the optimal solution. The numerical simulations demonstrate that network throughput can be improved by increasing the number of CCs. The obtained network throughput outperforms algorithms that without power control, spectrum aggregation or route optimization.

In order to identify the key transport process that determines the Cd concentration in brown rice, this study used 21 hybrid rice varieties as experimental materials and conducted field experiments in Qiyang (cadmium-contaminated site) and Yongding (low-cadmium site). Cd concentrations in 8 organs were measured, and bioconcentration factors and transfer factor were further calculated. The results showed that the Cd concentrations of the organs related to the xylem transport were as follows: root node stem leaf sheath leaf. In the phloem, the Cd concentrations were as follows: rachis brown rice rice husk. And the results of the correlation analysis found that Cd concentration between brown rice and root showed a significant positive correlation in Cd-contaminated site, but no significant correlation in low-cadmium site. Meanwhile, at both experimental sites, the Cd concentration of brown rice showed the most significant correlation with the phloem transfer factor from leaf and leaf sheath to brown rice. Principal Component Analysis (PCA) and stepwise regression analysis likewise found that Cd concentration in leaf and leaf sheath and their phloem transport of Cd to brown rice were significantly and positively correlated with Cd concentration in brown rice. The above results showed that the transport of leaf and leaf sheath to brown rice was a key process, and played a more important role in the accumulation of cadmium in brown rice than in root.

Silicon (Si) plays a pivotal role in mitigating phytotoxicity caused by cadmium (Cd). However, few former reports focused on the internal mechanism how Si assisted in alleviating Cd stress in rice under different durations of Cd exposure. Herein, the effects of Si on subcellular distribution of Cd in rice roots under short-term (12 h) and long-term (20 d) Cd exposure were explored. Results showed that Si decreased shoot Cd concentration but had little impact on root Cd levels. Under short-term Cd exposure, subcellular distribution analysis showed that Si increased the ratio of Cd in root cell wall by 23.2~24.0%, and decreased the ratio of Cd in root soluble fraction by 20.6~21.5%. This suggested that Si supply improved root retention of Cd by fixing it on the cell wall and thus restricted intracellular transportation of Cd. Further analysis unraveled that pectin (especially ionic-soluble pectin) of the cell wall was the main binding component, and Si supply induced more Cd accumulation in covalent-soluble pectin and hemicellulose. Moreover, the overexpression of germin-like proteins (GLPs) proved the role of cell wall in moderating Cd toxicity. Under long-term Cd exposure, Si promoted phytochelatin 2 (PC2) and phytochelatin 3 (PC3) synthesis in cytosol, at the same time, Si down-regulated the expression of the Cd efflux-related protein multidrug resistance-associated protein-like ATP-binding cassette transporters (MRP-like ABC transporters) and limited Cd transportation from vacuole to cytosol. Taken together, Si rather predominates in limiting Cd translocation by the cell wall of root under short-term Cd exposure and promoting vacuole compartmentalization to mitigate the Cd toxicity under long-term exposure, instead of reducing the absorption of Cd in rice roots, thereby decreasing Cd delivery into shoots.

This study aims to develop a method for verifying site-specific and/or beam path specific proton beam range, which could reduce range uncertainty margins and the associated treatment complications. It investigates the range uncertainties from both CT HU to relative stopping power conversion and patient positioning errors for prostate treatment using pelvic-like biological phantoms. Three 25 × 14 × 12 cm3phantoms, made of fresh animal tissues mimicking the pelvic anatomies of prostate patients, were scanned with a general electric CT simulator. A 22 cm circular passive scattering beam with 29 cm range and 8 cm modulation width was used to measure the water equivalent path lengths (WEPL) through the phantoms at multiple points using the dose extinction method with a MatriXXPT detector. The measured WEPLs were compared to those predicted by TOPAS simulations and ray-tracing WEPL calculations. For the three phantoms, the WEPL differences between measured and theoretical prediction (WDMT) are below 1.8% for TOPAS, and 2.5% for ray-tracing. WDMT varies with phantom anatomies by about 0.5% for both TOPAS and ray-tracing. WDMT also correlates with the tissue types of a specific treated region. For the regions where the proton beam path is parallel to sharp bone edges, the WDMTs of TOPAS and ray-tracing respectively reach up to 1.8% and 2.5%. For the region where proton beams pass through just soft tissues, the WDMT is mostly less than 1% for both TOPAS and ray-tracing. For prostate treatments, range uncertainty depends on the tissue types within a specific treated region, patient anatomies and the range calculation methods in the planning algorithms. Our study indicates range uncertainty is less than 2.5% for the whole treated region with both ray-tracing and TOPAS, which suggests the potential to reduce the current 3.5% range uncertainty margin used in the clinics by at least 1% even for single-energy CT data.

Mutant KRAS is a common tumor driver and frequently confers resistance to anti-cancer treatments such as radiation. DNA replication stress in these tumors may constitute a therapeutic liability but is poorly understood. Here, using single-molecule DNA fiber analysis, we first characterized baseline replication stress in a panel of unperturbed isogenic and non-isogenic cancer cell lines. Correlating with the observed enhanced replication stress we found increased levels of cytosolic double-stranded DNA in KRAS mutant compared to wild-type cells. Yet, despite this phenotype replication stress-inducing agents failed to selectively impact KRAS mutant cells, which were protected by CHK1. Similarly, most exogenous stressors studied did not differentially augment cytosolic DNA accumulation in KRAS mutant compared to wild-type cells. However, we found that proton radiation was able to slow fork progression and preferentially induce fork stalling in KRAS mutant cells. Proton treatment also partly reversed the radioresistance associated with mutant KRAS. The cellular effects of protons in the presence of KRAS mutation clearly contrasted that of other drugs affecting replication, highlighting the unique nature of the underlying DNA damage caused by protons. Taken together, our findings provide insight into the replication stress response associated with mutated KRAS, which may ultimately yield novel therapeutic opportunities.

In this study, the accurate effectiveness of CaO in mitigating Cd bioavailability in paddy soil-rice system was investigated and moreover, the potential for reversibility of CaO liming process was provided. Increasing soil pH to ≥6.5 by CaO was determined to be the minimal threshold for minimizing Cd transfer into rice in historically contaminated soils across light to severe Cd levels, while an elevated CaO ratio was needed for soil with recent input of Cd. In CaO remediation treatment, a reduced pool of bioavailable Cd in rhizosphere soil coupled with an increased Cd retention by Fe plaque and an inhibited planta Cd transfer was determined consistently and proposed to be largely responsible for the significant reduction in brown rice Cd. Under continuous simulated acid precipitation test, a negligible level of Cd in eluate with ∼1 unit higher pH than control was recorded with CaO. Significant acidification, however, increased Cd solubilization in the limed soil than in unlimited control, notably at pH 5.5–6.5. As indicated by Visual MINTEQ, a higher Cd-carbonate solubility and much decreased Cd complexation on Fe-(hydr)-oxides across this pH range occurred as a result of elevated Ca input. This suggests that a high soil pH (≥6.5) needs to be permanently maintained once liming has been performed to minimize Cd mobilization. Therefore, amending Cd-contaminated soils with CaO is a cost-effective remedial measure for reducing Cd bioavailability to paddy rice, while a high soil pH need to be permanently maintained to sustain this beneficial effect.

Purpose To report the first clinical results and value assessment of prompt gamma imaging for in vivo proton range verification in pencil beam scanning mode. Methods and Materials A stand-alone, trolley-mounted, prototype prompt gamma camera utilizing a knife-edge slit collimator design was used to record the prompt gamma signal emitted along the proton tracks during delivery of proton therapy for a brain cancer patient. The recorded prompt gamma depth detection profiles of individual pencil beam spots were compared with the expected profiles simulated from the treatment plan. Results In 6 treatment fractions recorded over 3 weeks, the mean (± standard deviation) range shifts aggregated over all spots in 9 energy layers were −0.8 ± 1.3 mm for the lateral field, 1.7 ± 0.7 mm for the right-superior-oblique field, and −0.4 ± 0.9 mm for the vertex field. Conclusions This study demonstrates the feasibility and illustrates the distinctive benefits of prompt gamma imaging in pencil beam scanning treatment mode. Accuracy in range verification was found in this first clinical case to be better than the range uncertainty margin applied in the treatment plan. These first results lay the foundation for additional work toward tighter integration of the system for in vivo proton range verification and quantification of range uncertainties.

Objectives: Prompt gamma (PG) imaging has previously been demonstrated for use in proton range verification of a brain treatment with a homogeneous target region. In this study, the feasibility of PG imaging to detect anatomic change within a heterogeneous region is presented. Methods: A prompt gamma camera recorded several fractions of a patient treatment to the base of skull. An evaluation CT revealed a decrease in sinus cavity filling during the treatment course. Comparison of PG profiles between measurement and simulation was performed to investigate range variations between planned and measured pencil beam spot positions. Results: For one field, an average over range of 3 mm due to the anatomic change could be detected for a subset of spots traversing the sinus cavity region. The two other fields appeared less impacted by the change but predicted range variations could not be detected. These results were partially consistent with the simulations of the evaluation CT. Conclusion: We report the first clinical application of PG imaging that detected some of the expected small regional proton range deviations due to anatomic change in a heterogeneous region. However, several limitations exist with the technology that may limit its sensitivity to detect range deviations in heterogeneous regions. Advances in knowledge: We report on the first detection of range variations due to anatomic change in a heterogeneous region using PGI. The results confirm the feasibility of using PG-based range verification in highly heterogeneous target regions to identify deviations from the treatment plan.

In on-orbit servicing, when the noncooperative target is captured by the servicing spacecraft, the inertial parameters of the combined spacecraft will have a drift change, which could degrade the control performance even lead to tumbling. This paper proposes an on-orbit identification scheme for inertial parameters by utilizing space manipulator. First, according to conservation of momentum, the kinematic model of combined spacecraft which is combined by the servicing spacecraft and the target with manipulator is established. Next, the linearized equations of the inertial parameters to be identified are obtained. Then, the recursive least square (RLS) method based on fading memory is adopted as the parameter identification criterion and method. Finally, numerical co-simulation is performed on the Adams/Matlab platform. The simulation results show the effectiveness and validity of the identification scheme proposed in this paper.

A major source of uncertainty in proton therapy is the conversion of Hounsfield unit (HU) to proton stopping power ratio relative to water (SPR). In this study, we measured and quantified the accuracy of a stoichiometric dual energy CT (DECT) SPR calibration. We applied a stoichiometric DECT calibration method to derive the SPR using CT images acquired sequentially at and . The dual energy index was derived based on the HUs of the paired spectral images and used to calculate the effective atomic number (Z eff), relative electron density (), and SPRs of phantom and biological materials. Two methods were used to verify the derived SPRs. The first method measured the sample's water equivalent thicknesses to deduce the SPRs using a multi-layer ion chamber (MLIC) device. The second method utilized Gafchromic EBT3 film to directly compare relative ranges between sample and water after proton pencil beam irradiation. Ex vivo validation was performed using five different types of frozen animal tissues with the MLIC and three types of fresh animal tissues using film. In addition, the residual ranges recorded on the film were used to compare with those from the treatment planning system using both DECT and SECT derived SPRs. Bland–Altman analysis indicates that the differences between DECT and SPR measurement of tissue surrogates, frozen and fresh animal tissues has a mean of 0.07% and standard deviation of 0.58% compared to 0.55% and 1.94% respectively for single energy CT (SECT) and SPR measurement. Our ex vivo study indicates that the stoichiometric DECT SPR calibration method has the potential to be more accurate than SECT calibration under ideal conditions although beam hardening effects and other image artifacts may increase this uncertainty.

The purpose of this study was to compare the radiation-induced second cancer risks for in-field and out-of-field organs and tissues for pencil beam scanning (PBS) and passive scattering proton therapy (PPT) and assess the impact of adding patient-specific apertures to sharpen the penumbra in pencil beam scanning for pediatric brain tumor patients. Five proton therapy plans were created for each of three pediatric patients using PPT as well as PBS with two spot sizes (average sigma of ~17 mm and ~8 mm at isocenter) and choice of patient-specific apertures. The lifetime attributable second malignancy risks for both in-field and out-of-field tissues and organs were compared among five delivery techniques. The risk for in-field tissues was calculated using the organ equivalent dose, which is determined by the dose volume histogram. For out-of-field organs, the organ-specific dose equivalent from secondary neutrons was calculated using Monte Carlo and anthropomorphic pediatric phantoms. We find that either for small spot size PBS or for large spot size PBS, a patient-specific aperture reduces the in-field cancer risk to values lower than that for PPT. The reduction for large spot sizes (on average 43%) is larger than for small spot sizes (on average 21%). For out-of-field organs, the risk varies only marginally by employing a patient-specific aperture (on average from -2% to 16% with increasing distance from the tumor), but is still one to two orders of magnitude lower than that for PPT. In conclusion, when pencil beam spot sizes are large, the addition of apertures to sharpen the penumbra decreases the in-field radiation-induced secondary cancer risk. There is a slight increase in out-of-field cancer risk as a result of neutron scatter from the aperture, but this risk is by far outweighed by the in-field risk benefit from using an aperture with a large PBS spot size. In general, the risk for developing a second malignancy in out-of-field organs for PBS remains much lower compared to PPT even if apertures are being applied.

The purpose of this study is to evaluate the effect of an intravenous (IV) contrast agent on proton therapy dose calculation using dual-energy computed tomography (DECT). Two DECT methods are considered. The first one, [Formula: see text], attempts to accurately predict the proton stopping powers relative to water (SPR) of contrast enhanced (CE) DECT images, while the second generates a virtual non-contrast (VNC) volume that can be processed as a native non-contrast (NC) one. Both methods are compared against single-energy computed tomography (SECT). The accuracy of SPR predicted for different concentrations of IV contrast diluted in water is first evaluated using simulated data. Results then are validated in an experimental set-up comparing SPR predictions for both NC and CE images to measurements made with a multi-layer ionisation chamber (MLIC). Finally, the impact of IV contrast on dose calculation using both SECT and DECT is evaluated for one liver and one head and neck patient. Using simulated data, DECT is shown to be less sensitive to the presence of IV contrast than SECT, although the performance of the [Formula: see text] method is sensitive to the level of beam hardening considered. For different concentrations of IV contrast diluted in water, experimental MLIC measurement of SPR agrees with DECT predictions within 3% while SECT introduce errors above 20%. This error in the SPR value results in a range error of up to 3.2 mm (2.6%) for proton beams calculated on SECT CE patient images. The error is reduced below 1 mm using DECT with the [Formula: see text] and VNC methods. Globally, it is observed that the influence of IV contrast on proton therapy dose calculation is mitigated using DECT over SECT. In patient anatomies, the VNC approach provides the best agreement with the reference dose distribution.

Proton Monte Carlo (MC) simulations model the physics processes between protons and medium and yield more accurate dose calculation compared to proton stopping power based pencil beam convolution algorithm. MC simulation is also essential for prompt gamma and proton-induced isotope production for in vivo proton range detection. It requires the tissue element composition to be determined from patient CT images. We propose a new hierarchical clustering based approach in extracting the atomic composition in human tissues from Dual Energy CT (DECT) scans and a method for validation using MC simulations. 70 published human tissues samples were used for the theoretical study of this approach. The tissues were first clustered by their composition similarities using hierarchical clustering. For each tissue cluster, three base tissues were randomly selected. Other tissues in this cluster were the weighted sum of these base tissues, where the weights were derived by fitting the attenuation coefficients calculated from DECT X-ray spectrums. The derived tissue atomic compositions and effective atomic number were compared with the ground truth. Animal tissues were scanned using a DECT scanner. The tissues were then irradiated using a PBS proton beam. A double Gaussian proton source has been modeled in GEANT4. Using these images, source model and extraction method, Monte Carlo simulations will be run mimicking the experimental setup. The soft tissues and bones were clustered into 8 subcategories, with cophenetic correlation 0.895 and inconsistency coefficient (IC) > 1.15 ( IC max = 1.1547 ). The mean and standard deviations of the difference in the derived atomic compositions and the ground truth for H, C, N, O, Ca, P were 0.05% (±0.07%), 1.56% (±2.02%), 0.61% (±0.55%), 1.81% (±2.37%), 0.03% (±0.07%), 0.13% (±0.16%), respectively. The Z eff from derived elemental composition was within 0.04 from the true values. We have investigated a new approach to extract the atomic composition from DECT scans. The accuracy of the extraction was demonstrated for published tissue samples. This approach will be validated using the DECT scans of animal tissues and GEANT4 source model, by comparing the Zeff derived from this method against measurements from proton beam irradiations.

Patterned alignment layers have been created through an approach using polarization holography and a photopolymerizable alignment layer. This technique enables continuously periodic boundary conditions on planar surfaces. Polarization gratings have been created using polarization interference from incident right-handed and left-handed circular polarization exposure conditions. A simple phenomenological model is derived to show that the Freedericksz threshold voltage vanishes when the cell gap and grating pitch are comparable.

A search for charged massive stable particles has been performed with the D0 detector using 1.1 fb{sup -1} of data. The speed of the particle has been calculated based on the time-of-flight and position information in the muon system. The present research is limited to direct pair-production of the charged massive long-lived particles. We do not consider CMSPs that result from the cascade decays of heavier particles. In this analysis, the exact values of the model parameters of the entire supersymmetric particle mass spectrum, relevant for cascade decays, are not important. We found no evidence of the signal. 95% CL cross-section upper limits have been set on the pair-productions of the stable scaler tau lepton, the gaugino-like charginos, and the higgsino-like charginos. The upper cross section limits vary from 0.31 pb to 0.04 pb, for stau masses in the range between 60 GeV and 300 GeV. We use the nominal value of the theoretical cross section to set limits on the mass of the pair produced charginos. We exclude the pair-produced stable gaugino-like charginos with mass below 206 GeV, and higgsino-like charginos below 171 GeV, respectively. Although the present sensitivity is insufficient to test the model of the pair produced stable staus, we do set cross section limits which can be applied to the pair production of any charged massive stable particle candidates with similar kinematics. These are the most restrictive limits to the present on the cross sections for CMSPs and the first published from the Tevatron Collider Run II. The manuscript has been published by Physical Review Letters in April 2009 and is available at arXiv as.

The D Level 3 data acquisition system for Run II of the Tevatron has been reliably operating since May 2002. Designed to handle average event sizes of 250 kilobytes at a rate of 1 kHz, the system has been upgraded to be able to process more events, doubling its typical output rate from 50 Hz to 100 Hz, while coping with higher event sizes at the beginning of high luminosity collider stores. The system routes and transfers event fragments from 63 VME crates to any of approximately 320 processing nodes. The addition of more farm nodes, the performance of the components, and the running experience are described here.

We present a novel method to create patterned alignment layers using holography with a photopolymerizable layer, and show the various types of alignments that are possible. The technique is very flexible and can create a rich variety of new configurations, not possible with conventional lithograph patterning techniques.