Development and evaluation of ultrasound image tracking technology based on Mask R-CNN applied to respiratory motion compensation system.

Background: For respiration induced tumor displacement during a radiation therapy, a common method to prevent the extra radiation is image-guided radiation therapy. Moreover, mask region-based convolutional neural networks (Mask R-CNN) is one of the state-of-the-art (SOTA) object detection frameworks capable of conducting object classification, localization, and pixel-level instance segmentation. Methods: We developed a novel ultrasound image tracking technology based on Mask R-CNN for stable tracking of the detected diaphragm motion and applied to the respiratory motion compensation system (RMCS). For training Mask R-CNN, 1800 ultrasonic images of the human diaphragm are collected. Subsequently, an ultrasonic image tracking algorithm was developed to compute the mean pixel coordinates of the diaphragm detected by Mask R-CNN. These calculated coordinates are then utilized by the RMCS for compensation purposes. The tracking similarity verification experiment of mask ultrasonic imaging tracking algorithm (M-UITA) is performed. Results: The correlation between the input signal and the signal tracked by M-UITA was evaluated during the experiment. The average discrete Fréchet distance was less than 4 mm. Subsequently, a respiratory displacement compensation experiment was conducted. The proposed method was compared to UITA, and the compensation rates of three different respiratory signals were calculated and compared. The experimental results showed that the proposed method achieved a 6.22% improvement in compensation rate compared to UITA. Conclusions: This study introduces a novel method called M-UITA, which offers high tracking precision and excellent stability for monitoring diaphragm movement. Additionally, it eliminates the need for manual parameter adjustments during operation, which is an added advantage.

Effectiveness of Stereotactic Ablative Radiotherapy for Systemic Therapy Respondents with Inoperable Pulmonary Oligometastases and Oligoprogression.

Stereotactic ablative radiotherapy (SABR) may improve survival in patients with inoperable pulmonary oligometastases. However, the impact of pulmonary oligometastatic status after systemic therapy on SABR outcomes remains unclear. Hence, we investigated the outcomes of SABR in 45 patients with 77 lung tumors and the prognostic value of pulmonary oligoprogression. Eligibility criteria were pulmonary oligometastases (defined as ≤5 metastatic lung tumors), controlled extrapulmonary disease (EPD) after front-line systemic therapy, SABR as primary local treatment for inoperable pulmonary metastases, and consecutive imaging follow-up. Oligometastatic lung tumor was classified into controlled or oligoprogressive status. Overall survival (OS), in-field progression-free survival (IFPFS), out-field progression-free survival (OFPFS), and prognostic variables were evaluated. With 21.8 months median follow-up, the median OS, IFPFS, and OFPFS were 28.3, not reached, and 6.5 months, respectively. Two-year OS, IFPFS, and OFPFS rates were 56.0%, 74.2%, and 17.3%, respectively. Oligoprogressive status (p = 0.003), disease-free interval < 24 months (p = 0.041), and biologically effective dose (BED10) < 100 Gy (p = 0.006) were independently associated with inferior OS. BED10 ≥ 100 Gy (p = 0.029) was independently correlated with longer IFPFS. Oligoprogressive status (p = 0.017) and EPD (p = 0.019) were significantly associated with inferior OFPFS. Grade ≥ 2 radiation pneumonitis occurred in four (8.9%) patients. Conclusively, SABR with BED10 ≥ 100 Gy could provide substantial in-field tumor control and longer OS for systemic therapy respondents with inoperable pulmonary oligometastases. Oligoprogressive lung tumors exhibited a higher risk of out-field treatment failure and shorter OS. Hence, systemic therapy should be tailored for patients with oligoprogression to reduce the risk of out-field treatment failure. However, in the absence of effective systemic therapy, SABR is a reasonable alternative to reduce resistant tumor burden.

Molten salt-induced vertical CoP/Co nanosheets array coupled with carbon for efficient water splitting.

The exploration of high-efficiency non-noble metal catalysts for improving the intrinsic activity and active sites for overall water splitting persists as a bottleneck issue. Herein, a facile heterogeneous molten salt strategy has been proposed to fabricate CoP/Co nanosheets array that is vertically attached to a carbon matrix. Such a hierarchical structure endows the hybrid with abundant active sites and favorable reaction kinetics. Experimental results reveal that the molten salt determines the final shape of metallic Co, which is not sensitive to the organic sources. After optimization of the molten salt mass, the CoP/Co/C-6 shows the best bifunctional performance, requiring an overpotential of 132 mV and 320 mV at 10 mA cm-2 for hydrogen evolution reaction and oxygen evolution reaction, respectively. Theoretical simulation results manifest the CoP/Co heterostructure alters the electronic structure of Co and CoP, and reduces the adsorption free energy of intermediates, thus further boosting the electrocatalysis activity. This work proposes a molten salt-assisted method for the rational design of novel two-dimensional nano-hybrids for energy conversion applications.

Ex Vivo Expanded Circulating Tumor Cells for Clinical Anti-Cancer Drug Prediction in Patients with Head and Neck Cancer.

The advanced-stage head and neck cancer (HNC) patients respond poorly to platinum-based treatments. Thus, a reliable pretreatment method for evaluating platinum treatment response would improve therapeutic efficiency and outcomes. This study describes a novel strategy to predict clinical drug responses in HNC patients by using eSelect, a lab-developed biomimetic cell culture system, which enables us to perform ex vivo expansion and drug sensitivity profiling of circulating tumor cells (CTCs). Forty liquid biopsies were collected from HNC patients, and the CTCs were expanded ex vivo using the eSelect system within four weeks. Immunofluorescence staining confirmed that the CTC-derived organoids were positive for EpCAM and negative for CD45. Two illustrative cases present the potential of this strategy for evaluating treatment response. The statistical analysis confirmed that drug sensitivity in CTC-derived organoids was associated with a clinical response. The multivariant logistic regression model predicted that the treatment accuracy of chemotherapy responses achieved 93.75%, and the area under the curves (AUCs) of prediction models was 0.8841 in the whole dataset and 0.9167 in cisplatin specific dataset. In summary, cisplatin sensitivity profiles of patient-derived CTCs expanded ex vivo correlate with a clinical response to cisplatin treatment, and this can potentially underpin predictive assays to guide HNC treatments.

The feasibility of an approximate irregular field dose distribution simulation program applied to a respiratory motion compensation system.

PURPOSE: This study optimized our previously proposed simulation program for the approximate irregular field dose distribution (SPAD) and applied it to a respiratory motion compensation system (RMCS) and respiratory motion simulation system (RMSS). The main purpose was to rapidly analyze the two-dimensional dose distribution and evaluate the compensation effect of the RMCS during radiotherapy. METHODS: This study modified the SPAD to improve the rapid analysis of the dose distribution. In the experimental setup, four different respiratory signal patterns were input to the RMSS for actuation, and an ultrasound image tracking algorithm was used to capture the real-time respiratory displacement, which was input to the RMCS for actuation. A linear accelerator simultaneously irradiated the EBT3 film. The gamma passing rate was used to verify the dose similarity between the EBT3 film and the SPAD, and conformity index (CI) and compensation rate (CR) were used to quantify the compensation effect. RESULTS: The Gamma passing rates were 70.48-81.39% (2%/2mm) and 88.23-96.23% (5%/3mm) for various collimator opening patterns. However, the passing rates of the SPAD and EBT3 film ranged from 61.85% to 99.85% at each treatment time point. Under the four different respiratory signal patterns, CR ranged between 21% and 75%. After compensation, the CI for 85%, 90%, and 95% isodose constraints were 0.78, 0.57, and 0.12, respectively. CONCLUSIONS: This study has demonstrated that the dose change during each stage of the treatment process can be analyzed rapidly using the improved SPAD. After compensation, applying the RMCS can reduce the treatment errors caused by respiratory movements.

Polyphyllin I reverses the resistance of osimertinib in non-small cell lung cancer cell through regulation of PI3K/Akt signaling.

Lung cancer is considered the main cause of cancer mortality worldwide. Osimertinib, a third-generation EGFR-TKI, has been approved and administrated for treating patients with either EGFR T790M mutation or EGFR sensitive mutation. However, resistance to osimertinib emerges and has been considered to be the main obstacle in lung cancer treatment. Polyphyllin I is isolated from the natural herb Paris polyphylla and exhibits anti-cancer activities. In the present study, we identify Polyphyllin I to reverse the resistance of osimertinib in vitro and in vivo. The results showed that Polyphyllin I reversed the resistance of osimertinib through promoting apoptosis, modulating the PI3K/Akt signaling, and regulating the expression of apoptosis-related proteins in osimertinib-resistant cell lines. In vivo study confirmed the results, showing that the tumor growth was significantly suppressed in the Polyphyllin I/osimertinib group compared to the osimertinib group. It has been clarified that Polyphyllin I could reverse the resistance of osimertinib in osimertinib-resistant non-small cell of lung cancer in vitro and in vivo. The underlying mechanism might be related to the downregulation of the PI3K/Akt signaling and increase of the expression of apoptosis-related proteins, suggesting that Polyphyllin I was a promising therapeutic agent for reversing the resistance of osimertinib.

Ex Vivo Expansion and Drug Sensitivity Profiling of Circulating Tumor Cells from Patients with Small Cell Lung Cancer.

Small cell lung cancer (SCLC) represents one of the most aggressive malignancies among cancer types. Not only tumor sample availability is limited, but also the ability for tumor cells to rapidly acquire drug resistance are the rate-limiting bottlenecks for overall survival in current clinical settings. A liquid biopsy capable of capturing and enriching circulating tumor cells (CTCs), together with the possibility of drug screening, is a promising solution. Here, we illustrate the development of a highly efficient ex vivo CTC expansion system based on binary colloidal crystals substrate. Clinical samples were enrolled from 22 patients with SCLC in the study. The CTCs were enriched and expanded from the collected peripheral blood samples. Expanded cells were analyzed for protein expression and observed for drug sensitivity with the use of immunofluorescence and ATP titer evaluation, respectively. Successful CTC spheroid proliferation was established after 4 weeks within 82% of all the collected peripheral blood samples from enrolled patients. Upon immunofluorescence analysis, the enriched cells showed positive markers for EpCAM, TTF-1, synaptophysin and negative for CD45. Additionally, the expanded CTCs demonstrated marked heterogeneity in the expression of E-cadherin and N-cadherin. In a preliminary case series, the drug sensitivity of patient-derived CTC to cisplatin and etoposide was studied to see the correlation with the corresponding therapeutic outcome. In conclusion, our study demonstrates that it is possible to efficiently expand CTCs from SCLC within a clinically relevant time frame; the biomarker information generated from enriched CTCs can assist the selection of effective drugs and improve disease outcome.

A Combined Systemic Strategy for Overcoming Cisplatin Resistance in Head and Neck Cancer: From Target Identification to Drug Discovery.

Cisplatin is the first-line chemotherapy agent for head and neck cancer (HNC), but its therapeutic effects are hampered by its resistance. In this study, we employed systemic strategies to overcome cisplatin resistance (CR) in HNC. CR cells derived from isogenic HNC cell lines were generated. The CR related hub genes, functional mechanisms, and the sensitizing candidates were globally investigated by transcriptomic and bioinformatic analyses. Clinically, the prognostic significance was assessed by the Kaplan-Meier method. Cellular and molecular techniques, including cell viability assay, tumorsphere formation assay, RT-qPCR, and immunoblot, were used. Results showed that these CR cells possessed highly invasive and stem-like properties. A total of 647 molecules was identified, and the mitotic division exhibited a novel functional mechanism significantly related to CR. A panel of signature molecules, MSRB3, RHEB, ULBP1, and spindle pole body component 25 (SPC25), was found to correlate with poor prognosis in HNC patients. SPC25 was further shown as a prominent molecule, which markedly suppressed cancer stemness and attenuated CR after silencing. Celastrol, a nature extract compound, was demonstrated to effectively inhibit SPC25 expression and reverse CR phenotype. In conclusion, the development of SPC25 inhibitors, such as the application of celastrol, maybe a novel strategy to sensitize cisplatin for the treatment of refractory HNC.

Paired double parallelogram flexure mechanism clamped by corrugated beam for underconstraint elimination.

This Note presents a kind of paired double parallelogram (DP) flexure mechanism clamped by a sinusoidal corrugated beam to solve the problem of underconstraint of its secondary stages. The results show that the proposed mechanism effectively constrains the undesired motions of the secondary stages without changing the stiffness and the first-order natural frequency in the working direction. The second- and third-order natural frequencies of the mechanism are increased by 9.2% and 30.8%, respectively, which can effectively improve the dynamic characteristics of the DP mechanism.

Stiffening, strengthening, and toughening of biodegradable poly(butylene adipate-co-terephthalate) with a low nanoinclusion usage.

Simultaneous stiffening, strengthening, and toughening of biodegradable polymers, such as poly(butylene adipate-co-terephthalate) (PBAT) and others, is necessary for their use in packaging and agriculture applications. However, a high content of nanoinclusions is usually required, leading to a tradeoff between composite toughness and strength or stiffness in the reinforcement. Herein, we report an iterative reinforcement strategy that uses one nanocomposite to reinforce PBAT. An in-situ grafting polymerized cellulose nanocrystal (CNC)/PBAT (CNC-g-PBAT) nanocomposite consisting of ungrafted/free PBAT (PBATf) was used as an inclusion directly to reinforce a commercial PBAT. At an exceptionally low CNC usage of 0.02 wt.%, we achieved a simultaneous enhancement of the Young's modulus by 26 %, tensile strength by 27 %, elongation at break by 37 %, and toughness by 56 % over those for PBAT. To the best of our knowledge, such reinforcement efficiency is the highest among similar biodegradable polymer nanocomposites reported in the literature. The rheology, differential scanning calorimetry, and wide-angle X-ray diffraction measurements confirmed the mechanical reinforcement attributed to a synergistic contribution from PBATf and CNC-g-PBAT. In particular, the use of PBATf enhanced both stiffness and toughness of the composites, while the CNC-g-PBAT interacted within the polymer matrix and increased the crystallinity of the polymer matrix, leading to the strengthening and toughening effect. The strategy proposed here is greatly beneficial to producing high-performance biodegradable polymer nanocomposite films for packaging and agricultural applications using a very low amount of nanoinclusion.

A Brain-Inspired Adaptive Space Representation Model Based on Grid Cells and Place Cells.

Grid cells and place cells are important neurons in the animal brain. The information transmission between them provides the basis for the spatial representation and navigation of animals and also provides reference for the research on the autonomous navigation mechanism of intelligent agents. Grid cells are important information source of place cells. The supervised learning and unsupervised learning models can be used to simulate the generation of place cells from grid cell inputs. However, the existing models preset the firing characteristics of grid cell. In this paper, we propose a united generation model of grid cells and place cells. First, the visual place cells with nonuniform distribution generate the visual grid cells with regional firing field through feedforward network. Second, the visual grid cells and the self-motion information generate the united grid cells whose firing fields extend to the whole space through genetic algorithm. Finally, the visual place cells and the united grid cells generate the united place cells with uniform distribution through supervised fuzzy adaptive resonance theory (ART) network. Simulation results show that this model has stronger environmental adaptability and can provide reference for the research on spatial representation model and brain-inspired navigation mechanism of intelligent agents under the condition of nonuniform environmental information.

LncRNA KCNQ1OT1 contributes to cardiomyocyte apoptosis by targeting FUS in heart failure.

Long noncoding RNAs (lncRNAs) have recently been recognized as the important regulators in cardiac diseases. This study was aimed to investigate the role and molecular mechanism of lncRNA KCNQ1OT1 in regulating cardiomyocyte apoptosis in heart failure (HF). The mouse model of HF was induced by doxorubicin (ADR). Cell apoptosis was detected by Hoechst and TUNEL staining. Molecule expressions were determined by qRT-PCR and western blot. The interaction between KCNQ1OT1 and Fused in sarcoma (FUS) was assessed by RNA immunoprecipitation (RIP) and RNA pull-down assays. KCNQ1OT1 was up-regulated in the myocardial tissues of HF mice and the ADR-stimulated mouse myocardial cell line (HL-1). KCNQ1OT1 overexpression promoted apoptosis of ADR-stimulated HL-1 cells, while KCNQ1OT1 knockdown caused the opposite effect. The RIP and RNA pull-down results showed that KCNQ1OT1 - bound to FUS and negatively regulated its protein level. Knockdown of FUS inhibited apoptosis of ADR-stimulated HL-1 cells and reversed the effect of KCNQ1OT1 overexpression on cardiomyocyte apoptosis. In vivo experiment showed that KCNQ1OT1 ovexpression improved myocardial histopathological changes, reduced myocardial fibrosis areas, down-regulated FUS expression, and inhibited cell apoptosis of HF mice. In conclusion, KCNQ1OT1 facilitates cardiomyocyte apoptosis by - targeting FUS in ADR-induced HF.

Tumor motion tracking based on a four-dimensional computed tomography respiratory motion model driven by an ultrasound tracking technique.

BACKGROUND: An ultrasound image tracking algorithm (UITA) was combined with four-dimensional computed tomography (4DCT) to create a real-time tumor motion-conversion model. The real-time position of a lung tumor phantom based on the real-time diaphragm motion trajectories detected by ultrasound imaging in the superior-inferior (SI) and medial-lateral (ML) directions were obtained. METHODS: Three different tumor motion-conversion models were created using a respiratory motion simulation system (RMSS) combined with 4DCT. The tumor tracking error was verified using cone-beam computed tomography (CBCT). The tumor motion-conversion model was produced by using the UITA to monitor the motion trajectories of the diaphragm phantom in the SI direction, and using 4DCT to monitor the motion trajectories of the tumor phantom in the SI and ML directions over the same time period, to obtain parameters for the motion-conversion model such as the tumor center position and the amplitude and phase ratios. RESULTS: The tumor movement was monitored for 90 s using CBCT to determine the real motion trajectories of the tumor phantom and using ultrasound imaging to simultaneously record the diaphragm movement. The absolute error of the motion trajectories of the real and estimated tumor varied between 0.5 and 2.1 mm in the two directions. CONCLUSIONS: This study has demonstrated the feasibility of using ultrasound imaging to track diaphragmatic motion combined with a 4DCT tumor motion-conversion model to track tumor motion in the SI and ML directions. The proposed method makes tracking a lung tumor feasible in real time, including under different breathing conditions.

Simulating the approximate irregular field dose distribution in radiotherapy using an ultrasound tracking technique.

PURPOSE: This study used an ultrasound image tracking algorithm (UITA) in combination with a proposed simulation program for the approximate irregular field dose distribution (SPAD) to assess the feasibility of performing dose distribution simulations for two-dimensional radiotherapy. METHODS: This study created five different types of multileaf collimator openings, and applied a SPAD to analyze the matrix position parameters for each regular field to generate a static program-simulation dose distribution map (PDDM), whose similarity was then compared with a static radiochromic film experimental-measurement dose distribution map (EDDM). A two-dimensional respiration motion simulation system (RMSS) was used to reproduce the respiration motion, and the UITA was used to capture the respiration signals. Respiration signals were input to the SPAD to generate two dynamic PDDMs, which were compared for similarity with the dynamic EDDM. RESULTS: In order to verify the dose distribution between different dose measurement techniques, the gamma passing rate with 2%/2 mm criterion was used for the EDDM and PDDM, the passing rates were between 94.31% and 99.71% in the static field analyses, and between 84.45% and 96.09% for simulations with the UITA signal input and between 89.35% and 97.78% for simulations with the original signal input in the dynamic field analyses. CONCLUSIONS: Static and dynamic dose distribution maps can be simulated based on the proposed matrix position parameters of various fields and by using the UITA to track respiration signals during radiation therapy. The present findings indicate that it is possible to develop a reusable and time-saving dose distribution measurement tool.

Chemoradiotherapy for Inoperable Carotid Body Leiomyosarcoma: A Case Report and Review of Literature.

Vascular leiomyosarcoma is an extremely rare tumor and is associated with poor prognosis among leiomyosarcoma. Surgical resection remains the main treatment option. But outcome of definitive treatment with chemoradiotherapy in inoperable patients is not clear. Here, we report treatment and outcome of definitive chemoradiotherapy in a case of vascular leiomyosarcoma. A 64-year-old man with the initial presentation of pulsatile right neck mass was diagnosed with right carotid body leiomyosarcoma. He refused surgical intervention due to risk of carotid body injury and ischemic stroke. Successful tumor control was achieved with carboplatin-based concurrent chemoradiotherapy. Investigational liquid biopsy for circulating sarcoma cells was also performed to analyze drug sensitivity profile of this rare tumor. One year after treatment, the disease remained well controlled and there was no evidence of baroreflex failure or treatment-related late toxicities. To our best knowledge, this is the first case report of right carotid body leiomyosarcoma controlled with definitive concurrent chemoradiotherapy. The approach of personalized multi-modality treatment will be a focus of our future investigation.

Cost Effectiveness of Ceritinib and Alectinib Versus Crizotinib in First-Line Anaplastic Lymphoma Kinase-Positive Advanced Non-small-cell Lung Cancer.

BACKGROUND: Crizotinib, ceritinib, and alectinib improved survival in patients with anaplastic lymphoma kinase (ALK) arrangement non-small-cell lung cancer (NSCLC); however, the long-term economic outcomes of using ceritinib and alectinib versus crizotinib are still unclear. OBJECTIVE: This analysis aimed to evaluate the cost effectiveness of ceritinib and alectinib versus crizotinib in the Chinese healthcare setting. METHODS: A Markov model was developed to project the economic and health outcomes for the treatment of advanced NSCLC with ceritinib, alectinib or crizotinib. A network meta-analysis was performed to calculate the hazard ratios of ceritinib and alectinib versus crizotinib by pooling published trials. Cost and utility values were obtained from the literature, and one-way and probabilistic sensitivity analyses were carried out to determine the robustness of the model outcomes. The primary outputs included total cost, life-years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratio (ICER). RESULTS: Treatment with alectinib and ceritinib yielded an additional 1.00 and 1.09 QALYs and incremental costs of $62,232 and $15,165, resulting in an ICER of $62,231 and $13,905 per QALY compared with crizotinib, respectively. Parameters related to drug costs and progression-free survival were the main drivers of the model outcomes. From the probabilistic sensitivity analysis, ceritinib and alectinib had a 99.9% and 0% probability of being cost effective, respectively, at a willingness-to-pay threshold of US$28,410/QALY. CONCLUSIONS: Our results indicate that compared with crizotinib and alectinib, ceritinib is a cost-effective option for treatment-naïve patients with ALK-positive advanced NSCLC.

Effectiveness of stereotactic ablative radiotherapy in patients with advanced hepatocellular carcinoma unsuitable for transarterial chemoembolization.

BACKGROUND: Stereotactic ablative radiotherapy (SABR) can deliver tumoricidal doses and achieve long-term control in early hepatocellular carcinoma (HCC). However, limited studies have investigated the safety and effectiveness of SABR in patients with advanced diseases that is unsuitable for transarterial chemoembolization (TACE). METHODS: In this observational study, we reviewed the medical records of patients with Barcelona Clinic Liver Cancer (BCLC) stage C disease treated with linear accelerator-based SABR between 2008 and 2016. Their tumors were either refractory to TACE or TACE was contraindicated. Overall survival (OS), in-field progression-free survival (IFPFS), and out-field progression-free survival were calculated using Kaplan-Meier analysis. The Cox regression model was used to examine the effects of variables. Treatment-related toxicities were scored according to the Common Terminology Criteria for Adverse Events (version 4.03) and whether patients developed radiation-induced liver disease (RILD) after SABR. RESULTS: This study included 32 patients. The mean maximal tumor diameter and tumor volumes were 4.7 cm and 135.9 ml, respectively. Patients received linear accelerator-based SABR with a median prescribed dose of 48 Gy (30-60 Gy) in three to six fractions. Based on the assessment of treatment response by using the Response Evaluation Criteria in Solid Tumors (version 1.1), 19% of patients achieved a complete response and 53% achieved a partial response. After a median follow-up of 18.1 months (4.0-65.9 months), 10, 19, and 9 patients experienced in-field failure, out-field hepatic recurrence, and extrahepatic metastases, respectively. The estimated 2-year OS and IFPFS rates were 54.4% and 62.7%, respectively. In a multivariate analysis, a pretreatment Cancer of the Liver Italian Program (CLIP) score of ⩾2 (p = 0.01) was a prognostic factor for shorter OS, and a biologically effective dose (BED) of < 85 Gy10 (p = 0.011) and a Child-Pugh score of ⩾6 (p = 0.014) were prognostic factors for inferior IFPFS. In this study five and eight patients developed classic and nonclassic RILD, respectively. CONCLUSIONS: SABR can serve as a salvage treatment for patients with HCC with BCLC stage C disease unsuitable for TACE, in particular, in those with a baseline CLIP score of ⩽1. A BED10 of ⩾85 Gy is an appropriate prescribed dose for tumor control. Because out-field relapse is the major cause of treatment failure, SABR in combination with novel systemic modalities should be investigated in future studies.

Development of a novel line structured light measurement instrument for complex manufactured parts.

This paper studies a novel structured light measurement instrument for complex manufactured parts. In this research, a quick and accurate light plane calibration method and a novel light strip center extraction method were used to establish the measurement instrument. First, the intrinsic and external parameters of the camera are calibrated by Zhang's method. Second, a novel light plane calibration technique is proposed by using the original parameters and images in the process of camera calibration, which can be used to improve the accuracy of the measurement system because both the camera calibration and light plane calibration are based on the same target. Third, a subpixel extraction method is presented to extract the light strip center on the basis of the geometric center method. Finally, the constructed instrument is used to detect the geometric information of the complex manufactured parts. The experimental results show that the maximum measurement error is 0.1 mm under a measurement range of 50 mm and the accuracy is 0.2%, which indicates that the measurement instrument is fast, robust, and accurate enough to be applied to many kinds of measurements, such as railroad track deformation, the inner wall of a pipe, and so on.

Design and analysis of a displacement amplifier with high load capacity by combining bridge-type and Scott-Russell mechanisms.

To improve the load capacity of flexure-based amplification mechanisms, a flexure-based displacement amplification mechanism is developed in this study by combining the bridge-type and the Scott-Russell mechanisms. The four arms of the traditional bridge mechanism are replaced by four Scott-Russell mechanisms that provide the advantages of good symmetry, compact structure, and higher load capacity. An analytical model is formulated using a stiffness matrix to analyze the natural frequency, input and output stiffnesses, displacement amplification ratio, and load capacity of the proposed mechanism. The design model was subjected to both experimental methods and finite element analysis for verification, and the two sets of results were in good agreement. This proves the effectiveness and applicability of the analytical model and the proposed amplification mechanism. The output stiffnesses of the modified bridge-type amplifier and the traditional bridge-type amplifier are 0.158 N/µm and 0.041 N/µm, respectively, indicating excellent load performance of the modified bridge-type amplifier.

Expression of AHI1 Rescues Amyloidogenic Pathology in Alzheimer's Disease Model Cells.

A hallmark of Alzheimer's disease (AD) pathogenesis is the accumulation of extracellular plaques mainly composed of amyloid-ß (Aß) derived from amyloid precursor protein (APP) cleavage. Recent reports suggest that transport of APP in vesicles with huntingtin-associated protein-1 (HAP1) negatively regulates Aß production. In neurons, HAP1 forms a stable complex with Abelson helper integration site-1 (AHI1), in which mutations cause neurodevelopmental and psychiatric disorders. HAP1 and AHI1 interact with tropomyosin receptor kinases (Trks), which are also associated with APP and mediate neurotrophic signaling. In this study, we hypothesize that AHI1 participates in APP trafficking and processing to rescue AD pathology. Indeed, AHI1 was significantly reduced in mouse neuroblastoma N2a cells expressing human Swedish and Indiana APP (designed as AD model cells) and in 3xTg-AD mouse brain. The AD model cells as well as Ahi1-knockdown cells expressing wild-type APP-695 exhibited a significant reduction in viability. In addition, the AD model cells were reduced in neurite outgrowth. APP C-terminal fragment-ß (CTFß) and Aß42 were increased in the AD cell lysates and the culture media, respectively. To investigate the mechanism how AHI1 alters APP activities, we overexpressed human AHI1 in the AD model cells. The results showed that AHI1 interacted with APP physically in mouse brain and transfected N2a cells despite APP genotypes. AHI1 expression facilitated intracellular translocation of APP and inhibited APP amyloidogenic process to reduce the level of APP-CTFß in the total lysates of AD model cells as well as Aß in the culture media. Consequently, AHI1-APP interactions enhanced neurotrophic signaling through Erk activation and led to restored cell survival and differentiation.