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More rigorous challenge is put forward by the demand on the structure and thermal protection system of super sonic air-crafts with faster flight speed and longer flight time. The integrated design of structure and thermal protection can give consideration to both load and thermal protection functions, which can give full play to the potential high temperature strength , reduce the thermal stress caused by temperature difference of different parts, and reduce the quality of the thermal protection and structure. It has higher structure efficiency than traditional thermal protection, and can be reused at the same time, reducing the cost. This paper briefly described the research status of integrated thermal protection technology at home and abroad.On this basis, the characteristics and shortcomings of integrated thermal protection were summarized, and the development trend of integrated thermal protection was discussed.China is still in a development stage. Widening the technical cognition of integral technology of structure and thermal protection, actively developing low-cost co-cured technology of structure material and thermal protection material, continuously introducing new thermal protective materials, and sparing no effort to strengthen research and development of the active cooling technology of integrated thermal protection systems is a feasible way of domestic integral technology of structure and thermal protection being quickly applied to models.

Purpose: To evaluate efficacy and safety of veliparib combined with carboplatin/paclitaxel in patients with advanced human epidermal growth factor receptor 2 (HER2)-negative, germline BRCA (g BRCA )-associated breast cancer defined by hormone receptor (HR) and g BRCA1 / 2 mutation status. Patients and Methods: In this phase-3, double-blind, placebo-controlled trial, patients ( N = 509) with advanced HER2-negative breast cancer and g BRCA1/2 mutations were randomized 2:1 to receive veliparib plus carboplatin/paclitaxel or placebo plus carboplatin/paclitaxel. Patients who discontinued chemotherapy prior to disease progression continued receiving blinded veliparib/placebo monotherapy. The primary endpoint was investigator-assessed progression-free survival (PFS). Subgroup analyses of PFS stratified by HR and g BRCA1/2 mutation status were prespecified. Results: In the intention-to-treat population, there were similar proportions of patients with g BRCA1 versus g BRCA2 mutations (51% vs 49%) and HR+ disease versus triple-negative breast cancer (TNBC) (52% vs 48%). Median PFS was longer in the veliparib arm compared with the placebo arm for all subgroups (HR+: 13.0 vs 12.5 months, hazard ratio (95% confidence interval (CI)): 0.69 (0.52, 0.93), p = 0.013; TNBC: 16.6 vs 14.1 months, hazard ratio (95% CI): 0.72 (0.52, 1.00), p = 0.052; g BRCA1 : 14.2 vs 12.6 months, hazard ratio (95% CI): 0.75 (0.55, 1.03), p = 0.073; g BRCA2 : 14.6 vs 12.6 months, hazard ratio (95% CI): 0.69 (0.50, 0.95); p = 0.021). Benefit was durable, with improved PFS rates at 2 years (HR+, 27.5% vs 15.3%; TNBC, 40.4% vs 25.0%) and 3 years (HR+, 17.5% vs 8.6%; TNBC, 35.3% vs 13.0%) in all subgroups. g BRCA status ( BRCA1 vs BRCA2 ) did not substantially affect the carboplatin/paclitaxel ± veliparib toxicity profile. Conclusion: Veliparib plus carboplatin/paclitaxel resulted in durable benefit in subgroups defined by HR status or by g BRCA1 versus g BRCA2 mutation. Overall, addition of veliparib to carboplatin/paclitaxel was tolerable, and there were no clinically meaningful differences in adverse events between the g BRCA1 versus g BRCA2 and HR+ versus TNBC subgroups. Trial Registration: NCT02163694, https://clinicaltrials.gov/ct2/show/NCT02163694

BACKGROUND The higher thermal maturity of organic matter and the shortage of terrestrial plants are the main characteristics of Lower Paleozoic marine shale in China, which results in the difficulty of distinguishing macerals. Nowadays the existing methods of vitrinite reflectance, rock eval, Tm/Ts and other biomarker indices cannot be effectively used to evaluate the maturity of organic matter in shale. OBJECTIVES To evaluate the maturity of organic matter in highly evolved shale. METHODS The shale of the Silurian Longmaxi Formation of Well Anye-1 in Zheng'an area of Guizhou Province is used in the experiments. Field Emission Scanning Electron Microscopy and Laser Raman Spectroscopy are used to obtain the Raman Spectra of organic matter in different occurrences of highly evolved shale, independent of the type of organic macerals. RESULTS It can be found that there are four types of organic matter in the Silurian Longmaxi Formation of Well Anye-1, i.e. bio-structural type, vein-like or clump-like type, euhedral and anhedral boundary filling gap shape. The euhdedral boundary filling gap shape has an organic aperture larger than 80nm, whereas the anhedral boundary filling gap shape has an organic aperture less than 60nm. These two types of organic matter are the main reservoir space of rock reservoirs, which account for more than 90%. Four types of organic matter have different thermal evolution degrees. Moreover, the Raman maturity ranges from 2.8% to 3.0%, which is calculated from the laser Raman surface scanning data. The proportion of Raman maturity of various organic matters to the total amount is consistent with the semi-quantitative statistical results observed by Field Emission Scanning Electron Microscopy. CONCLUSIONS The methods used in the experiments are effective in measuring the maturity of organic matter in highly evolved marine shale in China.

Due to differential treatment responses of patients to pharmacotherapy, drug development and practice in medicine are concerned with personalized medicine, which includes identifying subgroups of population that exhibit differential treatment effect. For time-to-event data, available methods only focus on detecting and testing treatment-by-covariate interactions and may not consider multiplicity. In this work, we introduce the Bayesian credible subgroups approach for time-to-event endpoints. It provides two bounding subgroups for the true benefiting subgroup: one which is likely to be contained by the benefiting subgroup and one which is likely to contain the benefiting subgroup. A personalized treatment effect is estimated by two common measures of survival time: the hazard ratio and restricted mean survival time. We apply the method to identify benefiting subgroups in a case study of prostate carcinoma patients and a simulated large clinical dataset.

BACKGROUND AnYe-1 well is a geological survey parameter well implemented by China Geological Survey. It has achieved shale gas breakthrough in the Wuling complex structural area outside the southern basin of China. BAOBJECTIVES To quantitatively characterize micro-and nano-pore structure and development characteristics of organic matter, by researching organic matter pore on Longmaxi shale of AnYe-1 well. METHODS Field Emission-Scanning Electron Microscope was used to study the reservoir type of the organic-rich shale of the Longmaxi Formation at the periphery of the basin in the Upper Yangtze region, and the PerGeos digital rock treatment system was introduced into the organic pores quantitative analysis. RESULTS The organic pore is the most important reservoir space of the organic-rich shale of the Longmaxi Formation in Anye-1 well. It is characterized by organic matter interstitially forming in the authigenic siliceous organic matter with uniform sponge-like pore structure, or organic matter that interacts with clay minerals with a bubble-like pore structure. Pores in two different types of organic matter are extremely developed. The PerGeos digital rock system reveals that the pore sizes of the two organic pores show a bimodal distribution, in which the pore size of the organic pores with the sponge-like structure is 5 to 10 nm, and the pore size of the organic pores with the bubble-like structure is 51 to 100 nm. The organic pores are mainly in the mesopore to macropore category. CONCLUSIONS The abundant development of organic matter pores in the Longmaxi Formation in AnYe-1 well indicates that the Longmaxi Formation shale in the periphery of the basin has experienced a strong hydrocarbon generation process and has a good storage capacity, showing a potential for development in the future.

Abstract Background Positron emission tomography (PET) is a molecular imaging technology that enables in vivo quantification of metabolic activity or receptor density, among other applications. Examples of applications of PET imaging in neuroscience include studies of neuroreceptor/neurotransmitter levels in neuropsychiatric diseases (e.g., measuring receptor expression in schizophrenia) and of misfolded protein levels in neurodegenerative diseases (e.g., beta amyloid and tau deposits in Alzheimer’s disease). Assessment of a PET tracer’s test-retest properties is an important component of tracer validation, and it is usually carried out using data from a small number of subjects. Results Here, we investigate advantages and limitations of test-retest metrics that are commonly used for PET brain imaging, including percent test-retest difference and intraclass correlation coefficient (ICC). In addition, we show how random effects analysis of variance, which forms the basis for ICC, can be used to derive additional test-retest metrics, which are generally not reported in the PET brain imaging test-retest literature, such as within-subject coefficient of variation and repeatability coefficient. We reevaluate data from five published clinical PET imaging test-retest studies to illustrate the relative merits and utility of the various test-retest metrics. We provide recommendations on evaluation of test-retest in brain PET imaging and show how the random effects ANOVA based metrics can be used to supplement the commonly used metrics such as percent test-retest. Conclusions Random effects ANOVA is a useful model for PET brain imaging test-retest studies. The metrics that ensue from this model are recommended to be reported along with the percent test-retest metric as they capture various sources of variability in the PET test-retest experiments in a succinct way.

Piezoelectric waveguide transducers possess great potential for the online monitoring of high temperature critical components, in order to improve their operational safety. Due to the use of a waveguide bar, the sensory device is not susceptible to high temperature environments, which enables the long-term service of the piezoelectric transducers. However, the coupling between the waveguide bar and the high-temperature component has been proven to be the most important part of the monitoring system. In order to effectively transmit waves through the junction of the waveguide bar and the monitoring target, it is necessary to research a reliable coupling method to connect the waveguide transducers with the host structure. In the present research, the feasibility of brazing coupling for wave propagation through the junction was investigated through experiments. Piezoelectric waveguide transducers were welded using various kinds of brazing filler metals. The experimental results indicate that the coupling effects of the brazing welding depend on the filler metals. At the same time, some filler metals for the effective coupling of the transducer and the target monitoring component were identified. The brazing coupling method was verified that it can non-dispersively and effectively propagate waves into the host structure with much better reliability than the conventional dry coupling approach. Moreover, the high-temperature experimental results show that the brazing-coupled waveguide bar system can work reliably and stably in high temperatures at 300 °C for a long time. This work strives to pave a solid foundation for the application of piezoelectric waveguide transducers for the structural health monitoring of high temperature critical components.

The objective of this study was to compare the scope and the discriminative power of Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) to those of semi-quantitative MRI scoring for evaluating treatments for rheumatoid arthritis (RA) in multicenter randomized clinical trials (RCTs). Sixty-one patients with active RA participated in a double-blind, parallel group, randomized, multicenter methodology study receiving infliximab or placebo through 14 weeks. The most symptomatic wrist and metacarpophalangeal joints (MCPs) were imaged using MRI. In addition to clinical assessments with DAS28(CRP), the severity of inflammation was measured as synovial leak of gadolinium based contrast agent (GBCA) using DCE-MRI (Ktrans, primary endpoint) at weeks 0, 2, 4, and 14. Two radiologists independently scored synovitis, osteitis and erosion using RA MRI Score (RAMRIS) and cartilage loss using a 9-point MRI scale (CARLOS). Infliximab showed greater decrease from baseline in DAS28(CRP), DCE-MRI Ktrans of wrist and MCP synovium, and RAMRIS synovitis and osteitis at all visits compared with placebo (p

BACKGROUND:Approximately 20% of the adult population suffer from chronic pain that is not adequately treated by current therapies, highlighting a great need for improved treatment options. To develop effective analgesics, experimental human and animal models of pain are critical. Topically/intra-dermally applied capsaicin induces hyperalgesia and allodynia to thermal and tactile stimuli that mimics chronic pain and is a useful translation from preclinical research to clinical investigation. Many behavioral and self-report studies of pain have exploited the use of the capsaicin pain model, but objective biomarker correlates of the capsaicin augmented nociceptive response in nonhuman primates remains to be explored. METHODOLOGY:Here we establish an aversive capsaicin-induced fMRI model using non-noxious heat stimuli in Cynomolgus monkeys (n = 8). BOLD fMRI data were collected during thermal challenge (ON:20 s/42°C; OFF:40 s/35°C, 4-cycle) at baseline and 30 min post-capsaicin (0.1 mg, topical, forearm) application. Tail withdrawal behavioral studies were also conducted in the same animals using 42°C or 48°C water bath pre- and post- capsaicin application (0.1 mg, subcutaneous, tail). PRINCIPAL FINDINGS:Group comparisons between pre- and post-capsaicin application revealed significant BOLD signal increases in brain regions associated with the 'pain matrix', including somatosensory, frontal, and cingulate cortices, as well as the cerebellum (paired t-test, p

Pre-clinical animal models are important to study the fundamental biological and functional mechanisms involved in the longitudinal evolution of heart failure (HF). Particularly, large animal models, like nonhuman primates (NHPs), that possess greater physiological, biochemical, and phylogenetic similarity to humans are gaining interest. To assess the translatability of these models into human diseases, imaging biomarkers play a significant role in non-invasive phenotyping, prediction of downstream remodeling, and evaluation of novel experimental therapeutics. This paper sheds insight into NHP cardiac function through the quantification of magnetic resonance (MR) imaging biomarkers that comprehensively characterize the spatiotemporal dynamics of left ventricular (LV) systolic pumping and LV diastolic relaxation. MR tagging and phase contrast (PC) imaging were used to quantify NHP cardiac strain and flow. Temporal inter-relationships between rotational mechanics, myocardial strain and LV chamber flow are presented, and functional biomarkers are evaluated through test-retest repeatability and inter subject variability analyses. The temporal trends observed in strain and flow was similar to published data in humans. Our results indicate a dominant dimension based pumping during early systole, followed by a torsion dominant pumping action during late systole. Early diastole is characterized by close to 65% of untwist, the remainder of which likely contributes to efficient filling during atrial kick. Our data reveal that moderate to good intra-subject repeatability was observed for peak strain, strain-rates, E/circumferential strain-rate (CSR) ratio, E/longitudinal strain-rate (LSR) ratio, and deceleration time. The inter-subject variability was high for strain dyssynchrony, diastolic strain-rates, peak torsion and peak untwist rate. We have successfully characterized cardiac function in NHPs using MR imaging. Peak strain, average systolic strain-rate, diastolic E/CSR and E/LSR ratios, and deceleration time were identified as robust biomarkers that could potentially be applied to future pre-clinical drug studies.

BACKGROUND: Pharmacological MRI (phMRI) is a neuroimaging technique where drug-induced hemodynamic responses can represent a pharmacodynamic biomarker to delineate underlying biological consequences of drug actions. In most preclinical studies, animals are anesthetized during image acquisition to minimize movement. However, it has been demonstrated anesthesia could attenuate basal neuronal activity, which can confound interpretation of drug-induced brain activation patterns. Significant efforts have been made to establish awake imaging in rodents and nonhuman primates (NHP). Whilst various platforms have been developed for imaging awake NHP, comparison and validation of phMRI data as translational biomarkers across species remain to be explored. METHODOLOGY: We have established an awake NHP imaging model that encompasses comprehensive acclimation procedures with a dedicated animal restrainer. Using a cerebral blood volume (CBV)-based phMRI approach, we have determined differential responses of brain activation elicited by the systemic administration of buprenorphine (0.03 mg/kg i.v.), a partial µ-opioid receptor agonist, in the same animal under awake and anesthetized conditions. Additionally, region-of-interest analyses were performed to determine regional drug-induced CBV time-course data and corresponding area-under-curve (AUC) values from brain areas with high density of µ-opioid receptors. PRINCIPAL FINDINGS: In awake NHPs, group-level analyses revealed buprenorphine significantly activated brain regions including, thalamus, striatum, frontal and cingulate cortices (paired t-test, versus saline vehicle, p

This paper presents an R package for magnetic resonance imaging (MRI) tissue classification. The methods include using normal mixture models, hidden Markov normal mixture models, and a higher resolution hidden Markov normal mixture model fitted by various optimization algorithms and by a Bayesian Markov chain Monte Carlo (MCMC) method. Functions to obtain initial values of parameters of normal mixture models and spatial parameters are provided. Supported input formats are ANALYZE, NIfTI, and a raw byte format. The function slices3d in misc3d is used for visualizing data and results. Various performance evaluation indices are provided to evaluate classification results. To improve performance, table lookup methods are used in several places, and vectorized computation taking advantage of conditional independence properties are used. Some computations are performed by C code, and OpenMP is used to parallelize key loops in the C code.