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In order to achieve low-cost, non-radiation imaging inspection of lithium-ion pouch cell, a new in situ imaging detection method based on guided waves for thin lithium-ion pouch cell was proposed in this paper. According to the propagation theory of ultrasonic guided wave in plate, the propagation of guided waves in a thin lithium-ion pouch cell was analyzed. A guided wave imaging detection system for lithium-ion pouch cell was built up and a pouch cell lithium-ion battery with a thickness of 3.5 mm in a fully charged state was used as the specimen. A piezoelectric transducer was used to excite guided waves, and a scanning laser Doppler vibrometer (SLDV) was used to collect three-dimensional wave field matrix. In the obtained transient guided wave field diagram, there were phenomena such as wavefront lag, irregular patterns, and scattered irregular dots, and a defect of size 22 × 18 mm2 was also identified. Analysis of the mode conversion during the guided wave propagation in the battery reveals that the energy spectrum imaging of main mode can achieve the same effect as the transient guided wave imaging, and reduces the time of the selection moment. The imaging detection method in this paper was the first attempt of ultrasonic guided wave in the in situ imaging of lithium-ion battery.

In this paper, the model of SiC reinforced superalloy composite with different fiber content is established by Monte Carlo simulation method. The process of hot isostatic pressing of SiC reinforced superalloy composite is simulated, and the residual stress distribution under different fiber content is obtained. The results show that not only the fiber content has a great influence on the residual stress of hot isostatic pressing of SiC reinforced superalloy composite, but also the fiber distribution has a great influence on the residual stress. It is necessary to establish a finite element model of different fiber distribution to simulate the process of hot isostatic pressing of SiC reinforced superalloy composite.

In this paper, the residual stress of SiC-reinforced GH4738 composites processed by hot isostatic pressing was studied using the finite element method. First, the unit cells with different fibers and uniform fiber content were constructed using Abaqus. Then, the pressure and temperature conditions were considered, and hot isostatic pressing process was simulated. The residual stresses of different unit cells were obtained, and the effect of the cell form on the residual stress of the SiC-reinforced GH4738 composites was analyzed. Finally, the maximum residual stresses of different unit cells were compared, and the effects of the simulation methods and models were discussed. The results show that different cell types have little effect on the maximum residual stress with the maximum deviation of approximately 20%, and the differences between most cells of less than 5%. The cell stress distributions in different forms are affected by the distribution of the fibers, and the maximum residual stress appears at the interface between the fiber and the matrix.

Ni-based catalysts have been extensively employed in the CO2 reforming of methane because of its superior activity, low cost, and exhaustive availability. The Ce, Zr or co-doped flower-like NiO-MgO solid solution catalysts, covered by (111) facets, were prepared by applying the solvothermal synthesis method in the CO2 reforming of methane. The high surface energy of (111) facets in the NiO-MgO solid solution contributed to the prominent reactivity. The addition of Ce and Zr into Ni0.1Mg0.9O (111) resulted in enhanced activity and coke resistance. It did this by providing a smaller nickel particle size due to stronger interactions, and an increase in surface oxygen species which improves the CO2 adsorption capacity. The Ce/Zr co-doped catalyst, possessing a molar ratio of 0.01:0.01, exhibited the highest catalytic activity and long-term stability.

Purpose While HER2 testing is well established in directing appropriate treatment for breast cancer, a small percentage of cases show equivocal results by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Alternative probes may be used in equivocal cases. We present a single community-based institution’s experience in further evaluating these cases. Patients and methods Between 2014 and 2016, 4255 samples were submitted for HER2 amplification testing by alternative probes, TP53, RAI1, and RARA. Of the patients tested by FISH, 505/3908 (12.9%) also had IHC data. Results Most (73.9%) FISH equivocal cases remained equivocal after IHC testing. However, 50.5% of equivocal cases were classified as HER2 amplified by alternative probes. Most cases were positive by more than one probe: 78% of positive cases by RAI1 and 73.9% by TP53. There was a significant difference between IHC and FISH alternative testing (p

// Maher Albitar 1 , Sucha Sudarsanam 1 , Wanlong Ma 1 , Shiping Jiang 1 , Wayne Chen 1 , Vincent Funari 1 , Forrest Blocker 1 and Sally Agersborg 1 1 NeoGenomics Laboratories, Aliso Viejo, CA, USA Correspondence to: Maher Albitar, email: maher.albitar@neogenomics.com Keywords: NSCLC; PD-L1; EGFR; MET; TP53 Received: October 06, 2017 Accepted: January 09, 2018 Published: February 08, 2018 ABSTRACT Background: The role of MET amplification in lung cancer, particularly in relation to checkpoint inhibition and EGFR WT, has not been fully explored. In this study, we correlated PD-L1 expression with MET amplification and EGFR , KRAS , or TP53 mutation in primary lung cancer. Methods: In this retrospective study, tissue collected from 471 various tumors, including 397 lung cancers, was tested for MET amplification by FISH with a MET /centromere probe. PD-L1 expression was evaluated using clone SP142 and standard immunohistochemistry, and TP53 , KRAS , and EGFR mutations were tested using next generation sequencing. Results: Our results revealed that PD-L1 expression in non-small cell lung cancer is inversely correlated with EGFR mutation (P=0.0003), and positively correlated with TP53 mutation (P=0.0001) and MET amplification (P=0.004). Patients with TP53 mutations had significantly higher MET amplification (P=0.007), and were more likely (P=0.0002) to be EGFR wild type. There was no correlation between KRAS mutation and overall PD-L1 expression, but significant positive correlation between PD-L1 expression and KRAS with TP53 co-mutation (P=0.0002). A cut-off for the ratio of MET : centromere signal was determined as 1.5%, and 4% of lung cancer patients were identified as MET amplified. Conclusions: This data suggests that in lung cancer both MET and TP53 play direct roles in regulating PD-L1 opposing EGFR . Moreover, KRAS and TP53 co-mutation may cooperate to drive PD-L1 expression in lung cancer. Adding MET or TP53 inhibitors to checkpoint inhibitors may be an attractive combination therapy in patients with lung cancer and MET amplification.

The safety of lithium-ion batteries (LIBs) remains the focus of engineering and scientific attention as its bending failure cannot be monitored by conventional means such as voltage and temperature due to its special failure mechanism. Therefore, it is of great significance to study the mechanical properties and failure mechanisms of LIBs during bending failure. In this paper, 18,650 LIBs are taken as the research object, and an in-situ experimental platform based on acoustic emission (AE) and three-dimensional digital image correlation (3D-DIC) methods is built to study the mechanical properties and failure mechanisms of LIBs in different states of charge (SOC) under bending loads. The results show that the bending modulus and stiffness of the battery increase with the increase of SOC. The main types of damage and the expansion process of the battery during the bending failure process are also obtained. The research results provide a theoretical basis for research on the bending failure of LIBs. Meanwhile, the experimental platform built in this article solves the failure of previous monitoring methods, including deformation and temperature during the bending failure of LIBs. In addition, this paper provides a new method for in-situ monitoring of LIBs.

Self-healing concrete designs can protect against deterioration and improve durability. However, there is no unified conclusion regarding the effective preparation and mechanical properties of self-healing concrete. In this paper, microcapsules are used in cement-based materials, the reasonable dosage of microcapsules is determined, and the self-healing performance of the microcapsule self-healing system under different curing agents is explored. The microcapsules and curing agent are shown to enhance the flexural and compressive strength of mortar specimens at relatively low contents. The optimal microcapsule content in terms of compressive strength is 1–3%. When the content of the microcapsule reaches 7%, the strength of the specimen decreases by approximately 30%. Sodium fluorosilicate is better-suited to the microcapsule self-healing cement-based system than the other two fluorosilicates, potassium fluorosilicate and magnesium, which have similarly poor healing performance as curing agents. Healing time also appears to significantly influence the microcapsule self-healing system, mortar specimens that healed for 28 days are significantly higher than those that healed for 7 days. This work may provide a valuable reference for the design and preparation of self-healing cementitious composite structures.

With the development of new energy technology, lithium-ion battery, as a common energy storage and driving structure, has been widely used in many fields. It is significant to accurately monitor and evaluate the state of charge (SOC) and state of health (SOH) of lithium-ion battery. This paper presents the estimation method of SOC and SOH of lithium-ion battery based on ultrasonic guided wave technology. In the experiment, the guided wave signals are activated by a single fixed piezoelectric transducer and the propagating guided waves are rapidly captured using a scanning laser Doppler vibrometer system. The multi-parameter analysis of the direct wave signals including time-domain, frequency-domain and time-frequency distribution are performed, and thus three guided-wave parameters, namely signal amplitude, time of flight and power spectral density connected with the charge discharge cycle and aging of battery, are successively set to comprehensively evaluate SOC/SOH of lithium-ion battery. The results show that the guided wave parameters in time-domain, frequency-domain and time-frequency distribution have well consistent correspondence with SOC/SOH, and the differential curve analysis of signal amplitude can effectively reflect the phase transitions in the charge-discharge cycle and the aging process. In addition, the sensitivity of ultrasonic guided wave technology to estimation of SOC/SOH gradually decreases with the battery aging.

The interaction mechanisms of dry reforming of methane, especially in the part of CO 2 activation on the reduced NiO-MgO catalyst, have been systematically investigated by in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and density functional theory (DFT) calculations. Based on the results, it is indicated that, what more favorable for CO generation is gaseous CO 2 reaction with deposited C intermediates, namely E-R type mechanism, rather than CO 2 direct dissociation to form CO and atomic O. In addition, with the help of H species, monodentate carbonate, which derives from the adsorbed CO 2 on the MgO surface, can be also activated and hydrogenated dissociation to generate CO.

Background: A cost effective and comprehensive genomic profiling (CGP) approach for diagnosis, risk stratification and therapy would be useful for the evaluation of oncologic specimens. Available approaches involving additive testing for DNA and RNA abnormalities through traditional methods (e.g. Sanger, FISH, cytogenetics, qRT-PCR) are not comprehensive, require multiple different workflows and are sample consuming, often resulting in incomplete testing. While there are next generation sequencing (NGS) assays designed for detecting DNA and RNA abnormalities, they have separate workflows that require twice the amount of sample and effort. To address this, we developed a novel total nucleic acid (TNA) extraction method and single tube workflow utilizing TNA and a custom multimodal chemistry designed for hematologic malignancies. This consolidated workflow enables an efficient discovery based approach for both DNA/RNA abnormalities including single nucleotide variants (SNVs), InDels, copy number variants (CNVs), large structural changes from DNA and gene fusions and gene expression levels from RNA. This method maximizes data derived from valuable samples while delivering a comprehensive profile of the patient's tumor which can help guide therapeutic and clinical decisions. Methods: Total nucleic acid (TNA) was extracted from bone marrow and peripheral blood of 95 patients (CML, CMML, CLL, AML and myeloid disorders). 297 genes that have DNA mutations specific to hematological cancers were targeted, along with 213 genes that were targeted for clinically significant RNA abnormalities. Enriched genomic and transcriptomic regions of interest from 85 patients were successfully sequenced with unique dual indices on an Illumina NovaSeq 6000. DNA variant detection as well as fusion detection from RNA were compared to traditional orthogonal NGS assays that use DNA input or compared to qRT-PCR and Sanger sequencing assays that use RNA as input. Results: In this study, we developed an efficient and high-quality TNA extraction method that can purify enough total nucleic acid from bone marrow, peripheral blood, cytogenetic pellets, flow suspension, and FFPE samples for the downstream NGS assay. The average OD 260/280 value was 1.9 and the OD 260/230 was 2.18. After sequencing, 256/262 (97.7% accuracy) SNV and Indel variants that were candidate pathogenic mutations were concordant from 38 patients. Meanwhile, 100% (7/7) of all BCR/ABL1 gene fusions which had an international scale (IS) value above 6.4% were concordant. In addition, 69 fusion positive samples containing 20 unique gene fusions which had been previously reported by an independent ArcherDX assay designed specifically for gene fusions were also evaluated with this chemistry. Analysis revealed a 92.5% (64/69) concordance. More importantly, the QIAseq multimodal TNA NGS assay detected both DNA and RNA abnormalities in a single tube. For example, in one myeloid leukemia patient, we not only identified pathogenic variants of ASXL1 and JAK2 which had been previously detected by a DNA NGS assay, but also detected a concurrent BCR-FGFR1 fusion which had been previously reported by a FISH assay. Moreover, we were able to provide more comprehensive genomic profiling by investigating many DNA and RNA abnormalities simultaneously. In our study, for 5 patients that previously been tested for BCR-ABL1 fusion only, we are able to assess BCR-ABL1 fusion status from RNA as well as identify pathogenic DNA variants at the same time, including JAK2 p.V617F, U2AF1 p.S34F, ASXL1 p.E635Rfs*15, BRCA p.S1982Rfs*22, and DNMT3A p.S708Vfs*71, which provides valuable information to assist diagnosis and treatment in a cost effective and efficient way. Conclusions: We developed a single tube TNA based workflow with a custom multimodal chemistry that simultaneously detects many DNA and RNA abnormalities in a cost effective and efficient way while reducing sample requirements. This unique TNA NGS assay provides comprehensive genomic profiling for hematologic malignancies and improves the diagnostic testing options for precise patient care. Disclosures Yu: NeoGenomics: Current Employment. Alarcon:NeoGenomics: Current Employment. Mou:NeoGenomics: Current Employment. Jung:NeoGenomics: Current Employment. Nam:NeoGenomics: Current Employment. Thomas:NeoGenomics: Current Employment. Keeler:NeoGenomics: Current Employment. Shinbrot:NeoGenomics: Current Employment. Magnan:NeoGenomics: Current Employment. Bender:NeoGenomics: Current Employment. Jiang:NeoGenomics: Current Employment. Agersborg:NeoGenomics: Current Employment. Weiss:Bayer: Other: speaker; Genentech: Other: Speaker; Merck: Other: Speaker; NeoGenomics: Current Employment. Ye:NeoGenomics: Current Employment. Funari:NeoGenomics: Current Employment.

Echinococcosis is a serious parasitic disease caused byEchinococcustapeworms. Protoscoleces are sometimes released during surgical treatment for hydatid cysts, causing the recurrence of echinococcosis. Protoscoleces may be susceptible to radiation therapy. In this studyEchinococcusprotoscoleces were culturedin vitroand then divided into four differentγ-ray irradiation dose groups (10 Gy, 20 Gy, 40 Gy, and 80 Gy) and a blank group. The protoscoleces were then implanted into the abdominal cavity of mice. Four months later, we observed that the incidence and weight of cysts declined with the increase of irradiation dose.γ-ray irradiation can suppress the generation ofEchinococcusoriginated from protoscolex, the reason of which is due to the damaging to the structure ofEchinococcus. Irradiation may prevent echinococcosis recurrence after surgical removal of hydatid cysts.

In this paper, the residual stresses in hot isostatic pressed SiC/GH4738 composites were investigated using numerical simulation. First, the finite element model of the SiC/GH4738 composites was built using ABAQUS. Then, the hot isostatic press process was simulated, where the paths of temperature and pressure were considered. The residual stress distributions were obtained, and the changes in interfacial residual stresses with angle were analyzed. Finally, the effect of process parameters on residual stresses was analyzed. The simulation results show that maximum temperature, holding time, and fiber volume content have little influence on the distribution of interface residual stress but have great influence on the magnitude of interfacial residual stress. The results will help to influence the design and preparation of SiC/GH4738 composites.

In this paper, the mechanical properties of 3D printed PLA lattice structures were studied using digital image correlation (DIC), and the effect of process parameters on the mechanical properties of the samples was discussed. First, tensile samples and lattice structures of the PLA were prepared by Fused Deposition Modeling (FDM). Then the tensile experiments were carried out on the tensile samples, and the tensile strength and elastic modulus were obtained. Moreover, the compressive experiments were carried out on the 3D printed PLA lattice structures, and the yield strength, plastic platform stress and densification strain were obtained. The full field displacements and strains were obtained using DIC. Finally, scanning electron microscope (SEM) was used to study the cross-section of the sample, and the mechanism of the influence of process parameters on the sample was analyzed. The experimental results show that as the printing temperature increases, the tensile strength and elastic modulus tend to rise first and then decrease. When the printing temperature is 230 °C, the maximum tensile strength is 50.16 MPa, and the tensile elastic modulus is 4340.38 MPa. While the yield strength, plastic platform stress and densification strain of lattice structures show a downward trend. As the printing speed increases, the tensile strength and elastic modulus show an upward trend, and when the printing speed is 60 mm/min, the tensile strength and elastic modulus are 51.47 MPa and 5102.12 MPa respectively. Moreover, the yield strength, plastic platform stress of lattice structures show a downward trend, densification strain show an upward trend.

Mechanical damage to lithium-ion batteries (LIBs) has always been a key problem in the practical application of LIBs. It is a hazard if LIB deformation and damage processes cannot be detected in time. In this paper, the acoustic emission (AE) technique was applied to monitor the 18,650 LIB three-points bending failure process, which solved the ineffective voltage monitoring problem in the 18,650 LIB three-points bending failure process. The acquired AE signals were analyzed in the time domain and also via factor analysis (FA) and the fuzzy clustering method (FCM). The characteristics of the AE signals of various damage types throughout the entire bending process of the 18,650 LIB, as well as the expansion of the various damage types throughout the entire bending failure process, were obtained. Results showed that the AE technique effectively monitored the entire mechanical failure process of LIBs and that the FA and FCM were effective at studying the mechanical damage types of LIBs as well as the expansion processes of various damage types.

We report on mechanical properties of blue phosphorus nanotubes (BluePNTs) from systematic molecular dynamics simulations, adopting a Stillinger-Weber potential with parameters determined by fitting to energetic and structural data from first-principles calculations. Our results corroborate the previously reported bending poison effect and size-dependent buckling behaviors. Under axial compression, current simulations predict a shell-to-column buckling mode transition for BluePNTs with increasing aspect ratios; further compression of BluePNTs with large aspect ratios results in a column-to-shell buckling mode transition. Associated critical buckling strains can be described by the continuum mechanics theory. We also simulated buckling behavior of black phosphorus nanotubes (BlackPNTs) and found that the buckling modes of BluePNTs exhibit much less chirality dependence compared to BlackPNTs, stemming from subtle structural differences between these two closely related yet distinct systems. The present results offer insights into key structural and mechanical properties of BluePNTs for fundamental understanding and potential applications of this relatively new member of the large and diverse nanotube family of materials.

Background The role of MET amplification in lung cancer, particularly in relation to checkpoint inhibition and EGFR WT, has not been fully explored. In this study, we correlated PD-L1 expression with MET amplification and EGFR, KRAS, or TP53 mutation in primary lung cancer. Methods In this retrospective study, tissue collected from 471 various tumors, including 397 lung cancers, was tested for MET amplification by FISH with a MET/centromere probe. PD-L1 expression was evaluated using clone SP142 and standard immunohistochemistry, and TP53, KRAS, and EGFR mutations were tested using next generation sequencing. Results Our results revealed that PD-L1 expression in non-small cell lung cancer is inversely correlated with EGFR mutation (P=0.0003), and positively correlated with TP53 mutation (P=0.0001) and MET amplification (P=0.004). Patients with TP53 mutations had significantly higher MET amplification (P=0.007), and were more likely (P=0.0002) to be EGFR wild type. There was no correlation between KRAS mutation and overall PD-L1 expression, but significant positive correlation between PD-L1 expression and KRAS with TP53 co-mutation (P=0.0002). A cut-off for the ratio of MET: centromere signal was determined as 1.5%, and 4% of lung cancer patients were identified as MET amplified. Conclusions This data suggests that in lung cancer both MET and TP53 play direct roles in regulating PD-L1 opposing EGFR. Moreover, KRAS and TP53 co-mutation may cooperate to drive PD-L1 expression in lung cancer. Adding MET or TP53 inhibitors to checkpoint inhibitors may be an attractive combination therapy in patients with lung cancer and MET amplification.

Background: Noni juice has been extensively used as folk medicine for the treatment of arthritis, infections, analgesic, colds, cancers, and diabetes by Polynesians for many years. Due to the lack of standard scientific evaluation methods, various kinds of commercial Noni juice with different quality and price were available on the market. Objective: To establish a sensitive, reliable, and accurate high-performance liquid chromatography with electrospray ionization triple quadrupole mass spectrometry (HPLC-ESI-MS/MS) method for separation, identification, and simultaneous quantitative analysis of bioactive constituents in Noni juice. Materials and Methods: The analytes and eight batches of commercially available samples from different origins were separated and analyzed by the HPLC-ESI-MS/MS method on an Agilent ZORBAX SB-C18 (150 mm × 4.6 mm i.d., 5 μm) column using a gradient elution of acetonitrile-methanol-0.05% glacial acetic acid in water (v/v) at a constant flow rate of 0.5 mL/min. Results: Seven components were identification and all of the assay parameters were within the required limits. Components were within the correlation coefficient values (R2 ≥ 0.9993) at the concentration ranges tested. The precision of the assay method was

PURPOSE While HER2 testing is well established in directing appropriate treatment for breast cancer, a small percentage of cases show equivocal results by IHC and FISH. Alternative probes may be used in equivocal cases. We present a single community-based institution's experience in further evaluating these cases. PATIENTS AND METHODS Between 2014-2016, 4255 samples were submitted for HER2 amplification testing by alternative probes, TP53, RAI1, and RARA. Of patients tested by FISH, 505/3908 (12.9%) also had IHC data. RESULTS Most (73.9%) FISH equivocal cases remained equivocal after IHC testing. Duplicate testing by IHC using a different paraffin block resulted in poor reproducibility as 44% of IHC negative became equivocal and 40% of IHC equivocal became negative. Of the equivocal cases by IHC, 52.3% became positive by alternative FISH. However, 50.5% of cases equivocal by conventional FISH were classified as HER2 amplified by alternative probes. Most cases were positive by more than one probe; 78% of positive cases were positive by RAI1 and 73.9% by TP53. There was a significant difference between IHC and FISH alternative testing (P CONCLUSION The prevalence of double HER2 equivocal cases and the discrepancy between IHC and alternative FISH testing suggest that FISH alternative testing using both RAI1 and TP53 probes is necessary for conclusive classification. Due to the significant difference between IHC repeat testing, reflexing on IHC alone in this group of cases may not be reproducible. Because almost half of FISH equivocal cases converted to HER2 amplified upon alternative testing, clinical studies to determine benefit of anti-HER2 therapy in these patients is urgently needed. Alternative FISHIHC Score 0 NegativeIHC Score 1 NegativeIHC Score 2 EquivocalIHC Score 3 PositiveNo%No%No%No%Negative1463.65454.517847.7436.4Positive836.44545.519552.3763.6Total22100.099100.0373100.011100.0 Citation Format: Sally Agersborg, Christopher Mixon, Thanh Nguyen, Sramila Aithal, Forrest Blocker, Lawrence Weiss, Robert Gasparini, Shiping Jiang, Wayne Chen, Gregory Hess, Maher Albitar. Immunohistochemistry and alternative FISH testing in breast cancer with HER2 equivocal amplification [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4524.

e15604Background: Microsatellite instability (MSI) and DNA mismatch repair defect (dMMR) are dependable predictive biomarkers of colorectal cancer (CRC) response to checkpoint inhibitors. We explor...

3022Background: DNA mismatch repair deficiency (dMMR) can be tested by immunohistochemistry (IHC) or microsatellite instability (MSI). While either IHC and MSI is adequate for establishing Lynch sy...

To study the early change of bone matrix and soft tissue around articulation in adjuvant-induced arthritic (AIA) rats non-invasively by X-ray phase-contrast imaging (XPCI), a new imaging method.Adjuvant-induced arthritis was established in male Sprague-Dawley (SD) rats (n=6, age 40 days) by subcutaneous injection of Freund's complete adjuvant (FCA) into the left hindpaw. In vivo XPCI evaluation of the early soft tissue and bone changes in AIA rats was consecutively performed and correlated with changes in volumes of right hindpaws and body weights. In comparison, the changes in the AIA rats were also evaluated with absorption-contrast imaging using the same X-ray source as XPCI and conventional radiography at the same time. After the imaging evaluation, AIA rats were subjected to histological examination.There was significant difference between the score of XPCI and the other two methods in demonstrating soft tissue (P0.01), bone details (P0.01) and lesions (P0.001). By day 10 after subcutaneous injection of FCA, bone changes in the right hindpaw were not obvious, but swelling of soft tissue appeared. By day 12, bone erosion in the articular facet and the area around the articular facet, was detected, along with osteoporosis, and swelling of soft tissue was aggravated. By day 14 bone erosions became fused and expanded, especially in the margin area around the articular facet. At day 16 bone erosion still existed. Joint interspaces seemed wider than normal, and swelling of soft tissue was significant. By day 18 periosteal new bone formation was seen definitely, destruction of bone decreased, bone density around the articular was enhanced, and swelling of soft tissue was relieved. XPCI could clearly distinguish all these alterations, which could not be demonstrated by absorption-contrast imaging and conventional radiography. During the test period, the volume of the right hindpaw and the body weight of the AIA rats also changed significantly compared with the normal rat. Histological examination confirmed that adjuvant-induced arthritis had occurred in all rats of the adjuvant group.Osteoporosis, bone erosion and periosteal new bone formation take place at the early stage of adjuvant-induced arthritis. XPCI can evaluate non-invasively these subtle bone changes that are "blind areas" for conventional radiography.

Introduction: MET gene activation has been reported to be associated with resistance to EGFR inhibitors in lung cancer. Resistance to EGFR inhibitors is also reported to be associated with upregulation of PD-L1. We studied PD-L1 expression levels with MET gene amplification and mutation in EGFR, KRAS, or TP53 in a large number of primary untreated lung cancers. Methods: Tissue samples collected from 397 core biopsies or resections from lung cancers were studied for MET gene amplification by fluorescent in-situ hybridization (FISH) using MET (7q31) probe and centromere 7 as a control. Signals were quantified. PD-L1 expression on the same samples was evaluated using clone SP142 and standard immunohistochemistry (IHC) procedure. Samples were also sequenced using next generation sequencing (NGS) for mutations in TP53, KRAS, and EGFR. Results: PD-L1 expression was detected in 166 patients (42%). Twenty seven (7%) had expression between 1% and 5%, 61 (15%) between 1% and 20%, 92 (23%) between 1% and 50%, and 105 (26%) had PD-L1 > 50% in tumor cells. Ratio of MET: centromere signals was > 1.5 in 16 (4%) of patients. Patients with MET ratio > 1.5% had significantly higher (P=0.004) percentage of PD-L1 as a continuous variable as well as when cut-off points of 5% (P=0.01), 20% (P=0.0006), and 50% (P=0.01) were used. Patients with EGFR mutation had significantly lower levels of PD-L1 expression (P=0.003). When a cut-off point of 50% is used for PD-L1 expression, the EGFR-mutant cases had significantly less number of positive cases (P=0.0003). There was no correlation between the presence of High MET: Ratio and EGFR mutation. There was no correlation between KRAS mutation and overall PD-L1 expression (P=0.4). There was no correlation between MET ratio and KRAS mutation. Patients with TP53 mutation had significantly higher MET ratio when a cut-off at 1.5 is used (P=0.01). Also there was significant correlation between TP53 mutation and overall PD-L1 expression (P=0.0001). This remained significant when cut-off point of 50% or 5% are used (P=0.0004 and P=0.007, respectively). TP53 mutation was significantly more common in EGFR wild-type cases (P=0.0002). Conclusions: Extra copies of MET gene as detected by FISH testing in therapy-naïve lung cancer patients is associated with higher expression of PD-L1, while EGFR-mutant lung cancers had significantly lower expression of PD-L1 when clone SP142 is used and NGS is used for detecting EGFR mutations. Patients with TP53 mutation had strikingly high expression of PD-L1 using SP142 clone and higher copy number of MET gene. This data suggests that in lung cancer, both MET and TP53 genes play a direct role in regulating PD-L1 expression opposing the EGFR gene, which appears to suppress PD-L1 expression. KRAS gene may not be involved in PD-L1 expression in lung cancer. Citation Format: Maher Albitar, Sucha Sudarsanam, Wanlong Ma, Shiping Jiang, Wayne Chen, Vincent Funari, Steven Brodie, Sally Agersborg. Correlation between MET gene amplification and TP53 mutation in upregulating PD-L1 expression in EGFR wild-type lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5618. doi:10.1158/1538-7445.AM2017-5618

e14500 Background: PD-L1 expression as detected by immunohistochemistry (IHC) is significantly lower in colorectal cancers (CRC) when compared with lung cancer or other types of cancer. We explored if mutations in the RAS/RAF gene family, TP53 or PIK3CA can define a subgroup of CRC that express PD-L1. Methods: Tissue samples collected from 107 patients with CRC were studied for the expression of PD-L1 using clone SP142. The same samples were also tested for mutations in NRAS, KRAS, HRAS, BRAF, TP53, and PIK3CA using Next Generation Sequencing (NGS). Results: Of the 107 CRC samples only 15 (14%) showed PD-L1 positive tumor cells (≥1%) and 8 of the 15 (7.5% of total) had PD-L1 in ≤5% of tumor cells. Detected mutations in these samples were as follows: TP53 65%, KRAS 49.5%, PI3KCA 22.5%, NRAS 5%, HRAS 1%, and BRAF 17%. There was no correlation between PD-L1 expression and mutation status in any of the RAS/RAF genes. There was also no correlation between TP53 mutation and PD-L1 expression. This was true irrespective if PD-L1 expression is considered as a continuous variable or when cut-off points of 5%, 20%, or 50% were used. However, patients without any mutation in RAS or TP53 had significantly (P = 0.005) more expression of PD-L1 when cut-off point of 5% is used. This remained true if PD-L1 expression is considered as a continuous variable (P = 0.04). There was no correlation between PIK3CA and PD-L1 expression. Conclusions: PD-L1 expression is significantly more common in CRC that lack mutations in RAS or TP53. PD-L1 expression is detected in 31% of patients with wild-type RAS/TP53 as compared with 12% in patients with RAS/TP53 mutations (P = 0.04). If a cut-off point of 5% is used, 31% of RAS/TP53-wild-type CRC were positive for PD-L1, while only 6% of RAS/TP53- mutant CRC were positive for PD-L1 (P = 0.005). This suggests that in CRC without RAS/TP53 mutation, the PD-L1 may play a more important role in oncogenesis. Exploring immunotherapy in this group of CRC patients might be justified.

e21050 Background: BRAF mutation and PD-L1 expression appear independent in melanoma. We have established that PD-L1 clones 22C3 and 28.8 show almost identical results. In this study we correlated between BRAF mutation and PD-L1 expression as detected by 22C3/28.8 and SP142 in melanoma clinical samples. Methods: Melanoma samples were tested for PD-L1 expression and BRAF mutation. IHC testing for PD-L1 22C3 or 28.8 were tested using FDA-approved kits as recommended. Testing with SP142 (Spring Biosciences; LDT) was performed using standard techniques. BRAF testing in combination with SP142 PD-L1 testing was performed using next generation sequencing covering exons 11 and 15. Samples tested with 22C3 and 28.8 clones were tested using FDA-cleared BRAF kits (Cobas, Therascreen) testing V600 only. Results: 68 samples were tested for PD-L1 expression with clone 22C3, 67 with 28.8, and 56 with SP142. There was no overall statistical difference between the three clones in PD-L1 expression (P = 0.41). For combined 22C3 and 28.8, 61 of 135 cases (45%) had PD-L1 expression and 31 (23%) had BRAF mutation detected using FDA kits (V600). There was no statistical correlation between PD-L1 expression and BRAF mutation in this group (P = 0.9) at any cut-off. In cases tested with SP142 clone, BRAF mutation was detected in 31 cases (55%) by NGS, higher than using the FDA kit (P < 0.0001). In V600 mutations by NGS, 14 cases (25%) were positive, similar FDA kits. In SP142 cases, PD-L1 was positive in 45% of cases. There was no correlation between BRAF mutation and PD-L1 using SP142 expression as a continuous variable (P = 0.59) or cut-off points of 5% or 50%. When cut-off of 20% was used, significant inverse correlation with BRAF mutation (P = 0.004) was identified and was maintained if V600 codon only was evaluated. Conclusions: There is no correlation between BRAF mutation and PD-L1 expression as detected using clones 22C3 and 28.8. With SP142, a negative correlation between PD-L1 expression and BRAF mutation is identified with a 20% cut-off. The rate of BRAF mutations practically doubles when NGS is used and exons 11 and 15 are included in the testing, in contrast to FDA approved testing.

The adsorption behavior of a polynaphthalenesulfonate (PNS) superplasticizer and its relation to the fluidity of cement paste has been investigated for six cements at a given dosage of PNS superplasticizer. The results show that incompatible cements have a higher adsorption capacity of PNS superplasticizer because of a lack of soluble alkali sulfates. There is an inverse relationship between the amount of PNS adsorbed and the mini-slump area value of the cement pastes at 30 min, that is, the higher the amount of PNS adsorbed, the lower the initial slump value, and the higher the slump loss. The addition of some Na2SO4 contributes to increase the slump area by reducing the amount of PNS adsorbed. Moreover, it has been found that additional calcium sulfate does not prevent the adsorption of PNS on cement particles as sodium sulfate does in cement pastes having W/C=0.35. The contribution of alkali sulfate on dispersing mechanism of PNS superplasticized cement pastes is explained in relation with initial slump and its loss.

The effect of soluble alkalis on cement/superplasticizer compatibility has not yet been thoroughly understood. This paper establishes the impact that soluble alkalis have on the compatibility of cement and polynaphthalene sulfonate superplasticizer during the first few minutes of hydration. The amount of soluble alkalis that go into solution during the first few minutes is a key parameter in controlling fluidity and fluidity loss of a cement paste made with superplasticizer. The optimum soluble alkali content for increasing initial fluidity and decreasing fluidity loss with time was found to be on the order of 0.4%–0.5% Na 2 O equivalent in the six cements under study. Furthermore, this optimum alkali content is independent of the superplasticizer dosage and cement type. In cement with an optimum amount of soluble alkalis, the C 3 A content has practically no effect on fluidity loss.

e15064Background: Current recommendations for colorectal cancer testing include KRAS and NRAS for anti-EGFR therapy, and BRAF mutational analysis with microsatellite instability (MSI) testing for p...

e23146Background: Companion diagnostic tests are currently recommended for the prescription of multiple therapeutic agents in oncology. Most of these companion tests are FDA-cleared kits. We compar...

11557Background: Expression of PD-L1 is, in general, associated with response to immunotherapy. However, it is believed that additional intrinsic factors play a role in determining the potential of...

The degradation rate of lignin was studied directly by ultrasonic radiation. The effects of ultrasonic power and initial concentrations were investigated. The results showed that the degradation rate of lignin increased with the decrease of initial concentrations, but it increased with the increase of ultrasonic power. At the same time, the degradation of lignin was studied by FTIR spectrum for functional groups measurement and the results showed the degradation was mainly because the ruptures of aromatic skelete.

The cell killing abilities of soft X-rays on and off the oxygen K-shell edges on yeast cells have been investigated using a micrometer soft X-ray microprobe from synchrotron radiation. The dose depositions at different X-ray energies in the cell were discussed. At the same time, the cells were irradiated by 60 Co gamma-rays and the abilities in inducing yeast cell killing were compared with those produced by soft X-rays. The results showed that soft X-rays on and off the O K edge had higher ability of radiation damage than 60 Co gamma-rays. The total killing abilities of the three soft X-rays on yeast cells were almost similar and the differences of the X-rays in inducing yeast cell killing on and off the O K edge were not obvious.

“Water window” soft X-ray has some advantages in the microimaging of biological specimens. Soft X-ray holography can give us three-dimensional images of biological cells in their natural condition. Quasi-monochromatic soft X-ray from the pdymonochromatic synchrotron radiation is obtained by a zone plate-pinhole linear monochromator at National Synchrotron Radiation Laboratory (NSRI,) at Hcfei. The pinhole is used to increase the temporal coherence of the soft X-ray. and also to increase the spatial coherence of it. An in-line holographic experiment has been finished with soft X-ray of main wavelength 4.5 nm and pinhole of diameter 0.03 mm. The magnified hologram is recowtructed with He-Ne laser. A smaller pinhole is wanted to be used to improve the cuherence of the soft X-ray so as to improve the quality of the hologram.

In this paper, we present some experimental results on X -ray holography, holographic tomography, and a new holographic tomography method called pre-amplified holographic tomography is proposed. Due to the shorter wavelength and the larger penetration depths, X -rays provide the potential of higher resolution in imaging techniques, and have the ability to image intact, living, hydrated cells without slicing, dehydration, chemical fixation or stain. Recently, using X -ray source in National Synchrotron Radiation Laboratory in Hefei, we have successfully performed some soft X -ray holography experiments on biological specimen. The specimens used in the experiments was the garlic clove epiderm is , we got their X -ray hologram , and then reconstructed them by computer programs, the feature of the cell walls, the nuclei and some cytoplasm were clearly resolved. However, there still exist some problems in realization of practical 3D microscopic imaging due to the near-unity refractive index of the matter. There is no X -ray optics having a sufficient high numerical aperture to achieve a depth resolution that is comparable to the transverse resolution. On the other hand, computer tomography needs a record of hundreds of views of the test object at different angles for high resolution. This is because the number of views required for a densely packed object is equal to the object radius divided by the desired depth resolution. Clearly, it is im practical for a radiation-sensitive biological specimen. More over, the X -ray diffraction effect makes projection data blur, this badly degrades the resolution of the reconstructed image. In order to observe 3D structure of the biological specimens, McNulty proposed a new method for 3D imaging called

Soft X-ray Microscopy station is one of the first constructed facilities at NSRL. The main instrument of the beamline is a monochromator which can provide the monochromized X-rays varying from 2.0 nm to 5.0 nm. Our holographic image employs the X-rays, so called “water window,” and experimental setup is arranged in a Gabor in-line way. Holograms are recorded on the photoresist polymethyl methacrylate (PMMA) and readout with ordinary light microscopes or atomic force microscopes (AFMs). They are reconstructed using optical or numerical methods. So far the holograms of some samples and their reconstructed images are acquired. Those samples include minute granules, cobweb and so on. The estimated resolution of the reconstructed images reaches the level of submicron. It is limited by the coherence of the X-rays used for these experiments. And it is possible to improve the resolution in the future.

With holographic-ion beam etching technique, a number of self-supporting transmission gratings have been fabricated for inertial confinement fusion diagnosis. In addition to the general process, a practical method for monitoring the evolution of the grating structures exposed in photoresist during development of the resist. The real-time monitor technique developed here is relatively simple in comparison with a He-Ne laser and detector, which needs delicate control.

How active is a filler and what is the mechanism of its activity? Is the activity related to a change in hydrate composition, hydrate (micro)texture, or hydration kinetics? Those are the questions that we tried to answer in our work by combining 2H NMR surface area determinations, calorimetric measurements and Portlandite determination, on a series of pastes prepared by mixing C3S with limestone, quartz or α-alumina filler. Our results point towards a selective influence of fillers on the kinetics of C3S hydration and of CSH surface area development, as shown by 2H NMR relaxation.