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At least 109 records · Page 6

BLZF1 expression is of prognostic significance in hepatocellular carcinoma

BLZF1, a member of b-ZIP family, has been implicated in epigenetic regulation and Wnt/β-catenin signaling. Its expression and clinical significance in human cancers remain largely unknown. In this study, we showed that BLZF1 expression was reduced in hepatocellular carcinoma (HCC) tissues, compared to the paracarcinoma tissues, at both mRNA and protein levels. Results of immunohistochemistry revealed that BLZF1 was presented in both nuclear and cytoplasm. Decreased expression of nuclear and cytosolic BLZF1 in HCC was depicted in 68.2% and 79.2% of the 634 cases. Nuclear BLZF1 expression was significantly associated with tumor multiplicity (P = 0.048) and tumor capsule (P = 0.028), while cytosolic BLZF1 expression was correlated with serum AFP level (P = 0.017), tumor differentiation (P = 0.001) and tumor capsule (P = 0.003). Kaplan–Meier analysis indicated both nuclear and cytosolic BLZF1 expression was associated with poor overall survival. Low nuclear BLZF1 also indicated unfavorable disease-free survival and high tendency of tumor recurrence. Furthermore, multiple Cox regression analysis revealed nuclear BLZF1 as an independent factor for overall survival (Hazard Ratio (HR) = 0.827, 95% confident interval (95%CI): 0.697–0.980, P = 0.029). The prognostic value of BLZF1 was further confirmed by stratified analyses. Collectively, our data suggest BLZF1 is a novel unfavorable biomarker for prognosis of patients with HCC. - Highlights: • BLZF1 expression was much lower in HCC tissues. • Low BLZF1 expression was associated with poor outcomes in a cohort of 634 HCC patients. • Multiple Cox regression analysis indicated nuclear BLZF1 as an independent predictor for overall survival.

60 APPLIED LIFE SCIENCES↗

High expression of hexokinase domain containing 1 is associated with poor prognosis and aggressive phenotype in hepatocarcinoma

Rapid progress and metastasis remain the major treatment failure modes of hepatocarcinoma (HCC). Unfortunately, the underlying molecular mechanisms of hepatoma cell proliferation and migration are poorly understood. Metabolic abnormalities play critical roles in tumorigenesis and progression. Hexokinase domain containing 1 (HKDC1) catalyzes the phosphorylation of glucose. However, the functions and mechanisms of HKDC1 in cancer remain unknown. In this study, real-time RT-PCR and Western blotting assays were used to detect the HKDC1 expression levels in HCC tissues and cell lines. The Oncomine™ Cancer Microarray Database was applied to analysis the correlations between HKDC1 expression and HCC clinical characteristics. MTT and Transwell migration assays were performed to determine the functions of HKDC1 in HCC cells. The effect of HKDC1 on Wnt/β-catenin signaling pathway was assessed using Western blotting assay. In this study, we found that HKDC1 expression levels were elevated in HCC tissues compared with the adjacent tissues. HCC patients with high expression levels of HKDC1 had poor overall survival (OS). Furthermore, higher HKDC1 levels also predicted a worse OS of patients within solitary, elevated pre-operated serum alpha fetoprotein (AFP) level and higher tumor diameter. Moreover, silencing HKDC1 suppressed HCC cells proliferation and migration in vitro. Downregulated HKDC1 expression repressed β-Catenin and c-Myc expression, which indicates that silencing HKDC1 may reduce proliferation and migration via inhibiting the Wnt/β-catenin signaling pathway in HCC. In summary, HKDC1 provides further insight into HCC tumor progression and may provide a novel prognostic biomarker and therapeutic target for HCC treatment. -- Highlights: •HKDC1 is upregulated in HCC. •Patients with high HKDC1 expressions perform worse OS. •Silencing HKDC1 suppresses proliferation and migration. •Silencing HKDC1 represses Wnt/β-catenin signaling pathway.

60 APPLIED LIFE SCIENCES↗

Anti-tumor effect of evodiamine by inducing Akt-mediated apoptosis in hepatocellular carcinoma

Background: Evodiamine is an alkaloid extracted from Euodia rutaecarpa (Juss.) Benth. There is little information about the mechanisms of evodiamine on the apoptosis of hepatocellular carcinoma (HCC). Materials and methods: A xenograft model and CCK8 assay were used to investigate the anti-HCC effect of evodiamine. The effect of evodiamine on apoptosis was evaluated by DAPI staining and flow cytometry. Western blot analyses and immunohistochemistry were processed to assess the protein expressions of Akt and apoptotic proteins. Results: Evodiamine suppressed tumor growth, improved the expression of cleaved-caspase3 and decreased tumor specific growth factor (TSGF) and alpha fetoprotein (AFP) activities. Furthermore, evodiamine inhibited cell viability and induced cell cycle arrest. DAPI staining revealed nuclear condensation in evodiamine-treated groups. Meanwhile, evodiamine increased the number of apoptotic cells. Furthermore, evodiamine suppressed Akt and regulated apoptotic proteins in HepG2 cells. Evodiamine decreased p-Akt levels activated by SC79, which led to the increase of bax/bcl-2 and cleaved-caspase3. Conclusions: Our findings suggested that evodiamine could exert anti-HCC effect through inducing Akt-mediated apoptosis. Evodiamine has the potential to be a therapeutic medicine for HCCs. - Highlights: • Anti-tumor effect of evodiamine in hepatocellular carcinoma. • Evodiamine induces apoptosis in hepatocellular carcinoma. • The correlation between induction of apoptosis and Akt expression.

60 APPLIED LIFE SCIENCES↗

UBE2S enhances the ubiquitination of p53 and exerts oncogenic activities in hepatocellular carcinoma

Highlights: • High expression of UBE2S is significantly correlated with poor outcomes in two independent cohorts containing 845 patients. • UBE2S promotes cell proliferation and migration in HCC. • UBE2S exerts oncogenic activities via enhancing the ubiquitination of p53. Ubiquitin-conjugating enzyme E2S (UBE2S) plays pivotal roles in the progression of human cancers. However, its clinical significance and role in hepatocellular carcinoma (HCC) remain unknown. Here, we show that UBE2S is upregulated in HCC and exhibits oncogenic activities via enhancing the ubiquitination of p53. Increased expression of UBE2S was significantly correlated with higher serum AFP level, higher pathological grade, advanced TNM stage, larger tumor size, vascular invasion and unfavorable patient survivals in two independent cohorts containing a total of 845 patients with HCC. Multivariate analyses by cox regression model suggested UBE2S as an independent factor for overall survival. In vitro experiments demonstrated that UBE2S overexpression promoted, whereas UBE2S knockdown suppressed cell proliferation and migration via modulation of p53 signaling pathway. Ectopic expression of UBE2S upregulated the expression of p53 and its downstream effectors, such as p21 and Cyclin D1. Mechanistically, UBE2S enhanced the ubiquitination of p53 protein to facilitate its degradation in HCC cells. Re-expression of p53 partially attenuated the UBE2S-promoted malignant phenotypes. Collectively, our study provides compelling evidence that UBE2S is a potential prognostic factor and functions as an oncogene in HCC.

60 APPLIED LIFE SCIENCES↗

Performance of the ATLAS forward proton Time-of-Flight detector in Run 2

We present performance studies of the Time-of-Flight (ToF) subdetector of the ATLAS Forward Proton (AFP) detector at the LHC. Efficiencies and resolutions are measured using high-statistics data samples collected at low and moderate pile-up in 2017, the first year when the detectors were installed on both sides of the interaction region. While low efficiencies are observed, of the order of a few percent, the resolutions of the two ToF detectors measured individually are 21 ps and 28 ps, yielding an expected resolution of the longitudinal position of the interaction, z vtx , in the central ATLAS detector of 5.3 ± 0.6 mm. This is in agreement with the observed width of the distribution of the difference between z vtx , measured independently by the central ATLAS tracker and by the ToF detector, of 6.0 ± 2.0 mm.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Validation of k eff Calculations for Extended BWR Burnup Credit

The US Nuclear Regulatory Commission and consensus standards recommend validation of the numerical methods used in criticality safety analyses. This validation requires the comparison of computational results with measurements of physical systems which are neutronically similar to those used in the safety analysis being performed. To this end, this document examines the methods available to generate sensitivity data to help identify systems similar to spent boiling- water reactor (BWR) fuel in a flooded spent nuclear fuel transportation or storage cask. A large number of critical benchmark experiments are surveyed using sensitivity/uncertainty (S/U) techniques to assess their applicability to BWR burnup credit (BUC) beyond the burnup of peak reactivity. Multiple burnups of BWR assemblies are considered herein, as well as the actinide-only (AO) and actinide-and-major-fission-product (AFP) isotope sets. Sample validations are completed for representative application models to demonstrate that appropriate validation is possible and to indicate the bias and bias uncertainty values expected for related applications.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Thermoplastic Composite Compressed Gas Storage (CGS) Tanks

This report summarizes the progress made on utilizing polyamide carbon fiber tapes for composite overwrapped pressure vessels (CPVs) using Automated Fiber Placement (AFP). This project is joint development project run through the Institute for Advance Composite Manufacturing Innovation (IACMI) with DuPont, Steelhead Composites, University of Dayton Research Institute, and the Composites Prototyping Center. Over the course of this program, the Team developed and/or demonstrated the materials and processes that are required to produce vessels for compressed gas storage, including polyamide matrix formulation, unidirectional polyamide/carbon fiber tape production, and automated fiber placement on a vessel liner. In addition, a cost of manufacture analysis was performed that compares Type III and Type IV vessels made with both thermoplastic and thermoset chemistries. This report summarizes the myriad of technical advances made during this project, culminating with production and testing of an aluminum-lined Type III pressure vessel. Each step was optimized locally so as to produce the best material. The end result was a test vessel that, while demonstrating some of the benefits of thermoplastic matrix composites, did not perform as well as those produced by filament winding of carbon fiber/epoxy prepregs. This was most likely due to the Team’s focus on local optimization rather than globally optimizing the entire process from beginning to end. Should further work be contemplated, a more focused effort on global optimization should be pursued.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

Gas and dust production by Comet P/Halley (1910 II)

Selected long-slit spectrograms of Comet P/Halley, photographed during the postperihelion period between April 16 and June 3, 1910 have been quantitatively analyzed for comparison with the 1985/86 apparition. The Fe-V-Na spark spectrum was used to determine characteristic curves for these plates, and flux calibrations based on contemporaneous broad-band photometric measurements were applied. Haser model production rates for C2 and values Afp were computed for each of the nights selected and compared with the photometric observations obtained by Schleicher et al. (1987) during the comparable postperihelion period of the 1985/86 apparition. As found for the 1985/86 apparation, the gas and dust production in 1910 varied in phase, but the rates of production were higher than observed in 1986 by a small but statistically significant amount.

Howell, Ellen S.↗

Superheavyweight missions SI versus DI: Ascent flight design options and recommendations

AFD has completed the trade study on Standard Insertion (SI) vs Direct Insertion (DI) for STS-50. RSOC Range Safety has developed acceptable DI targets from 130 n.mi. to 150 n.mi. and the corresponding performance assessment for these targets using STS-50 data has been completed. This mission has sufficient performance capability to perform this mission as a DI to 160 n.mi. A reduced OMS load corresponding to a DI mission is required for this option. The increase in altitude over the AFP baseline (SI to 145 n.mi.) is highly desirable for this mission. The orientation on orbit for the orbiter/USML-1 payload is such that orbital decay is maximized (maximum frontal cross-sectional area with vehicle normal to velocity vector). Increasing the operational altitude reduces the amount of vernier thruster firings necessary to maintain a constant gravity gradient. The results of this trade study can also be applied to other superheavyweight missions (EDO flights) and will allow for use of the DI technique for lower orbital altitudes, thereby eliminating the SI option for due east, low altitude missions. STSOC transmittal form no. 330-330-130, which documents the technical issues and assumptions used for this trade study effort in detail, should be referenced for further information. The main reason that a DI is desired for STS-50 and other superheavyweight flights (low altitude) is that ESMC range safety has expressed reservations about SI missions in general. The concern is that the current SI design underspeed exposes Africa and Madagascar to potential ET debris impact. In the past range safety has waived the requirement that these areas be protected in the event of an engine failure. With the advent of the pre-MECO OMS dump, the viability of DI and the high casualty expectations from the ACTA press to MECO hazard study, range safety has become more reluctant to approve SI flights. It is felt that to perform an SI mission there would have to be a large decrease in design underspeed to protect these landmasses, which would result in possible gaps between a late TAL and PTA. The assumed limit on a DI has been to altitudes greater than 160 n.mi. It was assumed that for altitudes less than 160 n.mi. the nominal ET impact envelope would overlap the Gilbert Islands.

Source record↗

STS-39 Space Shuttle mission report

The STS-39 Space Shuttle Program Mission Report contains a summary of the vehicle subsystem operations during the fortieth flight of the Space Shuttle and the twelfth flight of the Orbiter Vehicle Discovery (OV-103). In addition to the Discovery vehicle, the flight vehicle consisted of the following: an External Tank (ET) (designated as ET-46 (LWT-39); three Space Shuttle main engines (SSME's) (serial numbers 2026, 2030, and 2029 in positions 1, 2, and 3, respectively); and two Solid Rocket Boosters (SRB's) designated as BI-043. The primary objective of this flight was to successfully perform the planned operations of the Infrared Background Signature Survey (IBSS), Air Force Payload (AFP)-675, Space Test Payload (STP)-1, and the Multipurpose Experiment Canister (MPEC) payloads.

Fricke, Robert W.↗

NASTRAN DMAP Fuzzy Structures Analysis: Summary of Research

The main proposed tasks of Cooperative Agreement NCC1-382 were: (1) developing MSC/NASTRAN DMAP language scripts to implement the Soize fuzzy structures approach for modeling the dynamics of complex structures; (2) benchmarking the results of the new code to those for a cantilevered beam in the literature; and (3) testing and validating the new code by comparing the fuzzy structures results to NASA Langley experimental and conventional finite element results for two model test structures representative of aircraft fuselage sidewall construction: (A) a small aluminum test panel (SLP, single longeron panel) with a single longitudinal stringer attached with bolts; and (B) a 47 by 72 inch flat aluminum fuselage panel (AFP, aluminum fuselage panel) including six longitudinal stringers and four frame stiffeners attached with rivets.

Sparrow, Victor W.↗

P/2006 HR30 (Siding Spring): A Low-activity Comet in Near-Earth Space

The low cometary activity of P/2006 HR30 (Siding Spring) allowed a unique opportunity to study the nucleus of a periodic comet while near perihelion. P/2006 HR30 was originally targeted as a potential extinct comet, and we measured spectral reflectance and dust production using long-slit CCD spectroscopy and wide-field imaging obtained at the Palomar Mountain 200 inch telescope on 2006 August 3 and 4. The dust production Afp = 19.7 +/- 0.4 cm and mass-loss rate Q(dust) 4.1 +/- 0.1 kg/sec of the comet were approximately 2 orders of magnitude dust less than 1P/Halley at similar heliocentric distance. The VRI colors derived from the spectral reflectance were compared to Kuiper Belt objects, Centaurs, and other cometary nuclei. We found that the spectrum of P/2006 HR30 was consistent with other comets. However, the outer solar system bodies have a color distribution statistically distinct from cometary nuclei. It is our conjecture that cometary activity, most likely the reaccretion of ejected cometary dust, tends to moderate and mute the visible colors of the surface of cometary nuclei.

comets↗

Automated Fiber Placement Defects: Automated Inspection and Characterization

Automated Fiber Placement (AFP) is an additive composite manufacturing technique, and a pressing challenge facing this technology is defect detection and repair. Manual defect inspection is time consuming, which led to the motivation to develop a rapid automatic method of inspection. This paper suggests a new automated inspection system based on convolutional neural networks and image segmentation tasks. This creates a pixel by pixel classification of the defects of the whole part scan. This process will allow for greater defect information extraction and faster processing times over previous systems, motivating rapid part inspection and analysis. Fine shape, height, and boundary detail can be generated through our system as opposed to a more coarse resolution demonstrated in other techniques. These scans are analyzed for defects, and then each defect is stored for export, or correlated to machine parameters or part design. The network is further improved through novel optimization techniques. New training instances can also be created with every new part scan by including the machine operator as a post inspection check on the accuracy of the system. Having a continuously adapting inspection system will increase accuracy for automated inspections, cutting down on false readings.

Sacco, Christopher↗

TPSAS-NF1676L-32030-DND

Composite structures are often difficult to inspect due to the anisotropic nature of the material systems and the range of flaws and defects that can arise in the manufacturing process. NASA?s Advanced Composites Project, a public-private partnership between government, universities and industry, seeks to address improved methods, tools, and protocols to reduce the development and certification timeline for composite materials and structures. The rapid inspection of composites is one of the three focused research areas of the project. One deliverable of the project is to develop an NDE Methods and Capabilities Handbook. This Handbook provides a publically available guidance document that facilitates the selection of appropriate NDE techniques and provides recommended protocols for detecting and characterizing common flaw types in solid laminate polymer matrix composite (PMC) structures. The Handbook will reduce the time required to develop qualified inspection processes for composite aircraft structures during the development, certification, and manufacturing phases by providing a reference that helps minimize trial and error and provides guidance on best practices, techniques, and settings, for specific flaw types and geometries. The Handbook will include an NDE Guidance Matrix that provides an applicability rating for NDE techniques as they apply to given flaw types. NDE techniques will include, but is not limited to ultrasound, laser based ultrasound, infrared thermography, and x-ray CT. Flaw types will include, but are not limited to porosity, delamination, voids, AFP defects and impact damage. The Handbook will contain details that support the applicability rating including, but not limited to, specimen details, inspection parameters, data analysis techniques, inspection efficiency (speed & cost), and limitations. This presentation will describe key Handbook activities with examples of the techniques and flaw types examined by the Advanced Composite Consortium members.

Patricia A Howell↗

NDE Methods and Capabilities Handbook – Resources for the Composites NDE Community

Composite structures are often difficult to inspect due to the anisotropic nature of the material systems and the range of flaws and defects that can arise in the manufacturing process. NASA’s Advanced Composites Project, a public-private partnership between government, universities and industry, sought to address improved methods, tools, and protocols to reduce the development and certification timeline for composite materials and structures. The rapid inspection of composites was one of the three focused research areas of the project. One deliverable of the project was to develop an NDE Methods and Capabilities Handbook. This Handbook provides a publicly available guidance document that facilitates the selection of appropriate NDE techniques and provides recommended protocols for detecting and characterizing common flaw types in solid laminate carbon fiber reinforced polymer composite (CFRP) structures. The Handbook seeks to reduce the time required to develop qualified inspection processes for composite aircraft structures during the development, certification, and manufacturing phases by providing a reference that helps minimize trial and error and provides guidance on best practices, techniques, and settings, for specific flaw types and geometries. NDE techniques include, but are not limited to ultrasound, laser based ultrasound, infrared thermography, and x-ray CT. Flaw types include, but are not limited to porosity, delamination, voids, AFP defects and impact damage. The Handbook contains details such as inspection parameters, data analysis techniques, inspection efficiency (speed & cost), and limitations. This presentation will describe key Handbook activities with examples of the techniques and flaw types examined by the Advanced Composite Consortium members. Availability of the fabricated NDE standards as well as the raw data collected on the standards by the Consortium members to the NDE community is discussed.

Patricia A Howell↗

Design of a Manufacturing Demonstration Unit for a Composite Lunar Landing Gear Strut

The goal of the current work was to develop an analytical framework for design of composite struts using various levels of model fidelity. An additional goal of this work was to perform an initial assessment of using automated fiber placement (AFP) and other advanced manufacturing methods to explore their feasibility for the fabrication of struts for lunar landers, strut-braced wings, and other aerospace components. In particular, designs were considered for fabrication at the Integrated Structural Assembly of Advanced Composites (ISAAC) facility at Langley Research Center (LaRC). The designs presented in this paper do not represent the exact geometry and material systems currently in use by the Artemis landing system, but they are considered to be representative. The designs produced during this study will be used to develop manufacturing demonstration units (MDU) that can be fabricated at ISAAC and tested in lab facilities at LaRC

carbon-epoxy↗

NDE Methods and Capabilities Handbook - Resources for the Composites NDE Community

Composite structures are often difficult to inspect due to the anisotropic nature of the material systems and the range of flaws and defects that can arise in the manufacturing process. NASA’s Advanced Composites Project, a public-private partnership between government, universities and industry, sought to address improved methods, tools, and protocols to reduce the development and certification timeline for composite materials and structures. The rapid inspection of composites was one of the three focused research areas of the project. One deliverable of the project was to develop an NDE Methods and Capabilities Handbook. This Handbook provides a publicly available guidance document that facilitates the selection of appropriate NDE techniques and provides recommended protocols for detecting and characterizing common flaw types in solid laminate carbon fiber reinforced polymer composite (CFRP) structures. The Handbook seeks to reduce the time required to develop qualified inspection processes for composite aircraft structures during the development, certification, and manufacturing phases by providing a reference that helps minimize trial and error and provides guidance on best practices, techniques, and settings, for specific flaw types and geometries. Techniques include, but are not limited to ultrasound, laser based ultrasound, infrared thermography, and x-ray CT. Flaw types include, but are not limited to porosity, delaminations, voids, Automated Fiber Placement (AFP) defects and impact damage. The Handbook contains details such as inspection parameters, data analysis techniques, inspection efficiency and limitations. This presentation will describe key Handbook activities with examples of the techniques and flaw types examined by the Advanced Composite Consortium members. Availability to the NDE community of the fabricated NDE standards as well as the raw data collected on the standards by the Consortium members is discussed.

Nondestructive Evaluation↗