Destructive and Non-Destructive Testing of Bridge J857 Phelps County, Missouri : Feasibility Study on Damage Detection of RC Structures using Dynamic Signature Tests

This report presents the results of a research program aimed at investigating the constructability and effectiveness of externally bonded FRP strengthening systems for improving the flexural capacity of bridge decks and piers. The joint effort of two universities, industry, and a state DOT provided the premise for a successful outcome. Bridge J857 was constructed in 1932 and was scheduled for demolition in the fall of 1998 due to highway realignment. Two of the three solid reinforced concrete (RC) decks were strengthened using two FRP systems namely, near-surface mounted carbon FRP (CFRP) rods and surface bonded CFRP sheets. Bridge decks were tested to failure under quasi-static loading cycles. Flexural strengthening of bridge columns was achieved by mounting CFRP rods on two opposite sides of the columns. Columns were also jacketed with carbon and glass FRP laminates. The experimental moment capacities of the decks compared well with theoretical values. Strengthened decks exhibited ductile behavior prior to FRP failure. The columns were tested to failure by applying lateral load cycles. The proposed strengthening technique for the bridge columns is feasible and effective for improving the flexural capacity of RC columns. The capacity of the strengthened column sections could be predicted using classical methods of analysis. Dynamic tests were conducted on the deck strengthened with CFRP sheets. The objective of dynamic tests was to relate the change in fundamental frequency to the induced damage, which could be used as a tool to assess the damage level of RC structural members. An effective damage indicator was identified that requires no baseline for damage level detection

Repurposing Niclosamide as a Novel Anti-SARS-CoV-2 Drug by Restricting Entry Protein CD147

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the global coronavirus disease 2019 (COVID-19) pandemic, and the search for effective treatments has been limited. Furthermore, the rapid mutations of SARS-CoV-2 have posed challenges to existing vaccines and neutralizing antibodies, as they struggle to keep up with the increased viral transmissibility and immune evasion. However, there is hope in targeting the CD147-spike protein, which serves as an alternative point for the entry of SARS-CoV-2 into host cells. This protein has emerged as a promising therapeutic target for the development of drugs against COVID-19. Here, we demonstrate that the RNA-binding protein Human-antigen R (HuR) plays a crucial role in the post-transcriptional regulation of CD147 by directly binding to its 3′-untranslated region (UTR). We observed a decrease in CD147 levels across multiple cell lines upon HuR depletion. Furthermore, we identified that niclosamide can reduce CD147 by lowering the cytoplasmic translocation of HuR and reducing CD147 glycosylation. Moreover, our investigation revealed that SARS-CoV-2 infection induces an upregulation of CD147 in ACE2-expressing A549 cells, which can be effectively neutralized by niclosamide in a dose-dependent manner. Overall, our study unveils a novel regulatory mechanism of regulating CD147 through HuR and suggests niclosamide as a promising therapeutic option against COVID-19

MicroRNA miR-34 Inhibits Human Pancreatic Cancer Tumor-Initiating Cells

This is the published version, also available here: http://dx.doi.org/10.1371/journal.pone.0006816.Background MicroRNAs (miRNAs) have been implicated in cancer initiation and progression via their ability to affect expression of genes and proteins that regulate cell proliferation and/or cell death. Transcription of the three miRNA miR-34 family members was recently found to be directly regulated by p53. Among the target proteins regulated by miR-34 are Notch pathway proteins and Bcl-2, suggesting the possibility of a role for miR-34 in the maintenance and survival of cancer stem cells. Methodology/Principal Findings We examined the roles of miR-34 in p53-mutant human pancreatic cancer cell lines MiaPaCa2 and BxPC3, and the potential link to pancreatic cancer stem cells. Restoration of miR-34 expression in the pancreatic cancer cells by either transfection of miR-34 mimics or infection with lentiviral miR-34-MIF downregulated Bcl-2 and Notch1/2. miR-34 restoration significantly inhibited clonogenic cell growth and invasion, induced apoptosis and G1 and G2/M arrest in cell cycle, and sensitized the cells to chemotherapy and radiation. We identified that CD44+/CD133+ MiaPaCa2 cells are enriched with tumorsphere-forming and tumor-initiating cells or cancer stem/progenitor cells with high levels of Notch/Bcl-2 and loss of miR-34. More significantly, miR-34 restoration led to an 87% reduction of the tumor-initiating cell population, accompanied by significant inhibition of tumorsphere growth in vitro and tumor formation in vivo. Conclusions/Significance Our results demonstrate that miR-34 may restore, at least in part, the tumor suppressing function of the p53 in p53-deficient human pancreatic cancer cells. Our data support the view that miR-34 may be involved in pancreatic cancer stem cell self-renewal, potentially via the direct modulation of downstream targets Bcl-2 and Notch, implying that miR-34 may play an important role in pancreatic cancer stem cell self-renewal and/or cell fate determination. Restoration of miR-34 may hold significant promise as a novel molecular therapy for human pancreatic cancer with loss of p53–miR34, potentially via inhibiting pancreatic cancer stem cells

Restoration of tumor suppressor miR-34 inhibits human p53-mutant gastric cancer tumorspheres

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs), some of which function as oncogenes or tumor suppressor genes, are involved in carcinogenesis via regulating cell proliferation and/or cell death. MicroRNA miR-34 was recently found to be a direct target of p53, functioning downstream of the p53 pathway as a tumor suppressor. miR-34 targets Notch, HMGA2, and Bcl-2, genes involved in the self-renewal and survival of cancer stem cells. The role of miR-34 in gastric cancer has not been reported previously. In this study, we examined the effects of miR-34 restoration on p53-mutant human gastric cancer cells and potential target gene expression.</p> <p>Methods</p> <p>Human gastric cancer cells were transfected with miR-34 mimics or infected with the lentiviral miR-34-MIF expression system, and validated by miR-34 reporter assay using Bcl-2 3'UTR reporter. Potential target gene expression was assessed by Western blot for proteins, and by quantitative real-time RT-PCR for mRNAs. The effects of miR-34 restoration were assessed by cell growth assay, cell cycle analysis, caspase-3 activation, and cytotoxicity assay, as well as by tumorsphere formation and growth.</p> <p>Results</p> <p>Human gastric cancer Kato III cells with miR-34 restoration reduced the expression of target genes Bcl-2, Notch, and HMGA2. Bcl-2 3'UTR reporter assay showed that the transfected miR-34s were functional and confirmed that Bcl-2 is a direct target of miR-34. Restoration of miR-34 chemosensitized Kato III cells with a high level of Bcl-2, but not MKN-45 cells with a low level of Bcl-2. miR-34 impaired cell growth, accumulated the cells in G1 phase, increased caspase-3 activation, and, more significantly, inhibited tumorsphere formation and growth.</p> <p>Conclusion</p> <p>Our results demonstrate that in p53-deficient human gastric cancer cells, restoration of functional miR-34 inhibits cell growth and induces chemosensitization and apoptosis, indicating that miR-34 may restore p53 function. Restoration of miR-34 inhibits tumorsphere formation and growth, which is reported to be correlated to the self-renewal of cancer stem cells. The mechanism of miR-34-mediated suppression of self-renewal appears to be related to the direct modulation of downstream targets Bcl-2, Notch, and HMGA2, indicating that miR-34 may be involved in gastric cancer stem cell self-renewal/differentiation decision-making. Our study suggests that restoration of the tumor suppressor miR-34 may provide a novel molecular therapy for p53-mutant gastric cancer.</p

MicroRNA miR-34 Inhibits Human Pancreatic Cancer Tumor-Initiating Cells

Our results demonstrate that miR-34 may restore, at least in part, the tumor suppressing function of the p53 in p53-deficient human pancreatic cancer cells. Our data support the view that miR-34 may be involved in pancreatic cancer stem cell self-renewal, potentially via the direct modulation of downstream targets Bcl-2 and Notch, implying that miR-34 may play an important role in pancreatic cancer stem cell self-renewal and/or cell fate determination. Restoration of miR-34 may hold significant promise as a novel molecular therapy for human pancreatic cancer with loss of p53-miR34, potentially via inhibiting pancreatic cancer stem cells

The engineering of construction specifications for externally bonded FRP composites

This dissertation, consisting of six technical papers, presents the results of research on the theme of developing engineering and the construction specifications for externally bonded FRP composites. For particular, the work focuses on three critical aspects of the performance of FRP systems: fiber misalignment, comer radius, and lap splice length. Based on both experimental and theoretical investigations, the main contribution of this work is the development of recommendations on fiber misalignment limit, minimum comer radius, lap splice length to be used as guidance in the construction practice of FRP strengthening of concrete structures. The first three papers focus on the strength and stiffness degradation of CFRP laminates from fiber misalignment. It was concluded that misalignment affects strength more than stiffness. In practice, when all fibers in a laminate can be regarded as through fibers, it is recommended to use a reduction factor for strength and no reduction factor for stiffness to account for fiber misalignment. Findings from concrete beams strengthened with misaligned CFRP laminates verified these recommendations. The fourth and fifth papers investigate the effect of comer radius on the mechanical properties of CFRP laminates wrapped around a rectangular cross section. A unique reusable test device was fabricated to determine fiber stress and radial stress of CFRP laminates with different comer radii. Comparison performed with finite element analyses shows that the test method and the reusable device were viable and the stress concentration needs to be considered in FRP laminate wrapped comers. A minimum of 1.0 in. comer radius was recommended for practice. The sixth paper summarizes the research on the lap splice length of FRP laminates under static and repeated loads. Although a lap splice length of 1.5 in. is sufficient for CFRP laminates to develop the ultimate static tensile strength, a minimum of 4.0 in. is recommended in order to account for repeated loads --Abstract, page iv

Effect of Corner Radius on the Performance of Externally Bonded FRP Reinforcement

Externally bonded FRP reinforcement is wrapped around concrete members in order to provide confinement and/or shear strengthening. The need for bending the fibers over the member corners affects the performance of the FRP laminate and the efficiency of its confining/strengthening action. This paper presents an experimental study focusing on the effects of corner radius on FRP mechanical properties. A unique re-usable test device was designed and used for this purpose such that plies of FRP could be applied over interchangeable corner inserts. The radius of the inserts ranged from a minimum of 0 to a maximum of 50.8 mm, and one or two plies of carbon FRP were used. The monitored parameters were strain distribution in the FRP laminate and load. It was found that only a portion of the CFRP laminate capacity was developed when failure occurred at the corner. Increasing the number of plies from one to two slightly improved the efficiency of the laminate

Damage Detection of Concrete Beams Using Nonlinear Features of Forced Vibration

A new indicator is proposed to facilitate the detection of newly induced damage in reinforced concrete (RC) beams, based on the transient characteristics of nonlinear vibration. Two full-scale RC beams, one reinforced with externally bonded fiber-reinforced-polymer sheets, are tested to develop the proposed damage indicator. Both beams are statically and dynamically loaded to correlate the dynamic characteristics of the beams to the damage level. a phenomenological model is developed to simulate the general behavior of cracked concrete members with a softening Duffing oscillator. Numerical results and test data show that the indicator rapidly increases with the severity of damage and is very sensitive to cracking even under service loads. the indicator is directly related to the transient features along crack surfaces and requires no baseline in practical applications. Experimental test results also show that the fundamental natural frequency of the strengthened beam suddenly decreases at the initiation of cracking and then remains nearly constant while natural frequency of the unstrengthened beam decreases continuously as the beam experiences concrete cracking and reinforcement yielding