Evaluation of Heat-Induced Damage in Concrete Using Machine Learning of Ultrasonic Pulse Waves.

This study investigated the applicability of using ultrasonic wave signals in detecting early fire damage in concrete. This study analyzed the reliability of using the linear (wave velocity) and nonlinear (coherence) parameters from ultrasonic pulse measurements and the applicability of machine learning in assessing the thermal damage of concrete cylinders. While machine learning has been used in some damage detections for concrete, its feasibility has not been fully investigated in classifying thermal damage. Data was collected from laboratory experiments using concrete specimens with three different water-to-binder ratios (0.54, 0.46, and 0.35). The specimens were subjected to different target temperatures (100 °C, 200 °C, 300 °C, 400 °C, and 600 °C) and another set of cylinders was subjected to room temperature (20 °C) to represent the normal temperature condition. It was observed that P-wave velocities increased by 0.1% to 10.44% when the concretes were heated to 100 °C, and then decreased continuously until 600 °C by 48.46% to 65.80%. Conversely, coherence showed a significant decrease after exposure to 100 °C but had fluctuating values in the range of 0.110 to 0.223 thereafter. In terms of classifying the thermal damage of concrete, machine learning yielded an accuracy of 76.0% while the use of P-wave velocity and coherence yielded accuracies of 30.26% and 32.31%, respectively.

Prediction of Compressive Strength of Partially Saturated Concrete Using Machine Learning Methods.

The aim of this research is to recommend a set of criteria for estimating the compressive strength of concrete under marine environment with various saturation and salinity conditions. Cylindrical specimens from three different design mixtures are used as concrete samples. The specimens are subjected to different saturation levels (oven-dry, saturated-surface dry and three partially dry conditions: 25%, 50% and 75%) on water and water-NaCl solutions. Three parameters (P- and S-wave velocities and electrical resistivity) of concrete are measured using two NDT equipment in the laboratory while two parameters (density and water-to-binder ratio) are obtained from the design documents of the concrete cylinders. Three different machine learning methods, which include, artificial neural network (ANN), support vector machine (SVM) and Gaussian process regression (GPR), are used to obtain multivariate prediction models for compressive strength from multiple parameters. Based on the R-squared value, ANN results in the highest accuracy of estimation while GPR gives the lowest root-mean-squared error (RMSE). Considering both the data analysis and practicality of the method, the prediction model based on two NDE parameters (P-wave velocity measurement and electrical resistivity) and one design parameter (water-to-binder ratio) is recommended for assessing compressive strength under marine environment.

Effects of Saturation Levels on the Ultrasonic Pulse Velocities and Mechanical Properties of Concrete.

The main objective of this research is to investigate the effect of water content in concrete on the velocities of ultrasonic waves (P- and S-waves) and mechanical properties (elastic modulus and compressive strength) of concrete. For this study, concrete specimens (100 mm × 200 mm cylinders) were fabricated with three different water-to-binder ratios (0.52, 0.35, and 0.26). These cylinders were then submerged in water to be saturated in different degrees from 25% to 100% with an interval of 25% saturation. Another set of cylinders was also oven-dried to represent the dry condition. The dynamic properties of concrete were then assessed using a measurement of elastic wave accordance with ASTM C597-16 and using resonance tests following ASTM C215-19, before and after immersion in water. The static properties of saturated concrete were also assessed by the uniaxial compressive testing according to ASTM C39/C39M-20 and ASTM C469/C469M-14. It was observed that the saturation level of concrete affected the two ultrasonic wave velocities and the two static mechanical properties of concrete in various ways. The relationship between P-wave velocity and compressive strength of concrete was highly sensitive to saturation condition of concrete. In contrast, S-wave velocity of concrete was closely correlated with compressive strength of concrete, which was much less sensitive to water saturation level compared to P-wave velocity of concrete. Finally, it was noticed that water saturation condition only little affects the relationship between the dynamic and elastic moduli of elasticity of concrete studies in this study.

A Practical Guide to Source and Receiver Locations for Surface Wave Transmission Measurements across a Surface-Breaking Crack in Plate Structures.

The main objectives of this study are to investigate the interference of multiple bottom reflected waves in the surface wave transmission (SWT) measurements in a plate and to propose a practical guide to source-and-receiver locations to obtain reliable and consistent SWT measurements in a plate. For these purposes, a series of numerical simulations, such as finite element modelling (FEM), are performed to investigate the variation of transmission coefficient of surface waves across a surface-breaking crack in various source-to-receiver configurations in plates. Main variables in this study include the crack depths (0, 10, 20, 30, 40 and 50 mm), plate thicknesses (150, 200, 300, 400 and 800 mm), source-to-crack distances (100, 150, 200, 250 and 300 mm) and receiver-to-crack distances. The validity of numerical simulation results was verified by comparison with results from experiments using Plexiglas specimens using two types of noncontact sensors (laser vibrometer and air-coupled sensor) in the laboratory. Based on simulation and experimental results in this study, practical guidelines for sensor-to-receiver locations are proposed to reduce the effects of the interference of bottom reflected waves on the SWT measurements across a surface-breaking crack in a plate. The findings in this study will help obtain reliable and consistent SWT measurements across a surface-breaking crack in plate-like structures.

Evaluation of Static and Dynamic Residual Mechanical Properties of Heat-Damaged Concrete for Nuclear Reactor Auxiliary Buildings in Korea Using Elastic Wave Velocity Measurements.

The main objectives of this study are (1) to investigate the effects of heating and cooling on the static and dynamic residual properties of 35 MPa (5000 psi) concrete used in the design and construction of nuclear reactor auxiliary buildings in Korea; and (2) to establish the correlation between static and dynamic properties of heat-damaged concrete. For these purposes, concrete specimens (100 mm × 200 mm cylinder) were fabricated in a batch plant at a nuclear power plant (NPP) construction site in Korea. To induce thermal damages, the concrete specimens were heated to target temperatures from 100 °C to 1000 °C with intervals of 100 °C, at a heating rate of 5 °C/min and allowed to reach room temperature by natural cooling. The dynamic properties (dynamic elastic modulus and dynamic Poisson's ratio) of concrete were evaluated using elastic wave measurements (P-wave velocity measurements according to ASTM C597/C597M-16 and fundamental longitudinal and transverse resonance tests according to ASTM C215-14) before and after the thermal damages. The static properties (compressive strength, static elastic modulus and static Poisson's ratio) of heat-damaged concrete were measured by the uniaxial compressive testing in accordance with ASTM C39-14 and ASTM C469-14. It was demonstrated that the elastic wave velocities of heat-damaged concrete were proportional to the square root of the reduced dynamic elastic moduli. Furthermore, the relationship between static and dynamic elastic moduli of heat-damaged concrete was established in this study. The results of this study could improve the understanding of the static and dynamic residual mechanical properties of Korea NPP concrete under heating and cooling.

Evaluation of Delamination in Concrete by IE Testing Using Multi-Channel Elastic Wave Data.

The main objectives of this study are to develop a non-destructive test method for evaluating delamination defects in concrete by the Impact-echo test using multi-channel elastic wave data and to verify the validity of the proposed method by experimental studies in the laboratory. First, prototype equipment using an eight-channel linear sensor array was developed to perform elastic wave measurements on the surface of the concrete. In this study, three concrete slab specimens (1500 mm (width) by 1500 mm (length) by 300 mm (thickness)), with simulated delamination defects of various lateral dimensions and depth, were designed and constructed in the laboratory. Multi-channel elastic wave signals measured on the three concrete specimens were converted to the frequency-phase velocity image by using the phase-shift method. A data processing method was proposed to extract the dominant propagating waves and non-propagating waves from the dispersion images. The dominant wave modes were used to evaluate delamination defects in concrete. It was demonstrated that the surface wave velocity values were useful for characterizing the shallow delamination defects in concrete. In addition, the peak frequency of non-propagating wave modes extracted from the dispersion images gives information on the lateral dimensions and depths of the delamination defects. This study also discussed the feasibility of combined use of the results from propagating and non-propagating wave modes to better understand the information on delamination defects in concrete. As will be discussed, the multi-channel elastic wave measurements enable more accurate, consistent, and rapid measurements and data processing for evaluation of delamination defects in concrete than the single-channel sensing method.

Molecular determinants of efficacy for 5-FU-based treatments in advanced colorectal cancer: mRNA expression for 18 chemotherapy-related genes.

5-Fluorouracil (5-FU)-based regimens remain a cornerstone in the treatment of colorectal cancer (CRC). However, the attendant toxicity prevents these regimens from reaching maximum therapeutic potential. In this retrospective analysis, we examined the pretreatment expression of 18 genes in archival tumor bank samples from patients with advanced CRC to determine if one or more of the selected genes showed promise as either a prognostic or predictive marker of 5-FU-based treatment outcomes. One hundred and forty-four CRC patient samples (collected from 1983 to 2004) were analyzed via real-time PCR for gene expression. Univariate analyses were used to correlate gene expression with efficacy and time-to-event variables. Low thymidine phosphorylase (TP), dihydrofolate reductase, dihydropyrimidine dehydrogenase (DPD), excision repair cross-complementing 1 (ERCC1) and thymidylate synthase gene expression were associated with better time-to-progression in the entire population. Low TP, DPD and ERCC1 expression were independently associated with improved overall survival. Low TP gene expression was also predictive of response. This study suggests that TP gene expression in particular is a predictive as well as a prognostic biomarker for advanced CRC patients. Gene panels assessing pretreatment TP, DPD, ERCC1, dihydrofolate reductase and thymidylate synthase gene expression may help improve the therapeutic potential of 5-FU- or other novel antifolate-based regimens. Further analysis of the prognostic or predictive value of these genes in prospective trials in CRC patients seems warranted.

Correlations of mRNA expression and in vitro chemosensitivity to enzastaurin in freshly explanted human tumor cells.

PURPOSE: Enzastaurin (LY317615) is a novel serine/threonine kinase inhibitor, targeting Protein Kinase C-beta (PKC-beta), and PI3K/AKT pathways to inhibit angiogenesis and tumor cell proliferation. The aims of this study were to determine whether Enzastaurin has direct antitumor activity against freshly explanted tumor cells and to correlate mRNA expression of genes related to the proposed mechanism of action of enzastaurin with in vitro chemosensitivity. EXPERIMENTAL DESIGN: Freshly biopsied tumor cells were studied using soft-agar cell cloning experiments (SACCE) to determine the in vitro chemosensitivity to enzastaurin. An aliquot of the same tumor specimens was shock-frozen and total RNA was isolated for standardized multiplex rt-PCR experiments for gene expression of PKC-beta1, PKC-beta2, IL-8, IL-8RA, IL-8RB, Glycogen Synthase Kinase 3 beta (GSK-3beta) and TGF-beta1. Correlations, threshold optimization, sensitivity, specificity, and efficiency were analyzed using the appropriate statistical methodologies. RESULTS: Seventy-two tumor samples were collected and 63 were fully evaluable. Low levels of mRNA expression of GSK-3beta and high levels of mRNA expression of IL-8 were highly significantly correlated with chemosensitivity to enzastaurin. Optimization analyses demonstrated threshold values of 4,000 copies for IL-8 and three copies for GSK-3beta relative to 10(4) copies of beta-actin. However, no correlation between mRNA expression of PKC-beta1, PKC-beta2, IL-8RA, IL-8RB and chemosensitivity to enzastaurin was observed. Expression of TGF-beta1 mRNA was not detectable in the specimens investigated. CONCLUSIONS: mRNA expression levels of IL-8 and GSK-3beta correlate with antitumor activity of enzastaurin. These results form a rational basis for clinical trials to evaluate the expression of these genes as potential predictors for treatment outcome after enzastaurin chemotherapy.

A randomized, double-blind, phase II study of two doses of pemetrexed as first-line chemotherapy for advanced breast cancer.

PURPOSE: Pemetrexed has shown varied response rates in advanced breast cancer. This randomized, double-blind, phase II study was conducted to assess the efficacy and safety of two doses of pemetrexed in a homogeneous population. A secondary objective was to identify molecular biomarkers correlating with response and toxicity. EXPERIMENTAL DESIGN: Patients with newly diagnosed metastatic breast cancer or locally recurrent breast cancer received 600 mg/m(2) (P600 arm) or 900 mg/m(2) (P900 arm) of pemetrexed on day 1 of a 21-day cycle. All patients received folic acid and vitamin B(12) supplementation. RESULTS: The P600 (47 patients) and P900 (45 patients) arms had response rates of 17.0% (95% confidence interval, 7.7-30.8%) and 15.6% (95% confidence interval, 6.5-29.5%) with approximately 50% stable disease per arm, median progression-free survival of 4.2 and 4.1 months, and median times to tumor progression of 4.2 and 4.6 months, respectively. Both arms exhibited minimal toxicity (grade 3/4 neutropenia <20%, leukopenia <9%, and other toxicities <5%). Tumor samples from 49 patients were assessed for the expression levels of 12 pemetrexed-related genes. Folylpolyglutamate synthetase and thymidine phosphorylase correlated with efficacy. Best response rates and median time to tumor progression for high versus low thymidine phosphorylase expression were 27.6% versus 6.3% (P = 0.023) and 5.4 versus 1.9 months (P = 0.076), and for folylpolyglutamate synthetase were 37.5% versus 10.0% (P = 0.115) and 8.6 versus 3.0 months (P = 0.019), respectively. gamma-Glutamyl hydrolase expression correlated with grade 3/4 toxicities: 78.6% for high versus 27.3% for low gamma-glutamyl hydrolase (P = 0.024). CONCLUSION: The two pemetrexed doses yielded similar efficacy and safety profiles. Exploratory biomarker analysis identified efficacy and toxicity correlations and warrants further evaluation.

In vitro chemosensitivity of freshly explanted tumor cells to pemetrexed is correlated with target gene expression.

AIM OF THE STUDY: mRNA expression of genes involved in the mechanism of action of pemetrexed was correlated with in vitro chemosensitivity of freshly explanted human tumor specimens. EXPERIMENTAL DESIGN: Chemosensitivity to pemetrexed was studied in soft-agar. Multiplex rtPCR experiments for reduced folate carrier (RFC), folate receptor-alpha (FR-alpha), folylpolyglutamate synthetase (FPGS), thymidylate synthase (TS), dihydrofolate reductase (DHFR), glycinamide ribonucleotide formyl transferase (GARFT), mrp4, and mrp5 were performed in parallel. Correlations, threshold optimization, sensitivity, specificity, and efficiency were analyzed using the appropriate statistical methodologies. RESULTS: In 61 samples, low levels of TS, GARFT, DHFR, and mrp4 gene expression significantly correlated with chemosensitivity to pemetrexed. Optimization analyses demonstrated threshold values of 144 copies for TS and six copies for mrp4 relative to 10(4) copies of beta-actin. CONCLUSIONS: These results form a rational basis for the design of clinical trials to evaluate the expression of these enzymes as predictors for treatment outcome.

A randomized phase II trial of pemetrexed plus irinotecan (ALIRI) versus leucovorin-modulated 5-FU plus irinotecan (FOLFIRI) in first-line treatment of locally advanced or metastatic colorectal cancer.

BACKGROUND: This multicenter, randomized trial compared overall response rate between pemetrexed plus irinotecan (ALIRI) and leucovorin-modulated 5-fluorouracil plus irinotecan (FOLFIRI) in patients with advanced colorectal cancer. Secondary objectives included overall and progression-free survival, duration of response, toxicities, and biomarkers. PATIENTS AND METHODS: ALIRI patients received pemetrexed 500 mg/m(2) and irinotecan 350 mg/m(2) with vitamin supplementation on day 1 of each 21-day cycle. FOLFIRI patients received irinotecan 180 mg/m(2) on days 1, 15, 29; on days 1, 2, 15, 16, 29, 30, patients received leucovorin 200 mg/m(2), bolus 5-fluorouracil 400 mg/m(2), and 5-fluorouracil 600 mg/m(2) as 22-hour infusion. RESULTS: Of 132 patients randomly assigned, 130 patients (64 = ALIRI, 66 = FOLFIRI) received > or =1 dose of treatment. Response rates (ALIRI = 20.0%, FOLFIRI = 33.3%) were not significantly different between arms (p = 0.095). Progression-free survival was 5.7 months for ALIRI and 7.7 months for FOLFIRI (p < 0.001). Neutropenia, fatigue, diarrhea, nausea, and vomiting were the major toxicities. There were 5 drug-related deaths (ALIRI = 4, FOLFIRI = 1). Biomarker analysis failed to reveal that any of the 18 preselected genes were clearly associated with tumor response. CONCLUSIONS: Neither efficacy nor safety improved on the ALIRI arm compared to the FOLFIRI arm. Progression-free survival on FOLFIRI was significantly longer compared to ALIRI. Potential biomarkers capable of predicting response to either regimen in advanced or metastatic colorectal carcinoma need further characterization.

Expression levels of protein kinase C-alpha in non-small-cell lung cancer.

Current treatments of non-small-cell lung cancer (NSCLC) are inadequate and new therapies are being developed that target specific cellular signaling proteins associated with tumor growth. One potential target is protein kinase C (PKC)-alpha, a signaling molecule with an important role in cell regulation and proliferation. The present study examines the expression levels of PKC-alpha in NSCLC to better understand the distribution of PKC-alpha in NSCLC. We analyzed tumor specimens from an independent tumor tissue bank to determine PKC-alpha protein and messenger RNA gene expression in NSCLC. In addition, we used publicly available gene expression array data to further understand PKC-a-associated gene expression profiles in NSCLC. We found that PKC-alpha is highly expressed in < or = 20% of patients with NSCLC. We also found that PKC-alpha was preferentially expressed in adenocarcinoma compared with squamous cell carcinoma of the lung.

Discovery of cercosporamide, a known antifungal natural product, as a selective Pkc1 kinase inhibitor through high-throughput screening.

The Pkc1-mediated cell wall integrity-signaling pathway is highly conserved in fungi and is essential for fungal growth. We thus explored the potential of targeting the Pkc1 protein kinase for developing broad-spectrum fungicidal antifungal drugs through a Candida albicans Pkc1-based high-throughput screening. We discovered that cercosporamide, a broad-spectrum natural antifungal compound, but previously with an unknown mode of action, is actually a selective and highly potent fungal Pkc1 kinase inhibitor. This finding provides a molecular explanation for previous observations in which Saccharomyces cerevisiae cell wall mutants were found to be highly sensitive to cercosporamide. Indeed, S. cerevisiae mutant cells with reduced Pkc1 kinase activity become hypersensitive to cercosporamide, and this sensitivity can be suppressed under high-osmotic growth conditions. Together, the results demonstrate that cercosporamide acts selectively on Pkc1 kinase and, thus, they provide a molecular mechanism for its antifungal activity. Furthermore, cercosporamide and a beta-1,3-glucan synthase inhibitor echinocandin analog, by targeting two different key components of the cell wall biosynthesis pathway, are highly synergistic in their antifungal activities. The synergistic antifungal activity between Pkc1 kinase and beta-1,3-glucan synthase inhibitors points to a potential highly effective combination therapy to treat fungal infections.

Risk factors for early-onset group B streptococcal disease in neonates: a population-based case-control study.

BACKGROUND: Infection with group B streptococcus (GBS) is a major cause of neonatal illness and death. We examined the antenatal and perinatal risk factors for early-onset GBS disease among neonates. METHODS: We identified cases by population-based surveillance in all microbiology laboratories serving Alberta. A case was defined as any instance of a positive sterile-site GBS culture in an infant born between 1993 and 1997 who was either less than 7 days old or stillborn after 20 weeks' gestation. We randomly selected controls from a computer-compiled list of all hospital births, including stillbirths after 20 weeks' gestation, in Alberta during the study period. To increase power, we chose 5 or 6 control infants born in the same year as each case infant. We reviewed hospital, prenatal clinic and physician health records and, between 1997 and 1999, conducted maternal interviews by telephone. RESULTS: There were no differences between the 90 cases and 489 controls in sociodemographic variables or in many reproductive and behavioural variables. Case infants were more likely than control infants to be of low birth weight (odds ratio [OR] 3.60, 95% confidence interval [CI] 1.68-7.65), to have been delivered preterm (OR 3.89, 95% CI 2.08-7.27), or to have a mother with amnionitis (OR 15.03, 95% CI 5.58-41.89), intrapartum fever (OR 4.65, 95% CI 2.48-8.69) or premature rupture of the membranes (OR 2.39, 95% CI 1.38-4.14). After adjustment for potential confounders, intrauterine fetal monitoring was associated with a more than 2-fold increase in the risk of neonatal GBS disease (OR 2.24, 95% CI 1.22-4.13). INTERPRETATION: Intrauterine fetal monitoring should be added to the list of risk factors in risk-based screening. Since many of the cases had no identifiable maternal risk factors, universal screening for GBS may be appropriate.

Perinatal antibiotic usage and changes in colonization and resistance rates of group B streptococcus and other pathogens.

OBJECTIVE: To quantify current antibiotic usage during the perinatal period and impact on vaginal-rectal colonizing organism resistance rates. METHODS: Swabs were obtained for culture of group B streptococcus and other bacteria from a cohort of 1207 pregnant women in Calgary, Alberta, at 36 weeks' gestation. Those women who received antibiotics during labor or after pregnancy and a 10% subset who received no antibiotics had repeat cultures at 6 weeks postpartum. Cultured organisms were tested for sensitivity to several antibiotics. RESULTS: Group B streptococcus was identified in 235 women (19.5%) in the antepartum period. Fifty-one percent of all participants received antibiotics (31.4% intrapartum). Group B streptococcus prophylaxis was given to 215 (17.8%), whereas 83 (6.9%) group B streptococcus-negative women without fever during labor received antibiotics. Ampicillin (49%), cefazolin (28%), and penicillin (18%) were the most frequently used antibiotics. Resistance rates among group B streptococcus to erythromycin and clindamycin were 5.6% and 3.0%, respectively, whereas 20.6% of Escherichia coli were ampicillin resistant. Among antibiotic recipients, 6.3% of all bacteria that were initially sensitive on prenatal cultures to a specific antibiotic became resistant in the postnatal period, whereas 6.5% that were initially resistant became sensitive. CONCLUSION: Current prevention practices in our region were associated with perinatal antibiotic administration in over half of pregnant women. Ampicillin was the most common antibiotic administered. Some physicians are treating women who are group B streptococcus culture negative at term, a practice that is of no proven value. However, this was not associated with increased resistance for group B streptococcus or other organisms identified from maternal vaginal-rectal tracts.