2,185 research outputs found
Unbonded Portland Cement Concrete Overlay/Pavement Monitoring with Integrated Grating and Scattering Optical Fiber Sensors
This report summarizes the findings and results from a laboratory and field study on the strain distribution and crack development in 3 thick concrete panels cast on top of existing concrete pavements as a rapid rehabilitation strategy for roadways. Both fiber Bragg gratings (FBG) and Brillouin Optical Time Domain Reflectometry/Analysis (BOTDR/A) were applied and tested for their feasibility and effectiveness in distributed strain measurement and crack detection. For laboratory tests, six 6\u27×6 panels were cast similar to their corresponding field construction. Each was tested under both truck loads and under threepoint loads. The performance of distributed BOTDR/A strain measurements was compared with that of FBG sensors. In field study, the performance of FBG sensors was compared with that from strain gauges when the ambient temperature was measured with thermocouples. Overall, hairline to major cracks can be successfully detected with the distributed BOTDA measurements. The strain distributions measured from the FBG and BOTDR/A sensors are consistent. The FBG readings are in good agreement with those of strain gauges. Both FBG and BOTDR/A technologies are promising for pavement monitoring
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A high-throughput screen identifies that CDK7 activates glucose consumption in lung cancer cells.
Elevated glucose consumption is fundamental to cancer, but selectively targeting this pathway is challenging. We develop a high-throughput assay for measuring glucose consumption and use it to screen non-small-cell lung cancer cell lines against bioactive small molecules. We identify Milciclib that blocks glucose consumption in H460 and H1975, but not in HCC827 or A549 cells, by decreasing SLC2A1 (GLUT1) mRNA and protein levels and by inhibiting glucose transport. Milciclib blocks glucose consumption by targeting cyclin-dependent kinase 7 (CDK7) similar to other CDK7 inhibitors including THZ1 and LDC4297. Enhanced PIK3CA signaling leads to CDK7 phosphorylation, which promotes RNA Polymerase II phosphorylation and transcription. Milciclib, THZ1, and LDC4297 lead to a reduction in RNA Polymerase II phosphorylation on the SLC2A1 promoter. These data indicate that our high-throughput assay can identify compounds that regulate glucose consumption and that CDK7 is a key regulator of glucose consumption in cells with an activated PI3K pathway
Time to tackle clonorchiasis in China
Recent publication of the global epidemiology of clonorchiasis and its relationship with cholangiocarcinoma in the journal of Infectious Diseases of Poverty has stressed the importance of Clonorchis sinensis infection. To further demonstrate its threat on public health, especially in China, comparisons between clonorchiasis and hepatitis B are made in terms of epidemiology, clinical symptoms and carcinogenicity, disability, as well as changing trends. Furthermore, major problems and prioritized researches are argued, from basic biology to intervention. Imbalance between the majority of infected population and the minority of researches in China urges for more work from Chinese scientists and international cooperation
Recurrent stress cardiomyopathy with different electrocardiographic abnormalities on each presentation in a depressed post-menopausal woman
AbstractStress cardiomyopathy (SCM) is a syndrome of transient cardiac abnormalities precipitated by intense emotional or physical stress. Differentiating SCM from acute myocardial infarction is often difficult but vital to avoid subjecting SCM patients to unnecessary reperfusion therapy and invasive coronary angiography. For accurate diagnosis, it is important that physicians be familiar with the current diagnostic criteria, most susceptible populations, and typical triggers for SCM. SCM occurs almost exclusively in post-menopausal women, a group with a high frequency of psychiatric disorders. Thus, in addition to typical trigger events, comorbid psychiatric disorders may contribute to SCM onset. We report a rare case of recurrent SCM with distinct electrocardiographic abnormalities during each presentation in a post-menopausal woman with depression.<Learning objective: Recurrence of SCM was thought to be infrequent before but it has been increasingly reported recently. Although the underlying mechanism remains unclear, comorbid psychiatric disorders may contribute significantly to the pathogenesis of SCM and its influence may have been underestimated. Routine mental health screening should be done accompanying therapy for SCM.
Review of Fiber Optic Sensors for Structural Fire Engineering
Reliable and accurate measurements of temperature and strain in structures subjected to fire can be difficult to obtain using traditional sensing technologies based on electrical signals. Fiber optic sensors, which are based on light signals, solve many of the problems of monitoring structures in high temperature environments; however, they present their own challenges. This paper, which is intended for structural engineers new to fiber optic sensors, reviews various fiber optic sensors that have been used to make measurements in structure fires, including the sensing principles, fabrication, key characteristics, and recently-reported applications. Three categories of fiber optic sensors are reviewed: Grating-based sensors, interferometer sensors, and distributed sensors
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18F-FAC PET Visualizes Brain-Infiltrating Leukocytes in a Mouse Model of Multiple Sclerosis.
Brain-infiltrating leukocytes contribute to multiple sclerosis (MS) and autoimmune encephalomyelitis and likely play a role in traumatic brain injury, seizure, and stroke. Brain-infiltrating leukocytes are also primary targets for MS disease-modifying therapies. However, no method exists for noninvasively visualizing these cells in a living organism. 1-(2'-deoxy-2'-18F-fluoroarabinofuranosyl) cytosine (18F-FAC) is a PET radiotracer that measures deoxyribonucleoside salvage and accumulates preferentially in immune cells. We hypothesized that 18F-FAC PET could noninvasively image brain-infiltrating leukocytes. Methods: Healthy mice were imaged with 18F-FAC PET to quantify if this radiotracer crosses the blood-brain barrier (BBB). Experimental autoimmune encephalomyelitis (EAE) is a mouse disease model with brain-infiltrating leukocytes. To determine whether 18F-FAC accumulates in brain-infiltrating leukocytes, EAE mice were analyzed with 18F-FAC PET, digital autoradiography, and immunohistochemistry, and deoxyribonucleoside salvage activity in brain-infiltrating leukocytes was analyzed ex vivo. Fingolimod-treated EAE mice were imaged with 18F-FAC PET to assess if this approach can monitor the effect of an immunomodulatory drug on brain-infiltrating leukocytes. PET scans of individuals injected with 2-chloro-2'-deoxy-2'-18F-fluoro-9-β-d-arabinofuranosyl-adenine (18F-CFA), a PET radiotracer that measures deoxyribonucleoside salvage in humans, were analyzed to evaluate whether 18F-CFA crosses the human BBB. Results: 18F-FAC accumulates in the healthy mouse brain at levels similar to 18F-FAC in the blood (2.54 ± 0.2 and 3.04 ± 0.3 percentage injected dose per gram, respectively) indicating that 18F-FAC crosses the BBB. EAE mice accumulate 18F-FAC in the brain at 180% of the levels of control mice. Brain 18F-FAC accumulation localizes to periventricular regions with significant leukocyte infiltration, and deoxyribonucleoside salvage activity is present at similar levels in brain-infiltrating T and innate immune cells. These data suggest that 18F-FAC accumulates in brain-infiltrating leukocytes in this model. Fingolimod-treated EAE mice accumulate 18F-FAC in the brain at 37% lower levels than control-treated EAE mice, demonstrating that 18F-FAC PET can monitor therapeutic interventions in this mouse model. 18F-CFA accumulates in the human brain at 15% of blood levels (0.08 ± 0.01 and 0.54 ± 0.07 SUV, respectively), indicating that 18F-CFA does not cross the BBB in humans. Conclusion: 18F-FAC PET can visualize brain-infiltrating leukocytes in a mouse MS model and can monitor the response of these cells to an immunomodulatory drug. Translating this strategy into humans will require exploring additional radiotracers
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Rapid, efficient, and economical synthesis of PET tracers in a droplet microreactor: application to O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET).
BackgroundConventional scale production of small batches of PET tracers (e.g. for preclinical imaging) is an inefficient use of resources. Using O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET), we demonstrate that simple microvolume radiosynthesis techniques can improve the efficiency of production by consuming tiny amounts of precursor, and maintaining high molar activity of the tracers even with low starting activity.ProceduresThe synthesis was carried out in microvolume droplets manipulated on a disposable patterned silicon "chip" affixed to a heater. A droplet of [18F]fluoride containing TBAHCO3 was first deposited onto a chip and dried at 100 °C. Subsequently, a droplet containing 60 nmol of precursor was added to the chip and the fluorination reaction was performed at 90 °C for 5 min. Removal of protecting groups was accomplished with a droplet of HCl heated at 90 °C for 3 min. Finally, the crude product was collected in a methanol-water mixture, purified via analytical-scale radio-HPLC and formulated in saline. As a demonstration, using [18F]FET produced on the chip, we prepared aliquots with different molar activities to explore the impact on preclinical PET imaging of tumor-bearing mice.ResultsThe microdroplet synthesis exhibited an overall decay-corrected radiochemical yield of 55 ± 7% (n = 4) after purification and formulation. When automated, the synthesis could be completed in 35 min. Starting with < 370 MBq of activity, ~ 150 MBq of [18F]FET could be produced, sufficient for multiple in vivo experiments, with high molar activities (48-119 GBq/μmol). The demonstration imaging study revealed the uptake of [18F]FET in subcutaneous tumors, but no significant differences in tumor uptake as a result of molar activity differences (ranging 0.37-48 GBq/μmol) were observed.ConclusionsA microdroplet synthesis of [18F]FET was developed demonstrating low reagent consumption, high yield, and high molar activity. The approach can be expanded to tracers other than [18F]FET, and adapted to produce higher quantities of the tracer sufficient for clinical PET imaging
Atezolizumab and Bevacizumab Attenuate Cisplatin Resistant Ovarian Cancer Cells Progression Synergistically via Suppressing Epithelial-Mesenchymal Transition
The AURELIA trial demonstrated that adding Bevacizumab to chemotherapy significantly improved progression-free survival (PFS) for platinum resistant recurrent ovarian cancer. Recently, immunotherapy also presented potential anti-tumor effects in several malignant solid tumors. This study aimed to investigate whether combining anti-PD-L1 Atezolizumab with BEV may have a synergistic effect and enhance the efficacy of both treatments in cisplatin resistant epithelial ovarian cancer (CREOC). We retrospectively analyzed 124 epithelial ovarian cancer (EOC) patients from Gynecologic Oncology Department of Tianjin Cancer Hospital between January 2013 and June 2018, who all were diagnosed with cisplatin resistance due to progressing <6 months after completing platinum-based therapy. Based on responding to at least 2 cycles of Bevacizumab-containing chemotherapy (BC), these Patients were divided into BC response group and BC non-response group. Immunohistochemistry was used to detect that PD-L1 expression and tumor angiogenesis-related proteins (VEGF and Semaphorin4D) in tissues from 124 patients with CREOC. The positive expressions of PD-L1, VEGF, and Semaphorin4D (SEMA4D) were found in 58.73, 50.79, and 71.43% of the 63 cases CREOC tissues with BC response, respectively, which were significantly higher than that in the 61 cases BC non-response group (P < 0.05). PD-L1 expression correlated with SEMA4D and VEGF positively (r = 0.344 and 0.363, P < 0.001). Over-expressions of PD-L1, VEGF and SEMA4D are associated with more malignant clinicopathologic characteristics of CREOC Patients. In survival analysis, patients' response to BC was the independent factor for evaluation of PFS and overall survival (OS). Cell functional assays showed that Atezolizumab in combination with Bevacizumab inhibited the proliferation, migration, and invasion of cisplatin resistant ovarian cancer cell line A2780cis in vitro synergistically, which maybe associate with Bevacizumab suppressing the epithelial-mesenchymal transition (EMT) and PD-L1 expression by targeting STAT3. Furthermore, Bevacizumab and Atezolizumab induced synergistic anti-tumor effect in vivo. These findings suggest a novel therapeutic strategy for cisplatin resistant recurrent EOC and its mechanism warrants further study
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