This book provides the application of praxises in the field of engineering safety by learning from previous system failures. And it addresses the most recent developments in the theoretical and ...practical aspects of these important fields, which, due to their special nature, bring together in a systematic way, many disciplines of engineering, from the traditional to the most technologically advanced. The authors of these chapters are involved in using the system thinking and system engineering approaches at the scale of increased complexity and advanced computational solutions to such systems. The chapters cover the areas such as failure assessment in aeronautical engineering, seismic resistance of offshore pipeline engineering, electrical engineering, critical infrastructure failure, and system of system theory.
The promising anti-tumor effects of oncolytic vaccinia virus (OVV) have been demonstrated. Further, we previously showed that long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) ...enhances OVV cell-to-cell spread via the activation of Cdc42 in ovarian cancer. However, its role in other cancer types and the molecular mechanism underlying its effects remain to be explored. In this study, we first demonstrated that UCA1 upregulates OVV cell-to-cell spread but not its binding, entry, and replication in colorectal cancer cells. Functional analysis indicated that Cdc42 activation and filopodia formation play an important role in this process. Moreover, expression analysis of various miRNAs suggested that UCA1 inhibits both miR-18a and miR-182, thereby promoting Cdc42 activation, which in turn, regulates OVV cell-to-cell spread. Furthermore, UCA1 was found to modulate tumor malignancy, drug resistance, and sensitivity to OVV via different miRNAs in colorectal cancer. These findings indicate that a three-marker panel, which includes UCA1 expression, Cdc42 activation, and filopodia formation, could potentially be used to predict the therapeutic effect of OVV in colorectal cancer.
•UCA1 enhances OVV spread in colorectal cancer.•UCA1 specifically regulates OVV cell-to-cell spread.•Cdc42 activation enhances OVV spread via filopodia formation.•MiR-18a and miR-182 are regulated by UCA1.
This work focuses on the stabilization and speciation of lead (Pb) in a composite solid produced from an alkali-activated municipal solid waste incineration fly ash (MSWIFA)–pyophyllite-based system. ...The solid product was synthesized after mixtures of raw materials (dehydrated pyrophyllite, MSWIFA, 14 mol/L aqueous sodium hydroxide, and sodium silicate solution) were cured at 105 °C for 24 h. The product could reduce the leaching of Pb and the Pb concentration in the leachate was 7.0 × 10−3 using the Japanese leaching test and 9.7 × 10−4 mg/L using toxicity characteristics leaching procedure method, which satisfied the respective test criteria and successfully stabilized Pb in this system. The solid product had a compressive strength of 2 MPa and consisted mainly of crystalline phases. Scanning electron microscopy with X-ray analysis and X-ray absorption fine structure suggested that Pb was present along with Al, Si, and O, and that the atomic environment around the Pb was similar to that of PbSiO3. These results suggest that the alkali-activated MSWIFA–pyrophyllite-based system could be used to stabilize Pb in MSWIFA.
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•Stabilization and speciation of Pb in MSWIFA were investigated.•An alkali-activated MSWIFA–pyrophyllite-based system was used for the Pb stabilization.•Two leaching tests showed that the Pb stabilization in products were successful.•X-ray analyses suggested that PbSiO3 or a Pb-aluminosilicate formed in the products.
Abstract
We are developing the Gamma-Ray Astro-Imager with Nuclear Emulsion project, designed for 10 MeV–100 GeV cosmic
γ
-ray observations with a high angular resolution (5′/0.°08 at 1–2 GeV) and a ...polarization-sensitive large-aperture (∼10 m
2
) emulsion telescope for repeated long-duration balloon flights. In 2018, a balloon-borne experiment was carried out in Australia with a 0.38 m
2
sensitive area and a flight duration of 17.4 hr, including 6.7 hr of Vela observations. Significant improvements compared with the 2015 balloon-borne experiment were achieved by a factor of 5, including both an increase in effective area × time and a reduction in the background contribution. We aimed to demonstrate the telescope’s overall performance based on detection and imaging of a known
γ
-ray source, the Vela pulsar. A robust detection of the Vela pulsar was achieved with a 68% containment radius of 0.°42, at a significance of 6
σ
, at energies above 80 MeV. The resulting angular profile is consistent with that of a pointlike source. We achieved the current best imaging performance of the Vela pulsar using an emulsion
γ
-ray telescope with the highest angular resolution of any
γ
-ray telescope to date.
Purpose
Chronic inflammation is thought to cause ligamentum flavum (LF) degeneration and hypertrophy in lumbar spinal canal stenosis (LSCS). Angiopoietin-like protein 2 (Angptl2) is highly expressed ...in hypertrophied LF. Because Angptl2 regulates interleukin-6 (IL-6) expression in various tissues, we investigated whether IL-6 is expressed in hypertrophied LF and, if so, does Angptl2 induce IL-6 expression in LF fibroblasts.
Methods
LF tissue was obtained from LSCS patients and non-LSCS patients. Polymerase chain reaction (PCR) for
Angptl2
and
IL
-
6
genes and immunohistochemistry for IL-6 protein were performed in LF tissue. Fibroblasts from LF tissue were used for in vitro experiments. Expression of integrin α5β1 (an Angptl2 receptor) and Angptl2 binding to receptors on LF fibroblasts were examined by fluorescence-activated cell sorter analysis and cell adhesion assays. After Angptl2 recombinant protein treatment, NF-κB activation and IL-6 expression in LF fibroblasts were investigated by immunocytochemistry, PCR, and enzyme-linked immunosorbent assay.
Results
IL
-
6
mRNA expression was increased in hypertrophied LF tissue from LSCS patients and positively correlated with LF thickness and
Angptl2
mRNA expression. IL-6 protein was highly expressed in LF fibroblasts in hypertrophied LF tissue. In vitro experiments demonstrated integrin α5β1 expression on LF fibroblasts and Angptl2 binding to cells via receptors. Angptl2 stimulation promoted NF-κB nuclear translocation and induced IL-6 expression and secretion in LF fibroblasts.
Conclusions
Angptl2 promotes inflammation in LF tissue by activating IL-6 expression, leading to LF degeneration and hypertrophy.
Environmentally sound treatments are required to dispose of municipal solid waste incineration fly ash (MSWIFA) contaminated with radioactive cesium (Cs) from the Fukushima Daiichi nuclear power ...plant accident in Japan. This study focuses on the stabilization of Cs using an alkali-activated MSWIFA and pyophyllite-based system. Three composite solid products were synthesized after mixtures of raw materials (dehydrated pyrophyllite, MSWIFA, 14 mol/L aqueous sodium hydroxide, and sodium silicate solution) were cured at 105 °C for 24 h. Three types of MSWIFAs were prepared as raw fly ash, raw fly ash with 0.1% CsCl, and raw fly ash with 40% CsCl to understand the stabilization mechanism of Cs. Cs stabilization in two solid products was successful, with less than 6.9% leaching observed from two types tests, and was partly successful for the solid product with the highest concentration of Cs. X-ray diffraction showed that all of the solid products produced several crystalline phases, and that pollucite was formed in the highest Cs concentration product. The X-ray absorption fine structure and scanning electron microscopy with X-ray analysis suggested that most Cs species formed pollucite in the two solid products from MSWIFA with added CsCl. This system provides a technique for the direct stabilization of Cs in MSWIFA.
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•Stabilization and speciation of Cs in MSWIFA were investigated.•An alkali-activated MSWIF ash and pyrophyllite-based system was used.•The Cs stabilization in a product were successful for TCLP.•The Cs stabilization in two products were successful for a Japanese leaching test.•Pollucite was formed as the most abundant Cs species in two products.
Key points
The cortical mechanisms of grasping have been extensively studied in macaques and humans; here, we investigated whether common marmosets could rely on similar mechanisms despite strong ...differences in hand morphology and grip diversity.
We recorded electrocorticographic activity over the sensorimotor cortex of two common marmosets during the execution of different grip types, which allowed us to study cortical activity (power spectrum) and physiologically inferred connectivity (phase‐slope index).
Analyses were performed in beta (16–35 Hz) and gamma (75–100 Hz) frequency bands and our results showed that beta power varied depending on grip type, whereas gamma power displayed clear epoch‐related modulation.
Strength and direction of inter‐area connectivity varied depending on grip type and epoch.
These findings suggest that fundamental control mechanisms are conserved across primates and, in future research, marmosets could represent an adequate model to investigate primate brain mechanisms.
The cortical mechanisms of grasping have been extensively studied in macaques and humans. Here, we investigated whether common marmosets could rely on similar mechanisms despite striking differences in manual dexterity. Two common marmosets were trained to grasp‐and‐pull three objects eliciting different hand configurations: whole‐hand, finger and scissor grips. The animals were then chronically implanted with 64‐channel electrocorticogram arrays positioned over the left premotor, primary motor and somatosensory cortex. Power spectra, reflecting predominantly cortical activity, and phase‐slope index, reflecting the direction of information flux, were studied in beta (16–35 Hz) and gamma (75–100 Hz) bands. Differences related to grip type, epoch (reach, grasp) and cortical area were statistically assessed. Results showed that whole‐hand and scissor grips triggered stronger beta desynchronization than finger grip. Task epochs clearly modulated gamma power, especially for finger and scissor grips. Considering effective connectivity, finger and scissor grips evoked stronger outflow from primary motor to premotor cortex, whereas whole‐hand grip displayed the opposite pattern. These findings suggest that fundamental control mechanisms, relying on adjustments of cortical activity and connectivity, are conserved across primates. Consistently, marmosets could represent a good model to investigate primate brain mechanisms.
Key points
The cortical mechanisms of grasping have been extensively studied in macaques and humans; here, we investigated whether common marmosets could rely on similar mechanisms despite strong differences in hand morphology and grip diversity.
We recorded electrocorticographic activity over the sensorimotor cortex of two common marmosets during the execution of different grip types, which allowed us to study cortical activity (power spectrum) and physiologically inferred connectivity (phase‐slope index).
Analyses were performed in beta (16–35 Hz) and gamma (75–100 Hz) frequency bands and our results showed that beta power varied depending on grip type, whereas gamma power displayed clear epoch‐related modulation.
Strength and direction of inter‐area connectivity varied depending on grip type and epoch.
These findings suggest that fundamental control mechanisms are conserved across primates and, in future research, marmosets could represent an adequate model to investigate primate brain mechanisms.
Chronic inflammation and subsequent fibrosis induced by mechanical stress play an important role in ligamentum flavum (LF) hypertrophy and degeneration in patients with lumbar spinal canal stenosis ...(LSCS). Angiopoietin-like protein 2 (Angptl2) is a chronic inflammatory mediator induced under various pathological conditions and increases the expression of TGF-β1, which is a well-characterized mediator in LF hypertrophy. We investigated whether Angptl2 is induced by mechanical stress, and whether it contributes to LF hypertrophy and degeneration by activating the TGF-β1 signaling cascade. In this study, we investigated human LF tissue and LF fibroblasts isolated from patients who underwent lumbar surgery. We found that Angptl2 was abundantly expressed in fibroblasts of hypertrophied LF tissues at both the mRNA and protein levels. This expression was not only positively correlated with LF thickness and degeneration but also positively correlated with lumbar segmental motion. Our in vitro experiments with fibroblasts from hypertrophied LF tissue revealed that mechanical stretching stress increases the expression and secretion of Angptl2 via activation of calcineurin/NFAT pathways. In hypertrophied LF tissue, expression of TGF-β1 mRNA was also increased and TGF-β1/Smad signaling was activated. Angptl2 expression in LF tissue was positively correlated with the expression of TGF-β1 mRNA, suggesting cooperation between Angptl2 and TGF-β1 in the pathogenesis of LF hypertrophy. In vitro experiments revealed that Angptl2 increased levels of TGF-β1 and its receptors, and also activated TGF-β1/Smad signaling. Mechanical stretching stress increased TGF-β1 mRNA expression, which was partially attenuated by treatment with a calcineurin/NFAT inhibitor or Angptl2 siRNA, indicating that induction of TGF-β1 expression by mechanical stretching stress is partially mediated by Angptl2. We conclude that expression of Angptl2 induced by mechanical stress in LF fibroblasts promotes LF tissue degeneration by activation of TGF-β1/Smad signaling, which results in LF hypertrophy in patients with LSCS.
Abstract
This study develops a view of Hume’s
is/ought
distinction as an extension of Scottish jurisprudence that, in turn, was influenced by Pufendorf’s discussion of
entia moralia
. Further, it ...investigates the unique role that Hume’s sentimentalism played in the production of elements in the context of liberalism under the rule of law, independently of previous philosophical traditions.
First, we observe that Hume’s is/ought distinction corresponds to a distinction between uncivilized and civilized entities, rather than between amoral rationality and moral passions. Next, analyzing Hume’s argument for “moral evidence,” we find that such evidence is necessary for various activities, such as consent or trading, in the field of moral entities as civil societies. Finally, a study of Hume’s stance with respect to civil and common laws shows that his moral sentimentalism, which includes the is/ought distinction and moral evidence, suggests a new possibility for social development that is distinct from previous rational forms of jurisprudence. From this discussion, a unique sprout of modern liberalism can be seen in Hume’s theory of justice.
Foxp3+ CD4+CD25+ regulatory T (Treg) cells and immunoregulatory enzyme indoleamine 2,3‐dioxygenase (IDO) play an important role in immunoregulation. Accumulating evidence shows that IDO and Treg ...cells have potent regulatory properties for immune escape in cancer. To evaluate the expression of IDO and the localization of Foxp3+ Treg cells in the development and progression of uterine cervical cancer, IDO expression and Foxp3+ Treg cells in the primary and metastatic lesions were studied using immunohistochemistry. IDO expression in tumor cells appeared in cervical intraepithelial neoplasia (CIN)‐3 of the uterine cervix and marked expression in microinvasive cancer cells was observed. Interestingly, IDO expression in invasive cancer was confined to the cancer cells at the invasive front. Moreover, antigen‐presenting cells (APC) at the invasive front in primary and metastatic lesions were also expressing IDO. Stromal Foxp3+ Treg cells appeared in CIN‐3 and increased in microinvasive and invasive cancer. Intraepithelial Foxp3+ Treg cells were restricted within microinvasive and invasive cancer. No significant differences in the proportion of Foxp3+/CD4+ in the stroma or epithelium, or between non‐metastatic and metastatic invasive cancers, were observed in primary lesions of cervical cancer, while there was a significant increase (P < 0.005) in the proportion of Foxp3+/CD4+ in metastatic lymph nodes compared with non‐metastatic lymph nodes. Some of the Foxp3+ Treg cells in metastatic lymph nodes contacted the IDO+ APC. IDO expression at the invasive front of cancer cells and APC, and the localization of Foxp3+ Treg cells in front of cancer tissues, may create a network between IDO and Treg for the induction of immune escape. (Cancer Sci 2007; 98: 874–881)
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