Spatial variation in aragonite saturation state and the influencing factors in Jiaozhou Bay, China

Both natural processes and human activities affect seawater calcium carbonate saturation state (Ωarag), while the mechanisms are still far from being clearly understood. This study analysed the seawater surface Ωarag during summer and winter in Jiaozhou Bay (JZB), China, based on two cruises observations performed in January and June 2017. The ranges of Ωarag values were 1.55~2.92 in summer and 1.62~2.15 in winter. Regression analyses were conducted to identify the drivers of the change of Ωarag distribution, and then the relative contributions of temperature, mixing processes and biological processes to the spatial differences in Ωarag were evaluated by introducing the difference between total alkalinity (TA) and dissolved inorganic carbon (DIC) as a proxy for Ωarag. The results showed that biological processes were the main factor affecting the spatial differences in Ωarag, with relative contributions of 70% in summer and 50% in winter. The contributions of temperature (25% in summer and 20% in winter) and the mixing processes (5% in summer and 30% in winter) were lower. The increasing urbanization in offshore areas can further worsen acidification, therefore environmental protection in both offshore and onshore is needed

Dynamics-Based Vibration Signal Modeling for Tooth Fault Diagnosis of Planetary Gearboxes

Vibration analysis has been widely used to diagnose gear tooth fault inside a planetary gearbox. However, the vibration characteristics of a planetary gearbox are very complicated. Inside a planetary gearbox, there are multiple vibration sources as several sun-planet gear pairs, and several ring-planet gear pairs are meshing simultaneously. In addition, due to the rotation of the carrier, distance varies between vibration sources and a transducer installed on the planetary gearbox housing. Dynamics-based vibration signal modeling techniques can simulate the vibration signals of a planetary gearbox and reveal the signal generation mechanism and fault features effectively. However, these techniques are basically in the theoretical development stage. Comprehensive experimental validations are required for their future applications in real systems. This chapter describes the methodologies related to vibration signal modeling of a planetary gear set for gear tooth damage diagnosis. The main contents include gear mesh stiffness evaluation, gear tooth crack modeling, dynamic modeling of a planetary gear set, vibration source modeling, modeling of transmission path effect due to the rotation of the carrier, sensor perceived vibration signal modeling, and vibration signal decomposition techniques. The methods presented in this chapter can help understand the vibration properties of planetary gearboxes and give insights into developing new signal processing methods for gear tooth damage diagnosis

Personalized Estimate of Chemotherapy-Induced Nausea and Vomiting: Development and External Validation of a Nomogram in Cancer Patients Receiving Highly/Moderately Emetogenic Chemotherapy.

Chemotherapy-induced nausea and vomiting (CINV) is presented in over 30% of cancer patients receiving highly/moderately emetogenic chemotherapy (HEC/MEC). The currently recommended antiemetic therapy is merely based on the emetogenic level of chemotherapy, regardless of patient's individual risk factors. It is, therefore, critical to develop an approach for personalized management of CINV in the era of precision medicine.A number of variables were involved in the development of CINV. In the present study, we pooled the data from 2 multi-institutional investigations of CINV due to HEC/MEC treatment in Asian countries. Demographic and clinical variables of 881 patients were prospectively collected as defined previously, and 862 of them had full documentation of variables of interest. The data of 548 patients from Chinese institutions were used to identify variables associated with CINV using multivariate logistic regression model, and then construct a personalized prediction model of nomogram; while the remaining 314 patients out of China (Singapore, South Korea, and Taiwan) entered the external validation set. C-index was used to measure the discrimination ability of the model.The predictors in the final model included sex, age, alcohol consumption, history of vomiting pregnancy, history of motion sickness, body surface area, emetogenicity of chemotherapy, and antiemetic regimens. The C-index was 0.67 (95% CI, 0.62-0.72) for the training set and 0.65 (95% CI, 0.58-0.72) for the validation set. The C-index was higher than that of any single predictor, including the emetogenic level of chemotherapy according to current antiemetic guidelines. Calibration curves showed good agreement between prediction and actual occurrence of CINV.This easy-to-use prediction model was based on chemotherapeutic regimens as well as patient's individual risk factors. The prediction accuracy of CINV occurrence in this nomogram was well validated by an independent data set. It could facilitate the assessment of individual risk, and thus improve the personalized management of CINV

Design, Synthesis, and In vitro Antitumor Activity Evaluation of Novel 4‐pyrrylamino Quinazoline Derivatives

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/88050/1/j.1747-0285.2011.01234.x.pd

Natural IAP inhibitor Embelin enhances therapeutic efficacy of ionizing radiation in prostate cancer

This is the published version, also available here: http://www.ncbi.nlm.nih.gov/pubmed/21804946.Embelin is an active ingredient of traditional herbal medicine that exhibits anti-tumor effects in human prostate cancer cells. However, therapeutic effect of embelin in combination with conventional radiation therapy is not yet determined. In this study, we evaluate the sensitizing potential of embelin on ionizing radiation (IR) in a human prostate cancer model. In vitro, embelin combined with radiation potently suppressed prostate cancer PC-3 cell proliferation that was associated with S and G2/M arrest in cell cycle. Moreover, the combination treatment promoted caspase-independent apoptosis, as evidenced by the increased apoptotic cell death without caspase-3 activation, but not autophagy. Clonogenic survival assay showed that S-phase arrest was required for embelin-mediated radiosensitization. In vivo, embelin significantly improved tumor response to X-ray radiation in the PC-3 xenograft model. Combination therapy produced enhanced tumor growth delay and prolonged time to progression, with minimal systemic toxicity. Immunohistochemistry studies showed that embelin plus IR significantly inhibited cell proliferation, induced apoptosis, and decreased microvessel density in tumors as compared with either treatment alone, suggesting an enhanced combinatory inhibition on tumor suppression and angiogenesis. Our results demonstrate that embelin significantly facilitates tumor suppression by radiation therapy both in vitro and in vivo in the prostate cancer model. This finding warrants embelin as a novel adjuvant therapeutic candidate for the treatment of hormone-refractory prostate cancer that is resistant to radiation therapy

A Smac-mimetic sensitizes prostate cancer cells to TRAIL-induced apoptosis via modulating both IAPs and NF-kappaB

<p>Abstract</p> <p>Background</p> <p>Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising agent for human cancer therapy, prostate cancer still remains resistant to TRAIL. Both X-linked inhibitor of apoptosis (XIAP) and nuclear factor-kappaB function as key negative regulators of TRAIL signaling. In this study, we evaluated the effect of SH122, a small molecule mimetic of the second mitochondria-derived activator of caspases (Smac), on TRAIL-induced apoptosis in prostate cancer cells.</p> <p>Methods</p> <p>The potential of Smac-mimetics to bind XIAP or cIAP-1 was examined by pull-down assay. Cytotoxicity of TRAIL and/or Smac-mimetics was determined by a standard cell growth assay. Silencing of XIAP or cIAP-1 was achieved by transient transfection of short hairpin RNA. Apoptosis was detected by Annexin V-PI staining followed by flow cytometry and by Western Blot analysis of caspases, PARP and Bid. NF-kappaB activation was determined by subcellular fractionation, real time RT-PCR and reporter assay.</p> <p>Results</p> <p>SH122, but not its inactive analog, binds to XIAP and cIAP-1. SH122 significantly sensitized prostate cancer cells to TRAIL-mediated cell death. Moreover, SH122 enhanced TRAIL-induced apoptosis via both the death receptor and the mitochondrial pathway. Knockdown of both XIAP and cIAP-1 sensitized cellular response to TRAIL. XIAP-knockdown attenuated sensitivity of SH122 to TRAIL-induced cytotoxicity, confirming that XIAP is an important target for IAP-inhibitor-mediated TRAIL sensitization. SH122 also suppressed TRAIL-induced NF-kappaB activation by preventing cytosolic IkappaB-alpha degradation and RelA nuclear translocation, as well as by suppressing NF-kappaB target gene expression.</p> <p>Conclusion</p> <p>These results demonstrate that SH122 sensitizes human prostate cancer cells to TRAIL-induced apoptosis by mimicking Smac and blocking both IAPs and NF-kappaB. Modulating IAPs may represent a promising approach to overcoming TRAIL-resistance in human prostate cancer with constitutively active NF-kappaB signaling.</p

Natural Proteasome Inhibitor Celastrol Suppresses Androgen-Independent Prostate Cancer Progression by Modulating Apoptotic Proteins and NF-kappaB

Celastrol is a natural proteasome inhibitor that exhibits promising anti-tumor effects in human malignancies, especially the androgen-independent prostate cancer (AIPC) with constitutive NF-κB activation. Celastrol induces apoptosis by means of proteasome inhibition and suppresses prostate tumor growth. However, the detailed mechanism of action remains elusive. In the current study, we aim to test the hypothesis that celastrol suppresses AIPC progression via inhibiting the constitutive NF-κB activity as well as modulating the Bcl-2 family proteins.We examined the efficacy of celastrol both in vitro and in vivo, and evaluated the role of NF-κB in celastrol-mediated AIPC regression. We found that celastrol inhibited cell proliferation in all three AIPC cell lines (PC-3, DU145 and CL1), with IC₅₀ in the range of 1-2 µM. Celastrol also suppressed cell migration and invasion. Celastrol significantly induced apoptosis as evidenced by increased sub-G1 population, caspase activation and PARP cleavage. Moreover, celastrol promoted cleavage of the anti-apoptotic protein Mcl-1 and activated the pro-apoptotic protein Noxa. In addition, celastrol rapidly blocked cytosolic IκBα degradation and nuclear translocation of RelA. Likewise, celastrol inhibited the expression of multiple NF-κB target genes that are involved in proliferation, invasion and anti-apoptosis. Celastrol suppressed AIPC tumor progression by inhibiting proliferation, increasing apoptosis and decreasing angiogenesis, in PC-3 xenograft model in nude mouse. Furthermore, increased cellular IκBα and inhibited expression of various NF-κB target genes were observed in tumor tissues.Our data suggest that, via targeting the proteasome, celastrol suppresses proliferation, invasion and angiogenesis by inducing the apoptotic machinery and attenuating constitutive NF-κB activity in AIPC both in vitro and in vivo. Celastrol as an active ingredient of traditional herbal medicine could thus be developed as a new therapeutic agent for hormone-refractory prostate cancer