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Supplementary Fig. S1 from Antixenograft tumor activity of a humanized anti-insulin-like growth factor-I receptor monoclonal antibody is associated with decreased AKT activation and glucose uptake

Supplementary Table S1 from Antixenograft tumor activity of a humanized anti-insulin-like growth factor-I receptor monoclonal antibody is associated with decreased AKT activation and glucose uptake

The insulin-like growth factor (IGF) system consists of two ligands (IGF-I and IGF-II), which both signal through IGF-I receptor (IGF-IR) to stimulate proliferation and inhibit apoptosis, with activity contributing to malignant growth of many types of human cancers. We have developed a humanized, affinity-matured anti-human IGF-IR monoclonal antibody (h10H5), which binds with high affinity and specificity to the extracellular domain. h10H5 inhibits IGF-IR-mediated signaling by blocking IGF-I and IGF-II binding and by inducing cell surface receptor down-regulation via internalization and degradation, with the extracellular and intracellular domains of IGF-IR being differentially affected by the proteasomal and lysosomal inhibitors. In vitro, h10H5 exhibits antiproliferative effects on cancer cell lines. In vivo, h10H5 shows single-agent antitumor efficacy in human SK-N-AS neuroblastoma and SW527 breast cancer xenograft models and even greater efficacy in combination with the chemotherapeutic agent docetaxel or an anti–vascular endothelial growth factor antibody. Antitumor activity of h10H5 is associated with decreased AKT activation and glucose uptake and a 316-gene transcription profile with significant changes involving DNA metabolic and cell cycle machineries. These data support the clinical testing of h10H5 as a biotherapeutic for IGF-IR-dependent human tumors and furthermore illustrate a new method of monitoring its activity noninvasively in vivo via 2-fluoro-2-deoxy-d-glucose-positron emission tomography imaging. [Mol Cancer Ther 2008;7(9):2599–608]

Our work was to evaluate Exosome CircRNA EIF4G2 in cervical cancer development. Methods: Using Hela and Siha in our present study. Transfection vector, exosome cirEIF4G2, exosome si-NC or exosome si-circEIF4G2 in cells. Using RT-qPCR to measure circEIF4G2 gene expression in difference cell groups. Evaluating cell proliferation, apoptosis, invasion and wound healing rate by MTT, flow cytometry, transwell and wound healing assay. The relative proteins, HPV16 E6 and HPV16 E7, were evaluated by WB assay. With Exosome CircRNA EIF4G2 transfection, Hela and Siha cells proliferation, invasion cells number and wound healing rates were significantly increased and cells apoptosis were significantly depressed (P < 0.001, respectively) with HPV16 E6 and HPV16 E7 proteins expression were significantly up-regulation (P < 0.001, respectively). However, with Exosome si-CircRNA EIF4G2 transfection, Hela and Siha cells proliferation, invasion cells number and wound healing rates were significantly depressed and cells apoptosis were significantly increased (P < 0.001, respectively) with HPV16 E6 and HPV16 E7 proteins expression were significantly down-regulation (P < 0.001, respectively). Exosome CircRNA EIF4G2 as an oncology role in cervical cancer via regulation HPV16 E6/E7 up-regulation in vitro study.

Gearbox vibration signals are usually disturbed under strong noise. Therefore, the fault feature frequency cannot be extracted accurately and effectively. In order to extract the fault feature of the gearbox, a method based on compound time-frequency atomic dictionary and orthogonal matching pursuit (OMP) optimized by wingsuit flying search algorithm (WFSA) is proposed. Firstly, according to the feature of the gearbox fault vibration signal, a compound time-frequency atomic dictionary composed of steady state modulation dictionary and impact modulation dictionary is designed. In addition, in order to improve the accuracy and efficiency of signal sparse decomposition. In this paper, WFSA is used to optimize the dictionary atomic parameters in OMP, so that the dictionary atom approximated the original signal better. Through simulation analysis and experimental verification and compared with the commonly used gearbox fault feature extraction methods, the superiority and effectiveness of the method are verified.

Current encapsulating materials for white light–emitting diodes (WLEDs) have some insurmountable problems of unrecyclable encapsulating materials and the toxicity of phosphors. The much more promising encapsulating materials should have two characteristics: 1) the chip can be directly encapsulated without phosphors via the luminescence of encapsulating materials, and 2) the encapsulating materials can be reprocessed for recycling. To this end, blue-light emissive vitrimers (BEVs) were first prepared from the reaction of epoxy resin with aliphatic amines, which exhibited strong blue-light emission at 365-nm excitation and fast stress relaxation without an external catalyst. To design the white-light emission, a well-designed yellow element of perylenetetracarboxylic dianhydride was grafted into the BEVs to generate white-light emissive vitrimers (WEVs). In the WEVs, a rare combination of blue- and yellow-light emissions was achieved for designing white light. When the WEV was used as an encapsulating adhesive for 365-nm LED chips without phosphors, stable white light with CIE coordination (0.30, 0.32) was successfully achieved, which provided a promising future for WLED encapsulations.

Light Field (LF) imaging empowers many attractive applications by simultaneously recording spatial and angular information of light rays. In order to meet the challenges of LF storage and transmission, many view reconstruction-based LF compression methods are put forward. However, occlusion issue and under-exploitation of LF rich structure information limit the view reconstruction qualities, which further influence LF compression efficiency. In order to alleviate these problems, in this paper, we propose a geometry-aware view reconstruction network for LF compression. In our method, only sparsely-sampled LF views are encoded, which are further used as priors to reconstruct the un-sampled LF views at the decoder side. The proposed reconstruction process contains two stages including geometry-aware reconstruction and texture refinement. The geometry-aware reconstruction stage utilizes a multi-stream framework, which can fully explore LF spatial-angular, location and geometry information. The texture refinement stage can adequately fuse such rich LF information to further improve LF reconstruction quality. Comprehensive experimental results validate the superiority of the proposed method. The rate-distortion performance and the perceptual quality of reconstructed views further demonstrate that the proposed method can save more bitrate while increasing LF reconstruction quality.

A chemoselective as well as enantioselective fluorescent probe has been developed to determine both the concentration and enantiomeric composition of the biologically important amino acid histidine by measuring the fluorescence responses when excited at two different wavelengths.

Background Small cell-derived extracellular vesicles (EVs) can affect endothelial function. We previously found that patients with sickle cell disease (SCD) have greater numbers of circulating EVs than subjects without the disease, and the EVs differentially disrupt endothelial integrity in vitro. Because endothelial disruption is a critical component of acute chest syndrome (ACS), we hypothesized that EVs isolated during ACS would induce greater endothelial damage than those isolated at baseline. Methods Nine pediatric subjects had plasma isolated at baseline and during ACS from which EVs were isolated. Cultured microvascular endothelial cells were treated with EVs and then studied by immunofluorescence microscopy to localize VE-cadherin and F-actin. Results The EVs had a diameter of 95 nm. They contained CD63 and flotillin-1, which were increased in SCD patients (5-13-fold compared to control) and further increased between baseline and ACS (24-57%). The EVs contained hemoglobin, glycophorin A, and ferritin. Treatment with baseline EVs caused modest separation of endothelial cells, while ACS EVs caused substantial disruptions of the endothelial cell monolayers. EVs from subjects with ACS also caused a 50% decrease in protein levels of VE-cadherin. Conclusions These results suggest that circulating EVs can modulate endothelial integrity contributing to the development of ACS in SCD patients by altering cadherin-containing intercellular junctions. Impact Sickle cell disease patients have circulating extracellular vesicles (EVs) that modulate endothelial integrity by altering cadherin-containing intercellular junctions. Disruption is more severe by EVs obtained during acute chest syndrome (ACS). These results expand our knowledge of the pathophysiology of acute chest syndrome and the vasculopathies of sickle cell disease.

A series of BINOL-based monoaldehydes have been designed and synthesized as fluorescent probes for L- and D-tryptophan. It is found that in the presence of a diblock copolymer PEG-PLLA, these probes can be encapsulated into micelles which in combination with Zn2+ have exhibited chemo- and enantioselective fluorescent enhancement with tryptophan in aqueous media.

This retrospective study sought to characterize the incidence of mortality in elderly patients following bariatric surgery and assessed the association of geriatric status with postoperative outcomes and resource use.Bariatric surgery is a safe and efficacious intervention for obesity and related diseases. The clinical and economic impact of geriatric status on bariatric surgery is largely unexplored.Academic, university-affiliated hospital; US.Adults (≥45 yr) undergoing elective laparoscopic gastric bypass or sleeve gastrectomy were identified in the 2016-2019 Nationwide Readmissions Database. Patients ≥65 years were categorized into the geriatric cohort. Multivariable linear and logistic models were developed to evaluate the independent association of geriatric status with outcomes of interest.Of an estimated number of 351,292 patients meeting inclusion criteria, 44,183 (12.6%) comprised the geriatric cohort. Of these patients, .3% died during the index hospitalization. Geriatric status was associated with significantly increased odds of in-hospital mortality (adjusted odds ratio [AOR] = 2.39, 95% confidence interval [CI]: 1.33-4.30), respiratory (AOR = 1.34, 95% CI: 1.13-1.59), infectious (AOR = 1.65, 95% CI: 1.25-2.17), and renal complications (AOR = 1.27, 95% CI: 1.12-1.46), and prolonged hospitalization (AOR = 1.35, 95% CI: 1.24-1.48). Elderly patients experienced a .19-day increment in the length of stay (95% CI: .11-.27) and $620 in attributable hospitalization costs (95% CI: 310-930).While overall rates of postoperative death and complications are low, geriatric patients experience significantly increased mortality, morbidity, and resource use following bariatric operations relative to younger adults. These findings may aid in shared decision-making for obesity management in geriatric patients.

We previously found that the plasma of patients with sickle cell disease (SCD) contains large numbers of small extracellular vesicles (EVs) and that the EVs disrupt the integrity of endothelial cell monolayers (especially if obtained during episodes of acute chest syndrome, ACS). The present study was designed to test the generality of this finding to other complications of SCD, specifically to evaluate the possibility that circulating EVs isolated during a vaso-occlusive crises (VOC) also cause damage to the intercellular connections between endothelial cells. Plasma was obtained from nine pediatric subjects at baseline and during VOC episodes. EVs isolated from these samples were added to cultures of microvascular endothelial cells. Immunofluorescence microscopy was employed to assess monolayer integrity and to localize two intercellular junction proteins (VE-cadherin and connexin43). The EVs isolated during VOC caused significantly greater monolayer disruption than those isolated at baseline. The extent of disruption varied between different episodes of VOC or ACS in the same patient. The VOC EVs disrupted the integrity of both junction proteins at appositional membranes. These results suggest that circulating EVs may be involved in modulating endothelial integrity contributing to the pathogenesis of different complications of SCD.

Aim: Present research was to explore the effects and mechanisms of hydroxysafflor yellow A in treatment of isoproterenol-induced myocardial fibrosis in rats. Methods: Dividing 50 SD rats as the normal control, ISO and HSYA treated groups, 10 rats in each group. Administering Rats by ISO subcutaneously (2 mg/kg · d) for 10 days induce myocardial fibrosis. HSYA treated groups were treated with 10, 20 and 40 mg/kg · d HSYA for 4 weeks (ig). The normal control and the model groups were treated with saline at equivalent volume. Measurement of hemodynamics index to evaluate the changes of cardiac function. And evaluating the relative index of difference groups. Results: Treatment of HSYA significantly inhibited heart rate (HR) and LVEDP, meanwhile improving LVSP compared with model group with dose-dependent. HE staining and Masson staining showed that diltiazem improve heart structure disorder, excessive accumulation of collagen fibers, meanwhile decreasing the value of collagen volume fraction (CVF) (P < 0.05). The result showed diltiazem inhibited Collagen I and Collagen II which were up-regulation (P < 0.001). HSYA could significantly increase SOD, GSH-Px levels (P < 0.001), meanwhile reducing the MDA levels in ISO-induced myocardial fibrosis model (P < 0.001) with dose-dependent. In addition, the elevated NF-κB, TGF-β1, CTGF expressions were effectively restored by HSYA(P < 0.001). Conclusion: HSYA alleviated ISO induced myocardial fibrosis in rat, which might be correlation with the improvement of reduction of oxidative stress and inhibition of NF-κB signal pathway.

Under harsh conditions, the desorption of polyampholytes from bentonite (Bent) can affect the performance of drilling fluids. To study the desorption of polyampholyte from bentonite, partially hydrolyzed copolymers of acrylamide and diallyl dimethyl ammonium chloride (HPAD), containing carboxyl groups, quaternary ammonium groups and amide groups was synthesized via free radical copolymerization followed by hydrolyzation. The molecular structure of HPAD was characterized by 1H NMR and 13C NMR. The adsorption equilibrium of HPAD on Bent in the presence of 10 wt% NaCl was 106 mg·g–1. The adsorption-desorption behavior of HPAD on Bent was studied using a high pressure and high temperature (HPHT) filtration apparatus, to obtain the filtrate liquid and filter cakes. The content of HPAD in the filtration and the filter cakes was determined via UV and element analysis, respectively. As the temperature increased, the desorption of HPAD from Bent accelerated owing to molecular thermal motion and thermal degradation of the adsorptive groups. Notably, the decomposition rate of the amide group was more than twice that of the quaternary ammonium group. The critical temperature for HPAD desorption was 135°C, as the decomposition of the adsorptive groups became predominant over intensified molecular thermal motion at high temperatures.

Circular RNAs (circRNAs) serve important roles in tumorigenesis and may be used as novel molecular biomarkers for clinical diagnosis. However, the role and molecular mechanisms of circRNAs in cervical cancer (CC) remain unknown. In the present study, circRNA isoform of eukaryotic translation initiation factor 4γ2 (circEIF4G2) was revealed to be significantly upregulated in CC tissues and cell lines. Furthermore, increased expression of circEIF4G2 was associated with poor prognosis in patients with CC. circEIF4G2 knockdown suppressed the malignant features of CC cells, including cell proliferation, colony formation, migration and invasion. Additionally, circEIF4G2 was identified to serve as a sponge for microRNA‑218 (miR‑218), which targeted homeobox A1 (HOXA1). Furthermore, circEIF4G2 may increase the expression levels of HOXA1 by sponging miR‑218. Rescue experiments suggested that transfection with a miR‑218 inhibitor attenuated the inhibitory effects of circEIF4G2 knockdown on cell proliferation, migration and invasion. Furthermore, silencing HOXA1 reversed the effects of the miR‑218 inhibitor on CC cells. Collectively, the present findings suggested that circEIF4G2 promoted cell proliferation and migration via the miR‑218/HOXA1 pathway.

The vibration signal of gearbox is characterized by complex components and multiple modes of aliasing. In order to extract the fault feature of gearbox, a new method based on composite time-frequency atomic dictionary and fast kurtogram is proposed. Firstly, according to the characteristics of the gearbox fault vibration signal, a composite time-frequency atomic dictionary composed of steady-state modulation dictionary and impact modulation dictionary is constructed. Then, the vibration signal is denoised by OMP. Moreover, the optimal filter parameters are determined by fast kurtogram to filter the noise reduction signal, and the frequency spectrum analysis of the filtered signal is carried out to obtain the gearbox fault feature. At the same time, the performance of the composite time-frequency atomic dictionary and classical DCT, Fourier and LFMF dictionaries and their robustness under different noises are studied. The result shows that the composite time-frequency atomic dictionary is superior to other dictionaries in reconstruction accuracy and computational efficiency. Finally, the above method is applied to the experimental signal, which can accurately extract the gearbox fault feature.

Intelligent diagnosis is often biased toward common diseases due to data imbalance between common and rare diseases. Such bias may still exist even after applying re-balancing strategies during model training. To further alleviate the bias, we propose a novel method which works not in the training but in the inference phase. For any test input data, based on the difference between the temperature-tuned classifier output and a target probability distribution derived from the inverse frequency of different diseases, the input data can be slightly perturbed in a way similar to adversarial learning. The classifier prediction for the perturbed input would become less biased toward common diseases compared to that for the original one. The proposed inference-phase method can be naturally combined with any training-phase re-balancing strategies. Extensive evaluations on three different medical image classification tasks and three classifier backbones support that our method consistently improves the performance of the classifier which even has been trained by any re-balancing strategy. The performance improvement is substantial particularly on minority classes, confirming the effectiveness of the proposed method in alleviating the classifier bias toward dominant classes.

With the rapid development of the Internet, society is gradually entering the information age, and various data in enterprises have become the most important strategic core resources of all enterprises. The operation and decision-making of enterprises all require a large amount of data analysis. Nowadays, many companies do not pay enough attention to the monitoring of data asset distribution. In addition, various internal systems such as financial management and ERP systems are relatively independent. Each system has its own data organization standard, which makes it difficult to conduct a unified management of data. This also directly leads to the one-sided and subjective problem of enterprise managers' distribution of data assets. With the construction of the data center of each enterprise, the data of each system is aggregated to the center through data integration technology. Therefore, all enterprises need to build a multi-dimensional data distribution monitoring model around data links to comprehensively monitor the status of various data distributions across the company's entire network, and improve data service capabilities and sharing capabilities as well as the company's operational capabilities. This article uses OLAP technology to construct a multi-dimensional data distribution monitoring model for the data link in the process of power enterprise data integration. This article first selects the dimensions and metrics that need to be monitored in the multidimensional data, and then constructs the conceptual model, logical model and physical model of the multidimensional data using on line analytical processing technology. Finally, an example analysis of OLAP system architecture based on B/S structure is realized. The overall data distribution of the enterprise can be grasped by analyzing the various dimensions of the data link, such as System type, location distribution, and time.

Intercellular junctions maintain the integrity of the endothelium. We previously found that the adherens and tight junctions between endothelial cells are disrupted by plasma extracellular vesicles from patients with sickle cell disease (especially those with Acute Chest Syndrome). In the current study, we evaluated the effects of these vesicles on endothelial gap junctions. The vesicles from sickle cell patients (isolated during episodes of Acute Chest Syndrome) disrupted gap junction structures earlier and more severely than the other classes of intercellular junctions (as detected by immunofluorescence). These vesicles were much more potent than those isolated at baseline from the same subject. The treatment of endothelial cells with these vesicles led to reduced levels of connexin43 mRNA and protein. These vesicles severely reduced intercellular communication (transfer of microinjected Neurobiotin). Our data suggest a hierarchy of progressive disruption of different intercellular connections between endothelial cells by circulating extracellular vesicles that may contribute to the pathophysiology of the endothelial disturbances in sickle cell disease.

BACKGROUND The aim was to investigate the expression of circulating RNA EIF4G2 (CircEIF4G2) in cervical cancer and its correlation with clinicopathological features. METHODS Cervical tissue and peripheral blood serum samples were collected from 148 patients with cervical lesions, including 30 patients with low-grade squamous intraepithelial lesions (LSIL group), 35 patients with high squamous intraepithelial lesion (HSIL group), 28 patients with atypical squamous cells (ASC group), and 55 patients with cervical cancer (CC group). At the same time, cervical biopsy specimens and peripheral blood serum were collected from 40 healthy women (Normal group). RT-PCR was used to detect the expression of CircEIF4G2 in cervical tissues and peripheral blood of each group. Electron microscopy was used to observe the distribution of exosomes CircEIF4G2 in cervical tissues. Meanwhile, the correlation between the expression level of CircEIF4G2 and clinical pathological data of patients was analyzed. In vitro, HeLa cells and primary cervical epithelial cells were cultured for 24 hours. Then, the expression levels of CircEIF4G2 in the two kinds of cells were detected by RT-PCR in medium. Furthermore, primary cervical epithelial cells were co-cultured with HeLa cells to observe the effect of exosome CircEIF4G2 on primary cervical epithelial cells. RESULTS The expression of CircEIF4G2 in the cervical tissue and serum of the normal group was significantly lower than that in the CC group (p < 0.05), but there was no significant difference between the LSIL group and the HSIL group in the cervical tissue and serum (p < 0.05). The distribution and expression of exosomes CircEIF4G2 in each group were consistent with RT-PCR results under an electron microscope. The results of experiments in vitro showed that the expression level of CircEIF4G2 in HeLa cells was significantly higher than that in primary cervical epithelial cells (p < 0.05). The medium in which Hela cells were cultured for 24 hours was added to the culture medium of primary cervical epithelial cells. The process of exosomes CircEIF4G2 entering primary cervical cancer cells was observed by electron microscopy. CONCLUSIONS The increased expression of CircEIF4G2 in tissues and serum of cervical lesions may be caused by the secretion of exosomes containing CircEIF4G2 by cervical cancer cells. Therefore, CircEIF4G2 can be used as a marker for the diagnosis of cervical lesions.

A key performance metric in blockchains is the latency between when a transaction is broadcast and when it is confirmed (the so-called, confirmation latency). While improvements in consensus techniques can lead to lower confirmation latency, a fundamental lower bound on confirmation latency is the propagation latency of messages through the underlying peer-to-peer (p2p) network (inBitcoin, the propagation latency is several tens of seconds). The de facto p2p protocol used by Bitcoin and other blockchains is based on random connectivity: each node connects to a random subset of nodes. The induced p2p network topology can be highly suboptimal since it neglects geographical distance, differences in bandwidth, hash-power and computational abilities across peers. We present Perigee, a decentralized algorithm that automatically learns an efficient p2p topology tuned to the aforementioned network heterogeneities, purely based on peers' interactions with their neighbors. Motivated by the literature on the multi-armed bandit problem, Perigee optimally balances the tradeoff between retaining connections to known well-connected neighbors, and exploring new connections to previously-unseen neighbors. Experimental evaluations show that Perigee reduces the latency to broadcast by $33\%$. Lastly Perigee is simple, computationally lightweight, adversary-resistant, and compatible with the selfish interests of peers, making it an attractive p2p protocol for blockchains., Comment: Accepted at ACM PODC 2020

Chest radiography is widely used in annual medical screening to check whether lungs are healthy or not. Therefore it would be desirable to develop an intelligent system to help clinicians automatically detect potential abnormalities in chest X-ray images. Here with only healthy X-ray images, we propose a new abnormality detection approach based on an autoencoder which outputs not only the reconstructed normal version of the input image but also a pixel-wise uncertainty prediction. Higher uncertainty often appears at normal region boundaries with relatively larger reconstruction errors, but not at potential abnormal regions in the lung area. Therefore the normalized reconstruction error by the uncertainty provides a natural measurement for abnormality detection in images. Experiments on two chest X-ray datasets show the state-of-the-art performance by the proposed approach.