Abstract
Metastatic spread of a cancer to secondary sites is a coordinated, non-random process. Cancer cell-secreted vesicles, especially exosomes, have recently been implicated in the guidance of ...metastatic dissemination, with specific surface composition determining some aspects of organ-specific localization. Nevertheless, whether the tumor microenvironment influences exosome biodistribution has yet to be investigated. Here, we show that microenvironmental cytokines, particularly CCL2, decorate cancer exosomes via binding to surface glycosaminoglycan side chains of proteoglycans, causing exosome accumulation in specific cell subsets and organs. Exosome retention results in changes in the immune landscape within these organs, coupled with a higher metastatic burden. Strikingly, CCL2-decorated exosomes are directed to a subset of cells that express the CCL2 receptor CCR2, demonstrating that exosome-bound cytokines are a crucial determinant of exosome-cell interactions. In addition to the finding that cytokine-conjugated exosomes are detected in the blood of cancer patients, we discovered that healthy subjects derived exosomes are also associated with cytokines. Although displaying a different profile from exosomes isolated from cancer patients, it further indicates that specific combinations of cytokines bound to exosomes could likewise affect other physiological and disease settings.
A mathematical model that considers coupled mass transport, charge transport, and electrochemical reactions in an anion-exchange membrane (AEM) water electrolyzer is developed. Validations against ...the literature experimental data show that the present model can accurately predict the performance of the water electrolyzer. Numerical results show that the voltage loss in the electrolyzer is majorly due to the activation polarizations of hydrogen and oxygen evolution reactions. The effects of the exchange current density, the membrane thickness, and the liquid saturation on the performance are also studied; it is shown that the performance of the water electrolyzer improves with an increase in the exchange current density and liquid saturation, but with a decrease in the membrane thickness.
Abstract
Artificial neural networks are notoriously power- and time-consuming when implemented on conventional von Neumann computing systems. Consequently, recent years have seen an emergence of ...research in machine learning hardware that strives to bring memory and computing closer together. A popular approach is to realise artificial neural networks in hardware by implementing their synaptic weights using memristive devices. However, various device- and system-level non-idealities usually prevent these physical implementations from achieving high inference accuracy. We suggest applying a well-known concept in computer science—committee machines—in the context of memristor-based neural networks. Using simulations and experimental data from three different types of memristive devices, we show that committee machines employing ensemble averaging can successfully increase inference accuracy in physically implemented neural networks that suffer from faulty devices, device-to-device variability, random telegraph noise and line resistance. Importantly, we demonstrate that the accuracy can be improved even without increasing the total number of memristors.
Background
Hepatic vein tumour thrombus (HVTT) is a major determinant of survival outcomes for patients with hepatocellular carcinoma (HCC). An Eastern Hepatobiliary Surgery Hospital (EHBH)‐HVTT ...model was established to predict the prognosis of patients with HCC and HVTT after liver resection, in order to identify optimal candidates for liver resection.
Methods
Patients with HCC and HVTT from 15 hospitals in China were included. The EHBH‐HVTT model with contour plot was developed using a non‐linear model in the training cohort, and subsequently validated in internal and external cohorts.
Results
Of 850 patients who met the inclusion criteria, there were 292 patients who had liver resection and 198 who did not in the training cohort, and 124 and 236 in the internal and external validation cohorts respectively. Contour plots for the EHBH‐HVTT model were established to predict overall survival (OS) rates of patients visually, based on tumour diameter, number of tumours and portal vein tumour thrombus. This differentiated patients into low‐ and high‐risk groups with distinct long‐term prognoses in the liver resection cohort (median OS 34·7 versus 12·0 months; P < 0·001), internal validation cohort (32·8 versus 10·4 months; P = 0·002) and external validation cohort (15·2 versus 6·5 months; P = 0·006). On subgroup analysis, the model showed the same efficacy in differentiating patients with HVTT in peripheral and major hepatic veins, the inferior vena cava, or in patients with coexisting portal vein tumour thrombus.
Conclusion
The EHBH‐HVTT model was accurate in predicting prognosis in patients with HCC and HVTT after liver resection. It identified optimal candidates for liver resection among patients with HCC and HVTT, including tumour thrombus in the inferior vena cava, or coexisting portal vein tumour thrombus.
Antecedentes
La trombosis tumoral de la vena hepática (hepatic vein tumour thrombus, HVTT) es un determinante importante de los resultados de supervivencia en pacientes con carcinoma hepatocelular (hepatocellular carcinoma, HCC). Se desarrolló el modelo llamado Eastern Hepatobiliary Surgery Hospital (EHBH)‐HVTT para predecir el pronóstico de los pacientes con HCC y HVTT después de la resección hepática (liver resection, LR), con el fin de identificar los candidatos óptimos para LR entre estos pacientes.
Métodos
Se incluyeron pacientes con HCC y HVTT de 15 hospitales en China. El modelo EHBH‐HVTT con gráfico de contorno se desarrolló utilizando un modelo no lineal en la cohorte de entrenamiento, siendo posteriormente validado en cohortes internas y externas.
Resultados
De 850 pacientes que cumplieron con los criterios de inclusión, hubo 292 pacientes en el grupo LR y 198 pacientes en el grupo no LR en la cohorte de entrenamiento, y 124 y 236 en las cohortes de validación interna y externa. Los gráficos de contorno del modelo EHBH‐HVTT se establecieron para predecir visualmente las tasas de supervivencia global (overall survival, OS) de los pacientes, en función del diámetro del tumor, número de tumores y del trombo tumoral de la vena porta (portal vein tumour thrombus, PVTT). Esto diferenciaba a los pacientes en los grupos de alto y bajo riesgo, con distinto pronóstico a largo plazo en las 3 cohortes (34,7 versus 12,0 meses, 32,8 versus 10,4 meses y 15,2 versus 6,5 meses, P < 0,001). En el análisis de subgrupos, el modelo mostró la misma eficacia en la diferenciación de pacientes con HVTT, con trombo tumoral en la vena cava inferior (inferior vena cava tumour thrombus, IVCTT) o en pacientes con PVTT coexistente.
Conclusión
El modelo EHBH‐HVTT fue preciso para la predicción del pronóstico en pacientes con HCC y HVTT después de la LR. Identificó candidatos óptimos para LR en pacientes con HCC y HVTT, incluyendo IVCTT o PVTT coexistente.
The Eastern Hepatobiliary Surgery Hospital–hepatic vein tumour thrombus (EHBH‐HVTT) model was accurate in predicting prognosis in patients with hepatocellular carcinoma (HCC) and HVTT after liver resection. It identified optimal candidates for liver resection among patients with HCC and HVTT, including inferior vena cava tumour thrombus, or coexisting portal vein tumour thrombus (PVTT).
predicts prognosis
A one-dimensional model is developed for alkaline direct ethanol fuel cells (DEFC) by considering the complicated physicochemical processes, including mass transport, charge transport, and ...electrochemical reactions. The model is validated against experiments and shows good agreement with the literature data. The model is then used to investigate the effects of various operating and structural design parameters on the cell performance. Numerical results show that the cell performance increases with increasing the ethanol concentration from 1.0 M to 3.0 M and with increasing the OH− concentration from 1.0 M to 5.0 M. The model is further applied to the study of the effect of the design of the anode diffusion layer (DL) on the performance; it is shown that the cell performance improves when the porosity of the DL is increased and the thickness of the DL is decreased.
•A one-dimensional model is developed for alkaline direct ethanol fuel cells (DEFC).•The integrated mass transport, charge transport, and electrochemical reactions are considered.•Effects of operating and design parameters on performance are numerically examined.
Parkinson’s disease (PD) is the second most common neurodegenerative disease with gradual loss of dopaminergic neurons. Despite extensive research in the past decades, the etiology of PD remains ...elusive. Nevertheless, multiple lines of evidence suggest that oxidative stress is one of the common causes in the pathogenesis of PD. It has also been suggested that heavy metal-associated oxidative stress may be implicated in the etiology and pathogenesis of PD. Here we review the roles of redox metals, including iron, copper and cobalt, in PD. Iron is a highly reactive element and deregulation of iron homeostasis is accompanied by concomitant oxidation processes in PD. Copper is a key metal in cell division process, and it has been shown to have an important role in neurodegenerative diseases such as PD. Cobalt induces the generation of reactive oxygen species (ROS) and DNA damage in brain tissues.
Summary Background Autologous haemopoietic stem-cell transplantation (HSCT) benefits patients with systemic sclerosis but has been associated with significant treatment-related mortality and failure ...to improve diffusion capacity of carbon monoxide (DLCO). We aimed to assess efficacy of HSCT and use of rigorous cardiac screening in this group. Methods We assessed patients with diffuse systemic sclerosis or limited systemic sclerosis and interstitial lung disease who were treated with HSCT as part of a study or on a compassionate basis at Northwestern University (Chicago, IL, USA) or the University of São Paulo (Ribeirão Preto, Brazil). Unselected peripheral blood stem cells were harvested with cyclophosphamide (2 g/m2 ) and filgrastim. The transplant regimen was a non-myeloablative regimen of cyclophosphamide (200 mg/kg) and rabbit anti-thymocyte globulin (rATG; 4·5–6·5 mg/kg). We followed patients up to 5 years for overall survival, relapse-free survival, modified Rodnan skin score, and pulmonary function tests. Findings Five (6%) of 90 patients died from treatment-related causes. Despite standard guidelines that recommend echocardiogram for screening before transplantation, four treatment-related deaths occurred because of cardiovascular complications (one constrictive pericarditis, two right heart failures without underlying infection, and one heart failure during mobilisation), and one death was secondary to sepsis without documented underlying heart disease. Kaplan-Meier analysis showed survival was 78% at 5 years (after eight relapse-related deaths) and relapse-free survival was 70% at 5 years. Compared with baseline, we noted improvements after HSCT in modified Rodnan skin scores at 1 year (58 patients; p<0·0001), 2 years (42 patients; p<0·0001), and 3 years (27 patients; p<0·0001) and forced vital capacity at 1 year (58 patients; p=0·009), 2 years (40 patients; p=0·02), and 3 years (28 patients; p=0·004), but total lung capacity and DLCO were not improved significantly after HSCT. Overall mean DLCO was significantly improved in patients with normal baseline echocardiograms (p=0·005) or electrocardiographs (p=0·05). Interpretation Autologous HSCT with a non-myeloablative regimen of cyclophosphamide and rATG with a non-selected autograft results in sustained improvement in skin thickness and forced vital capacity. DLCO is affected by baseline cardiac function. Guidelines for cardiac screening of patients with systemic sclerosis to assess treatment-related risk from pulmonary artery hypertension, primary cardiac involvement, or pericardial disease should be reconsidered and updated. Funding None.
A one-dimensional mathematical model is developed for the study of the mixed potential associated with the hydrogen peroxide oxidation reaction (HPOR) at the cathode of hydrogen peroxide-based fuel ...cells. The complicated physicochemical processes, including mass transport, charge transport, and three simultaneous electrochemical reactions (the hydrogen peroxide reduction, hydrogen peroxide oxidation, and oxygen reduction reactions) are considered. The model is experimentally validated and shows good agreement with the literature experimental data. The model is then applied to the study of the mixed potential by varying the current density. It is found that the largest potential loss due to the HPOR occurs under the open-circuit condition (OCC), and the potential loss decreases with the superficial current density. In addition, the numerical results suggest that under the OCC, an increase in the concentrations of hydrogen peroxide and H super(+) ions leads to a decrease in the potential loss, but an increase in the hydrogen peroxide decomposition rate and the oxygen evolution rate.
In this paper, based on multicomponent phase-field theory we intend to develop an efficient lattice Boltzmann (LB) model for simulating three-phase incompressible flows. In this model, two LB ...equations are used to capture the interfaces among three different fluids, and another LB equation is adopted to solve the flow field, where a new distribution function for the forcing term is delicately designed. Different from previous multiphase LB models, the interfacial force is not used in the computation of fluid velocity, which is more reasonable from the perspective of the multiscale analysis. As a result, the computation of fluid velocity can be much simpler. Through the Chapman-Enskog analysis, it is shown that the present model can recover exactly the physical formulations for the three-phase system. Numerical simulations of extensive examples including two circular interfaces, ternary spinodal decomposition, spreading of a liquid lens, and Kelvin-Helmholtz instability are conducted to test the model. It is found that the present model can capture accurate interfaces among three different fluids, which is attributed to its algebraical and dynamical consistency properties with the two-component model. Furthermore, the numerical results of three-phase flows agree well with the theoretical results or some available data, which demonstrates that the present LB model is a reliable and efficient method for simulating three-phase flow problems.
Animals are exposed to many microbes in their environment, some of which have been shown to colonize various tissues including the intestine. The composition of the intestinal microbiota affects many ...aspects of the host's physiology and health. Despite this, very little is known about whether host behavior contributes to the colonization. We approach this question in the nematode C. elegans, which feeds on bacteria and also harbors an intestinal microbiome. We examined the behavior of C. elegans towards CeMbio, a simplified microbiome consisting of twelve strains that represent the bacteria found in the animal's natural environment. We observed that C. elegans raised on E. coli shows a strong preference for three members of CeMbio (Lelliottia amnigena JUb66, Enterobacter hormaechei CEent1, and Pantoea nemavictus BIGb0393) compared to E. coli. Previously, these three bacterial strains have been shown to support faster C. elegans development time than E. coli OP50 and are low colonizers compared to eight other members of CeMbio. We then used gas chromatography coupled to mass spectrometry to identify that these three bacteria release isoamyl alcohol, a previously described C. elegans chemoattractant. We suggest that C. elegans seeks bacteria that release isoamyl alcohol and support faster growth.
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