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At least 235 records · Page 13

Emulating a System Dynamics Model with Agent-Based Models: A Methodological Case Study in Simulation of Diabetes Progression

An agent-based simulation model hierarchy emulating disease states and behaviors critical to progression of diabetes type 2 was designed and implemented in the DEVS framework. The models are translations of basic elements of an established system dynamics model of diabetes. In this model hierarchy, which mimics diabetes progression over an aggregated U.S. population, was dis-aggregated and reconstructed bottom-up at the individual (agent) level. Four levels of model complexity were defined in order to systematically evaluate which parameters are needed to mimic outputs of the system dynamics model. Moreover, the four estimated models attempted to replicate stock counts representing disease states in the system dynamics model, while estimating impacts of an elderliness factor, obesity factor and health-related behavioral parameters. Health-related behavior was modeled as a simple realization of the Theory of Planned Behavior, a joint function of individual attitude and diffusion of social norms that spread over each agent s social network. Although the most complex agent-based simulation model contained 31 adjustable parameters, all models were considerably less complex than the system dynamics model which required numerous time series inputs to make its predictions. In all three elaborations of the baseline model provided significantly improved fits to the output of the system dynamics model. The performances of the baseline agent-based model and its extensions illustrate a promising approach to translate complex system dynamics models into agent-based model alternatives that are both conceptually simpler and capable of capturing main effects of complex local agent-agent interactions.

59 BASIC BIOLOGICAL SCIENCES↗

A Progress Report on Metal–Sulfur Batteries

Nonaqueous conversion-reaction sulfur chemistry has been attracting increasing attention over the past decade for the development of next-generation lithium-based batteries. Li–S batteries are currently approaching a nexus stage from lab-scale experiments to possible pragmatic applications. Inspired by the success of Li–S chemistry, other metal–sulfur batteries with a variety of metallic anodes, such as sodium, potassium, magnesium, calcium, and aluminum, have also started to attract attention. In comparison to lithium, Na, Mg, Al, K, and Ca are naturally more abundant and affordable. The Na-S, Mg-S, Al-S, K-S, and Ca-S battery systems provide a great potential for improving the volumetric energy density of sulfur-based batteries. The multivalent metal-sulfur systems, Mg-S, Al-S, and Ca-S, offer better safety features as well. However, the research and development on Na-S, Mg-S, Al-S, K-S, and Ca-S batteries is far behind the Li–S system due to many critical challenges. In this progress report, the fundamental principles of various metal–sulfur chemistries are first presented and compared. Then, the historical progress, recent advances, and key challenges of the Li–S, Na-S, Mg-S, Al-S, K-S, and Ca-S systems are summarized and discussed. Finally, future efforts and directions for both the fundamental and practical research are prospected.

25 ENERGY STORAGE↗

Progress in Epitaxial Thin-Film Na 3 Bi as a Topological Electronic Material

Trisodium bismuthide (Na 3 Bi) is the first experimentally verified topological Dirac semimetal, and is a 3D analogue of graphene hosting relativistic Dirac fermions. Its unconventional momentum-energy relationship is interesting from a fundamental perspective, yielding exciting physical properties such as chiral charge carriers, the chiral anomaly, and weak anti-localization. It also shows promise for realizing topological electronic devices such as topological transistors. Herein, an overview of the substantial progress achieved in the last few years on Na 3 Bi is presented, with a focus on technologically relevant large-area thin films synthesized via molecular beam epitaxy. Key theoretical aspects underpinning the unique electronic properties of Na 3 Bi are introduced. Next, the growth process on different substrates is reviewed. Spectroscopic and microscopic features are illustrated, and an analysis of semiclassical and quantum transport phenomena in different doping regimes is provided. Furthermore, the emergent properties arising from confinement in two dimensions, including thickness-dependent and electric-field-driven topological phase transitions, are addressed, with an outlook toward current challenges and expected future progress.

36 MATERIALS SCIENCE↗

Research Progress towards Understanding the Unique Interfaces between Concentrated Electrolytes and Electrodes for Energy Storage Applications

The electrolyte is an indispensable component in all electrochemical energy storage and conversion devices with batteries being a prime example. While most research efforts have been pursued on the materials side, the progress for the electrolyte is slow due to the decomposition of salts and solvents at low potentials, not to mention their complicated interactions with the electrode materials. The general properties of bulk electrolytes such as ionic conductivity, viscosity, and stability all affect the cell performance. However, for a specific electrochemical cell in which the cathode, anode, and electrolyte are optimized, it is the interface between the solid electrode and the liquid electrolyte, generally referred to as the solid electrolyte interphase (SEI), that dictates the rate of ion flow in the system. The commonly used electrolyte is within the range of 1–1.2 m based on the prior optimization experience, leaving the high concentration region insufficiently recognized. Recently, electrolytes with increased concentration (>1.0 m ) have received intensive attention due to quite a few interesting discoveries in cells containing concentrated electrolytes. The formation mechanism and the nature of the SEI layers derived from concentrated electrolytes could be fundamentally distinct from those of the traditional SEI and thus enable unusual functions that cannot be realized using regular electrolytes. In this article, we provide an overview on the recent progress of high concentration electrolytes in different battery chemistries. The experimentally observed phenomena and their underlying fundamental mechanisms are discussed. New insights and perspectives are proposed to inspire more revolutionary solutions to address the interfacial challenges.

25 ENERGY STORAGE↗

Variation in the contribution of macroinvertebrates to wood decomposition as it progresses

Abstract Although necromass decay rates are limited by the slowest portions to decompose, most decomposition studies examine only the earliest stage of decay. As such, these studies run the risk of yielding misleading results regarding the relative contributions of different decomposers. For example, the contributions of macroinvertebrates to wood decomposition remain mostly unknown beyond the first 50% of mass lost, despite drastic changes in substrate conditions over time. We sought to clarify how the macroinvertebrate contribution to decay changes over the course of wood decomposition in the Southeastern United States—a region with a long history of wood decomposition research. To this end, we (1) compiled data from published studies comparing wood decay with and without macroinvertebrates; and (2) conducted a field study assessing wood mass loss, with and without macroinvertebrate access, at three sites across the region over four years. With these combined data, we analyzed macroinvertebrate contribution as decay progressed, revealing a quadratic relationship, wherein macroinvertebrate contribution increased early in decomposition and then began to decline as decay progressed. Strong local site effects, particularly the abundance and activity of termites, determine the time required for wood to reach this point of mass loss.

Environmental Sciences & Ecology↗

Progress Towards a Comprehensive Approach for Habitat Restoration in the Columbia Basin: Case Study in the Grande Ronde River

Abstract Despite immense resources directed towards habitat restoration, recovering fish populations remains a daunting and perplexing issue. In 2015, recommendations for a comprehensive approach to habitat restoration in the Columbia River basin were published in Fisheries, which included elements of landscape ecology and resilience, broad public support, governance for collaboration and integration, and capacity for learning and adaptation. Using the Grande Ronde River basin as a case study, we convened a working group consisting of local restoration practitioners, managers, and researchers involved in habitat restoration research, monitoring, and evaluation to assess progress towards meeting these recommendations. We concluded that partnerships and collaborations in governance have been formed and research using a landscape perspective has been integrated into decision making, but efforts would benefit from gaining broader public support, formalizing an adaptive management strategy, and defining objectives and indicators for biological and ecological diversity. Continued progress will require consistent policy and funding support from the broader region. We envision this self-assessment at the 5-year milestone would be helpful to other groups facing similar challenges.

White, Seth M. (ORCID:0000000349186865)↗

Distinct progression pattern of susceptibility MRI in the substantia nigra of Parkinson's patients

Abstract Background: Susceptibility MRI may capture Parkinson's disease‐related pathology. This study delineated longitudinal changes in different substantia nigra regions. Methods: Seventy‐two PD patients and 62 controls were studied at both baseline and after 18 months with MRI. R2* and quantitative susceptibility mapping values from the substantia nigra pars compacta and substantia nigra pars reticulata were calculated. Mixed‐effects models compared controls with PD or PD subgroups having different disease durations: early (<1 year), middle (<5 years, middle‐stage PD), and late (>5 years, late‐stage PD). Pearson's correlation assessed associations between imaging and clinical measures. Results: At baseline, R2* and quantitative susceptibility mapping were higher in both the substantia nigra pars compacta and substantia nigra pars reticulata in all PD patients (group effect, P ≤ 0.003). Longitudinally, the substantia nigra pars compacta R2* showed a faster increase in PD compared with controls (time × group, P = 0.002), whereas quantitative susceptibility mapping did not ( P = 0.668). The substantia nigra pars reticulata R2* and quantitative susceptibility mapping did not differ between PD and controls (time × group, P ≥ 0.084), although both decreased longitudinally (time effect, P ≤ 0.004). Baseline substantia nigra pars compacta R2* was higher in all PD subgroups (group, P ≤ 0.006), but showed a significantly faster increase only in later‐stage PD (time × group, P < 0.0001) that correlated with changes in nonmotor symptoms ( r = 0.746, P = 0.002). Baseline substantia nigra pars reticulata quantitative susceptibility mapping was higher in middle‐stage PD and later‐stage PD (group, P ≤ 0.002), but showed a longitudinal decrease (time × group, P = 0.004) only in later‐stage PD that correlated with changes in motor signs ( r = 0.837, P < 0.001). Conclusion: Susceptibility MRI revealed distinct patterns of PD progression in the substantia nigra pars compacta and substantia nigra pars reticulata. The different patterns are particularly clear in later‐stage patients. These findings may resolve past controversies and have implications in the pathophysiological processes during PD progression. © 2018 International Parkinson and Movement Disorder Society

Du, Guangwei↗

Photovoltaic Devices Based on Colloidal PbX Quantum Dots: Progress and Prospects

Here, a certified power conversion efficiency (PCE) of 12.0% and an outstanding air stability has been achieved for PbX quantum dots (QDs) solar cells, indicating strong potential for next generation low-cost solution-processed photovoltaics. Similar progress has been made in several other solar cell architectures employing PbX QD absorbers. This article aims to review the recent progress in understanding the photovoltaic-relevant properties of PbX QDs and highlight their application in various types of photovoltaic devices. In doing so, we hope that the unique properties of PbX QDs can be better understood in a broader context, and their potential can be fully realized with the aiding of other photovoltaic materials and novel device structures.

14 SOLAR ENERGY↗

Targeted mutagenesis with sequence–specific nucleases for accelerated improvement of polyploid crops: Progress, challenges, and prospects

Many of the world's most important crops are polyploid. The presence of more than two sets of chromosomes within their nuclei and frequently aberrant reproductive biology in polyploids present obstacles to conventional breeding. The presence of a larger number of homoeologous copies of each gene makes random mutation breeding a daunting task for polyploids. Genome editing has revolutionized improvement of polyploid crops as multiple gene copies and/or alleles can be edited simultaneously while preserving the key attributes of elite cultivars. Most genome–editing platforms employ sequence–specific nucleases (SSNs) to generate DNA double–stranded breaks at their target gene. Such DNA breaks are typically repaired via the error–prone nonhomologous end–joining process, which often leads to frame shift mutations, causing loss of gene function. Genome editing has enhanced the disease resistance, yield components, and end–use quality of polyploid crops. However, identification of candidate targets, genotyping, and requirement of high mutagenesis efficiency remain bottlenecks for targeted mutagenesis in polyploids. In this review, we will survey the tremendous progress of SSN–mediated targeted mutagenesis in polyploid crop improvement, discuss its challenges, and identify optimizations needed to sustain further progress.

60 APPLIED LIFE SCIENCES↗

Margin Size is an Independent Predictor of Local Tumor Progression After Ablation of Colon Cancer Liver Metastases

This study was designed to evaluate the relationship between the minimal margin size and local tumor progression (LTP) following CT-guided radiofrequency ablation (RFA) of colorectal cancer liver metastases (CLM). An institutional review board-approved, HIPPA-compliant review identified 73 patients with 94 previously untreated CLM that underwent RFA between March 2003 and May 2010, resulting in an ablation zone completely covering the tumor 4-8 weeks after RFA dynamic CT. Comparing the pre- with the post-RFA CT, the minimal margin size was categorized to 0, 1-5, 6-10, and 11-15 mm. Follow-up included CT every 2-4 months. Kaplan-Meier methodology and Cox regression analysis were used to evaluate the effect of the minimal margin size, tumor location, size, and proximity to a vessel on LTP. Forty-five of 94 (47.9 %) CLM progressed locally. Median LTP-free survival (LPFS) was 16 months. Two-year LPFS rates for ablated CLM with minimal margin of 0, 1-5 mm, 6-10 mm, 11-15 mm were 26, 46, 74, and 80 % (p < 0.011). Minimal margin (p = 0.002) and tumor size (p = 0.028) were independent risk factors for LTP. The risk for LTP decreased by 46 % for each 5-mm increase in minimal margin size, whereas each additional 5-mm increase in tumor size increased the risk of LTP by 22 %. An ablation zone with a minimal margin uniformly larger than 5 mm 4-8 weeks postablation CT is associated with the best local tumor control.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Hamiltonian Light-Front Field Theory: Recent Progress and Tantalizing Prospects

Fundamental theories, such as quantum electrodynamics and quantum chromodynamics promise great predictive power addressing phenomena over vast scales from the microscopic to cosmic scales. However, new non-perturbative tools are required for physics to span from one scale to the next. I outline recent theoretical and computational progress to build these bridges and provide illustrative results for Hamiltonian Light Front Field Theory. One key area is our development of basis function approaches that cast the theory as a Hamiltonian matrix problem while preserving a maximal set of symmetries. Regulating the theory with an external field that can be removed to obtain the continuum limit offers additional possibilities as seen in an application to the anomalous magnetic moment of the electron. Recent progress capitalizes on algorithm and computer developments for setting up and solving very large sparse matrix eigenvalue problems. Matrices with dimensions of 20 billion basis states are now solved on leadership-class computers for their low-lying eigenstates and eigenfunctions.

Physics↗

Could FDG-PET imaging play a role in the detection of progressing atherosclerosis in HIV-infected patients?

Important progresses in the management of patients with human immunodeficiency virus, in particular the advent of new anti-retroviral therapies (ART), have turned this rapidly fatal condition into a controllable chronic disease with a life expectancy that approaches the one from the general population. Cardiovascular diseases have now become one of the leading causes of non-HIV-related mortality in this population. Several factors including the presence of HIV in the vascular wall and the development of dyslipidemia and alteration in body fat distribution under ART might play a role the progression of atherosclerosis in HIV-infected patients. The use of imaging biomarkers may help to identify the factors associated with an increased risk of cardiovascular events and select high-risk patients who will benefit the most from the early implementation of preventive treatments.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Recent progresses on thermal–hydraulics evaluations of accident tolerant fuel cladding materials

Thermal–hydraulics (T-H) experiments have been on the progress to evaluate boiling heat transfer characteristics of accident tolerant fuel (ATF) candidates for further supporting the core-loading of these advanced ATF concepts in light water reactors (LWRs). Here this study covers recent experimental studies of ATF claddings and summarizes some significant results. Recent T-H experimental results of ATF cladding candidates demonstrated that the material thermal–physical properties have pronounced effects on critical heat flux (CHF). Such effects have not been well resolved in the current physics-governing models. These effects of cladding materials on CHF could be potentially rationalized by the material-conjugated boiling heat transfer, where the material-dominated heat conduction competes with the flow boiling-dominated heat convection. As progressively increasing the mass flux and/or liquid subcooling, CHF differences between different materials gradually decrease, which is in agreement with the recent T-H experimental results of ATF claddings. This is because the dominance of heat convection over heat conduction is primarily improved by liquid subcooling and/or mass flow rate. It is noteworthy that surface oxidization of claddings may have unknown impacts on T-H performances because the formation of oxide layers on cladding surfaces introduces variations of material thermal–physical properties and then changes the surface morphological features, which results in some difficulties in evaluating the thermal safety margins of ATF claddings.

36 MATERIALS SCIENCE↗

DACH1 regulates cell cycle progression of myeloid cells through the control of cyclin D, Cdk 4/6 and p21{sup Cip1}

Highlights: Black-Right-Pointing-Pointer DACH1 increases cyclin D, F and Cdk 1, 4, 6 in mouse myeloid progenitor cells. Black-Right-Pointing-Pointer The knockdown of DACH1 blocked the cell cycle progression of HL-60 cells. Black-Right-Pointing-Pointer The novel effect of DACH1 related with cell cycle regulation and leukemogenesis. -- Abstract: The cell-fate determination factor Dachshund, a component of the Retinal Determination Gene Network (RDGN), has a role in breast tumor proliferation through the repression of cyclin D1 and several key regulators of embryonic stem cell function, such as Nanog and Sox2. However, little is known about the role of DACH1 in a myeloid lineage as a cell cycle regulator. Here, we identified the differential expression levels of extensive cell cycle regulators controlled by DACH1 in myeloid progenitor cells. The forced expression of DACH1 induced p27{sup Kip1} and repressed p21{sup Cip1}, which is a pivotal characteristic of the myeloid progenitor. Furthermore, DACH1 significantly increased the expression of cyclin D1, D3, F, and Cdk 1, 4, and 6 in myeloid progenitor cells. The knockdown of DACH1 blocked the cell cycle progression of HL-60 promyeloblastic cells through the decrease of cyclin D1, D3, F, and Cdk 1, 4, and 6 and increase in p21{sup Cip1}, which in turn decreased the phosphorylation of the Rb protein. The expression of Sox2, Oct4, and Klf4 was significantly up-regulated by the forced expression of DACH1 in mouse myeloid progenitor cells.

60 APPLIED LIFE SCIENCES↗

CHL1 is involved in human breast tumorigenesis and progression

Highlights: •CHL1 is down-regulation in breast cancer tissues. •Down-regulation of CHL1 is related to high grade. •Overexpression of CHL1 inhibits breast cancer cell proliferation and invasion in vitro. •CHL1 deficiency induces breast cancer cell proliferation and invasion both in vitro and in vivo. -- Abstract: Neural cell adhesion molecules (CAM) play important roles in the development and regeneration of the nervous system. The L1 family of CAMs is comprised of L1, Close Homolog of L1 (CHL1, L1CAM2), NrCAM, and Neurofascin, which are structurally related trans-membrane proteins in vertebrates. Although the L1CAM has been demonstrated play important role in carcinogenesis and progression, the function of CHL1 in human breast cancer is limited. Here, we found that CHL1 is down-regulated in human breast cancer and related to lower grade. Furthermore, overexpression of CHL1 suppresses proliferation and invasion in MDA-MB-231 cells and knockdown of CHL1 expression results in increased proliferation and invasion in MCF7 cells in vitro. Finally, CHL1 deficiency promotes tumor formation in vivo. Our results may provide a strategy for blocking breast carcinogenesis and progression.

60 APPLIED LIFE SCIENCES↗

A PAUF-neutralizing antibody targets both carcinoma and endothelial cells to impede pancreatic tumor progression and metastasis

Highlights: • PMAb83, a human monoclonal antibody against PAUF, impaired tumor progression in vivo. • PMAb83 attenuated aggressiveness of tumor cells and suppressed angiogenesis. • PMAb83 in combination with gemcitabine conferred improved survival of mouse model. - Abstract: Pancreatic adenocarcinoma up-regulated factor (PAUF) is expressed in pancreatic ductal adenocarcinoma (PDAC) and plays an important role in tumor progression and metastasis. Here we evaluate the anti-tumor efficacy of a human monoclonal antibody against PAUF, PMAb83, to provide a therapeutic intervention to treat the disease. PMAb83 reduced tumor growth and distant metastasis in orthotopically xenografted mice of human PDAC cells. PMAb83 treatment retarded proliferation along with weakened aggressiveness traits of the carcinoma cells. AKT/β-catenin signaling played a role in the carcinoma cell proliferation and the treated xenograft tumors exhibited reduced levels of β-catenin and cyclin D1. Moreover PMAb83 abrogated the PAUF-induced angiogenic responses of endothelial cells, reducing the density of CD31{sup +} vessels in the treated tumors. In combination with gemcitabine, PMAb83 conferred enhanced survival of xenografted mice by about twofold compared to gemcitabine alone. Taken together, our findings show that PMAb83 treatment decreases the aggressiveness of carcinoma cells and suppresses tumor vascularization, which culminates in mitigated tumor growth and metastasis with improved survival in PDAC mouse models.

60 APPLIED LIFE SCIENCES↗

The single N-glycan deletion mutant of soluble ErbB3 protein attenuates heregulin β1-induced tumor progression by blocking of the HIF-1 and Nrf2 pathway

Highlights: • The sErbB3 N418Q mutant blocks heregulin β1 induced nuclear accumulation of HIF-1α. • The sErbB3 N418Q mutant attenuates cancer cell migration induced by heregulin β1. • The sErbB3 N418Q mutant blocks heregulin β1 induced nuclear accumulation of Nrf2. • The sErbB3 N418Q mutant may be a potential therapeutic application for tumor. - Abstract: It has been well documented that activation of the ErbB3–PI3K–Akt pathway is implicated in tumor survival and progression. We previously demonstrated that the single N-glycan deletion mutant of soluble ErbB3 protein (sErbB3 N418Q) attenuates heregulin β1-induced ErbB3 signaling. The active PI3K–Akt pathway augments the nuclear accumulation of hypoxia inducible factor (HIF)-1α, which activates the transcription of many target genes and drives cancer progression. In this study, we focused on the effects of sErbB3 N418Q mutant on nuclear accumulation of HIF-1α. Pretreatment with the sErbB3 N418Q mutant suppressed heregulin β1-induced HIF-1α activation in MCF7 cells. Similar results were also obtained in other breast cancer cell lines, T47D and BT474. Interestingly, these suppressive effects were not observed with the sErbB3 wild type. In addition, pretreatment with the sErbB3 N418Q mutant suppressed the cell migration of MCF7 cells induced by heregulin β1. Furthermore, incubation with heregulin β1 also induced the nuclear accumulation of Nrf2, and this effect was also reduced by the sErbB3 N418Q mutant, but not the sErbB3 wild type. These findings indicated that the sErbB3 N418Q mutant suppressed malignant formation of cancer cells by blocking of the HIF-1α and Nrf2 pathways.

60 APPLIED LIFE SCIENCES↗

Androgen receptor regulated microRNA miR-182-5p promotes prostate cancer progression by targeting the ARRDC3/ITGB4 pathway

Abstracts: MicroRNAs (miRNAs) are important endogenous gene regulators that play key roles in prostate cancer development and metastasis. However, specific miRNA expression patterns in prostate cancer tissues from Chinese patients remain largely unknown. In this study, we compared miRNA expression patterns in 65 pairs of prostate cancer and para-cancer tissues by RNA sequencing and found that miR-182-5p was the most up-regulated miRNA in prostate cancer tissues. The result was validated using realtime PCR in 18 pairs of prostate cancer and para-cancer tissues. In in vitro analysis, it was confirmed that miR-182-5p promotes prostate cancer cell proliferation, invasion and migration and inhibit apoptosis. In addition, the androgen receptor directly regulated the transcription of miR-182-5p, which could target to the 3′UTR of ARRDC3 mRNA and affect the expression of ARRDC3 and its downstream gene ITGB4. For the in vivo experiment, miR-182-5p overexpression also promoted the growth and progression of prostate cancer tumors. In this regard, we suggest that miR-182-5p may be a key androgen receptor-regulated factor that contributes to the development and metastasis of Chinese prostate cancers and may be a potential target for the early diagnosis and therapeutic studies of prostate cancer. -- Highlights: •miR-182-5p is the mostly up-regulated miRNA in Chinese prostate cancer. •miR-182-5p is regulated by androgen receptor. •miR-182-5p promotes prostate cancer progression. •miR-182-5p regulates ARRDC3/ITGB4 pathway.

60 APPLIED LIFE SCIENCES↗