Miracle-dz/UniFAR-FTUs huggingface dataset:
Development and calibration of discrete element method inputs to mechanical responses of granular materials

Simulation of soil excavation is difficult. Tools which manipulate soil are difficult to evaluate in a virtual environment prior to prototype or manufacture. Soil behaves as a discontinuous material in normal excavation activities. Therefore, numerical methods which naturally model discontinuous media, such as the Discrete Element Method (DEM), can be used to perform simulations of soil excavation. However, DEM input parameters must be calibrated to accurately model the mechanical behavior of soil. The goal of this research was to develop intelligent methodologies to calibrate DEM input parameters to reproduce the mechanical responses of soil and other granular materials subject to traditional laboratory tests, such as triaxial and direct shear tests. A mechanistic understanding of the interaction between sliding and rolling friction was developed and correlated with the critical state strength of drained granular media. In addition, the fundamental soil mechanics concept of relative density was successfully applied to the DEM calibration methodology to predict peak granular strength and dilatancy. Sensitivity analyses of DEM input parameters were used to enhance the characterization of mechanical behavior of DEM specimens. A calibration algorithm was developed to quickly and mechanistically relate DEM input parameters to laboratory measured mechanical behavior of soils. The algorithm eliminates unnecessary iterations during the DEM parameter calibration by enforcing a sophisticated understanding of the mechanisms of granular shear strength. The outcomes of this research greatly simplify the calibration of DEM parameters of soil for use in industrial excavation problems.
A new pair of enantiomeric lignans from the fruits of Morinda citrifolia and their absolute configuration

Abstract A new pair of sesamin-type lignan enantiomers (±)-morifolia A (1a/1b) together with eight known analogues (2–9) were isolated from the fruits of Morinda citrifolia. Their structures were established by spectroscopic data and the absolute configurations of 1a/1b were determined by ECD calculation. All compounds were examined for their inhibitory effects on the nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages, and compounds 1a, 1b, 2–4 and 7–9 exhibited pronounced inhibition with IC50 values in the range of 1.97–8.01 (μM, being more active than the positive control, quercetin (IC50 = 15.32 (M).
Effects of microwave ablation on T-cell subsets and cytokines of patients with hepatocellular carcinoma

Abstract Objectives: To investigate the effects of microwave ablation on T-lymphocyte subsets and cytokines in patients with hepatocellular carcinoma. Material and methods: Peripheral blood was collected from 45 patients with hepatocellular carcinoma treated by microwave ablation before treatment, one week and one month after treatment. T cells (CD3+, CD4+ and CD8+ cells), CD4+ CD25+ Tregs, and CD16+ CD56+ NK cells were analyzed by flow cytometry. Levels of cytokines (IL-2, IFN-γ, TNF-α, IL-12, IL-4, IL-6, IL-8, and IL-10) were determined by a Luminex 200 analyzer. Results: Compared with before treatment, CD3+ cells, CD4+ cells and IL-12 increased significantly at one month after the microwave ablation treatment, while IL-4, IL-10 decreased significantly. Conclusions: Microwave ablation could relieve the suppression of immune function caused by tumors, promote the deviation of Th2/Th1, and improve immune dysfunction in patients with hepatocellular carcinoma.
Slow stabilization of concurrently acquired hippocampal context representations

Hippocampal neurons exhibit spatially localized firing patterns that, at the population level, represent a particular environment or context. Many studies have examined how hippocampal neurons switch from an existing representation to a new one when the environment is changed, a process referred to as remapping. New representations were commonly thought to emerge rapidly, within a few minutes and then remain remarkably stable thereafter. However, a number of recent studies suggest that hippocampal representations may be more fluid than previously thought and most of the previous studies only required that subjects switch from a familiar environment to a novel one. In the present study, we examined the concurrent development of two distinct hippocampal representations by exposing rats to two distinct environmental contexts in an ABAB pattern and we recorded neuronal activity for eight daily training sessions. Hippocampal neurons exhibited normal place fields with typical firing properties during the initial exposure to each context on the first day. However, when the rats were returned to the original context after having spent 15 min in the second context, many of the neurons fired in new locations (i.e., they remapped) as if the rat had encountered a new environment. By the third day, the representations had stabilized and were highly consistent across visits to the same context. These results suggest that when subjects concurrently encode multiple contexts, hippocampal representations may require repeated experiences to fully stabilize. © 2016 Wiley Periodicals, Inc.
Myocardial perfusion assessment in humans using steady‐pulsed arterial spin labeling

Although arterial spin labeling (ASL) has become a routinely performed method in the rodent heart, its application to the human heart remains challenged by low tissue blood flow and cardiac and respiratory motion. We hypothesized that an alternative steady‐pulsed ASL (spASL) method would provide more efficient perfusion signal averaging by driving the tissue magnetization into a perfusion‐dependent steady state.
Observability and Controllability of Nonlinear Networks: The Role of Symmetry

Observability and controllability are essential concepts to the design of predictive observer models and feedback controllers of networked systems. For example, noncontrollable mathematical models of real systems have subspaces that influence model behavior, but cannot be controlled by an input. Such subspaces can be difficult to determine in complex nonlinear networks. Since almost all of the present theory was developed for linear networks without symmetries, here we present a numerical and group representational framework, to quantify the observability and controllability of nonlinear networks with explicit symmetries that shows the connection between symmetries and nonlinear measures of observability and controllability. We numerically observe and theoretically predict that not all symmetries have the same effect on network observation and control. Our analysis shows that the presence of symmetry in a network may decrease observability and controllability, although networks containing only rotational symmetries remain controllable and observable. These results alter our view of the nature of observability and controllability in complex networks, change our understanding of structural controllability, and affect the design of mathematical models to observe and control such networks.
Investigation of vitamin D status and its correlation with insulin resistance in a Chinese population

Abstract Objective Although many studies worldwide have focused on the relationship between vitamin D and insulin resistance, results remain controversial. Furthermore, concentrations of serum 25-hydroxyvitamin D (25(OH)D) in the Chinese population are unclear. We aimed to investigate vitamin D status and its correlation with insulin resistance among a Chinese adult population. Design Serum 25(OH)D, fasting blood glucose, fasting insulin, glycated Hb (HbA1c) and other metabolic parameters were assessed. Neck circumference, waist circumference, hip circumference, weight and height were also measured. Lifestyle factors including smoking and drinking status were obtained. Diabetes mellitus was diagnosed by HbA1c according to the 2010 American Diabetes Association criteria. Setting Eastern China. Subjects Of 7200 residents included, 6597 individuals were ultimately analysed. Results We enrolled 2813 males (mean age 52·7 (sd 13·5) years) and 3784 females (52·3 (sd 13·5) years); mean serum 25(OH)D concentration was 43·1 (sd 11·6) and 39·6 (sd 9·8) nmol/l, respectively. Additionally, 83·3 % of participants were 25(OH)D deficient. A significant difference in 25(OH)D was observed between males and females in winter and spring (P<0·001). Furthermore, 25(OH)D concentrations were inversely associated with the homeostasis model assessment of insulin resistance (HOMA-IR) in the overweight and pre-diabetic populations. After adjusting for several variables, 25(OH)D was significantly associated with HOMA-IR in winter. When 25(OH)D values were categorized into quartiles, HOMA-IR was significantly associated with decreasing 25(OH)D. Conclusions The majority of the Chinese population was vitamin D deficient and this deficiency was negatively associated with insulin resistance, particularly in the overweight and pre-diabetic populations. Moreover, these associations might be more evident in the winter.
Radiographic and Clinical Results of Freehand S2 Alar-Iliac Screw Placement for Spinopelvic Fixation: An Analysis of 45 Consecutive Screws

Study Design: This was a retrospective clinical case series. Objective: The purpose of this study was to evaluate mid-term outcomes of S2 ala-iliac (S2AI) screw fixation in patients who underwent multilevel posterior spinal fusion surgery. Summary of Background Data: There have been few reports on radiographic and clinical outcomes in patients who underwent spinopelvic reconstruction surgery using S2AI screw installation. Materials and Methods: Twenty-three patients were treated by a single spinal surgeon between September 2013 and June 2014 utilizing segmental instrumentation with pedicle and S2AI screw. Instrumentation including S2AI screw was performed by a freehand technique. Surgical, radiographic, clinical outcomes and complications were evaluated to determine surgical results of S2AI screw fixation. Results: The mean follow-up period was 16.9 months (ranged, 13–22 mo). The average number of fusion levels was 7.9 vertebral bodies. There were no cases of neurological deficit and violation of acetabulum or sciatic notch. A peri-screw halo was found in 1 patient and cortical wall violation was observed in 4 patients. The number of lateral and medial breaches was 2 and 3, respectively. All of them were asymptomatic. One patient experienced sacroiliac joint pain after S2AI screw installation. There was no case of screw/rod fracture and revision surgery for S2AI screw. Conclusions: Radiographic and clinical outcomes of freehand S2AI screw fixation was acceptable. Sacroiliac joint irritation symptoms after S2AI screw fixation were rare. S2AI screw instrumentation can be a good alternative for spinopelvic fixation. Level of Evidence: Level 4.
Combination activity of neuraminidase inhibitor oseltamivir and α-tocopherol in influenza virus A (H3N2) infection in mice

Background Influenza is a highly contagious viral infection of the respiratory system. To attack two processes involved in flu pathogenesis—viral replication in the infected body and oxidative damages, we studied the combination effect of neuraminidase inhibitor oseltamivir and antioxidant α-tocopherol in experimental model of influenza. Methods After inoculation of albino mice with 10 MLD50 (50% mouse lethal dose) of influenza virus A/Aichi/2/68 (H3N2), oseltamivir was applied orally at three doses, 2.5 mg/kg, 1.25 mg/kg, and 0.625 mg/kg, for five days post infection. α-Tocopherol (120 mg/kg, in sunflower oil) was administered intraperitoneally. Three schemes of α-tocopherol five-day course were tested: onset five or two days before infection, or on the virus inoculation day. Results Strongly dose-dependent augmented antiviral effect of the combination α-tocopherol and 0.625 mg/kg oseltamivir was demonstrated when α-tocopherol was administered simultaneously with oseltamivir: a pronounced decrease in mortality rate (a 78% protection), and a lengthening of mean survival time by 3.2–4 days. Lung parameters showed a substantial decrease in infectious virus content (Δ logs = 3.8/4.1) and a marked diminishment of lung index and pathology. Combination α-tocopherol with 1.25 mg/kg oseltamivir manifested a marked protective effect, but the effect on lung parameters was less. The combination effect of α-tocopherol with 2.5 mg/kg oseltamivir did not surpass the monotherapeutic effect of oseltamivir. When α-tocopherol was applied in courses starting five or two days before infection, its combination with oseltamivir was ineffective. Conclusions Evidently, α-tocopherol could be considered as prospective component of influenza therapy in combination with oseltamivir.
Low molecular weight heparin and aspirin exacerbate human endometrial endothelial cell responses to antiphospholipid antibodies

Women with antiphospholipid antibodies (aPL) are at risk for pregnancy complications despite treatment with low molecular weight heparin (LMWH) or aspirin (ASA). aPL recognizing beta2 glycoprotein I can target the uterine endothelium, however, little is known about its response to aPL. This study characterized the effect of aPL on human endometrial endothelial cells (HEECs), and the influence of LMWH and ASA.
Negative regulator of E2F transcription factors links cell cycle checkpoint and DNA damage repair

Significance DNA is frequently damaged by both endogenous and exogenous factors. In response to DNA damage, cells activate checkpoints to arrest cell cycle progression, allowing sufficient time for DNA repair. Defects in DNA repair cause many diseases including cancers. The E2F transcription factors are key players in cell cycle progression and are negatively regulated by the tumor suppressor protein Retinoblastoma. In this study, we demonstrated that the DNA repair protein SNI1, a subunit of SMC5/6 complex, is a negative regulator of E2Fs. In addition, this study also suggests that checkpoint and DNA repair are directly linked by SNI1, providing insights into DNA damage responses. DNA damage poses a serious threat to genome integrity and greatly affects growth and development. To maintain genome stability, all organisms have evolved elaborate DNA damage response mechanisms including activation of cell cycle checkpoints and DNA repair. Here, we show that the DNA repair protein SNI1, a subunit of the evolutionally conserved SMC5/6 complex, directly links these two processes in Arabidopsis. SNI1 binds to the activation domains of E2F transcription factors, the key regulators of cell cycle progression, and represses their transcriptional activities. In turn, E2Fs activate the expression of SNI1, suggesting that E2Fs and SNI1 form a negative feedback loop. Genetically, overexpression of SNI1 suppresses the phenotypes of E2F-overexpressing plants, and loss of E2F function fully suppresses the sni1 mutant, indicating that SNI1 is necessary and sufficient to inhibit E2Fs. Altogether, our study revealed that SNI1 is a negative regulator of E2Fs and plays dual roles in DNA damage responses by linking cell cycle checkpoint and DNA repair.
Critical impact of vegetation physiology on the continental hydrologic cycle in response to increasing CO2

Significance Predicting how increasing atmospheric CO2 will affect the hydrologic cycle is of utmost importance for a wide range of applications. It is typically thought that future dryness will depend on precipitation changes, i.e., change in water supply, and changes in evaporative demand due to either increased radiation or temperature. Opposite to this viewpoint, using Earth system models, we show that changes in key water-stress variables will be strongly modified by vegetation physiological effects in response to increased [CO2] at the leaf level. These results emphasize that the continental carbon and water cycles have to be studied as an interconnected system. Predicting how increasing atmospheric CO2 will affect the hydrologic cycle is of utmost importance for a range of applications ranging from ecological services to human life and activities. A typical perspective is that hydrologic change is driven by precipitation and radiation changes due to climate change, and that the land surface will adjust. Using Earth system models with decoupled surface (vegetation physiology) and atmospheric (radiative) CO2 responses, we here show that the CO2 physiological response has a dominant role in evapotranspiration and evaporative fraction changes and has a major effect on long-term runoff compared with radiative or precipitation changes due to increased atmospheric CO2. This major effect is true for most hydrological stress variables over the largest fraction of the globe, except for soil moisture, which exhibits a more nonlinear response. This highlights the key role of vegetation in controlling future terrestrial hydrologic response and emphasizes that the carbon and water cycles are intimately coupled over land.
An analysis of Dutch hallmark studies confirms the outcome of the PACE trial: cognitive behaviour therapy with a graded activity protocol is not effective for chronic fatigue syndrome and Myalgic Encephalomyelitis

Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) are considered to be enigmatic diseases. Several studies propose that the combination of cognitive behaviour therapy with a graded activity protocol (CBT+), justified by a so-called (bio)psychosocial (explanatory) model, is an effective treatment option for CFS (ME). Objective A critical review of five Dutch hallmark studies that allegedly support this claim. Methods An analysis of the five CBT+ studies with special attention to the patients studied, the criteria (subjective and objective measures and cut-off scores) used to select participants and to define improvement and recovery, the consistency of the definitions of caseness (being diagnosed as a CFS patient at entry) versus the definitions of improvement and recovery after CBT+, and the objective effects. Results The studies investigated suffer from various methodological flaws. Apart from these methodological shortcomings, the claim that CBT+ is an effective treatment option for CFS is not substantiated by the data reported. Some studies investigated CFS patients, other studies investigated CF patients, labelled as CFS patients, or combinations of CFS and CF patients. No study investigated the effect of CBT+ in a group of patients meeting the (original) diagnostic criteria for ME. The effects of CBT+ on subjective measures, for example fatigue and disability, if present, are insufficient to achieve normal values. Impressive recovery and improvement rates are based on very loose criteria for subjective measures. Cut-off scores for subjective measures used to define improvement and recovery in studies show overlap with cut-off scores for CFS caseness in one or more of the other studies. More importantly, looking at the objective measures, the proof of clinical improvement after CBT+ is lacking. Conclusion Solid evidence of effectiveness of CBT+ for CFS, let alone ME, is lacking in the five hallmark studies. The lack of objective improvement indicates CBT+ is ineffective. This finding confirms the outcome of the large-scale PACE-trial in the UK. Correspondence to: Frank NM Twisk MBA MBI BEd BEc, ME-de-patiënten Foundation, Limmen, The Netherlands, Tel: +31-72-505 4775; E-mail: frank. twisk@hetnet.nl
Migration History, Language Acculturation, and Mammographic Breast Density

Background: Breast cancer incidence is lower in many U.S. ethnic minority and foreign-born population groups. Investigating whether migration and acculturation patterns in risk are reflected in disease biomarkers may help to elucidate the underlying mechanisms. Methods: We compared the distribution of breast cancer risk factors across U.S.-born white, African American and Hispanic women, and foreign-born Hispanic women (n = 477, ages 40–64 years, 287 born in Caribbean countries). We used linear regression models to examine the associations of migration history and linguistic acculturation with mammographic breast density (MBD), measured using computer-assisted methods as percent and area of dense breast tissue. Results: The distribution of most breast cancer risk factors varied by ethnicity, nativity, and age at migration. In age- and body mass index–adjusted models, U.S.-born women did not differ in average MBD according to ethnicity, but foreign-born Hispanic women had lower MBD [e.g., −4.50%; 95% confidence interval (CI), −7.12 to −1.89 lower percent density in foreign- vs. U.S.-born Hispanic women]. Lower linguistic acculturation and lower percent of life spent in the United States were also associated with lower MBD [e.g., monolingual Spanish and bilingual vs. monolingual English speakers, respectively, had 5.09% (95% CI, −8.33 to −1.85) and 3.34% (95% CI, −6.57 to −0.12) lower percent density]. Adjusting for risk factors (e.g., childhood body size, parity) attenuated some of these associations. Conclusions: Hispanic women predominantly born in Caribbean countries have lower MBD than U.S.-born women of diverse ethnic backgrounds, including U.S.-born Hispanic women of Caribbean heritage. Impact: MBD may provide insight into mechanisms driving geographic and migration variations in breast cancer risk. Cancer Epidemiol Biomarkers Prev; 27(5); 566–74. ©2018 AACR.
Determination of the small RNA GcvB regulon in the Gram-negative bacterial pathogen Pasteurella multocida and identification of the GcvB seed binding region

Pasteurella multocida is a Gram-negative bacterium responsible for many important animal diseases. While a number of P. multocida virulence factors have been identified, very little is known about how gene expression and protein production is regulated in this organism. Small RNA (sRNA) molecules are critical regulators that act by binding to specific mRNA targets, often in association with the RNA chaperone protein Hfq. In this study, transcriptomic analysis of the P. multocida strain VP161 revealed a putative sRNA with high identity to GcvB from Escherichia coli and Salmonella enterica serovar Typhimurium. High-throughput quantitative liquid proteomics was used to compare the proteomes of the P. multocida VP161 wild-type strain, a gcvB mutant, and a GcvB overexpression strain. These analyses identified 46 proteins that displayed significant differential production after inactivation of gcvB, 36 of which showed increased production. Of the 36 proteins that were repressed by GcvB, 27 were predicted to be involved in amino acid biosynthesis or transport. Bioinformatic analyses of putative P. multocida GcvB target mRNAs identified a strongly conserved 10 nucleotide consensus sequence, 5′-AACACAACAT-3′, with the central eight nucleotides identical to the seed binding region present within GcvB mRNA targets in E. coli and S. Typhimurium. Using a defined set of seed region mutants, together with a two-plasmid reporter system that allowed for quantification of sRNA–mRNA interactions, this sequence was confirmed to be critical for the binding of the P. multocida GcvB to the target mRNA, gltA.