bluuebunny/crossref_metadata_2025_split huggingface dataset:
Data-driven acceleration of multiscale methods for uncertainty quantification: application in transient multiphase flow in porous media
Authors: Chan Shing , Elsheikh Ahmed H. 
Published: December 2019

AbstractMultiscale methods aim to address the computational cost of elliptic problems on extremely large grids, by using numerically computed basis functions to reduce the dimensionality and complexity of the task. When multiscale methods are applied in uncertainty quantification to solve for a large number of parameter realizations, these basis functions need to be computed repeatedly for each realization. In our recent work (Chan et al. in J Comput Phys 354:493–511, 2017), we introduced a data-driven approach to further accelerate multiscale methods within uncertainty quantification. The basic idea is to construct a surrogate model to generate such basis functions at a much faster speed. The surrogate is modeled using a dataset of computed basis functions collected from a few runs of the multiscale method. Our previous study showed the effectiveness of this framework where speedups of two orders of magnitude were achieved in computing the basis functions while maintaining very good accuracy, however the study was limited to tracer flow/steady state flow problems. In this work, we extend the study to cover transient multiphase flow in porous media and provide further assessments.
X-ray microanalysis of dentine in primary teeth diagnosed Dentinogenesis Imperfecta type II
Authors: Sabel N. , Norén J. G. , Robertson A. , Cornell D. H. 
Published: December 2019

Abstract
Aim
To analyse the elemental composition of dentine in primary teeth from children diagnosed with Dentinogenesis Imperfecta type II (DI) and from normal sound primary teeth using X-ray microanalysis.

Materials and methods
X-ray microanalysis of the elements C, O, Na, Mg, P, Cl, K and Ca were performed in the dentine of five normal primary teeth and in seven primary teeth diagnosed DI. The analysis was made in a low magnification in 10 points from the enamel-dentine junction/root surface toward the pulp. The data was also evaluated with an inductive analysis.

Results
Lower values for C were found in DI-dentine compared with normal dentine. Na had significantly higher values in DI-dentine while Mg had significantly lower values. The inductive analysis revealed that Na and Mg were the most important elements for discriminating DI-dentine from normal dentine.

Conclusions
Dentine in primary teeth from patients diagnosed with Dentinogenesis Imperfecta type II analysed with XRMA have lower values of C and Mg and higher values of O and Na compared with normal primary dentine.
Elastoplastic Analysis of a Functionally Graded Material Beam Subjected to Uniformly Distributed Load
Authors: Xue L. J. , Bian X. Y. , Feng J. J. , Liu J. N. 
Published: December 2019

ABSTRACTThe elastoplastic behavior of a Functionally Graded Material (FGM) simply supported beam consisting of elastic material A and elastoplastic material B under uniformly distributed load is investigated. A power function is used to describe the volume fractions of the constituent materials, and the average stress of the FGM beam is obtained by using the averaging method. This method can avoid the assumption of the varying properties of the whole material, and can consider the different Possion’s ratios of the different constituent materials. What’s more, only the elastoplastic material B in the FGM beam will yield, and the yield function is determined by the stress of material B only, rather than the average stress of the whole material. The method used in this work is more closer to the real material than the method by assuming the variation of the whole properties of FGM. The theoretical results show a good agreement with the finite element results, which indicates that the method provided in this work is valid. With this method, the variation of the elastic and plastic areas, the stress distribution on the cross section, variation of the curvature and neutral layer, and the residual stress distribution of the FGM beam are discussed through numerical results. This work can provide a new way for the design and in-depth investigation of FGM material.
Stress Analysis of Improper Femur Cut in Total Knee Arthroplasty by Finite Element Method
Authors: Su W. L. , You K. D. , Yang C. C. , Wu J. J. , Yeh M. K. 
Published: December 2019

ABSTRACTPrecise bone cut is fundamental in total knee arthroplasty. However, notching of anterior femoral is not uncommon in clinical practice. Reviewing the article, notching and its complication may reach up to 30% and 2.5%, and there is scanty study of notching on the femoral strength. We therefore conduct the finite element analysis to elucidate the effect of notching on femoral mechanical strength. The computerized tomography images were used as the basis to develop the knee model, which was assumed mainly to consist of cortical and cancellous bones. For the implant joint, Zimmer data was considered partly as the basis to develop the model. This study investigated the femoral improper cut effect on the surgery with a static standing condition. The results show that the anterior femoral cut should be undercut 2 mm to overcut 1 mm during the surgery, in order to prevent bone materials from yielding. The exposure of the cancellous bone may cause bone materials to yield when the femur overcut was 2 mm; the cancellous bone may load too much and result in a fracture when the undercut was 3 mm. The effect of undercut, which was rarely discussed, was particularly addressed in our study. Precise femoral cut is crucial for the longevity of total knee arthroplasty.
The Influence of Corrosion on the Anti-Loosening Performance of a Precision Locknut Subjected to Rotation and Periodic Impact
Authors: Chen C. M. , Chang H. L. , Lee C. Y. 
Published: December 2019

ABSTRACTThe influence of combined corrosion and vibration to the anti-loosening performance of a precision locknut used in a machine tool is investigated. Firstly, the locknut was submerged in 5% NaCl solution according to ASTM B895 standard for corrosion testing. The locknuts, after submerged in 1-hr, 2-hr and 4-hr periods, respectively, were then installed on the rotating spindle in a vertical dynamic impact tester for performing anti-loosening test. The initial installed pretension was 9800 N and the spindle was rotating in a constant speed of 1000 rpm. Turmogrease Li 802 EP lubricant was used on the contact surface between spindle thread and locknut. The set screws on the locknut were tightened sequentially and evenly in three-stage of torque: 1.96 N-m, 3.92 N-m and 5.88 N-m. Its real-time pretension variation with the periodic transverse impact and its final loosening torque were measured. Accordingly, the axial force ratio and anti-loosening torque ratio were calculated and discussed. It was found that corrosion treatment had similar influence on both the axial force ratio and the anti-loosening torque ratio. More corrosion on the locknut with longer submersion in NaCl solution deteriorated its anti-loosening characteristics. The result could serve as the reference for evaluating the fastening performance of precision locknut and guide the design and manufacturing for the application improvement.
An Online Trajectory Generator on SE(3) for Human–Robot Collaboration
Authors: Huber Gerold , Wollherr Dirk 
Published: December 2019

SummaryWith the increasing demand for humans and robots to collaborate in a joint workspace, it is essential that robots react and adapt instantaneously to unforeseen events to ensure safety. Constraining robot dynamics directly on SE(3), that is, the group of 3D translation and rotation, is essential to comply with the emerging Human–Robot Collaboration (HRC) safety standard ISO/TS 15066. We argue that limiting coordinate-independent magnitudes of physical dynamic quantities at the same time allows more intuitive constraint definitions. We present the first real-time capable online trajectory generator that constrains translational and rotational magnitude values of 3D translation and 3D rotation dynamics in a singularity-free formulation. Simulations as well as experiments on a hardware platform show the utility in HRC contexts.
CDC’s Multiple Approaches to Safeguard the Health, Safety, and Resilience of Ebola Responders
Authors: Klomp Richard W. , Jones Laurie , Watanabe Emi , Thompson William W. 
Published: December 2019

AbstractOver 27,000 people were sickened by Ebola and over 11,000 people died between March of 2014 and June of 2016. The US Centers for Disease Control and Prevention (CDC; Atlanta, Georgia USA) was one of many public health organizations that sought to stop this outbreak. This agency deployed almost 2,000 individuals to West Africa during that timeframe. Deployment to these countries exposed these individuals to a wide variety of dangers, stressors, and risks.Being concerned about the at-risk populations in Africa, and also the well-being of its professionals who willingly deployed, the CDC did several things to help safeguard the health, safety, and resilience of these team members before, during, and after deployment.The accompanying special report highlights innovative pre-deployment training initiatives, customized screening processes, and post-deployment outreach efforts intended to protect and support the public health professionals fighting Ebola. Before deploying, the CDC team members were expected to participate in both internally-created and externally-provided trainings. These ranged from pre-deployment briefings, to Preparing for Work Overseas (PFWO) and Public Health Readiness Certificate Program (PHRCP) courses, to Incident Command System (ICS) 100, 200, and 400 courses.A small subset of non-clinical deployers also participated in a three-day training designed in collaboration with the Center for the Study of Traumatic Stress (CSTS; Bethesda, Maryland USA) to train individuals to assess and address the well-being and resilience of themselves and their teammates in the field during a deployment. Participants in this unique training were immersed in a Virtual Reality Environment (VRE) that simulated deployment to one of seven different types of emergencies.The CDC leadership also requested a pre-deployment screening process that helped professionals in the CDC’s Occupational Health Clinic (OHC) determine whether or not individuals were at an increased risk of negative outcomes by participating in a rigorous deployment at that time.When deployers returned from the field, they received personalized invitations to participate in a voluntary, confidential, post-deployment operational debriefing one-on-one or in a group.Implementing these approaches provided more information to clinical decision makers about the readiness of deployers. It provided deployers with a greater awareness of the kinds of challenges they were likely to face in the field. The post-deployment outreach efforts reminded staff that their contributions were appreciated and there were resources available if they needed help processing any of the potentially-traumatizing things they may have experienced.
Efficacy of phytosomal curcumin among patients with non-alcoholic	fatty liver disease
Authors: Mirhafez Seyed Reza , Rezai Azam , Dehabeh Maryam , Nobakht M. Gh B. Fatemeh , Bidkhori Mohammad , Sahebkar Amirhosein , Hariri Mitra 
Published: December 2019

Abstract. Scientists proposed that curcumin could be used for treatment of non-alcoholic fatty liver disease (NAFLD). In this article, we aimed to identify the effect of curcumin on NAFLD improvement. Fifty patients with NAFLD, were divided into two groups in this randomized, double-blind, and controlled clinical trial. Patients in the curcumin group received 250 mg/day of phytosomal curcumin, while those in the control group received 250 mg/day of placebo for duration of eight weeks. Anthropometric measurements and fasting blood samples were taken once at the baseline and once at the end of the study. Analysis was performed on 45 patients (curcumin group n = 22, placebo group n = 22). According to between groups analysis, curcumin significantly reduced the carboxymethyl lisine (CML) (148 ± 108 ng/mL vs 197 ± 101 ng/mL, P = 0.04), 8-hydroxy-2’ -deoxyguanosine (8-OHdG) (46.9 ± 31.1 ng/mL vs 52.1 ± 43.1 ng/mL P = 0.03), liver enzymes (P < 0.001), weight (P < 0.001), waist circumference (P < 0.001), body fat percent (P < 0.01), and body mass index (BMI) (P < 0.01) in comparison with placebo. However, curcumin supplementation compared to placebo did not reduce soluble receptors for advanced glycation end products (sRAGE), hip circumference, waist/hip, and fat free mass by the end of the study. Our study indicated that phytosamal curcumin might be able to reduce the NAFLD progress by reducing the anthropometric measures, AGEs, and DNA damage. However, we need more studies with longer intervention duration, and larger sample size.
Window of opportunity clinical trial designs to study cancer metabolism
Authors: Aroldi Francesca , Lord Simon R. 
Published: December 2019

AbstractWindow of opportunity trials exploit the ‘window’ of time after cancer diagnosis, typically prior to initiation of cancer therapy. In recent years this study design has become a more regular feature of drug development, as this ‘window’ provides an opportunity to carry out a thorough pharmacodynamic assessment of a therapy of interest in tumours that are unperturbed by prior treatment. Many of the first window trials interrogated the bioactivity of drugs being repurposed for cancer treatment, in particular the anti-mitochondrial agent, metformin. In this review, we describe examples of window study designs that have been used to assess drugs that target cancer metabolism with a focus on metformin. In addition, we discuss how window studies may aid the development of molecular metabolic cancer imaging.
Enhanced glutamine uptake influences composition of immune cell infiltrates in breast cancer
Authors: Ansari Rokaya El , Craze Madeleine L. , Althobiti Maryam , Alfarsi Lutfi , Ellis Ian O. , Rakha Emad A. , Green Andrew R. 
Published: December 2019

Abstract
Background
Cancer cells must alter their metabolism to support proliferation. Immune evasion also plays a role in supporting tumour progression. This study aimed to find whether enhanced glutamine uptake in breast cancer (BC) can derive the existence of specific immune cell subtypes, including the subsequent impact on patient outcome.

Methods
SLC1A5, SLC7A5, SLC3A2 and immune cell markers CD3, CD8, FOXP3, CD20 and CD68, in addition to PD1 and PDL1, were assessed by using immunohistochemistry on TMAs constructed from a large BC cohort (n = 803). Patients were stratified based on SLC protein expression into accredited clusters and correlated with immune cell infiltrates and patient outcome. The effect of transient siRNA knockdown of SLC7A5 and SLC1A5 on PDL1 expression was evaluated in MDA-MB-231 cells.

Results
High SLCs were significantly associated with PDL1 and PD1 +, FOXP3 +, CD68 + and CD20 + cells (p < 0.001). Triple negative (TN), HER2 + and luminal B tumours showed variable associations between SLCs and immune cell types (p ≤ 0.04). The expression of SLCs and PDL1, PD1 +, FOXP3 + and CD68 + cells was associated with poor patient outcome (p < 0.001). Knockdown of SLC7A5 significantly reduced PDL1 expression.

Conclusion
This study provides data that altered glutamine pathways in BC that appears to play a role in deriving specific subtypes of immune cell infiltrates, which either support or counteract its progression.
Increased inflammatory lipid metabolism and anaplerotic mitochondrial activation follow acquired resistance to vemurafenib in BRAF-mutant melanoma cells
Authors: Delgado-Goñi Teresa , Galobart Teresa Casals , Wantuch Slawomir , Normantaite Deimante , Leach Martin O. , Whittaker Steven R. , Beloueche-Babari Mounia 
Published: December 2019

Abstract
Background
BRAF inhibitors, such as vemurafenib, have shown efficacy in BRAF-mutant melanoma treatment but acquired-resistance invariably develops. Unveiling the potential vulnerabilities associated with vemurafenib resistance could provide rational strategies for combinatorial treatment.

Methods
This work investigates the metabolic characteristics and vulnerabilities of acquired resistance to vemurafenib in three generated BRAF-mutant human melanoma cell clones, analysing metabolic profiles, gene and protein expression in baseline and nutrient withdrawal conditions. Preclinical findings are correlated with gene expression analysis from publicly available clinical datasets.

Results
Two vemurafenib-resistant clones showed dependency on lipid metabolism and increased prostaglandin E2 synthesis and were more responsive to vemurafenib under EGFR inhibition, potentially implicating inflammatory lipid and EGFR signalling in ERK reactivation and vemurafenib resistance. The third resistant clone showed higher pyruvate-carboxylase (PC) activity indicating increased anaplerotic mitochondrial metabolism, concomitant with reduced GLUT-1, increased PC protein expression and survival advantage under nutrient-depleted conditions. Prostaglandin synthase (PTGES) expression was inversely correlated with melanoma patient survival. Increases in PC and PTGES gene expression were observed in some patients following progression on BRAF inhibitors.

Conclusions
Altogether, our data highlight heterogeneity in metabolic adaptations during acquired resistance to vemurafenib in BRAF-mutant melanoma, potentially uncovering key clinically-relevant mechanisms for combinatorial therapeutic targeting.
Serotonin activates glycolysis and mitochondria biogenesis in human breast cancer cells through activation of the Jak1/STAT3/ERK1/2 and adenylate cyclase/PKA, respectively
Authors: Sola-Penna Mauro , Paixão Larissa P. , Branco Jessica R. , Ochioni Alan C. , Albanese Jamille M. , Mundim Davi M. , Baptista-de-Souza Daniela , Figueiredo Claudia P. , Coelho Wagner S. , Marcondes Mariah C. , Zancan Patricia 
Published: December 2019

Abstract
Background
Although produced by several types of tumours, the role of serotonin on cancer biology is yet to be understood.

Methods
The effects of serotonin (5-HT) on human breast cancer cells proliferation, signalling pathways and metabolic profile were evaluated by cytometry, western blotting, qPCR, enzymology and confocal microscopy.

Results
Our results revealed that incubation of MCF-7 cells with 10 µM 5-HT increased cell growth rate by 28%, an effect that was prevented by the 5-HTR2A/C antagonist, ketanserin. Conversely, increasing concentrations of 5-HT promoted glucose consumption and lactate production by MCF-7 cells. We also showed that increased glucose metabolism is provoked by the upregulation of pyruvate kinase M2 (PKM2) isoform through 5-HTR2A/C-triggered activation of Jak1/STAT3 and ERK1/2 subcellular pathways. However, we noticed a decrease in the rate of produced lactate per consumed glucose as a function of the hormone concentration, suggesting a disruption of the Warburg effect. The latter effect is due to 5-HTR2A/C-dependent mitochondrial biogenesis and metabolism, which is triggered by adenylyl cyclase/PKA, enhancing the oxidation of lactate within these cells.

Conclusions
We showed that serotonin, through 5-HTR2A/C, interferes with breast cancer cells proliferation and metabolism by triggering two distinct signalling pathways: Jak1/STAT3 that boosts glycolysis through upregulation of PKM2, and adenylyl cyclase/PKA that enhances mitochondrial biogenesis.
Metabolic response patterns in brain microdialysis fluids and serum during interstitial cisplatin treatment of high-grade glioma
Authors: Björkblom Benny , Jonsson Pär , Tabatabaei Pedram , Bergström Per , Johansson Mikael , Asklund Thomas , Bergenheim A. Tommy , Antti Henrik 
Published: December 2019

AbstractBackgroundHigh-grade gliomas are associated with poor prognosis. Tumour heterogeneity and invasiveness create challenges for effective treatment and use of systemically administrated drugs. Furthermore, lack of functional predictive response-assays based on drug efficacy complicates evaluation of early treatment responses.MethodsWe used microdialysis to deliver cisplatin into the tumour and to monitor levels of metabolic compounds present in the tumour and non-malignant brain tissue adjacent to tumour, before and during treatment. In parallel, we collected serum samples and used multivariate statistics to analyse the metabolic effects.ResultsWe found distinct metabolic patterns in the extracellular fluids from tumour compared to non-malignant brain tissue, including high concentrations of a wide range of amino acids, amino acid derivatives and reduced levels of monosaccharides and purine nucleosides. We found that locoregional cisplatin delivery had a strong metabolic effect at the tumour site, resulting in substantial release of glutamic acid, phosphate, and spermidine and a reduction of cysteine levels. In addition, patients with long-time survival displayed different treatment response patterns in both tumour and serum. Longer survival was associated with low tumour levels of lactic acid, glyceric acid, ketoses, creatinine and cysteine. Patients with longer survival displayed lower serum levels of ketohexoses, fatty acid methyl esters, glycerol-3-phosphate and alpha-tocopherol, while elevated phosphate levels were seen in both tumour and serum during treatment.ConclusionWe highlight distinct metabolic patterns associated with high-grade tumour metabolism, and responses to cytotoxic cisplatin treatment.
The therapeutic potential of targeting tryptophan catabolism in cancer
Authors: Opitz Christiane A. , Somarribas Patterson Luis F. , Mohapatra Soumya R. , Dewi Dyah L. , Sadik Ahmed , Platten Michael , Trump Saskia 
Published: December 2019

AbstractBased on its effects on both tumour cell intrinsic malignant properties as well as anti-tumour immune responses, tryptophan catabolism has emerged as an important metabolic regulator of cancer progression. Three enzymes, indoleamine-2,3-dioxygenase 1 and 2 (IDO1/2) and tryptophan-2,3-dioxygenase (TDO2), catalyse the first step of the degradation of the essential amino acid tryptophan (Trp) to kynurenine (Kyn). The notion of inhibiting IDO1 using small-molecule inhibitors elicited high hopes of a positive impact in the field of immuno-oncology, by restoring anti-tumour immune responses and synergising with other immunotherapies such as immune checkpoint inhibition. However, clinical trials with IDO1 inhibitors have yielded disappointing results, hence raising many questions. This review will discuss strategies to target Trp-degrading enzymes and possible down-stream consequences of their inhibition. We aim to provide comprehensive background information on Trp catabolic enzymes as targets in immuno-oncology and their current state of development. Details of the clinical trials with IDO1 inhibitors, including patient stratification, possible effects of the inhibitors themselves, effects of pre-treatments and the therapies the inhibitors were combined with, are discussed and mechanisms proposed that might have compensated for IDO1 inhibition. Finally, alternative approaches are suggested to circumvent these problems.