bluuebunny/crossref_metadata_2025 huggingface dataset:
Separation of hyperfine interactions in Mössbauer spectrocsopy
Authors: Szymański Krzysztof R.
Published: December 2019

Problem of determination of isomer shift, all components of the electric field gradient and hyperfine magnetic field in case of mixed hyperfine interactions is presented. Orientation of hyperfine fields in the absorber Cartesian frame can be determined by few measurements with use of unpolarized radiation under different directions of wave vector with respect to the absorber. The method can be applied for absorbers with well separated absorption lines in their spectra. Explicit formulas for tensor components of hyperfine interactions derived from velocity moments formalism are presented.
What is Parent Engagement in Early Learning? Depends Who You Ask
Authors: Gross Deborah , Bettencourt Amie F. , Taylor Kathryn , Francis Lucine , Bower Kelly , Singleton Demetria L.
Published: December 2019

Objectives

Parent engagement in early learning has historically been defined quite broadly and it is unclear whether those designing, implementing, evaluating, or participating in parent engagement initiatives conceptualize parent engagement in the same way. Lack of consensus could contribute to poor quality of parent-school partnerships and reliance on parent engagement measures and strategies that lack meaning and utility. We explored and compared definitions and characteristics of parent engagement in early learning across multiple stakeholders in one urban school district serving predominantly low-income, African American, and Latinx families.

Methods

Using a qualitative descriptive design, we individually interviewed 63 parents (n = 23), teachers (n = 8), early childhood staff (n = 8), district leaders (n = 7), and community leaders (n = 8) to understand how each defined parent engagement in early learning and the characteristics they believed were indicative of an engaged parent.

Results

Nine different definitions were described; the majority centering on parents’ responsibilities for ensuring engagement. We found wide differences within and across stakeholder groups in how parent engagement is defined and operationalized.

Conclusions

There was little consensus in how parent engagement was conceptualized, suggesting there may be different working models for how stakeholders believe parent engagement supports early learning. Three potential parent engagement models are discussed in relation to the qualitative findings. This is the first study to directly compare different stakeholders’ perspectives about parent engagement in early learning in an urban school system serving a large number of low income families and families of color.
On Minimal Copulas under the Concordance Order
Authors: Ahn Jae Youn , Fuchs Sebastian
Published: December 2019

In the present paper, we study extreme negative dependence focussing on the concordance order for copulas. With the absence of a least element for dimensions $$d\ge 3$$d≥3, the set of all minimal elements in the collection of all copulas turns out to be a natural and quite important extreme negative dependence concept. We investigate several sufficient conditions, and we provide a necessary condition for a copula to be minimal. The sufficient conditions are related to the extreme negative dependence concept of d-countermonotonicity and the necessary condition is related to the collection of all copulas minimizing multivariate Kendall’s tau. The concept of minimal copulas has already been proved to be useful in various continuous and concordance order preserving optimization problems including variance minimization and the detection of lower bounds for certain measures of concordance. We substantiate this key role of minimal copulas by showing that every continuous and concordance order preserving functional on copulas is minimized by some minimal copula, and, in the case the continuous functional is even strictly concordance order preserving, it is minimized by minimal copulas only. Applying the above results, we may conclude that every minimizer of Spearman’s rho is also a minimizer of Kendall’s tau.
Diagnosis, treatment and follow-up of patients with acromegaly in a clinical practice setting in Spain: the ACROPRAXIS program Delphi survey
Authors: de Pablos-Velasco Pedro , Venegas Eva María , Álvarez Escolá Cristina , Fajardo Carmen , de Miguel Paz , González Natividad , Bernabéu Ignacio , Valdés Nuria , Paja Miguel , Díez Juan José , Biagetti Betina
Published: December 2019

Aim

The ACROPRAXIS program aims to describe the management of acromegaly in Spain and provide guidance.

Methods

Ninety-three endocrinologists were organized into 13 panels to discuss the practical issues in managing acromegaly. Based on the key learnings, an online Delphi survey with 62 statements was performed, so those statements achieving consensus could be used as guidance. Statements were rated on a 9-point scale (9, full agreement; consensus > 66.6% of response in the same tertile).

Results

Ninety-two endocrinologists (98.8%) answered two rounds of the survey (mean age 47.6 years; 59.8% women; median 18.5 years of experience). Consensus was achieved for 49 (79%) statements. Diagnosis: The levels of insulin-like growth factor I (IGFI) is the preferred screening test. If IGFI levels 1–1.3 ULN, the test is repeated and growth hormone (GH) after oral glucose tolerance test (OGTT) is assessed. A pituitary magnetic resonance is performed after biochemical diagnosis. Treatment: Surgery is the first treatment choice for patients with microadenoma or macroadenoma with/without optical pathway compression. Pre-surgical somatostatin analogues (SSA) are indicated when surgery is delayed and/or to reduce anaesthesia-associated risks. After unsuccessful surgery, reintervention is performed if the residual tumor is resectable, while if non-resectable, SSA are administered. Follow-up First biochemical and clinical controls are performed 1–3 months after surgery. Disease remission is considered if random GH levels are < 1 µg/L or OGTT is < 1 or ≤ 0.4 µg/L, depending on the assay’s sensitivity.

Conclusion

Current clinical management for acromegaly is homogeneous across Spain and generally follows clinical guidelines.
Simulation of the forming process for curved composite sandwich panels
Authors: Chen S. , McGregor O. P. L. , Endruweit A. , Harper L. T. , Warrior N. A.
Published: December 2019

For affordable high-volume manufacture of sandwich panels with complex curvature and varying thickness, fabric skins and a core structure are simultaneously press-formed using a set of matched tools. A finite-element-based process simulation was developed, which takes into account shearing of the reinforcement skins, multi-axial deformation of the core structure, and friction at the interfaces. Meso-scale sandwich models, based on measured properties of the honeycomb cell walls, indicate that panels deform primarily in bending if out-of-plane movement of the core is unconstrained, while local through-thickness crushing of the core is more important in the presence of stronger constraints. As computational costs for meso-scale models are high, a complementary macro-scale model was developed for simulation of larger components. This is based on experimentally determined homogenised properties of the honeycomb core. The macro-scale model was employed to analyse forming of a generic component. Simulations predicted the poor localised conformity of the sandwich to the tool, as observed on a physical component. It was also predicted accurately that fibre shear angles in the skins are below the critical angle for onset of fabric wrinkling.
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

Multiscale 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

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

The 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

Precise 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

The 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

With 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

Over 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.
How to Turn Your Smartphone into an Earthquake Detector
Authors: Duncombe Jenessa
Published: December 2019

A free smartphone app tracks earthquakes using your phone’s accelerometer. One day, the app could issue emergency warnings to those in danger.
Scientists Explore How Best to Communicate About Climate Change
Authors: Showstack Randy
Published: December 2019

An AGU Fall Meeting session focuses on communicating with appropriate urgency about climate change.
Momentum Grows for Mapping the Seafloor
Authors: Showstack Randy
Published: December 2019

Initiatives like the Nippon Foundation-GEBCO Seabed 2030 Project can help us better understand the ocean.
Correction: Exploration of surgical blood pressure management and expected motor recovery in individuals with traumatic spinal cord injury
Authors: Ehsanian Reza , Haefeli Jenny , Quach Nhung , Kosarchuk Jacob , Torres Dolores , Stuck Ellen D. , Endo Jessica , Crew James D. , Dirlikov Benjamin , Bresnahan Jacqueline C. , Beattie Michael S. , Ferguson Adam R. , McKenna Stephen L.
Published: December 2019

A correction to this paper has been published and can be accessed via a link at the top of the paper.
Window of opportunity clinical trial designs to study cancer metabolism
Authors: Aroldi Francesca , Lord Simon R.
Published: December 2019

Window 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

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

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

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

Background

High-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.

Methods

We 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.

Results

We 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.

Conclusion

We 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

Based 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.
Cutting off the fuel supply to calcium pumps in pancreatic cancer cells: role of pyruvate kinase-M2 (PKM2)
Authors: James Andrew D. , Richardson Daniel A. , Oh In-Whan , Sritangos Pishyaporn , Attard Thomas , Barrett Lisa , Bruce Jason I. E.
Published: December 2019

Background

Pancreatic ductal adenocarcinoma (PDAC) has poor survival and treatment options. PDAC cells shift their metabolism towards glycolysis, which fuels the plasma membrane calcium pump (PMCA), thereby preventing Ca2+-dependent cell death. The ATP-generating pyruvate kinase-M2 (PKM2) is oncogenic and overexpressed in PDAC. This study investigated the PKM2-derived ATP supply to the PMCA as a potential therapeutic locus.

Methods

PDAC cell growth, migration and death were assessed by using sulforhodamine-B/tetrazolium-based assays, gap closure assay and poly-ADP ribose polymerase (PARP1) cleavage, respectively. Cellular ATP and metabolism were assessed using luciferase/fluorescent-based assays and the Seahorse XFe96 analyzer, respectively. Cell surface biotinylation identified membrane-associated proteins. Fura-2 imaging was used to assess cytosolic Ca2+ overload and in situ Ca2+ clearance. PKM2 knockdown was achieved using siRNA.

Results

The PKM2 inhibitor (shikonin) reduced PDAC cell proliferation, cell migration and induced cell death. This was due to inhibition of glycolysis, ATP depletion, inhibition of PMCA and cytotoxic Ca2+ overload. PKM2 associates with plasma membrane proteins providing a privileged ATP supply to the PMCA. PKM2 knockdown reduced PMCA activity and reduced the sensitivity of shikonin-induced cell death.

Conclusions

Cutting off the PKM2-derived ATP supply to the PMCA represents a novel therapeutic strategy for the treatment of PDAC.
More than one antibody of individual B cells revealed by single-cell immune profiling
Authors: Shi Zhan , Zhang Qingyang , Yan Huige , Yang Ying , Wang Pingzhang , Zhang Yixiao , Deng Zhenling , Yu Meng , Zhou Wenjing , Wang Qianqian , Yang Xi , Mo Xiaoning , Zhang Chi , Huang Jing , Dai Hui , Sun Baofa , Zhao Yongliang , Zhang Liang , Yang Yun-Gui , Qiu Xiaoyan
Published: December 2019

Antibodies have a common structure consisting of two identical heavy (H) and two identical light (L) chains. It is widely accepted that a single mature B cell produces a single antibody through restricted synthesis of only one VHDJH(encoding the H-chain variable region) and one VLJL(encoding the L-chain variable region) via recombination. Naive B cells undergo class-switch recombination (CSR) from initially producing membrane-bound IgM and IgD to expressing more effective membrane-bound IgG, IgA, or IgE when encountering antigens. To ensure the “one cell — one antibody” paradigm, only the constant region of the H chain is replaced during CSR, while the rearranged VHDJHpattern and the L chain are kept unchanged. To define those long-standing classical concepts at the single-cell transcriptome level, we applied the Chromium Single-Cell Immune Profiling Solution and Sanger sequencing to evaluate the Ig transcriptome repertoires of single B cells. Consistent with the “one cell — one antibody” rule, most of the B cells showed one V(D)J recombination pattern. Intriguingly, however, two or more VHDJHor VLJLrecombination patterns of IgH chain or IgL chain were also observed in hundreds to thousands of single B cells. Moreover, each Ig class showed unique VHDJHrecombination pattern in a single B-cell expressing multiple Ig classes. Together, our findings reveal an unprecedented presence of multi-Ig specificity in some single B cells, implying regulation of Ig gene rearrangement and class switching that differs from the classical mechanisms of both the “one cell — one antibody” rule and CSR.
Author Correction: A genomics approach reveals insights into the importance of gene losses for mammalian adaptations
Authors: Sharma Virag , Hecker Nikolai , Roscito Juliana G. , Foerster Leo , Langer Bjoern E. , Hiller Michael
Published: December 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Sodium Selenate Ameliorates Cardiac Injury Developed from High-Fat Diet in Mice through Regulation of Autophagy Activity
Authors: Zhang Shuqiang , Xu Jialiang , He Zhisong , Xue Feng , Jiang Tingbo , Xu Mingzhu
Published: December 2019

Obesity is often accompanied by dyslipidemia, high blood glucose, hypertension, atherosclerosis, and myocardial dysfunction. Selenate is a vital antioxidant in the cardiovascular system. The beneficial effects of selenate on obesity-associated cardiac dysfunction and potential molecular mechanism were identified in both H9C2 cells and C57BL/6J mice hearts. The cardiac histological preformation in C57BL/6J mice were evaluated by cross-sectional area (CSA) of cardiomyocytes and percent area of fibrosis in the left ventricles. The cardiac autophagy flux in H9C2 cells and C57BL/6J mice hearts was analyzed by Western blots and the number of autophagosomes and autolysosome in H9C2 cells. In the present study, we found that lipid overload caused increases in serum lipid, CSA, and percent area of fibrosis. We further found that lipid-induced accumulation of autophagosomes  was due to depressed autophagy degradation, which was not restored in the pretreatment with 3-methyladenine and chloroquine, whereas, it was improved by rapamycin. Moreover, we demonstrated that increased levels of serum lipid, CSA, percent area of fibrosis and mRNA expression related to cardiomyocytes hypertrophy and fibrosis were significantly reduced after selenate treatments of mice. We also found selenate treatment significantly down-regulated activity of the Akt pathway, which was activated in response to lipid-overload. Furthermore, selenate dramatically improved cardiac autophagic degradation which was suppressed after exposure to lipid-overload in both H9C2 cells and C57BL/6J mice hearts. Taken together, selenate offers therapeutic intervention in lipid-related metabolic disorders, and protection against cardiac remodeling, likely through regulation of the activity of autophagic degradation and Akt pathway.
Insight into diversity of bacteria belonging to the order Rickettsiales in 9 arthropods species collected in Serbia
Authors: Li Kun , Stanojević Maja , Stamenković Gorana , Ilić Bojan , Paunović Milan , Lu Miao , Pešić Branislav , Đurić Maslovara Ivana , Siljic Marina , Cirkovic Valentina , Zhang Yongzhen
Published: December 2019

Rickettsiales bacteria in arthropods play a significant role in both public health and arthropod ecology. However, the extensive genetic diversity of Rickettsiales endosymbionts of arthropods is still to be discovered. In 2016, 515 arthropods belonging to 9 species of four classes (Insecta, Chilopoda, Diplopoda and Arachnida) were collected in Serbia. The presence and genetic diversity of Rickettsiales bacteria were evaluated by characterizing the 16S rRNA (rrs), citrate synthase (gltA) and heat shock protein (groEL) genes. The presence of various Rickettsiales bacteria was identified in the majority of tested arthropod species. The results revealed co-circulation of five recognized Rickettsiales species including Rickettsia, Ehrlichia and Wolbachia, as well as four tentative novel species, including one tentative novel genus named Neowolbachia. These results suggest the remarkable genetic diversity of Rickettsiales bacteria in certain arthropod species in this region. Furthermore, the high prevalence of spotted fever group Rickettsia in Ixodes ricinus ticks highlights the potential public health risk of human Rickettsia infection.
Highly Responsive Ultraviolet Sensor Based on ZnS Quantum Dot Solid with Enhanced Photocurrent
Authors: Premkumar Sellan , Nataraj Devaraj , Bharathi Ganapathi , Ramya Subramaniam , Thangadurai T. Daniel
Published: December 2019

Detection of visible blind UV radiation is not only interesting but also of technologically important. Herein, we demonstrate the efficient detection of UV radiation by using cluster like ZnS quantum dot solid nanostructures prepared by simple reflux condensation technique. The short-chain ligand 3-mercaptopropionic acid (MPA) involved in the synthesis lead to the cluster like formation of ZnS quantum dots into solids upon prolonged synthesis conditions. The ZnS QD solid formation resulted in the strong delocalization of electronic wave function between the neighboring quantum dots. It increases the photocurrent value, which can be further confirmed by the decrease in the average lifetime values from 64 to 4.6 ns upon ZnS cluster like QD solid formation from ZnS QDs. The ZnS quantum dot solid based UV sensor shows good photocurrent response and a maximum responsivity of 0.31 (A/W) at a wavelength of 390 nm, is not only competitive when compared with previous reports but also better than ZnS and metal oxide-based photodetectors. The device exhibits a high current value under low-intensity UV light source and an on/off ratio of IUV/Idark = 413 at zero biasing voltage with a fast response. Further, photocurrent device has been constructed using ZnS quantum dot solid nanostructures with graphene hybrids as an active layer to improve the enhancement of photoresponsivity.
Phonon density of states for α-plutonium from density-functional theory
Authors: Söderlind Per , Yang Lin H.
Published: December 2019

The ground-state α phase of plutonium has an extraordinary 16-atom per cell, monoclinic crystal structure defined by 20 parameters, including the cell dimensions, not dictated by the symmetry. The electronic, magnetic, and elastic properties of this complicated material have been predicted in the past but here we compute its phonon spectra. Employing a density-functional-theory (DFT) model, that is fully relativistic and accounts for orbital–orbital coupling (orbital polarization, OP), we determine the phonon density of states of α-plutonium and find good agreement with inelastic x-ray scattering. The calculated specific heat also compares very favorably with experiment. An analysis of the partial atom-projected phonon spectra suggests that atom type 8, that is located in a more open space of the structure, dominates the intensity at very high phonon frequencies. This feature of the model is essential for a good agreement with the experimental spectra. The satisfactory comparison between theory and experiment for the phonons and specific heat suggests that the DFT (+OP) approach is appropriate and accurate for α-plutonium.
High frequency DNA rearrangement at qγ27 creates a novel allele for Quality Protein Maize breeding
Authors: Liu Hongjun , Huang Yongcai , Li Xiaohan , Wang Haihai , Ding Yahui , Kang Congbin , Sun Mingfei , Li Fangyuan , Wang Jiechen , Deng Yiting , Yang Xuerong , Huang Xing , Gao Xiaoyan , Yuan Lingling , An Dong , Wang Wenqin , Holding David R. , Wu Yongrui
Published: December 2019

Copy number variation (CNV) is a major source of genetic variation and often contributes to phenotypic variation in maize. The duplication at the 27-kDa γ-zein locus (qγ27) is essential to convert soft endosperm into hard endosperm in quality protein maize (QPM). This duplication is unstable and generally produces CNV at this locus. We conducted genetic experiments designed to directly measure DNA rearrangement frequencies occurring in males and females of different genetic backgrounds. The average frequency with which the duplication rearranges to single copies is 1.27 × 10−3 and varies among different lines. A triplication of γ27 gene was screened and showed a better potential than the duplication for the future QPM breeding. Our results highlight a novel approach to directly determine the frequency of DNA rearrangements, in this case resulting in CNV at the qγ27 locus. Furthermore, this provides a highly effective way to test suitable parents in QPM breeding.
A hydrophilic covalent organic framework for photocatalytic oxidation of benzylamine in water
Authors: Liu Ziqian , Su Qing , Ju Pengyao , Li Xiaodong , Li Guanghua , Wu Qiaolin , Yang Bing
Published: December 2019

The highly hydrophilic COF exhibits superior photocatalytic activity and recyclability together with environmental benignity in photocatalytic oxidation of benzylamine in water under ambient conditions.
MnOx MFs as a coreaction accelerator for the construction of a novel ternary electrochemiluminescence system: ultrasensitive detection of microRNA
Authors: Yang Rong , Liu Jia-Li , Chai Ya-Qin , Yuan Ruo
Published: December 2019

An ultrasensitive biosensing platform was constructed based on a novel ternary ECL system (luminol/dissolved oxygen/MnOx MFs) for ultrasensitive microRNA assay from tumour cells.
Designing a near-infrared circularly polarized luminescent dye by dissymmetric spiro-fusion
Authors: Feng Jiajing , Fu Lulu , Geng Hua , Jiang Wei , Wang Zhaohui
Published: December 2019

A chiral spiro-fused terrylene dimer (SDT) with near-infrared circularly polarized luminescent properties was designed by dissymmetric spiro-fusion.
Palladium-catalyzed denitrative Sonogashira-type cross-coupling of nitrobenzenes with terminal alkynes
Authors: Feng Boya , Yang Yudong , You Jingsong
Published: December 2019

Described herein is a palladium-catalyzed cross-coupling reaction between nitroarenes and terminal alkynes, offering a facile method for C(sp2)–C(sp) bond formation.
Homocoupling of CO and isocyanide mediated by a C,C′-bis(silylenyl)-substituted ortho-carborane
Authors: Xiong Yun , Yao Shenglai , Szilvási Tibor , Ruzicka Ales , Driess Matthias
Published: December 2019

A new mode of homocoupling of carbon monoxide and isocyanide with an ortho-carborane-supported bis-silylene selectively leads to unprecedented polycyclic organosilanes with Si–C and SiC bonds.
Ultrahigh oxygen-scavenging norbornene copolymers bearing imidazolyl iron complexes for fabricating active and sustainable packaging films
Authors: Wang Yu , Hasegawa Yui , Serikawa Takuma , Oyaizu Kenichi , Nishide Hiroyuki
Published: December 2019

A tough and transparent polynorbornene film affixing an iron–salen catalyst exhibited an ultra-high oxygen-scavenging capacity up to 300 mL g−1.
Controlling spontaneous mirror symmetry breaking in cubic liquid crystalline phases by the cycloaliphatic ring size
Authors: Reppe Tino , Dressel Christian , Poppe Silvio , Tschierske Carsten
Published: December 2019

Achiral compounds with an alicyclic apex form a chiral cubic phase either for a specific ring-size or by mixing of small- and large-ring compounds.
Plastically bendable pregabalin multi-component systems with improved tabletability and compressibility
Authors: Khandavilli U. B. Rao , Yousuf Mustafa , Schaller Barbara E. , Steendam René R. E. , Keshavarz Leila , McArdle Patrick , Frawley Patrick J.
Published: December 2019

Pregabalin (SPG) is brittle in nature without the presence of any slip planes. The coformer (OX/SA) facilitates the slip planes in order to make the brittle structure plastically bendable.
Sublimation thermodynamics of nucleobases derived from fast scanning calorimetry
Authors: Abdelaziz A. , Zaitsau D. H. , Buzyurov A. V. , Verevkin S. P. , Schick C.
Published: December 2019

Fast scanning calorimetry was utilized to measure the sublimation thermodynamics of nucleobases. The results were rationalized at the molecular level.
Strain-engineering the in-plane electrical anisotropy of GeSe monolayers
Authors: Li Zongbao , Liu Xinsheng , Wang Xia , Yang Yusi , Liu Shun-Chang , Shi Wei , Li Yong , Xing Xiaobo , Xue Ding-Jiang , Hu Jin-Song
Published: December 2019

The anisotropic ratio of the effective mass and mobility of charge carriers of GeSe monolayer along two principle axes can be controlled by using simple strain conditions.
3-D bond-paths of QTAIM and the stress tensor in neutral lithium clusters, Lim(m= 2–5), presented on the Ehrenfest force molecular graph
Authors: Azizi Alireza , Momen Roya , Kirk Steven R. , Jenkins Samantha
Published: December 2019

Top left: Ehrenfest ForceF(r) ∇ρ(r)·σ(r) trajectory map for Li4. Top right: The {qFA,qFA′} path-packets are presented on theF(r) molecular graph. Bottom left and right: The {qF,qF′} and {qσHF,qσHF′} path-packets, using QTAIM on theF(r) molecular graph, the green circles indicate (BCPs).
About the origin of the large Stokes shift in aminoalkyl substituted heptamethine cyanine dyes
Authors: Sissa Cristina , Painelli Anna , Terenziani Francesca , Trotta Massimo , Ragni Roberta
Published: December 2019

Aminoalkyl substituted heptamethine cyanines show a large Stokes shift, ascribed to the geometry relaxation upon photoexcitation that drives the molecule from a distorted ground state structure to a planar and cyanine-like excited state.