bluuebunny/crossref_metadata_2025 huggingface dataset:
Recessively‐Inherited Adult‐Onset Alexander Disease Caused by a Homozygous Mutation in the GFAP Gene
Authors: Fu Mu‐Hui , Chang Yung‐Yee , Lin Ni‐Hsuan , Yang Ai‐Wen , Chang Chiung‐Chih , Liu Jia‐Shou , Peng Cheng‐Huei , Wu Kay, L.H. , Perng Ming‐Der , Lan Min‐Yu
Published: May 2020

Background

Alexander disease (AxD) is an autosomal‐dominant leukodystrophy caused by heterozygous mutations in the glial fibrillary acidic protein (GFAP) gene.

Objectives

The objective of this report is to characterize the clinical phenotype and identify the genetic mutation associated with adult‐onset AxD.

Methods

A man presented with progressive unsteadiness since age 16. Magnetic resonance imaging findings revealed characteristic features of AxD. The GFAP gene was screened, and a candidate variant was functionally tested to evaluate causality.

Results

A homozygous c.197G > A (p.Arg66Gln) mutation was found in the proband, and his asymptomatic parents were heterozygous for the same mutation. This mutation affected GFAP solubility and promoted filament aggregation. The presence of the wild‐type protein rescued mutational effects, consistent with the recessive nature of this mutation.

Conclusions

This study is the first report of AxD caused by a homozygous mutation in GFAP. The clinical implication is while examining patients with characteristic features on suspicion of AxD, GFAP screening is recommended even without a supportive family history. © 2020 International Parkinson and Movement Disorder Society
Boundary‐domain integral equation systems to the Dirichlet and Neumann problems for compressible Stokes equations with variable viscosity in 2D
Authors: Ayele Tsegaye G. , Dagnaw Mulugeta A.
Published: May 2020

In this paper, the Dirichlet and Neumann boundary value problems for the steady‐state Stokes system of partial differential equations for a compressible viscous fluid with variable viscosity coefficient is considered in two‐dimensional bounded domain. Using an appropriate parametrix, this problem is reduced to a system of direct segregated boundary‐domain integral equations (BDIEs). The BDIEs in the two‐dimensional case have special properties in comparison with the three dimension because of the logarithmic term in the parametrix for the associated partial differential equations. Consequently, we need to set conditions on the function spaces or on the domain to ensure the invertibility of corresponding parametrix‐based hydrodynamic single layer and hypersingular potentials and hence the unique solvability of BDIEs. Equivalence of the BDIE systems to the Dirichlet and Neumann BVPs and the invertibility of the corresponding boundary‐domain integral operators in appropriate Sobolev spaces are shown.
Existence of positive solutions for prescribed mean curvature problems with nonlocal term via sub‐ and supersolution method
Authors: Figueiredo Giovany , Suarez Antonio
Published: May 2020

In this paper, we are concerned with the existence of solution to the class of nonlocal quasilinear problem of the type

where Ω is a smooth bounded domain on
,
,
, and
are functions whose hypotheses will be detailed later. We use sub‐ and supersolution method to find solutions to problem (P). Further, we apply our result to some specific nonlocal prescribed mean curvature problems.
In Celiac Disease Patients the In Vivo Challenge with the Diploid Triticum monococcum Elicits a Reduced Immune Response Compared to Hexaploid Wheat
Authors: Picascia Stefania , Camarca Alessandra , Malamisura Monica , Mandile Roberta , Galatola Martina , Cielo Donatella , Gazza Laura , Mamone Gianfranco , Auricchio Salvatore , Troncone Riccardo , Greco Luigi , Auricchio Renata , Gianfrani Carmen
Published: May 2020

Scope

Gluten from the diploid wheat Triticum monococcum (TM) has low content of immunostimulatory sequences and a high gastro‐intestinal digestibility. Gluten‐reactive T cells elicited by diploid and hexaploid (Triticum aestivum‐TA) wheat in celiac disease (CD) patients upon a brief oral challenge are analyzed.

Methods and results

Seventeen patients with CD (median age 13 years) consumed for 3 days sandwiches made with TM (cultivar Norberto‐ID331, N=11), or TA (cultivar Sagittario, N=11) flours, corresponding to 12 gr of gluten/die. Immunostimulatory properties are assessed in blood by measuring the IFN‐γ‐secreting T cells by EliSpot and the expression of inflammatory cytokines/receptors (IL‐12A, IL‐15, IL‐18RAP, IFN‐γ) by qPCR. TA mobilizes a remarkable number of gliadin‐specific, IFN‐γ‐secreting T cells (p<0.05), while no significant cell mobilization is induced by TM (p=ns). Similar results are obtained in response to five immunogenic peptides from α‐, ω‐, and γ‐gliadins, although with a large individual variability. An increased mRNA expression for IL‐12A and IFN‐γ is detected in the group eating TA compared to those consuming TM (p<0.05).

Conclusions

Although T. monococcum is a cereal not suitable for the diet of celiacs, this diploid wheat elicits a reduced in vivo T‐cell response compared to T. aestivum in celiac patients.
Design and packaging of dual‐band and dual‐polarized planar antenna for automotive applications
Authors: Agrawal Niraj , Gautam Anil Kumar , Mishra Rajesh , Pandey Vijay
Published: May 2020

This paper presents a CPW‐fed novel structure of dual‐band and dual‐polarized planar antenna consisting of protrudent‐shaped radiator and spiral‐ and cross‐shaped strips loaded ground plane for GPS L1 and SDARS band applications. The right hand circular polarization at GPS L1 and left‐hand circular polarization at SDARS bands were excited by attaching cross‐ and spiral‐shaped strips to the ground plane. The total volume of the presented structure is only 67.5 × 65.5 × 1.6 mm3, rendering it very useful for surveying and geo‐informatics applications. The proposed antenna displays the center frequencies at 1.57542 GHz (BW of 429 MHz from 1.420‐1.849 GHz) with 3‐dB RHCP axial ratio bandwidth of 51 MHz and at 2.3325 GHz (BW of 1900 MHz from 2.130‐4.030 GHz) with 3‐dB LHCP axial ratio bandwidth of 175 MHz. Experimental results confirmed that the proposed structure successfully operates at two separate bands with independent polarization that is, RHCP at GPS L1 band and LHCP at SDARS band. The antenna performance were also tested and found to be satisfactory in practical scenario by installing it at the automobile's roof and also by changing dielectric constant of the housing material.
LPS‐mediated release of ATP from urothelial cells occurs by lysosomal exocytosis
Authors: Silberfeld Andrew , Chavez Brittany , Obidike Chinonso , Daugherty Stephanie , de Groat William C. , Beckel Jonathan M.
Published: May 2020

Background

While numerous studies have confirmed ATP's importance in bladder physiology/pathophysiology, the literature is still conflicted regarding the mechanism of ATP release from the urothelium. Multiple mechanisms have been identified including non‐vesicular release via pannexin channels as well as vesicular release via a mechanism blocked by botulinum toxin. Recently, it has been shown that lysosomes contain significant stores of ATP which can be released extracellularly in response to Toll‐like receptor (TLR) stimulation.

Objective

The goal of the current study was to determine if lysosomal exocytosis occurs in urothelial cells in response to TLR4 stimulation by its agonist, bacterial lipopolysaccharide (LPS).

Materials and Methods

Human urothelial cells from an immortalized cell line (TRT‐HU1) were treated with bacterial LPS (100 μg/ml) or the nicotinic agoinist cytisine (100 μM) and extracellular release of ATP and lysosomal acid phosphatase were measured. Pannexin‐mediated ATP release and lysosomal ATP release were differentiated using Brilliant Blue FCF to inhibit pannexin channels and glycyl‐l‐phenylalanine‐β‐naphthylamide (GPN) to destroy lysosomes. The mechanisms controlling lysosomal exocytosis were examined using lysosomal pH measurements using LysoSensor dye and intracellular calcium signaling using Fura‐2.

Results

Stimulation of TRT‐HU1 cells with LPS significantly increased ATP release, which was inhibited by GPN, but not by Brilliant Blue FCF. Conversely, stimulation with cytisine induced ATP release that was sensitive to Brilliant Blue FCF but not GPN. LPS stimulation also induced the release of the lysosomal acid phosphatases. LPS increased lysosomal pH and direct alkalization of lysosomal pH using chloroquine or bafilomycin A1 induced ATP and acid phosphatase release, indicating an important role for pH in lysosomal exocytosis. Additionally, stimulation of lysosomal transient receptor potential mucolipin 1 calcium channels evoked intracellular calcium transients as well as ATP release.

Conclusion

These data indicate that LPS‐induced ATP release from urothelial cells is mediated by lysosomal exocytosis, a vesicular mechanism distinctly separate from non‐vesicular release via pannexin channels.
Charged Tags for the Identification of Oxidative Drug Metabolites Based on Electrochemistry and Mass Spectrometry
Authors: Gutmann Alexandra , Wesenberg Lars Julian , Peez Nadine , Waldvogel Siegfried R. , Hoffmann Thorsten
Published: May 2020

Most of the active pharmaceutical ingredients like Metoprolol are oxidatively metabolized by liver enzymes, such as Cytochrome P450 monooxygenases into oxygenates and therefore hydrophilic products. It is of utmost importance to identify the metabolites and to gain knowledge on their toxic impacts. By using electrochemistry, it is possible to mimic enzymatic transformations and to identify metabolic hot spots. By introducing charged‐tags into the intermediate, it is possible to detect and isolate metabolic products. The identification and synthesis of initially oxidized metabolites are important to understand possible toxic activities. The gained knowledge about the metabolism will simplify interpretation and predictions of metabolitic pathways. The oxidized products were analyzed with high performance liquid chromatography‐mass spectrometry using electrospray ionization (HPLC‐ESI‐MS) and nuclear magnetic resonance (NMR) spectroscopy. For proof‐of‐principle, we present a synthesis of one pyridinated main oxidation product of Metoprolol.
Environmental aesthetics: A synthetic review
Authors: Brady Emily , Prior Jonathan
Published: May 2020

The main aim of the article is to provide up‐to‐date knowledge of environmental aesthetics for an interdisciplinary audience, and to signal the importance of research in this area for studying people–nature relationships.

Environmental aesthetics has emerged in the last 50 years from the philosophical fields of aesthetics and environmental philosophy. Other disciplinary perspectives have also shaped environmental aesthetics, including landscape architecture, human geography, restoration ecology and empirical studies on landscape preferences in developmental and environmental psychology.

This review and synthesis mainly addresses the theoretical approaches and concepts that provide a framework to the key debates in the field, but also considers how empirical approaches have shaped recent developments, and how conceptual issues arise with respect to empirical cases.

We outline the background and context of environmental aesthetics, its key concepts, and provide a critical review of contemporary theories in the field. We then consider how aesthetics features in issues pertaining to the conservation, preservation, and restoration of nature.

Finally, we identify some new directions for environmental aesthetics scholarship that can productively contribute to ongoing debates regarding various relationships between people and nature.

A freePlain Language Summarycan be found within the Supporting Information of this article.
Observation of Undamped 3D Brownian Motion of Nanoparticles Using Liquid‐Cell Scanning Transmission Electron Microscopy
Authors: Welling Tom A. J. , Sadighikia Sina , Watanabe Kanako , Grau‐Carbonell Albert , Bransen Maarten , Nagao Daisuke , van Blaaderen Alfons , van Huis Marijn A.
Published: May 2020

In theory, liquid‐cell (scanning) transmission electron microscopy (LC(S)TEM) is the ideal method to measure 3D diffusion of nanoparticles (NPs) on a single particle level, beyond the capabilities of optical methods. However, particle diffusion experiments have been especially hard to explain in LC(S)TEM as the observed motion thus far has been slower than theoretical predictions by 3–8 orders of magnitude due to electron beam effects. Here, direct experimental evidence of undamped diffusion for two systems is shown; charge‐neutral 77 nm gold nanoparticles in glycerol and negatively charged 350 nm titania particles in glycerol carbonate. The high viscosities of the used media and a low electron dose rate allow observation of Brownian motion that is not significantly altered by the electron beam. The resulting diffusion coefficient agrees excellently with a theoretical value assuming free diffusion. It is confirmed that the particles are also moving in the direction parallel to the electron beam by simulating STEM images using Monte Carlo simulations. Simulations and experiments show blurring of the particles when these move out of focus. These results make clear that direct observation of 3D diffusion of NPs is possible, which is of critical importance for the study of interparticle interactions or in situ colloidal self‐assembly using LC(S)TEM.
Substrate‐Modulated Electromagnetic Resonances in Colloidal Cu2O Nanospheres
Authors: Li Nannan , Wang Hao , Lai Yunhe , Chen Huanjun , Wang Jianfang
Published: May 2020

Dielectric nanoparticles are expected to complement or even replace plasmonic nanoparticles in many optical and optoelectronic applications, because they exhibit small absorption losses and support strong electric and magnetic resonances simultaneously. Dielectric nanoparticles need to be deposited on various substrates in many applications. Understanding the substrate effect on the electromagnetic resonances of dielectric nanoparticles is of great importance for engineering their resonance properties and designing optical devices. In this study, moderate‐refractive‐index cuprous oxide nanospheres with uniform sizes and shapes are synthesized. The scattering spectra and images of the nanospheres deposited on three types of substrates are analyzed experimentally and theoretically. When supported on indium tin oxide–coated glass slides and Si wafers, the color of the nanospheres varies from blue, cyan, green, yellow, orange and red, covering almost the entire visible region. When deposited on gold films, the electromagnetic resonances of the nanospheres redshift intensively and a new effective magnetic resonance mode appears. The enhanced Raman scattering reveals that large electromagnetic field enhancements are produced in the gap region between the nanosphere and the substrate. The results shed light on the manipulation of the electromagnetic responses of dielectric nanoparticles and the design of dielectric metamaterials in the presence of various substrates.
NICE on the use of cannabis‐based medicinal products
Authors: Chaplin Steve
Published: May 2020

This article provides a summary of the recent NICE recommendations on the use of cannabis‐based medicinal products (CBMPs) in the treatment of epilepsy, spasticity, pain, and nausea and vomiting. It also discusses the guidance on cannabidiol (Epidyolex) plus clobazam for the treatment of Dravet syndrome and Lennox‐Gastaut syndrome, two rare forms of epilepsy.
Estimands and inference incluster‐randomizedvaccine trials
Authors: Kilpatrick Kayla W. , Hudgens Michael G. , Halloran M. Elizabeth
Published: May 2020

Cluster‐randomized trials are often conducted to assess vaccine effects. Defining estimands of interest before conducting a trial is integral to the alignment between a study's objectives and the data to be collected and analyzed. This paper considers estimands and estimators for overall, indirect, and total vaccine effects in trials, where clusters of individuals are randomized to vaccine or control. The scenario is considered where individuals self‐select whether to participate in the trial, and the outcome of interest is measured on all individuals in each cluster. Unlike the overall, indirect, and total effects, the direct effect of vaccination is shown in general not to be estimable without further assumptions, such as no unmeasured confounding. An illustrative example motivated by a cluster‐randomized typhoid vaccine trial is provided.
An approximate semi‐analytical model of sediment and nutrient transport on slopes under rainfall conditions
Authors: Shao Fanfan , Wu Junhu , Li Yibo , Ren Min
Published: May 2020

Under natural rainfall, the surface runoff erosion of sloping farmland tends to remove large quantities of soil particles and constitutes nonpoint source pollution. The existing sediment and nutrient loss models focus on estimating the total amount of pollutants in the long term. The Existing mathematical models that describe the nutrient loss process on slopes have some shortcomings, which have not accounted for the effect of infiltration on nutrient concentrations in the exchange layer before runoff starts. Here, an approximate semianalytical model of sediment yield and nutrient loss was based on surface runoff processes. Simulated rainfall experiments were performed to calibrate the model's parameters and verify its reliability. The established model incorporated raindrop splashing, diffusion, and water infiltration effects on nutrient transfer in the exchange layer. Raindrop splashing played a leading role in nutrient translocation from the exchange layer to runoff. The simulated runoff, sediment, and nutrient matched their measured values reasonably well (R2 > 0.8; Nash–Sutcliffe efficiency > 0.347). The model's sediment yield items were more sensitive to runoff erosion than splash erosion. The raindrop‐induced water transfer rate in the nutrient loss simulation dramatically affected the peak nutrient loss rates, whereas the depth of the exchange layer clearly affected the overall range of change in nutrient loss rate and boosted the total nutrient loss. Therefore, measures such as vegetation coverage or deep fertilization should be adopted to weaken raindrops’ kinetic energy and reduce nutrient concentrations in the exchange layer to prevent agricultural nonpoint source pollution in the Loess Plateau.
Research on application of variable coding modulation system based on Digital Video Broadcasting ‐ Satellite ‐ 2nd Generation in data transmission of near‐earth remote sensing satellite
Authors: Zhang Shasha , Cao Haiyi , Zhang Xinwei , Yao Xinyu , Zhao Chenguang
Published: May 2020

In order to make full use of the link resources for data transmission from near‐earth remote sensing satellites, variable coding modulation (VCM) system is used to fully utilize the system link margin to improve the satellite data transmission performance. By analyzing the dynamic link under the VCM data transmission system, the contribution of the VCM system to the satellite data link optimization is studied from the perspective of engineering application, which can provide reference for the data link design of remote sensing satellites. Applying the flow design, for the currently adopted transmission system of X band, compared with traditional constant coding modulation (CCM) system, the average link performance of VCM system can be increased by 42.1% in single‐station transmission mode and 53.3% in dual‐station relay mode through the exampled analysis.
Hydrothermal Assisted Synthesis of ZnFe2O4 Embedded g‐C3N4 Nanocomposite with Enhanced Charge Transfer Ability for Effective Removal of Nitrobenzene and Cr(VI)
Authors: Shanavas Shajahan , Ahamad Tansir , Alshehri Saad M. , Acevedo Roberto , Munusamy Anbarasan Ponnusamy
Published: May 2020

A novel hybrid nanocomposite of g‐C3N4/ZnFe2O4 was successfully prepared by a facile hydrothermal method followed by an annealing process. The obtain hybrid catalyst was systematically characterized by XRD, TEM, HRTEM, FT‐IR, UV‐DRS and XPS analysis in order to study the structural, morphological, optical properties and chemical states. The cubic phase ZnFe2O4 crystalline structure and spherical morphology with sizes in the range of 30–35 nm were adequately anchored on the g‐C3N4 sheets. The HR‐TEM image suggests the successful embedment of ZnFe2O4 nanostructures on g‐C3N4 sheets. The photocatalytic activity of the catalyst was investigated using nitrobenzene (NB) and Cr (VI) under visible light. The improved activity of ZnFe2O4/ g‐C3N4 is due to the synergetic effect of superior visible‐light utilization and effective charge carrier separation between g‐C3N4 and ZnFe2O4 nanoparticles. Hence, this heterostructure could be used as a favorable applicant for environmental remediation application for the removal of organic pollutants and metal ions in practical application.
Recent Advances in Microwave Assisted Multicomponent Reactions
Authors: Fairoosa Jaleel , Saranya Salim , Radhika Sankaran , Anilkumar Gopinathan
Published: May 2020

Microwave (MW) assisted multicomponent reactions (MCRs) provide facile and expeditious procedures for the synthesis of several diversely functionalised molecules. Significant enhancement in selectivity, purity and reproducibility is offered by this process. Shorter reaction times as well as higher product yield are attained efficiently using MW assisted MCRs. The present review focuses on the developments in this field covering literature from 2013–2019 and the topic is categorised based on the final products obtained.
A Structure Comparison of Ni(II) Complexes Supported by PNCNP and POCOP Pincer Ligands
Authors: Fang Fei , Chang Jiarui , Kang Jiaxin , Zhang Jie , Li Shujun , Chen Xuenian
Published: May 2020

In order to compare the structure and property of the same metal center supported by different types of pincer ligands, a series of Ni(II) pincer complexes, [2,6‐(iPr2PNH)2C6H3]NiX (X=SH, 1 a; SPh, 1 b; SBn, 1 c; BH4, 1 d), were synthesized based on m‐(iPr2PNH)2C6H4 (PNCNP) and fully characterized by multinuclear NMR, FTIR, X‐ray crystallography and elemental analysis. The structures of complexes 1 a–d were compared with those of the corresponding Ni(II) complexes supported by a bis(phosphinite) (POCOP) pincer ligand, [2,6‐(iPr2PO)2C6H3]NiX (X=SH, 2 a; SPh, 2 b; SBn, 2 c; BH4, 2 d). It was found that the Ni‐Cipso and Ni−S bond lengths and the Ni⋅⋅⋅B distance in complexes 1 a–d are comparable to those in complexes 2 a–d; however, the Ni−P bond lengths in complexes 1 a–d are longer than those in complexes 2 a–d. As a result, the nickel center is less tightly chelated by the PNCNP backbone compared with the POCOP framework. Natural population analysis (NPA) of complexes 1 a, 2 a, 1 b and 2 b indicated that the nickel center supported by a PNCNP pincer ligand is less electron‐rich. Cyclic voltammetry study of 1 a and 2 a showed that 2 a is easier to be oxidized.
Daily effects of continuous ICT demands on work–family conflict: Negative spillover and role conflict
Authors: Cho Seonghee , Kim Sooyeol , Chin Sean W. , Ahmad Unber
Published: May 2020

Growing concerns about intensive information and communication technology (ICT) use led to abundant research on its debilitating effects on employees' abilities to meet family demands. Drawing on the stressor–strain model, we conducted a daily diary study to investigate how different types of daily ICT demands experienced during work hours and after work influence work–family conflict (WFC) in the evening. We collected data from 98 full‐time employees (793 day‐level observations) for 10 consecutive workdays to understand employees' work‐nonwork interface experiences, namely, negative spillover and role conflict. First, we examined a multilevel mediation model to test the negative spillover effect of on‐the‐job ICT demands on WFC in the evening via negative affect (NA) at the end of the workday. Second, we investigated the effects of off‐the‐job ICT demands on WFC to provide evidence of role conflict in the nonwork domain. Further, we tested the protective role of boundary control in these phenomena. The multilevel analysis results revealed that different types of ICT demands experienced at work have idiosyncratic impacts on WFC. Also, while extended availability after work hours yields greater WFC, this link was weaker for the employees who perceive high boundary control.
Implantation of the clinical-grade human neural stem cell line, CTX0E03, rescues the behavioral and pathological deficits in the quinolinic acid-lesioned rodent model of Huntington's disease
Authors: Yoon Yongwoo , Kim Hyun Sook , Jeon Iksoo , Noh Jeong-Eun , Park Hyun Jung , Lee Suji , Park In-Hyun , Stevanato Lara , Hicks Caroline , Corteling Randolph , Barker Roger A. , Sinden John D. , Song Jihwan
Published: May 2020

Huntington's disease (HD) is a devastating, autosomal-dominant neurodegenerative disease, for which there are currently no disease-modifying therapies. Clinical trials to replace the damaged striatal medium spiny neurons (MSNs) have been attempted in the past two decades but have met with only limited success. In this study, we investigated whether a clonal, conditionally immortalized neural stem cell line (CTX0E03), which has already shown safety and signals of efficacy in chronic ischemic stroke patients, could rescue deficits seen in an animal model of HD. After CTX0E03 transplantation into the quinolinic acid-lesioned rat model of HD, behavioral changes were measured using the rotarod, stepping, and staircase tests. In vivo differentiation and neuronal connections of the transplanted CTX0E03 cells were evaluated with immunohistochemical staining and retrograde tracing with Fluoro-Gold. We found that transplantation of CTX0E03 gave rise to a significant behavioral improvement compared with the sham- or fibroblast-transplanted group. Transplanted CTX0E03 formed MSNs (DARPP-32) and GABAergic neurons (GABA, GAD65/67) with BDNF expression in the striatum, while cortically transplanted cells formed Tbr1-positive neurons. Using a retrograde label, we also found stable engraftment and connection of the transplanted cells with host brain tissues. CTX0E03 transplantation also reduced glial scar formation and inflammation, as well as increasing endogenous neurogenesis and angiogenesis. Overall, our results demonstrate that CTX0E03, a clinical-grade neural stem cell line, is effective for preclinical test in HD, and, therefore, will be useful for clinical development in the treatment of HD patients.
Experimental study and numerical analysis on seismic behavior of composite RCS frames
Authors: Li Wei , Xiong Jingang , Wu Lingjie , Yang Kejia
Published: May 2020

An experimental study of the seismic performance of composite frames consisting of reinforced concrete (RC) columns and steel beams (S) is presented in this paper. Three frame specimens—one bare composite RCS frame without slab and two composite RCS frames with slab—were tested under cyclic loading. The test results indicate that two frame specimens with small‐scale steel beams exhibited better ductile behavior and dissipated energy, and the strength and stiffness degradation of the postelastic stage was not obvious. The results indicate that using a slab in the frame is not a good way to improve structural bearing capacity when the linear stiffness of steel beams is large. A plastic limit analysis method is proposed to calculate the lateral ultimate bearing capacity of an RCS frame under seismic action. The calculated results agree well with the test. Three RCS frame specimens were simulated using ABAQUS finite element analysis software. A comparison of the results of the numerical study with the experimental results demonstrates that the finite element model can accurately predict the structural behavior.
Using care navigation to address caregiver burden in dementia: A qualitative case study analysis
Authors: Bernstein Alissa , Merrilees Jennifer , Dulaney Sarah , Harrison Krista L. , Chiong Winston , Ong Paulina , Heunis Julia , Choi Jeff , Walker Reilly , Feuer Julie E. , Lee Kirby , Dohan Daniel , Bonasera Stephen J. , Miller Bruce L. , Possin Katherine L.
Published: May 2020

Introduction

Many caregivers of people with dementia experience burden and resulting health effects due to the intensive nature of caregiving. Phone‐ and web‐based care navigation is an innovative model of care that may be useful in addressing caregiver burden in dementia.

Methods

Qualitative methods (interviews, focus groups, and case study analysis) were used to identify care navigator approaches used to address caregiver burden in dementia as part of a dementia care navigation program.

Results

Care navigators targeted caregiver burden by focusing on strategies to reduce caregiver guilt and frustration, manage patient‐related behavior, address caregiver depression, and improve the relationship between the caregiver and person with dementia. The case studies presented demonstrate the ways that care navigators identified patient and caregiver needs and tailored their approaches to meet the specific social, cultural, economic, and geographic contexts of the dyads with which they worked.

Discussion

Findings provide insights into strategies used to address caregiver burden through care navigation. Care navigators who speak the same language as the caregivers with whom they work and who have an in‐depth understanding of the symptoms of different dementia syndromes may be particularly effective.
If ineffective levels of transforming growth factors and their receptor account for old age being a risk factor for Alzheimer's disease, then increasing TGFBR2 might be therapeutic
Authors: Fessel Jeffrey
Published: May 2020

If it is correct that ineffective levels of transforming growth factors beta and their receptor account for old age being a risk factor for Alzheimer's disease (AD), then increasing TGFBR2 might be therapeutic. Pacltaxel is a direct way to increase TGFBR2 levels. Indirect ways that will increase TGFBR2, include decreasing the levels of c‐myc because that will lower the miRNA cluster 17‐92, particularly its miR‐17 and miR‐20a components; and raising EGFR because that also will increase TGFBR2. Metformin and desferrioxamine are drugs that decrease c‐myc; and statins increase levels of EGF. Clinical trials using those drugs, would demonstrate whether they decrease the progression from amnestic mild cognitive impairment to AD.
Differences in plasma metabolites related to Alzheimer's disease, APOE ε4 status, and ethnicity
Authors: Vardarajan Badri , Kalia Vrinda , Manly Jennifer , Brickman Adam , Reyes‐Dumeyer Dolly , Lantigua Rafael , Ionita‐Laza Iuliana , Jones Dean P. , Miller Gary W. , Mayeux Richard
Published: May 2020

Introduction

We investigated metabolites in plasma to capture systemic biochemical changes associated with Alzheimer's disease (AD).

Methods

Metabolites in plasma were measured in 59 AD cases and 60 healthy participants of African American (AA), Caribbean Hispanic (CH), and non‐Hispanic white (NHW) ancestry using untargeted liquid‐chromatography–based ultra‐high‐resolution mass spectrometry. Metabolite differences between AD and healthy, ethnic groups and apolipoprotein E gene (APOE) ε4 status were analyzed. Untargeted network analysis identified pathways enriched in AD‐associated metabolites.

Results

A total of 5929 annotated metabolites were measured. Partial least squares discriminant analysis (PLS‐DA) inferred that AD clustered separately from healthy controls (area under the curve [AUC] = 0.9816); discriminating pathways included glycerophospholipid, sphingolipid, and non‐essential amino acid (alanine, aspartate, glutamate) metabolism. Metabolic features in AA clustered differently from CH and NHW (AUC = 0.9275), and differed between APOE ε4 carriers and non‐carriers (AUC = 0.9972).

Discussion

Metabolites, specifically lipids, were associated with AD, APOE ε4, and ethnic group. Metabolite profiling can identify perturbed AD pathways, but genetic and ancestral background need to be considered.
Exclusive quarkonium production or decay in soft gluon factorization
Authors: Li Rong , Feng Yu , Ma Yan-Qing
Published: May 2020

Abstract

In this paper, we study the application of the recently proposed soft gluon factorization (SGF) to exclusive quarkonium production or decay. We find that in the nonrelativistic QCD factorization framework there are too many nonperturbative parameters. Thanks to the factorization of kinematical physics from dynamical physics, the SGF significantly reduces the number of nonperturbative parameters. Therefore, the SGF can improve our predictive power of exclusive quarkonium production or decay. By applying to ηc + γ production at B-factories, our result is the closest one to data among all theoretical calculations.
Third-order relativistic hydrodynamics: dispersion relations and transport coefficients of a dual plasma
Authors: Diles Saulo M. , Mamani Luis A.H. , Miranda Alex S. , Zanchin Vilson T.
Published: May 2020

Abstract

Hydrodynamics is nowadays understood as an effective field theory that describes the dynamics of the long-wavelength and slow-time fluctuations of an underlying microscopic theory. In this work we extend the relativistic hydrodynamics to third order in the gradient expansion for neutral fluids in a general curved spacetime of d dimensions. We find 58 new transport coefficients, 19 due to third-order scalar corrections and 39 due to tensorial corrections. In the particular case of a conformal fluid, the number of new transport coefficients is reduced to 19, all of them due to third-order tensorial corrections. The dispersion relations of linear fluctuations in the third-order relativistic hydrodynamics is obtained, both in the rest frame of the fluid and in a general moving frame. As an application we obtain some of the transport coefficients of a relativistic conformal fluid in three dimensions by using the AdS/CFT correspondence. These transport coefficients are extracted from the dispersion relations of the linear fluctuations. The gravity dual of the fluctuations in this conformal fluid is described by the gravitational perturbations of four-dimensional anti-de Sitter black branes, which are solutions of the Einstein equations with a negative cosmological constant. To find the hydrodynamic quasinormal modes (QNMs) of the scalar sector we use the SUSY quantum mechanics of the gravitational perturbations of four-dimensional black branes. Such a symmetry allows us to find the wavefunction of the scalar (or sound) sector in the hydrodynamic limit directly from the wavefunction of the vector (or shear) sector, which is usually easier to be found because the perturbation wave equations for the vector sector are much simpler than the ones for the scalar sector.
Oncological outcome and recurrence pattern analysis after involved-field irradiation in combination with rituximab for early-stage nodal and extranodal follicular lymphoma
Authors: König Laila , Herfarth Klaus , Hörner-Rieber Juliane , Dietrich Sascha , Wiegel Thomas , Debus Jürgen , Viardot Andreas
Published: May 2020

Purpose

Combined radioimmunotherapy (RIT) in follicular lymphomas (FL) has shown promising treatment efficacy in the Mabthera® and Involved field Radiation (MIR) study. Aim of this study was to analyze treatment efficacy and recurrence patterns after RIT in early-stage nodal and extranodal FL.

Methods

We reviewed 107 patients who were treated with combined RIT in two centers. Treatment consisted of 4 × rituximab followed by RIT with 4 × rituximab and involved field (IF) radiotherapy with 30/40 Gy. Median follow-up period was 71 months. In contrast to the MIR study, extranodal involvement and grade 3A histology were included in the analysis.

Results

Extranodal involvement and grade 3A histology were present in 21.8% and 13.1%, respectively. Overall response rate (ORR) after 4 × rituximab, after completion of RIT, and after 6 months was 78.1%, 98.8%, and 98.8%, respectively, with increasing rates of complete remissions (CR). Predictive factors associated with superior PFS were tumor size, completely excised lymphomas, and response to first 4 × rituximab. 5‑year PFS rate was 87.3%, with mostly outfield recurrences (94.1%). Second-line treatment was effective, with 53.3% CR and 46.7% partial remissions (PR). 5‑year OS was 98.1%. RIT was tolerated well, with mainly grade 1–2 acute side effects.

Conclusion

The real-world efficacy of RIT is comparable with the results of the MIR study. Additionally, this analysis shows that extranodal involvement and grade 3A histology are not associated with inferior PFS.
Higher pyruvate levels after Achilles tendon rupture surgery could be used as a prognostic biomarker of an improved patient outcome
Authors: Capone Gianluigi , Svedman Simon , Juthberg Robin , Edman Gunnar , Ackermann Paul W.
Published: May 2020

Purpose

The primary aim of this study was to assess the relationship between the metabolites lactate and pyruvate in the healing tendon after Achilles tendon rupture (ATR) and patient-reported outcome at 6 and 12 months. A secondary aim was to evaluate which underlying factors regulate lactate and pyruvate concentrations.

Methods

Lactate and pyruvate concentrations were measured two weeks post-operatively in both the healing- and healthy Achilles tendon in 109 patients (90 men, 19 women; mean age 40 ± 7.9 years). Patient demographics, degree of physical activity, timing of surgery, operation time, patient-reported loading and step counts were investigated in relation to metabolite concentrations. At 6 and 12 months, the Achilles tendon Total Rupture Score (ATRS) questionnaire was used to assess patient outcome.

Results

The mean number of steps taken during the post-operative days 1–10 was the only factor significantly related to the mean concentration of lactate (R2 = 0.34, p = 0.038), and pyruvate (R2 = 0.46, p = 0.006). Pyruvate was demonstrated as the only factor significantly associated with ATRS at both 6 months (R2 = 0.32, p = 0.003) and at 12 months (R2 = 0.37, p = 0.004) using multiple linear regression.

Conclusion

The mean concentration of pyruvate during early ATR healing may predict patient outcome at 6 and 12 months post-operatively and possibly be used as a biomarker of healing. Early mobilization with an increased number of steps taken is an important clinical strategy to improve the metabolite concentrations during healing.

Level of evidence

III
On the empirical estimator of the boundary in inverse first-exit problems
Authors: Gür Sercan , Pötzelberger Klaus
Published: May 2020

First-exit problems for the Brownian motion (W(t)) or general diffusion processes, have important applications. Given a boundary b(t), the distribution of the first-exit time $$\tau $$
τ
has to be computed, in most cases numerically. In the inverse first-passage-time problems, the distribution of $$\tau $$
τ
is given and the boundary b has to be found. The boundary and the density of $$\tau $$
τ
satisfy a Volterra integral equation. Again numerical methods approximate the solution b for given distribution of $$\tau $$
τ
. We propose and analyze estimators of b for a given sample $$\tau _1,\ldots ,\tau _n$$

τ
1

,
…
,

τ
n

of first-exit times. The first estimator, the empirical estimator, is the solution of a stochastic version of the Volterra equation. We prove that it is strongly consistent and we derive an upper bound for its asymptotics convergence rate. Finally, this estimator is compared to a Bayesian estimator, which is based on an approximate likelihood function. Monte Carlo experiments suggests that the empirical estimator is simple, computationally manageable and outperforms the alternative procedure considered in this paper.
The evolution of strategies to minimise the risk of human drug-induced liver injury (DILI) in drug discovery and development
Authors: Walker Paul A. , Ryder Stephanie , Lavado Andrea , Dilworth Clive , Riley Robert J.
Published: May 2020

Early identification of toxicity associated with new chemical entities (NCEs) is critical in preventing late-stage drug development attrition. Liver injury remains a leading cause of drug failures in clinical trials and post-approval withdrawals reflecting the poor translation between traditional preclinical animal models and human clinical outcomes. For this reason, preclinical strategies have evolved over recent years to incorporate more sophisticated human in vitro cell-based models with multi-parametric endpoints. This review aims to highlight the evolution of the strategies adopted to improve human hepatotoxicity prediction in drug discovery and compares/contrasts these with recent activities in our lab. The key role of human exposure and hepatic drug uptake transporters (e.g. OATPs, OAT2) is also elaborated.
Solving high-level Petri games
Authors: Gieseking Manuel , Olderog Ernst-Rüdiger , Würdemann Nick
Published: May 2020

The manual implementation of local controllers for autonomous agents in a distributed and concurrent setting is an ambitious and error-prune task. Synthesis algorithms, however, allow for the automatic generation of such controllers given a formal specification of the system’s goal. Recently, high-level Petri games were introduced to allow for a concise modeling technique of distributed systems with a safety objective. One way of solving these games is by a translation to low-level Petri games and applying an existing solving algorithm. In this paper we present a new solving technique for a subclass of high-level Petri games with a single uncontrollable player, a bounded number of controllable players, and a local safety objective. The technique exploits symmetries in the high-level Petri game. We report on encouraging experimental results of a prototype implementation generating the reduced state space. The results for four existing and one new benchmark family show a state space reduction by up to three orders of magnitude.
Off-the-shelf automated analysis of liveness properties for just paths
Authors: Bouwman Mark , Luttik Bas , Willemse Tim
Published: May 2020

We enrich the operational semantics of a simple process calculus with ACP-style communication with a concurrency relation, so that for every process expression there exists an associated notion of just path. We then present sufficient conditions on the communication function and the syntax of process expressions that facilitate the formulation of justness on the level of labels rather than on individual transitions, taking a designated set of signals into account. This paves the way for the formulation of liveness properties under justness assumptions in the modal $$\mu $$μ-calculus and their verification on process specifications with the mCRL2 toolset.
Out for coffee: with Rob
Authors: Fehnker Ansgar
Published: May 2020

I have known Rob van Glabbeek as a colleague for 16 years, of which eight years were in the same research group. However, this only amounts to less than half of his professional life which started in the mid-1980s at the Centrum voor Wiskunde en Informatica in Amsterdam. In this article, I am trying to piece together the information I got from colleagues as well as from Rob himself—to the best of my recollection—to give an insight into Rob as a colleague, researcher, and person.
Development of chitosan-coated agar-gelatin particles for probiotic delivery and targeted release in the gastrointestinal tract
Authors: Albadran Hanady A. , Monteagudo-Mera Andrea , Khutoryanskiy Vitaliy V. , Charalampopoulos Dimitris
Published: May 2020

This study reports the development of a novel and simple formulation for probiotic delivery using chitosan-coated agar-gelatin gel particles. This methodology involves the production of agar-gelatin particles by thermally treating a mixture of agar and gelatin solutions at high temperatures (121 °C) and subsequently coating with chitosan. The particles were able to protect the probiotic strain Lactobacillus plantarum NCIMB 8826 during incubation for 2 h in simulated gastric fluid (pH 2), as no statistically significant loss (P > 0.05) in cell concentration was observed, and also resist dissolution in simulated intestinal fluid (pH 7.2). Interestingly, this protection is related to the fact that the intense thermal treatment affected the physicochemical properties of agars and resulted in the formation of a strong and tight polymer network, as indicated by the X-ray diffraction (XRD) analysis. Using an in vitro faecal batch fermentation model simulating the conditions of the distal part of the large intestine (pH 6.7–6.9), it was demonstrated by quantitative real-time PCR that the majority of L. plantarum cells were released from the agar-gelatin particles within 30 to 48 h. Overall, this work led to the development of a novel methodology for the production of probiotic-containing particles, which is simpler compared with current encapsulation technologies and has a lot of potential to be used for the controlled release of probiotics and potentially other solid bioactives in the large intestine.

Key Points

• Chitosan gel particles is a simple and scalable method of probiotic encapsulation.

• Autoclaving agar-gelatin particles increases their stability at low pH.

• Chitosan gel particles protected L. plantarum during gastrointestinal conditions.

• Probiotics could be controlled release in the colon using chitosan gel particles.
Osteoporosis in patients with rheumatoid arthritis: trends in the German National Database 2007–2017
Authors: Lindner Lisa , Callhoff Johanna , Alten Rieke , Krause Andreas , Ochs Wolfgang , Zink Angela , Albrecht Katinka
Published: May 2020

Osteoporosis is a frequent comorbidity in rheumatoid arthritis (RA). Due to the improved treatment options for RA, we expect a long-term decrease in osteoporosis as an accompanying disease. Data from the German National Database (NDB) were used to investigate whether the frequency of osteoporosis has changed in the last 10 years. From 2007 to 2017, approximately 4000 patients were documented annually with data on therapy and comorbidity. The cross-sectional data were summarised descriptively. Age, sex, disease duration, disease activity and glucocorticoids were considered as influencing factors. The Cochrane-Armitage test for trend was used to test whether the frequency of osteoporosis at the first visit changed from 2007 to 2017. Osteoporosis frequency in RA patients (mean age 63 years, 75% female) decreased from 20% in 2007 to 6% in 2017 (p < 0.001). The decrease affected women (22% to 17%) and men (14% to 8%) in all age groups and both short-term (≤ 2-year disease duration: 9% to 3%) and long-term RA patients (> 10-year disease duration: 28% to 20%). Patients with high disease activity and patients who took glucocorticoids (GC) were more often affected by osteoporosis than patients in remission or without GC. Drug prophylaxis in patients without osteoporosis increased (20% to 41% without GC, 48% to 55% with GC). Men with GC received less prophylactic treatment than women (48% vs. 57% in 2017). In this cohort, osteoporosis in patients with RA is less frequently observed compared to former years. RA-specific risk factors for osteoporosis such as disease activity and GC therapy have declined but long-term GC use is still present. Assessment of osteoporosis in RA patients should be investigated more consistently by bone density measurement. Male RA patients still need to be given greater consideration regarding osteoporosis drug prophylaxis, especially when GC therapy is needed.