bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Interfaces on the Deformation Mechanisms in Bimodal Al Laminates Produced by Accumulative Roll Bonding
Authors: Höppel Heinz-Werner , Westermeyer Martin , Kümmel Frank , Göken Mathias
Published: April 2020

Laminated metallic materials with an ultrafine‐grained (UFG) microstructure can easily be produced by accumulative roll bonding (ARB). Combining two different Al alloys, commercially pure (CP) and high‐purity (HP) aluminum, a layerwise bimodal microstructure is formed, where the CP layers consist of ultrafine grains whereas the HP layers show large grains as these layers undergo dynamic recrystallization during rolling. By applying different numbers of ARB passes and in addition by applying a subsequent heat treatment, the microstructure of the laminate can be changed significantly. Thus, different types of interfaces, specifically the grain boundaries of the ultrafine grains and the interfaces between the different layers of CP and HP aluminum are dominating the deformation behavior and the mechanical properties of these laminates. This article addresses how the UFG boundaries and the layer interfaces affect the mechanical properties under monotonic and cyclic loading, and discusses the relevant deformation mechanisms.
Probing the Role of Bone Lamellar Patterns through Collagen Microarchitecture Mapping, Numerical Modeling, and 3D‐Printing
Authors: Grezzana Gabriele , Loh Hyun-Chae , Qin Zhao , Buehler Markus J. , Masic Admir , Libonati Flavia
Published: April 2020

The fibrillar organization is crucial for the mechanics of osteonal bone and for its anisotropy. Different collagen fiber orientation (CFO) patterns are observed in bone and correlated to the main local loading, leading to the hypothesis that the fibers are preferentially aligned to bear specific loading types. A heterogeneous distribution of osteon morphotypes (OMs) is noticed in long bones, although the relationship between the OM spatial distribution and the local predominant loading is still unclear. This study aims to shed light on the reasons why Nature uses specific OMs in diverse stress‐dominated regions. A multimodal approach is adopted, including collagen fiber orientation mapping, numerical modeling of different OMs under tensile and compressive loading, and 3D‐printing of OM‐inspired samples, to unravel the relationship between different OMs and their mechanical behavior. Simulation results suggest a better performance of the vertical OM (VOM) under tensile loading and of the twisted OM (TOM) under compression, confirming earlier hypotheses. The outcomes of mechanical testing, conducted on 3D‐printed samples, highlight a possible buckling‐induced failure of fibers with preferential vertical orientation and provide evidence that OMs are stress‐tailored, opening new venues for the design of stress‐tuned bioinspired composites.
Functional Materials from Nanocellulose: Utilizing Structure–Property Relationships in Bottom‐Up Fabrication
Authors: De France Kevin , Zeng Zhihui , Wu Tingting , Nyström Gustav
Published: April 2020

It is inherently challenging to recapitulate the precise hierarchical architectures found throughout nature (such as in wood, antler, bone, and silk) using synthetic bottom‐up fabrication strategies. However, as a renewable and naturally sourced nanoscale building block, nanocellulose—both cellulose nanocrystals and cellulose nanofibrils—has gained significant research interest within this area. Altogether, the intrinsic shape anisotropy, surface charge/chemistry, and mechanical/rheological properties are some of the critical material properties leading to advanced structure‐based functionality within nanocellulose‐based bottom‐up fabricated materials. Herein, the organization of nanocellulose into biomimetic‐aligned, porous, and fibrous materials through a variety of fabrication techniques is presented. Moreover, sophisticated material structuring arising from both the alignment of nanocellulose and via specific process‐induced methods is covered. In particular, design rules based on the underlying fundamental properties of nanocellulose are established and discussed as related to their influence on material assembly and resulting structure/function. Finally, key advancements and critical challenges within the field are highlighted, paving the way for the fabrication of truly advanced materials from nanocellulose.
An Electron‐Rich Cyclic (Alkyl)(Amino)Carbene on Au(111), Ag(111), and Cu(111) Surfaces
Authors: Bakker Anne , Freitag Matthias , Kolodzeiski Elena , Bellotti Peter , Timmer Alexander , Ren Jindong , Schulze Lammers Bertram , Moock Daniel , Roesky Herbert W. , Mönig Harry , Amirjalayer Saeed , Fuchs Harald , Glorius Frank
Published: April 2020

The structural properties and binding motif of a strongly σ‐electron‐donating N‐heterocyclic carbene have been investigated on different transition‐metal surfaces. The examined cyclic (alkyl)(amino)carbene (CAAC) was found to be mobile on surfaces, and molecular islands with short‐range order could be found at high coverage. A combination of scanning tunneling microscopy (STM), X‐ray photoelectron spectroscopy (XPS), and density functional theory (DFT) calculations highlights how CAACs bind to the surface, which is of tremendous importance to gain an understanding of heterogeneous catalysts bearing CAACs as ligands.
In Situ Electropolymerization Enables Ultrafast Long Cycle Life and High‐Voltage Organic Cathodes for Lithium Batteries
Authors: Zhao Chen , Chen Zifeng , Wang Wei , Xiong Peixun , Li Benfang , Li Mengjie , Yang Jixing , Xu Yunhua
Published: April 2020

Organic cathode materials have attracted extensive attention because of their diverse structures, facile synthesis, and environmental friendliness. However, they often suffer from insufficient cycling stability caused by the dissolution problem, poor rate performance, and low voltages. An in situ electropolymerization method was developed to stabilize and enhance organic cathodes for lithium batteries. 4,4′,4′′‐Tris(carbazol‐9‐yl)‐triphenylamine (TCTA) was employed because carbazole groups can be polymerized under an electric field and they may serve as high‐voltage redox‐active centers. The electropolymerized TCTA electrodes demonstrated excellent electrochemical performance with a high discharge voltage of 3.95 V, ultrafast rate capability of 20 A g−1, and a long cycle life of 5000 cycles. Our findings provide a new strategy to address the dissolution issue and they explore the molecular design of organic electrode materials for use in rechargeable batteries.
Nitridophosphate‐Based Ultra‐Narrow‐Band Blue‐Emitters: Luminescence Properties of AEP8N14:Eu2+ (AE=Ca, Sr, Ba)
Authors: Wendl Sebastian , Eisenburger Lucien , Strobel Philipp , Günther Daniel , Wright Jonathan P. , Schmidt Peter J. , Oeckler Oliver , Schnick Wolfgang
Published: April 2020

The nitridophosphates AEP8N14 (AE=Ca, Sr, Ba) were synthesized at 4–5 GPa and 1050–1150 °C applying a 1000 t press with multianvil apparatus, following the azide route. The crystal structures of CaP8N14 and SrP8N14 are isotypic. The space group Cmcm was confirmed by powder X‐ray diffraction. The structure of BaP8N14 (space group Amm2) was elucidated by a combination of transmission electron microscopy and diffraction of microfocused synchrotron radiation. Phase purity was confirmed by Rietveld refinement. IR spectra are consistent with the structure models and the chemical compositions were confirmed by X‐ray spectroscopy. Luminescence properties of Eu2+‐doped samples were investigated upon excitation with UV to blue light. CaP8N14 (λem=470 nm; fwhm=1380 cm−1) and SrP8N14 (λem=440 nm; fwhm=1350 cm−1) can be classified as the first ultra‐narrow‐band blue‐emitting Eu2+‐doped nitridophosphates. BaP8N14 shows a notably broader blue emission (λem=417/457 nm; fwhm=2075/3550 cm−1).
The First Use of a ReX5 Synthon to Modulate FeIII Spin Crossover via Supramolecular Halogen⋅⋅⋅Halogen Interactions
Authors: Busch Rebecca , Carter Anthony B. , Konidaris Konstantis F. , Kühne Irina A. , González Ricardo , Anson Christopher E. , Powell Annie K.
Published: April 2020

We have added the {ReIVX5}− (X=Br, Cl) synthon to a pocket‐based ligand to provide supramolecular design using halogen⋅⋅⋅halogen interactions within an FeIII system that has the potential to undergo spin crossover (SCO). By removing the solvent from the crystal lattice, we “switch on” halogen⋅⋅⋅halogen interactions between neighboring molecules, providing a supramolecular cooperative pathway for SCO. Furthermore, changes to the halogen‐based interaction allow us to modify the temperature and nature of the SCO event.
A decrease in temperature during the late Middle Pleistocene interglacial stage (MIS 7.3) altered montane zone floral diversity: Plant macrofossil evidence from central Japan
Authors: Momohara Arata , Tsuji Hisa , Mizuno Kiyohide
Published: April 2020

Plant fossils from the Early and Middle Pleistocene have mainly been obtained from lowland sediments, and consequently, there is currently limited information on changes in montane zone vegetation prior to the last glacial stage. However, fossil plant assemblages occurring at high altitudes can be used to assess the influence of climate change on the vertical distribution of plants and vegetation. In this study, we analysed plant macrofossil assemblages from fluvial deposits in the upper Middle Pleistocene strata outcropping in a riverbed at 1160–1180 m a.s.l. in the southeastern foothills of Mt. Yatsugatake, central Japan. Ages of the assemblages were constrained by two widespread tephras that were detected above the interglacial peak of marine isotope stage (MIS) 7.3 (~212 ka). The annual mean temperature in the lower and middle sections of the profile was estimated to be warmer than that at present, based on the coldest temperatures limiting the distribution of Phytolacca japonica and Selaginella remotifolia, and the temperature decreased in the upper section. Since MIS 7.4, the fluctuation in plant altitudinal distribution has been exemplified by changes in the limits of S. remotifolia and Larix kaempferi distribution, and their coexistence at the same altitude varied depending on climate settings. Species diversity, estimated by rarefaction analysis of plant macrofossil assemblage composition, declined as temperatures decreased after the peak of MIS 7.3. Decreasing floral diversity during the subsequent cooling phase possibly coincided with a downward migration of the vegetation zone and extirpation of plants from the inland basin in central Japan.
Technical Note: Design and characterization of a large diameter parallel plate ionization chamber for accurate integral depth dose measurements with proton beams
Authors: Farr Jonathan B. , Moskvin Vadim , Lukose Renin C. , Yao Weiguang , Schwamm Frank
Published: April 2020

Purpose

The goal was to develop and test a large diameter parallel plate ionization chamber capable of intercepting at least 98% of the proton beamlets tested with the system.

Methods

A commercial synchrotron proton therapy system was used for the study (Hitachi, Ltd, Hitachi City, Japan; Model: Probeat‐V). The energies investigated were in the range of 100 to 192 MeV. Three beam spot options available from the system were used. A PTW Bragg peak IC of diameter 84 mm (BP84) (Model PTW34070) was employed for comparison in a scanning water phantom. A prototype of 150 mm diameter was produced (PTW, Freiburg, Germany; model: T34089) and used for the testing. Monte Carlo calculations were also performed with FLUKA to guide the BP150 design and for comparison to the radiological measurements. For comparison, a 40 cm diameter ideal virtual detector was included in the Monte Carlo model.

Results

The measured proton range R90 agrees between the BP84 and BP150 ionization chambers within +0.06/−0.27 mm across the energies 100–192 MeV, which is less than the daily experimental setup uncertainty of 0.4 mm. The differences in the absolute integral depth dose curves (IDDs) between the BP84 and BP150 ranged from 0.3% to 1.0% for the spot sizes and beam energies tested. As predicted by the Monte Carlo modeling, the greatest differences were found in the plateau region of the IDDs. Also, the IDDs measured with the BP150 were very similar to those of the ideal 40 cm diameter detector Monte Carlo simulations.

Conclusions

We conclude that the BP150 offers a small, but a useful reduction in uncertainty from the nuclear halo effect for the system under test.
Theoretical study of a novel organic electride with large nonlinear optical responses
Authors: Teng Yunyang , Sheng Qi , Weng Hui , Zhou Zhongjun , Huang Xuri , Li Zhiru , Zhang Tao
Published: April 2020

The design of stable organic electrides with high nonlinear optical (NLO) properties is a challenge in organic and materials chemistry. Here we theoretically design of a novel organic molecular electride model, Li+(C20H15Li5)e−, by modifying the lithiation and Li‐doping based on dodecahedrane (C20H20). Its electride characteristic is verified by the quantum theory of atoms in molecules and electron localization function analyses. For the first time, the strategy of steric protection is applied to improve the stability of the organic electride Li+@(C20H15Li5)e−, in which the closed C20 cage serves not only as the ligand with a negative inner electric field to stabilize the Li cation but also as a barrier to prevent the Li cation from escaping. Meanwhile, the released excess electron is firmly captured in the cavity of Li5. Moreover, Li+(C20H15Li5)e− displays a remarkably large first hyperpolarizability of 1.4 × 104 au with potential application in organic second‐order NLO materials.
Young men in sports are at highest risk of acromioclavicular joint injuries: a prospective cohort study
Authors: Skjaker Stein Arve , Enger Martine , Engebretsen Lars , Brox Jens Ivar , Bøe Berte
Published: April 2020

Purpose

To study the incidence of acromioclavicular joint injuries in a general population.

Methods

All acute shoulder injuries admitted to an orthopaedic emergency department were registered prospectively, using electronic patient records and a patient-reported questionnaire. The regional area was the city of Oslo with 632,990 inhabitants. Patients with symptoms from the acromioclavicular joint without fracture were registered as a dislocation (type II–VI) if the radiologist described widening of the joint space or coracoclavicular distance on standard anteroposterior radiographs. Patients without such findings were diagnosed as sprains (type I).

Results

Acromioclavicular joint injuries constituted 11% of all shoulder injuries (287 of 2650). The incidence was 45 per 105 person-years (95% confidence interval [CI] 40–51). 196 (68%) were diagnosed as sprains and 91 (32%) as dislocations. Median age of all acromioclavicular joint injuries was 32 years (interquartile range 24–44), and 82% were men. Thirty percent of all acromioclavicular joint injuries were registered in men in their twenties. Sports injuries accounted for 53%, compared to 27% in other shoulder injuries [OR 3.1 (95% CI 2.4–4.0; p < 0.001)]. The most common sports associated with acromioclavicular joint injuries were football (24%), cycling (16%), martial arts (11%), alpine skiing and snowboarding (both 9%), and ice hockey (6%).

Conclusion

Our study suggests that in the general population, one in ten shoulder injuries involves the acromioclavicular joint and young men in sports are at highest risk. A prognostic level II cohort study.
Neuroendocrine tumours and their microenvironment
Authors: de Hosson Lotte D. , Takkenkamp Tim J. , Kats-Ugurlu Gursah , Bouma Grietje , Bulthuis Marian , de Vries Elisabeth G. E. , van Faassen Martijn , Kema Ido P. , Walenkamp Annemiek M. E.
Published: April 2020

Tumours can escape the immune system by expressing programmed death-ligand-1 (PD-L1), which allows them to bind to PD-1 on T-cells and avoid recognition by the immune system. Regulatory T-cells (Tregs), indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) also play a role in immune suppression. Knowledge about the interaction of neuroendocrine tumours (NETs) with their immune microenvironment and the role of immunotherapy in patients with NET is scarce. Here, we investigated the immune microenvironment of serotonin-producing (SP) and non-serotonin-producing NETs (NSP-NETs). Tumours of 33 patients with SP-NET and 18 patients with NSP-NET were studied. Immunohistochemical analyses were performed for PD-L1, T-cells, IDO, TDO, mismatch repair proteins (MMRp) and activated fibroblasts. PD-L1 expression was seen in < 1% of tumour and T-cells. T-cells were present in 33% of NETs, varying between 1 and 10% T-cells per high power field. IDO was expressed in tumour cells in 55% of SP-NETs and 22% of NSP-NETs (p = 0.039). TDO was expressed in stromal cells in 64% of SP-NETs and 13% of NSP-NETs (p = 0.001). No tumours had loss of MMRp. TDO-expressing stromal cells also strongly expressed α-SMA and were identified as cancer-associated fibroblasts (CAFs). Factors that are associated with a response to checkpoint inhibitor treatment were absent or only present to a limited extent in the tumour microenvironment of NETs. The expression of IDO and TDO in a substantial part of NETs and the presence of CAFs suggest two mechanisms that could be responsible for the cold immune microenvironment, which should be explored to enhance anti-tumour immunity and clinical responses.
Memento for interprofessional learning
Authors: Groenen Patricia J. T. A. , Langerak A. W. , Fend F. , van Krieken J. H. J. M.
Published: April 2020

The vast increase of technical, diagnostic, and treatment possibilities and deepened understanding of molecular biology has revolutionized diagnosis and treatment of cancer and thus has great impact on pathology. Different professionals are responsible for proper evaluation of the results and their translating into an accurate diagnosis and appropriate treatment. Next to expertise, a close interaction between clinical molecular biologists, pathologists, and oncologists is required; it is crucial that these professionals speak “the same language.” Key to this is communication skills and creating possibilities for collaboration in a meaningful context. Here, we present an interprofessional, educational workshop model and we describe the parameters that contribute to effective learning by specialists.
Climate change-driven elevational changes among boreal nocturnal moths
Authors: Keret Netta M. , Mutanen Marko J. , Orell Markku I. , Itämies Juhani H. , Välimäki Panu M.
Published: April 2020

Climate change has shifted geographical ranges of species northwards or to higher altitudes on elevational gradients. These changes have been associated with increases in ambient temperatures. For ectotherms in seasonal environments, however, life history theory relies largely on the length of summer, which varies somewhat independently of ambient temperature per se. Extension of summer reduces seasonal time constraints and enables species to establish in new areas as a result of over-wintering stage reaching in due time. The reduction of time constraints is also predicted to prolong organisms’ breeding season when reproductive potential is under selection. We studied temporal change in the summer length and its effect on species’ performance by combining long-term data on the occurrence and abundance of nocturnal moths with weather conditions in a boreal location at Värriötunturi fell in NE Finland. We found that summers have lengthened on average 5 days per decade from the late 1970s, profoundly due to increasing delays in the onset of winters. Moth abundance increased with increasing season length a year before. Most of the species occurrences expanded upwards in elevation. Moth communities in low elevation pine heath forest and middle elevation mountain birch forest have become inseparable. Yet, the flight periods have remained unchanged, probably due to unpredictable variation in proximate conditions (weather) that hinders life histories from selection. We conclude that climate change-driven changes in the season length have potential to affect species’ ranges and affect the structure of insect assemblages, which may contribute to alteration of ecosystem-level processes.
The economic costs of Hurricane Harvey attributable to climate change
Authors: Frame David J. , Wehner Michael F. , Noy Ilan , Rosier Suzanne M.
Published: April 2020

Hurricane Harvey is one of the costliest tropical cyclones in history. In this paper, we use a probabilistic event attribution framework to estimate the costs associated with Hurricane Harvey that are attributable to anthropogenic influence on the climate system. Results indicate that the “fraction of attributable risk” for the rainfall from Harvey was likely about at least a third with a preferable/best estimate of three quarters. With an average estimate of damages from Harvey assessed at about US$90bn, applying this fraction gives a best estimate of US$67bn, with a likely lower bound of at least US$30bn, of these damages that are attributable to the human influence on climate. This “bottom-up” event-based estimate of climate change damages contrasts sharply with the more “top-down” approach using integrated assessment models (IAMs) or global macroeconometric estimates: one IAM estimates annual climate change damages in the USA to be in the region of US$21.3bn. While the two approaches are not easily comparable, it is noteworthy that our “bottom-up” results estimate that one single extreme weather event contributes more to climate change damages in the USA than an entire year by the “top-down” method. Given that the “top-down” approach, at best, parameterizes but does not resolve the effects of extreme weather events, our findings suggest that the “bottom-up” approach is a useful avenue to pursue in future attempts to refine estimates of climate change damages.
A case of cardiac strangulation following epicardial pacemaker implantation
Authors: Miyagi Chihiro , Ochiai Yoshie , Ando Yusuke , Hisahara Manabu , Baba Hironori , Takigawa Tomoya , Tokunaga Shigehiko
Published: April 2020

An 8-year-old boy had undergone permanent epicardial pacemaker implantation with a Y-shaped bipolar ventricular lead on day 6 after birth for treatment of congenital complete atrioventricular block. He was found to have pulmonary stenosis and mitral stenosis by follow-up echocardiography. Further studies including computed tomography and cardiac catheterization revealed that the pacemaker lead had completely encircled the cardiac silhouette and was in a state of “cardiac strangulation”. We removed the previous pacing leads and generator and implanted a new epicardial dual-chamber pacing system in the right atrium and right ventricle. Additionally, an expanded polytetrafluoroethylene sheet was placed between the new leads and the heart to prevent recurrence of cardiac strangulation.
Variation and change in the short vowels of Delhi English
Authors: Domange Raphaël
Published: April 2020

Although the sound system of Indian English has been the object of numerous publications over the years, there has been a remarkable scarcity of variationist sociolinguistic research carried out on the topic. The present study addresses this gap by describing the short front vowels of 22 lifelong English-speaking Delhi residents born between 1948 and 1992. Focusing more specifically on variation in the relative configuration oftrap/æ/,dress/ɛ/, andkit/ɪ/, the study provides apparent-time evidence for a series of interrelated changes affecting the system. Those include an ongoing lowering of /æ/ and /ɛ/, as well as age-related variation in a previously unreported allophonic split of /ɪ/. I argue that these apparent-time patterns are amenable to an analysis in terms of chain shift, and I discuss the implications of such a claim, linking the phenomenon described to similar patterns reported in various other parts of the English-speaking world.
Correction: Examining the complexity of functioning in persons with spinal cord injury attending first rehabilitation in Switzerland using structural equation modelling
Authors:   and the SwiSCI Study Group, Hodel Jsabel , Ehrmann Cristina , Stucki Gerold , Bickenbach Jerome E. , Prodinger Birgit
Published: April 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Magnetically responsive horseradish peroxidase@ZIF-8 for biocatalysis
Authors: Ricco Raffaele , Wied Peter , Nidetzky Bernd , Amenitsch Heinz , Falcaro Paolo
Published: April 2020

A porous model bioreactor is obtained combining zeolitic imidazolate framework ZIF-8 with horseradish peroxidase and iron oxide magnetic nanoparticles in a one-pot process, in water at room temperature.
On the entropy cost of making solvates
Authors: Cruz-Cabeza Aurora J. , Wright Sarah E. , Bacchi Alessia
Published: April 2020

We present a simple way of estimating the entropy cost of solvate formation in crystals.
Discovery of new polymorphs of the tuberculosis drug isoniazid
Authors: Zhang Keke , Fellah Noalle , Shtukenberg Alexander G. , Fu Xiaoyan , Hu Chunhua , Ward Michael D.
Published: April 2020

Two new metastable polymorphs of the tuberculosis drug isoniazid, considered monomorphic for sixty years, were discovered using melt crystallization and nanoscale confinement.
Performance of the asymptotic expansion method to derive equations of state for hard polyhedron fluids
Authors: Tian Jianxiang , Jiang Hua , Mulero A.
Published: April 2020

The asymptotic expansion method is used to derive analytical expressions for the equations of state of 14 hard polyhedron fluids such as cube, octahedron, rhombic dodecahedron, etc., by knowing the values of only the first eight virial coefficients.
Structural and thermodynamic study of Ca A- or Co B-site substituted SrFeO3−δ perovskites for low temperature chemical looping applications
Authors: Luongo Giancarlo , Donat Felix , Müller Christoph R.
Published: April 2020

Partial substitution of the A- or B-site of the perovskite SrFeO3 with Ca or Co, respectively, alters the oxygen transfer properties of the material for chemical looping applications.
Signature of a conical intersection in the dissociative photoionization of formaldehyde
Authors: Zanchet Alexandre , García Gustavo A. , Nahon Laurent , Bañares Luis , Marggi Poullain Sonia
Published: April 2020

Electron/ion coincidence experiments and ab initio calculations of the dissociative photoionization of formaldehyde reveal the presence of a conical intersection controlling the dynamics and favoring dissociation into the molecular channel, CO+ + H2.
Conversion of ethanol to 1,3-butadiene over high-performance Mg–ZrOx/MFI nanosheet catalysts via the two-step method
Authors: Li Xianquan , Pang Jifeng , Wang Chan , Li Lin , Pan XiaoLi , Zheng Mingyuan , Zhang Tao
Published: April 2020

High stability and outstanding catalytic performance of Mg–Zr/MFI(NS) for the conversion of ethanol and acetaldehyde to butadiene.
In–Fe mixed oxide as an oxygen-evolution photocatalyst for visible-light-driven Z-scheme water splitting
Authors: Miseki Yugo , Fujita Kana , Iguchi Shoji , Kitao Osamu , Gunji Takahiro , Sayama Kazuhiro
Published: April 2020

In–Fe mixed oxide with the bixbyite-type structure functions as a new oxygen evolution photocatalyst for visible light driven Z-scheme water splitting.
Integrative genomics analysis of eQTL and GWAS summary data identifies PPP1CB as a novel bone mineral density risk genes
Authors: Zhai Yu , Yu Lu , Shao Yang , Wang Jianwei
Published: April 2020

In recent years, multiple genome-wide association studies (GWAS) have identified numerous susceptibility variants and risk genes that demonstrate significant associations with bone mineral density (BMD). However, exploring how these genetic variants contribute risk to BMD remains a major challenge. We systematically integrated two independent expression quantitative trait loci (eQTL) data (N = 1890) and GWAS summary statistical data of BMD (N = 142,487) using Sherlock integrative analysis to reveal whether expression-associated variants confer risk to BMD. By using Sherlock integrative analysis and MAGMA gene-based analysis, we found there existed 36 promising genes, for example, PPP1CB, XBP1, and FDFT1, whose expression alterations may contribute susceptibility to BMD. Through a protein–protein interaction (PPI) network analysis, we further prioritized the PPP1CB as a hub gene that has interactions with predicted genes and BMD-associated genes. Two eSNPs of rs9309664 (PeQTL = 1.42 × 10−17 and PGWAS = 1.40 × 10−11) and rs7475 (PeQTL = 2.10 × 10−6 and PGWAS = 1.70 × 10−7) in PPP1CB were identified to be significantly associated with BMD risk. Consistently, differential gene expression analysis found that the PPP1CB gene showed significantly higher expression in low BMD samples than that in high BMD samples based on two independent expression datasets (P = 0.0026 and P = 0.043, respectively). Together, we provide a convergent line of evidence to support that the PPP1CB gene involves in the etiology of osteoporosis.
Comprehensive analysis of PPARγ agonist activities of stereo-, regio-, and enantio-isomers of hydroxyoctadecadienoic acids
Authors: Umeno Aya , Sakashita Mami , Sugino Sakiko , Murotomi Kazutoshi , Okuzawa Tsugumi , Morita Naoki , Tomii Kentaro , Tsuchiya Yuko , Yamasaki Kazuhiko , Horie Masanori , Takahara Kentaro , Yoshida Yasukazu
Published: April 2020

Hydroxyoctadecadienoic acids (HODEs) are produced by oxidation and reduction of linoleates. There are several regio- and stereo-isomers of HODE, and their concentrations in vivo are higher than those of other lipids. Although conformational isomers may have different biological activities, comparative analysis of intracellular function of HODE isomers has not yet been performed. We evaluated the transcriptional activity of peroxisome proliferator-activated receptor γ (PPARγ), a therapeutic target for diabetes, and analyzed PPARγ agonist activity of HODE isomers. The lowest scores for docking poses of 12 types of HODE isomers (9-, 10-, 12-, and 13-HODEs) were almost similar in docking simulation of HODEs into PPARγ ligand-binding domain (LBD). Direct binding of HODE isomers to PPARγ LBD was determined by water-ligand observed via gradient spectroscopy (WaterLOGSY) NMR experiments. In contrast, there were differences in PPARγ agonist activities among 9- and 13-HODE stereo-isomers and 12- and 13-HODE enantio-isomers in a dual-luciferase reporter assay. Interestingly, the activity of 9-HODEs was less than that of other regio-isomers, and 9-(E,E)-HODE tended to decrease PPARγ-target gene expression during the maturation of 3T3-L1 cells. In addition, 10- and 12-(Z,E)-HODEs, which we previously proposed as biomarkers for early-stage diabetes, exerted PPARγ agonist activity. These results indicate that all HODE isomers have PPARγ-binding affinity; however, they have different PPARγ agonist activity. Our findings may help to understand the biological function of lipid peroxidation products.
Cytotoxicity of snake venom enzymatic toxins: phospholipase A2 and l-amino acid oxidase
Authors: Hiu Jia Jin , Yap Michelle Khai Khun
Published: April 2020

The phospholipase A2 (PLA2) and l-amino acid oxidase (LAAO) are two major enzymes found in the venoms from most snake species. These enzymes have been structurally and functionally characterised for their pharmacological activities. Both PLA2 and LAAO from different venoms demonstrate considerable cytotoxic effects on cancer cells via induction of apoptosis, cell cycle arrest and suppression of proliferation. These enzymes produce more pronounced cytotoxic effects in cancer cells than normal cells, thus they can be potential sources as chemotherapeutic agents. It is proposed that PLA2 and LAAO contribute to an elevated oxidative stress due to their catalytic actions, for instance, the ability of PLA2 to produce reactive oxygen species during lipolysis and formation of H2O2 from LAAO catalytic activity which consequently lead to cell death. Nonetheless, the cell-death signalling pathways associated with exposure to these enzymatic toxins are not fully elucidated yet. Here in this review, we will discuss the cytotoxic effects of PLA2 and LAAO in relationship to their catalytic mechanisms and the underlying mechanisms of cytotoxic actions.
50 Jahre Nierentransplantation am Universitätsklinikum Hamburg-Eppendorf
Authors: Freude Stefanie
Published: April 2020

Das Universitäre Transplantations Centrum des UKE (Universitätsklinikum Hamburg-Eppendorf) ist eines der größten Transplantationszentren in Deutschland. Das Zentrum behandelt Patienten und Patientinnen vor und nach Transplantation von Leber, Niere, Pankreas, Herz und Lunge. Zurzeit stehen im UKE mehr als 640 Patientinnen und Patienten auf der Warteliste von Eurotransplant, die dringend ein Organ benötigen.
Immunomodulating Effects Depend on Prolactin Levels in Patients with
Hyperprolactinemia
Authors: Ernerudh Jan , Wahlberg Jeanette , Ewerman Lea , Landberg Eva , Hellberg Sandra , Hovland Mina , Sundin Anna , Jenmalm Maria C. , Ekman Bertil
Published: April 2020

Prolactin is known to have immune modulatory effects acting through the prolactin
receptor, which is present on a variety of immune cells. Certain chemokines
contribute to form the type of T helper (Th) preponderance in the immune
response. The objective of this work was to assess if hyperprolactinemia not
related to pregnancy is associated with changes in circulating levels of
chemokines and other immunological markers. In this cross sectional study, 35
patients with hyperprolactinemia (5 men), and 102 healthy blood donors (19 men)
were included. Serum levels of Th1- Th2- and Th17-associated chemokines,
C-reactive protein, immunoglobulins, and the B cell attracting chemokine CXCL13
were assessed. The hyperprolactinemic group had significantly higher levels of
Th2 associated CCL22 (p=0.022), Th17 associated CXCL1 (p=0.001),
B cell attracting CXCL13 (p=0.003), and C-reactive protein
(p<0.001) compared to controls, and these proteins were also positively
correlated with prolactin levels. While differences in CCL22, CXCL1, CXCL13, and
C-reactive protein were present in patients with low or moderate
hyperprolactinemia, no differences were observed at high
(>3600 mU/l) prolactin levels. To evaluate a possible
dose-associated response to prolactin, an in vitro model was used, showing
prolactin-induced increase in T-helper cell activation at moderate levels, while
activation decreased at higher levels. Hyperprolactinemia seems to have several
immunomodulatory effects and was associated with increased levels of chemokines
associated with Th2 and Th17 responses and B cell attraction. However, patients
with greatly increased prolactin had normal levels of chemokines, and in vitro,
high levels of prolactin decreased T-helper cell activation.
Adipositas und Depression in der Primärversorgung
Authors: Schwenke Maria , Löbner Margrit , Riedel-Heller Steffi , Luppa Melanie
Published: April 2020

Anliegen Untersuchung der Prävalenz von depressiven Störungen bei von Adipositas betroffenen Patienten einer Mitteldeutschen Allgemeinarztstichprobe.

Methoden 131 Patienten der INTERACT-Studie mit Adipositas (BMI ≥ 30); Einsatz des PHQ-9 zur Erfassung depressiver Störungen.

Ergebnisse 29 % der Patienten mit Adipositas zeigen eine Major Depression, 31 % eine subklinische depressive Störung.

Schlussfolgerung Die hohe Komorbidität von Adipositas mit depressiven Störungen auf klinischem sowie subklinischem Niveau birgt besondere Herausforderungen für die Behandlung in der Primärversorgung.
Zervikale Lymphadenitis durch atypische Mykobakterien bei Kindern mit unterschiedlichem Wohnsitz
Authors: Papatsoutsos Efstathios , Aumann Volker , Vorwerk Peter , Redlich Antje , Tammer Ina , Arens Christoph , Vorwerk Ulrich
Published: April 2020

Hintergrund Die atypischen Mykobakterien stellen eine inhomogene Gruppe dar. Obwohl mehr als 140 Spezies identifiziert wurden, stehen nur 25 mit der atypischen Mykobakteriose beim Menschen in Beziehung. Die häufigste Manifestation bei immunkompetenten Kindern ist die zervikale Lymphadenitis. Das Ziel der vorliegenden Arbeit ist die Korrelation des Lebensraums mit den Patientendaten und dem Krankheitsbild, die Auswertung der sonografischen Befunde und der operativen Therapiemethoden und die Erstellung eines Diagnose- und Therapiealgorithmus.

Material und Methoden Die Patienten wurden nach einer systematischen Suche in der klinischen, mikrobiologischen und pathologischen Datenbank der HNO-Klinik identifiziert. Eine statistische Analyse der Ergebnisse wurde durchgeführt.

Ergebnisse 32 Patienten wurden ausgewertet. Eine signifikante Korrelation zwischen dem Wohnort und der Manifestation oder dem Verlauf der Erkrankung konnte nicht nachgewiesen werden. Echoarme Lymphknoten mit intraglandulärer Nekrose und niedriger Durchblutung wurden bei der Mehrheit der Patienten beobachtet. Die verwendeten operativen Methoden schlossen die Abszessinzision mit Biopsie, die diagnostische Lymphadenektomie, die selektive Neck-Dissection und die laterale Parotidektomie ein. Die Rezidivrate war signifikant höher nach Abszessinzision als nach Lymphadenektomie oder selektiver Neck-Dissection.

Schlussfolgerungen Um den Einfluss des Wohnsitzes auf das Krankheitsbild deutlich zu definieren, sind größere prospektive Studien notwendig. Die sonografischen Befunde sind diagnostisch wegweisend. Eine vollständige Resektion trägt zur Diagnose und Therapie bei und stellt eine risikoarme Therapieoption dar.
Silver-Catalyzed [3+3] Annulation of Glycine Imino Esters with Seyferth–Gilbert Reagent To Access Tetrahydro-1,2,4-triazinecarboxylate Esters
Authors: Cheung Chi Wai , Ma Jun-An , Huang Yin-Jun , Nie Jing
Published: April 2020

A silver-catalyzed protocol for [3+3] annulation of glycine imino esters with Seyferth–Gilbert reagent was developed. A variety of phosphorylated tetrahydro-1,2,4-triazinecarboxylate esters were synthesized in moderate to good yields and with excellent diastereoselectivities. The dehydrogenation of a tetrahydro-1,2,4-triazine product to the corresponding triazine counterpart was also demonstrated.
Historical overview of the interleukin-6 family cytokine
Authors: Kang Sujin , Narazaki Masashi , Metwally Hozaifa , Kishimoto Tadamitsu
Published: April 2020

Interleukin-6 (IL-6) has been identified as a 26-kD secreted protein that stimulates B cells to produce antibodies. Later, IL-6 was revealed to have various functions that overlap with other IL-6 family cytokines and use the common IL-6 signal transducer gp130. IL-6 stimulates cells through multiple pathways, using both membrane and soluble IL-6 receptors. As indicated by the expanding market for IL-6 inhibitors, it has become a primary therapeutic target among IL-6 family cytokines. Here, we revisit the discovery of IL-6; discuss insights regarding the roles of this family of cytokines; and highlight recent advances in our understanding of regulation of IL-6 expression.
Early Virus Clearance and Delayed Antibody Response in a Case of Coronavirus Disease 2019 (COVID-19) With a History of Coinfection With Human Immunodeficiency Virus Type 1 and Hepatitis C Virus
Authors: Zhao Juanjuan , Liao Xuejiao , Wang Haiyan , Wei Lanlan , Xing Mingzhao , Liu Lei , Zhang Zheng
Published: April 2020

The effect of host immune status on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unknown. Here, we report the first case of coronavirus disease 2019 (COVID-19) with human immunodeficiency virus type 1 (HIV-1)/hepatitis C virus coinfection, who showed a persistently negative SARS-CoV-2 RNA test but delayed antibody response in the plasma. This case highlights the influence of HIV-1–induced immune dysfunction on early SARS-CoV-2 clearance.
Parental dependence on the nest’s spatial cues in offspring recognition decreases with nestling growth in the azure-winged magpie
Authors: Gao Li-Fang , Zhang Wen , Zhang Hai-Yang , Zhu Zhen-Qin , Zhang Xiao-Dan , Du Bo
Published: April 2020

In altricial birds, to address which cues are used by parents to recognize their offspring, and when they switch between cues during reproduction, it has not been well determined. In this study, we address this question in a Tibetan population of the azure-winged magpie Cyanopica cyanus, by examining the dependence of parents on a nest’s spatial position in offspring recognition. During the egg and nestling phases, azure-winged magpie nests were translocated to new positions across various distances from their original site, and parental responses to the translocated nests were investigated. Our findings show that a nest’s spatial position is not connected with the survival of its young, but might be used as a cue in parental offspring recognition. When nests are translocated to a new position within a certain distance, parents could recognize their nests and returned to resume their parenting behaviors. Parental dependence on the nest’s spatial position in offspring recognition is higher during the egg phase than during the nestling phase, and it decreases with the growth of nestlings. After nestlings reach a certain age, the nest’ s spatial position was no longer used by parents as the single cue for offspring recognition. These findings suggest that azure-winged magpies switch their cues in offspring recognition during the different stages of reproduction. After parent–offspring communication has been established, the offspring’s phenotypic traits may become a more reliable cue than the nest’s spatial position in offspring recognition.
Genital Shedding of Human Immunodeficiency Virus Type-1 (HIV) When Antiretroviral Therapy Suppresses HIV Replication in the Plasma
Authors: Bull Marta , Mitchell Caroline , Soria Jaime , Styrchak Sheila , Williams Corey , Dragavon Joan , Ryan Kevin J , Acosta Edward , Onchiri Frankline , Coombs Robert W , La Rosa Alberto , Ticona Eduardo , Frenkel Lisa M
Published: April 2020

Background

During antiretroviral treatment (ART) with plasma HIV RNA below the limit of quantification, HIV RNA can be detected in genital or rectal secretions, termed discordant shedding (DS). We hypothesized that proliferating cells produce virions without HIV replication.

Methods

ART-naive Peruvians initiating ART were observed for DS over 2 years. HIV env and pol genomes were amplified from DS. Antiretrovirals and cytokines/chemokines concentrations were compared at DS and control time points.

Results

Eighty-two participants had ART suppression. DS was detected in 24/82 (29%) participants: 13/253 (5%) cervicovaginal lavages, 20/322 (6%) seminal plasmas, and 6/85 (7%) rectal secretions. HIV RNA in DS specimens was near the limit of quantification and not reproducible. HIV DNA was detected in 6/13 (46%) DS cervicovaginal lavages at low levels. Following DNase treatment, 5/39 DS specimens yielded HIV sequences, all without increased genetic distances. Women with and without DS had similar plasma antiretroviral levels and DS in 1 woman was associated with inflammation.

Conclusions

HIV RNA and DNA sequences and therapeutic antiretroviral plasma levels did not support HIV replication as the cause of DS from the genital tract. Rather, our findings infer that HIV RNA is shed due to proliferation of infected cells with virion production.
M16-Type Metallopeptidases Are Involved in Virulence for Invasiveness and Diffusion of Leptospira interrogans and Transmission of Leptospirosis
Authors: Ge Yu-Mei , Sun Ai-Hua , Ojcius David M , Li Shi-Jun , Hu Wei-Lin , Lin Xu’ai , Yan Jie
Published: April 2020

Background

Leptospirosis is a global zoonotic infectious disease caused by Leptospira interrogans. The pathogen rapidly invades into hosts and diffuses from bloodstream into internal organs and excretes from urine to cause transmission of leptospirosis. However, the mechanism of leptospiral invasiveness remains poorly understood.

Methods

Proteolytic activity of M16-type metallopeptidases (Lep-MP1/2/3) of L. interrogans was determined by spectrophotometry. Expression and secretion of Lep-MP1/2/3 during infection of cells were detected by quantitative reverse-transcription polymerase chain reaction, Western blot assay, and confocal microscopy. Deletion and complementation mutants of the genes encoding Lep-MP1/2/3 were generated to determine the roles of Lep-MP1/2/3 in invasiveness using transwell assay and virulence in hamsters.

Results

Leptospira interrogans but not saprophytic Leptospira biflexa strains were detectable for Lep-MP-1/2/3-encoding genes. rLep-MP1/2/3 hydrolyzed extracellular matrix proteins, but rLep-MP1/3 displayed stronger proteolysis than rLep-MP2, with 123.179/340.136 μmol/L Km and 0.154/0.159 s-1 Kcat values. Expression, secretion and translocation of Lep-MP1/2/3 during infection of cells were increased. ΔMP1/3 but not ΔMP2 mutant presented attenuated transmigration through cell monolayers, decreased leptospiral loading in the blood, lungs, liver, kidneys, and urine, and 10/13-fold decreased 50% lethal dose and milder histopathologic injury in hamsters.

Conclusions

Lep-MP1 and 3 are involved in virulence of L. interrogans in invasion into hosts and diffusion in vivo, and transmission of leptospirosis.
Detectability of 21-cm signal during the epoch of reionization with 21-cm-Lyman-α emitter cross-correlation – III. Model dependence
Authors: Kubota Kenji , Inoue Akio K , Hasegawa Kenji , Takahashi Keitaro
Published: April 2020

Detecting H i 21-cm line in the intergalactic medium during the epoch of reionization suffers from foreground contamination such as Galactic synchrotron and extragalactic radio sources. Cross-correlation between the 21-cm line and Lyman-α emitter (LAE) galaxies is a powerful tool to identify the 21-cm signal since the 21-cm line emission has correlation with LAEs, while the LAEs are statistically independent of the foregrounds. So far, the detectability of 21-cm-LAE cross-power spectrum has been investigated with simple LAE models where the observed Lyα luminosity is proportional to the dark matter halo mass. However, the previous models were inconsistent with the latest observational data of LAEs obtained with Subaru/Hyper Suprime-Cam (HSC). Here, we revisit the detectability of 21-cm-LAE cross-power spectrum adopting a state-of-the-art LAE model consistent with all Subaru/HSC observations such as the Lyα luminosity function, LAE angular autocorrelation, and the LAE fractions in the continuum selected galaxies. We find that resultant cross-power spectrum with the updated LAE model is reduced at small scales ($k\sim 1\ \rm Mpc^{-1}$) compared to the simple models, while the amplitudes at large scales ($k \lesssim 0.2 \ \rm Mpc^{-1}$) are not affected so much. We conclude that the large-scale signal would be detectable with Square Kilometre Array (SKA) and HSC LAE cross-correlation but detecting the small-scale signal would require an extended HSC LAE survey with an area of $\sim 75\ \rm deg^2$ or 3000 h observation time of 21-cm line with SKA.