bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complement 5a Receptor deficiency does not influence adverse cardiac remodeling after pressure-overload in mice
Authors: de Haan Judith J. , Bosch Lena , Borgman Anouska , Bastemeijer Marissa , Brans Maike A. D. , van de Weg Sander M. , de Kleijn Dominique P. V. , Sluijter Joost P. G. , el Azzouzi Hamid , de Jager Saskia C. A. 
Published: November 2017

AbstractHypertension is one of the most common risk factors for the development heart failure in the general population. Inflammation plays a central role in this adverse remodeling and eventually to the development of heart failure. Circulating levels of Complement factor 5a (C5a) are increased in hypertensive patients and the C5a receptor is associated with the presence of cardiac fibrosis and inflammation in an experimental hypertension model. To test if C5aR is involved in adverse cardiac remodeling following pressure-overload, we induced transverse aortic constriction (TAC) in wildtype and C5a receptor deficient mice (C5aR−/−). Six weeks after TAC, C5aR-/- animals showed a similar degree of cardiac hypertrophy and decrease in cardiac function as wild type mice (End Systolic Volume; 50.30±5.32 µl vs. 55.81±8.16 µl). In addition, other features of adverse cardiac remodeling like cardiomyocyte cell size (WGA staining), fibrosis (picrosirius red staining) or collagen degradation (matrix metalloproteinase activity assay) did not differ either. In conclusion, full body C5aR deficiency does not affect adverse cardiac remodeling after pressure-overload. However, our finding are in contrast with C5a inhibition studies. Our observations do present the role of C5a-C5aR in adverse cardiac remodeling and heart failure as controversial at the least.
GWAS of the electrocardiographic QT interval in Hispanics/Latinos generalizes previously identified loci and identifies population-specific signals
Authors: Méndez-Giráldez Raúl , Gogarten Stephanie M. , Below Jennifer E. , Yao Jie , Seyerle Amanda A. , Highland Heather M. , Kooperberg Charles , Soliman Elsayed Z. , Rotter Jerome I. , Kerr Kathleen F. , Ryckman Kelli K. , Taylor Kent D. , Petty Lauren E. , Shah Sanjiv J. , Conomos Matthew P. , Sotoodehnia Nona , Cheng Susan , Heckbert Susan R. , Sofer Tamar , Guo Xiuqing , Whitsel Eric A. , Lin Henry J. , Hanis Craig L. , Laurie Cathy C. , Avery Christy L. 
Published: November 2017

AbstractQT interval prolongation is a heritable risk factor for ventricular arrhythmias and can predispose to sudden death. Most genome-wide association studies (GWAS) of QT were performed in European ancestral populations, leaving other groups uncharacterized. Herein we present the first QT GWAS of Hispanic/Latinos using data on 15,997 participants from four studies. Study-specific summary results of the association between 1000 Genomes Project (1000G) imputed SNPs and electrocardiographically measured QT were combined using fixed-effects meta-analysis. We identified 41 genome-wide significant SNPs that mapped to 13 previously identified QT loci. Conditional analyses distinguished six secondary signals at NOS1AP (n = 2), ATP1B1 (n = 2), SCN5A (n = 1), and KCNQ1 (n = 1). Comparison of linkage disequilibrium patterns between the 13 lead SNPs and six secondary signals with previously reported index SNPs in 1000G super populations suggested that the SCN5A and KCNE1 lead SNPs were potentially novel and population-specific. Finally, of the 42 suggestively associated loci, AJAP1 was suggestively associated with QT in a prior East Asian GWAS; in contrast BVES and CAP2 murine knockouts caused cardiac conduction defects. Our results indicate that whereas the same loci influence QT across populations, population-specific variation exists, motivating future trans-ethnic and ancestrally diverse QT GWAS.
Phagosomal transport depends strongly on phagosome size
Authors: Keller S. , Berghoff K. , Kress H. 
Published: November 2017

AbstractMacrophages internalize pathogens for intracellular degradation. An important part of this process is the phagosomal transport from the cell periphery to the perinuclear region. Biochemical factors are known to influence the fate of phagosomes. Here, we show that the size of phagosomes also has a strong influence on their transport. We found that large phagosomes are transported persistently to the nucleus, whereas small phagosomes show strong bidirectional transport. We show that dynein motors play a larger role in the transport of large phagosomes, whereas actin filament-based motility plays a larger role in the transport of small phagosomes. Furthermore, we investigated the spatial distribution of dyneins and microtubules around phagosomes and hypothesize that dynein and microtubule density differences between the nucleus-facing side of phagosomes and the opposite side could explain part of the observed transport characteristics. Our findings suggest that a size-dependent cellular sorting mechanism might exist that supports macrophages in their immunological roles.
Superconductivity in two-dimensional ferromagnetic MnB
Authors: Farooq M. Umar , Hashmi Arqum , Khan Imran , Hong Jisang 
Published: November 2017

AbstractUsing the universal structure predictor algorithm, we proposed that two-dimensional MnB structures with p4mmm (α-MnB) and pmma (β-MnB) symmetries could be synthesized. This finding was verified by calculating the dynamical stability, molecular dynamics, and mechanical properties. The α-MnB had an in-plane stiffness Y
x
(=Y
y
) around 100 N/m while the β-Mn displayed an asymmetric mechanical stiffness of Y
x
= 186 N/m and Y
y
= 139 N/m. Both systems displayed a ferromagnetic ground state with metallic band structures. The calculated magnetic moments were 2.14 and 2.34 µB per Mn-B pair in the α-MnB and β-MnB. Furthermore, we investigated the potential superconductivity. In the α-MnB, we found the unique feature of Kohn anomaly at q~2kF in the diagonal direction of the Brillouin zone. The β-MnB phonon spectra showed a valley of degenerated localized softening vibration modes at the edge of the Brillouin zone. The ZA and LA phonon branches in this valley induced the largest contribution to electron-phonon coupling strength. The calculated total electron-phonon coupling parameters were 1.20 and 0.89 in α-MnB and β-MnB systems. Overall, we predict that the α-MnB and β-MnB systems can display 2D ferromagnetic superconducting states with the estimated critical temperatures of Tc ≈ 10−13 K.
Multivalent Fcγ-receptor engagement by a hexameric Fc-fusion protein triggers Fcγ-receptor internalisation and modulation of Fcγ-receptor functions
Authors: Qureshi O. S. , Rowley T. F. , Junker F. , Peters S. J. , Crilly S. , Compson J. , Eddleston A. , Björkelund H. , Greenslade K. , Parkinson M. , Davies N. L. , Griffin R. , Pither T. L. , Cain K. , Christodoulou L. , Staelens L. , Ward E. , Tibbitts J. , Kiessling A. , Smith B. , Brennan F. R. , Malmqvist M. , Fallah-Arani F. , Humphreys D. P. 
Published: November 2017

AbstractEngagement of Fcγ-receptors triggers a range of downstream signalling events resulting in a diverse array of immune functions. As a result, blockade of Fc-mediated function is an important strategy for the control of several autoimmune and inflammatory conditions. We have generated a hexameric-Fc fusion protein (hexameric-Fc) and tested the consequences of multi-valent Fcγ-receptor engagement inin vitroandin vivosystems.In vitroengagement of hexameric-Fc with FcγRs showed complex binding interactions that altered with receptor density and triggered the internalisation and degradation of Fcγ-receptors. This caused a disruption of Fc-binding and phagocytosis.In vivo, in a mouse ITP model we observed a short half-life of hexameric-Fc but were nevertheless able to observe inhibition of platelet phagocytosis several days after hexameric-Fc dosing. In cynomolgus monkeys, we again observed a short half-life, but were able to demonstrate effective FcγR blockade. These findings demonstrate the ability of multi-valent Fc-based therapeutics to interfere with FcγR function and a potential mechanism through which they could have a sustained effect; the internalisation and degradation of FcγRs.
Tuning Alginate Bioink Stiffness and Composition for Controlled Growth Factor Delivery and to Spatially Direct MSC Fate within Bioprinted Tissues
Authors: Freeman Fiona E. , Kelly Daniel J. 
Published: November 2017

AbstractAlginate is a commonly used bioink in 3D bioprinting. Matrix stiffness is a key determinant of mesenchymal stem cell (MSC) differentiation, suggesting that modulation of alginate bioink mechanical properties represents a promising strategy to spatially regulate MSC fate within bioprinted tissues. In this study, we define a printability window for alginate of differing molecular weight (MW) by systematically varying the ratio of alginate to ionic crosslinker within the bioink. We demonstrate that the MW of such alginate bioinks, as well as the choice of ionic crosslinker, can be tuned to control the mechanical properties (Young’s Modulus, Degradation Rate) of 3D printed constructs. These same factors are also shown to influence growth factor release from the bioinks. We next explored if spatially modulating the stiffness of 3D bioprinted hydrogels could be used to direct MSC fate inside printed tissues. Using the same alginate and crosslinker, but varying the crosslinking ratio, it is possible to bioprint constructs with spatially varying mechanical microenvironments. Moreover, these spatially varying microenvironments were found to have a significant effect on the fate of MSCs within the alginate bioinks, with stiffer regions of the bioprinted construct preferentially supporting osteogenesis over adipogenesis.
Features of electronic and lattice mechanisms of transboundary heat transfer in multilayer nanolaminate TiAlN/Ag coatings
Authors: Kovalev A. I. , Wainstein D. L. , Vakhrushev V. O. , Gago R. , Soldera F. , Endrino J. L. , Fox-Rabinovich G. S. , Veldhuis S. 
Published: November 2017

AbstractPlasmon resonance heterogeneities were identified and studied along Ag and TiAlN layers within a multilayer stack in nanolaminate TiAlN/Ag coatings. For this purpose, a high-resolution plasmon microscopy was used. The plasmons intensity, energy, and depth of interface plasmon-polariton penetration were studied by scanning reflected electron energy loss spectroscopy. The heat conductivity of such metal-insulator-metal (MIM) nanolaminate coatings was measured by laser reflectometry. Dependencies of thermal conductivity coefficient of coatings, MIM interfaces, and resistivity of Ag layers as a function of the Ag-TiAlN bilayer thickness were calculated on the basis of experimental data. The contribution of plasmon resonance confinement to the abnormal lower thermal conductivity in the MIM metamaterial with Ag layer thickness below 25 nm is discussed. In particular, the results highlight the relevant role of different heat transfer mechanisms between MI and IM interfaces: asymmetry of plasmon-polariton interactions on upper and lower boundaries of Ag layer and asymmetry of LA and TA phonons propagation through interfaces.
Stationary Rossby waves dominate subduction of anthropogenic carbon in the Southern Ocean
Authors: Langlais C. E. , Lenton A. , Matear R. , Monselesan D. , Legresy B. , Cougnon E. , Rintoul S. 
Published: November 2017

AbstractThe Southern Ocean has taken up more than 40% of the total anthropogenic carbon (Cant) stored in the oceans since the preindustrial era, mainly in subantarctic mode and intermediate waters (SAMW-AAIW). However, the physical mechanisms responsible for the transfer of Cant into the ocean interior remain poorly understood. Here, we use high resolution (1/10°) ocean simulations to investigate these mechanisms at the SAMW-AAIW subduction hotspots. Mesoscale Stationary Rossby Waves (SRWs), generated where the Antarctic Circumpolar Current interacts with topography, make the dominant contribution to the Cant transfer in SAMW-AAIW in the Indian and Pacific sectors (66% and 95% respectively). Eddy-resolving simulations reproduce the observed Cant sequestration in these layers, while lower spatial resolution models, that do not reproduce SRWs, underestimate the inventory of Cant in these layers by 40% and overestimate the storage in denser layers. A key implication is that climate model simulations, that lack sufficient resolution to represent sequestration by SRWs, are therefore likely to overestimate the residence time of Cant in the ocean, with implications for simulated rates of climate change.
CRISPR/Cas9 mediated mutation of mouse IL-1α nuclear localisation sequence abolishes expression
Authors: Daniels Michael J. D. , Adamson Antony D. , Humphreys Neil , Brough David 
Published: November 2017

AbstractInflammation is a host defense process against infection. Inflammatory mediators include cytokines of the interleukin-1 family, such as IL-1α and IL-1β. Unlike IL-1β, IL-1α carries an N-terminal nuclear localisation sequence (NLS) and is trafficked to the nucleus. The importance of IL-1α nuclear localisation is poorly understood. Here, we used CRISPR/Cas9 to make inactivating mutations to the NLS on the Il1a gene. A colony of NLS mutant mice was successfully generated with precise knock-in mutations to incapacitate NLS function. NLS mutant mice had no gross changes in immunophenotype or inflammatory response but, surprisingly, failed to express IL-1α. We deduced that, in making specific mutations in the Il1a gene, we also mutated a long-noncoding (lnc)RNA in the complementary strand which has cis-regulatory transcriptional control of the Il1a gene itself. The mutations generated in the Il1a gene also result in mutation of the lncRNA sequence and a predicted alteration of its secondary structure, potentially explaining a subsequent failure to function as a transcriptional activator of Il1a expression. Thus, lncRNA secondary structure may regulate IL-1α expression. Our results serve as a cautionary note that CRISPR –mediated genome editing without full knowledge of genomic context can result in unexpected, yet potentially informative observations.
Growth of Graphene/h-BN Heterostructures on Recyclable Pt Foils by One-Batch Chemical Vapor Deposition
Authors: Qian Yongteng , Van Ngoc Huynh , Kang Dae Joon 
Published: November 2017

AbstractHigh-quality large-area graphene/h-BN vertical heterostructures are promising building blocks for many viable applications such as energy harvesting/conversion, electronics and optoelectronics. Here, we successfully grew high-quality large-area graphene/h-BN vertical heterostructures on Pt foils by one-batch low-pressure chemical vapor deposition (LPCVD). We obtained the high quality of about 200-µm-wide graphene/h-BN film having uniform layer thickness. Moreover, the obtained graphene/h-BN heterostructures exhibited field effect mobility of up to 7,200 cm2V−1s−1 at room temperature. These results suggest that such graphene/h-BN heterostructures on recyclable Pt foils grown by LPCVD are promising for high-performance graphene-based electronics.
Chemotherapie beim älteren Patienten mit nicht kleinzelligem Lungenkarzinom: Eine nichtinterventionelle, prospektive, multizentrische Beobachtungsstudie
Authors: Heigener David , Hoeffken Gert , Wuerflein Dieter , Feurer Matthias , Rittmeyer Achim , Huber Roland , Pietsch Markus , Ring Arne , Deppermann Karl-Matthias 
Published: November 2017

Zusammenfassung
Hintergrund Auch für ältere Patienten (> 70 Jahre) ist der Nutzen einer palliativen Chemotherapie beim NSCLC durch Studien gut belegt. Wir haben eine multizentrische, prospektive Datensammlung über die Therapieentscheidungen bei Patienten älter als 70 Jahre durchgeführt, um die klinische Versorgungsrealität in Hinblick auf Überlebensdaten und Komorbiditäten in Deutschland zu analysieren.
Material und Methoden Eingeschlossen wurden Patienten die 70 Jahre oder älter waren und ein Lungenkarzinom im Stadium IIIB oder IV hatten. Die Zentren durften jeweils 20 konsekutive Patienten einschließen. Es wurden die Komorbiditäten dokumentiert und mittels des Charlson-Comorbidity-Scores bewertet sowie die Überlebensdaten erfasst.
Ergebnisse 253 Patienten wurden dokumentiert. Das mediane Alter betrug 75,5 Jahre (Bereich 70 – 92 Jahre) und 75 % der Patienten waren männlich. 2 % der Patienten wiesen keinerlei Komorbiditäten auf, 5 % eine, 15 % zwei, 24 % drei und 55 % mehr als drei. 237 Patienten (94 %) erhielten eine systemische Chemotherapie: 172 (73 %) als Kombinationstherapie und 58 (24 %) als Monotherapie, von sieben Patienten gibt es keine Angaben bezüglich der Therapie. Von den Kombinationstherapien beinhalteten 66 % Carboplatin und 30 % Cisplatin. Die am häufigsten gegebene Monotherapie war Vinorelbin in 50 % der Fälle. In der Gruppe der über Achtzigjährigen (n = 38) erhielten 53 % eine Monotherapie, 29 % eine Carboplatin-haltige Kombinationstherapie und 16 % keine systemische Therapie. Cisplatin wurde in dieser Gruppe nicht verabreicht. Das mediane Überleben im Gesamtkollektiv betrug 16,9 Monate. Patienten mit einem Charlson-Score von ≤ 6 erreichten 17,9 Monate, solche mit einem von > 6 erreichten 12,0 Monate. In der Gruppe der Patienten, welche eine Kombinationstherapie erhielten, war das Gesamtüberleben median 23,5 Monate. Patienten, die älter als 80 Jahre waren, erreichten hier nur 5,7 Monate.
Schlussfolgerung Patienten älter als 70 Jahre erhielten zu einem hohen Anteil eine systemische Therapie. Das Überleben hing stärker von den Komorbiditäten als von dem Alter der Patienten ab.
Amitabh Bachchan
Authors: Singh Sunny 
Published: November 2017

In this unique study of the star, Sunny Singh examines Amitabh Bachchan's film performances and his star persona, locating them in the context of cultural phenomena and global branding, and explores the reasons behind the longevity of his stardom. This illuminating analysis assesses the full range of Bachchan's work, personality and influence - political, social, economic and technological. With in-depth analyses of key films and their wide-ranging social contexts, Singh offers a provocative and in-depth study of the superstar, his extensive career to date as well as the nature of Indian, Asian, and global stardom.
An ideal resource for undergraduate and postgraduate students of film and television studies, this fascinating guide will also appeal to film lovers and anyone interested in this famed actor's transnational career.
Crystalline arthropathy and bone health
Authors: Chang Ian , Gazeley David 
Published: November 2017

Purpose of review
The purpose of this review is to provide insight on the proposed association between crystal arthritis and bone health. Crystal arthritis is the most common type of inflammatory arthritis, and fractures contribute to significant morbidity and mortality, therefore, the relationship between the two is of clinical importance.

Recent findings
There have been variable findings regarding hyperuricemia, low bone density and risk of fracture. A recent systematic review and meta-analysis of available literature showed a correlation between increased serum uric acid and lower risk of fracture. Less is known about calcium pyrophosphate deposition disease and bone health, although two large studies have suggested an association with osteopenia.

Summary
A systematic review and meta-analysis of available data suggest a correlation between increased serum uric acid and lower risk of fracture. Findings support an association between bone health and crystal arthritis which warrants further study and may have implications for how we treat gout.
Evaluation of a Trabecular Microbypass Stent With Cataract Extraction in Severe Primary Open-angle Glaucoma
Authors: Ferguson Tanner , Swan Russell , Ibach Mitch , Schweitzer Justin , Sudhagoni Ramu , Berdahl John P. 
Published: November 2017

Purpose:
To evaluate the safety and efficacy of a trabecular microbypass stent combined with cataract surgery in patients with severe open-angle glaucoma.

Patients:
The series included 59 eyes with severe primary open-angle glaucoma and severe visual field loss as defined by American Academy of Ophthalmology preferred practice pattern criteria.

Materials and Methods:
Retrospective case series. Patients were implanted with 1 trabecular microbypass stent with concomitant cataract surgery. Primary outcome measures were intraocular pressure (IOP) and number of glaucoma medications. Safety measures included postoperative IOP pressure spikes ≥15 mm Hg or IOP<6 mm Hg at any time point, and the need for additional surgery.

Results:
The mean preoperative IOP was 19.25±6.97 mm Hg. Postoperatively, the mean IOP was 14.38±3.63 mm Hg (P<0.01) at 12 months and 14.92±3.86 mm Hg (P<0.01) at 24 months. The mean number of glaucoma medications was 2.27±1.06 preoperatively and 1.63±1.17 (P<0.01) at 24 months postoperative, indicating a 28% reduction in medication use. In total, 4 (7%) eyes required additional surgery. In total, 5 eyes (8%) experienced IOP spikes ≥15 mm Hg, 14 (24%) eyes had IOP spikes ≥10 mm Hg. Overall 55% of eyes had a 20% IOP reduction after 24 months of surgery. Eyes with baseline IOP≤19 had a mean reduction of 2.24 mm Hg 36 months after surgery.

Conclusions:
Trabecular microbypass stent implantation during cataract surgery safely and effectively lowers IOP and medication use in patients with severe primary open-angle glaucoma.
Penetrance of polygenic obesity susceptibility loci across the body mass index distribution: an update on scaling effects
Authors: Abadi Arkan , Alyass Akram , Robiou du Pont Sebastien , Bolker Ben , Singh Pardeep , Mohan Viswanathan , Diaz Rafael , Engert James C. , Gerstein Hertzel C. , Anand Sonia S. , Meyre David 
Published: November 2017

ABSTRACTA growing number of single nucleotide polymorphisms (SNPs) have been associated with body mass index (BMI) and obesity, but whether the effect of these obesity susceptibility loci is uniform across the BMI distribution remains unclear. We studied the effects of 37 BMI/obesity-associated SNPs in 75,230 adults of European ancestry along BMI percentiles using conditional quantile regression (CQR) and meta-regression (MR) models. The effects of 9 SNPs (24%) increased significantly across the sample BMI distribution including, FTO (rs1421085, p=8.69×10−15), PCSK1 (rs6235, p=7.11×10−06), TCF7L2 (rs7903146, p=9.60×10−06), MC4R (rs11873305, p=5.08×10−05), FANCL (rs12617233, p=5.30×10−05), GIPR (rs11672660, p=1.64×−04), MAP2K5 (rs997295, p=3.25×10−04), FTO (rs6499653, p=6.23×10−04) and NT5C2 (rs3824755, p=7.90×10−04). We showed that such increases stem from unadjusted gene interactions that enhanced the effects of SNPs in persons with high BMI. When 125 height-associated were analyzed for comparison, only one (<1%), IGF1 (rs6219, p=1.80×10−04), showed effects that varied significantly across height percentiles. Cumulative gene scores of these SNPs (GS-BMI and GS-Height, respectively) showed that only GS-BMI had effects that increased significantly across the sample distribution (BMI: p=7.03×10−37, Height: p=0.499). Overall, these findings underscore the importance of gene-gene and gene-environment interactions in shaping the genetic architecture of BMI and advance a method to detect such interactions using only the sample outcome distribution.