bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative risk assessment of tobacco smoke constituents using the margin of exposure approach: the neglected contribution of nicotine
Authors: Baumung Claudia , Rehm Jürgen , Franke Heike , Lachenmeier Dirk W. 
Published: October 2016

AbstractNicotine was not included in previous efforts to identify the most important toxicants of tobacco smoke. A health risk assessment of nicotine for smokers of cigarettes was conducted using the margin of exposure (MOE) approach and results were compared to literature MOEs of various other tobacco toxicants. The MOE is defined as ratio between toxicological threshold (benchmark dose) and estimated human intake. Dose-response modelling of human and animal data was used to derive the benchmark dose. The MOE was calculated using probabilistic Monte Carlo simulations for daily cigarette smokers. Benchmark dose values ranged from 0.004 mg/kg bodyweight for symptoms of intoxication in children to 3 mg/kg bodyweight for mortality in animals; MOEs ranged from below 1 up to 7.6 indicating a considerable consumer risk. The dimension of the MOEs is similar to those of other tobacco toxicants with high concerns relating to adverse health effects such as acrolein or formaldehyde. Owing to the lack of toxicological data in particular relating to cancer, long term animal testing studies for nicotine are urgently necessary. There is immediate need of action concerning the risk of nicotine also with regard to electronic cigarettes and smokeless tobacco.
An artificial photosynthesis anode electrode composed of a nanoparticulate photocatalyst film in a visible light responsive GaN-ZnO solid solution system
Authors: Imanaka Yoshihiko , Anazawa Toshihisa , Manabe Toshio , Amada Hideyuki , Ido Sachio , Kumasaka Fumiaki , Awaji Naoki , Sánchez-Santolino Gabriel , Ishikawa Ryo , Ikuhara Yuichi 
Published: October 2016

AbstractThe artificial photosynthesis technology known as the Honda-Fujishima effect, which produces oxygen and hydrogen or organic energy from sunlight, water, and carbon dioxide, is an effective energy and environmental technology. The key component for the higher efficiency of this reaction system is the anode electrode, generally composed of a photocatalyst formed on a glass substrate from electrically conductive fluorine-doped tin oxide (FTO). To obtain a highly efficient electrode, a dense film composed of a nanoparticulate visible light responsive photocatalyst that usually has a complicated multi-element composition needs to be deposited and adhered onto the FTO. In this study, we discovered a method for controlling the electronic structure of a film by controlling the aerosol-type nanoparticle deposition (NPD) condition and thereby forming films of materials with a band gap smaller than that of the prepared raw material powder, and we succeeded in extracting a higher current from the anode electrode. As a result, we confirmed that a current approximately 100 times larger than those produced by conventional processes could be obtained using the same material. This effect can be expected not only from the materials discussed (GaN-ZnO) in this paper but also from any photocatalyst, particularly materials of solid solution compositions.
A combined method for correlative 3D imaging of biological samples from macro to nano scale
Authors: Kellner Manuela , Heidrich Marko , Lorbeer Raoul-Amadeus , Antonopoulos Georgios C. , Knudsen Lars , Wrede Christoph , Izykowski Nicole , Grothausmann Roman , Jonigk Danny , Ochs Matthias , Ripken Tammo , Kühnel Mark P. , Meyer Heiko 
Published: October 2016

AbstractCorrelative analysis requires examination of a specimen from macro to nano scale as well as applicability of analytical methods ranging from morphological to molecular. Accomplishing this with one and the same sample is laborious at best, due to deformation and biodegradation during measurements or intermediary preparation steps. Furthermore, data alignment using differing imaging techniques turns out to be a complex task, which considerably complicates the interconnection of results. We present correlative imaging of the accessory rat lung lobe by combining a modified Scanning Laser Optical Tomography (SLOT) setup with a specially developed sample preparation method (CRISTAL). CRISTAL is a resin-based embedding method that optically clears the specimen while allowing sectioning and preventing degradation. We applied and correlated SLOT with Multi Photon Microscopy, histological and immunofluorescence analysis as well as Transmission Electron Microscopy, all in the same sample. Thus, combining CRISTAL with SLOT enables the correlative utilization of a vast variety of imaging techniques.
Vildagliptin and its metabolite M20.7 induce the expression of S100A8 and S100A9 in human hepatoma HepG2 and leukemia HL-60 cells
Authors: Asakura Mitsutoshi , Karaki Fumika , Fujii Hideaki , Atsuda Koichiro , Itoh Tomoo , Fujiwara Ryoichi 
Published: October 2016

AbstractVildagliptin is a potent, orally active inhibitor of dipeptidyl peptidase-4 (DPP-4) for the treatment of type 2 diabetes mellitus. It has been reported that vildagliptin can cause hepatic dysfunction in patients. However, the molecular-mechanism of vildagliptin-induced liver dysfunction has not been elucidated. In this study, we employed an expression microarray to determine hepatic genes that were highly regulated by vildagliptin in mice. We found that pro-inflammatory S100 calcium-binding protein (S100) a8 and S100a9 were induced more than 5-fold by vildagliptin in the mouse liver. We further examined the effects of vildagliptin and its major metabolite M20.7 on the mRNA expression levels of S100A8 and S100A9 in human hepatoma HepG2 and leukemia HL-60 cells. In HepG2 cells, vildagliptin, M20.7, and sitagliptin – another DPP-4 inhibitor – induced S100A9 mRNA. In HL-60 cells, in contrast, S100A8 and S100A9 mRNAs were significantly induced by vildagliptin and M20.7, but not by sitagliptin. The release of S100A8/A9 complex in the cell culturing medium was observed in the HL-60 cells treated with vildagliptin and M20.7. Therefore, the parental vildagliptin- and M20.7-induced release of S100A8/A9 complex from immune cells, such as neutrophils, might be a contributing factor of vildagliptin-associated liver dysfunction in humans.
Spatial Dependence of DNA Damage in Bacteria due to Low-Temperature Plasma Application as Assessed at the Single Cell Level
Authors: Privat-Maldonado Angela , O’Connell Deborah , Welch Emma , Vann Roddy , van der Woude Marjan W. 
Published: October 2016

AbstractLow temperature plasmas (LTPs) generate a cocktail of reactive nitrogen and oxygen species (RNOS) with bactericidal activity. The RNOS however are spatially unevenly distributed in the plasma. Here we test the hypothesis that this distribution will affect the mechanisms underpinning plasma bactericidal activity focussing on the level of DNA damage in situ. For the first time, a quantitative, single cell approach was applied to assess the level of DNA damage in bacteria as a function of the radial distance from the centre of the plasma jet. Salmonella enterica on a solid, dry surface was treated with two types of LTP: an atmospheric-pressure dielectric barrier discharge plasma jet (charged and neutral species) and a radio-frequency atmospheric-pressure plasma jet (neutral species). In both cases, there was an inverse correlation between the degree of DNA damage and the radial distance from the centre of the plasma, with the highest DNA damage occurring directly under the plasma. This trend was also observed with Staphylococcus aureus. LTP-generated UV radiation was eliminated as a contributing factor. Thus valuable mechanistic information can be obtained from assays on biological material, which can inform the development of LTP as a complementary or alternative therapy for (topical) bacterial infections.
Communities as cliques
Authors: Fried Yael , Kessler David A. , Shnerb Nadav M. 
Published: October 2016

AbstractHigh-diversity species assemblages are very common in nature, and yet the factors allowing for the maintenance of biodiversity remain obscure. The competitive exclusion principle and May’s complexity-diversity puzzle both suggest that a community can support only a small number of species, turning the spotlight on the dynamics of local patches or islands, where stable and uninvadable (SU) subsets of species play a crucial role. Here we map the question of the number of different possible SUs a community can support to the geometric problem of finding maximal cliques of the corresponding graph. This enables us to solve for the number of SUs as a function of the species richness in the regional pool, N, showing that the growth of this number is subexponential in N, contrary to long-standing wisdom. To understand the dynamics under noise we examine the relaxation time to an SU. Symmetric systems relax rapidly, whereas in asymmetric systems the relaxation time grows much faster with N, suggesting an excitable dynamics under noise.
Plant functional trait diversity regulates the nonlinear response of productivity to regional climate change in Tibetan alpine grasslands
Authors: Wu Jianshuang , Wurst Susanne , Zhang Xianzhou 
Published: October 2016

AbstractThe biodiversity-productivity relationship is still under debate for alpine grasslands on the Tibetan Plateau. We know little about direct and indirect effects of biotic and abiotic drivers on this relationship, especially in regard to plant functional trait diversity. Here, we examine how aboveground net primary productivity (ANPP) and precipitation use efficiency (PUE) respond to climate, soil and community structure across alpine grasslands on the Northern Tibetan Plateau. We found that both ANPP and PUE showed nonlinear patterns along water availability and site altitude variation, which together accounted for 80.3% and 68.8% of variation in ANPP and PUE, respectively, by optimal generalized additive models. Functional trait divergence (FTD) and community weighted mean (CWM) of plant functional traits were as important as plant species diversity (PSD) for explaining the nonlinear productivity-climate relationship. These findings were confirmed by results from principal component analyses and structural equation models. We also found that FTD was negatively correlated with PSD across different alpine grasslands. Our results implicate: first, the combinatorial influences of temperature and precipitation gradients are important for predicting alpine grassland dynamics; second, the convergence and divergence of plant functional traits may have the potential to elucidate the effect of plant diversity on ecosystem functionality.
Enzymatic diversity of the Clostridium thermocellum cellulosome is crucial for the degradation of crystalline cellulose and plant biomass
Authors: Hirano Katsuaki , Kurosaki Masahiro , Nihei Satoshi , Hasegawa Hiroki , Shinoda Suguru , Haruki Mitsuru , Hirano Nobutaka 
Published: October 2016

AbstractThe cellulosome is a supramolecular multienzyme complex comprised of a wide variety of polysaccharide-degrading enzymes and scaffold proteins. The cellulosomal enzymes that bind to the scaffold proteins synergistically degrade crystalline cellulose. Here, we report in vitro reconstitution of the Clostridium thermocellum cellulosome from 40 cellulosomal components and the full-length scaffoldin protein that binds to nine enzyme molecules. These components were each synthesized using a wheat germ cell-free protein synthesis system and purified. Cellulosome complexes were reconstituted from 3, 12, 30, and 40 components based on their contents in the native cellulosome. The activity of the enzyme-saturated complex indicated that greater enzymatic variety generated more synergy for the degradation of crystalline cellulose and delignified rice straw. Surprisingly, a less complete enzyme complex displaying fewer than nine enzyme molecules was more efficient for the degradation of delignified rice straw than the enzyme-saturated complex, despite the fact that the enzyme-saturated complex exhibited maximum synergy for the degradation of crystalline cellulose. These results suggest that greater enzymatic diversity of the cellulosome is crucial for the degradation of crystalline cellulose and plant biomass, and that efficient degradation of different substrates by the cellulosome requires not only a different enzymatic composition, but also different cellulosome structures.
Crystal structure of human aldehyde dehydrogenase 1A3 complexed with NAD+ and retinoic acid
Authors: Moretti Andrea , Li Jianfeng , Donini Stefano , Sobol Robert W. , Rizzi Menico , Garavaglia Silvia 
Published: October 2016

AbstractThe aldehyde dehydrogenase family 1 member A3 (ALDH1A3) catalyzes the oxidation of retinal to the pleiotropic factor retinoic acid using NAD+. The level of ALDHs enzymatic activity has been used as a cancer stem cell marker and seems to correlate with tumour aggressiveness. Elevated ALDH1A3 expression in mesenchymal glioma stem cells highlights the potential of this isozyme as a prognosis marker and drug target. Here we report the first crystal structure of human ALDH1A3 complexed with NAD+ and the product all-trans retinoic acid (REA). The tetrameric ALDH1A3 folds into a three domain-based architecture highly conserved along the ALDHs family. The structural analysis revealed two different and coupled conformations for NAD+ and REA that we propose to represent two snapshots along the catalytic cycle. Indeed, the isoprenic moiety of REA points either toward the active site cysteine, or moves away adopting the product release conformation. Although ALDH1A3 shares high sequence identity with other members of the ALDH1A family, our structural analysis revealed few peculiar residues in the 1A3 isozyme active site. Our data provide information into the ALDH1As catalytic process and can be used for the structure-based design of selective inhibitors of potential medical interest.
Effect of solidification rate on microstructure evolution in dual phase microalloyed steel
Authors: Kostryzhev A. G. , Slater C. D. , Marenych O. O. , Davis C. L. 
Published: October 2016

AbstractIn steels the dependence of ambient temperature microstructure and mechanical properties on solidification rate is not well reported. In this work we investigate the microstructure and hardness evolution for a low C low Mn NbTi-microalloyed steel solidified in the cooling rate range of 1–50 Cs−1. The maximum strength was obtained at the intermediate solidification rate of 30 Cs−1. This result has been correlated to the microstructure variation with solidification rate.
Network Meta-Analysis of the Efficacy of Acupuncture, Alpha-blockers and Antibiotics on Chronic Prostatitis/Chronic Pelvic Pain Syndrome
Authors: Qin Zongshi , Wu Jiani , Tian Jinhui , Zhou Jing , Liu Yali , Liu Zhishun 
Published: October 2016

AbstractAlpha-blockers and antibiotics are most commonly used to treat chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in clinical practice. Currently, increasing evidence also suggests acupuncture as an effective strategy. This network meta-analysis intended to assess the comparative efficacy and safety of acupuncture, alpha-blockers and antibiotics for CP/CPPS. Twelve trials involving 1203 participants were included. Based on decreases in the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score, a network meta-analysis indicated that electro-acupuncture (standard mean difference [SMD]: 4.29; 95% credible interval [CrI], 1.96–6.65), acupuncture (SMD: 3.69; 95% CrI, 0.27–7.17), alpha-blockers (SMD: 1.85; 95% CrI, 1.07–2.64), antibiotics (SMD: 2.66; 95% CrI, 1.57–3.76), and dual therapy (SMD: 3.20; 95% CrI, 1.95–4.42) are superior to placebo in decreasing this score. Additionally, electro-acupuncture (SMD: 2.44; 95% CrI, 0.08–4.83) and dual therapy (SMD: 1.35; 95% CrI, 0.07–2.62) were more effective than alpha-blockers in decreasing the total NIH-CPSI total score. Other network meta-analyses did not show significant differences between interventions other placebo. The incidence of adverse events of acupuncture was relatively rare (5.4%) compared with placebo (17.1%), alpha-blockers (24.9%), antibiotics (31%) and dual therapy (48.6%). Overall, rank tests and safety analyses indicate that electro-acupuncture/acupuncture may be recommended for the treatment of CP/CPPS.
The Fleur-de-PAP Flap for Bilateral Breast Reconstruction
Authors: Saussy Katharine , Stalder Mark , Delatte Stephen , Allen Robert , St Hilaire Hugo 
Published: October 2016

AbstractThe authors present the case of a 42-year-old female patient who underwent autologous breast reconstruction using a new perforator flap designed from the medial and posterior thigh. Due to a prior abdominoplasty, the patient's abdominal donor site was unavailable to reconstruct her large, ptotic breasts, so an alternate approach was undertaken. The fleur-de-PAP flap is based on the same perforators employed by the standard profunda artery perforator (PAP) flap, but simultaneously incorporates tissue from both the transverse and vertical PAP flap skin paddles. This design maximizes flap volume at a single donor site and provides a reasonable secondary option for autologous reconstruction in large-breasted patients in whom the abdomen is not available.
Crystal structure of the cohesin loader Scc2 and insight into cohesinopathy
Authors: Kikuchi Sotaro , Borek Dominika M. , Otwinowski Zbyszek , Tomchick Diana R. , Yu Hongtao 
Published: October 2016

Significance
The ring-shaped cohesin traps chromosomes inside its ring and regulates chromosome segregation during mitosis and transcription during interphase. The sister chromatid cohesion 2 protein (Scc2) opens the cohesin ring and loads it onto chromosomes. Mutations of cohesin subunits and regulators perturb transcription and cause human developmental diseases called cohesinopathy. Scc2 is the most frequently mutated cohesin regulator in cohesinopathy. In this study, we report the crystal structure of a fungal Scc2 protein, which represents a high-resolution snapshot of the cohesin loader. We have identified a set of Scc2 mutations in cohesinopathy that disrupt the binding of Scc2 to the kleisin subunit of cohesin. Our results provide critical insight into cohesin loading and cohesinopathy.
Tilting the balance between RNA interference and replication eradicatesLeishmaniaRNA virus 1 and mitigates the inflammatory response
Authors: Brettmann Erin A. , Shaik Jahangheer S. , Zangger Haroun , Lye Lon-Fye , Kuhlmann F. Matthew , Akopyants Natalia S. , Oschwald Dayna M. , Owens Katherine L. , Hickerson Suzanne M. , Ronet Catherine , Fasel Nicolas , Beverley Stephen M. 
Published: October 2016

SignificanceLeishmaniaparasites can be infected withLeishmaniavirus(LRV1), a double-stranded RNA virus whose presence inLeishmania guyanensisparasites exacerbates disease severity in both mouse models and humans. Studies of the role of the virus on parasite biology and virulence are hampered by the dearth of isogenic lines bearing and lacking LRV, particularly in the clinically important speciesLeishmania braziliensis. Here, we describe a method to systematically generate LRV1-freeLeishmaniaparasites using the parasite RNA interference (RNAi) pathway. The ability of transgene-driven RNAi to overcome the ability of LRV1 to withstand the endogenous RNAi attack suggests a third paradigm of virus–RNAi interaction where RNAi and virus replication exist in balance to maintain persistent infection.
Single-electron devices in silicon
Authors: Schupp Felix J. 
Published: October 2016

Miniaturisation of silicon microelectronics continues to be a major driving force for the technological progress in computing and electronics. As modern device fabrication is approaching the nanometre scale, quantum effects are dominating device properties. This may set a lower bound for the size of conventional devices, and therefore ultimately limit their performance. On the other hand, quantum effects could enable the development of new types of devices, which might overcome the limitations of classical physics. This review outlines the recent progress in the field of single-electron devices for charge sensing and metrological applications. It illustrates the gap between large-scale commercial fabrication and research prototypes as well as technologies that could close this gap in the future. Any viable roadmap towards commercialisation of single-electron devices is likely to leverage the highly developed silicon-based fabrication methods that have enabled impressive progress in information and communication technology. The scope of this review ranges from random dopant fluctuations in classical devices to single-dopant transistors, and covers electron pumps as well as top-down fabricated single-electron transistors in direct-current and radio-frequency operation. This review was submitted as part of the 2016 Materials Literature Review Prize of the Institute of Materials, Minerals and Mining run by the Editorial Board of MST. Sponsorship of the prize by TWI Ltd is gratefully acknowledged
Beyond access: barriers to internet health information seeking among the urban poor
Authors: McCloud Rachel F , Okechukwu Cassandra A , Sorensen Glorian , Viswanath K 
Published: October 2016

AbstractObjective Communication inequalities deepen health disparities even when internet access is achieved. The goal of this study is to understand how a range of barriers may inhibit individuals from low socioeconomic position (SEP) from engaging with online health information even when it is freely available.Materials and methods Detailed data were collected from 118 low-SEP individuals from a randomized controlled trial providing internet access. Measures triangulated the health-seeking experience through internet use tracked in real-time, call log data, and self-reported barriers. Negative binomial regression models were fitted with technology and perceived predictors, and our outcome, health information seeking, and then stratified by medical status.Results Participants experienced a median of two computer issues (median 6 days) and two internet issues (median 6.5 days). Duration of internet problems was associated with a decrease in the rate of internet health information seeking by a factor of 0.990 ( P = .03) for each additional day. Participants with a medical problem who were frustrated in their search for health information had half the rate of health information seeking of those who were not frustrated (incidence rate ratio = 0.395, P = .030).Discussion Despite IT support, participants still experienced internet connectivity issues that negatively impacted their health information seeking. Frustration in their search to find information may serve as an additional barrier to those who have medical issues.Conclusion After initial internet access, a second-level digital divide emerged due to connectivity issues, highlighting the need to understand the complex network of barriers experienced by low-SEP internet users.