bluuebunny/crossref_metadata_2025_split huggingface dataset:
ProcessAtlas: A scalable and extensible platform for business process analytics
Authors: Beheshti Amin , Benatallah Boualem , Motahari‐Nezhad Hamid Reza 
Published: January 2018

SummaryIn today's knowledge‐, service‐, and cloud‐based economy, an overwhelming amount of business‐related data are being generated at a fast rate daily from a wide range of sources. These data increasingly show all the typical properties of big data: wide physical distribution, diversity of formats, nonstandard data models, and independently managed and heterogeneous semantics. In this context, there is a need for new scalable and process‐aware services for querying, exploration, and analysis of process data in the enterprise because (1) process data analysis services should be capable of processing and querying large amount of data effectively and efficiently and, therefore, have to be able to scale well with the infrastructure's scale and (2) the querying services need to enable users to express their data analysis and querying needs using process‐aware abstractions rather than other lower‐level abstractions. In this paper, we introduce ProcessAtlas, ie, an extensible large‐scale process data querying and analysis platform for analyzing process data in the enterprise. The ProcessAtlas platform offers an extensible architecture by adopting a service‐based model so that new analytical services can be plugged into the platform. In ProcessAtlas, we present a domain‐specific model for representing process knowledge, ie, process‐level entities, abstractions, and the relationships among them modeled as graphs. We provide services for discovering, extracting, and analyzing process data. We provide efficient mapping and execution of process‐level queries into graph‐level queries by using scalable process query services to deal with the process data size growth and with the infrastructure's scale. We have implemented ProcessAtlas as a MapReduce‐based prototype and report on experiments performed on both synthetic and real‐world datasets.
A facilitated expert‐based approach to architecting “openable” complex systems
Authors: Szajnfarber Zoe , Vrolijk Ademir 
Published: January 2018

AbstractOpen innovation methods, which broadly include: prize competitions, grand challenges, and collaborative communities, are increasingly being applied to complex systems problems. While external solvers (i.e., the crowd) have historically contributed some important innovations, there appears to be a limit to the kind of systems where open innovation can be successful. We contend that open innovation activities can be more broadly effective if seekers (i.e., problem owners) formulated their system architectures with “openability” in mind. In this paper, we build on existing theory to categorize the kinds of problems that are most amenable to crowd contributions, based on the mechanisms of solving. We call these “openable” problems. We then develop and demonstrate an architecting process that uses a facilitated expert workshop to elicit “openable” subproblems within a given systems‐level problem. It treats the need for some openable subproblems as a constraint on the architecture. While not all systems should be designed with “openability” in mind, many organizations have faced political‐level pressure to better leverage the crowd. In that context, we provide guidance on how to do so effectively. We demonstrate the potential value of our approach through application to the NASA Asteroid Grand Challenge—a highly complex system. The paper concludes by reflecting on the implications of this exercise for open innovation and system decomposition in general.
Building models of product development processes: An integrative approach to managing organizational knowledge
Authors: Browning Tyson R. 
Published: January 2018

AbstractThe process for designing and developing complex system products—all of the activities performed and the information and other work products produced—is essential to innovative and competitive enterprises. This process is dynamic, complex, and complicated, and the people who understand it best are in short supply and may not be around for the next project. For a variety of reasons, models of this process are important to systems engineers and managers. A 2006 paper in this journal discussed key concepts in modeling product development (PD) processes. This paper follows by presenting a general approach to building PD process models, integrative process modeling (IPM), which support a wide variety of purposes, such as providing evidence for external certifications, planning projects and programs, and more—but especially serving as a salient repository for crucial organizational information. Although a centralized team of modeling experts leads the overall IPM endeavor, distributed agents define various processes and activities, thereby capturing PD information across very large organizations. The paper discusses management of the model‐building project and subsequent operations, as well as software tool support and model storage. A collection of helpful heuristics guides IPM to help organizations improve the long‐term value provided by PD process modeling.
Geochemistry and Petrogenesis of 2.8 Ga Old Rare Metal Bearing Fertile Granite at Allapatna, Mandya District, Karnataka
Authors: Sarbajna Chanchal , Pandey U. K. , Krishnamurthy P. 
Published: January 2018

ABSTRACT
This paper reports petrography, geochemistry and Rb-Sr age data on the rare metal bearing Neoarchean fertile (Nb-Ta) granite at Allapatna and elucidates its petrogenesis and role in Nb-Ta-Li-Be mineralization. The Allapatna granite (AG) intrudes the Tonalitic-Trondhjemitic - Granodioritic (TTG) Peninsular Gneiss and analysed SiO2 (72.3-75.6 wt%), K2O (4.0-5.7wt%), Na2O (3.0-4.4wt%), CaO (0.7-1wt%), MgO (0.13-0.25wt%) and K2O/Na2O (&gt;1) indicating evolved nature. The presence of muscovite, biotite and garnet in the mode, peraluminous nature and high initial 87Sr/86Sr ratio (0.7284±0.0083) attest to their S-type characteristics. Varying Nb/Ta ratio and high Li with moderate abundance of Cs further indicate affinity to Li-Cs-Ta (LCT) type granite-pegmatite system. The AG showing whole rock Rb-Sr isochron age of 2803± 68 Ma, is the oldest reported fertile granite in India parental to rare metal pegmatites hosting Nb-Ta, Be, and Li resources. Partial melting of a mixed source consisting of both basement TTG rocks and metapelites has generated such type of granitic magma. Fractionation of such granitic magma possibly has given rise to the rare metal (Ta-Nb-Li-Be) bearing pegmatites intruding the nearby schist belt.
Differential effect of disease-associated ST8SIA2 haplotype on cerebral white matter diffusion properties in schizophrenia and healthy controls
Authors: Fullerton Janice M. , Klauser Paul , Lenroot Rhoshel K. , Shaw Alex D. , Overs Bronwyn , Heath Anna , Cairns Murray J. , Atkins Joshua , Scott Rodney ,   The Australian Schizophrenia Research Bank, Schofield Peter R. , Weickert Cyndi Shannon , Pantelis Christos , Fornito Alex , Whitford Thomas J. , Weickert Thomas W. , Zalesky Andrew 
Published: January 2018

AbstractBrain white matter abnormalities are evident in individuals with schizophrenia, and also their first-degree relatives, suggesting that some alterations may relate to underlying genetic risk. The ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 2 (ST8SIA2)gene, which encodes the alpha-2,8-sialyltransferase 8B enzyme that aids neuronal migration and synaptic plasticity, was previously implicated as a schizophrenia susceptibility gene. This study examined the extent to which specific haplotypes inST8SIA2influence white matter microstructure using diffusion-weighted imaging of individuals with schizophrenia (n = 281) and healthy controls (n = 172), recruited across five Australian sites. Interactions between diagnostic status and the number of haplotype copies (0 or ≥1) were tested across all white matter voxels with cluster-based statistics. Fractional anisotropy (FA) in the right parietal lobe was found to show a significant interaction between diagnosis andST8SIA2protective haplotype (p < 0.05, family-wise error rate (FWER) cluster-corrected). The protective haplotype was associated with increased FA in controls, but this effect was reversed in people with schizophrenia. White matter fiber tracking revealed that the region-of-interest was traversed by portions of the superior longitudinal fasciculus, corona radiata, and posterior limb of internal capsule. Post hoc analysis revealed that reduced FA in this regional juncture correlated with reduced IQ in people with schizophrenia. TheST8SIA2risk haplotype copy number did not show any differential effects on white matter. This study provides a link between a common disease-associated haplotype and specific changes in white matter microstructure, which may relate to resilience or risk for mental illness, providing further compelling evidence for involvement ofST8SIA2in the pathophysiology of schizophrenia.
Polo-like kinase 4 mediates epithelial–mesenchymal transition in neuroblastoma via PI3K/Akt signaling pathway
Authors: Tian Xiangdong , Zhou Dejun , Chen Lu , Tian Yao , Zhong Benfu , Cao Yanna , Dong Qiuping , Zhou Meng , Yan Jie , Wang Yalei , Qiu Yanli , Zhang Lianmin , Li Zhongyuan , Wang Huijuan , Wang Daowei , Ying Guoguang , Zhao Qiang 
Published: January 2018

AbstractNeuroblastoma (NB) is the most common malignant tumor in infancy and most common extracranial solid tumor in childhood. With the improvement of diagnosis and treatment, the survival rate of patients with low-risk and intermediate-risk NB can reach up to 90%. In contrast, for high-risk NBs, the long-term survival rate is still <40% because of heterogeneity of this tumor. The pathogenesis of NB is still not explicit, therefore it is of great significance to explore the mechanism of NB tumorigenesis and discover new therapeutic targets for NB. Polo-like kinase 4 (PLK4), one of the polo-like kinase family members, is an important regulator of centriole replication. The aberrant expression of PLK4 was found in several cancers and a recent study has unraveled a novel function of PLK4 as a mediator of invasion and metastasis in Hela and U2OS cells. However, the function of PLK4 in NB development and progression remains to be elucidated. The study showed the expression level of PLK4 in NB tissues was remarkably upregulated and high expression of PLK4 was negatively correlated with clinical features and survival, which suggested that PLK4 could be a potential tumor-promoting factor of NB. Functional studies indicated downregulation of PLK4 suppressed migration and invasion and promoted apoptosis in NB cells. Further experiments showed that downregulation of PLK4 in NB cells inhibited EMT through the PI3K/Akt signaling pathway. Animal experiments demonstrated that the downregulation of PLK4 in SK-N-BE(2) cells dramatically suppressed tumorigenesis and metastasis. PLK4 may be a promising therapeutic target for NB.
Characterization of bone only metastasis patients with respect to tumor subtypes
Authors: Parkes Amanda , Clifton Katherine , Al-Awadhi Aydah , Oke Oluchi , Warneke Carla L. , Litton Jennifer K. , Hortobagyi Gabriel N. 
Published: January 2018

AbstractMetastatic breast cancer (MBC) patients with bone only metastasis (BOM) are a unique population with limited characterization. We identified patients followed at MD Anderson Cancer Center from 01/01/1997 to 12/31/2015 for at least 6 months with a BOM diagnosis as first site of metastasis. Tumor subtype (TS) was assessed by initial breast biopsy immunohistochemistry using hormonal receptor (HR) and HER2 status, with four subtypes identified: HR+/HER2−, HR+/HER2+, HR−/HER2−, HR−/HER2+. HR+ was defined as estrogen receptor or progesterone receptor ≥1%. We identified 1445 patients with BOM, 1048 with TS data available. Among these patients, the majority were HR+/HER2− (78%). Median time from breast cancer diagnosis to first bone metastasis was 2.3 years (95% CI 2.1, 2.5) and varied significantly by TS, with longer time to distant disease in HR+/HER2− patients relative to all other TS (p < .0001). Median overall survival (OS) from breast cancer diagnosis was 8.7 years (95% CI 8.0, 9.7) and varied significantly by TS with poorer OS for HR−/HER2− and HR-/HER2+ patients relative to HR+/HER2− TS (p < .0001). The 442 patients with de novo BOM disease, defined as bone metastasis diagnosis within 4 months of breast cancer diagnosis, had significantly shorter OS (p < .0001). Overall, several higher risk BOM subsets were identified in this analysis, most notably HR−/HER2+ and HR−/HER2− TS and de novo BOM patients.
Enhanced Skin Permeation of Anti-wrinkle Peptides via Molecular Modification
Authors: Lim Seng Han , Sun Yuanyuan , Thiruvallur Madanagopal Thulasi , Rosa Vinicius , Kang Lifeng 
Published: January 2018

AbstractWrinkles can have a negative effect on quality of life and Botox is one of the most effective and common treatments. Argireline (Arg0), a mimetic of Botox, has been found to be safer than Botox and effective in reducing wrinkles, with efficacies up to 48% upon 4 weeks of twice daily treatment. However, the skin permeation of Arg0 is poor, due to its large molecular weight and hydrophilicity. Arg0 exists in zwitterionic form and this charged state hindered its skin permeation. Chemical modification of the peptide structure to reduce the formation of zwitterions may result in increased skin permeability. We investigated a total of 4 peptide analogues (Arg0, Arg1, Arg2, Arg3), in terms of skin permeation and wrinkle reduction. The 4 peptides were dissolved in various propylene glycol and water co-solvents. Enhanced human skin permeation was demonstrated by both Arg2 and Arg3 in vitro. On the other hand, the abilities of the 4 analogues to reduce wrinkle formation were also compared using primary human dental pulp stem cells derived neurons. By measuring the inhibition of glutamate release from the neurons in vitro, it was shown that Arg3 was the most effective, followed by Arg1, Arg0 and Arg2.
Immunization with Transgenic Rodent Malaria Parasites Expressing Pfs25 Induces Potent Transmission-Blocking Activity
Authors: Sala K. A. , Angrisano F. , Da D. F. , Taylor I. J. , Churcher T. S. , Blagborough A. M. 
Published: January 2018

AbstractAn anti-malarial transmission blocking vaccine (TBV) would be an important tool for disease control or elimination, though current candidates have failed to induce high efficacy in clinical studies. The ookinete surface protein P25 is a primary target for TBV development, but heterologous expression of P25 with appropriate conformation is problematic and a pre-requisite for achieving functional titers. A potential alternative to recombinant/sub-unit vaccine is immunization with a non-pathogenic, whole-parasite vaccine. This study examines the ability of a purified transgenic rodent-malaria parasite (PbPfs25DR3), expressing Plasmodium falciparum P25 in native conformation on the P. berghei ookinete surface, to act as a TBV. Vaccination with purified PbPfs25DR3 ookinetes produces a potent anti-Pfs25 response and high transmission-blocking efficacy in the laboratory, findings that are then translated to experimentation on natural field isolates of P. falciparum from infected individuals in Burkina Faso. Efficacy is demonstrated in the lab and the field (up to 93.3%/97.1% reductions in transmission intensity respectively), with both a homologous strategy with one and two boosts, and as part of a prime-boost regime, providing support for the future development of a whole-parasite TBV.
Molecular Mechanism of Resveratrol’s Lipid Membrane Protection
Authors: Fei Qinqin , Kent David , Botello-Smith Wesley M. , Nur Fariah , Nur Saadia , Alsamarah Abdelaziz , Chatterjee Payal , Lambros Maria , Luo Yun 
Published: January 2018

AbstractResveratrol, a natural compound found in red wine and various vegetables, has drawn increasing interest due to its reported benefit in cardiovascular protection, neurodegenerative disorders, and cancer therapy. The mechanism by which resveratrol exerts such pleiotropic effects remains unclear. It remains as one of the most discussed polyphenol compounds in the debating "French Paradox". In this study, using molecular dynamics simulations of dipalmitoyl phosphatidylcholine (DPPC) bilayer with resveratrol, we generated a free energy map of resveratrol’s location and orientation of inside the lipid bilayer. We found that resveratrol increases the surface area per lipid and decreases membrane thickness, which is the opposite effect of the well-studied cholesterol on liquid phase DPPC. Most importantly, based on the simulation observation that resveratrol has a high probability of forming hydrogen bonds with sn-1 and sn-2 ester groups, we discovered a new mechanism using experimental approach, in which resveratrol protects both sn-1 and sn-2 ester bonds of DPPC and distearoyl phosphatidylcholine (DSPC) from phospholipase A1 (PLA1) and phospholipase A2 (PLA2) cleavage. Our study elucidates the new molecular mechanism of potential health benefits of resveratrol and possibly other similar polyphenols and provides a new paradigm for drug design based on resveratrol and its analogs.
Luminance gradient at object borders communicates object location to the human oculomotor system
Authors: Kilpeläinen Markku , Georgeson Mark A. 
Published: January 2018

AbstractThe locations of objects in our environment constitute arguably the most important piece of information our visual system must convey to facilitate successful visually guided behaviour. However, the relevant objects are usually not point-like and do not have one unique location attribute. Relatively little is known about how the visual system represents the location of such large objects as visual processing is, both on neural and perceptual level, highly edge dominated. In this study, human observers made saccades to the centres of luminance defined squares (width 4 deg), which appeared at random locations (8 deg eccentricity). The phase structure of the square was manipulated such that the points of maximum luminance gradient at the square’s edges shifted from trial to trial. The average saccade endpoints of all subjects followed those shifts in remarkable quantitative agreement. Further experiments showed that the shifts were caused by the edge manipulations, not by changes in luminance structure near the centre of the square or outside the square. We conclude that the human visual system programs saccades to large luminance defined square objects based on edge locations derived from the points of maximum luminance gradients at the square’s edges.
Biologically active constituents of the secretome of human W8B2+ cardiac stem cells
Authors: Nie Shuai , Wang Xin , Sivakumaran Priyadharshini , Chong Mark M. W. , Liu Xin , Karnezis Tara , Bandara Nadeeka , Takov Kaloyan , Nowell Cameron J. , Wilcox Stephen , Shambrook Mitch , Hill Andrew F. , Harris Nicole C. , Newcomb Andrew E. , Strappe Padraig , Shayan Ramin , Hernández Damián , Clarke Jordan , Hanssen Eric , Davidson Sean M. , Dusting Gregory J. , Pébay Alice , Ho Joshua W. K. , Williamson Nicholas , Lim Shiang Y. 
Published: January 2018

AbstractThe benefits of adult stem cells for repair of the heart have been attributed to the repertoire of salutary paracrine activities they appear to exert. We previously isolated human W8B2+cardiac stem cells (CSCs) and found they powerfully influence cardiomyocytes and endothelial cells to collectively promote cardiac repair and regeneration. Here, the complexity of the W8B2+CSC secretomes was characterised and examined in more detail. Using ion exchange chromatography to separate soluble proteins based on their net surface charge, the secreted factors responsible for the pro-survival activity of W8B2+CSCs were found within the low and medium cation fractions. In addition to the soluble proteins, extracellular vesicles generated from W8B2+CSCs not only exhibited pro-survival and pro-angiogenic activities, but also promoted proliferation of neonatal cardiomyocytes. These extracellular vesicles contain a cargo of proteins, mRNA and primary microRNA precursors that are enriched in exosomes and are capable of modulating collectively many of the cellular pathways involved in protein metabolism, cell growth, as well as cellular responses to stress and organisation of the extracellular matrix. Thus the W8B2+CSC secretome contains a multitude of bioactive paracrine factors we have now characterised, that might well be harnessed for therapeutic application for cardiac repair and regeneration.
Nanoparticle Properties Modulate Their Attachment and Effect on Carrier Red Blood Cells
Authors: Pan Daniel C. , Myerson Jacob W. , Brenner Jacob S. , Patel Priyal N. , Anselmo Aaron C. , Mitragotri Samir , Muzykantov Vladimir 
Published: January 2018

AbstractAttachment of nanoparticles (NPs) to the surface of carrier red blood cells (RBCs) profoundly alters their interactions with the host organism, decelerating NP clearance from the bloodstream while enabling NP transfer from the RBC surface to the vascular cells. These changes in pharmacokinetics of NPs imposed by carrier RBCs are favorable for many drug delivery purposes. On the other hand, understanding effects of NPs on the carrier RBCs is vital for successful translation of this novel drug delivery paradigm. Here, using two types of distinct nanoparticles (polystyrene (PSNP) and lysozyme-dextran nanogels (LDNG)) we assessed potential adverse and sensitizing effects of surface adsorption of NPs on mouse and human RBCs. At similar NP loadings (approx. 50 particles per RBC), adsorption of PSNPs, but not LDNGs, induces RBCs agglutination and sensitizes RBCs to damage by osmotic, mechanical and oxidative stress. PSNPs, but not LDNGs, increase RBC stiffening and surface exposure of phosphatidylserine, both known to accelerate RBC clearancein vivo. Therefore, NP properties and loading amounts have a profound impact on RBCs. Furthermore, LDNGs appear conducive to nanoparticle drug delivery using carrier RBCs.
Re-initiation of bottom water formation in the East Sea (Japan Sea) in a warming world
Authors: Yoon Seung-Tae , Chang Kyung-Il , Nam SungHyun , Rho TaeKeun , Kang Dong-Jin , Lee Tongsup , Park Kyung-Ae , Lobanov Vyacheslav , Kaplunenko Dmitry , Tishchenko Pavel , Kim Kyung-Ryul 
Published: January 2018

AbstractThe East Sea (Japan Sea), a small marginal sea in the northwestern Pacific, is ventilated deeply down to the bottom and sensitive to changing surface conditions. Addressing the response of this marginal sea to the hydrological cycle and atmospheric forcing would be helpful for better understanding present and future environmental changes in oceans at the global and regional scales. Here, we present an analysis of observations revealing a slowdown of the long-term deepening in water boundaries associated with changes of water formation rate. Our results indicate that bottom (central) water formation has been enhanced (reduced) with more (less) oxygen supply to the bottom (central) layer since the 2000s. This paper presents a new projection that allows a three-layered deep structure, which retains bottom water, at least until 2040, contrasting previous results. This projection considers recent increase of slope convections mainly due to the salt supply via air-sea freshwater exchange and sea ice formation and decrease of open-ocean convections evidenced by reduced mixed layer depth in the northern East Sea, resulting in more bottom water and less central water formations. Such vigorous changes in water formation and ventilation provide certain implications on future climate changes.