bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppression, disaggregation, and modulation of γ‐Synuclein fibrillation pathway by green tea polyphenol EGCG
Authors: Roy Sneha , Bhat Rajiv 
Published: November 2018

AbstractOligomerization of γ‐Synuclein is known to have implications for both neurodegeneration and cancer. Although it is known to co‐exist with the fibrillar deposits of α‐Synuclein (Lewy bodies), a hallmark in Parkinson's disease (PD), the effect of potential therapeutic modulators on the fibrillation pathway of γ‐Syn remains unexplored. By a combined use of various biophysical tools and cytotoxicity assays we demonstrate that the flavonoid epigallocatechin‐3‐gallate (EGCG) significantly suppresses γ‐Syn fibrillation by affecting its nucleation and binds with the unstructured, nucleus forming oligomers of γ‐Syn to modulate the pathway to form α‐helical containing higher‐order oligomers (~158 kDa and ~ 670 kDa) that are SDS‐resistant and conformationally restrained in nature. Seeding studies reveal that these oligomers although “on‐pathway” in nature, are kinetically retarded and rate‐limiting species that slows down fibril elongation. We observe that EGCG also disaggregates the protofibrils and mature γ‐Syn fibrils into similar SDS‐resistant oligomers. Steady‐state and time‐resolved fluorescence spectroscopy and isothermal titration calorimetry (ITC) reveal a weak non‐covalent interaction between EGCG and γ‐Syn with the dissociation constant in the mM range (Kd ~ 2–10 mM). Interestingly, while EGCG‐generated oligomers completely rescue the breast cancer (MCF‐7) cells from γ‐Syn toxicity, it reduces the viability of neuroblastoma (SH‐SY5Y) cells. However, the disaggregated oligomers of γ‐Syn are more toxic than the disaggregated fibrils for MCF‐7cells. These findings throw light on EGCG‐mediated modulation of γ‐Syn fibrillation and suggest that investigation on the effects of such modulators on γ‐Syn fibrillation is critical in identifying effective therapeutic strategies using small molecule modulators of synucleopathies.
Probing the modularity of megasynthases by rational engineering of a fatty acid synthase Type I
Authors: Rittner Alexander , Paithankar Karthik S. , Drexler David Jan , Himmler Aaron , Grininger Martin 
Published: November 2018

AbstractModularity is a fundamental property of megasynthases such as polyketide synthases (PKSs). In this study, we exploit the close resemblance between PKSs and animal fatty acid synthase (FAS) to re‐engineer animal FAS to probe the modularity of the FAS/PKS family. Guided by sequence and structural information, we truncate and dissect animal FAS into its components, and reassemble them to generate new PKS‐like modules as well as bimodular constructs. The novel re‐engineered modules resemble all four common types of PKSs and demonstrate that this approach can be a powerful tool to deliver products with higher catalytic efficiency. Our data exemplify the inherent plasticity and robustness of the overall FAS/PKS fold, and open new avenues to explore FAS‐based biosynthetic pathways for custom compound design.
Investigation of amodiaquine localization in liver lobules using matrix‐assisted laser desorption/ionization imaging mass spectrometry
Authors: Grove Kerri J. , Hoque Shaila , Rudewicz Patrick J. 
Published: November 2018

RationaleHigh mass and high spatial resolution matrix‐assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) opens new possibilities for the detailed study of the hepatic metabolism of drugs. The spatial and temporal distribution of drug metabolites within liver lobules, anatomical subunits of the liver, may aid in the understanding of the formation of reactive metabolites that bind to liver proteins and cause drug‐induced liver injury.MethodsFrozen livers obtained from rats dosed orally with amodiaquine (100 mg/kg) were sectioned at 10 μm and coated with a MALDI matrix. The liver sections were then analyzed using a Fourier transform ion cyclotron resonance mass spectrometer. Images corresponding to amodiaquine and its metabolites were obtained at a spatial resolution of 25 μm.ResultsMolecular images of amodiaquine within liver lobules have higher intensities near the portal triad and lower intensities near the central vein.ConclusionsThis study demonstrates that MALDI IMS can be used to investigate the metabolism of drugs within liver lobules. The results are consistent with existing knowledge of amodiaquine metabolism and reactive metabolite formation.
Mesenchymal Stem Cells and Induced Bone Marrow-Derived Macrophages Synergistically Improve Liver Fibrosis in Mice
Authors: Watanabe Yusuke , Tsuchiya Atsunori , Seino Satoshi , Kawata Yuzo , Kojima Yuichi , Ikarashi Shunzo , Starkey Lewis Philip J. , Lu Wei-Yu , Kikuta Junichi , Kawai Hirokazu , Yamagiwa Satoshi , Forbes Stuart J. , Ishii Masaru , Terai Shuji 
Published: November 2018

Abstract
We describe a novel therapeutic approach for cirrhosis using mesenchymal stem cells (MSCs) and colony-stimulating factor-1-induced bone marrow-derived macrophages (id-BMMs) and analyze the mechanisms underlying fibrosis improvement and regeneration. Mouse MSCs and id-BMMs were cultured from mouse bone marrow and their interactions analyzed in vitro. MSCs, id-BMMs, and a combination therapy using MSCs and id-BMMs were administered to mice with CCl4-induced cirrhosis. Fibrosis regression, liver regeneration, and liver-migrating host cells were evaluated. Administered cell behavior was also tracked by intravital imaging. In coculture, MSCs induced switching of id-BMMs toward the M2 phenotype with high phagocytic activity. In vivo, the combination therapy reduced liver fibrosis (associated with increased matrix metalloproteinases expression), increased hepatocyte proliferation (associated with increased hepatocyte growth factor, vascular endothelial growth factor, and oncostatin M in the liver), and reduced blood levels of liver enzymes, more effectively than MSCs or id-BMMs monotherapy. Intravital imaging showed that after combination cell administration, a large number of id-BMMs, which phagocytosed hepatocyte debris and were retained in the liver for more than 7 days, along with a few MSCs, the majority of which were trapped in the lung, migrated to the fibrotic area in the liver. Host macrophages and neutrophils infiltrated after combination therapy and contributed to liver fibrosis regression and promoted regeneration along with administered cells. Indirect effector MSCs and direct effector id-BMMs synergistically improved cirrhosis along with host cells in mice. These studies pave the way for new treatments for cirrhosis. Stem Cells Translational Medicine 2019;8:271&284
Metal‐Free Assemblage of Four C−N and Two C−C Bonds via a Cascade Five Component Diastereoselective Synthesis of Pyrido[1,2‐a]Pyrimidines
Authors: Rezvanian Atieh , Alinaghian Fereshteh , Heravi Majid M. 
Published: November 2018

AbstractAn efficient heteroannulation synthesis of N‐fused, pyrido[1,2‐a]pyrimidines was successfully achieved via a sequential, one‐pot five‐component reaction, involving primary amines, diketene (DK), differently substituted aromatic aldehydes, nitro ketene dithioacetal and propanediamine in ethanol at 70 °C. This new protocol constructs two rings through the formation of four C–N and two C–C bonds via a one pot sequential reaction involving ring‐opening/ Knoevenagel condensation, /nucleophilic substitution (SN)/ Michael addition followed by imine−enamine tautomerization and final N‐heterocyclization. The method is particularly attractive due to the advantages such as: atom economy, optimum convergence, commercially available or readily accessible starting materials, high bond‐forming efficiency, free metal‐catalyst and mild reaction conditions. The products were isolated by just decantation of the solvent and purification without using column chromatography method.
1,4‐Piperazinium Hydrogen Sulfate {[H‐pi]HSO4} a Novel Di‐Cationic Ionic Liquid: Synthesis, Characterization and Its Applications as a Catalyst in Various Organic Transformations
Authors: Jashnani S. , Seddighi M. , Langarudi M. S. N. , Shirini F. 
Published: November 2018

AbstractIn this work, a new nitrogen and sulfur based di‐cationic ionic liquid (IL), named 1,4‐piperazinium hydrogen sulfate ([H‐pi]HSO4), was simply synthesized from the reaction of piperazine with sulfuric acid, and then characterized with a variety of techniques, including Infrared (IR) and Nuclear Magnetic Resonance (NMR) spectroscopies, Thermo‐gravimetric analysis (TGA), Scanning Electron Microscope (SEM), and pH analysis. This new ionic liquid was employed as an efficient catalyst for the synthesis of 2,2′‐arylmethylene‐bis(3‐hydroxy‐5,5‐dimethyl‐2‐cyclohexene‐1‐one) and 1,8‐dioxooctahydroxanthene derivatives in C2H5OH:H2O media and under solvent‐free conditions, respectively. Also, this adequate catalyst was employed for the synthesis of imidazo[1,2‐a]pyrimidines and triazolo[4,3‐a]pyrimidinesviathree‐component reaction of aldehydes, malononitrile and 2‐aminobenzimidazole and/or 3‐amino[1,2,4]triazole. The new functionally‐structured products, synthesized through these methods, were characterized with IR,1H NMR,13C NMR and mass spectroscopy. Moreover, the procedures gave the products in good yields and short reaction times as well as reusability of the catalyst.
Evaluation of owners’ attitudes towards veterinarian attire in the small animal specialty setting in North America
Authors: Robb Kathryn A. , Rossi Tracey A. , Tansey Colleen , Hybki Gabrielle C. , Murphy Lisa A. , Nakamura Reid K. , Chen Dillon Y. 
Published: November 2018

AbstractPrevious studies in human medicine have found that patients prefer their doctors to be more formally attired, and that this influences their trust and confidence in their physician. The purpose of this study was to evaluate how veterinarians’ attire affected owners’ impressions and trust in the small animal specialty medicine setting. A questionnaire based study conducted during a 2‐month period at an urban based small animal private practice specialty hospital. Respondents completed a written survey after reviewing pictures of the same male and female veterinarian in five different dress styles. Respondents were asked for their preference for male and female veterinarian attire in different clinical scenarios and whether it would affect their willingness to discuss sensitive issues. Two hundred and thirty‐eight questionnaires were completed during the study period with 76.1% of respondents being female. Female respondents did not have a preference to how a male or female veterinarian was attired with the attire examples provided. However, male respondents tended to have fairly equal response rates between no preference and preferring a male veterinarian to be in either clinical or professional attire. Male owners either had no preference or preferred their male veterinarian to be attired in clinical or professional attire and had no preference or preferred their female veterinarian to be clinical attire. Most respondents do not feel it is necessary for a veterinarian to wear a white coat or neck ties and most do not feel it is inappropriate for a veterinarian to wear blue jeans, have coloured hair, or have visible tattoos.
Distance‐based clustering of mixed data
Authors: van de Velden Michel , Iodice D'Enza Alfonso , Markos Angelos 
Published: November 2018

Cluster analysis comprises of several unsupervised techniques aiming to identify a subgroup (cluster) structure underlying the observations of a data set. The desired cluster allocation is such that it assigns similar observations to the same subgroup. Depending on the field of application and on domain‐specific requirements, different approaches exist that tackle the clustering problem. In distance‐based clustering, a distance metric is used to determine the similarity between data objects. The distance metric can be used to cluster observations by considering the distances between objects directly or by considering distances between objects and cluster centroids (or some other cluster representative points). Most distance metrics, and hence the distance‐based clustering methods, work either with continuous‐only or categorical‐only data. In applications, however, observations are often described by a combination of both continuous and categorical variables. Such data sets can be referred to as mixed or mixed‐type data. In this review, we consider different methods for distance‐based cluster analysis of mixed data. In particular, we distinguish three different streams that range from basic data preprocessing (where all variables are converted to the same scale), to the use of specific distance measures for mixed data, and finally to so‐called joint data reduction (a combination of dimension reduction and clustering) methods specifically designed for mixed data.This article is categorized under:
Statistical Learning and Exploratory Methods of the Data Sciences > Clustering and Classification
Statistical Learning and Exploratory Methods of the Data Sciences > Exploratory Data Analysis
Statistical and Graphical Methods of Data Analysis > Dimension Reduction
Generalised Born-Infeld models, Lax operators and the $$ \mathrm{T}\overline{\mathrm{T}} $$ perturbation
Authors: Conti Riccardo , Iannella Leonardo , Negro Stefano , Tateo Roberto 
Published: November 2018

Abstract

Surprising links between the deformation of 2D quantum field theories induced by the composite

$$ \mathrm{T}\overline{\mathrm{T}} $$

T

T
¯

operator, effective string models and the AdS/CFT correspondence, have recently emerged. The purpose of this article is to discuss various classical aspects related to the deformation of 2D interacting field theories. Special attention is given to the sin(h)-Gordon model, for which we were able to construct the

$$ \mathrm{T}\overline{\mathrm{T}} $$

T

T
¯

-deformed Lax pair. We consider the Lax pair formulation to be the first essential step toward a more satisfactory geometrical interpretation of this deformation within the integrable model framework.
Furthermore, it is shown that the 4D Maxwell-Born-Infeld theory, possibly with the addition of a mass term or a derivative-independent potential, corresponds to a natural extension of the 2D examples. Finally, we briefly comment on 2D Yang-Mills theory and propose a modification of the heat kernel, for a generic surface with genus p and n boundaries, which fully accounts for the

$$ \mathrm{T}\overline{\mathrm{T}} $$

T

T
¯

contribution.
Scaphoid Fracture Repair Does Not Significantly Diminish Short-Term Participation in the National Football League
Authors: Knapik Derrick M. , Tu Leigh-Anne , Sheehan Joseph , Salata Michael J. , Voos James E. , Malone Kevin J. 
Published: November 2018

Background Fixation of scaphoid fractures is recommended in elite athletes to hasten healing and return-to-sport times. Complications such as nonunion negatively affect athletic performance. Questions/Purposes The purpose of this study was to examine the prevalence and impact of scaphoid repair on National Football League (NFL) participation during athletes’ first season in the NFL, while identifying significant predictors for development of carpal arthritis and scaphoid nonunion. Methods A total of 1311 football athletes invited to the NFL Scouting Combine from 2012 to 2015 were evaluated for history of scaphoid fracture repair. Athlete demographics, surgical history, and imaging and physical examination findings were recorded. Future NFL participation based on draft status, games played, and games started during athletes’ first season were gathered using publicly available databases. Results Nineteen (1.4%) athletes underwent 24 operations for scaphoid repair. Limitations in wrist range of motion or strength were present in 47.4% of athletes with a history of repair. Arthritic changes were present in 32% of wrists, while radiographic nonunion was present in two athletes following scaphoid fracture. Defensive backs were observed to have a higher incidence for arthritic changes following repair compared to other positions. No significant difference in prospective NFL participation was found in athletes with a history of scaphoid repair than in those without. Conclusions Athletes with a history of scaphoid repair are not at significant risk for diminished participation during their first season in the NFL.
Introduction to Machine Learning in Digital Healthcare Epidemiology
Authors: Roth Jan A. , Battegay Manuel , Juchler Fabrice , Vogt Julia E. , Widmer Andreas F. 
Published: November 2018

AbstractTo exploit the full potential of big routine data in healthcare and to efficiently communicate and collaborate with information technology specialists and data analysts, healthcare epidemiologists should have some knowledge of large-scale analysis techniques, particularly about machine learning. This review focuses on the broad area of machine learning and its first applications in the emerging field of digital healthcare epidemiology.
A recipe for antimicrobial stewardship success: Using intervention mapping to develop a program to reduce antibiotic overuse in long-term care
Authors: Chambers Andrea , MacFarlane Sam , Zvonar Rosemary , Evans Gerald , Moore Julia E. , Langford Bradley J. , Augustin Anne , Cooper Sue , Quirk Jacquelyn , McCreight Liz , Garber Gary 
Published: November 2018

AbstractObjectiveTo better understand barriers and facilitators that contribute to antibiotic overuse in long-term care and to use this information to inform an evidence and theory-informed program.MethodsInformation on barriers and facilitators associated with the assessment and management of urinary tract infections were identified from a mixed-methods survey and from focus groups with stakeholders working in long-term care. Each barrier or facilitator was mapped to corresponding determinants of behavior change, as described by the theoretical domains framework (TDF). The Rx for Change database was used to identify strategies to address the key determinants of behavior change.ResultsIn total, 19 distinct barriers and facilitators were mapped to 8 domains from the TDF: knowledge, skills, environmental context and resources, professional role or identity, beliefs about consequences, social influences, emotions, and reinforcements. The assessment of barriers and facilitators informed the need for a multifaceted approach with the inclusion of strategies (1) to establish buy-in for the changes; (2) to align organizational policies and procedures; (3) to provide education and ongoing coaching support to staff; (4) to provide information and education to residents and families; (5) to establish process surveillance with feedback to staff; and (6) to deliver reminders.ConclusionsThe use of a stepped approach was valuable to ensure that locally relevant barriers and facilitators to practice change were addressed in the development of a regional program to help long-term care facilities minimize antibiotic prescribing for asymptomatic bacteriuria. This stepped approach provides considerable opportunity to advance the design and impact of antimicrobial stewardship programs.
Facing uncertainty: An entrepreneurial view of the future?
Authors: Bridge Simon 
Published: November 2018

AbstractIn business the future is not predetermined, and the unexpected often happens. So how should entrepreneurs (and businesses) try to address that future uncertainty? This paper suggests that there are two main options:1.The often-preferred approach seeks to reduce uncertainty by forecasting and planning, using ‘left-brained’ logic and analysis.2.The alternative way seeks to live with, and to benefit from, uncertainty by using ideas derived from exploration, effectuation, antifragility and ‘trial and error’.This paper compares the two approaches and considers their rationales and potential effectiveness. It suggests that forecasting and planning has many drawbacks and is often not the best way to operate in uncertain conditions. Nevertheless, it is often advocated and its thinking seems to have been adopted as the default philosophy for business. Therefore if, as has been suggested, uncertainty is the norm, do we need to advocate adopting a different way of thinking?
‘Sometimes you just need someone to take a chance on you’: An internship programme for autistic graduates at Deutsche Bank, UK
Authors: Remington Anna , Pellicano Elizabeth 
Published: November 2018

AbstractAutistic individuals often face significant challenges to obtaining and maintaining meaningful employment – more so than other disability groups. Work placements appear to be an important step to promote employment outcomes, yet there remains a lack of knowledge about the real-life experiences of those involved in such schemes. This study is the first to take a multi-informant, longitudinal approach to examine corporate work-placement schemes: specifically, an internship for autistic graduates at Deutsche Bank, UK. Semi-structured interviews were carried out with interns, their hiring managers and the colleagues who worked alongside them. Results demonstrated positive, meaningful experiences for the majority of those involved, however, some interns also reported anxiety, difficulties in judging communication and confusion regarding office rules. The current findings contribute to a better understanding of the experiences of skilled autistic individuals in work, and should inform the creation of subsequent programmes aimed to promote employment opportunities for autistic people.
Existence of outsiders as a characteristic of online communication networks
Authors: TAKAGUCHI TARO , MAEHARA TAKANORI , KAWARABAYASHI KEN-ICHI , TOYODA MASASHI 
Published: November 2018

AbstractOnline social networking services involve communication activities between large number of individuals over the public Internet and their crawled records are often regarded as proxies of real (i.e., offline) interaction structure. However, structure observed in these records might differ from real counterparts because individuals may behave differently online and non-human accounts may even participate. To understand the difference between online and real social networks, we investigate an empirical communication network between users on Twitter, which is perhaps one of the largest social networking services. We define a network of user pairs that send reciprocal messages. Based on the correlation between degree of adjacent nodes observed in this network, we hypothesize that this network differs from conventional understandings in the sense that there is a small number of distinctive users that we call outsiders. Outsiders do not belong to any user groups but they are connected with different groups, while not being well connected with each other. We identify outsiders by maximizing the degree assortativity coefficient of the network via node removal, thereby confirming that local structural properties of outsiders identified are consistent with our hypothesis. Our findings suggest that the existence of outsiders should be considered when using Twitter communication networks for social network analysis.