bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tunable Bifunctional Phosphine–Squaramide Promoted Morita–Baylis–Hillman Reaction of N‐Alkyl Isatins with Acrylates
Authors: Dong Ze , Yan Chao , Gao Yongzhi , Dong Chune , Qiu Guofu , Zhou Hai‐Bing 
Published: April 2015

AbstractA series of highly tunable bifunctional phosphine‐squaramide H‐bond donor organocatalysts 6 has been synthesized from inexpensive and commercially available β‐amino alcohols in moderate yields. Catalyst 6 f can efficiently promote the asymmetric Morita–Baylis–Hillman (MBH) reaction of N‐alkyl isatins with acrylate esters providing the chiral 3‐substituted 3‐hydroxy‐2‐oxindoles in good yields and enantioselectivities (up to 93 % yield and 95 % ee), in which the challenging substrate tert‐butyl acrylate 9 d, provided the best ee value to date. Moreover, this methodology was applied successfully in the synthesis of chiral cyclic spiropyrrolizidineoxindole and γ‐butyrolactone derivatives without enantioselectivity deterioration. The possible mechanism of this MBH reaction was also investigated by 31P NMR, ESI‐MS and KIE studies. The KIE experiments show that the electrophilic addition of N‐methyl isatin to the complex of acrylate ester and phophine‐squaramide is the rate‐determing step of the asymmetric MBH reaction.magnified image
Mitochondrial diversity of Iñupiat people from the Alaskan North Slope provides evidence for the origins of the Paleo‐ and Neo‐Eskimo peoples
Authors: Raff Jennifer A. , Rzhetskaya Margarita , Tackney Justin , Hayes M. Geoffrey 
Published: April 2015

ABSTRACTObjectives:All modern Iñupiaq speakers share a common origin, the result of a recent (∼800 YBP) and rapid trans‐Arctic migration by the Neo‐Eskimo Thule, who replaced the previous Paleo‐Eskimo inhabitants of the region. Reduced mitochondrial haplogroup diversity in the eastern Arctic supports the archaeological hypothesis that the migration occurred in an eastward direction. We tested the hypothesis that the Alaskan North Slope served as the origin of the Neo‐ and Paleo‐Eskimo populations further east.Materials and Methods:We sequenced HVR I and HVR II of the mitochondrial D‐loop from 151 individuals in eight Alaska North Slope communities, and compared genetic diversity and phylogenetic relationships between the North Slope Inupiat and other Arctic populations from Siberia, the Aleutian Islands, Canada, and Greenland.Results:Mitochondrial lineages from the North Slope villages had a low frequency (2%) of non‐Arctic maternal admixture, and all haplogroups (A2, A2a, A2b, D2a, and D4b1a–formerly known as D3) found in previously sequenced Neo‐ and Paleo‐Eskimos and living Inuit and Eskimo peoples from across the North American Arctic. Lineages basal for each haplogroup were present in the North Slope. We also found the first occurrence of two haplogroups in contemporary North American Arctic populations: D2a, previously identified only in Aleuts and Paleo‐Eskimos, and the pan‐American C4.Discussion:Our results yield insight into the maternal population history of the Alaskan North Slope and support the hypothesis that this region served as an ancestral pool for eastward movements to Canada and Greenland, for both the Paleo‐Eskimo and Neo‐Eskimo populations. Am J Phys Anthropol 157:603–614, 2015. © 2015 Wiley Periodicals, Inc.
Dendrimeric siRNA for Efficient Gene Silencing
Authors: Hong Cheol Am , Eltoukhy Ahmed A. , Lee Hyukjin , Langer Robert , Anderson Daniel G. , Nam Yoon Sung 
Published: April 2015

AbstractProgrammable molecular self‐assembly of siRNA molecules provides precisely controlled generation of dendrimeric siRNA nanostructures. The second‐generation dendrimers of siRNA can be effectively complexed with a low‐molecular‐weight, cationic polymer (poly(β‐amino ester), PBAE) to generate stable nanostructures about 160 nm in diameter via strong electrostatic interactions. Condensation and gene silencing efficiencies increase with the increased generation of siRNA dendrimers due to a high charge density and structural flexibility.
High‐Fidelity Noncovalent Synthesis of Hydrogen‐Bonded Macrocyclic Assemblies
Authors: Montoro‐García Carlos , Camacho‐García Jorge , López‐Pérez Ana M. , Bilbao Nerea , Romero‐Pérez Sonia , Mayoral María J. , González‐Rodríguez David 
Published: April 2015

AbstractA hydrogen‐bonded cyclic tetramer is assembled with remarkably high effective molarities from a properly designed dinucleoside monomer. This self‐assembled species exhibits an impressive thermodynamic and kinetic stability and is formed with high fidelities within a broad concentration range.
Low‐Temperature Isolation of the Bicyclic Phosphinophosphonium Salt [Mes*2P4Cl][GaCl4]
Authors: Bresien Jonas , Faust Kirill , Schulz Axel , Villinger Alexander 
Published: April 2015

AbstractThe reaction of [ClP(μ‐PMes*)]2 (1) with the Lewis acid GaCl3 yielded a hitherto unknown tetraphosphabicyclo[1.1.0]butan‐2‐ium salt, [Mes*P4(Cl)Mes*][GaCl4] (3[GaCl4]), which incorporates a positively charged phosphonium center within its bicyclic P4 scaffold. The formation of the title compound was studied by means of low‐temperature NMR experiments. This led to the identification of an intermediate cyclotetraphosphenium cation, which was trapped by reaction with dimethylbutadiene (dmb). All of the compounds were fully characterized by experimental and computational methods.
Balance and Strength—Estimating the Maximum Prey‐Lifting Potential of the Large Predatory Dinosaur Carcharodontosaurus saharicus
Authors: Henderson Donald M. , Nicholls Robert 
Published: April 2015

ABSTRACTMotivated by the work of palaeo‐art “Double Death (2011),” a biomechanical analysis using three‐dimensional digital models was conducted to assess the potential of a pair of the large, Late Cretaceous theropod dinosaur Carcharodontosaurus saharicus to successfully lift a medium‐sized sauropod and not lose balance. Limaysaurus tessonei from the Late Cretaceous of South America was chosen as the sauropod as it is more completely known, but closely related to the rebbachisaurid sauropods found in the same deposits with C. saharicus. The body models incorporate the details of the low‐density regions associated with lungs, systems of air sacs, and pneumatized axial skeletal regions. These details, along with the surface meshes of the models, were used to estimate the body masses and centers of mass of the two animals. It was found that a 6 t C. saharicus could successfully lift a mass of 2.5 t and not lose balance as the combined center of mass of the body and the load in the jaws would still be over the feet. However, the neck muscles were found to only be capable of producing enough force to hold up the head with an added mass of 424 kg held at the midpoint of the maxillary tooth row. The jaw adductor muscles were more powerful, and could have held a load of 512 kg. The more limiting neck constraint leads to the conclusion that two, adult C. saharicus could successfully lift a L. tessonei with a maximum body mass of 850 kg and a body length of 8.3 m. Anat Rec, 298:1367–1375, 2015. © 2015 Wiley Periodicals, Inc.
Brief Report: Endothelial Progenitor Cell Phenotype and Function Are Impaired in Childhood‐Onset Systemic Lupus Erythematosus
Authors: Mohan Smriti , Barsalou Julie , Bradley Timothy J. , Slorach Cameron , Reynolds John A. , Hasni Sarfaraz , Thompson Becky , Ng Lawrence , Levy Deborah , Silverman Earl , Kaplan Mariana J. 
Published: April 2015

ObjectiveSystemic lupus erythematosus (SLE) is characterized by increased cardiovascular risk in adult‐onset and childhood‐onset SLE. Type I interferons (IFNs) appear to play a prominent role in premature vascular damage in adult‐onset SLE, at least in part, by inducing impairments in the phenotype and function of endothelial progenitor cells (EPCs), thereby hampering vascular repair. It is not clear whether EPC dysfunction is present in childhood‐onset SLE in association with a type I IFN signature.MethodsThe phenotype and numbers of EPCs were quantified in patients with childhood‐onset SLE, patients with juvenile idiopathic arthritis (JIA), and matched healthy control subjects. In a separate cohort of patients with childhood‐onset SLE, markers of subclinical atherosclerosis and endothelial dysfunction were quantified using standardized protocols and analyzed for associations with serum type I IFN activity.ResultsEPC numbers and function were significantly decreased in patients with childhood‐onset SLE compared with patients with JIA and healthy control subjects. Serum from patients with childhood‐onset SLE impaired differentiation of EPCs into mature endothelial cells in healthy controls, and this effect was blocked by inhibition of the type I IFN pathway. Type I IFN activity in serum was not significantly associated with subclinical atherosclerosis and endothelial function in patients with childhood‐onset SLE.ConclusionAs in adult‐onset SLE, childhood‐onset SLE is characterized by phenotypic and functional EPC abnormalities, which are likely triggered by type I IFNs. Although cross‐sectional analysis revealed no global association between type I IFN signatures and vascular measures of subclinical atherosclerosis, longitudinal assessments are needed to evaluate whether progression of vascular damage in patients with childhood‐onset SLE is associated with type I IFNs, as observed in patients with adult‐onset SLE.
CD147/Basigin Limits Lupus Nephritis and Th17 Cell Differentiation in Mice by Inhibiting the Interleukin‐6/STAT‐3 Pathway
Authors: Maeda Kayaho , Kosugi Tomoki , Sato Waichi , Kojima Hiroshi , Sato Yuka , Kamimura Daisuke , Kato Noritoshi , Tsuboi Naotake , Yuzawa Yukio , Matsuo Seiichi , Murakami Masaaki , Maruyama Shoichi , Kadomatsu Kenji 
Published: April 2015

ObjectiveInterleukin‐17 (IL‐17)–producing T cells (Th17 cells) play critical roles in the pathogenesis of immune‐related diseases, including systemic lupus erythematosus. However, the fundamental mechanism regulating Th17 cell differentiation is not fully understood. Recently, we demonstrated that plasma levels of CD147/basigin (Bsg) in patients with lupus nephritis (LN) were closely associated with disease activity. but the molecular mechanism involving Bsg has been elusive. Here, we addressed the role of Bsg in the pathogenesis of LN.MethodsInjections of pristane (2,6,10,14‐tetramethylpentadecane [TMPD]) were administered to Bsg−/− or Bsg+/+ mice to induce LN. The mice were killed 6 months after being injected, for histologic and biochemical analyses of the kidneys and spleens.ResultsPristane induced LN more strikingly in Bsg−/− mice than in Bsg+/+ mice, even though humoral autoimmunity was similarly increased in both genotypes. The increased number of Th17, but not Th1, Treg cells, was augmented in Bsg−/− mice. The expression of IL‐17 was also increased in the kidneys of Bsg−/− mice, in proportion to LN disease activity. Furthermore, treatment with anti–IL‐17 antibody reduced LN disease activity in Bsg−/− mice. Complementary to these phenotypes of Bsg−/− mice, Bsg expression was enhanced in activated CD4+ T cells in vivo and in vitro. Bsg deficiency selectively augmented in vitro differentiation of naive CD4+ T cells to Th17 cells and STAT‐3 phosphorylation during this differentiation. Moreover, STAT‐3 phosphorylation was suppressed by crosslinking of Bsg with its antibody.ConclusionBsg plays an indispensable role in Th17 cell differentiation as a negative regulator by suppressing the IL‐6/STAT‐3 pathway.
Shared Epitope–Antagonistic Ligands: A New Therapeutic Strategy in Mice With Erosive Arthritis
Authors: Ling Song , Liu Ying , Fu Jiaqi , Colletta Alessandro , Gilon Chaim , Holoshitz Joseph 
Published: April 2015

ObjectiveThe mechanisms underlying bone damage in rheumatoid arthritis (RA) are incompletely understood. We recently identified the shared epitope (SE), an HLA–DRB1–coded 5–amino acid sequence motif carried by the majority of RA patients as a signal transduction ligand that interacts with cell surface calreticulin and accelerates osteoclast (OC)–mediated bone damage in collagen‐induced arthritis (CIA). Given the role of the SE/calreticulin pathway in arthritis‐associated bone damage, we sought to determine the therapeutic targetability of calreticulin.MethodsA library of backbone‐cyclized peptidomimetic compounds, all carrying an identical core DKCLA sequence, was synthesized. The ability of these compounds to inhibit SE‐activated signaling and OC differentiation was tested in vitro. The effect on disease severity and OC‐mediated bone damage was studied by weekly intraperitoneal administration of the compounds to DBA/1 mice with CIA.ResultsTwo members of the peptidomimetics library were found to have SE‐antagonistic effects and antiosteoclast differentiation effects at picomolar concentrations in vitro. The lead mimetic compound, designated HS(4‐4)c Trp, potently ameliorated arthritis and bone damage in vivo when administered in picogram doses to mice with CIA. Another mimetic analog, designated HS(3‐4)c Trp, was found to lack activity, both in vitro and in vivo. The differential activity of the 2 analogs depended on minor differences in their respective ring sizes and correlated with distinctive geometry when computationally docked to the SE binding site on calreticulin.ConclusionThese findings identify calreticulin as a novel therapeutic target in erosive arthritis and provide sound rationale and early structure/activity relationships for future drug design.
The Anergy Induction of M3 Muscarinic Acetylcholine Receptor–Reactive CD4+ T Cells Suppresses Experimental Sialadenitis‐like Sjögren's Syndrome
Authors: Asashima Hiromitsu , Tsuboi Hiroto , Takahashi Hiroyuki , Hirota Tomoya , Iizuka Mana , Kondo Yuya , Matsui Minoru , Matsumoto Isao , Sumida Takayuki 
Published: April 2015

ObjectiveAutoreactive CD4+ T cells are involved in the pathogenesis of Sjögren's syndrome (SS). The aim of the present study was to clarify the dominant T cell epitopes of M3 muscarinic acetylcholine receptor (M3R) and to establish a new antigen‐specific therapy for SS using an experimental mouse model.MethodsProduction of cytokines from M3R‐reactive CD4+ T cells, after culture with various M3R peptides, was analyzed by enzyme‐linked immunosorbent assay. Adoptive cell transfer was performed using splenocytes from M3R−/− mice that were immunized with M3R peptides or phosphate buffered saline plus H37Ra as a control. Rag1−/− mice were inoculated with the splenocytes and examined for the development of sialadenitis. Altered peptide ligands (APLs) of the T cell epitopes, with substitutions in amino acid residues at T cell receptor contact sites, were synthesized, and the ability of the APLs to suppress sialadenitis was evaluated. The mechanisms underlying such effects were assessed.ResultsCD4+ M3R‐reactive T cells produced interleukin‐17 (IL‐17) and interferon‐γ (IFNγ) in response to the N‐terminal 1 (N1) and 1st extracellular loop peptides of M3R, and Rag1−/− mice that received N1‐ and/or 1st peptide–immunized splenocytes developed sialadenitis. Among the designed APLs, N1‐APL7 (N→S at amino acid 15) significantly suppressed IFNγ production in vitro, and also suppressed sialadenitis in vivo. Levels of early growth response 2 in CD4+ T cells from the cervical lymph nodes of N1‐APL7–treated mice were significantly higher than those of control mice, and cell proliferation was reversed by administration of exogenous IL‐2. Levels of the anergy‐related molecules itchy homolog E3 ubiquitin‐protein ligase, Casitas B‐lineage lymphoma b, gene related to anergy in lymphocytes, and Deltex‐1 were significantly higher in CD4+ T cells cultured with N1‐APL7.ConclusionThe major T cell epitopes were from the N1 and 1st peptide regions. Moreover, N1‐APL7, selected as the antagonistic APL in vitro, also suppressed sialadenitis through the induction of anergy. This is a potentially useful strategy for regulating pathogenic T cell infiltration in SS.
Verbalization of Decision Strategies in Multiple‐Cue Probabilistic Inference
Authors: Walsh Matthew M. , Gluck Kevin A. 
Published: April 2015

AbstractIn multiple‐cue probabilistic inference, people choose between alternatives based on several cues, each of which is differentially associated with an alternative's overall value. Various strategies have been proposed for probabilistic inference (e.g., weighted additive, tally, and take‐the‐best). These strategies differ in how many cue values they require to enact and in how they weight each cue. Do decision makers actually use any of these strategies? Ways to investigate this question include analyzing people's choices and the cues that they reveal. However, different strategies often predict the same decisions, and search behavior says nothing about whether or how people use the information that they acquire. In this research, we attempt to elucidate which strategies participants use in a multiple‐cue probabilistic inference task by examining verbal protocols, a high‐density source of process data. The promise of verbal data is in their utility for testing detailed information processing models. To that end, we apply protocol analysis in conjunction with computational simulations. We find converging evidence across outcome measures, search measures, and verbal reports that most participants use simplifying heuristics, namely take‐the‐best. Copyright © 2015 John Wiley & Sons, Ltd.
Understanding and managing taxonomies as economic goods and services
Authors: Bedford Denise A. D. 
Published: April 2015

EDITOR'S SUMMARYAs pervasive as taxonomies have become in knowledge management, their economic value is not often scrutinized, documented or fulfilled. Taxonomies range in cost and sophistication from flat lists through thesauri, semantic nets and faceted systems. Each can be an asset or liability to varying degrees relative to the resources expended to design, manage and implement it. A well‐designed taxonomy produces value by enabling consistent information management, facilitating records management and compliance, building domain understanding and saving time through efficient access to information. Yet numerous potential liabilities can rise from a taxonomy generating poor search results or being incomplete, out of date, confusing to users or simply not used. Taxonomies must be viewed from a perspective informed by economics, considering assets and liabilities, actual and indirect costs, external effects on third parties, their value as a public good and the opportunity costs of resources invested. As advocates for taxonomies, we should present the case as knowledge and information economists, fully aware of the range of economic decisions and effects involved.
Government knowledge organization systems: Valuing a public good
Authors: Hodge Gail 
Published: April 2015

EDITOR'S SUMMARYKnowledge organization systems (KOS) for government information facilitate access, management and dissemination of information produced with government funding. Supported by taxpayers, the information product is a public good with potential impact on the economy, and ready access to it extends its value. Determining the economic value of KOS in the government setting is complicated by the idea of return on investment, given the drive for free and open public access and difficulty identifying a presumed economic benefit and beneficiaries. Intellectual property use and technology transfer based on government information fuel industries and economic markets, demonstrating the value of the information, while the systems for organizing that information promote easy access and rapid dissemination. KOS are critical tools that expand paths to government information, opening a broader range of topics for wider audiences, providing semantic resources to enrich information and promote discovery and machine readable metadata to support automated processes and interoperability.
The importance of knowledge organization
Authors: Szostak Rick 
Published: April 2015

EDITOR'S SUMMARYKnowledge organization systems (KOS) are ubiquitous and helpful, but from an economist's perspective their value and contribution to economic productivity are hard to quantify. Though estimating the aggregate impact of KOS is a challenge, it is possible to enhance that impact through the use of a shared or interoperable controlled vocabulary with rules for interpreting text. Like RDF triplets underlying the Semantic Web, elements can be identified to represent phenomena, relationships and properties, and then combined using a synthetic approach to generate complex concepts. Such a vocabulary would be enhanced with related concept information, expanding a user's discovery through a web of hierarchical and associative relationships. The vocabulary would be interdisciplinary and applicable to any database, geared to building upon simple expressions for generic phenomena. The KOS could serve as a universal thesaurus complementing the combinable elements used to classify content with the potential to be a landmark classification system.
Developing a data curation service: Step #1: Work with what you've got
Authors: Johnston Lisa R. 
Published: April 2015

EDITOR'S SUMMARYThe mandate by the White House Office of Science and Technology Policy to improve access to federally funded research makes responsible data curation by academic libraries more important than ever. Libraries should provide curation services covering not only deposit and access but also appraisal, description, metadata creation, format transformation, archiving and preservation. A data curation pilot project by the University of Minnesota Libraries demonstrated an effective workflow model to curate research data and facilitate its reuse. Five research datasets were selected for the pilot, each analyzed by a separate team of library, information and technology professionals. The pilot provided groundwork for more robust data curation services and identified necessary support infrastructure.
Mechanical properties study of SW480 cells based on AFM
Authors: Liu Xiaogang , Song Zhengxun , Qu Yingmin , Wang Guoliang , Wang Zuobin 
Published: April 2015

AbstractSince the invention of the atomic force microscope (AFM), it has been widely applied in biomedicine. One of the most important applications is used as an indenter tool to do the indentation experiment in order to get the mechanical properties of cells. In this paper, SW480 cells were used as the test subjects. Through the analysis of the contact and indentation, Young's modulus (E), which is an important parameter of cancer cells, has been estimated. Experimental results show that different mechanical models should be chosen to calculate the E in different indentation depths. Here, the E of SW480 cells was (2.5 ± 0.8) KPa at the indentation depth of 99 nm.
Suppression of postsurgical recurrence of hepatocellular carcinoma treated with autologous formalin‐fixed tumor vaccine, with special reference to glypican‐3
Authors: Kawashima Issei , Kawashima Yuri , Matsuoka Yasuo , Fujise Kiyotaka , Sakai Hideki , Takahashi Mari , Yoshikawa Toshiaki , Nakatsura Tetsuya , Ishihara Takeshi , Ohno Tadao 
Published: April 2015

Key Clinical MessageAutologous formalin‐fixed tumor vaccine (AFTV) suppressed re‐recurrence for more than 32 months of multiple‐recurrent hepatocellular carcinoma based on hepatitis C virus‐induced liver cirrhosis in a case with previous recurrence interval, 51‐, 28‐, 12‐, and 4‐months. We detected glypican‐3‐specific cytotoxic T lymphocytes in the peripheral blood at 12 months after AFTV.