bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis of C1–C9 Domain of the Nominal Didemnaketal A
Authors: Zhang Shunji , Shi Yong , Tian Weisheng 
Published: June 2015

AbstractBased on chiral pool strategy, a synthesis of the C1–C9 domain of the proposed structure of didemnaketal A, a natural product with potent HIV‐1 protease inhibitory activity, has been achieved. Key transformations are a Sharpless asymmetric dihydroxylation and a chelation‐controlled allylation.
Classical pathology and mutational load of breast cancer – integration of two worlds
Authors: Budczies Jan , Bockmayr Michael , Denkert Carsten , Klauschen Frederick , Lennerz Jochen K , Györffy Balázs , Dietel Manfred , Loibl Sibylle , Weichert Wilko , Stenzinger Albrecht 
Published: June 2015

AbstractBreast cancer is a complex molecular disease comprising several biological subtypes. However, daily routine diagnosis is still based on a small set of well‐characterized clinico‐pathological variables. Here, we try to link the two worlds of surgical pathology and multilayered molecular profiling by analyzing the relationships between clinico‐pathological phenotypes and mutational loads of breast cancer. We evaluated the number of mutated genes with somatic non‐silent mutations in different subgroups of breast cancer based on clinico‐pathological, including immunohistochemical and tumour characteristics. The analysis was performed for a cohort of 687 primary breast cancer patients with mutational profiling, gene expression and clinico‐pathological data available from The Cancer Genome Atlas (TCGA) project. The number of mutated genes was strongly positively associated with higher tumour grade (p = 1.4e−14) and with the different immunohistochemical and PAM50 molecular subtypes of breast cancer (p = 1.4e−10 and p = 4.3e−10, respectively). We observed significant associations (|R| > 0.4) between the abundance of mutated genes and expression levels of genes related to proliferation in the overall cohort and hormone receptor positive cohort, including the Recurrence Score gene signature (e.g., MYBL2 and BIRC5). Specific mutated genes (TP53, NCOR1, NF1, PTPRD and RB1) were highly significantly associated with high loads of mutated genes. Multivariate analysis for overall survival (OS) revealed a worse survival for patients with high numbers of mutated genes (hazard ratio = 4.6, 95% CI: 1.0 – 20.0, p = 0.044). Here, we report a strong association of the number of mutated genes with immunohistochemical and PAM50 subtypes and tumour grade in breast cancer. We provide evidence that specific levels of the mutational load underlie different morphological and biological phenotypes, which collectively constitute the current basis of pathological diagnosis. Our study is a step towards genomics‐informed breast pathology and will provide a basis for future studies in this field bridging the gap between morphology, tumour biology and medical oncology.
Freezing the Bioactive Conformation to Boost Potency: The Identification of BAY 85‐8501, a Selective and Potent Inhibitor of Human Neutrophil Elastase for Pulmonary Diseases
Authors: von Nussbaum Franz , Li Volkhart M.‐J. , Allerheiligen Swen , Anlauf Sonja , Bärfacker Lars , Bechem Martin , Delbeck Martina , Fitzgerald Mary F. , Gerisch Michael , Gielen‐Haertwig Heike , Haning Helmut , Karthaus Dagmar , Lang Dieter , Lustig Klemens , Meibom Daniel , Mittendorf Joachim , Rosentreter Ulrich , Schäfer Martina , Schäfer Stefan , Schamberger Jens , Telan Leila A. , Tersteegen Adrian 
Published: June 2015

AbstractHuman neutrophil elastase (HNE) is a key protease for matrix degradation. High HNE activity is observed in inflammatory diseases. Accordingly, HNE is a potential target for the treatment of pulmonary diseases such as chronic obstructive pulmonary disease (COPD), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), bronchiectasis (BE), and pulmonary hypertension (PH). HNE inhibitors should reestablish the protease–anti‐protease balance. By means of medicinal chemistry a novel dihydropyrimidinone lead‐structure class was identified. Further chemical optimization yielded orally active compounds with favorable pharmacokinetics such as the chemical probe BAY‐678. While maintaining outstanding target selectivity, picomolar potency was achieved by locking the bioactive conformation of these inhibitors with a strategically positioned methyl sulfone substituent. An induced‐fit binding mode allowed tight interactions with the S2 and S1 pockets of HNE. BAY 85‐8501 ((4S)‐4‐[4‐cyano‐2‐(methylsulfonyl)phenyl]‐3,6‐dimethyl‐2‐oxo‐1‐[3‐(trifluoromethyl)phenyl]‐1,2,3,4‐tetrahydropyrimidine‐5‐carbonitrile) was shown to be efficacious in a rodent animal model related to ALI. BAY 85‐8501 is currently being tested in clinical studies for the treatment of pulmonary diseases.
Cinnamamide Derivatives for Central and Peripheral Nervous System Disorders—A Review of Structure–Activity Relationships
Authors: Gunia‐Krzyżak Agnieszka , Pańczyk Katarzyna , Waszkielewicz Anna M. , Marona Henryk 
Published: June 2015

AbstractThe cinnamamide scaffold has been incorporated in to the structure of numerous organic compounds with therapeutic potential. The scaffold enables multiple interactions, such as hydrophobic, dipolar, and hydrogen bonding, with important molecular targets. Additionally, the scaffold has multiple substitution options providing the opportunity to optimize and modify the pharmacological activity of the derivatives. In particular, cinnamamide derivatives have exhibited therapeutic potential in animal models of both central and peripheral nervous system disorders. Some have undergone clinical trials and were introduced on to the pharmaceutical market. The diverse activities observed in the nervous system included anticonvulsant, antidepressant, neuroprotective, analgesic, anti‐inflammatory, muscle relaxant, and sedative properties. Over the last decade, research has focused on the molecular mechanisms of action of these derivatives, and the data reported in the literature include targeting the γ‐aminobutyric acid type A (GABAA) receptors, N‐methyl‐D‐aspartate (NMDA) receptors, transient receptor potential (TRP) cation channels, voltage‐gated potassium channels, histone deacetylases (HDACs), prostanoid receptors, opioid receptors, and histamine H3 receptors. Here, the literature data from reports evaluating cinnamic acid amide derivatives for activity in target‐based or phenotypic assays, both in vivo and in vitro, relevant to disorders of the central and peripheral nervous systems are analyzed and structure–activity relationships discussed.
Resonance Character of Copper/Silver/Gold Bonding in Small Molecule⋅⋅⋅MX (X=F, Cl, Br, CH3, CF3) Complexes
Authors: Zhang Guiqiu , Yue Huanjing , Weinhold Frank , Wang Hui , Li Hong , Chen Dezhan 
Published: June 2015

AbstractThe resonance character of Cu/Ag/Au bonding is investigated in B⋅⋅⋅MX (M=Cu, Ag, Au; X=F, Cl, Br, CH3, CF3; B=CO, H2O, H2S, C2H2, C2H4) complexes. The natural bond orbital/natural resonance theory results strongly support the general resonance‐type three‐center/four‐electron (3c/4e) picture of Cu/Ag/Au bonding, B:MX↔B+M:X−, which mainly arises from hyperconjugation interactions. On the basis of such resonance‐type bonding mechanisms, the ligand effects in the more strongly bound OC⋅⋅⋅MX series are analyzed, and distinct competition between CO and the axial ligand X is observed. This competitive bonding picture directly explains why CO in OC⋅⋅⋅AuCF3 can be readily replaced by a number of other ligands. Additionally, conservation of the bond order indicates that the idealized relationship bB⋅⋅⋅M+bMX=1 should be suitably generalized for intermolecular bonding, especially if there is additional partial multiple bonding at one end of the 3c/4e hyperbonded triad.
The Active Molybdenum Oxide Phase in the Methanol Oxidation to Formaldehyde (Formox Process): A DFT Study
Authors: Rellán‐Piñeiro Marcos , López Núria 
Published: June 2015

AbstractMethanol is oxidised to formaldehyde by the Formox process, in which molybdenum oxides, usually doped with iron, are the catalyst. The active phase of the catalysts and the reasons for the selectivity observed are still unknown. We present a density functional theory based study that indicates the unique character of MoVIMoIV pairs as the most active and selective sites and indicates the active sites on the surface, the controlling factors of selectivity, and the role of the dopant. Iron reduces the energy requirements of the redox MoVIMoIV pair by acting as an electron reservoir that sets in if required. Our present study paves the way towards a better understanding of the process.
Reactive T cells by flow cytometry distinguish Hodgkin lymphomas from T cell/histiocyte‐rich large B cell lymphoma
Authors: Wu David , Thomas Anju , Fromm Jonathan R. 
Published: June 2015

BackgroundClassical Hodgkin lymphoma (CHL), nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), and T‐cell/histiocyte rich large B‐cell lymphoma (T/HRLBCL) are B‐cell lymphomas in which tumor cells are rare as compared with the background reactive infiltrate. We hypothesized that characterization of the reactive infiltrates can provide information to help diagnose these lymphomas.MethodsLymphocyte subsets by flow cytometry were analyzed for 27 NLPHL, 20 T/HRLBCL, 34 CHL, and 49 reactive lymph nodes (RLN). CD4+ T cells with bright expression of CD7 and CD45 (CD3+CD4+CD7brightCD45bright), CD4:CD8 ratio, and percentage of T cells, B cells, NK cells, CD4+ T cells, CD8+ T cells, T cells coexpressing CD4, and CD8 (CD4+CD8+), and plasma cells were measured.ResultsThe CD3+CD4+CD7brightCD45bright T‐cell population was present in the reactive infiltrate of CHL (76.5%) and T/HRLBCL (92.3%) but not in NLPHL (8.3%) or RLN (4.1%). In a separate analysis of 387 samples, the CD3+CD4+CD7brightCD45bright T‐cell population was also observed in some CD10+ B‐NHL. The mean percentage of CD4+CD8+ T cells was highest for NLPHL (11.7%) and differed significantly from T/HRLBCL, CHL, and RLN. Interestingly, the highest CD4:CD8 ratios were seen with T/HRLBCL. Finally, the percentage of B cells is decreased in T/HRLBCL relative to CHL and NLPHL.ConclusionsDifferences in the reactive inflammatory infiltrate of CHL, NLPHL, and T/HRLBCL and can suggest these diagnoses. Additionally, in contrast to published studies, T/HRLBCL demonstrates both low and very high CD4 to CD8 T‐cell ratios. © 2015 International Clinical Cytometry Society
Consumer trait variation influences tritrophic interactions in salt marsh communities
Authors: Hughes Anne Randall , Hanley Torrance C. , Orozco Nohelia P. , Zerebecki Robyn A. 
Published: June 2015

AbstractThe importance of intraspecific variation has emerged as a key question in community ecology, helping to bridge the gap between ecology and evolution. Although much of this work has focused on plant species, recent syntheses have highlighted the prevalence and potential importance of morphological, behavioral, and life history variation within animals for ecological and evolutionary processes. Many small‐bodied consumers live on the plant that they consume, often resulting in host plant‐associated trait variation within and across consumer species. Given the central position of consumer species within tritrophic food webs, such consumer trait variation may play a particularly important role in mediating trophic dynamics, including trophic cascades. In this study, we used a series of field surveys and laboratory experiments to document intraspecific trait variation in a key consumer species, the marsh periwinkle Littoraria irrorata, based on its host plant species (Spartina alterniflora or Juncus roemerianus) in a mixed species assemblage. We then conducted a 12‐week mesocosm experiment to examine the effects of Littoraria trait variation on plant community structure and dynamics in a tritrophic salt marsh food web. Littoraria from different host plant species varied across a suite of morphological and behavioral traits. These consumer trait differences interacted with plant community composition and predator presence to affect overall plant stem height, as well as differentially alter the density and biomass of the two key plant species in this system. Whether due to genetic differences or phenotypic plasticity, trait differences between consumer types had significant ecological consequences for the tritrophic marsh food web over seasonal time scales. By altering the cascading effects of the top predator on plant community structure and dynamics, consumer differences may generate a feedback over longer time scales, which in turn influences the degree of trait divergence in subsequent consumer populations.
Early vs. late worsening heart failure during acute heart failure hospitalization: insights from the PROTECT trial
Authors: Mentz Robert J. , Metra Marco , Cotter Gad , Milo Olga , McKendry Colleen , Chiswell Karen , Davison Beth A. , Cleland John G.F. , Bloomfield Daniel M. , Dittrich Howard C. , Fiuzat Mona , Ponikowski Piotr , Givertz Michael M. , Voors Adriaan A. , Teerlink John R. , O'Connor Christopher M. 
Published: June 2015

BackgroundWorsening heart failure (WHF) symptoms despite initial therapy during admission for acute heart failure (AHF) is associated with worse outcomes. The association between the time of the WHF event and the intensity of WHF therapy with outcomes is unknown.Methods and resultsIn the PROTECT trial of 2033 AHF patients, we investigated the association between time of occurrence of WHF and intensity of therapy, with subsequent outcomes. WHF was defined by standardized, physician‐determined assessment. Early WHF was defined as occurring on days 2–3 and late on days 4–7. Low intensity included restarting/increasing diuretics or vasodilators and high intensity included initiation of inotropes, vasopressors, inodilators, or mechanical support. Outcomes were death or cardiovascular/renal hospitalization over 60 days and death over 180 days. Of the 1879 patients with complete follow‐up after day 7, 12.7% (n = 238) experienced WHF: 47.9% early and 52.1% late. Treatment intensity was low in 72.3% and high in 24.8% (2.9% missing). After adjusting for baseline predictors of outcome, WHF was associated with a trend toward increased 60‐day death or cardiovascular/renal hospitalization [hazard ratio (HR) 1.26; 95% confidence interval (CI) 0.99–1.60; P = 0.063] and increased 180‐day death (HR 1.77; 95% CI 1.33–2.34; P < 0.001). There was no evidence of a differential association between the time of occurrence of WHF and outcomes. High‐intensity therapy was not significantly associated with increased event rates (180‐day mortality: HR 1.44; 95% CI 0.80–2.59 vs. low).ConclusionsInhospital WHF was associated with increased 180‐day death. The time of occurrence and intensity of WHF therapy may provide less prognostic information than whether or not WHF occurred.
10β‐Acetoxy‐8α,9α‐epoxy‐14β‐hydroxy‐7‐oxodolastane – A New Diterpene Isolated from the Brazilian Brown Macroalga Canistrocarpus cervicornis
Authors: Bianco Éverson Miguel , Martins Francisco Thiago , Basílio Pinheiro Carlos , Bagueira de Vasconcellos Azeredo Rodrigo , Laneuville Teixeira Valéria , Crespo Pereira Renato 
Published: June 2015

AbstractChemical investigation on the nonpolar extract of the Brazilian brown alga Canistrocarpus cervicornis (Dictyotaceae) has led to the isolation of a new diterpene 1 and four known seco‐dolastane diterpenes 2–5. Their chemical structures were elucidated by 1D‐ and 2D‐NMR spectroscopy, and the data was compared with the literature. A full X‐ray diffraction analysis confirmed the absolute configuration of 1.
Oxepine‐Containing Diketopiperazine Alkaloids from the Algal‐Derived Endophytic Fungus Paecilomyces variotii EN‐291
Authors: Zhang Peng , Li Xiao‐Ming , Wang Jia‐Ning , Wang Bin‐Gui 
Published: June 2015

AbstractTwo new oxepine‐containing diketopiperazine‐type alkaloids, varioloids A and B (1 and 2, resp.), were isolated from the algal‐derived fungus Paecilomyces variotii EN‐291. The structures and absolute configurations were determined by detailed interpretation of 1D‐ and 2D‐NMR spectroscopic data and by analysis of acidic hydrolysates. Compounds 1 and 2 exhibited potent activity against the plant‐pathogenic fungus Fusarium graminearum with MIC values of 8 and 4 μg/ml, respectively.
(R)‐2,3‐Cyclohexylideneglyceraldehyde, a Chiral Pool Synthon for the Synthesis of 2‐Azido‐1,3‐diols
Authors: Rouf Abdul , Aga Mushtaq A. , Kumar Brijesh , Taneja Subhash C. 
Published: June 2015

AbstractA new approach was proposed for the synthesis of 2‐azido‐1,3‐diols from easily available and inexpensive chiral pool synthon (R)‐2,3‐O‐cyclohexylidene‐D‐glyceraldehyde, through Mitsunobu azidation of 1,2‐diols. Both C(2) and C(1) azides in variable ratios were obtained in alkyl substituted diols with C(2) as the major one.
VaRSOM: A Tool to Monitor Markets' Stability Based on Value at Risk and Self‐Organizing Maps
Authors: Resta Marina 
Published: June 2015

SummaryWe introduce a variant of self‐organizing maps (SOMs) termed VaRSOM that evaluates the similarity among inputs and nodes of the map employing value at risk (VaR). In this way we embed risk measurement within a machine‐learning architecture, thus becoming particularly well‐suited to analysing financial data. We tested the visualization capabilities and the explicative power of VaRSOM on data from the German Stock Exchange; we then evaluated the results in a comparative perspective, opposing the VaRSOM outcomes to those of SOM trained with more conventional similarity measures. The results lead to the conclusion that VaRSOM is a tool particularly well suited to visualize and exploit critical patterns in financial markets. This, in turn, opens perspectives for a general machine‐learning framework sensitive to financial distress and contagion effects. Copyright © 2015 John Wiley & Sons, Ltd.
Distribution and biomarker of carbon‐14 labeled fullerene C60 ([14C(U)]C60) in pregnant and lactating rats and their offspring after maternal intravenous exposure
Authors: Snyder Rodney W. , Fennell Timothy R. , Wingard Christopher J. , Mortensen Ninell P. , Holland Nathan A. , Shannahan Jonathan H. , Pathmasiri Wimal , Lewin Anita H. , Sumner Susan C. J. 
Published: June 2015

AbstractA comprehensive distribution study was conducted in pregnant and lactating rats exposed to a suspension of uniformly carbon‐14 labeled C60 ([14C(U)]C60). Rats were administered [14C(U)]C60 (~0.2 mg [14C(U)]C60 kg–1 body weight) or 5% polyvinylpyrrolidone (PVP)‐saline vehicle via a single tail vein injection. Pregnant rats were injected on gestation day (GD) 11 (terminated with fetuses after either 24 h or 8 days), GD15 (terminated after 24 h or 4 days), or GD18 (terminated after 24 h). Lactating rats were injected on postnatal day 8 and terminated after 24 h, 3 or 11 days. The distribution of radioactivity in pregnant dams was influenced by both the state of pregnancy and time of termination after exposure. The percentage of recovered radioactivity in pregnant and lactating rats was highest in the liver and lungs. Radioactivity was quantitated in over 20 tissues. Radioactivity was found in the placenta and in fetuses of pregnant dams, and in the milk of lactating rats and in pups. Elimination of radioactivity was < 2% in urine and feces at each time point. Radioactivity remained in blood circulation up to 11 days after [14C(U)]C60 exposure. Biomarkers of inflammation, cardiovascular injury and oxidative stress were measured to study the biological impacts of [14C(U)]C60 exposure. Oxidative stress was elevated in female pups of exposed dams. Metabolomics analysis of urine showed that [14C(U)]C60 exposure to pregnant rats impacted the pathways of vitamin B, regulation of lipid and sugar metabolism and aminoacyl‐tRNA biosynthesis. This study demonstrated that [14C(U)]C60 crosses the placenta at all stages of pregnancy examined, and is transferred to pups via milk. Copyright © 2015 John Wiley & Sons, Ltd.
A rabbit maxillary sinus model with simultaneous customized‐implant placement: Comparative microscopic analysis for the evaluation of surface‐treated implants
Authors: Park Sang‐Hyun , Choi Hyunmin , Lee Sang‐Bae , Zhang Chenghao , Otgonbold Jamiyandori , Cho Jang‐Gi , Han Jin Soo 
Published: June 2015

ABSTRACTWe describe the use of a rabbit maxillary sinus model, characterized by thin osseous tissue and low bone density, for the evaluation of surface‐treated implants by histologically and histomorphometrically comparing the osseointegration patterns depending on the surface treatment methods. Twenty rabbits were randomly assigned to two groups of 10 animals, one receiving 5 × 3 mm customized implants (machined, MA or sandblasted and acid etched, SLA) placed in sinus and the other receiving implants placed in a tibia. Histological observation of the implant placed in sinus shows relatively more active new bone formation, characterized by trabecular bone pattern underneath the cortical bone in sinus as compared with that in tibia. Histomorphometric analysis in the rabbits receiving implants in a tibia, the NBIC (%) associated with the SLA surface implant was greater than that associated with the MA implant at 2 weeks (55.63 ± 8.65% vs. 47.87 ± 10.01%; P > 0.05) and at 4 weeks (61.76 ± 9.49% vs. 42.69 ± 10.97%; P < 0.05). Among rabbits receiving implants in a sinus, the NBIC (%) associated with the SLA surface implant was significantly greater than that associated with the MA surface implant both at 2 weeks (37.25 ± 7.27% vs. 20.98 ± 6.42%; P < 0.05) and at 4 weeks (48.82 ± 6.77% vs. 31.51 ± 9.14%; P < 0.05). As a result, we suggest that the maxillary sinus model is an appropriate animal model for assessing surface‐treated implants and may be utilized for the evaluation of surface‐treated implants in poor bone quality environment. Microsc. Res. Tech. 78:697–706, 2015. © 2015 Wiley Periodicals, Inc.
An Investigation of Mechanical and Thermal Properties of Polypropylene Clay Nanocomposites Containing Different Nanoclays
Authors: Arunachalam Sundaresan , Battisti Markus Gottfried , Vijayakumar Chinnaswamy Thangavel , Friesenbichler Walter 
Published: June 2015

AbstractIn the present investigation, polypropylene clay nanocomposites (PP‐CNs) are prepared by melt compounding using the Polymer NanoComposite Injection Molding Compounder (PNC‐IMC) with different nanoclays and at varying compatibilizer/nanoclay ratios. A specially devised hyperbolical nozzle is used to induce elongational flow for better mechanical properties. Statistical analysis of the mechanical properties reveal that PP‐CNs based on mica‐phlogopite is superior to other PP‐CNs. Beside intercalated and exfoliated structures the SAXS results confirms that the PP‐CNs show well aligned and also randomly disordered structures. TGA shows among the investigated nanoclays organic modified montmorillonite (OMMT) shows substantial improvement in thermal stability of PP‐CNs.
Presence and Absence: An Exploration of Scurvy in the Commingled Subadults in the Spring Street Presbyterian Church Collection, Lower Manhattan
Authors: Ellis M. A. B. 
Published: June 2015

AbstractThis paper presents the results of an examination of scurvy in the commingled subadult remains (minimum number of individuals = 70) of the Spring Street Presbyterian Church. This historic congregation in New York City had active burial vaults from 1820 to 1846. Scurvy is a vitamin C deficiency that results in haemorrhaging at the sites of muscle origin and insertion, particularly around the skull. These resulting lesions can occur in subadults undergoing growth, weaning and dietary stress. Applying diagnoses suggested by recent research, this article examines specific sites on the skull for lesions consistent with and suggestive of scurvy. Findings include 30 elements that display associated pathology. This population data are drawn from maxillae, sphenoids and orbits. Two osteobiographies are also presented. By connecting the biological data to the socio‐cultural environment of the church, this article raises questions of how to interpret the presence and absence of scurvy in a commingled collection. Copyright © 2016 John Wiley & Sons, Ltd.