bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anderson transition for Google matrix eigenstates
Authors: Zhirov O. V. , Shepelyansky D. L. 
Published: March 2015

We introduce a number of random matrix models describing the Google matrix G of directed networks. The properties of their spectra and eigenstates are analyzed by numerical matrix diagonalization. We show that for certain models it is possible to have an algebraic decay of PageRank vector with the exponent similar to real directed networks. At the same time the spectrum has no spectral gap and a broad distribution of eigenvalues in the complex plain. The eigenstates of G are characterized by the Anderson transition from localized to delocalized states and a mobility edge curve in the complex plane of eigenvalues.
image
Synthesis, characterization, and in vitro drug release study of 3‐arm poly‐β‐alanine
Authors: Kumar Krishna , Adhikary Pubali , Tungala Kranthikumar , Azmeera Venkanna , Krishnamoorthi S. 
Published: March 2015

ABSTRACTSynthesis of three arms star‐shaped poly‐β‐alanine (3‐b‐ala) based on tri(prop‐2‐yn‐1‐yl) benzene‐1,3,5‐tricarboxylate (TBT) and azido terminated poly‐β‐alanine (N3‐P‐ala) was performed using click reaction. TBT was synthesized by nucleophilic substitution reaction between propargyl alcohol and 1,3,5‐benzenetricarbonyltrichloride. For the first time, N3‐P‐ala was synthesized through anionic polymerization of acrylamide using sodium azide as an initiator. TBT was characterized by FT‐IR and 1HNMR. N3‐p‐ala was characterized by FT‐IR, GPC, and 1HNMR and 3‐b‐ala was characterized by FT‐IR, GPC, 1HNMR, TGA, and XRD. The synthesized 3‐b‐ala was used for drug loading and releasing studies. Polymer loaded drug (3‐b‐ala‐D) hybrid was used in in vitro studies of drug (Diclofenac sodium) release in phosphate buffer solution (PBS) at 37 ± 0.5°C and pH 7.4. The drug loading and releasing studies were analyzed by UV‐visible spectrophotometer. 3‐b‐ala‐D was examined by AFM to analyze the surface morphology and roughness. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42124.
Interdisciplinary archaeological prospection, excavation and 3D documentation exemplified through the investigation of a burial at the Iron Age settlement site of Uppåkra in Sweden
Authors: Larsson Lars , Trinks Immo , Söderberg Bengt , Gabler Manuel , Dell'unto Nicolo , Neubauer Wolfgang , Ahlström Torbjörn 
Published: March 2015

ABSTRACTThis paper presents the archaeological prospection, excavation and digital three‐dimensional documentation of a previously unknown neolithic grave, presumably late neolithic, at the outstanding Iron Age site of Uppåkra in southern Sweden, and exemplifies a multidisciplinary approach to modern archaeological fieldwork. In the framework of a large‐scale archaeological prospection pilot study conducted at the archaeological site of Uppåkra using remote sensing and large‐scale near‐surface geophysical prospection methods a peculiar circular structure was discovered and mapped using both manual and motorized high‐resolution ground‐penetrating radar (GPR) measurements. The structure, consisting of a ring ditch of ca. 10 m diameter, encloses an east–west oriented strongly reflecting rectangular body in the centre, which therefore was interpreted as being caused by the buried remains of a prehistoric barrow. Subsequent archaeological excavation was conducted across this structure in order to determine the exact cause of the GPR anomaly. This excavation resulted in detailed confirmation of the archaeological prospection results as well as in the discovery of dateable finds. The excavation was documented using the latest image‐based three‐dimensional modelling techniques. Copyright © 2015 John Wiley & Sons, Ltd.
Disease Activity in Rheumatoid Arthritis and the Risk of Cardiovascular Events
Authors: Solomon D. H. , Reed G. W. , Kremer J. M. , Curtis J. R. , Farkouh M. E. , Harrold L. R. , Hochberg M. C. , Tsao P. , Greenberg J. D. 
Published: March 2015

ObjectiveUse of several immunomodulatory agents has been associated with reduced numbers of cardiovascular (CV) events in epidemiologic studies of rheumatoid arthritis (RA). However, it is unknown whether time‐averaged disease activity in RA correlates with CV events.MethodsWe studied patients with RA whose cases were followed in a longitudinal US‐based registry. Time‐averaged disease activity was assessed during followup using the area under the curve of the Clinical Disease Activity Index (CDAI), a validated measure of RA disease activity. Age, sex, presence of diabetes mellitus, hypertension, or hyperlipidemia, body mass index, family history of myocardial infarction (MI), use of aspirin or nonsteroidal antiinflammatory drugs (NSAIDs), presence of CV disease, and baseline use of an immunomodulator were assessed at baseline. Cox proportional hazards regression models were examined to determine the risk of a composite CV end point that included MI, stroke, and death from CV causes.ResultsA total of 24,989 patients who had been followed up for a median of 2.7 years were included in these analyses. During followup, we observed 534 confirmed CV end points, for an incidence rate of 7.8 per 1,000 person‐years (95% confidence interval [95% CI] 6.7–8.9). In models adjusted for variables noted above, a 10‐point reduction in the time‐averaged CDAI was associated with a 21% reduction in CV risk (95% CI 13–29). These results were robust in subgroup analyses stratified by the presence of CV disease, use of corticosteroids, use of NSAIDs or selective cyclooxygenase 2 inhibitors, and change in RA treatment, as well as when restricted to events adjudicated as definite or probable.ConclusionOur findings showed that reduced time‐averaged disease activity in RA is associated with fewer CV events.
Outcomes of Nonsevere Relapses in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis Treated With Glucocorticoids
Authors: Miloslavsky E. M. , Specks U. , Merkel P. A. , Seo P. , Spiera R. , Langford C. A. , Hoffman G. S. , Kallenberg C. G. M. , St.Clair E. W. , Tchao N. K. , Ding L. , Iklé D. , Villareal M. , Lim N. , Brunetta P. , Fervenza F. C. , Monach P. A. , Stone J. H. ,   for the Rituximab in ANCA‐Associated Vasculitis–Immune Tolerance Network Research Group
Published: March 2015

ObjectiveNonsevere relapses are more common than severe relapses in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV), but their clinical course and treatment outcomes remain largely unexamined. We undertook this study to analyze the outcomes of patients with nonsevere relapses in the Rituximab in ANCA‐Associated Vasculitis (RAVE) trial who were treated with prednisone according to a prespecified protocol.MethodsRAVE was a randomized, double‐blind, placebo‐controlled trial comparing rituximab (RTX) to cyclophosphamide (CYC) followed by azathioprine (AZA) for induction of remission. Patients who experienced nonsevere relapses between months 1 and 18 were treated with a prednisone increase without a concomitant change in their nonglucocorticoid immunosuppressants, followed by a taper.ResultsForty‐four patients with a first nonsevere relapse were analyzed. In comparison to the 71 patients who maintained relapse‐free remission over 18 months, these patients were more likely to have proteinase 3–ANCAs, diagnoses of granulomatosis with polyangiitis (Wegener's), and a history of relapsing disease at baseline. A prednisone increase led to remission in 35 patients (80%). However, only 13 patients (30%) were able to maintain second remissions through the followup period (mean 12.5 months); 31 patients (70%) had a second disease relapse, 14 of them with severe disease. The mean time to second relapse was 9.4 months (4.7 months in the group treated with RTX versus 13.7 months in the group treated with CYC/AZA; P < 0.01). Patients who experienced nonsevere relapses received more glucocorticoids than those who maintained remission (6.7 grams versus 3.8 grams; P < 0.01).ConclusionTreatment of nonsevere relapses in AAV with an increase in glucocorticoids is effective in restoring temporary remission in the majority of patients, but recurrent relapses within a relatively short interval remain common. Alternative treatment approaches are needed for this important subset of patients.
Brief Report: Main Contribution of DRB1*04:05 Among the Shared Epitope Alleles and Involvement of DRB1 Amino Acid Position 57 in Association With Joint Destruction in Anti–Citrullinated Protein Antibody–Positive Rheumatoid Arthritis
Authors: Terao Chikashi , Yano Koichiro , Ikari Katsunori , Furu Moritoshi , Yamakawa Noriyuki , Yoshida Shinji , Hashimoto Motomu , Ito Hiromu , Fujii Takao , Ohmura Koichiro , Yurugi Kimiko , Miura Yasuo , Maekawa Taira , Taniguchi Atsuo , Momohara Shigeki , Yamanaka Hisashi , Mimori Tsuneyo , Matsuda Fumihiko 
Published: March 2015

ObjectiveThe shared epitope is associated with increased joint destruction in rheumatoid arthritis (RA) as well as susceptibility to RA and the production of anti–citrullinated protein antibody (ACPA). However, previous studies addressing whether the association of the shared epitope with joint destruction is independent of ACPA have shown different results in different populations. Different allele distributions in the shared epitope may explain this ethnic heterogeneity. This study was undertaken to assess the associations of the shared epitope and HLA–DRB1*04:05, the most common shared epitope allele in the Japanese population, with joint destruction in patients with ACPA‐positive RA.MethodsA total of 861 patients with ACPA‐positive RA who had not received any biologic agents were recruited from the institute of Rheumatology, Rheumatoid Arthritis cohort (sets 1 and 2) and the Kyoto University Rheumatoid Arthritis Management Alliance cohort (set 3). Joint destruction was assessed using the modified Sharp/van der Heijde score (SHS). The associations of the shared epitope alleles, HLA–DRB1*04:05, and other shared epitope allele groups with the SHS were analyzed in a linear regression analysis. Amino acid variations associated with the SHS were also analyzed.ResultsThe shared epitope was significantly associated with an increased SHS (P = 0.0017). Although HLA–DRB1*04:05 was significantly associated with an increased SHS (P = 2.7 × 10−5), the group of other shared epitope alleles, including HLA–DRB1*01:01, did not show an association with the SHS in spite of sufficient power (P = 0.67). HLA–DRB1*04:05 was associated with joint destruction in a dose‐dependent manner. Analyses of amino acid associations of HLA–DRB1 revealed that serine at position 57, recently shown to have a susceptibility effect for ACPA‐positive RA in Asian populations, showed a significant association (P = 5.0 × 10−6).ConclusionHLA–DRB1*04:05, characterized by serine at position 57, accounts for the detrimental association between the shared epitope and SHS in Japanese patients with ACPA‐positive RA.
Brief Report: IFIH1 Mutation Causes Systemic Lupus Erythematosus With Selective IgA Deficiency
Authors: Van Eyck Lien , De Somer Lien , Pombal Diana , Bornschein Simon , Frans Glynis , Humblet‐Baron Stéphanie , Moens Leen , de Zegher Francis , Bossuyt Xavier , Wouters Carine , Liston Adrian 
Published: March 2015

ObjectiveTo identify the underlying genetic defect in a 16‐year‐old girl with severe early‐onset and refractory systemic lupus erythematosus (SLE), IgA deficiency, and mild lower limb spasticity without neuroradiologic manifestations.MethodsWhole‐exome sequencing and extensive immunologic analysis were performed on samples from the index patient.ResultsWe identified a de novo p.R779H IFIH1 gain‐of‐function mutation in a patient with severe early‐onset SLE, selective IgA deficiency, and mild lower limb spasticity. The same mutation in IFIH1 was recently identified in patients with Aicardi‐Goutières syndrome, a rare neuroimmunologic disorder associated with elevated levels of type I interferon (IFN). IFN induced with helicase C domain 1 functions as an intracellular innate immune receptor that senses viral nucleic acids and leads to the induction of type I IFN and proinflammatory cytokines. Despite systemic immunosuppressive treatment, disease activity persisted in the patient and was associated with elevated serum levels of IFNα and up‐regulation of IFIH1 itself.ConclusionThis finding adds a new genetic causation for Mendelian lupus and greatly extends the disease spectrum associated with mutations in IFIH1 (ranging from inflammatory encephalopathy to prototypic systemic autoimmune disease). This marked phenotypic heterogeneity, despite an identical mutation, demonstrates the importance of modifying factors in type I IFN–dependent pathologies caused by mutations in IFIH1.
Rosuvastatin‐Induced Carotid Plaque Regression in Patients With Inflammatory Joint Diseases: The Rosuvastatin in Rheumatoid Arthritis, Ankylosing Spondylitis and Other Inflammatory Joint Diseases Study
Authors: Rollefstad S. , Ikdahl E. , Hisdal J. , Olsen I. C. , Holme I. , Hammer H. B. , Smerud K. T. , Kitas G. D. , Pedersen T. R. , Kvien T. K. , Semb A. G. 
Published: March 2015

ObjectivePatients with rheumatoid arthritis (RA) and carotid artery plaques have an increased risk of acute coronary syndromes. Statin treatment with the goal of achieving a low‐density lipoprotein (LDL) cholesterol level of ≤1.8 mmoles/liter (≤70 mg/dl) is recommended for individuals in the general population who have carotid plaques. The aim of the ROsuvastatin in Rheumatoid Arthritis, Ankylosing Spondylitis and other inflammatory joint diseases (RORA‐AS) study was to evaluate the effect of 18 months of intensive lipid‐lowering treatment with rosuvastatin with regard to change in carotid plaque height.MethodsEighty‐six patients (60.5% of whom were female) with carotid plaques and inflammatory joint disease (55 with RA, 21 with AS, and 10 with psoriatic arthritis) were treated with rosuvastatin to obtain the LDL cholesterol goal. Carotid plaque height was evaluated by B‐mode ultrasonography.ResultsThe mean ± SD age of the patients was 60.8 ± 8.5 years, and the median compliance with rosuvastatin treatment was 97.9% (interquartile range [IQR] 96.0–99.4). At baseline, the median number and height of the carotid plaques were 1.0 (range 1–8) and 1.80 mm (IQR 1.60–2.10), respectively. The mean ± SD change in carotid plaque height after 18 months of treatment with rosuvastatin was −0.19 ± 0.35 mm (P < 0.0001). The mean ± SD baseline LDL cholesterol level was 4.0 ± 0.9 mmoles/liter (154.7 ± 34.8 mg/dl), and the mean reduction in the LDL cholesterol level was −2.3 mmoles/liter (95% confidence interval [95% CI] −2.48, −2.15) (−88.9 mg/dl [95% CI −95.9, −83.1]). The mean ± SD LDL cholesterol level during the 18 months of rosuvastatin treatment was 1.7 ± 0.4 mmoles/liter (area under the curve). After adjustment for age/sex/blood pressure, no linear relationship between a reduction in carotid plaque height and the level of LDL cholesterol exposure during the study period was observed. Attainment of the LDL cholesterol goal of ≤1.8 mmoles/liter (≤70 mg/dl) or the amount of change in the LDL cholesterol level during the study period did not influence the degree of carotid plaque height reduction.ConclusionIntensive lipid‐lowering treatment with rosuvastatin induced atherosclerotic regression and reduced the LDL cholesterol level significantly in patients with inflammatory joint disease.
Pantethine Prevents Murine Systemic Sclerosis Through the Inhibition of Microparticle Shedding
Authors: Kavian Niloufar , Marut Wioleta , Servettaz Amélie , Nicco Carole , Chéreau Christiane , Lemaréchal Hervé , Guilpain Philippe , Chimini Giovanna , Galland Franck , Weill Bernard , Naquet Philippe , Batteux Frédéric 
Published: March 2015

ObjectiveEndothelial cell (EC) damage in systemic sclerosis (SSc) is reflected by the shedding of microparticles (MPs). The aim of this study was to show that inhibiting MP release using pantethine or by inactivating ATP‐binding cassette transporter A1 (ABCA1) ameliorates murine SSc.MethodsFirst, the effects of pantethine on MP shedding and on basal oxidative and nitrosative stresses in ECs and fibroblasts were determined in vitro. The effects of pantethine were then tested in vivo. SSc was induced in BALB/c mice by daily intradermal injection of HOCl. Mice were simultaneously treated daily with pantethine by oral gavage.ResultsIn vitro, pantethine inhibited MP shedding from tumor necrosis factor–stimulated ECs and abrogated MP‐induced oxidative and nitrosative stresses in ECs and fibroblasts. Ex vivo, pantethine also restored redox homeostasis in fibroblasts from mice with SSc. In vivo, mice with SSc displayed skin and lung fibrosis associated with increased levels of circulating MPs and markers of oxidative and endothelial stress, which were normalized by administration of pantethine or inactivation of ABCA1.ConclusionPantethine is a well‐tolerated molecule that represents a potential treatment of human SSc.
Homology modeling and virtual screening of inhibitors against TEM‐ and SHV‐type‐resistant mutants: A multilayer filtering approach
Authors: Baig Mohammad H. , Balaramnavar Vishal M. , Wadhwa Gulshan , Khan Asad U. 
Published: March 2015

AbstractTEM and SHV are class‐A‐type β‐lactamases commonly found inEscherichia coliandKlebsiella pneumoniae. Previous studies reported S130G and K234R mutations in SHVs to be 41‐ and 10‐fold more resistant toward clavulanic acid than SHV‐1, respectively, whereas TEM S130G and R244S also showed the same level of resistance. These selected mutants confer higher level of resistance against clavulanic acid. They also show little susceptibility against other commercially available β‐lactamase inhibitors. In this study, we have used docking‐based virtual screening approach in order to screen potential inhibitors against some of the major resistant mutants of SHV and TEM types β‐lactamase. Two different inhibitor‐resistant mutants from SHV and TEM were selected. Moreover, we have retained the active site water molecules within each enzyme. Active site water molecules were placed within modeled structure of the mutant whose structure was unavailable with protein databank. The novelty of this work lies in the use of multilayer virtual screening approach for the prediction of best and accurate results. We are reporting five inhibitors on the basis of their efficacy against all the selected resistant mutants. These inhibitors were selected on the basis of their binding efficacies and pharmacophore features.
In vitro inhibition and induction of human cytochrome P450 enzymes by SIPI5357, a potential antidepressant
Authors: Fan Gaoning , Cao Yun , Yang Jin 
Published: March 2015

AbstractThis study investigated the in vitro drug–drug interaction potential of SIPI5357, an arylalkanol‐piperazine derivative used in the treatment of depression. Drug–drug interaction occurs via inhibition or induction of enzymes involved in their metabolism. In human liver microsomes, SIPI5357 showed the strongest inhibition of CYP2D6, followed by CYP3A4 (testosterone) and CYP2C8. Inhibition was observed in a concentration‐dependent manner, with IC50 values of 18.45 µM, 36.63 µM (CYP3A4/testosterone), 89.23 µM, respectively. SIPI5357 was predicted not to cause significant metabolic drug–drug interaction via inhibition of CYP1A2, CYP2C9, CYP2C19, CYP2E1 or CYP3A4 (midazolam) because the IC50 values for these enzymes were both >100 µM (200 times maximum plasma concentration [Cmax]). SIPI5357 showed a mixed model inhibition of CYP2D6 (Ki = 11.12 µM). The value of [I]/Ki for CYP2D6 inhibition by SIPI5357 is below the FDA cut‐off value of 0.1; it is therefore reasonable to assume that SIPI5357 will not cause significant CYP2D6 inhibition. However, positive controls (50 µM omeprazole and 25 µM rifampin) caused the anticipated CYP induction, but the highest concentration of SIPI5357 (5 µM; 10 times plasma Cmax) had a minimal effect on CYP1A2 and CYP3A4 mRNA levels in freshly isolated human hepatocytes, suggesting that SIPI5357 is not an inducer of these enzymes. However, significant induction of CYP2B6 was observed at 0.5 µM and 5 µM. In conclusion, SIPI5357 might cause drug–drug interaction via induction of CYP2B6. The in vivo drug–drug interaction potential deserves further investigation. Copyright © 2015 John Wiley & Sons, Ltd.
Novel mutation in the BMPR1B gene (R486L) in a polish family and further delineation of the phenotypic features of BMPR1B‐Related brachydactyly
Authors: Badura‐Stronka Magdalena , Mróz Dariusz , Beighton Peter , Łukawiecki Sebastian , Wicher Katarzyna , Latos‐Bieleńska Anna , Kozłowski Kazimierz 
Published: March 2015

BackgroundLehmann et al., [2003, 2006] have documented two different substitutions at position 486 of the BMPR1B gene which resulted in a phenotype of brachydactyly A2 [MIM 112600] or brachydactyly C with symphalangism [MIM 113100].MethodsIn this article we report a family of Polish extraction with a novel mutation: c.1457G>T (R486L) which segregated with a complex brachydactyly. Clinical and radiological data are presented and details of previously reported patients with a pathogenic change of an amino acid at position 486 of the BMPR1B gene are summarized.ConclusionOur data extends the previously known mutational and radiological spectrum associated with mutations in the BMPR1B gene and confirms the existence of a universal hotspot in the BMPR1B gene in this distinctive autosomal dominant brachydactyly disorder.It is of interest that an affected female in the Polish family had a severe congenital malformation of the venous system in addition to her digital anomalies. This observation raises the possibility of disturbance of embryonic angiogenesis by specific mutations in BMPR1B. Birth Defects Research (Part A) 103:567–572, 2015. © 2015 Wiley Periodicals, Inc.