bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gatekeeping Testing via Adaptive Alpha Allocation
Authors: Li Jianjun(David) , Mehrotra Devan V. 
Published: October 2008

AbstractIn a typical clinical trial, there are one or two primary endpoints, and a few secondary endpoints. When at least one primary endpoint achieves statistical significance, there is considerable interest in using results for the secondary endpoints to enhance characterization of the treatment effect. Because multiple endpoints are involved, regulators may require that the familywise type I error rate be controlled at a pre‐set level. This requirement can be achieved by using “gatekeeping” methods. However, existing methods suffer from logical oddities such as allowing results for secondary endpoint(s) to impact the likelihood of success for the primary endpoint(s). We propose a novel and easy‐to‐implement gatekeeping procedure that is devoid of such deficiencies. A real data example and simulation results are used to illustrate efficiency gains of our method relative to existing methods. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Rubrenes: Planar and Twisted
Authors: Paraskar Abhimanyu S. , Reddy A. Ravikumar , Patra Asit , Wijsboom Yair H. , Gidron Ori , Shimon Linda J. W. , Leitus Gregory , Bendikov Michael 
Published: October 2008

AbstractSurprisingly, despite its very high mobility in a single crystal, rubrene shows very low mobility in vacuum‐sublimed or solution‐processed organic thin‐film transistors. We synthesized several rubrene analogues with electron‐withdrawing and electron‐donating substituents and found that most of the substituted rubrenes are not planar in the solid state. Moreover, we conclude (based on experimental and calculated data) that even parent rubrene is not planar in solution and in thin films. This discovery explains why high mobility is reported in rubrene single crystals, but rubrene shows very low field‐effect mobility in thin films. The substituted rubrenes obtained in this work have significantly better solubility than parent rubrene and some even form films and not crystals after evaporation of the solvent. Thus, substituted rubrenes are promising materials for organic light‐emitting diode (OLED) applications.
π‐Bonding in Complexes of Benzannulated Biscarbenes, ‐germylenes, and ‐stannylenes: An Experimental and Theoretical Study
Authors: Hahn F. Ekkehardt , Zabula Alexander V. , Pape Tania , Hepp Alexander , Tonner Ralf , Haunschild Robin , Frenking Gernot 
Published: October 2008

AbstractBenzannulated bisstannylenes, exhibiting a CH2C(CH3)2CH2 linking unit and CH2tBu (1) or CH2CH2CH2NMe2 (2) N‐substituents, and their molybdenum tetacarbonyl complexes 3 and 4 have been prepared. The complexes 3 and 4 exhibit remarkably short MoE bond lengths compared to the related biscarbene and bisgermylene complexes. The experimentally determined bonding parameters of the molybdenum bisstannylene complexes are discussed based on DFT calculations.
A phase 1 trial of 2 dose schedules of ABT‐510, an antiangiogenic, thrombospondin‐1‐mimetic peptide, in patients with advanced cancer
Authors: Gordon Michael S. , Mendelson David , Carr Robert , Knight Raymond A. , Humerickhouse Rod A. , Iannone Maria , Stopeck Alison T. 
Published: October 2008

AbstractBACKGROUND.ABT‐510 is a substituted nonapeptide that mimics the antiangiogenic activity of the endogenous protein thrombospondin‐1 (TSP‐1). The current study was designed to establish the safety of ABT‐510 in the treatment of patients with advanced malignancies on a once‐daily (QD) and twice‐daily dosing schedule.METHODS.Patients were randomly assigned to 1 of 6 dosing regimens: 20 mg, 50mg, or 100 mg QD or 10 mg, 25 mg, or 50 mg twice daily. ABT‐510 was administered by subcutaneous bolus injection in cycles of 28 days. Tumor response and disease progression were monitored at 8‐week intervals by computed tomography scan or magnetic resonance imaging.RESULTS.Thirty‐six patients were randomly assigned in equal numbers to the 6 study regimens, with an additional 13 patients randomized to the 10‐mg‐twice‐daily and 50‐mg‐twice‐daily ABT‐510 regimens. The expected pharmacokinetic target was achieved at all dose levels tested. The majority of adverse events were grade 1 or 2 (according to National Cancer Institute Common Toxicity Criteria [version 2]) and were not found to be dose related. The most frequently reported adverse events that were possibly related to ABT‐510 included injection site reactions, asthenia, headache, and nausea. Grade 3 events considered to possibly be related included nausea, dyspnea, bone pain, constipation, vomiting, asthenia, and chills and tremors. One partial response was observed in a patient with carcinosarcoma who received 20 mg QD. The 6‐month progression‐free survival rate was 6%. Approximately 42% of patients (21 of 50 patients) had stable disease for ≥3 months.CONCLUSIONS.ABT‐510 can be administered at doses of 20 mg/day to 100 mg/day without significant toxicity. In the current study, minimal antitumor activity was observed, which was similar to observations in other single‐agent antiangiogenic trials. Cancer 2008. © 2008 American Cancer Society.
Expression of granulocyte‐macrophage colony‐stimulating factor in rheumatoid arthritis: Regulation by tumor necrosis factor‐α
Authors: Haworth Catherine , Brennan Fionula M. , Chantry David , Turner Martin , Maini Ravinder N. , Feldmann Mare 
Published: October 2008

AbstractGranulocyte‐macrophage colony‐stimulating factor (GM‐CSF), in addition to being a growth factor for granulocytes and macrophages, is an activator of cells of the monocyte/macrophage lineage and induces HLA class II expression and cytokine synthesis in these target cells. Macrophage activation and class II expression are prominent features in rheumatoid arthritis (RA) joints, but the mechanism of their stimulation is not understood, since interferon‐y, the major stimulus of class II expression, is not usually detectable at the protein level in synovial cell culture supernatants. We have, therefore, studied GM‐CSF expression in cultures of cells derived from joints affected by RA and osteoarthritis (OA), and show that GM‐CSF is produced spontaneously both by RA synovial cells and to a lesser extent by OA synovial cells in the absence of extrinsic stimuli. GM‐CSF production continues for the 5‐day duration of the culture period. Using neutralizing antibodies to tumor necrosis factor (TNF)‐a we demonstrated that GM‐CSF production in RA synovial cell cultures is dependent on the continued presence of active TNF‐a. This result supports our concept that continued activation of the cytokine network is a marked feature of RA, and that TNF‐a plays a pivotal role in this network, by regulating the production of other pro‐inflammatory cytokines, such as interleukin 1, as demonstrated previously, and GM‐CSF.
Sulfoxygenation Catalysed by Oxidovanadium Complexes
Authors: Wu Pingsong , Çelik Cem , Santoni Gabriella , Dallery Jérome , Rehder Dieter 
Published: October 2008

AbstractModel complexes of vanadate‐dependent peroxidases, viz. oxidovanadium(V) complexes of the general composition [VO(Hn–xL)], have been prepared and characterised. HnL is an n‐basic di‐ or trichiral aminodiethanol [HOCH(Ph)CH2]2NR, with R = N‐methylimidazolyl (H2LA), tris(hydroxymethyl)methyl (H5LB, 2 isomers), 2,3‐dihydroxypropyl (H4LC, 2 isomers) and 2‐hydroxy‐3‐trityloxypropyl (H3LD). These ligands form the complexes [VO(OH)(LA)], [VO(H2LB)], trigonal‐bipyramidal [VO(HLC)]tbp and octahedral Λ‐[VO(HLC)]oct. The ligands R,R,S‐H4LC and R,R,R‐H3LD, and the complexes Λ‐[VO(R,R,S‐HLC)]oct and [VO(R,R,S‐HLC)]tbp have been characterised by X‐ray structure analysis. The complexes [VO(H2LB)] and [VO(HLC)] were immobilised on Merrifield and Barlos resin by anchoring through a free alcoholic group in the ligand side‐chain R. {[VO(H2O)LE]}, an oxidovanadium(IV) complex tethered to Merrifield resin, was prepared by treating [VO(acac)2] with {HLE}, the immobilised Schiff base ligand obtained by condensation of salicylaldehyde with resin‐anchored lysine. The complexes and in situ systems ([VO(OiPr)3] + ligand) as well as the immobilised complexes were investigated for their catalytic activity in the oxygenation, by cumyl hydroperoxide, of thioanisol to its sulfoxide. All of the systems were active, with a selectivity (sulfoxide vs. sulfone) of 95–98 %. Satisfactory turnover rates and a chiral induction up to 37 % ee were observed.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Numerical simulation of two East Asian dust storms in spring 2006
Authors: Sun Jianhua , Zhao Linna 
Published: October 2008

AbstractIn this study we focus the investigation on two dust‐storm events that occurred in spring 2006 over northern China. The first event occurred on 9–11 April and was the most severe in spring 2006 (Case I), whereas the second event occurred on 16–17 April (Case II) and caused widespread dust deposition in northern China, especially in the vicinity of Beijing. The weather systems that generated these dust storms were cold fronts associated with Mongolia cyclones. These events are simulated using a dust‐storm model developed at the Institute of Atmospheric Physics, Beijing. The simulated dust concentrations are found to agree well with the synoptic records and satellite images. The simulated results are also compared with PM10 measurements at the several stations. The comparisons show that the model can predict the rate of dust emission and airborne dust concentration reasonably well. The numerical results are used to analyse the dust emission, transport and deposition associated with the dust storms. The different characteristics of the weather systems that generated the two dust storms are examined in detail. Copyright © 2008 John Wiley & Sons, Ltd.
Reconstruction of a Civil War landscape: Little Folly Island, South Carolina
Authors: Hippensteel Scott P. 
Published: October 2008

AbstractThe inlet dividing Little Folly Island and Big Folly Island was relocated through the use of Union Navy and Army maps and a global positioning system device. Identification of the inlet was confirmed through foraminiferal analysis of marsh sediments retrieved with gouge‐auger cores. The inlet was 1.8 km closer to Confederate batteries on Morris Island than previously believed. In addition to identifying the inlet, sedimentary structures were used to differentiate anthropogenic and natural sand mounds and dunes, resulting in the identification of four previously undocumented Union gun parapets. The results of this study suggest foraminifers are a useful tool for reconstructing coastal military landscapes from the Civil War and potentially earlier conflicts. © 2008 Wiley Periodicals, Inc.
Pilot study experiments sourcing quartzite, Gunnison Basin, Colorado
Authors: Pitblado Bonnie L. , Dehler Carol , Neff Hector , Nelson Stephen T. 
Published: October 2008

AbstractThis paper reports the results of pilot‐study efforts to develop methods to profile quartzite, a rock type to which geochemical and other sourcing techniques have only rarely been applied. The long‐term goal of the research is to fingerprint sources of quartzite in the Gunnison Basin, southwest Colorado, used by Paleoindian people ca. 11,500–8,000 years ago to make stone tools. Success would facilitate reconstruction of Paleoindian mobility in the Southern Rocky Mountains and potentially anywhere prehistoric people used quartzite. The goals of this paper are more modest: to demonstrate that a small‐scale exploration of sourcing techniques suggests reason for optimism that quartzites may be amenable to source discrimination. For the same twenty Gunnison Basin quartzite samples, this study evaluated petrography, ultraviolet fluorescence (UVF), wavelength dispersive X‐ray fluorescence (WD‐XRF), instrumental neutron activation analysis (INAA), and inductively coupled plasma mass spectrometry—both acid‐digestion (AD‐ICP‐MS) and laser ablation (LA‐ICP‐MS)—as means to differentiate among the specimens and the sources they represent. Although more testing is needed to verify and refine our results, the study suggests there is potential for petrography, INAA, and both versions of ICP‐MS to discriminate among quartzites from different source localities in the Gunnison Basin. The greatest potential for discriminating among different sources of quartzite in the Gunnison Basin may lie in a methodology combining petrographic analysis and LA‐ICPMS. Future testing is required to evaluate this two‐fold approach. © 2008 Wiley Periodicals, Inc.
Leptin treatment prevents type I diabetic marrow adiposity but not bone loss in mice
Authors: Motyl Katherine J. , McCabe Laura R. 
Published: October 2008

AbstractLeptin is a hormone secreted by adipocytes that is implicated in the regulation of bone density. Serum leptin levels are decreased in rodent models of type 1 (T1‐) diabetes and in diabetic patients. Whether leptin mediates diabetic bone changes is unclear. Therefore, we treated control and T1‐diabetic mice with chronic (28 days) subcutaneous infusion of leptin or saline to elucidate the therapeutic potential of leptin for diabetic osteoporosis. Leptin prevented the increase of marrow adipocytes and the increased aP2 expression that we observed in vehicle‐treated diabetic mice. However, leptin did not prevent T1‐diabetic decreases in trabecular bone volume fraction or bone mineral density in tibia or vertebrae. Consistent with this finding, markers of bone formation (osteocalcin RNA and serum levels) in diabetic mice were not restored to normal levels with leptin treatment. Interestingly, markers of bone resorption (TRAP5 RNA and serum levels) were decreased in diabetic mice by leptin treatment. In summary, we have demonstrated a link between low leptin levels in T1‐diabetes and marrow adiposity. However, leptin treatment alone was not successful in preventing bone loss. J. Cell. Physiol. 218: 376–384, 2009. © 2008 Wiley‐Liss, Inc.
Regulation of Kir2.1 channels by the Rho‐GTPase, Rac1
Authors: Boyer Stephanie B. , Slesinger Paul A. , Jones S.V. Penelope 
Published: October 2008

AbstractMutations in Kir2.1 inwardly rectifying potassium channels are associated with Andersen syndrome, a disease characterized by potentially fatal cardiac arrhythmias. While several Andersen‐associated mutations affect membrane expression, the cytoplasmic signals that regulate Kir2.1 trafficking are poorly understood. Here, we investigated whether the Rho‐family of small GTPases regulates trafficking of Kir2.1 channels expressed in HEK‐293 cells. Treatment withClostridium difficiletoxin B, an inhibitor of Rho‐family GTPases, or co‐expression of the dominant‐negative mutant of Rac1 (Rac1DN) increased Kir2.1 channels ∼2‐fold. However, the dominant‐negative forms of other Rho‐family GTPases, RhoA or Cdc42, did not alter Kir2.1 currents, suggesting a selective effect of Rac1 on Kir2.1 channels. Single‐channel properties (γ, τo, τc) and total protein levels of Kir2.1 were unchanged with co‐expression of Rac1DN; however, studies using TIRF microscopy and CFP‐tagged Kir2.1 revealed increased channel surface expression. Immunohistochemical detection of extracellularly tagged HA‐Kir2.1 channels showed that Rac1DNreduced channel internalization when co‐expressed. Finally, the dominant‐negative mutant of dynamin, which interferes with endocytosis, occluded the Rac1DN‐induced potentiation of Kir2.1 currents. These data suggest that inhibition of Rac1 increases Kir2.1 surface expression by interfering with endocytosis, likely via a dynamin‐dependent pathway. Surprisingly, Rac1DNdid not alter Kir2.2 current density or internalization, suggesting subunit specific modulation of Kir2.1 channels. Consistent with this, construction of Kir2.1/2.2 chimeras implicated the C‐terminal domain of Kir2.1 in mediating the potentiating effect of Rac1DN. This novel pathway for regulating surface expression of cardiac Kir2.1 channels could have implications for normal and diseased cardiac states. J. Cell. Physiol. 218: 385–393, 2009. © 2008 Wiley‐Liss, Inc.
Mass spectrometric analysis of the S‐layer proteins from Clostridium difficile demonstrates the absence of glycosylation
Authors: Qazi Omar , Hitchen Paul , Tissot Bérangère , Panico Maria , Morris Howard R. , Dell Anne , Fairweather Neil 
Published: October 2008

AbstractLike many other bacterial cell surfaces, the cell wall of Clostridium difficile is also encapsulated by a proteinaceous paracrystalline layer, the surface (S)‐layer. In many bacterial species, the S‐layer proteins (SLPs) have been shown to be glycosylated, whereas in other species glycosylation is absent. Unusually, the S‐layer of C. difficile is composed of two distinct proteins, the high‐molecular weight (HMW) and low‐molecular‐weight (LMW) SLPs. Previous investigations have reported that one or both of these SLPs are glycosylated, though no definitive study has been conducted. We have used a variety of mass spectrometric approaches to analyse SLPs from a number of strains of C. difficile for the presence of associated glycans. Analysis of intact SLPs by matrix assisted laser desorption/ionisation time of flight (MALDI‐ToF) mass spectrometry demonstrated that the observed molecular masses matched the predicted masses of the LMW and HMW SLPs. Furthermore, analysis of Cyanogen bromide (CNBr) and tryptic peptides displayed no evidence of post‐translational modification. In the first in‐depth study of its kind, we unequivocally demonstrate that the S‐layer proteins from the C. difficile strains investigated are not glycosylated. Copyright © 2008 John Wiley & Sons, Ltd.
Rotating three‐dimensional dynamic culture of adult human bone marrow‐derived cells for tissue engineering of hyaline cartilage
Authors: Sakai Shinsuke , Mishima Hajime , Ishii Tomoo , Akaogi Hiroshi , Yoshioka Tomokazu , Ohyabu Yoshimi , Chang Fei , Ochiai Naoyuki , Uemura Toshimasa 
Published: October 2008

AbstractThe method of constructing cartilage tissue from bone marrow‐derived cells in vitro is considered a valuable technique for hyaline cartilage regenerative medicine. Using a rotating wall vessel (RWV) bioreactor developed in a NASA space experiment, we attempted to efficiently construct hyaline cartilage tissue from human bone marrow‐derived cells without using a scaffold. Bone marrow aspirates were obtained from the iliac crest of nine patients during orthopedic operation. After their proliferation in monolayer culture, the adherent cells were cultured in the RWV bioreactor with chondrogenic medium for 2 weeks. Cells from the same source were cultured in pellet culture as controls. Histological and immunohistological evaluations (collagen type I and II) and quantification of glycosaminoglycan were performed on formed tissues and compared. The engineered constructs obtained using the RWV bioreactor showed strong features of hyaline cartilage in terms of their morphology as determined by histological and immunohistological evaluations. The glycosaminoglycan contents per µg DNA of the tissues were 10.01 ± 3.49 µg/µg DNA in the case of the RWV bioreactor and 6.27 ± 3.41 µg/µg DNA in the case of the pellet culture, and their difference was significant. The RWV bioreactor could provide an excellent environment for three‐dimensional cartilage tissue architecture that can promote the chondrogenic differentiation of adult human bone marrow‐derived cells. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 517–521, 2009
MRI‐based surgical simulation of transtrochanteric rotational osteotomy for femoral head osteonecrosis
Authors: Koyama Tsuyoshi , Sugano Nobuhiko , Nishii Takashi , Miki Hidenobu , Takao Masaki , Sato Yoshinobu , Yoshikawa Hideki , Tamura Shinichi 
Published: October 2008

AbstractTranstrochanteric rotational osteotomy (TRO) is one of the joint‐preserving surgical treatments for osteonecrosis of the femoral head (ONFH). It can prevent collapse of the femoral head as necrotic lesions in the weight‐bearing portion can be moved sufficiently to a less weight‐bearing portion by anterior rotation, posterior rotation, or varus angulation. Patient selection and preoperative planning are important to determine indications for TRO. It has been reported that successful TRO requires at least 34% of the weight‐bearing area supported by the intact part of the femoral head. However, this ratio is difficult to preoperatively quantify according to the rotation angle using conventional two‐dimensional MR images or X‐rays. Therefore, we developed a method of simulating TRO using three‐dimensional (3D) models reconstructed from 3D MR images and applied it to serial patients with types C1 and C2 osteonecrosis at stage 1 or 2. The simulation visualized positional changes of the necrotic lesion in the weight‐bearing area and enabled quantitation of the postoperative intact ratio. Our surgical simulation is useful for evaluating the postoperative intact ratio and for determining indications for TRO as well as the optimal angle of femoral head rotation and varus angulation. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 447–451, 2009
Altered gene expression in early osteochondrosis lesions
Authors: Mirams Michiko , Tatarczuch Liliana , Ahmed Yasser A. , Pagel Charles N. , Jeffcott Leo B. , Davies Helen M.S. , Mackie Eleanor J. 
Published: October 2008

AbstractOsteochondrosis is a condition involving defective endochondral ossification and retention of cartilage in subchondral bone. The pathophysiology of this condition is poorly characterized, but it has been proposed that the fundamental defect is failure of chondrocyte hypertrophy. The aim of the current study was to characterize phenotypic changes in chondrocytes associated with the initiation of osteochondrosis. Early lesions were induced in an equine model of osteochondrosis by feeding foals a high energy diet for 8 or 15 weeks. Lesions in articular‐epiphyseal growth cartilage were examined histologically and by quantitative PCR analysis of expression of a number of genes representative of pathways that regulate chondrocyte behavior during endochondral ossification. There were more cells present in clusters in the lesions compared to normal articular cartilage. Expression of matrix metalloproteinase‐13, type I collagen, type X collagen, and Runx2 mRNA was significantly greater in the lesions compared to normal cartilage from the same joint. Expression of vascular endothelial growth factor, type II collagen, connective tissue growth factor, aggrecan, Sox9, and fibroblast growth factor receptor 3 mRNA was not significantly different in lesions than in control cartilage. These observations suggest that osteochondrosis does not result from failure of chondrocytes to undergo hypertrophy. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 452–457, 2009