bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating levels of MCP‐1, sIL‐2R, IL‐15, and IL‐8 predict anemia response to pomalidomide therapy in myelofibrosis
Authors: Pardanani Animesh , Begna Kebede , Finke Christy , Lasho Terra , Tefferi Ayalew 
Published: January 2011

AbstractCytokine‐phenotype associations have recently been described in primary myelofibrosis and increased levels of IL‐8, sIL‐2R, IL‐12, and IL‐15 were found to be independently predictive of inferior survival. Pomalidomide therapy is effective for alleviating anemia in myelofibrosis; we examined the relationship between plasma cytokine/chemokine levels and response to treatment with pomalidomide. The study population included 32 Mayo Clinic patients (median age 66 years) who participated in two consecutive clinical trials of pomalidomide therapy for myelofibrosis‐associated anemia. Ten (31%) patients achieved anemia response per International Working Group criteria. Anemia response was seen only in the presence of JAK2V617F (P = 0.04) and, in addition, predicted by lower circulating levels of MCP‐1 (P = 0.003), IL‐2R (P = 0.008), IL‐15 (0.01), and IL‐8 (P = 0.02). Marked splenomegaly and increased serum LDH level were associated with poor response (P = 0.02 and 0.03, respectively) and with each other (P = 0.02), but not with JAK2V617F. The aforementioned cytokines were not significantly associated with JAK2V617F but increased levels of sIL‐2R (P = 0.01), IL‐15 (P = 0.06), and MCP‐1 (P = 0.07) clustered with marked splenomegaly. Current data suggest that, in the context of pomalidomide treatment, response is more likely in the presence of JAK2V617F and further predicted by the absence of marked splenomegaly or increased levels of proinflammatory cytokines. Am. J. Hematol. 86:343–345, 2011. © 2011 Wiley‐Liss, Inc.
Platelet‐induced thrombin generation by the calibrated automated thrombogram assay is increased in patients with essential thrombocythemia and polycythemia vera
Authors: Panova‐Noeva Marina , Marchetti Marina , Spronk Henri Maria , Russo Laura , Diani Erika , Finazzi Good , Salmoiraghi Silvia , Rambaldi Aueesandrd , Barbui Titiano , Ten Cate Huao , Falanga Anna 
Published: January 2011

AbstractThe platelet contribution to the thrombophilic state of patients with myeloproliferative neoplasms (MPNs), i.e., essential thrombocythemia (ET) and polycythemia vera (PV), remains uncertain. In this study we aimed to characterize the thrombin generation (TG) potential expressed by platelets from these subjects, compare it to normal platelets, and identify what factors might be responsible for platelet TG. In a group of 140 MPN patients (80 ET and 60 PV) and 72 healthy subjects we measured the global procoagulant potential of platelet rich plasma (PRP) utilizing the TG assay by the calibrated automated thrombogram (CAT). To characterize the procoagulant contribution of platelets in PRP, the TG of both isolated platelets and platelet poor plasma was measured, and the platelet surface expression of TF was determined. Finally, the activation status of platelets was assessed by the levels of P‐selectin expressed on platelet surface. MPN patients had significantly increased PRP and isolated platelet TG potential compared to controls. This was associated to the occurrence of platelet activation. Patients carriers of the JAK2V617F mutation showed the highest values of TG and platelet surface TF and P‐selectin. Platelet TG potential was significantly lower in hydroxyurea (HU) compared to non‐HU‐treated patients and was lowest in HU‐treated JAK2V617F carriers. In subjects not receiving HU, platelet TG significantly increased by JAK2V617F allele burden increment (P < 0.05). This study demonstrates a platelet‐dependent form of hypercoagulability in MPN patients, particularly in those carriers of the JAK2V617F mutation. The cytoreductive therapy with HU significantly affects this prothrombotic phenotype. Am. J. Hematol. 86:337–342, 2011. © 2011 Wiley‐Liss, Inc.
Synthesis and characterization of some bis(cyclopentadienyl)titanium(IV) complexes with internally functionalized oximes(LH): sol–gel transformations of Cp2TiCl2, Cp2TiClL and Cp2TiL2 to nano‐sized anatase titania
Authors: Chaudhary Archana , Sharma Namita , Dhayal Veena , Saxena Arpita , Nagar Meena , Bohra Rakesh 
Published: January 2011

AbstractSome bis(cyclopentadienyl)titanium(IV) complexes of the type [Cp2TiCl2−n{L}n] {where, n = 1 or 2; L = ONC(R)Ar; R = H or CH3 and Ar = C5H4N‐2, C4H3O‐2 or C4H3S‐2} have been synthesized by the metathetical reactions of Cp2TiCl2 with the sodium salt of internally functionalized oximes in 1:1 and 1:2 stoichiometry in anhydrous THF. All these red to brown colored solid derivatives have been characterized by elemental analyses, FT‐IR and NMR (1H and 13C{1H}) spectral studies. The FAB mass spectra of some representative derivatives indicate their monomeric nature. Oximato ligands in all the complexes appear to bind the titanium via N and O in a dihapto (${\bf \eta}^{2}$‐N, O) manner in the solid state. Thermogravimetric curves of [Cp2TiCl{ONC(CH3)C5H4N‐2}] and [Cp2Ti{ONC(CH3)C5H4N‐2}2] suggest the formation of hybrid materials CpTiO(Cl) and Cp2TiO, respectively, as the final products at 900 °C under nitrogen atmosphere. Sol–gel transformations of Cp2TiCl2, [Cp2TiCl{ONC(CH3)C5H4N‐2}] and [Cp2Ti{ONC(CH3)C5H4N‐2}2] yielded titania a–c, respectively, at low sintering temperature (600 °C). The powder XRD patterns, IR as well as Raman spectra of all these oxides indicate the formation of nano‐sized anatase phase. The SEM images of titania a–c indicate agglomers like surface morphologies. The absorption spectra of a–c exhibit an energy band gap in the range of 3.47–3.71 eV. Copyright © 2011 John Wiley & Sons, Ltd.
Synthesis of 1H‐Pyrazole‐1‐carboxamide Derivatives and Their Antiproliferative Activity against Melanoma Cell Line
Authors: El‐Gamal Mohammed I. , Sim Tae Bo , Hong Jun Hee , Cho Jung‐Hyuck , Yoo Kyung Ho , Oh Chang‐Hyun 
Published: December 2010

AbstractSynthesis of a new series of 1H‐pyrazole‐1‐carboxamide derivatives is described. Their antiproliferative activity against A375 human melanoma cell line was tested and the effect of substituents on the diarylpyrazole scaffold was investigated. The pharmacological results indicated that most of the newly synthesized compounds showed moderate activity against A375, compared with sorafenib. Among all of these derivatives, compound IIe which has N‐methylpiperazinyl and phenolic moieties showed the most potent antiproliferative activity against A375 human melanoma cell line.
Behavioral profiles of mouse models for autism spectrum disorders
Authors: Ey Elodie , Leblond Claire S. , Bourgeron Thomas 
Published: January 2011

AbstractAutism spectrum disorders (ASD) are characterized by impairments in reciprocal social communication, and stereotyped verbal and nonverbal behaviors. In approximately 10–25% of the affected individuals, a genetic mutation associated with the condition can be identified. Recently, mutations altering synapse formation, cellular/synaptic growth rate and regulation of excitatory and inhibitory currents were identified in patients with intellectual disability, typical autism, Asperger syndrome or neurological syndromes associated with autistic traits. Following these genetic findings, mouse models carrying mutations similar to those identified in patients have been generated. These models offer the opportunity to investigate in vivo the physiological and behavioral consequences of the mutations. Here, we review the existing data on the phenotypes of mice carrying mutations in genes associated with ASD including neuroligin, neurexin and Shank mutant mice as well as the Fmr1, Mecp2, Ube3a, Nf1, Pten and Tsc1/Tsc2 mutant mice. The diversity and complexity of the phenotype of these mouse models reflect the broad range of phenotypes observed in patients with ASD. Remarkably, results from therapeutic approaches (e.g., modulation of gene expression, administration of pharmacological and nonpharmacological substances, enriched environment) are encouraging since some behavioral alterations could be reversed even when treatment was performed on adult mice. These ongoing studies should therefore increase our understanding of the biological alterations associated with ASD as well as the development of knowledge‐based treatments.
‘It all boils down to respect doesn't it?’: Enacting a sense of community in a deprived inner‐city area
Authors: Patterson Anne , Cromby John , Brown Steven D. , Gross Harriet , Locke Abigail 
Published: January 2011

AbstractAudio recordings of meetings of two community groups in a deprived inner‐city area were analysed, using discursive psychological and conversation analytic techniques to explore situated enactments of ‘community’. Participants situated themselves as members of a geographical community, of an ‘imagined’ community and of other constitutive communities. A sense of community was enacted through five interactional strategies: Affirming moral codes, ‘defending’ other members, distinguishing insiders from outsiders, enacting empowerment and challenging institutions. Participants regularly employed emotional displays and affirmed moral positions, both to constitute ‘community’ and to take action in it. In so doing they worked up social capital and positioned community concerns in ways more reflective of their own situated values than of criminal law or government policy. Copyright © 2011 John Wiley & Sons, Ltd.
Structure and Function of Histone H3 Lysine 9 Methyltransferases and Demethylases
Authors: Krishnan Swathi , Horowitz Scott , Trievel Raymond C. 
Published: January 2011

AbstractHistone lysine methylation is a dynamic chromatin modification that plays key regulatory roles in gene expression and other genomic functions. Methylation of Lys9 in histone H3 (H3K9) is a prominent modification that has been implicated in diverse processes, including transcriptional silencing, heterochromatin formation, and DNA methylation. In this review, we summarize recent advances in understanding the structure and substrate specificity of the H3K9‐specific methyltransferases G9A and GLP and explore current efforts to develop inhibitors of these enzymes. In addition, we discuss the structure and specificity of the recently discovered PHF8 family of histone demethylases that target H3K9 as well as other methylation sites in histones H3 and H4. Finally, we conclude by comparing the H3K9 binding modes displayed by these enzymes and examine the relevance of these studies to their biological functions and to structure‐based inhibitor design.
Luminescent Organic 1D Nanomaterials Based on Bis(β‐diketone)carbazole Derivatives
Authors: Liu Xingliang , Xu Defang , Lu Ran , Li Bin , Qian Chong , Xue Pengchong , Zhang Xiaofei , Zhou Huipeng 
Published: January 2011

AbstractA series of new triphenylamine‐functionalized bis(β‐diketone)s bridged by a carbazole (CnBDKC, n=1, 4, 8, 16) with twisted intramolecular charge‐transfer emission in polar solvents has been synthesized. The length of the carbon chains has a significant effect on the self‐assembling properties of the compounds. Well‐defined 1D nanowires were easily generated from C1BDKC with a methyl group by a reprecipitation approach directed by π‐stacking interaction, and the molecules packed into J‐aggregates in the nanowires. In addition, 1D nanofibers based on C16BDKC bearing a long hexadecyl chain were prepared through the organogelation process, and H‐aggregates were formed driven by the synergistic effect of π‐stacking interaction and van der Waals force in the gel phase. C4BDKC and C8BDKC containing butyl and octyl side chains, respectively, cannot arrange into dispersed nanostructures, probably because π–π interaction between conjugated moieties might be disturbed by the interaction between the side chains, which is, however, not strong enough to dominate the self‐assembling process. Notably, the nanowires based on C1BDKC and the gel nanofibers from C16BDKC can emit strong green light under irradiation, which suggests that these 1D nanomaterials may have potential applications in emitting materials as well as photonic devices.
Elucidating the Origin of Diastereoselectivity in a Self‐Replicating System: Selfishness versus Altruism
Authors: Dieckmann Arne , Beniken Sabrina , Lorenz Christian D. , Doltsinis Nikos L. , von Kiedrowski Günter 
Published: January 2011

AbstractWe have investigated a diastereoselective self‐replicating system based on a cycloaddition of a fulvene derivative and a maleimide using a two‐pronged approach of combining NMR spectroscopy with computational modelling. Two diastereomers are formed with identical rates in the absence of replication. When replication is enabled, one diastereomer takes over the resources as a “selfish” autocatalyst, while exploiting the competitor as a weak “altruist”, resulting in a diastereoselectivity of 16:1. We applied 1D and 2D NMR spectroscopic techniques supported by ab initio chemical shifts as well as ab initio molecular dynamics simulations to study the structure and dynamics of the underlying network. This powerful combination allowed us to decipher the energetic and structural rationale behind the observed behaviour, while static computational methods currently used in the field did not.
A Solution NMR Study of the Interactions of Oligomannosides and the Anti‐HIV‐1 2G12 Antibody Reveals Distinct Binding Modes for Branched Ligands*
Authors: Enríquez‐Navas Pedro M. , Marradi Marco , Padro Daniel , Angulo Jesús , Penadés Soledad 
Published: January 2011

AbstractThe structural and affinity details of the interactions of synthetic oligomannosides, linear (di‐, tri‐, and tetra‐) and branched (penta‐ and hepta‐), with the broadly neutralizing anti‐HIV‐1 antibody 2G12 (HIV=human immunodeficiency virus) have been investigated in solution by using ligand‐based NMR techniques, specifically saturation transfer difference (STD) NMR spectroscopy and transferred NOE experiments. Linear oligomannosides show similar binding modes to the antibody, with the nonreducing terminal disaccharide Manα(1→2)Man (Man=mannose) making the closest protein/ligand contacts in the bound state. In contrast, the branched pentamannoside shows two alternate binding modes, involving both ligand arms (D2‐ and D3‐like), a dual binding description of the molecular recognition of this ligand by 2G12 in solution that differs from the single binding mode deduced from X‐ray studies. On the contrary, the antibody shows an unexpected selectivity for one arm (D1‐like) of the other branched ligand (heptamannoside). This result explains the previously reported lack of affinity enhancement relative to that of the D1‐like tetramannoside. Single‐ligand STD NMR titration experiments revealed noticeable differences in binding affinities among the linear and branched ligands in solution, with the latter showing decreased affinity. Among the analyzed series of ligands, the strongest 2G12 binders were the linear tri‐ and tetramannosides because both show similar affinity for the antibody. These results demonstrate that NMR spectroscopic techniques can deliver abundant structural, dynamics, and affinity information for the characterization of oligomannose‐2G12 binding in solution, thus complementing, and, as in the case of the pentamannoside, extending, the structural view from X‐ray crystallography. This information is of key importance for the development of multivalent synthetic gp120 high‐mannose glycoconjugate mimics in the context of vaccine development.
Revealing Atropisomer Axial Chirality in Drug Discovery
Authors: LaPlante Steven R. , Edwards Paul J. , Fader Lee D. , Jakalian Araz , Hucke Oliver 
Published: January 2011

AbstractAn often overlooked source of chirality is atropisomerism, which results from slow rotation along a bond axis due to steric hindrance and/or electronic factors. If undetected or not managed properly, this time‐dependent chirality has the potential to lead to serious consequences, because atropisomers can be present as distinct enantiomers or diastereoisomers with their attendant different properties. Herein we introduce a strategy to reveal and classify compounds that have atropisomeric chirality. Energy barriers to axial rotation were calculated using quantum mechanics, from which predicted high barriers could be experimentally validated. A calculated rotational energy barrier of 20 kcal mol−1was established as a suitable threshold to distinguish between atropisomers and non‐atropisomers with a prediction accuracy of 86 %. This methodology was applied to subsets of drug databases in the course of which atropisomeric drugs were identified. In addition, some drugs were exposed that were not yet known to have this chiral attribute. The most valuable utility of this tool will be to predict atropisomerism along the drug discovery pathway. When used in concert with our compound classification scheme, decisions can be made during early discovery stages such as “hit‐to‐lead” and “lead optimization,” to foresee and validate the presence of atropisomers and to exercise options of removing, further stabilizing, or rendering the chiral axis of interest more freely rotatable via SAR design, thereby decreasing this potential liability within a compound series. The strategy can also improve drug development plans, such as determining whether a drug or series should be developed as a racemic mixture or as an isolated single compound. Moreover, the work described herein can be extended to other chemical fields that require the assessment of potential chiral axes.
Long form of latent TGF‐β binding protein 1 (Ltbp1L) regulates cardiac valve development
Authors: Todorovic Vesna , Finnegan Erin , Freyer Laina , Zilberberg Lior , Ota Mitsuhiko , Rifkin Daniel B. 
Published: December 2010

AbstractTransforming Growth Factor β (TGF‐β) is crucial for valve development and homeostasis. The long form of Latent TGF‐β binding protein 1 (LTBP1L) covalently binds all TGF‐β isoforms and regulates their bioavailability. Ltbp1L expression analysis during valvulogenesis revealed two patterns of Ltbp1L production: an early one (E9.5–11.5) associated with endothelial‐to‐mesenchymal transformation (EMT); and a late one (E12.5 to birth) contemporaneous with valve remodeling. Similarly, histological analysis of Ltbp1L−/− developing valves identified two different pathologies: generation of hypoplastic endocardial cushions in early valvulogenesis, followed by development of hyperplastic valves in late valvulogenesis. Ltbp1L promotes valve EMT, as Ltbp1L absence yields hypoplastic endocardial cushions in vivo and attenuated EMT in vitro. Ltbp1L−/− valve hyperplasia in late valvuogenesis represents a consequence of prolonged EMT. We demonstrate that Ltbp1L is a major regulator of Tgf‐β activity during valvulogenesis since its absence results in a perturbed Tgf‐β pathway that causes all Ltbp1L−/− valvular defects. Developmental Dynamics, 2011. © 2010 Wiley‐Liss, Inc.
Cuboidal Mo3S4 and Mo3NiS4 Complexes Bearing Dithiophosphates and Chiral Carboxylate Ligands: Synthesis, Crystal Structure and Fluxionality
Authors: Hernandez‐Molina Rita , Gonzalez‐Platas Javier , Kovalenko Konstantin A. , Sokolov Maxim N. , Virovets Alexandre V. , Llusar Rosa , Vicent Cristian 
Published: January 2011

AbstractNew triangular Mo and W cluster complexes incorporating (S)‐lactic acid (HLac), [Mo3S4(μ‐Lac)(dtp)3(py)] (1) and [W3S4(μ‐Lac)(dtp)3(py)] (2), were prepared [dtp = (EtO)2PS2]. Analogous synthetic procedures were adapted for the synthesis of cuboidal Mo3NiS4 to yield [Mo3(Nipy)S4(py)(μ‐OAc)(dtp)3(py)] (3). The crystal structures of 1 and 3 were determined. A detailed variable‐temperature 31P{1H} and 1H NMR study of compounds 1 and 3 indicated fluxional behaviour in non‐coordinating solvents (CDCl3, CD2Cl2 and CDCl2CDCl2). A number of dynamic processes were identified involving the Mo–py site that include configuration inversion [(P) to (M)], hindered Mo–N rotation and pyridine exchange. Experiments with deuterated pyridine revealed a faster substitutional lability of Mo–py compared with Ni–py.
Dinuclear Ru–Cu Complexes: Electronic Characterisation and Application to Dye‐Sensitised Solar Cells
Authors: McCall Keri L. , Jennings James R. , Wang Hongxia , Morandeira Ana , Peter Laurence M. , Durrant James R. , Yellowlees Lesley J. , Robertson Neil 
Published: December 2010

AbstractWe prepared the complexes [Ru{4,4′‐(CO2R‐bpy)2}{Cu(exoO2‐cyclam)}][NO3]2 [R = Et (1), H (2)], which possess a CuII centre covalently linked to a (bipyridyl)RuII fragment. The complexes were characterised by cyclic voltammetry, UV/Vis spectroscopy, hybrid DFT and TD‐DFT (time‐dependent density‐functional theory) calculations, EPR (electron paramagnetic resonance), emission spectroscopy and UV/Vis spectroelectrochemistry, with the latter showing reversible conversion to the mono‐ and di‐oxidised and mono‐ and di‐reduced species. The data suggest the first oxidation to be largely based on the Ru centre but with little energetic difference between the highest occupied orbitals based on Ru and based on Cu. There was also evidence of solvent coordination in both the electrochemistry and spectroelectrochemistry experiments. The redox potentials and the strongvisible absorptions of 2 (λmax = 562 nm, ϵmax = 22200 M–1 cm–1)make it appropriate for study as a sensitiser in a dye‐sensitised solar cell. Charge‐separated lifetime of photoexcited 2 on TiO2 and incident photon‐to‐current conversion efficiency (IPCE) as a function of wavelength were studied and are discussed alongside the formation of dye‐sensitised solar cells with the best efficiency achieved of η = 2.55 %, Voc = 608 mV, Isc = 5.84 mA cm–2 and ff = 0.72. Limitations to the maximum efficiency obtained were attributed to a mismatch between the bipyridyl‐based unoccupied orbital of the dye and the TiO2 conduction band edge.
Effects of bed width and planting date on water productivity of wheat grown on vertisols in the Ethiopian Highlands
Authors: Erkossa Teklu , Menker Michael , Betrie Getnet D. 
Published: December 2010

AbstractWaterlogging is a challenge to wheat (Triticum durum Desf.) productivity under the rainfed system on Vertisols in the Ethiopian Highlands. However using suitable seedbed types and manipulating planting dates can minimize the effects. A four‐year (2000–2003) field experiment was conducted to evaluate three seedbed types broad bed and furrows (BBF) with early planting the traditional ridge and furrows (RF) and its modified version (wide ridge and furrows (WRF)) both under early and late planting in terms of water productivity of wheat. The FAO AquaCrop model was used to estimate crop water requirements. The result indicated that late planting on WRF or RF significantly (p < 0.05) increased grain yield and water productivity. Late planting on WRF (LWRF) increased rainfall water productivity by 66 44 and 51% respectively as compared to BBF early‐planted WRF (EWRF) and late‐planted RF (LRF). This was because of its increased effective area for crop growth over the RF and its relative suitability of planting time over the BBF. Therefore late‐planted WRF can be used for enhanced water productivity of wheat while introducing fast‐grow crops that are tolerant to waterlogging and growing early in the season may further enhance the land and water productivity in the area. Copyright © 2010 John Wiley & Sons Ltd.