bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating MicroRNA Expression Profiles Associated With Systemic Lupus Erythematosus
Authors: Carlsen Anting Liu , Schetter Aaron J. , Nielsen Christoffer T. , Lood Christian , Knudsen Steen , Voss Anne , Harris Curtis C. , Hellmark Thomas , Segelmark Mårten , Jacobsen Søren , Bengtsson Anders A. , Heegaard Niels H. H. 
Published: February 2013

AbstractObjectiveTo evaluate the specificity of expression patterns of cell‐free circulating microRNAs (miRNAs) in systemic lupus erythematosus (SLE).MethodsTotal RNA was purified from plasma, and 45 different specific, mature miRNAs were determined using quantitative reverse transcription–polymerase chain reaction assays. A total of 409 plasma samples were obtained from 364 different patients with SLE, healthy control subjects, and control subjects with other autoimmune diseases. The results in the primary cohort of 62 patients with SLE and 29 healthy control subjects were validated in 2 independent cohorts: a validation cohort comprising 68 patients with SLE and 68 healthy control subjects, and a disease control cohort comprising 20 patients with SLE (19 of whom were from the other validation cohort), 46 healthy control subjects, 38 patients with vasculitis, 18 patients with rheumatoid arthritis, and 20 immunosuppressed patients.ResultsSeven miRNAs were statistically significantly differentially expressed in plasma from patients with SLE. The expression of miRNA‐142‐3p (miR‐142‐3p) and miR‐181a was increased, and the expression of miR‐106a, miR‐17, miR‐20a, miR‐203, and miR‐92a was decreased. In addition, the expression of miR‐342‐3p, miR‐223, and miR‐20a was significantly decreased in SLE patients with active nephritis. A predictive model for SLE based on 2 or 4 miRNAs differentiated patients with SLE from control subjects (76% accuracy) when validated independently (P < 2 × 10−9). Use of the 4‐miRNA model provided highly significant differentiation between the SLE group and disease controls, except for those with vasculitis.ConclusionCirculating miRNAs are systematically altered in SLE. A 4‐miRNA signature was diagnostic of SLE, and a specific subset of miRNA profiles was associated with nephritis. All of the signature miRNAs target genes in the transforming growth factor β signaling pathways. Other targets include regulation of apoptosis, cytokine–cytokine receptors, T cell development, and cytoskeletal organization. These findings highlight possible dysregulated pathways in SLE and suggest that circulating miRNA patterns distinguish SLE from other immunoinflammatory phenotypes.
A Hot Spot for Systemic Lupus Erythematosus, but Not for Psoriatic Arthritis, Identified by Spatial Analysis Suggests an Interaction Between Ethnicity and Place of Residence
Authors: Al‐Maini Mustafa , Jeyalingam Thurarshen , Brown Patrick , Lee Jennifer J. Y. , Li Lennon , Su Jiandong , Gladman Dafna D. , Fortin Paul R. 
Published: February 2013

ObjectiveTo describe the spatial distribution of incident cases of systemic lupus erythematosus (SLE) using geographic information systems (GIS).MethodsSpatial analyses were carried out on 890 SLE patients and 541 psoriatic arthritis (PsA) patients (controls). Age‐ and sex‐adjusted rates for SLE/PsA for each census tract were calculated using denominator population values from the Canadian census. Spatial variations in relative risk were estimated by modeling risk as the product of a time effect, an age effect, and a spatially autocorrelated risk surface to identify hot spots. Patients within the detected hot spot were compared to those outside the hot spot to identify explanatory factors.ResultsSLE patients were predominantly female (87.75%) and the incidence rate was highest among those 15–19 years of age (2.4 cases/100,000 person‐years). In an SLE hot spot containing 59 patients, 100% of the patients were female and 49.1% (n = 29) were Caucasian, while outside of the hot spot, 86.9% (n = 722) of the patients were female and 68.4% (n = 568) were Caucasian. The proportion of cases of Chinese ethnicity was significantly greater within the hot spot. An interaction was found between Chinese ethnicity and residence within the hot spot, with the risk of SLE to the Chinese population found to be twice the risk to the non‐Chinese population.ConclusionGIS was used to map SLE cases and a hot spot was identified after adjustment for age and sex. Ethnicity by itself did not confer an increased risk of SLE, but the interaction of ethnicity with location of residence significantly increased the risk of SLE.
Alginate‐Based Microcapsules with a Molecule Recognition Linker and Photosensitizer for the Combined Cancer Treatment
Authors: Du Cuiling , Zhao Jie , Fei Jinbo , Gao Liang , Cui Wei , Yang Yang , Li Junbai 
Published: February 2013

AbstractA reactive template method was used to fabricate alginate‐based hydrogel microcapsules. The uniform and well‐dispersed hydrogel capsules have a high drug loading capacity. After they are coated by a folate‐linked lipid mixture on the surface, the capsules possess higher cell uptake efficiency by the molecule recognition between folate and the folate‐receptor overexpressed by the cancer cells. Moreover, in this bioconjugate, the lipid could remarkably reduce the release rate of hydrophilic doxorubicin from the hydrogel microcapsules and encapsulate the hydrophobic photosensitizer hypocrellin B. The biointerfaced capsules could be used as drug carriers for combined treatment against cancer cell proliferation in vitro; this was much more effective than chemotherapy or photodynamic therapy alone.
Insights into the Roles of Desolvation and π‐Electron Interactions during DNA Polymerization
Authors: Motea Edward A. , Lee Irene , Berdis Anthony J. 
Published: February 2013

AbstractThis report describes the use of several isosteric non‐natural nucleotides as probes to evaluate the roles of nucleobase shape, size, solvation energies, and π‐electron interactions as forces influencing key kinetic steps of the DNA polymerization cycle. Results are provided using representative high‐ and low‐fidelity DNA polymerases. Results generated with the E. coli Klenow fragment reveal that this high‐fidelity polymerase utilizes hydrophobic nucleotide analogues with higher catalytic efficiencies compared to hydrophilic analogues. These data support a major role for nucleobase desolvation during nucleotide selection and insertion. In contrast, the low‐fidelity HIV‐1 reverse transcriptase discriminates against hydrophobic analogues and only tolerates non‐natural nucleotides that are capable of hydrogen‐bonding or π‐stacking interactions. Surprisingly, hydrophobic analogues that function as efficient substrates for the E. coli Klenow fragment behave as noncompetitive or uncompetitive inhibitors against HIV‐1 reverse transcriptase. In these cases, the mode of inhibition depends upon the absence or presence of a templating nucleobase. Molecular modeling studies suggest that these analogues bind to the active site of reverse transcriptase as well as to a nearby hydrophobic binding pocket. Collectively, the studies using these non‐natural nucleotides reveal important mechanistic differences between representative high‐ and low‐fidelity DNA polymerases during nucleotide selection and incorporation.
Are β‐H‐Eliminations or Alkene Insertions Feasible Elementary Steps in Catalytic Cycles Involving Gold(I) Alkyl Species or Gold(I) Hydrides?
Authors: Klatt Günter , Xu Rong , Pernpointner Markus , Molinari Lise , Quang Hung Tran , Rominger Frank , Hashmi A. Stephen K. , Köppel Horst 
Published: February 2013

AbstractThe β‐H‐elimination in the (IPr)AuEt complex and its microscopic reverse, the insertion of ethene into (IPr)AuH, were investigated in a combined experimental and computational study. Our DFT‐D3 calculations predict free‐energy barriers of 49.7 and 36.4 kcal mol−1 for the elimination and insertion process, respectively, which permit an estimation of the rate constants for these reactions according to classical transition‐state theory. The elimination/insertion pathway is found to involve a high‐energy ethene hydride species and is not significantly affected by continuum solvent effects. The high barriers found in the theoretical study were then confirmed experimentally by measuring decomposition temperatures for several different (IPr)AuI‐alkyl complexes which, with a slow decomposition at 180 °C, are significantly higher than those of other transition‐metal alkyl complexes. In addition, at the same temperature, the decomposition of (IPr)AuPh and (IPr)AuMe, both of which cannot undergo β‐H‐elimination, indicates that the pathway for the observed decomposition at 180 °C is not a β‐H‐elimination. According to the calculations, the latter should not occur at temperatures below 200 °C. The microscopic reverse of the β‐H‐elimination, the insertion of ethene into the (IPr)AuH could neither be observed at pressures up to 8 bar at RT nor at 1 bar at 80 °C. The same is true for the strain‐activated norbornene.
Speciation of [Cp*2M2O5] in Polar and Donor Solvents
Authors: Sözen‐Aktaş Pelin , Del Rosal Iker , Manoury Eric , Demirhan Funda , Lledós Agustí , Poli Rinaldo 
Published: February 2013

AbstractThe speciation of compounds [Cp*2M2O5] (M=Mo, W; Cp*=pentamethylcyclopentadienyl) in different protic and aprotic polar solvents (methanol, dimethyl sulfoxide, acetone, acetonitrile), in the presence of variable amounts of water or acid/base, has been investigated by 1H NMR spectrometry and electrical conductivity. Specific hypotheses suggested by the experimental results have been further probed by DFT calculations. The solvent (S)‐assisted ionic dissociation to generate [Cp*MO2(S)]+ and [Cp*MO3]− takes place extensively for both metals only in water/methanol mixtures. Equilibrium amounts of the neutral hydroxido species [Cp*MO2(OH)] are generated in the presence of water, with the relative amount increasing in the order MeCN≈acetone<MeOH<DMSO. Addition of a base (Et3N) converts [Cp*2M2O5] into [Et3NH]+[Cp*MO3]−, for which the presence of a NH⋅⋅⋅OM interaction is revealed by 1H NMR spectroscopy in comparison with the sodium salts, Na+[Cp*MO3]−. These are fully dissociated in DMSO and MeOH, but display a slow equilibrium between free ions and the ion pair in MeCN and acetone. Only one resonance is observed for mixtures of [Cp*MO3]− and [Cp*MO2(OH)] because of a rapid self‐exchange. In the presence of extensive ionic dissociation, only one resonance is observed for mixtures of the cationic [Cp*MO2(S)]+ product and the residual undissociated [Cp*2M2O5] because of a rapid associative exchange via the trinuclear [Cp*3M3O7]+ intermediate. In neat methanol, complex [Cp*2W2O5] reacts to yield extensive amounts of a new species, formulated as the mononuclear methoxido complex [Cp*WO2(OMe)] on the basis of the DFT study. An equivalent product is not observed for the Mo system. The addition of increasing amounts of water results in the rapid decrease of this product in favor of [Cp*2W2O5] and [Cp*WO2(OH)].
Azatrioxa[8]circulenes: Planar Anti‐Aromatic Cyclooctatetraenes
Authors: Nielsen Christian B. , Brock‐Nannestad Theis , Hammershøj Peter , Reenberg Theis K. , Schau‐Magnussen Magnus , Trpcevski Denis , Hensel Thomas , Salcedo Roberto , Baryshnikov Gleb V. , Minaev Boris F. , Pittelkow Michael 
Published: February 2013

AbstractWe describe herein the first synthesis of a new class of anti‐aromatic planar cyclooctatetraenes: the azatrioxa[8]circulenes. This was achieved by treating a suitably functionalised 3,6‐dihydroxycarbazole with 1,4‐benzoquinones or a 1,4‐naphthoquinone. We fully characterised the azatrioxa[8]circulenes by using optical, electrochemical and computational techniques as well as by single‐crystal X‐ray crystallography. The results of a computational study (NICS) suggest that the central planar cyclooctatetraene is anti‐aromatic when the molecules are in neutral or oxidised states (2+), and that the corresponding dianions are aromatic. We discuss the aromatic/anti‐aromatic nature of the planar cyclooctatetraenes and compare them with the isoelectronic tetraoxa[8]circulenes.
E/Z Oxime Isomerism in PhC(NOH)CN
Authors: Bohle D. Scott , Chua Zhijie , Perepichka Inna , Rosadiuk Kristopher 
Published: February 2013

AbstractThe reaction of nitric oxide with benzyl cyanide in the presence of potassium methoxide at low temperature gave the dipotassium salt of a bis‐diazeniumdiolate 2 in excellent yield. Two new stereospecific syntheses of E or Z 2‐(hydroxyimino)‐2‐phenylacetonitrile from 2 have been found. The thermodynamics of the E/Z isomerization has been investigated spectroscopically in solution, in the solid state by differential scanning calorimetry (DSC), and theoretically in the gas phase. Evidence of catalysis by NO of E/Z oxime isomerization has been observed.
Using Calixarenes To Model Polyelectrolyte Surfactant Nucleation Sites
Authors: Basilio Nuno , Gómez Borja , Garcia‐Rio Luis , Francisco Vitor 
Published: February 2013

AbstractThe formation of mixed micelles composed of dodecyltrimethylammonium bromide (C12TAB) and a hexamethylated p‐sulfonatocalix[6]arene (SC6HM) was studied by several techniques. It was found that above the critical aggregation concentration the concentrations of free and micellized surfactant are strongly related to that of SC6HM. When there is free SC6HM in solution, the addition of C12TAB mainly results in an increase in the concentration of micellized surfactant, but when all SC6HM has been aggregated, the addition of C12TAB results in a substantial increase in the concentration of free surfactant in solution. When the concentration of free surfactant is equal to the critical micelle concentration of the pure system, a second independent aggregation process is observed. This aggregation behavior has many features that are similar to those of more complex systems that involve surfactants in the presence of oppositely charged polyelectrolytes. In this way, calixarenes can serve as simple models to mimic polyelectrolytes and to gain insight into the complex behavior displayed by these macromolecules.
Synthesis of the Carbon Framework of Scholarisine A by Intramolecular Oxidative Coupling
Authors: Watanabe Tsugunori , Umezawa Naoki , Kato Nobuki , Higuchi Tsunehiko 
Published: February 2013

AbstractScholarisine A, isolated from the leaves of Alstonia scholaris, is a monoterpene indole alkaloid with an unprecedented cage‐like structure. In this paper, preparation of the distinctive cage‐like core skeleton of scholarisine A is described. The key feature of this synthetic strategy is an intramolecular oxidative coupling reaction at the late stage to construct a 10‐oxa‐tricyclo[5.3.1.03, 8]undecan‐9‐one structure fused with indolenine. Intramolecular oxidative coupling by using N‐iodosuccinimide gave the carbon framework of scholarisine A in moderate yield, which is the first example of intramolecular oxidative‐coupling reaction between non‐activated enolate and indole. This study lays the foundation for continued investigations towards the total synthesis of scholarisine A.
Diels–Alder and Retro‐Diels–Alder Cycloadditions of (1,2,3,4,5‐Pentamethyl)cyclopentadiene to La@C2v‐C82: Regioselectivity and Product Stability
Authors: Garcia‐Borràs Marc , Luis Josep M. , Swart Marcel , Solà Miquel 
Published: February 2013

AbstractOne of the most important reactions in fullerene chemistry is the Diels–Alder (DA) reaction. In two previous experimental studies, the DA cycloaddition reactions of cyclopentadiene (Cp) and 1,2,3,4,5‐pentamethylcyclopentadiene (Cp*) with La@C2v‐C82 were investigated. The attack of Cp was proposed to occur on bond 19, whereas that of Cp* was confirmed by X‐ray analysis to be over bond o. Moreover, the stabilities of the Cp and Cp* adducts were found to be significantly different, that is, the decomposition of La@C2v‐C82Cp was one order of magnitude faster than that of La@C2v‐C82Cp*. Herein, we computationally analyze these DA cycloadditions with two main goals: First, to compute the thermodynamics and kinetics of the cycloadditions of Cp and Cp* to different bonds of La@C2v‐C82 to assess and compare the regioselectivity of these two reactions. Second, to understand the origin of the different thermal stabilities of the La@C82Cp and La@C82Cp* adducts. Our results show that the regioselectivity of the two DA cycloadditions is the same, with preferred attack on bond o. This result corrects the previous assumption of the regioselectivity of the Cp attack that was made based only on the shape of the La@C82 singly occupied molecular orbital. In addition, we show that the higher stability of the La@C82Cp* adduct is not due to the electronic effects of the methyl groups on the Cp ring, as previously suggested, but to higher long‐range dispersion interactions in the Cp* case, which enhance the stabilization of the reactant complex, transition state, and products with respect to the separated reactants. This stabilization for the La@C82Cp* case decreases the Gibbs reaction energy, thus allowing competition between the direct and retro reactions and making dissociation more difficult.
Microwave‐Assisted Solid‐Phase Synthesis of Antifreeze Glycopeptides
Authors: Izumi Ryukou , Matsushita Takahiko , Fujitani Naoki , Naruchi Kentaro , Shimizu Hiroki , Tsuda Sakae , Hinou Hiroshi , Nishimura Shin‐Ichiro 
Published: February 2013

AbstractMicrowave‐assisted solid‐phase synthesis allows for the rapid and large‐scale preparation and structure–activity characterization of tandem repeating glycopeptides, namely monodispersed synthetic antifreeze glycopeptides (syAFGPs, H‐[Ala‐Thr(Galβ1,3GalNAcα1→)‐Ala]n‐OH, n=2–6). By employing novel AFGP analogues, we have demonstrated that of the monodispersed syAFGPn (n=2–6, degree of polymerization, DP=2–6, Mw=1257–3690 Da), syAFGP5 (DP=5, Mw=3082 Da) and syAFGP6 (DP=6, Mw=3690 Da) exhibit the ability to form typical hexagonal bipyramidal ice crystals and satisfactory thermal hysteresis activity. Structural characterization by NMR and CD spectroscopy revealed that syAFGP6 forms a typical poly‐L‐proline type II helix‐like structure in aqueous solution whereas enzymatic modification by sialic acid of the residues at the C‐3 positions of the nonreducing Gal residues disturbs this conformation and eliminates the antifreeze activity.
Proton‐Assisted Hydrogen Activation on Polyhedral Cations
Authors: Calvo Beatriz , Macías Ramón , Artigas Maria Jose , Lahoz Fernando J. , Oro Luis A. 
Published: February 2013

AbstractThe treatment of [1,1‐(PR3)2‐3‐(Py)‐closo‐1,2‐RhSB9H8] (PR3=PMe3 (2) or PPh3 and PMe3 (3); Py=pyridine) with triflic acid (TfOH) affords [1,3‐μ‐(H)‐1,1‐(PR3)2‐3‐(Py)‐1,2‐RhSB9H8]+ (PR3=PMe3 (4) or PMe3 and PPh3 (5)). These products result from the protonation of the 11‐vertex closo‐cages along the Rh(1)B(3) edge. These unusual cationic rhodathiaboranes are stable in solution and in the solid state and they have been fully characterized by multinuclear NMR spectroscopy. In addition, compound 5 was characterized by single‐crystal X‐ray diffraction. One remarkable feature in these structures is the presence of three {Rh(PPh3)(PMe3)}‐to‐{ηn‐SB9H8(Py)} (n=4 or 5) conformers in the unit cell, thus giving an uncommon case of conformational isomerism. [1,1‐(PPh3)2‐3‐(Py)‐closo‐1,2‐RhSB9H8] (1), that is, the bis‐PPh3‐ligated analogue of compounds 2 and 3, is also protonated by TfOH, but, in marked contrast, the resulting cation, [1,3‐μ‐(H)‐1,1‐(PPh3)2‐3‐(Py)‐1,2‐RhSB9H8]+ (6), is attacked by a triflate anion with the release of a PPh3 ligand and the formation of [8,8‐(OTf)(PPh3)‐9‐(Py)‐nido‐8,7‐RhSB9H9] (9). The result is an equilibrium that involves cationic species 6, neutral OTf‐ligated compound 9, and [HPPh3]+, which is formed upon protonation of the released PPh3 ligand. The resulting ionic system reacts readily with H2 to give cationic species [8,8,8‐(H)(PPh3)2‐9‐(Py)‐nido‐8,7‐RhSB9H9]+ (7). This reactivity is markedly higher than that previously found for compound 1 and it introduces a new example of proton‐assisted H2 activation that occurs on a polyhedral boron‐containing compound.
Chiral Fluorinated α‐Sulfonyl Carbanions: Enantioselective Synthesis and Electrophilic Capture, Racemization Dynamics, and Structure
Authors: Hellmann Gunther , Hack Achim , Thiemermann Eric , Luche Olaf , Raabe Gerhard , Gais Hans‐Joachim 
Published: February 2013

AbstractEnantiomerically pure triflones R1CH(R2)SO2CF3 have been synthesized starting from the corresponding chiral alcohols via thiols and trifluoromethylsulfanes. Key steps of the syntheses of the sulfanes are the photochemical trifluoromethylation of the thiols with CF3Hal (Hal=halide) or substitution of alkoxyphosphinediamines with CF3SSCF3. The deprotonation of RCH(Me)SO2CF3 (R=CH2Ph, iHex) with nBuLi with the formation of salts [RC(Me)SO2CF3]Li and their electrophilic capture both occurred with high enantioselectivities. Displacement of the SO2CF3 group of (S)‐MeOCH2C(Me)(CH2Ph)SO2CF3 (95 % ee) by an ethyl group through the reaction with AlEt3 gave alkane MeOCH2C(Me)(CH2Ph)Et of 96 % ee. Racemization of salts [R1C(R2)SO2CF3]Li follows first‐order kinetics and is mainly an enthalpic process with small negative activation entropy as revealed by polarimetry and dynamic NMR (DNMR) spectroscopy. This is in accordance with a CαS bond rotation as the rate‐determining step. Lithium α‐(S)‐trifluoromethyl‐ and α‐(S)‐nonafluorobutylsulfonyl carbanion salts have a much higher racemization barrier than the corresponding α‐(S)‐tert‐butylsulfonyl carbanion salts. Whereas [PhCH2C(Me)SO2tBu]Li/DMPU (DMPU = dimethylpropylurea) has a half‐life of racemization at −105 °C of 2.4 h, that of [PhCH2C(Me)SO2CF3]Li at −78 °C is 30 d. DNMR spectroscopy of amides (PhCH2)2NSO2CF3 and (PhCH2)N(Ph)SO2CF3 gave NS rotational barriers that seem to be distinctly higher than those of nonfluorinated sulfonamides. NMR spectroscopy of [PhCH2C(Ph)SO2R]M (M=Li, K, NBu4; R=CF3, tBu) shows for both salts a confinement of the negative charge mainly to the Cα atom and a significant benzylic stabilization that is weaker in the trifluoromethylsulfonyl carbanion. According to crystal structure analyses, the carbanions of salts {[PhCH2C(Ph)SO2CF3]Li⋅L}2 (L=2 THF, tetramethylethylenediamine (TMEDA)) and [PhCH2C(Ph)SO2CF3]NBu4 have the typical chiral CαS conformation of α‐sulfonyl carbanions, planar Cα atoms, and short CαS bonds. Ab initio calculations of [MeC(Ph)SO2tBu]− and [MeC(Ph)SO2CF3]− showed for the fluorinated carbanion stronger nC→σ* and nO→σ* interactions and a weaker benzylic stabilization. According to natural bond orbital (NBO) calculations of [R1C(R2)SO2R]− (R=tBu, CF3) the nC→σ*SR interaction is much stronger for R=CF3. Ab initio calculations gave for [MeC(Ph)SO2tBu]Li⋅2 Me2O an O,Li,Cα contact ion pair (CIP) and for [MeC(Ph)SO2CF3]Li⋅2 Me2O an O,Li,O CIP. According to cryoscopy, [PhCH2C(Ph)SO2CF3]Li, [iHexC(Me)SO2CF3]Li, and [PhCH2C(Ph)SO2CF3]NBu4 predominantly form monomers in tetrahydrofuran (THF) at −108 °C. The NMR spectroscopic data of salts [R1(R2)SO2R3]Li (R3=tBu, CF3) indicate that the dominating monomeric CIPs are devoid of CαLi bonds.
Preparation of Stereodefined Secondary Alkyllithium Compounds
Authors: Seel Stephanie , Dagousset Guillaume , Thaler Tobias , Frischmuth Annette , Karaghiosoff Konstantin , Zipse Hendrik , Knochel Paul 
Published: February 2013

AbstractWe have developed a practical stereoretentive iodine/lithium‐exchange process that allows the stereodefined preparation of cis‐ and trans‐cycloalkyllithium compounds from their corresponding stereodefined iodides. Quenching with electrophiles offers stereospecific access to both cis‐ (up to 96 % cis) and trans‐cycloalkyl derivatives (up to 99 % trans). A detailed study of the thermodynamic stabilities, stereochemical behavior, and reactivities of axially and equatorially substituted cyclohexyllithium reagents is reported. Ab initio calculations demonstrate that the formation of oligomeric cyclohexyllithium structures is pivotal for explaining the observed stereochemical preference.