bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery of Adamantyl Ethanone Derivatives as Potent 11β‐Hydroxysteroid Dehydrogenase Type 1 (11β‐HSD1) Inhibitors
Authors: Su Xiangdong , Pradaux‐Caggiano Fabienne , Thomas Mark P. , Szeto Michelle W. Y. , Halem Heather A. , Culler Michael D. , Vicker Nigel , Potter Barry V. L. 
Published: May 2010

Abstract11β‐Hydroxysteroid dehydrogenases (11β‐HSDs) are key enzymes regulating the pre‐receptor metabolism of glucocorticoid hormones. The modulation of 11β‐HSD type 1 activity with selective inhibitors has beneficial effects on various conditions including insulin resistance, dyslipidemia and obesity. Inhibition of tissue‐specific glucocorticoid action by regulating 11β‐HSD1 constitutes a promising treatment for metabolic and cardiovascular diseases. A series of novel adamantyl ethanone compounds was identified as potent inhibitors of human 11β‐HSD1. The most active compounds identified (52, 62, 72, 92, 103 and 104) display potent inhibition of 11β‐HSD1 with IC50 values in the 50–70 nM range. Compound 72 also proved to be metabolically stable when incubated with human liver microsomes. Furthermore, compound 72 showed very weak inhibitory activity for human cytochrome P450 enzymes and is therefore a candidate for in vivo studies. Comparison of the publicly available X‐ray crystal structures of human 11β‐HSD1 led to docking studies of the potent compounds, revealing how these molecules may interact with the enzyme and cofactor.
NMR‐Guided Molecular Docking of a Protein–Peptide Complex Based on Ant Colony Optimization
Authors: Korb Oliver , Möller Heiko M. , Exner Thomas E. 
Published: May 2010

AbstractStandard docking approaches used for the prediction of protein–ligand complexes in the drug development process have problems identifying the correct binding mode of large flexible ligands. Herein we show how additional experimental data from NMR experiments can be used to predict the binding mode of a mucin 1 (MUC‐1) pentapeptide recognized by the breast‐cancer‐selective monoclonal antibody SM3. Distance constraints derived from trNOE and saturation transfer difference NMR experiments are combined with the docking approach PLANTS. The resulting complex structures show excellent agreement with the NMR data and with a published X‐ray crystal structure. The method was then further tested on two complexes in order to demonstrate its more general applicability: T‐antigen disaccharide bound to Maclura pomifera agglutinin, and the inhibitor SBi279 bound to S100B protein. Our new approach has the advantages of being fully automatic, rapid, and unbiased; moreover, it is based on relatively easily obtainable experimental data and can greatly increase the reliability of the generated structures.
Towards MRI contrast agents responsive to Ca(II) and Mg(II) ions: metal‐induced oligomerization of dota–bisphosphonate conjugates
Authors: Kubíček Vojtěch , Vitha Tomáš , Kotek Jan , Hermann Petr , Vander Elst Luce , Muller Robert N. , Lukeš Ivan , Peters Joop A. 
Published: May 2010

AbstractIn magnetic resonance imaging (MRI), paramagnetic complexes are utilized as contrast agents. Much attention has been paid to the development of new contrast agents responsive to pH, temperature or concentration of various components of body liquids. We report a new type of MRI probe sensing the concentrations of calcium and magnesium in biological media. The ligand do3apBP combines a dota‐like chelator with a bisphosphonate group. In the complex, the Gd(III) ion is entrapped in the macrocyclic cavity whereas the bisphosphonate group is not coordinated and therefore is available for coordination with endogenous metal ions. In the presence of metal ions, Gd–do3apBP appears to show formation of coordination oligomers leading to an unprecedented increase in r1 up to 200–500%. The extremely high relaxivity response makes this type of compound interesting for further studies as MRI ion‐responsive probes for biomedical research. Copyright © 2010 John Wiley & Sons, Ltd.
NMR relaxation and magnetic properties of superparamagnetic nanoworms
Authors: Gossuin Yves , Disch Sabrina , Vuong Quoc L. , Gillis Pierre , Hermann Raphaël P. , Park Ji‐Ho , Sailor Michael J. 
Published: May 2010

AbstractMaghemite particles are used as T2 contrast agents for magnetic resonance imaging, especially for molecular and cellular imaging. Linear clusters of particles – called nanoworms – were recently developed to enhance the targeting efficiency. In this work, the magnetic and NMR relaxation properties of these nanoworms are studied at multiple magnetic fields. After the usual saturation at 0.5 T, the magnetization of the worms is still increasing, which results in an appreciable increase of the transverse relaxivity at high magnetic fields. The obtained relaxivities are typical of superparamagnetic particles of iron oxide (SPIOs). The transverse relaxation of the worms is clearly more efficient than for the isolated grains, which is confirmed by computer simulations. At high field, the longitudinal relaxation of the worms is less pronounced than for the grains, as expected for SPIOs. The nanoworms thus constitute a promising T2 agent for cellular and molecular imaging. Copyright © 2010 John Wiley & Sons, Ltd.
Inflammatory breast cancer in Italy
Authors: Ionta Maria Teresa , Atzori Francesco , Massidda Bruno 
Published: May 2010

AbstractBreast cancer represents the most common cancer among women in Italy. In the last decade, an increase in incidence and a decrease in mortality from breast cancer have been observed in Italy. These findings may be explained at least in part by the implementation of organized screening programs (SMPs). The screening programs are not diffused homogeneously throughout Italy, where approximately 60% of the population in covered, which explains in part the different outcomes observed across Italy. On the basis of the available data, the authors of this report performed a retrospective analysis on the incidence of 2 different groups of breast cancer patients: those covered or and those not covered by SMPs in Italy. The rates of incidence of T4a, T4b, and T4c breast cancer and of T4 inflammatory breast cancer (IBC) overtime appeared to be lower for the population that was covered by SMPs. On the basis of the estimated 40,000 new cases of breast cancer in Italy per year, the authors attempted to extrapolate the approximate incidence of new cases of T4 breast cancer and calculated that there were between 2800 and 3600 new cases per year taking into account the differences in incidence observed in areas covered or not covered by SMPs. Following the same extrapolations, the estimated incidence of IBC was approximately 200 to 800 new cases per year, representing from 0.6% to 2% of all breast cancers diagnosed every year in Italy. Cancer 2010;116(11 suppl):2736–40. © 2010 American Cancer Society.
Gene expression profiling of inflammatory breast cancer
Authors: Bertucci François , Finetti Pascal , Birnbaum Daniel , Viens Patrice 
Published: May 2010

AbstractBACKGROUND:Inflammatory breast cancer (IBC) is a rare but aggressive form of breast cancer. Despite multimodality treatment, the long‐term survival rate for patients with IBC has remained inferior at 50%. Until recently, IBC was understudied at the molecular level. Since 2004, new high‐throughput molecular profiling technologies have been applied to clinical samples with the aim of identifying genes or pathways potentially involved in disease development that may represent new, clinically relevant targets.METHODS:The authors conducted gene expression profiling studies of IBC clinical samples and investigated issues that may be addressed in the future to allow the “omics” approach to reach its full potential in IBC.RESULTS:Starting in December 2004, 6 research groups compared the expression profiles of IBC samples and non‐IBC samples. The series of samples were small (37 IBCs for the largest study) and heterogeneous (various tumor selection criteria and technologic platforms were used). The results indicated the feasibility of messenger RNA expression profiling from IBC biopsies, and they demonstrated the great transcriptional heterogeneity of IBC and the existence of molecular subtypes similar to non‐IBC that more frequently were basal and positive for ERBB2. Supervised analyses demonstrated differences in gene expression levels between the IBC and non‐IBC variable across studies with sometimes no or very subtle differences and, to date, no gene overlap across the reported signatures. No signature predictive of therapeutic response or clinical outcome has been reliably identified or validated.CONCLUSIONS:Because of the great heterogeneity of IBC, future studies will have to include larger series of IBC samples that are selected using homogeneous criteria. This calls for urgent international collaborations. Cancer 2010;116(11 suppl):2783–93. © 2010 American Cancer Society.
Angiogenesis, lymphangiogenesis, growth pattern, and tumor emboli in inflammatory breast cancer
Authors: Vermeulen Peter B. , van Golen Kenneth L. , Dirix Luc Y. 
Published: May 2010

AbstractThis objective of the current review was to provide the reader with a comprehensive summary of the literature related to 3 important and inter‐related features of the biology of inflammatory breast cancer (IBC): angiogenesis, lymphangiogenesis, and the formation of tumor emboli. Information derived from animal models of IBC as well as from translational studies using tissue samples of patients with IBC are discussed. Cancer 2010;116(11 suppl):2748–54. © 2010 American Cancer Society.
Overcoming radiation resistance in inflammatory breast cancer
Authors: Woodward Wendy A. , Debeb Bisrat G. , Xu Wei , Buchholz Thomas A. 
Published: May 2010

AbstractThe clinical‐pathological features of inflammatory breast cancer include enrichment of factors that have been previously associated with radioresistant disease, including negative hormone receptor status and a phenotype enriched for relatively radioresistant breast cancer stem/progenitor cells. The risks and benefits of accelerated postmastectomy radiation treatment regimens in the multimodality management of inflammatory breast cancer were reviewed at the first International Inflammatory Breast Cancer Conference at The University of Texas M. D. Anderson Cancer Center. The biological basis for radiation resistance and strategies to radiosensitize these tumors were also presented. The prevalent basal phenotype of inflammatory breast cancer makes it an ideal clinical model to examine stem cell hypotheses, which the authors believe can help guide future trials to continue making incremental progress against this aggressive disease. Cancer 2010;116(11 suppl):2840–5. © 2010 American Cancer Society.
Characterization of the roles of RHOC and RHOA GTPases in invasion, motility, and matrix adhesion in inflammatory and aggressive breast cancers
Authors: Wu Mei , Wu Zhi‐fen , Rosenthal Devin T. , Rhee Elliot M. , Merajver Sofia D. 
Published: May 2010

AbstractBACKGROUND:The 2 closely related small GTPases, RHOC and RHOA, are involved in mammary gland carcinogenesis; however, their specific roles in determining cancer cell adhesion and invasion have not been elucidated.METHODS:RHOA and RHOC are highly homologous, thereby posing a major challenge to study their individual functions in cancer cells. By selectively knocking down these proteins, we have been able to alternatively inhibit RHOC and RHOA, while preserving expression of the other rho protein. Quantitative analyses of the growth patterns and invasion in the aggressive estrogen receptor negative cell lines MDA‐231 and SUM149 were carried out on collagen I and Matrigel substrates.RESULTS:RHOC, and not RHOA, modulates surface expression and colocalization of α2 and β1 integrins in MDA‐MB‐231 on collagen I. Neither RHOC or RHOA affected integrin expression in the inflammatory breast cancer cell line SUM149, further highlighting the different regulation of adhesion and motility in inflammatory breast cancer.CONCLUSIONS:This work shows that RHOC and RHOA play different roles in cell‐matrix adhesion, motility, and invasion of MDA‐MB‐231 and reaffirms the crucial role of RHOC‐GTPase in inflammatory breast cancer cell invasion. Cancer 2010;116(11 suppl):2768–82. © 2010 American Cancer Society.
Vanishing viscosity limit of the Navier‐Stokes equations to the euler equations for compressible fluid flow
Authors: Chen Gui‐Qiang G. , Perepelitsa Mikhail 
Published: May 2010

AbstractWe establish the vanishing viscosity limit of the Navier‐Stokes equations to the isentropic Euler equations for one‐dimensional compressible fluid flow. For the Navier‐Stokes equations, there exist no natural invariant regions for the equations with the real physical viscosity term so that the uniform sup‐norm of solutions with respect to the physical viscosity coefficient may not be directly controllable. Furthermore, convex entropy‐entropy flux pairs may not produce signed entropy dissipation measures.To overcome these difficulties, we first develop uniform energy‐type estimates with respect to the viscosity coefficient for solutions of the Navier‐Stokes equations and establish the existence of measure‐valued solutions of the isentropic Euler equations generated by the Navier‐Stokes equations. Based on the uniform energy‐type estimates and the features of the isentropic Euler equations, we establish that the entropy dissipation measures of the solutions of the Navier‐Stokes equations for weak entropy‐entropy flux pairs, generated by compactly supported C2 test functions, are confined in a compact set in H−1, which leads to the existence of measure‐valued solutions that are confined by the Tartar‐Murat commutator relation.A careful characterization of the unbounded support of the measure‐valued solution confined by the commutator relation yields the reduction of the measurevalued solution to a Dirac mass, which leads to the convergence of solutions of the Navier‐Stokes equations to a finite‐energy entropy solution of the isentropic Euler equations with finite‐energy initial data, relative to the different end‐states at infinity. © 2010 Wiley Periodicals, Inc.
Donor/Acceptor Adsorbates on the Surface of Metal Oxide Nanoporous Films: A Spectroscopic Probe for Different Electron Transfer Pathways
Authors: Matylitsky Victor V. , Dworak Lars , Wachtveitl Josef 
Published: May 2010

AbstractA composite model system which consists of a molecular donor/acceptor pair coupled to the surface of metal oxide nanoporous films is proposed to study the contribution of the surface trap states and their influence on the interfacial ET as well as charge trapping and spatial diffusion processes in films. The photophysics of this donor/acceptor system is investigated by time‐resolved transient absorbance spectroscopy in the UV/Vis (347–675 nm) spectral region. Variation of the band gap allows one to disentangle the ET pathways. Adsorption of the donor/acceptor pair on the nonreactive Al2O3 surface shows that coupling to the surface assists electron transfer between adsorbed donor and acceptor molecules, resulting in ultrafast intermolecular electron transfer of ∼100 fs. On the other hand, a competition between interfacial and intermolecular electron transfer is observed for the donor/acceptor pair coupled to a reactive TiO2 surface. The subsequent transfer of the conduction band electron to the electron acceptor is examined by monitoring the free charge carrier absorption in the mid‐IR (∼5 μm) spectral region.
Dynamic expression patterns of Nkx6.1 and Nkx6.2 in the developing mes‐diencephalic basal plate
Authors: Moreno‐Bravo Juan Antonio , Perez‐Balaguer Ariadna , Martinez Salvador , Puelles Eduardo 
Published: May 2010

AbstractThe components of the molecular codes needed to specify the different neuronal populations present in the basal neural tube are being identified. These codes become more intricate as we move to more anterior regions of the central nervous system. The aim of this study is to thoroughly analyze the expression pattern of Nkx6.1, Nkx6.2, and Pou4f1. These three genes are candidates to play an important role in the determination and differentiation of the basal nuclei of the mesencephalon and diencephalon. The results obtained have shown that there is a longitudinal domain positive for both Nkx6.1 and Nkx6.2 that is medial to the Pou4f1‐positive red nucleus. This domain could correspond to part of the reticular formation, which extends from the diencephalon and the mesencephalon. The nuclei integrated in this domain would be the rostral interstitial nucleus, the interstitial nucleus of Cajal, and a mesencephalic equivalent to these nuclei. Developmental Dynamics 239:2094–2101, 2010. © 2010 Wiley‐Liss, Inc.
Highly Crystalline, Idiomorphic Na2Ti6O13 Whiskers Grown from a NaCl Flux at a Relatively Low Temperature
Authors: Teshima Katsuya , Lee SunHyung , Murakoshi Serika , Suzuki Sayaka , Yubuta Kunio , Shishido Toetsu , Endo Morinobu , Oishi Shuji 
Published: May 2010

AbstractWell‐developed, highly crystalline Na2Ti6O13 whiskers were successfully grown by cooling a NaCl flux at a relatively low temperature of 700 °C. The obtained Na2Ti6O13 whiskers were colorless and transparent. The whiskers grown at 700 °C were single phase and exhibit the lowest sizes of up to about 3.5 μm × 0.1 μm. From the results of SEM, XRD, and TEM, it was confirmed that the Na2Ti6O13 whiskers have very good crystallinity and elongated in the [lang]010[rang] directions. Furthermore, the whiskers exhibited good photocatalytic activity under ultraviolet light irradiation. It is reasonable to suppose that NaCl can be adequately used to synthesize high quality and well‐developed titanate whiskers in an environmentally friendly process of crystal growth.
Bora‐Amidinate Complexes of Lanthanide(II) Metals
Authors: Harder Sjoerd , Naglav Dominik 
Published: May 2010

AbstractReaction of (2‐Me2N‐α‐Me3Si‐benzyl)2Ln·(thf)2 (Ln = Yb, Eu and Sm) with one equivalent of DIPP(H)N‐BH‐N(H)DIPP (DIPPNBN‐H2, DIPP = 2,6‐iPr‐phenyl) gave the first LnII bora‐amidinate complexes which crystallized in the presence of THF as DIPPNBN‐Ln·(thf)4. Although only the Sm and Eu complex crystallize isomorphic, all three show similar structures. The very small N–Ln–N′ bite angles of 59.74(6)–63.28(9)° leave a large part of the metal coordination sphere available for neutral thf ligands.
New Approaches to 12‐Coordination: Structural Consequences of Steric Stress, Lanthanoid Contraction and Hydrogen Bonding
Authors: Chesman Anthony S. R. , Turner David R. , Deacon Glen B. , Batten Stuart R. 
Published: May 2010

AbstractThe anionic dinitrile ligand dicyanonitrosomethanide (dcnm), C(CN)2(NO)–, and the anion resulting from its addition product with water, carbamoylcyanonitrosomethanide (ccnm), C(CN)(CONH2)(NO)–, have been incorporated into lanthanoid complexes and display unusual η2(N,O) nitroso coordination modes. (Et4N)3[Ln(ccnm)6] (1Ln;1Ln=1La,1Ce,1Pr,1Nd,1Sm) and (Me4N)3[Ln(ccnm)6] (2Ln;2Ln=2La,2Ce,2Pr,2Nd) are systems containing 12‐coordinate homoleptic trianionic lanthanoidate complexes. The nitroso groups of the ccnm ligands form three‐membered ring chelates with the lanthanoid metal centre, with the asymmetry of the nitroso η2interactions dependent upon the intramolecular N–H···O=N hydrogen bonding. Additional intermolecular hydrogen bonding interactions exist between adjacent amide and nitrile groups giving rise to 3D α‐Po and 6,8‐connected (412.63)(420.68) networks in1Lnand2Ln, respectively. The compounds (Me4N)3[Ln(dcnm)6] (3Ln;3Ln=3La,3Ce,3Nd,3Sm) also contain a 12‐coordinate trianionic lanthanoidate complex with the nitroso group exhibiting a highly symmetrical η2interaction. The sterically crowded environments of [Ln(18‐crown‐6)(dcnm)3] (4Ln;4Ln = 4La,4Ce,4Pr,4Nd) result in a shift towards a more asymmetric η2bonding of the nitroso group with decrease in the Ln3+radius. There is a corresponding increase of the Ln–O–N angle, and one ligand is η1(O) binding in4Nd. The dcnm ligands in the discrete complexes [La(phen)3(dcnm)(3–x)Clx],x≈ 0.25 (5) (phen = 1,10‐phenanthroline), (Et4N)[Ce(phen)2(dcnm)4] (6a/b,6c) and [Ce(phen)2(dcnm)Cl2H2O] (7) display a variety of coordination modes. Complex5has 1D chains formed by π–π stacking of adjacent phen co‐ligands. Complexes6contain the monoanionic complex [Ce(phen)2(dcnm)4]–with two geometric isomers present in the crystal structure of6a/b. Complex7forms extended 1D chains via hydrogen bonding between coordinated water and chloride atoms and an extensive array of face‐to‐face π interactions.
Alkoxy‐5‐nitrosopyrimidines: Useful Building Block for the Generation of Biologically Active Compounds
Authors: Marchal Antonio , Nogueras Manuel , Sánchez Adolfo , Low John N. , Naesens Lieve , De Clercq Erik , Melguizo Manuel 
Published: May 2010

AbstractSeveral alkoxy‐5‐nitrosopyrimidines were synthesised and high regioselective and sequential nucleophilic aromatic substitution of methoxy groups in 2‐amino‐4,6‐dimethoxy‐5‐nitrosopyrimidine was observed. The approach was applied to the synthesis of valuable polyfunctionalised aminopyrimidines capable of mimicking fused heterobicyclic derivatives of biological interest. In addition, new compounds were evaluated as antivirals and their usefulness as synthetic intermediates was demonstrated.
Self‐Acylation of 1‐Adamantylacetic Acid in Trifluoroacetic Anhydride Medium: A Route to 2,4‐Bis(1‐adamantyl)acetoacetic Acid and Its Derivatives
Authors: Kovalev Vladimir , Shokova Elvira , Shmailov Alexander , Vatsouro Ivan , Tafeenko Viktor 
Published: May 2010

AbstractThe self‐acylation of 1‐adamantylacetic acid (1) in trifluoroacetic anhydride, catalyzed by triflic acid, proceeds through the formation of the mixed 2,4‐bis(1‐adamantyl)acetoacetic–trifluoroacetic anhydride 2, and it was used as an efficient approach to previously unknown 2,4‐bis(1‐adamantyl)acetoacetic acid (3), its esters 4–6 and amides 7–11, and the sterically hindered 1‐adamantyl(1‐adamantylacetyl)ketene (12). The latter is stable in solution and can be isolated as a neat solid. Addition of methanol or primary amines to 12 gave the corresponding derivatives of acid 3. Acid 3 was decarboxylated to 1,3‐bis(1‐adamantyl)acetone (22), whereas theheterocyclization of phenyl ester 6 with thiourea gave two isomeric adamantylated thiouracils 23 and 24. The structures of N‐benzylamide 7 and thiouracil 23 were confirmed by single‐crystal X‐ray analysis. The utilization of the self‐acylation method for the conversion of some other aliphatic acids is discussed and preliminarily tested.
Novel Approach for the Synthesis of Five‐Membered‐Ring‐Fused Pyrazinones
Authors: Gembus Vincent , Janvier Solenn , Lecouvé Jean‐Pierre , Gloanec Philippe , Marsais Francis , Levacher Vincent 
Published: May 2010

AbstractWe describe a new route to access important pharmaceutical intermediates for the synthesis of constrained fused pyrazinones. These compounds are prepared in five to seven steps with a good overall yield from glycine methyl ester and commercial propanediol derivatives involving an intramolecular alkylation of a glycine moiety as key step.