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941.
Lewis HD Leveridge M Strack PR Haldon CD O'neil J Kim H Madin A Hannam JC Look AT Kohl N Draetta G Harrison T Kerby JA Shearman MS Beher D 《Chemistry & biology》2007,14(2):209-219
In this report, inhibitors of the gamma-secretase enzyme have been exploited to characterize the antiproliferative relationship between target inhibition and cellular responses in Notch-dependent human T cell acute lymphoblastic leukemia (T-ALL) cell lines. Inhibition of gamma-secretase led to decreased Notch signaling, measured by endogenous NOTCH intracellular domain (NICD) formation, and was associated with decreased cell viability. Flow cytometry revealed that decreased cell viability resulted from a G(0)/G(1) cell cycle block, which correlated strongly to the induction of apoptosis. These effects associated with inhibitor treatment were rescued by exogenous expression of NICD and were not mirrored when a markedly less active enantiomer was used, demonstrating the gamma-secretase dependency and specificity of these responses. Together, these data strengthen the rationale for using gamma-secretase inhibitors therapeutically and suggest that programmed cell death may contribute to reduction of tumor burden in the clinic. 相似文献
942.
Connor Yap Dr. Gabriel M. J. Lenagh-Snow Dr. Somnath Narayan Karad Dr. William Lewis Dr. Louis J. Diorazio Prof. Hon Wai Lam 《Angewandte Chemie (International ed. in English)》2017,56(28):8216-8220
Enantioselective nickel-catalyzed arylative cyclizations of substrates containing a Z-allylic phosphate tethered to an alkyne are described. These reactions give multisubstituted chiral aza- and carbocycles, and are initiated by the addition of an arylboronic acid to the alkyne, followed by cyclization of the resulting alkenylnickel species onto the allylic phosphate. The reversible E/Z isomerization of the alkenylnickel species is essential for the success of the reactions. 相似文献
943.
Dr. Benjamin M. Partridge Michael Callingham Dr. William Lewis Prof. Hon Wai Lam 《Angewandte Chemie (International ed. in English)》2017,56(25):7227-7232
Alkenyl-to-allyl 1,4-rhodium(I) migration enables the generation of nucleophilic allylrhodium(I) species by remote C−H activation. This new mode of reactivity was employed in the diastereoselective reaction of arylboron reagents with substrates containing a 1,3-enyne tethered to a ketone, to give products containing three contiguous stereocenters. The products can be obtained in high enantioselectivities using a chiral sulfur-alkene ligand. 相似文献
944.
In a recent paper, Ghenciu and Lewis studied strong Dunford-Pettis sets and made the following two assertions:
While the statements are correct, the proofs are flawed. The difficulty with the proofs is discussed, and a fundamental result
of Elton is used to establish a simple lemma which leads to quick proofs of both (1) and (2). 相似文献
(1) | The Banach space X * contains a nonrelatively compact strong Dunford-Pettis set if and only if ℓ∞ ↪ X *. |
(2) | If c 0 ↪ Y and H is a complemented subspace of X so that H * is a strong Dunford-Pettis space, then W(X, Y) is not complemented in L(X, Y). |
945.
We investigate evaporative lithography as a route for patterning colloidal films. Films are dried beneath a mask that induces periodic variations between regions of free and hindered evaporation. Direct imaging reveals that particles segregate laterally within the film, as fluid and entrained particles migrate towards regions of higher evaporative flux. The films exhibit remarkable pattern formation that can be regulated by tuning the initial suspension composition, separation distance between the mask and underlying film, and mask geometry. 相似文献
946.
With a view of finding a route toward microstructural stability in alloys, we numerically study the impact of elastic inhomogeneities on the growth of inclusions in multiphase systems. We show that growth can proceed either continuously at rough interfaces, or in a layer-by-layer fashion following an elastically induced kinetic faceting process. In the former case, the chemical potential of the inclusions is a smooth function of size, while in the latter case, elasticity increases the barrier for nucleation of new terraces on the facets, leading to an oscillatory behavior of the chemical potential and hence a strong resistance against coarsening, opening up the possibility to stabilize the structure. 相似文献
947.
Dickie DA Lee PT Labeodan OA Schatte G Weinberg N Lewis AR Bernard GM Wasylishen RE Clyburne JA 《Dalton transactions (Cambridge, England : 2003)》2007,(27):2862-2869
A series of tin(II) amido complexes possessing m-terphenyl carboxylate ligands have been prepared. These complexes, namely [(Me(3)Si)(2)NSn(mu-O(2)CC(6)H(2)Ph(3))](2), [(Me(3)Si)(2)NSn(mu-O(2)CC(6)H(3)Mes(2))](2), and [(Me(3)Si)(2)NSn(mu-O(2)CC(6)H(2)Mes(2)Me)](2) [Mes = 2,4,6-trimethylphenyl], are the first structurally characterized examples of tin(II) carboxylate complexes exhibiting discrete Sn(2)O(4)C(2) heterocyclic cores. Initial reactivity studies led to the isolation of a 1,3-diaza-2,4-distannacyclobutanediyl, [(Mes(2)C(6)H(3)CO(2))Sn(mu-NSiMe(3))](2). This molecule possesses a Sn(2)N(2) heterocyclic core and it was crystallised as both the CH(2)Cl(2) and Et(2)O solvates. Although the tin atoms in this molecule have a formal oxidation state of 3+, preliminary computational studies on this molecule suggest that it is best described as a ground state singlet. Finally, the X-ray crystal structure of (CH(2)Cl)(Cl)Sn[N(SiMe(3))(2)](2), the product of oxidative addition of CH(2)Cl(2) to Sn[N(SiMe(3))(2)](2), is also presented herein. 相似文献
948.
Fermi's golden rule is used to develop relationships between rate constants for electron transfer in donor-bridge-acceptor and electrode-bridge-acceptor systems and resistances across metal-bridge-electrode and metal-bridge-tip junctions. Experimental data on electron-transfer rates through alkanethiolate, oligophenylene, and DNA bridges are used to calculate the electronic coupling matrix element per state through these moieties. The formulation is then used to predict the resistance of these bridges between two gold contacts. This approach provides a straightforward method for experimentalists to assess the self-consistency between intramolecular electron-transfer rate constants and low-bias resistances measured for molecularly bridged junctions between two metallic contacts. Reported resistances for alkanethiolate bridges vary by a factor of 20, with predicted resistances falling within this range. However, comparisons between carboxylato and directly linked alkanethiolate bridges suggest differences between the coupling at the interface to either the redox center or the gold electrode in such systems. Calculated resistances for oligophenylene bridges are close to those measured experimentally in a similar oligophenylene system. 相似文献
949.
Self-assembling cyclic D,L-peptide nanotubes are electronically insulating and possess wide band gaps (E(g) > 4 eV). Our ab initio electronic structure calculations indicate that the presence of aromatic rings in the side chain of peptide nanotubes significantly reduces the band gap. We investigate the conductivity of the modified peptide nanotubes through calculations of the electron tunneling probability. The electron tunneling probability through a molecule depends on the length of the molecule, L, as e-beta(E)L, where the tunneling beta(E)-factor is strongly energy-dependent. We have calculated beta(E) in three types of peptide nanotubes that have different sequences of amino acid residue, (L-Gln, D-Ala)(4), (L-Gln, D-Leu)(4) and (L-Gln, D-Phe)(4), using the complex band structure approach. We find large beta values near midgap, making these peptide nanotubes a poor tunneling conductor. 相似文献
950.
We report experiments on dendritic molecules with integrated conjugated chromophores that provide microscopic mechanistic information about their solvation dynamics. The fluorescence of a series of immobilized dendritically organized oligothiophenes is studied as they are exposed to good solvents. Initially, the pi-stacking of the oligothiophene units in the dendrimer is destabilized, but full separation of the oligothiophene dendrons takes a time that is orders of magnitude longer due to barriers to torsional motion of the ester linkages. The metastable state prior to separation of the conjugated segments exhibits solution-like spectroscopy but low fluorescence quantum yield relative to the fully solvated segments. This species may play an important role in the photophysics of conjugated oligomer and polymer films. Unusual non-exponential kinetics for the oligothiophene separation step are observed and can be understood in terms of energy transfer among the dendrons. 相似文献