99 research outputs found
Mediterranean-type diet and brain structural change from 73 to 76 years in a Scottish cohort
STUDY FUNDING The data were collected by a Research into Ageing programme grant; research continues as part of the Age UKāfunded Disconnected Mind project. The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross-council Lifelong Health and Wellbeing Initiative (MR/K026992/1), with funding from the BBSRC and Medical Research Council. Imaging and image analysis was performed at the Brain Research Imaging Centre (sbirc.ed.ac.uk/), Edinburgh, supported by the Scottish Funding Council SINAPSE Collaboration. Derivation of mean cortical thickness measures was funded by the Scottish Funding Councilās Postdoctoral and Early Career Researchers Exchange Fund awarded by SINAPSE to David Alexander Dickie. L.C.A.C. acknowledges funding from the Scottish Government's Rural and Environment Science and Analytical Services (RESAS) division.Peer reviewedPublisher PD
Palladium-Catalyzed Direct Arylation of 5āHalouracils and 5āHalouracil Nucleosides with Arenes and Heteroarenes Promoted by TBAF
The
1-<i>N</i>-benzyl-5-iodoĀ(or bromo)Āuracil undergoes
Pd-catalyzed [Pd<sub>2</sub>(dba)<sub>3</sub>] direct arylation with
benzene and other simple arenes in the presence of TBAF in DMF without
the necessity of adding any ligands or additives to give 5-arylated
uracil analogues. The TBAF-promoted coupling also occurs efficiently
with electron rich heteroarenes at 100 Ā°C (1 h) even with only
small excess of heteroarenes. The protocol avoids usage of the arylboronic
acid or stannane precursors for the synthesis of 5-(2-furyl, or 2-thienyl,
or 2-pyrrolyl)Āuracil nucleosides, which are used as important RNA
and DNA fluorescent probes. The fact that 1-<i>N</i>-benzyl-3-<i>N</i>-methyl-5-iodouracil did not undergo the TBAF-promoted
couplings with arenes or heteroarenes suggests that the C4-alkoxide
(enol form of uracil) facilitates coupling by participation in the
intramolecular processes of hydrogen abstraction from arenes. TBAF-promoted
arylation was extended into the other enolizable heterocyclic systems
such as 3-bromo-2-pyridone. The Ļ-excessive heteroarenes also
coupled with 5-halouracils in the presence of PdĀ(OAc)<sub>2</sub>/Cs<sub>2</sub>CO<sub>3</sub>/PivOH combination in DMF (100 Ā°C, 2 h)
to yield 5-arylated uracils
Mechanisms and Origins of Switchable Chemoselectivity of Ni-Catalyzed C(aryl)āO and C(acyl)āO Activation of Aryl Esters with Phosphine Ligands
Many experiments have shown that
nickel with monodentate phosphine
ligands favors the CĀ(aryl)āO activation over the CĀ(acyl)āO
activation for aryl esters. However, Itami and co-workers recently
discovered that nickel with bidentate phosphine ligands can selectively
activate the CĀ(acyl)āO bond of aryl esters of aromatic carboxylic
acids. The chemoselectivity with bidentate phosphine ligands can be
switched back to CĀ(aryl)āO activation when aryl pivalates are
employed. To understand the mechanisms and origins of this switchable
chemoselectivity, density functional theory (DFT) calculations have
been conducted. For aryl esters, nickel with bidentate phosphine ligands
cleaves CĀ(acyl)āO and CĀ(aryl)āO bonds via three-centered
transition states. The CĀ(acyl)āO activation is more favorable
due to the lower bond dissociation energy (BDE) of CĀ(acyl)āO
bond, which translates into a lower transition-state distortion energy.
However, when monodentate phosphine ligands are used, a vacant coordination
site on nickel creates an extra NiāO bond in the five-centered
CĀ(aryl)āO cleavage transition state. The additional interaction
energy between the catalyst and substrate makes CĀ(aryl)āO activation
favorable. In the case of aryl pivalates, nickel with bidentate phosphine
ligands still favors the CĀ(acyl)āO activation over the CĀ(aryl)āO
activation at the cleavage step. However, the subsequent decarbonylation
generates a very unstable <i>t</i>Bu-NiĀ(II) intermediate,
and this unfavorable step greatly increases the overall barrier for
generating the CĀ(acyl)āO activation products. Instead, the
subsequent CāH activation of azoles and CāC coupling
in the CĀ(aryl)āO activation pathway are much easier, leading
to the observed CĀ(aryl)āO activation products
Theoretical Elucidation of the Origins of Substituent and Strain Effects on the Rates of DielsāAlder Reactions of 1,2,4,5-Tetrazines
The DielsāAlder
reactions of seven 1,2,4,5-tetrazines with
unstrained and strained alkenes and alkynes were studied with quantum
mechanical calculations (M06-2X density functional theory) and analyzed
with the distortion/interaction model. The higher reactivities of
alkenes compared to alkynes in the DielsāAlder reactions with
tetrazines arise from the differences in both interaction and distortion
energies. Alkenes have HOMO energies higher than those of alkynes
and therefore stronger interaction energies in inverse-electron-demand
DielsāAlder reactions with tetrazines. We have also found that
the energies to distort alkenes into the DielsāAlder transition-state
geometries are smaller than for alkynes in these reactions. The strained
dienophiles, <i>trans</i>-cyclooctene and cyclooctyne, are
much more reactive than unstrained <i>trans</i>-2-butene
and 2-butyne, because they are predistorted toward the DielsāAlder
transition structures. The reactivities of substituted tetrazines
correlate with the electron-withdrawing abilities of the substituents.
Electron-withdrawing groups lower the LUMO+1 of tetrazines, resulting
in stronger interactions with the HOMO of dienophiles. Moreover, electron-withdrawing
substituents destabilize the tetrazines, and this leads to smaller
distortion energies in the DielsāAlder transition states
Feature Selection and Cancer Classification via Sparse Logistic Regression with the Hybrid L<sub>1/2 +2</sub> Regularization
<div><p>Cancer classification and feature (gene) selection plays an important role in knowledge discovery in genomic data. Although logistic regression is one of the most popular classification methods, it does not induce feature selection. In this paper, we presented a new hybrid L<sub>1/2 +2</sub> regularization (HLR) function, a linear combination of L<sub>1/2</sub> and L<sub>2</sub> penalties, to select the relevant gene in the logistic regression. The HLR approach inherits some fascinating characteristics from L<sub>1/2</sub> (sparsity) and L<sub>2</sub> (grouping effect where highly correlated variables are in or out a model together) penalties. We also proposed a novel univariate HLR thresholding approach to update the estimated coefficients and developed the coordinate descent algorithm for the HLR penalized logistic regression model. The empirical results and simulations indicate that the proposed method is highly competitive amongst several state-of-the-art methods.</p></div
Contour plots (two-dimensional) for the regularization methods.
<p>The regularization parameters are <i>Ī»</i> = 1 and <i>Ī±</i> = 0.2 for the HLR method.</p
The most frequently selected 10 genes found by the five sparse logistic regression methods from the lung cancer dataset.
<p>The most frequently selected 10 genes found by the five sparse logistic regression methods from the lung cancer dataset.</p
The performance of the AUC from ROC analyzes of each method on prostate, lymphoma and lung cancer datasets.
<p>The performance of the AUC from ROC analyzes of each method on prostate, lymphoma and lung cancer datasets.</p
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