Homogeneous catalysts have many attractive properties, such as high selectivities. However, many homogeneous catalytic systems cannot be commercialized because of difficulties associated with ...separating the products from the catalyst. Recent approaches to tackling this problem are reviewed and compared.
Objective
The long‐term effects of traumatic brain injury (TBI) can resemble observed in normal ageing, suggesting that TBI may accelerate the ageing process. We investigate this using a neuroimaging ...model that predicts brain age in healthy individuals and then apply it to TBI patients. We define individuals' differences in chronological and predicted structural "brain age," and test whether TBI produces progressive atrophy and how this relates to cognitive function.
Methods
A predictive model of normal ageing was defined using machine learning in 1,537 healthy individuals, based on magnetic resonance imaging–derived estimates of gray matter (GM) and white matter (WM). This ageing model was then applied to test 99 TBI patients and 113 healthy controls to estimate brain age.
Results
The initial model accurately predicted age in healthy individuals (r = 0.92). TBI brains were estimated to be "older," with a mean predicted age difference (PAD) between chronological and estimated brain age of 4.66 years (±10.8) for GM and 5.97 years (±11.22) for WM. This PAD predicted cognitive impairment and correlated strongly with the time since TBI, indicating that brain tissue loss increases throughout the chronic postinjury phase.
Interpretation
TBI patients' brains were estimated to be older than their chronological age. This discrepancy increases with time since injury, suggesting that TBI accelerates the rate of brain atrophy. This may be an important factor in the increased susceptibility in TBI patients for dementia and other age‐associated conditions, motivating further research into the age‐like effects of brain injury and other neurological diseases. Ann Neurol 2015;77:571–581
To image β-amyloid (Aβ) plaque burden in long-term survivors of traumatic brain injury (TBI), test whether traumatic axonal injury and Aβ are correlated, and compare the spatial distribution of Aβ to ...Alzheimer disease (AD).
Patients 11 months to 17 years after moderate-severe TBI underwent (11)C-Pittsburgh compound B ((11)C-PiB)-PET, structural and diffusion MRI, and neuropsychological examination. Healthy aged controls and patients with AD underwent PET and structural MRI. Binding potential (BPND) images of (11)C-PiB, which index Aβ plaque density, were computed using an automatic reference region extraction procedure. Voxelwise and regional differences in BPND were assessed. In TBI, a measure of white matter integrity, fractional anisotropy, was estimated and correlated with (11)C-PiB BPND.
Twenty-eight participants (9 with TBI, 9 controls, 10 with AD) were assessed. Increased (11)C-PiB BPND was found in TBI vs controls in the posterior cingulate cortex and cerebellum. Binding in the posterior cingulate cortex increased with decreasing fractional anisotropy of associated white matter tracts and increased with time since injury. Compared to AD, binding after TBI was lower in neocortical regions but increased in the cerebellum.
Increased Aβ burden was observed in TBI. The distribution overlaps with, but is distinct from, that of AD. This suggests a mechanistic link between TBI and the development of neuropathologic features of dementia, which may relate to axonal damage produced by the injury.
Development of vehicle active steering collision avoidance systems calls for mathematical models capable of predicting a human driver's response so as to reduce the cost involved in field tests while ...accelerating product development. This paper provides a discussion on the paradigms that may be used for modeling a driver's steering interaction with vehicle collision avoidance control in path-following scenarios. Four paradigms, namely decentralized, noncooperative Nash, noncooperative Stackelberg, and cooperative Pareto are established. The decentralized paradigm, which is developed on the basis of optimal control theory, represents a driver's interaction with the collision avoidance controllers that disregard driver steering control. The noncooperative Nash and Stackelberg paradigms are used for predicting a driver's steering behavior in response to the collision avoidance control that actively compensates for driver steering action. These two are devised based on the principles of equilibria in noncooperative game theory. The cooperative Pareto paradigm is derived from cooperative game theory to model a driver's interaction with the collision avoidance systems that take into account the driver's target path. The driver and the collision avoidance controllers' optimization problems and their resulting steering strategies arise in each paradigm are delineated. Two mathematical approaches applicable to these optimization problems namely the distributed model predictive control and the linear quadratic dynamic optimization approaches are described in detail. A case study illustrating a conflict in steering control between driver and vehicle collision avoidance system is performed via simulation. It was found that the variation of driver path-error cost function weights results in a variety of steering behaviors, which are distinct between paradigms.
We report a redox-neutral method for nucleophilic fluorination of N-hydroxyphthalimide esters using an Ir photocatalyst under visible light irradiation. The method provides access to a broad range of ...aliphatic fluorides, including primary, secondary, and tertiary benzylic fluorides as well as unactivated tertiary fluorides, that are typically inaccessible by nucleophilic fluorination due to competing elimination. In addition, we show that the decarboxylative fluorination conditions are readily adapted to radiofluorination with 18FKF. We propose that the reactions proceed by two electron transfers between the Ir catalyst and redox-active ester substrate to afford a carbocation intermediate that undergoes subsequent trapping by fluoride. Examples of trapping with O- and C-centered nucleophiles and deoxyfluorination via N-hydroxyphthalimidoyl oxalates are also presented, suggesting that this approach may offer a general blueprint for affecting redox-neutral SN1 substitutions under mild conditions.
Traumatic brain injury is associated with elevated rates of neurodegenerative diseases such as Alzheimer's disease and chronic traumatic encephalopathy. In experimental models, diffuse axonal injury ...triggers post-traumatic neurodegeneration, with axonal damage leading to Wallerian degeneration and toxic proteinopathies of amyloid and hyperphosphorylated tau. However, in humans the link between diffuse axonal injury and subsequent neurodegeneration has yet to be established. Here we test the hypothesis that the severity and location of diffuse axonal injury predicts the degree of progressive post-traumatic neurodegeneration. We investigated longitudinal changes in 55 patients in the chronic phase after moderate-severe traumatic brain injury and 19 healthy control subjects. Fractional anisotropy was calculated from diffusion tensor imaging as a measure of diffuse axonal injury. Jacobian determinant atrophy rates were calculated from serial volumetric T1 scans as a measure of measure post-traumatic neurodegeneration. We explored a range of potential predictors of longitudinal post-traumatic neurodegeneration and compared the variance in brain atrophy that they explained. Patients showed widespread evidence of diffuse axonal injury, with reductions of fractional anisotropy at baseline and follow-up in large parts of the white matter. No significant changes in fractional anisotropy over time were observed. In contrast, abnormally high rates of brain atrophy were seen in both the grey and white matter. The location and extent of diffuse axonal injury predicted the degree of brain atrophy: fractional anisotropy predicted progressive atrophy in both whole-brain and voxelwise analyses. The strongest relationships were seen in central white matter tracts, including the body of the corpus callosum, which are most commonly affected by diffuse axonal injury. Diffuse axonal injury predicted substantially more variability in white matter atrophy than other putative clinical or imaging measures, including baseline brain volume, age, clinical measures of injury severity and microbleeds (>50% for fractional anisotropy versus <5% for other measures). Grey matter atrophy was not predicted by diffuse axonal injury at baseline. In summary, diffusion MRI measures of diffuse axonal injury are a strong predictor of post-traumatic neurodegeneration. This supports a causal link between axonal injury and the progressive neurodegeneration that is commonly seen after moderate/severe traumatic brain injury but has been of uncertain aetiology. The assessment of diffuse axonal injury with diffusion MRI is likely to improve prognostic accuracy and help identify those at greatest neurodegenerative risk for inclusion in clinical treatment trials.
A detailed mechanism for alkyne alkoxycarbonylation mediated by a palladium catalyst has been characterised at the B3PW91‐D3/PCM level of density functional theory (including bulk solvation and ...dispersion corrections). This transformation, investigated via the methoxycarbonylation of propyne, involves a uniquely dual role for the P,N hemilabile ligand acting co‐catalytically as both an in situ base and proton relay coupled with a Pd0 centre, allowing for surmountable barriers (highest ΔG≠ of 22.9 kcal mol−1 for alcoholysis). This proton‐shuffle between methanol and coordinated propyne accounts for experimental requirements (high acid concentration) and reproduces observed regioselectivities as a function of ligand structure. A simple ligand modification is proposed, which is predicted to improve catalytic turnover by three orders of magnitude.
Through the laptop looking glass: DFT calculations afford insights into the precise way how Pd catalysts steer the reaction of three molecules with enzyme‐like efficiency and selectivity, for instance producing methyl methacrylate—you are looking through its polymer if you read this on a laptop or tablet computer.
Head injury survivors can develop neurodegeneration associated with persistent neuroinflammation, but whether the latter is harmful or beneficial is unclear. Scott et al. report that minocycline ...reduces neuroinflammation months and years after injury but increases a blood marker of neurodegeneration, suggesting that persistent neuroinflammation has reparative effects long after injury.
Abstract
Survivors of a traumatic brain injury can deteriorate years later, developing brain atrophy and dementia. Traumatic brain injury triggers chronic microglial activation, but it is unclear whether this is harmful or beneficial. A successful chronic-phase treatment for traumatic brain injury might be to target microglia. In experimental models, the antibiotic minocycline inhibits microglial activation. We investigated the effect of minocycline on microglial activation and neurodegeneration using PET, MRI, and measurement of the axonal protein neurofilament light in plasma. Microglial activation was assessed using 11C-PBR28 PET. The relationships of microglial activation to measures of brain injury, and the effects of minocycline on disease progression, were assessed using structural and diffusion MRI, plasma neurofilament light, and cognitive assessment. Fifteen patients at least 6 months after a moderate-to-severe traumatic brain injury received either minocycline 100 mg orally twice daily or no drug, for 12 weeks. At baseline, 11C-PBR28 binding in patients was increased compared to controls in cerebral white matter and thalamus, and plasma neurofilament light levels were elevated. MRI measures of white matter damage were highest in areas of greater 11C-PBR28 binding. Minocycline reduced 11C-PBR28 binding (mean Δwhite matter binding = −23.30%, 95% confidence interval −40.9 to −5.64%, P = 0.018), but increased plasma neurofilament light levels. Faster rates of brain atrophy were found in patients with higher baseline neurofilament light levels. In this experimental medicine study, minocycline after traumatic brain injury reduced chronic microglial activation while increasing a marker of neurodegeneration. These findings suggest that microglial activation has a reparative effect in the chronic phase of traumatic brain injury.
Hydrogenation of amides in the presence of Ru(acac)3 (acacH=2,4‐pentanedione), triphos 1,1,1‐tris‐ (diphenylphosphinomethyl)ethane and methanesulfonic acid (MSA) produces secondary and tertiary ...amines with selectivities as high as 93 % provided that there is at least one aromatic ring on N. The system is also active for the synthesis of primary amines. In an attempt to probe the role of MSA and the mechanism of the reaction, a range of methanesulfonato complexes has been prepared from Ru(acac)3, triphos and MSA, or from reactions of RuX(OAc)(triphos) (X=H or OAc) or RuH2(CO)(triphos) with MSA. Crystallographically characterised complexes include: Ru(OAc‐κ1O)2(H2O)(triphos), Ru(OAc‐κ2O,O′)(CH3SO3‐κ1O)(triphos), Ru(CH3SO3‐κ1O)2(H2O)(triphos) and Ru2(μ‐CH3SO3)3(triphos)2CH3SO3, whereas other complexes, such as Ru(OAc‐κ1O)(OAc‐κ2O,O′)(triphos), Ru(CH3SO3‐κ1O)(CH3SO3‐κ2O,O′)(triphos), HRu(CH3SO3‐κ1O)3(triphos), RuH(CH3SO3‐κ1O)(CO)(triphos) and RuH(CH3SO3‐κ2O,O′)(triphos) have been characterised spectroscopically. The interactions between these various complexes and their relevance to the catalytic reactions are discussed.
Triphos be with you: A homogeneous catalytic system based on complexes prepared in situ from Ru(acac)3 and triphos has been developed for the hydrogenation of amides to amines with preservation of the CN bond (see scheme). This is the first system of any kind that can catalyse the hydrogenation of amides to amines in the presence of aromatic rings without cleavage of the CN bond.
The European Chemical Society (EuChemS) coordinates the work of almost all the European Chemical Societies. As an organization, it provides an independent and authoritative voice on all matters ...relating to chemistry, and try to place chemistry at the heart of policy in Europe. Furthermore, EuChemS seeks to develop its members through various activities, workshops and awards. Particularly, EuChemS has fostered growth in its young members through the European Young Chemists′ Network. Beyond Europe, EuChemS has collaborated with various organizations in bringing chemistry out of the lab and into society in building a sustainable future for everyone.
All you need is EuCheMS! The former President of the European Chemical Society, David Cole‐Hamilton (see photo), walks us through the work of this organization in shaping chemistry‐related policies across Europe, fostering its members through workshops, conferences and awards, as well as in building a sustainable future through its international collaboration with other societies.
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