Poly(methyl methacrylate) (PMMA) anchored chains were grown on porous silicon (p-Si) and anodically etched aluminum oxide (AAO) substrates via surface-initiated atom transfer radical polymerization ...(ATRP). Using hydrogen fluoride, the chains could be cleaved from the substrates, as evidenced by infrared spectroscopy. The molecular weights and molecular weight distributions of PMMA could be analyzed directly on these substrates (after cleaving the chains from the support) using direct ionization mass spectrometry (DIOS-MS) and matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). Two principal conclusions were drawn from the study. First, matrix-free DIOS-MS was effective at direct analysis of the polymers up to a molecular weight of ≈6 kDa; the signal-to-noise ratio for heavier polymer chains diminished rapidly. Second, under the same polymerization conditions, PMMA grown on both p-Si and AAO substrates had a much lower molecular weight and a broader molecular weight distribution than that grown in solution. Confinement effects imposed by the pores during the polymerization are proposed as the likely mechanism for the reduced growth rates and more polydisperse chains.
Fast Directed Motion of “Fakir” Droplets Petrie, Randall J; Bailey, Tiffani; Gorman, Christopher B ...
Langmuir,
11/2004, Letnik:
20, Številka:
23
Journal Article
Recenzirano
In this Letter, we report on the motion of water droplets on surfaces decorated with molecular gradients comprising semifluorinated (SF) organosilanes. SF molecular gradients deposited on flat silica ...substrates facilitate faster motion of water droplets relative to the specimens covered with an analogous hydrocarbon gradient. Further increase in the drop speed is achieved by advancing it along porous substrates coated with the SF wettability gradients. The results of our experiments are in quantitative agreement with a simple scaling theory that describes the faster liquid motion in terms of reduced friction at the liquid/substrate interface.
Three pairs of isomeric, iron−sulfur core dendrimers were prepared. Each isomer pair was distinguished by a 3,5-aromatic substitution pattern (extended) versus 2,6-aromatic substitution pattern ...(backfolded). Several observations were made that supported the hypothesis that the iron−sulfur cluster cores were encapsulated more effectively in the backfolded isomers as compared to their extended isomeric counterparts. The backfolded isomers were more difficult to reduce electrochemically, consistent with encapsulation in a more hydrophobic microenvironment. Furthermore, heterogeneous electron-transfer rates for the backfolded molecules were attenuated compared to the extended molecules. From diffusion measurements obtained by pulsed field gradient spin−echo NMR and chronoamperometry, the backfolded dendrimers were found to be smaller than the extended dendrimers. Comparison of longitudinal proton relaxation (T 1) values also indicated a smaller, more compact dendrimer conformation for the backfolded architectures. These findings indicated that the dendrimer size was not the major factor in determining electron-transfer rate attenuation. Instead, the effective electron-transfer distance, as determined by the relative core position and mobility in a dendrimer, is most relevant for encapsulation.
The total synthesis of clitocine 6-amino-5-nitro-4-(beta-D-ribofuranosylamino)pyrimidine (1), a nucleoside recently isolated from the mushroom Clitocybe inversa, has been accomplished. Glycosylation ...of 4,6-diamino-5-nitropyrimidine (4) with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose afforded the protected nucleoside 6-amino-5-nitro-4-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl) aminopyrimidine (5) in good yield exclusively as the beta-anomer. Deprotection of 5 with NaOMe/MeOH gave 1 as an 11.5:1 mixture of the beta- and alpha-anomers, respectively. Recrystallization from MeOH, followed by chromatography, afforded 1 containing less than 1% of its alpha-anomer. X-ray crystal data revealed a planar aglycon moiety in clitocine with each oxygen atom of the nitro group intramolecularly hydrogen bonded to the hydrogen atoms of the two adjacent amino functions. Clitocine inhibited L1210 cells in vitro with an ID50 of 3 X 10(-8) M. Clitocine was also found to be a substrate and inhibitor of adenosine kinase with a Ki value of 3 X 10(-6) M.
Allopurinol is a urate-lowering therapy used to treat patients with gout. Previous studies have shown that allopurinol has positive effects on several cardiovascular parameters. The ALL-HEART study ...aimed to determine whether allopurinol therapy improves major cardiovascular outcomes in patients with ischaemic heart disease.
ALL-HEART was a multicentre, prospective, randomised, open-label, blinded-endpoint trial done in 18 regional centres in England and Scotland, with patients recruited from 424 primary care practices. Eligible patients were aged 60 years or older, with ischaemic heart disease but no history of gout. Participants were randomly assigned (1:1), using a central web-based randomisation system accessed via a web-based application or an interactive voice response system, to receive oral allopurinol up-titrated to a dose of 600 mg daily (300 mg daily in participants with moderate renal impairment at baseline) or to continue usual care. The primary outcome was the composite cardiovascular endpoint of non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death. The hazard ratio (allopurinol vs usual care) in a Cox proportional hazards model was assessed for superiority in a modified intention-to-treat analysis (excluding randomly assigned patients later found to have met one of the exclusion criteria). The safety analysis population included all patients in the modified intention-to-treat usual care group and those who took at least one dose of randomised medication in the allopurinol group. This study is registered with the EU Clinical Trials Register, EudraCT 2013-003559-39, and ISRCTN, ISRCTN32017426.
Between Feb 7, 2014, and Oct 2, 2017, 5937 participants were enrolled and then randomly assigned to receive allopurinol or usual care. After exclusion of 216 patients after randomisation, 5721 participants (mean age 72·0 years SD 6·8, 4321 75·5% males, and 5676 99·2% white) were included in the modified intention-to-treat population, with 2853 in the allopurinol group and 2868 in the usual care group. Mean follow-up time in the study was 4·8 years (1·5). There was no evidence of a difference between the randomised treatment groups in the rates of the primary endpoint. 314 (11·0%) participants in the allopurinol group (2·47 events per 100 patient-years) and 325 (11·3%) in the usual care group (2·37 events per 100 patient-years) had a primary endpoint (hazard ratio HR 1·04 95% CI 0·89–1·21, p=0·65). 288 (10·1%) participants in the allopurinol group and 303 (10·6%) participants in the usual care group died from any cause (HR 1·02 95% CI 0·87–1·20, p=0·77).
In this large, randomised clinical trial in patients aged 60 years or older with ischaemic heart disease but no history of gout, there was no difference in the primary outcome of non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death between participants randomised to allopurinol therapy and those randomised to usual care.
UK National Institute for Health and Care Research.
Positive effects of methylphenidate (MPH) on attention and cognitive processing speed have been reported in studies of patients with moderate to severe traumatic brain injury (TBI). Studies which ...have acquired functional brain imaging before and while using MPH have also found alteration of brain activation while performing a cognitive task; in some studies, this alteration of activation in selective brain regions was also related to improved performance on cognitive tests administered outside of the scanning environment. Enhanced cognitive performance has been reported after single doses of MPH and after daily treatment over durations of up to and exceeding 1 month. Preclinical research and both positron emission tomography and single photon emission tomography of humans have shown that MPH increases extracellular dopamine and norepinephrine; the dose effects of MPH have an inverted
-shaped function where high doses may cause insomnia, nervousness, and increased heart rate among other symptoms and impair cognitive performance, whereas too low a dose fails to improve cognitive performance. In the past 5 years, small clinical trials, and experimental pilot studies have found therapeutic effects of single and repeated low doses of MPH in patients with mild TBI who reported cognitive dysfunction. This literature also suggests that MPH may interact with concurrent cognitive interventions to enhance their effects. This focused review will critically evaluate the recent literature on MPH effects on cognitive dysfunction after mild to moderate TBI. To elucidate the neural mechanisms of MPH effects, this review will also include recent imaging research, preclinical, and experimental human studies.
Objectives
The chronic effects of neurotrauma consortium (CENC) observational study is a multisite investigation designed to examine the long‐term longitudinal effects of mild traumatic brain injury ...(mTBI). All participants in this initial CENC cohort had a history of deployment in Operation Enduring Freedom (Afghanistan), Operation Iraqi Freedom (Iraq), and/or their follow‐on conflicts (Operation Freedom's Sentinel). All participants undergo extensive medical, neuropsychological, and neuroimaging assessments and either meet criteria for any lifetime mTBI or not. These assessments are integrated into six CENC core studies—Biorepository, Biostatistics, Data and Study Management, Neuroimaging, and Neuropathology.
Methods
The current study outlines the quantitative neuroimaging methods managed by the Neuroimaging Core using FreeSurfer automated software for image quantification.
Results
At this writing, 319 participants from the CENC observational study have completed all baseline assessments including the imaging protocol and tertiary data quality assurance procedures.
Conclusions/Discussion
The preliminary findings of this initial cohort are reported to describe how the Neuroimaging Core manages neuroimaging quantification for CENC studies.
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