41 research outputs found
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High-resolution infrared studies of perdeutero-spiropentane, C₅D₈
Perdeutero-spiropentane (C₅D₈) has been synthesized and infrared and Raman spectra are reported for the first time. Wavenumber assignments are made for most of the fundamental vibrational modes. Gas phase infrared spectra were recorded at a resolution (0.002 cm⁻¹) sufficient to resolve individual rovibrational lines and show evidence of strong Coriolis and/or Fermi resonance interactions for most bands. However a detailed rovibrational analysis of the fundamental ν₁₅ (b₂) parallel band proved possible and a fit of more than 1600 lines yielded a band origin of 1053.84465(10) cm⁻¹ and ground state constants (in units of cm⁻¹): B0 = 0.1120700(9), DJ = 1.51(3) x10⁻⁸, DJK = 3.42(15) x10⁻⁸. We note that the B0 value is significantly less than a value of Ba = 0.1140 cm⁻¹ calculated using structural parameters from an earlier electron diffraction (ED) study, whereas one expects Ba to be lower than B0 because of thermal averaging over higher vibrational levels. A similar discrepancy was noted in an earlier study of C₅H₈ [1]. The structural and spectroscopic results are in good accord with values computed at the anharmonic level using the B3LYP density functional method with a cc-pVTZ basis set
Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease
BACKGROUND:
Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes.
METHODS:
We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization.
RESULTS:
During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events.
CONCLUSIONS:
Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)
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Extending Time-Resolved Photoelectron Spectroscopy to the Extreme Ultraviolet
The interaction of ultraviolet (UV) light with cellular media is a problem of fundamentalinterest in a wide variety of fields. Specifically, this thesis focuses on the elucidation of the
electronic dynamics of nucleobases (NBs), the building blocks of DNA, after they have absorbed
UV light. Understanding the different photochemical and photophysical pathways
that lead to DNA damage, and those that prevent it, is the primary focus of this thesis
work. These processes are monitored via time-resolved photoelectron spectroscopy (TRPES)
applied to a water microjet. In these experiments, a UV pump pulse is used to excite
valence electrons in the NBs, and a time-delayed probe pulse is used to photoionize the
excited species. The arrival time of the ejected electrons is detected by a magnetic bottle
time-of-flight spectrometer. By varying the time delay between the pump and probe pulse
the electronic dynamics occurring on the excited state surface(s) are mapped out.The NB thymine (T) and its derivatives thymidine (Thd) and thymidine-5’-monophosphate(TMP) are studied by TRPES using two UV pulses, one tuned over 4.74 – 5.17 eV and the
other at 6.2 eV. The tunable UV pulse excites valence electrons into the lowest lying ππ*
state which is found to decay back into the ground state in ∼400 fs in both T and Thd
independent of pump photon energy, and in 670 – 840 fs in TMP with a small amount of
pump energy dependence. The longer lifetime of TMP compared to T and Thd is found to
be a result of the conformational differences between the molecules in solution by QM/MM
calculations done at the XMS-CASPT2//CASSCF/AMBER level. Notably, no signal in any
of the three molecules is found to persist for longer than a few ps, contradicting previous
experiments that claimed a portion of the initially excited electron population is trapped in
an intermediate state for tens of ps before decaying. When using the 6.2 eV pulse as the
pump pulse, a band of multiple ππ* states is populated and found to decay into the lowest
lying ππ* state within the cross correlation of our laser pulses before decaying back into the
ground state.A major drawback of the previous study is the relatively low energy of the probe pulse. Whilephotoionization signal is observed from the excited ππ* states, no signal is observed from the
ground state as it is bound in excess of the probe photon energy. To remedy this problem a
new light source was designed and built to generate probe photons in the XUV regime with
sufficient energy to ionize both the ground and any excited states in these molecules. XUV
pulses are generated at 21.7 eV with very high flux (up to 100 nJ/pulse). This XUV light
has been applied to a wide variety of gaseous, liquid, and solvated species as discussed in
Chapter 4 of this thesis. The laser-assisted photoelectric effect (LAPE) has been utilized to
characterize the temporal profile of the XUV beam. This new source is now being applied
to NBs, and a variety of other systems, to further elucidate the dynamics described above
and to explore other ultrafast phenomena in solution