737 research outputs found
Rapid iododeboronation with and without gold catalysis: application to radiolabelling of arenes
Radiopharmaceuticals incorporating radioactive iodine in combination with SPECT imaging play a key role in nuclear medicine, with applications in drug development and disease diagnosis. Despite this importance, there are relatively few general methods for incorporating radioiodine into small molecules. Here we describe a rapid, air- and moisture-stable ipso-iododeboronation procedure using NIS, in the non-toxic and green solvent dimethyl carbonate. The fast reaction and mild conditions of the gold-catalysed method led to the development of a highly efficient process for radiolabelling of arenes, which constitutes the first example of an application of homogenous gold catalysis to selective radiosynthesis. This has been exemplified with an effective synthesis of radiolabelled meta-[125I]iodobenzylguanidine, a radiopharmaceutical used for the imaging and therapy of human norepinephrine transporter-expressing tumours
Tunable far-infrared laser spectroscopy of hydrogen bonds: The K_a = O(u)â1(g) rotation-tunneling spectrum of the HCI dimer
The ground state K_a =0(u)â1(g) bâtype subband of the rotationâtunneling spectrum of the symmetric ^(35)Clâ^(35)Cl,^(37)Clâ^(37)Cl, and the mixed ^(35)Clâ^(37)Cl hydrogen chloride dimers have been recorded near 26.3 cm^(â1) with subâDoppler resolution in a continuous twoâdimensional supersonic jet with a tunable farâinfrared laser spectrometer. Quadrupole hyperfine structure from the chlorine nuclei has been resolved. From the fitted rotational constants a (H^(35)Cl)_2 centerâofâmass separation of 3.81 Ă
is derived for the K_a =1(g) levels, while the nuclear quadrupole coupling constants yield a vibrationally averaged angular structure for both tunneling states of approximately 20â25 deg for the hydrogen bonded proton and at least 70â75 deg for the external proton. This nearly orthogonal structure agrees well with that predicted by ab initio theoretical calculations, but the observed splittings and intensity alterations of the lines indicate that the chlorine nuclei are made equivalent by a large amplitude tunneling motion of the HCl monomers. A similar geared internal rotation tunneling motion has been found for the HF dimer, but here the effect is much greater. The ground state tunneling splittings are estimated to lie between 15â18 cm^(â1), and the selection rules observed indicate that the trans tunneling path dominates the large amplitude motion, as expected, provided the dimer remains planar. From the observed hyperfine constants, we judge the dimer and its associated tunneling motion to be planar to within 10°
ASSESSMENT OF PROCEDURAL ASPECTS AND QUALITY CONTROL IN HUMAN PLACENTAL RNA ISOLATION PROTOCOLS
poster abstractHigh quality RNA is of paramount importance in accurately interpreting gene expression changes in the placenta throughout pregnancy, as well as in common placental pathologies. The purpose of this study was to develop a standard operating procedure for the collection of human placental tissue and isolation of high quality RNA for pregnancy-related molecular studies. To accomplish this task, we compared several different parameters to minimize RNA degradation, including preservation (liquid nitrogen vs. RNAlater), dis-ruption (mortar/pestle vs. homogenization), and isolation (Trizol vs. RNeasy). We performed 150 RNA isolations from 30 term placentas. The overall yield was 365 ± 197 ng RNA per mg of tissue. The A260/280 ratio for all samples was 2.11 ± 0.1 (mean ± s.d.) and the RQI was 7.1 ± 1.4. No significant differences in RNA purity, yield, or quality were observed between different placental collections or RNA isolation techniques. However, poor RQI values of 2.7 to 3.3 were obtained after brief thawing of frozen placental samples. We also compared storage of RNAlater stabilized tissue at 4 de-grees or room temperature for 1 day, 7 days, and 30 days. The integrity of RNA stored at room temperature for 1 day was significantly better (Pâč0.05 RQI 7.3 ± 0.58, mean ± s.d) than RNA stored at room temperature for 30 days (RQI 5.0 ±1.2, mean ± s.d). The results of these studies will be useful for establishing standard procedures for placenta collection for pregnancy biobanks
A perfusion-capable microfluidic bioreactor for assessing microbial heterologous protein production
We present an integrated microfluidic bioreactor for fully continuous perfusion cultivation of suspended microbial cell cultures. This system allowed continuous and stable heterologous protein expression by sustaining the cultivation of Pichia pastoris over 11 days. This technical capability also allowed testing the impact of perfusion conditions on protein expression. This advance should enable small-scale models for process optimization in continuous biomanufacturing.United States. Defense Advanced Research Projects Agency (N66001-13-C-4025)National Cancer Institute (U.S.) (P30-CA14051)United States. National Institutes of Health (2T32GM008334-26
Measurement of the perpendicular rotation-tunneling spectrum of the water dimer by tunable far infrared laser spectroscopy in a planar supersonic jet
Fifty-six transitions from the K=1 lower-->K=2 lower tunnelingârotation band of water dimer have been measured and assigned at 22 cm^â1 by direct absorption spectroscopy in a cw planar supersonic jet expansion using a tunable far infrared laser spectrometer. Two different models were used to fit the data and several spectroscopic constants were determined for the upper and lower states. This work supports the local IAM model recently proposed by Coudert and Hougen for the hydrogen bond tunneling dynamics of the water dimer. This model includes four different tunneling motions, all of which contribute to the observed tunneling splittings. This is the most complicated hydrogen bonded system considered to be well understood at this time, at least in the lowest few K states
Tunable far infrared laser spectroscopy of van der Waals bonds: Extended measurements on the lowest Sigma bend of ArHCl
A tunable far infrared laser system has been used to measure the vibrationârotation spectrum of the lowest Sigma bending state of ArHCl near 24 cm^â1 in a cw planar jet operating with a terminal jet temperature near 3 K. Over 60 transitions have been observed for both 35Cl and 37Cl isotopes with resolution of the quadrupole hyperfine structure. An improved set of molecular parameters was determined, including B, D, H, and eqQ for both upper and lower states. Very narrow linewidths (approximately 300 kHz) resulting in high resolution and sensitivity make this technique a powerful new method for the detailed investigation of intermolecular forces
Tunable far infrared laser spectroscopy of van der Waals bonds: Vibrationârotationâtunneling spectra of ArâH2O
The first high resolution spectra of a rare gasâH2O cluster have been observed using a tunable far infrared laser to probe the vibrationârotationâtunneling levels of ArâH2O formed in a continuous planar supersonic jet. The high sensitivity of this spectrometer facilitated extensive measurements of two perpendicular subbands which are assigned to transitions from the ground state to the upper component of a hydrogen exchange tunneling doublet (c-type) at 21 cm^â1, and to vb1 =1+ (b-type) at 25 cm^â1, the lower tunneling component of a bending vibration which is perpendicular to the tunneling coordinate. The tunneling splitting is shown to be in the range 2.5â7 cm^â1 and the lower tunneling component of the excited bending vibration lies between 39 and 43 cm^â1 above the ground state of the complex. The experimentally determined center-of-mass separation (Rc.m. =3.75 Ă
) and harmonic stretching force constant (ks =0.0134 mdyn/Ă
) are compared to those of related first and second row hydrides. The large amplitude motions occurring within this complex make it difficult to establish its structure
Coronary-artery bypass surgery in patients with ischemic cardiomyopathy
BACKGROUND
The survival benefit of a strategy of coronary-artery bypass grafting (CABG) added to
guideline-directed medical therapy, as compared with medical therapy alone, in patients
with coronary artery disease, heart failure, and severe left ventricular systolic
dysfunction remains unclear.
METHODS
From July 2002 to May 2007, a total of 1212 patients with an ejection fraction of 35%
or less and coronary artery disease amenable to CABG were randomly assigned to
undergo CABG plus medical therapy (CABG group, 610 patients) or medical therapy
alone (medical-therapy group, 602 patients). The primary outcome was death from any
cause. Major secondary outcomes included death from cardiovascular causes and death
from any cause or hospitalization for cardiovascular causes. The median duration of
follow-up, including the current extended-follow-up study, was 9.8 years.
RESULTS
A primary outcome event occurred in 359 patients (58.9%) in the CABG group and in
398 patients (66.1%) in the medical-therapy group (hazard ratio with CABG vs. medical
therapy, 0.84; 95% confidence interval [CI], 0.73 to 0.97; P=0.02 by log-rank test). A
total of 247 patients (40.5%) in the CABG group and 297 patients (49.3%) in the
medical-therapy group died from cardiovascular causes (hazard ratio, 0.79; 95% CI,
0.66 to 0.93; P=0.006 by log-rank test). Death from any cause or hospitalization for
cardiovascular causes occurred in 467 patients (76.6%) in the CABG group and in 524
patients (87.0%) in the medical-therapy group (hazard ratio, 0.72; 95% CI, 0.64 to 0.82;
P<0.001 by log-rank test).
CONCLUSIONS
In a cohort of patients with ischemic cardiomyopathy, the rates of death from any
cause, death from cardiovascular causes, and death from any cause or hospitalization
for cardiovascular causes were significantly lower over 10 years among patients who
underwent CABG in addition to receiving medical therapy than among those who received
medical therapy alone. (Funded by the National Institutes of Health; STICH [and
STICHES] ClinicalTrials.gov number, NCT00023595.
Importance of clinical measures of ischemia in the prognosis of patients with documented coronary artery disease
AbstractTo examine the value of clinical measures of ischemia for stratifying prognosis, 5,886 consecutive patients who had symptomatic significant (â„75% stenosis) coronary artery disease were studied. Using the Cox regression model in a randomly selected half of the patients, the prognostically independent clinical variables were weighted and arranged into a simple angina score: angina score = angina course Ă (1 + daily angina frequency) + ST-T changes, where angina course was equal to 3 if unstable or variant angina was present, 2 if the patient's angina was progressive with nocturnal episodes, 1 if it was progressive without nocturnal symptoms and 0 if it was stable; 6 points were added for the presence of âischemicâ ST-T changes. This angina score was then validated in an independent patient sample.The score was a more powerful predictor of prognosis than was any individual anginal descriptor. Furthermore, the angina score added significant independent prognostic information to the patient's age, sex, coronary anatomy and left ventricular function. Patients with three vessel disease and a normal ventricle (n = 1,233) had a 2 year infarction-free survival rate of 90% with an angina score of 0 and a 68% survival rate with an angina score â„9. With an ejection fraction <50% and three vessel disease (n = 1,116), the corresponding infarction-free survival figures were 76 and 56%. Thus, a careful summarization of clinical markers of ischemia in the form of an angina score can provide a powerful prognostic tool and may aid clinicians in identifying high risk patients who are candidates for aggressive therapeutic interventions
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