673 research outputs found
Research on Solid Waste Recycling at the Forest Products Laboratory
In the late 1960\u27s a large segment of the American public became alarmed at what was seen as wasteful depletion and polluting use of our natural resources. The hue and cry that was raised carried us into the environmental decade a time for positive action to solve the perplexing problems that beset man in an increasingly crowded world
Identification, Ki determination and CoMFA analysis of nuclear receptor ligands as competitive inhibitors of OATP1B1-mediated estradiol-17β-glucuronide transport
Evidence shows that drug-drug interactions can occur at the level of drug transporters such as the organic anion transporting polypeptides (OATPs), a group of membrane solute carriers that mediate the sodium-independent transport of a wide range of amphipathic organic compounds. The polyspecific OATP1B1 is exclusively expressed at the basolateral membrane of hepatocytes and mediates uptake of amphipathic organic compounds from blood into hepatocytes. Nuclear receptors are ligand-activated transcription factors that play an important role in xenobiotic disposition and human diseases. Quite a few nuclear receptor ligands interact with transport proteins.
A high-resolution three-dimensional structure is critical to understand the polyspecificity of OATP1B1 to predict and prevent adverse drug-drug interactions. Unfortunately there are no crystal structures of OATPs/Oatps available to date. Therefore, in this study we attempted to elucidate the characteristics of the substrate binding site of OATP1B1 based on small molecules interacting with it. First, we identified inhibitors of the OATP1B1 model substrate estradiol-17β-glucuronide from about forty nuclear receptor ligands. Among them, GW1929, paclitaxel and troglitazone were strong inhibitors, while 5α-androstane, 5α-androstane-3β, 17β-diol-17-hexahydrobenzoate and estradiol-3-benzoate were weak inhibitors. Then, we selected 25 compounds and performed inhibition kinetic studies to identify competitive inhibitors and determine their Ki values which ranged from submicromolar to submillimolar. Finally, we performed CoMFA analysis on the identified competitive inhibitors. The CoMFA results indicate that the substrate binding site of OATP1B1 consists of a large hydrophobic middle part with basic residues at both ends that could be very important for substrate binding
Are you suffering from a large arterial occlusion? Please raise your arm!
Background and purpose:
Triage tools to identify candidates for thrombectomy are of utmost importance in acute stroke. No prognostic tool has yet gained any widespread use. We compared the predictive value of various models based on National Institutes of Health Stroke Scale (NIHSS) subitems, ranging from simple to more complex models, for predicting large artery occlusion (LAO) in anterior circulation stroke.
Methods:
Patients registered in the SITS international Stroke Register with available NIHSS and radiological arterial occlusion data were analysed. We compared 2042 patients harbouring an LAO with 2881 patients having no/distal occlusions. Using binary logistic regression, we developed models ranging from simple 1 NIHSS-subitem to full NIHSS-subitems models. Sensitivities and specificities of the models for predicting LAO were examined.
Results:
The model with highest predictive value included all NIHSS subitems for predicting LAO (area under the curve (AUC) 0.77), yielding a sensitivity and specificity of 69% and 76%, respectively. The second most predictive model (AUC 0.76) included 4-NIHSS-subitems (level of consciousness commands, gaze, facial and arm motor function) yielding a sensitivity and specificity of 67% and 75%, respectively. The simplest model included only deficits in arm motor-function (AUC 0.72) for predicting LAO, yielding a sensitivity and specificity of 67% and 72%, respectively.
Conclusions:
Although increasingly more complex models yield a higher discriminative performance for predicting LAO, differences between models are not large. Assessing grade of arm dysfunction along with an established stroke-diagnosis model may serve as a surrogate measure of arterial occlusion-status, thereby assisting in triage decisions
Clinical selection strategies to identify ischemic stroke patients with large anterior vessel occlusion: results from SITS-ISTR (Safe Implementation of Thrombolysis in Stroke International Stroke Thrombolysis Registry)
Background and Purpose—The National Institutes of Health Stroke Scale (NIHSS) correlates with presence of large anterior vessel occlusion (LAVO). However, the application of the full NIHSS in the prehospital setting to select patients eligible for treatment with thrombectomy is limited. Therefore, we aimed to evaluate the prognostic value of simple clinical selection strategies.
Methods—Data from the Safe Implementation of Thrombolysis in Stroke International Stroke Thrombolysis Registry (January 2012–May 2014) were analyzed retrospectively. Patients with complete breakdown of NIHSS scores and documented vessel status were included. We assessed the association of prehospital stroke scales and NIHSS symptom profiles with LAVO (internal carotid artery, carotid-terminus or M1-segment of the middle cerebral artery).
Results—Among 3505 patients, 23.6% (n=827) had LAVO. Pathological finding on the NIHSS item best gaze was strongly associated with LAVO (adjusted odds ratio 4.5, 95% confidence interval 3.8–5.3). All 3 face–arm–speech–time test (FAST) items identified LAVO with high sensitivity. Addition of the item gaze to the original FAST score (G-FAST) or high scores on other simplified stroke scales increased specificity. The NIHSS symptom profiles representing total anterior syndromes showed a 10-fold increased likelihood for LAVO compared with a nonspecific clinical profile. If compared with an NIHSS threshold of ≥6, the prehospital stroke scales performed similarly or even better without losing sensitivity.
Conclusions—Simple modification of the face–arm–speech–time score or evaluating the NIHSS symptom profile may help to stratify patients’ risk of LAVO and to identify individuals who deserve rapid transfer to comprehensive stroke centers. Prospective validation in the prehospital setting is required
Re II and Other Exotic Spectra in HD 65949
Powerful astronomical spectra reveal an urgent need for additional work on
atomic lines, levels, and oscillator strengths. The star HD 65949 provides some
excellent examples of species rarely identified in stellar spectra. For
example, the Re II spectrum is well developed, with 17 lines between 3731 and
4904 [A], attributed wholly or partially to Re II. Classifications and
oscillator strengths are lacking for a number of these lines. The spectrum of
Os II is well identified. Of 14 lines attributed wholly or partially to Os II,
only one has an entry in the VALD database. We find strong evidence that Te II
is present. There are NO Te II lines in the VALD database. Ru II is clearly
present, but oscillator strengths for lines in the visual are lacking. There is
excellent to marginal evidence for a number of less commonly identified
species, including Kr II, Nb II, Sb II, Xe II, Pr III, Ho III, Au II, and Pt II
(probably Pt-198), to be present in the spectrum of HD 65949. The line Hg II at
3984 [A] is of outstanding strength, and all three lines of Multiplet 1 of Hg I
are present, even though the surface temperature of HD 65949 is relatively
high. Finally, we present the case of an unidentified, 24 [mA], line at 3859.63
[A], which could be the same feature seen in magnetic CP stars. It is typically
blended with a putative U II line used in cosmochronology.Comment: ASOS9 Poster (Lund, Sweden, August 2007), to be published in Journal
of Physics: Conference Series (JPCS), 6 pages 1 figur
The Virtual International Stroke Trials Archive
BACKGROUND AND PURPOSE: Stroke has global importance and it causes an increasing amount of human suffering and economic burden, but its management is far from optimal. The unsuccessful outcome of several research programs highlights the need for reliable data on which to plan future clinical trials. The Virtual International Stroke Trials Archive aims to aid the planning of clinical trials by collating and providing access to a rich resource of patient data to perform exploratory analyses.
METHODS: Data were contributed by the principal investigators of numerous trials from the past 16 years. These data have been centrally collated and are available for anonymized analysis and hypothesis testing.
RESULTS: Currently, the Virtual International Stroke Trials Archive contains 21 trials. There are data on \u3e15,000 patients with both ischemic and hemorrhagic stroke. Ages range between 18 and 103 years, with a mean age of 69+/-12 years. Outcome measures include the Barthel Index, Scandinavian Stroke Scale, National Institutes of Health Stroke Scale, Orgogozo Scale, and modified Rankin Scale. Medical history and onset-to-treatment time are readily available, and computed tomography lesion data are available for selected trials.
CONCLUSIONS: This resource has the potential to influence clinical trial design and implementation through data analyses that inform planning
Tunneling between two Luttinger liquids with long range interaction
The non linear charge transfer through a tunnel junction between two
Luttinger systems is studied for repulsive, finite range interaction between
electrons on the same, V_{11}, and on different,V_{12}, sides of the junction.
Features of the Coulomb blockade effect are observed if V_{12}=0. We predict a
novel interaction induced enhancement of the current if V_{12}>0. When
V_{12}=V_{11}, the current is suppressed at small bias, but the ``charging
energy'', obtained from the asymptotic behavior at high bias voltage, vanishes.Comment: 4 pages, RevTeX, to be published in Physical Review B (Brief Report
Dynamical evolution of titanium, strontium, and yttrium spots on the surface of the HgMn star HD 11753
Aims. We gathered about 100 high-resolution spectra of three typical HgMn
(mercury-manganese) stars, HD 11753, HD 53244, and HD 221507, to search for
slowly pulsating B-like pulsations and surface inhomogeneous distribution of
various chemical elements. Methods. Classical frequency analysis methods were
used to detect line profile variability and to determine the variation period.
Doppler imaging reconstruction was performed to obtain abundance maps of
chemical elements on the stellar surface. Results. For HD 11753, which is the
star with the most pronounced variability, distinct spectral line profile
changes were detected for Ti, Sr, Y, Zr, and Hg, whereas for HD 53244 and HD
221507 the most variable line profiles belong to the elements Hg and Y,
respectively. We derived rotation periods for all three stars from the
variations of radial velocities and equivalent widths of spectral lines
belonging to inhomogeneously distributed elements: P_rot (HD 11753)=9.54 d,
P_rot (HD 53244)=6.16 d, and P_rot (HD 221507)=1.93 d. For HD 11753 the Doppler
imaging technique was applied to derive the distribution of the most variable
elements Ti, Sr, and Y using two datasets separated by ~65 days. Results of
Doppler imaging reconstruction revealed noticeable changes in the surface
distributions of TiII, SrII, and YII between the datasets, indicating the
hitherto not well understood physical processes in stars with radiative
envelopes that cause a rather fast dynamical chemical spot evolution.Comment: Accepted for publication in Astronomy and Astrophysics, 6 pages, 9
figures, 2 tables
Strong dust processing in circumstellar discs around 6 RV Tauri stars. Are dusty RV Tauri stars all binaries?
We present extended Spectral Energy Distributions (SEDs) of seven classical
RV Tauri stars, using newly obtained submillimetre continuum measurements and
Geneva optical photometry supplemented with literature data. The broad-band
SEDs show a large IR excess with a black-body slope at long wavelengths in six
of the seven stars, R Sct being the noticeable exception. This long wavelength
slope is best explained assuming the presence of a dust component of large
grains in the circumstellar material. We show that the most likely distribution
of the circumstellar dust around the six systems is that the dust resides in a
disc. Moreover, very small outflow velocities are needed to explain the
presence of dust near the sublimation temperature and we speculate that the
discs are Keplerian. The structure and evolution of these compact discs are as
yet not understood but a likely prerequisite for their formation is that the
dusty RV Tauri stars are binaries.Comment: 10 pages, will be published in A&
Comparative Modelling of the Spectra of Cool Giants
Our ability to extract information from the spectra of stars depends on
reliable models of stellar atmospheres and appropriate techniques for spectral
synthesis. Various model codes and strategies for the analysis of stellar
spectra are available today. We aim to compare the results of deriving stellar
parameters using different atmosphere models and different analysis strategies.
The focus is set on high-resolution spectroscopy of cool giant stars. Spectra
representing four cool giant stars were made available to various groups and
individuals working in the area of spectral synthesis, asking them to derive
stellar parameters from the data provided. The results were discussed at a
workshop in Vienna in 2010. Most of the major codes currently used in the
astronomical community for analyses of stellar spectra were included in this
experiment. We present the results from the different groups, as well as an
additional experiment comparing the synthetic spectra produced by various codes
for a given set of stellar parameters. Similarities and differences of the
results are discussed. Several valid approaches to analyze a given spectrum of
a star result in quite a wide range of solutions. The main causes for the
differences in parameters derived by different groups seem to lie in the
physical input data and in the details of the analysis method. This clearly
shows how far from a definitive abundance analysis we still are.Comment: accepted for publication in A&A. This version includes also the
online tables. Reference spectra will later be available via the CD
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