29,783 research outputs found
Detection of Planetary Transits Across a Sun-like Star
We report high precision, high cadence photometric measurements of the star
HD 209458, which is known from radial velocity measurements to have a planetary
mass companion in a close orbit. We detect two separate transit events at times
that are consistent with the radial velocity measurements. In both cases, the
detailed shape of the transit curve due to both the limb darkening of the star
and the finite size of the planet is clearly evident. Assuming stellar
parameters of 1.1 R_Sun and 1.1 M_Sun, we find that the data are best
interpreted as a gas giant with a radius of 1.27 +/- 0.02 R_Jup in an orbit
with an inclination of 87.1 +/- 0.2 degrees. We present values for the
planetary surface gravity, escape velocity, and average density, and discuss
the numerous observations that are warranted now that a planet is known to
transit the disk of its parent star.Comment: 10 pages, 3 figures, accepted by ApJ Letter
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A Two-Dimensional Mesh Refinement Method for Problems with One-Dimensional Singularities
This paper introduces a method for resolving internal layers that can occur in the solutions of time-dependent differential equations in two space dimensions. Singular features in these solutions that are essentially one-dimensional in nature but are not oriented with the computational mesh are resolved using one-dimensional mesh refinement techniques with a procedure that is similar to an ADI method. A careful interpolation procedure assures that the resolution obtained in each ADI step is not lost in the succeeding ADI step
Plasma membrane association by N-acylation governs PKG function in Toxoplasma gondii
ABSTRACT
Cyclic GMP (cGMP)-dependent protein kinase (protein kinase G [PKG]) is essential for microneme secretion, motility, invasion, and egress in apicomplexan parasites, However, the separate roles of two isoforms of the kinase that are expressed by some apicomplexans remain uncertain. Despite having identical regulatory and catalytic domains, PKG
I
is plasma membrane associated whereas PKG
II
is cytosolic in
Toxoplasma gondii
. To determine whether these isoforms are functionally distinct or redundant, we developed an auxin-inducible degron (AID) tagging system for conditional protein depletion in
T. gondii
. By combining AID regulation with genome editing strategies, we determined that PKG
I
is necessary and fully sufficient for PKG-dependent cellular processes. Conversely, PKG
II
is functionally insufficient and dispensable in the presence of PKG
I
. The difference in functionality mapped to the first 15 residues of PKG
I
, containing a myristoylated Gly residue at position 2 that is critical for membrane association and PKG function. Collectively, we have identified a novel requirement for cGMP signaling at the plasma membrane and developed a new system for examining essential proteins in
T. gondii
.
IMPORTANCE
Toxoplasma gondii
is an obligate intracellular apicomplexan parasite and important clinical and veterinary pathogen that causes toxoplasmosis. Since apicomplexans can only propagate within host cells, efficient invasion is critically important for their life cycles. Previous studies using chemical genetics demonstrated that cyclic GMP signaling through protein kinase G (PKG)-controlled invasion by apicomplexan parasites. However, these studies did not resolve functional differences between two compartmentalized isoforms of the kinase. Here we developed a conditional protein regulation tool to interrogate PKG isoforms in
T. gondii
. We found that the cytosolic PKG isoform was largely insufficient and dispensable. In contrast, the plasma membrane-associated isoform was necessary and fully sufficient for PKG function. Our studies identify the plasma membrane as a key location for PKG activity and provide a broadly applicable system for examining essential proteins in
T. gondii
.
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Methadone and Corrected QT Prolongation in Pain and Palliative Care Patients: A Case–Control Study
Background: Methadone (ME) is commonly used in pain and palliative care (PPC) patients with refractory pain or intolerable opioid adverse effects (AEs). A unique ME AE is its corrected QT (QTc) interval prolongation risk, but most evidence exists in methadone maintenance therapy patients.
Objective: Our goal was to identify QTc interval prolongation risk factors in PPC patients receiving ME and other medications known to prolong the QTc interval and develop a risk stratification tool.
Design: We performed a case–control study of adult inpatients receiving ME for pain management.
Settings/Subjects: Adult inpatients receiving ME with a QTc \u3e470 msec (males) and \u3e480 msec (females) were matched 1:2 according to age, history of QTc prolongation, and gender with ME patients who did not have a prolonged QTc interval. QTc prolongation risk factors were collected for both groups. Covariates were analyzed using conditional logistic regression. Classification and regression tree analysis was used to identify the ME dose associated with QTc prolongation.
Results: Predictors of QTc prolongation included congestive heart failure (CHF) (OR: 11.9; 95% CI: 3.7–38.2; p \u3c 0.00), peptic ulcer disease (PUD) (odds ratio [OR]: 8.3; 95% confidence interval [95% CI]: 2.4–28.9; p \u3c 0.00), hypokalemia (OR: 6.5; 95% CI: 1.5–28.2; p \u3c 0.01), rheumatologic diseases (OR: 4.7; 95% CI: 1.6–13.9; p \u3c 0.00), taking medications with a known torsades de pointes (TdP) risk (OR: 4.4; 95% CI: 1.8–10.7; p \u3c 0.01), malignancy (OR: 3.3; 95% CI: 1.2–9.3; p \u3c 0.03), hypocalcemia (OR: 2.1; 95% CI: 0.9–4.8; p \u3c 0.07), and ME doses \u3e45 mg per day (OR: 1.9; 95% CI: 0.8–4.8; p \u3c 0.16). Mild liver disease was protective against QTc prolongation (OR: 0.05; 95% CI: 0.0–0.46; p \u3c 0.01).
Conclusions: Predictors of QTc prolongation in our multivariate conditional logistic regression model included CHF, PUD, hypokalemia, rheumatologic disorders, use of medications with a known TdP risk, malignancy, hypocalcemia, and ME doses \u3e45 mg per day
Catalyst for carbon monoxide oxidation
A catalyst is disclosed for the combination of CO and O2 to form CO2, which includes a platinum group metal (e.g., platinum); a reducable metal oxide having multiple valence states (e.g., SnO2); and a compound which can bind water to its structure (e.g., silica gel). This catalyst is ideally suited for application to high-powered pulsed, CO2 lasers operating in a sealed or closed-cycle condition
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