3,766 research outputs found
Modeling transcription factor binding events to DNA using a random walker/jumper representation on a 1D/2D lattice with different affinity sites
Surviving in a diverse environment requires corresponding organism responses.
At the cellular level, such adjustment relies on the transcription factors
(TFs) which must rapidly find their target sequences amidst a vast amount of
non-relevant sequences on DNA molecules. Whether these transcription factors
locate their target sites through a 1D or 3D pathway is still a matter of
speculation. It has been suggested that the optimum search time is when the
protein equally shares its search time between 1D and 3D diffusions. In this
paper, we study the above problem using a Monte Carlo simulation by considering
a very simple physical model. A 1D strip, representing a DNA, with a number of
low affinity sites, corresponding to non-target sites, and high affinity sites,
corresponding to target sites, is considered and later extended to a 2D strip.
We study the 1D and 3D exploration pathways, and combinations of the two modes
by considering three different types of molecules: a walker that randomly walks
along the strip with no dissociation; a jumper that represents dissociation and
then re-association of a TF with the strip at later time at a distant site; and
a hopper that is similar to the jumper but it dissociates and then
re-associates at a faster rate than the jumper. We analyze the final
probability distribution of molecules for each case and find that TFs can
locate their targets fast enough even if they spend 15% of their search time
diffusing freely in the solution. This indeed agrees with recent experimental
results obtained by Elf et al. 2007 and is in contrast with theoretical
expectation.Comment: 24 pages, 9 figure
The shadow knows: using shadows to investigate the structure of the pretransitional disk of HD 100453
We present GPI polarized intensity imagery of HD 100453 in Y-, J-, and K1
bands which reveals an inner gap ( au), an outer disk ( au) with
two prominent spiral arms, and two azimuthally-localized dark features also
present in SPHERE total intensity images (Wagner 2015). SED fitting further
suggests the radial gap extends to au. The narrow, wedge-like shape of the
dark features appears similar to predictions of shadows cast by a inner disk
which is misaligned with respect to the outer disk. Using the Monte Carlo
radiative transfer code HOCHUNCK3D (Whitney 2013), we construct a model of the
disk which allows us to determine its physical properties in more detail. From
the angular separation of the features we measure the difference in inclination
between the disks 45, and their major axes, PA = 140 east
of north for the outer disk and 100for the inner disk. We find an
outer disk inclination of from face-on in broad agreement
with the Wagner 2015 measurement of 34. SPHERE data in J- and H-bands
indicate a reddish disk which points to HD 100453 evolving into a young debris
disk
Erythropoietin response in critically ill mechanically ventilated patients: a prospective observational study
INTRODUCTION: Anemia is a common problem in critically ill patients. The etiology of anemia of critical illness is often determined to be multifactorial in the clinical setting, but the pathophysiology remains to be elucidated. Erythropoietin (EPO) is an endogenous glycoprotein hormone that serves as the primary stimulus for erythropoiesis. Recent evidence has demonstrated a blunted EPO response as a factor contributing to anemia of critical illness in specific subsets of patients. Critically ill patients requiring mechanical ventilation who exhibit anemia have not been the subject of previous studies. Our goal was to evaluate the erythropoietic response to anemia in the critically ill mechanically ventilated patient. METHODS: A prospective observational study was undertaken in the medical intensive care unit of a tertiary care, military hospital. Twenty patients admitted to the medical intensive care unit requiring mechanical ventilation for at least 72 hours were enrolled as study patients. EPO levels and complete blood count were measured 72 hours after admission and initiation of mechanical ventilation. Admission clinical and demographic data were recorded, and patients were followed for the duration of mechanical ventilation. Twenty patients diagnosed with iron deficiency anemia in the outpatient setting were enrolled as a control population. Control patients had baseline complete blood count and iron panel recorded by primary care physicians. EPO levels were measured at the time of enrollment in conjunction with complete blood count. RESULTS: The mean EPO level for the control population was 60.9 mU/ml. The mean EPO level in the mechanically ventilated patient group was 28.7 mU/ml, which was significantly less than in the control group (P = 0.035). The mean hemoglobin value was not significantly different between groups (10.6 g/dl in mechanically ventilated patients versus 10.2 g/dl in control patients; P > 0.05). CONCLUSION: Mechanically ventilated patients demonstrate a blunted EPO response to anemia. Further study of therapies directed at treating anemia of critical illness and evaluating its potential impact on mechanical ventilation outcomes and mortality is warranted
Recommended from our members
Selective nitrogen adsorption via backbonding in a metal-organic framework with exposed vanadium sites.
Industrial processes prominently feature π-acidic gases, and an adsorbent capable of selectively interacting with these molecules could enable important chemical separations1-4. Biological systems use accessible, reducing metal centres to bind and activate weakly π-acidic species, such as N2, through backbonding interactions5-7, and incorporating analogous moieties into a porous material should give rise to a similar adsorption mechanism for these gaseous substrates8. Here, we report a metal-organic framework featuring exposed vanadium(II) centres capable of back-donating electron density to weak π acids to successfully target π acidity for separation applications. This adsorption mechanism, together with a high concentration of available adsorption sites, results in record N2 capacities and selectivities for the removal of N2 from mixtures with CH4, while further enabling olefin/paraffin separations at elevated temperatures. Ultimately, incorporating such π-basic metal centres into porous materials offers a handle for capturing and activating key molecular species within next-generation adsorbents
- …