7,521 research outputs found
Clustered bottlenecks in mRNA translation and protein synthesis
We construct an algorithm that generates large, band-diagonal transition
matrices for a totally asymmetric exclusion process (TASEP) with local hopping
rate inhomogeneities. The matrices are diagonalized numerically to find
steady-state currents of TASEPs with local variations in hopping rate. The
results are then used to investigate clustering of slow codons along mRNA.
Ribosome density profiles near neighboring clusters of slow codons interact,
enhancing suppression of ribosome throughput when such bottlenecks are closely
spaced. Increasing the slow codon cluster size, beyond , does not
significantly reduce ribosome current. Our results are verified by extensive
Monte-Carlo simulations and provide a biologically-motivated explanation for
the experimentally-observed clustering of low-usage codons
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Thromboembolic Risks of Recombinant Factor VIIa Use in Warfarin-Associated Intracranial Hemorrhage: A Case–Control Study
Background: Recombinant factor VIIa (rFVIIa) may be used for rapid hemostasis in life-threatening hemorrhage. In warfarin-associated intracerebral hemorrhage (wICH), FVIIa use is controversial and may carry significant thromboembolic risks. We compared incidence of baseline thromboembolic risk factors and thromboembolism rates in wICH patients treated with additional rFVIIa to those treated with standard therapy of fresh frozen plasma (FFP) and vitamin K alone. Methods: We identified 45 consecutive wICH patients treated with additional rFVIIa over 5-year period, and 34 consecutive wICH patients treated with standard therapy alone as comparison group. We compared the incidence of post-hemorrhage cardiac and extra-cardiac thromboembolic complications between two treatment groups, and used logistic regression to adjust for significant confounders such as baseline thromboembolic risk factors. We performed secondary analysis comparing the quantity of FFP transfused between two treatment cohorts. Results: Both rFVIIa-treated and standard therapy-treated wICH patients had a high prevalence of pre-existing thromboembolic diseases including atrial fibrillation (73% vs 68%), deep venous thrombosis (DVT) or pulmonary embolism (PE) (22% vs 18%), coronary artery disease (CAD) (38% vs 32%), and abnormal electrocardiogram (EKG) (78% vs 85%). Troponin elevation following wICH was prevalent in both groups (47% vs 41%). Clinically significant myocardial infarction (MI), defined as troponin > 1.0 ng/dL, occurred in 13% of rFVIIa-treated and 6% of standard therapy-treated patients (p=0.52). Past history of CAD (p=0.0061) and baseline abnormal EKG (p=0.02) were independently associated with clinically significant MI following wICH while rFVIIa use was not. The incidences of DVT/PE (2% vs 9%; p=0.18) and ischemic stroke (2% vs 0%; p=0.38) were similar between two treatment groups. Recombinant FVIIa-treated patients had lower mean INR at 3 (p=0.0001) and 6 hours (p<0.0001) and received fewer units of FFP transfusion (3 vs 5; p=0.003). Conclusions: Pre-existing thromboembolic risk factors as well as post-hemorrhage troponin elevation are prevalent in wICH patients. Clinically significant MI occurs in up to 13% of wICH patients. rFVIIa use was not associated with increased incidence of clinically significant MI or other venous or arterial thromboembolic events in this wICH cohort
Graduate Entry Medicine: Selection Criteria and Student Performance
Background: Graduate entry medicine raises new questions about the suitability of students with different backgrounds. We examine this, and the broader issue of effectiveness of selection and assessment procedures. Methods: The data included background characteristics, academic record, interview score and performance in pre-clinical modular assessment for two years intake of graduate entry medical students. Exploratory factor analysis is a powerful method for reducing a large number of measures to a smaller group of underlying factors. It was used here to identify patterns within and between the selection and performance data. Principal Findings: Basic background characteristics were of little importance in predicting exam success. However, easily interpreted components were detected within variables comprising the ‘selection ’ and ‘assessment ’ criteria. Three selection components were identified (‘Academic’, ‘GAMSAT’, ‘Interview’) and four assessment components (‘General Exam’, ‘Oncology’, ‘OSCE’, ‘Family Case Study’). There was a striking lack of relationships between most selection and performance factors. Only ‘General Exam ’ and ‘Academic ’ showed a correlation (Pearson’s r = 0.55, p,0.001). Conclusions: This study raises questions about methods of student selection and their effectiveness in predicting performance and assessing suitability for a medical career. Admissions tests and most exams only confirmed previous academic achievement, while interview scores were not correlated with any consequent assessment
Environments of the Four Tryptophans in the Extracellular Domain of Human Tissue Factor: Comparison of Results from Absorption and Fluorescence Difference Spectra of Tryptophan Replacement Mutants with the Crystal Structure of the Wild-Type Protein
The local environments of the four tryptophan residues of the extracellular domain of human tissue factor (sTF) were assessed from difference absorption and fluorescence spectra. The difference spectra were derived by subtracting spectra from single Trp-to-Phe or Trp-to-Tyr replacement mutants from the corresponding spectrum of the wild-type protein. Each of the mutants was capable of enhancing the proteolytic activity of factor Vila showing that the mutations did not introduce major structural changes, although the mutants were more susceptible to denaturation by guanidinium chloride. The difference spectra indicate that the Trp residues are buried to different extents within the protein matrix. This evaluation was compared with the x-ray crystal structure of sTF. There is excellent agreement between predictions from the difference spectra and the environments of the Trp residues observed in the x-ray crystal structure, demonstrating that difference absorption and particularly fluorescence spectra derived from functional single-Trp replacement mutants can be used to obtain information about the local environments of individual Trp residues in multi-tryptophan proteins
Evidence for t\bar{t}\gamma Production and Measurement of \sigma_t\bar{t}\gamma / \sigma_t\bar{t}
Using data corresponding to 6.0/fb of ppbar collisions at sqrt(s) = 1.96 TeV
collected by the CDF II detector, we present a cross section measurement of
top-quark pair production with an additional radiated photon. The events are
selected by looking for a lepton, a photon, significant transverse momentum
imbalance, large total transverse energy, and three or more jets, with at least
one identified as containing a b quark. The ttbar+photon sample requires the
photon to have 10 GeV or more of transverse energy, and to be in the central
region. Using an event selection optimized for the ttbar+photon candidate
sample we measure the production cross section of, and the ratio of cross
sections of the two samples. Control samples in the dilepton+photon and
lepton+photon+\met, channels are constructed to aid in decay product
identification and background measurements. We observe 30 ttbar+photon
candidate events compared to the standard model expectation of 26.9 +/- 3.4
events. We measure the ttbar+photon cross section to be 0.18+0.08 pb, and the
ratio of the cross section of ttbar+photon to ttbar to be 0.024 +/- 0.009.
Assuming no ttbar+photon production, we observe a probability of 0.0015 of the
background events alone producing 30 events or more, corresponding to 3.0
standard deviations.Comment: 9 pages, 3 figure
Observation of the Baryonic Flavor-Changing Neutral Current Decay Lambda_b -> Lambda mu+ mu-
We report the first observation of the baryonic flavor-changing neutral
current decay Lambda_b -> Lambda mu+ mu- with 24 signal events and a
statistical significance of 5.8 Gaussian standard deviations. This measurement
uses ppbar collisions data sample corresponding to 6.8fb-1 at sqrt{s}=1.96TeV
collected by the CDF II detector at the Tevatron collider. The total and
differential branching ratios for Lambda_b -> Lambda mu+ mu- are measured. We
find B(Lambda_b -> Lambda mu+ mu-) = [1.73+-0.42(stat)+-0.55(syst)] x 10^{-6}.
We also report the first measurement of the differential branching ratio of B_s
-> phi mu+ mu- using 49 signal events. In addition, we report branching ratios
for B+ -> K+ mu+ mu-, B0 -> K0 mu+ mu-, and B -> K*(892) mu+ mu- decays.Comment: 8 pages, 2 figures, 4 tables. Submitted to Phys. Rev. Let
Precision Top-Quark Mass Measurements at CDF
We present a precision measurement of the top-quark mass using the full
sample of Tevatron TeV proton-antiproton collisions collected
by the CDF II detector, corresponding to an integrated luminosity of 8.7
. Using a sample of candidate events decaying into the
lepton+jets channel, we obtain distributions of the top-quark masses and the
invariant mass of two jets from the boson decays from data. We then compare
these distributions to templates derived from signal and background samples to
extract the top-quark mass and the energy scale of the calorimeter jets with
{\it in situ} calibration. The likelihood fit of the templates from signal and
background events to the data yields the single most-precise measurement of the
top-quark mass, \mtop = 172.85 \pm\pmComment: submitted to Phys. Rev. Let
Evidence for the exclusive decay Bc+- to J/psi pi+- and measurement of the mass of the Bc meson
We report first evidence for a fully reconstructed decay mode of the
B_c^{\pm} meson in the channel B_c^{\pm} \to J/psi \pi^{\pm}, with J/psi \to
mu^+mu^-. The analysis is based on an integrated luminosity of 360 pb$^{-1} in
p\bar{p} collisions at 1.96 TeV center of mass energy collected by the Collider
Detector at Fermilab. We observe 14.6 \pm 4.6 signal events with a background
of 7.1 \pm 0.9 events, and a fit to the J/psi pi^{\pm} mass spectrum yields a
B_c^{\pm} mass of 6285.7 \pm 5.3(stat) \pm 1.2(syst) MeV/c^2. The probability
of a peak of this magnitude occurring by random fluctuation in the search
region is estimated as 0.012%.Comment: 7 pages, 3 figures. Version 3, accepted by PR
Combined search for the standard model Higgs boson decaying to a bb pair using the full CDF data set
We combine the results of searches for the standard model Higgs boson based
on the full CDF Run II data set obtained from sqrt(s) = 1.96 TeV p-pbar
collisions at the Fermilab Tevatron corresponding to an integrated luminosity
of 9.45/fb. The searches are conducted for Higgs bosons that are produced in
association with a W or Z boson, have masses in the range 90-150 GeV/c^2, and
decay into bb pairs. An excess of data is present that is inconsistent with the
background prediction at the level of 2.5 standard deviations (the most
significant local excess is 2.7 standard deviations).Comment: To be published in Phys. Rev. Lett (v2 contains minor updates based
on comments from PRL
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