652 research outputs found
A quantitative comparison of sRNA-based and protein-based gene regulation
Small, non-coding RNAs (sRNAs) play important roles as genetic regulators in
prokaryotes. sRNAs act post-transcriptionally via complementary pairing with
target mRNAs to regulate protein expression. We use a quantitative approach to
compare and contrast sRNAs with conventional transcription factors (TFs) to
better understand the advantages of each form of regulation. In particular, we
calculate the steady-state behavior, noise properties, frequency-dependent gain
(amplification), and dynamical response to large input signals of both forms of
regulation. While the mean steady-state behavior of sRNA-regulated proteins
exhibits a distinctive tunable threshold-linear behavior, our analysis shows
that transcriptional bursting leads to significantly higher intrinsic noise in
sRNA-based regulation than in TF-based regulation in a large range of
expression levels and limits the ability of sRNAs to perform quantitative
signaling. Nonetheless, we find that sRNAs are better than TFs at filtering
noise in input signals. Additionally, we find that sRNAs allow cells to respond
rapidly to large changes in input signals. These features suggest a niche for
sRNAs in allowing cells to transition quickly yet reliably between distinct
states. This functional niche is consistent with the widespread appearance of
sRNAs in stress-response and quasi-developmental networks in prokaryotes.Comment: 26 pages, 8 figures; accepted for publication in Molecular Systems
Biolog
Residentsā perceptions of simulation as a clinical learning approach
Background: Simulation is increasingly being integrated into medical education; however, there is little research into traineesā perceptions of this learning modality. We elicited traineesā perceptions of simulation-based learning, to inform how simulation is developed and applied to support training.Methods: We conducted an instrumental qualitative case study entailing 36 semi-structured one-hour interviews with 12 residents enrolled in an introductory simulation-based course. Trainees were interviewed at three time points: pre-course, post-course, and 4-6 weeks later. Interview transcripts were analyzed using a qualitative descriptive analytic approach.Results: Residentsā perceptions of simulation included: 1) simulation serves pragmatic purposes; 2) simulation provides a safe space; 3) simulation presents perils and pitfalls; and 4) optimal design for simulation: integration and tension. Key findings included residentsā markedly narrow perception of simulationās capacity to support non-technical skills development or its use beyond introductory learning.Conclusion: Traineesā learning expectations of simulation were restricted. Educators should critically attend to the way they present simulation to learners as, based on theories of problem-framing, traineesā a priori perceptions may delimit the focus of their learning experiences. If they view simulation as merely a replica of real cases for the purpose of practicing basic skills, they may fail to benefit from the full scope of learning opportunities afforded by simulation.
OpenContrails: Benchmarking Contrail Detection on GOES-16 ABI
Contrails (condensation trails) are line-shaped ice clouds caused by aircraft
and are likely the largest contributor of aviation-induced climate change.
Contrail avoidance is potentially an inexpensive way to significantly reduce
the climate impact of aviation. An automated contrail detection system is an
essential tool to develop and evaluate contrail avoidance systems. In this
paper, we present a human-labeled dataset named OpenContrails to train and
evaluate contrail detection models based on GOES-16 Advanced Baseline Imager
(ABI) data. We propose and evaluate a contrail detection model that
incorporates temporal context for improved detection accuracy. The human
labeled dataset and the contrail detection outputs are publicly available on
Google Cloud Storage at gs://goes_contrails_dataset
Chiral symmetry in linear Sigma model in magnetic environment
We study the chiral symmetry structure in a linear sigma model with fermions
in the presence of an external, uniform magnetic field in the 'effective
potential' approach at the one loop level. We also study the chiral phase
transition as a function of density in the core of magnetized neutron stars.Comment: LaTex2e file with six postscript figures. journal ref: Physical
Review D 62 (2000) 02502
A scalable system to measure contrail formation on a per-flight basis
Persistent contrails make up a large fraction of aviation's contribution to
global warming. We describe a scalable, automated detection and matching (ADM)
system to determine from satellite data whether a flight has made a persistent
contrail. The ADM system compares flight segments to contrails detected by a
computer vision algorithm running on images from the GOES-16 Advanced Baseline
Imager. We develop a 'flight matching' algorithm and use it to label each
flight segment as a 'match' or 'non-match'. We perform this analysis on 1.6
million flight segments. The result is an analysis of which flights make
persistent contrails several orders of magnitude larger than any previous work.
We assess the agreement between our labels and available prediction models
based on weather forecasts. Shifting air traffic to avoid regions of contrail
formation has been proposed as a possible mitigation with the potential for
very low cost/ton-CO2e. Our findings suggest that imperfections in these
prediction models increase this cost/ton by about an order of magnitude.
Contrail avoidance is a cost-effective climate change mitigation even with this
factor taken into account, but our results quantify the need for more accurate
contrail prediction methods and establish a benchmark for future development.Comment: 25 pages, 6 figure
STK35L1 Associates with Nuclear Actin and Regulates Cell Cycle and Migration of Endothelial Cells
BACKGROUND: Migration and proliferation of vascular endothelial cells are essential for repair of injured endothelium and angiogenesis. Cyclins, cyclin-dependent kinases (CDKs), and cyclin-dependent kinase inhibitors play an important role in vascular tissue injury and wound healing. Previous studies suggest a link between the cell cycle and cell migration: cells present in the G(1) phase have the highest potential to migrate. The molecular mechanism linking these two processes is not understood. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we explored the function of STK35L1, a novel Ser/Thr kinase, localized in the nucleus and nucleolus of endothelial cells. Molecular biological analysis identified a bipartite nuclear localization signal, and nucleolar localization sequences in the N-terminal part of STK35L1. Nuclear actin was identified as a novel binding partner of STK35L1. A class III PDZ binding domains motif was identified in STK35L1 that mediated its interaction with actin. Depletion of STK35L1 by siRNA lead to an accelerated G(1) to S phase transition after serum-stimulation of endothelial cells indicating an inhibitory role of the kinase in G(1) to S phase progression. Cell cycle specific genes array analysis revealed that one gene was prominently downregulated (8.8 fold) in STK35L1 silenced cells: CDKN2A alpha transcript, which codes for p16(INK4a) leading to G(1) arrest by inhibition of CDK4/6. Moreover in endothelial cells seeded on Matrigel, STK35L1 expression was rapidly upregulated, and silencing of STK35L1 drastically inhibited endothelial sprouting that is required for angiogenesis. Furthermore, STK35L1 depletion profoundly impaired endothelial cell migration in two wound healing assays. CONCLUSION/SIGNIFICANCE: The results indicate that by regulating CDKN2A and inhibiting G1- to S-phase transition STK35L1 may act as a central kinase linking the cell cycle and migration of endothelial cells. The interaction of STK35L1 with nuclear actin might be critical in the regulation of these fundamental endothelial functions
Electroencephalographic Abnormalities in Clozapine-Treated Patients: A Cross-Sectional Study
The objective of our study was to examine the electroencephalogram (EEG) abnormalities associated with clozapine treatment. It was a cross-sectional study on 87 psychiatric patients on clozapine treatment. 32 channel digital EEG was recorded and analysed visually for abnormalities. EEG abnormalities were observed in 63.2% of patients. Both slowing and epileptiform activities were noted in 41.4% of patients. The EEG abnormalities were not associated with dose or duration of clozapine exposure
TAS-120 overcomes resistance to atp-competitive FGFR inhibitors in patients with FGFR2 fusion–positive intrahepatic cholangiocarcinoma
LEADER 5: prevalence and cardiometabolic impact of obesity in cardiovascular high-risk patients with type 2 diabetes mellitus: baseline global data from the LEADER trial
Background:
Epidemiological data on obesity are needed, particularly in patients with type 2 diabetes mellitus (T2DM) and high cardiovascular (CV) risk. We used the baseline data of liraglutide effect and action in diabetes: evaluation of CV outcome resultsāA long term Evaluation (LEADER) (a clinical trial to assess the CV safety of liraglutide) to investigate: (i) prevalence of overweight and obesity; (ii) relationship of the major cardiometabolic risk factors with anthropometric measures of adiposity [body mass index (BMI) and waist circumference (WC)]; and (iii) cardiometabolic treatment intensity in relation to BMI and WC.
Methods:
LEADER enrolled two distinct populations of high-risk patients with T2DM in 32 countries: (1) aged ā„50 years with prior CV disease; (2) aged ā„60 years with one or more CV risk factors. Associations of metabolic variables, demographic variables and treatment intensity with anthropometric measurements (BMI and WC) were explored using regression models (ClinicalTrials.gov identifier: NCT01179048).
Results:
Mean BMI was 32.5 Ā± 6.3 kg/m2 and only 9.1 % had BMI <25 kg/m2. The prevalence of healthy WC was also extremely low (6.4 % according to International Joint Interim Statement for the Harmonization of the Metabolic Syndrome criteria). Obesity was associated with being younger, female, previous smoker, Caucasian, American, with shorter diabetes duration, uncontrolled blood pressure (BP), antihypertensive agents, insulin plus oral antihyperglycaemic treatment, higher levels of triglycerides and lower levels of high-density lipoprotein cholesterol.
Conclusions:
Overweight and obesity are prevalent in high CV risk patients with T2DM. BMI and WC are related to the major cardiometabolic risk factors. Furthermore, treatment intensity, such as insulin, statins or oral antihypertensive drugs, is higher in those who are overweight or obese; while BP and lipid control in these patients are remarkably suboptimal. LEADER confers a unique opportunity to explore the longitudinal effect of weight on CV risk factors and hard endpoints
Design and characterization of molecular tools for a Synthetic Biology approach towards developing cyanobacterial biotechnology
Cyanobacteria are suitable for sustainable, solar-powered biotechnological applications. Synthetic biology connects biology with computational design and an engineering perspective, but requires efficient tools and information about the function of biological parts and systems. To enable the development of cyanobacterial Synthetic Biology, several molecular tools were developed and characterized: (i) a broad-host-range BioBrick shuttle vector, pPMQAK1, was constructed and confirmed to replicate in Escherichia coli and three different cyanobacterial strains. (ii) The fluorescent proteins Cerulean, GFPmut3B and EYFP have been demonstrated to work as reporter proteins in cyanobacteria, in spite of the strong background of photosynthetic pigments. (iii) Several promoters, like PrnpB and variants of PrbcL, and a version of the promoter Ptrc with two operators for enhanced repression, were developed and characterized in Synechocystis sp. strain PCC6803. (iv) It was shown that a system for targeted protein degradation, which is needed to enable dynamic expression studies, is working in Synechocystis sp. strain PCC6803. The pPMQAK1 shuttle vector allows the use of the growing numbers of BioBrick parts in many prokaryotes, and the other tools herein implemented facilitate the development of new parts and systems in cyanobacteria
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