30,612 research outputs found
Combining queueing theory with information theory for multiaccess
Caption title.Includes bibliographical references (leaf [7]).Supported by the U.S. Army Research Office. DAAL03-86-K-0171Ä°. Emre Telatar and Robert G. Gallager
Zero error decision feedback capacity of discrete memoryless channels
Cover title.Includes bibliographical references (p. 14).Research supported by the Army Research Office. DAAL03-86-K-0171I. Emre Telatar, Robert G. Gallager
Dual-topology insertion of a dual-topology membrane protein.
Some membrane transporters are dual-topology dimers in which the subunits have inverted transmembrane topology. How a cell manages to generate equal populations of two opposite topologies from the same polypeptide chain remains unclear. For the dual-topology transporter EmrE, the evidence to date remains consistent with two extreme models. A post-translational model posits that topology remains malleable after synthesis and becomes fixed once the dimer forms. A second, co-translational model, posits that the protein inserts in both topologies in equal proportions. Here we show that while there is at least some limited topological malleability, the co-translational model likely dominates under normal circumstances
Lipid bilayer composition influences small multidrug transporters
Background:
Membrane proteins are influenced by their surrounding lipids. We investigate the effect of bilayer composition on the membrane transport activity of two members of the small multidrug resistance family; the Escherichia coli transporter, EmrE and the Mycobacterium tuberculosis, TBsmr. In particular we address the influence of phosphatidylethanolamine and anionic lipids on the activity of these multidrug transporters. Phosphatidylethanolamine lipids are native to the membranes of both transporters and also alter the lateral pressure profile of a lipid bilayer. Lipid bilayer lateral pressures affect membrane protein insertion, folding and activity and have been shown to influence reconstitution, topology and activity of membrane transport proteins.
Results:
Both EmrE and TBsmr are found to exhibit a similar dependence on lipid composition, with phosphatidylethanolamine increasing methyl viologen transport. Anionic lipids also increase transport for both EmrE and TBsmr, with the proteins showing a preference for their most prevalent native anionic lipid headgroup; phosphatidylglycerol for EmrE and phosphatidylinositol for TBsmr.
Conclusion:
These findings show that the physical state of the membrane modifies drug transport and that substrate translocation is dependent on in vitro lipid composition. Multidrug transport activity seems to respond to alterations in the lateral forces exerted upon the transport proteins by the bilayer
Computation of biochemical pathway fluctuations beyond the linear noise approximation using iNA
The linear noise approximation is commonly used to obtain intrinsic noise
statistics for biochemical networks. These estimates are accurate for networks
with large numbers of molecules. However it is well known that many biochemical
networks are characterized by at least one species with a small number of
molecules. We here describe version 0.3 of the software intrinsic Noise
Analyzer (iNA) which allows for accurate computation of noise statistics over
wide ranges of molecule numbers. This is achieved by calculating the next order
corrections to the linear noise approximation's estimates of variance and
covariance of concentration fluctuations. The efficiency of the methods is
significantly improved by automated just-in-time compilation using the LLVM
framework leading to a fluctuation analysis which typically outperforms that
obtained by means of exact stochastic simulations. iNA is hence particularly
well suited for the needs of the computational biology community.Comment: 5 pages, 2 figures, conference proceeding IEEE International
Conference on Bioinformatics and Biomedicine (BIBM) 201
Recommended from our members
Boron content of Lake Ulubat sediment: A key to interpret the morphological history of NW Anatolia, Turkey
Freshwater Lake Ulubat (c. 1.5 m deep and c. 138 km2) receives sediment from a 10.414 km2 area in the seismically active Susurluk Drainage Basin (SDB) of NW Turkey. The B and trace element contents of the lake infill seem to be a link between the fresh landforms of the SDB and the lacustrine sediment. Deposition in Lake Ulubat has been 1.60 cm.a-1 for the last 50 a according to radionucleides; however the sedimentation rate over the last millennium was 0.37 cm.a-1 based on 14C dating. The B content of the lacustrine infill displays a slight increase at 0.50 m and a drastic increase at 4 m depth occurring c. 31 a and c. 1070 a ago respectively. Probably the topmost change corresponds to the start of open mining in the SDB and the second one to the natural trenching of borate ore-deposits. These dates also show indirectly a 1.4 cm.a-1 erosion rate during the last millennium as the borate beds were trenched up to 15 m. By extrapolation, it is possible to establish that the formation of some of the present morphological features of the southern Marmara region, especially river incision, began in the late Pleistocene, and developed especially over the last 75 ka
Dynamics of Co-translational Membrane Protein Integration and Translocation via the Sec Translocon
An important aspect of cellular function is the correct targeting and delivery of newly synthesized proteins. Central to this task is the machinery of the Sec translocon, a transmembrane channel that is involved in both the translocation of nascent proteins across cell membranes and the integration of proteins into the membrane. Considerable experimental and computational effort has focused on the Sec translocon and its role in nascent protein biosynthesis, including the correct folding and expression of integral membrane proteins. However, the use of molecular simulation methods to explore Sec-facilitated protein biosynthesis is hindered by the large system sizes and long (i.e., minute) timescales involved. In this work, we describe the development and application of a coarse-grained simulation approach that addresses these challenges and allows for direct comparison with both in vivo and in vitro experiments. The method reproduces a wide range of experimental observations, providing new insights into the underlying molecular mechanisms, predictions for new experiments, and a strategy for the rational enhancement of membrane protein expression levels
Localization Recall Precision (LRP): A New Performance Metric for Object Detection
Average precision (AP), the area under the recall-precision (RP) curve, is
the standard performance measure for object detection. Despite its wide
acceptance, it has a number of shortcomings, the most important of which are
(i) the inability to distinguish very different RP curves, and (ii) the lack of
directly measuring bounding box localization accuracy. In this paper, we
propose 'Localization Recall Precision (LRP) Error', a new metric which we
specifically designed for object detection. LRP Error is composed of three
components related to localization, false negative (FN) rate and false positive
(FP) rate. Based on LRP, we introduce the 'Optimal LRP', the minimum achievable
LRP error representing the best achievable configuration of the detector in
terms of recall-precision and the tightness of the boxes. In contrast to AP,
which considers precisions over the entire recall domain, Optimal LRP
determines the 'best' confidence score threshold for a class, which balances
the trade-off between localization and recall-precision. In our experiments, we
show that, for state-of-the-art object (SOTA) detectors, Optimal LRP provides
richer and more discriminative information than AP. We also demonstrate that
the best confidence score thresholds vary significantly among classes and
detectors. Moreover, we present LRP results of a simple online video object
detector which uses a SOTA still image object detector and show that the
class-specific optimized thresholds increase the accuracy against the common
approach of using a general threshold for all classes. At
https://github.com/cancam/LRP we provide the source code that can compute LRP
for the PASCAL VOC and MSCOCO datasets. Our source code can easily be adapted
to other datasets as well.Comment: to appear in ECCV 201
The Mitochondrial Ca(2+) Uniporter: Structure, Function, and Pharmacology.
Mitochondrial Ca(2+) uptake is crucial for an array of cellular functions while an imbalance can elicit cell death. In this chapter, we briefly reviewed the various modes of mitochondrial Ca(2+) uptake and our current understanding of mitochondrial Ca(2+) homeostasis in regards to cell physiology and pathophysiology. Further, this chapter focuses on the molecular identities, intracellular regulators as well as the pharmacology of mitochondrial Ca(2+) uniporter complex
- …