35,055 research outputs found
A Discrete Tchebichef Transform Approximation for Image and Video Coding
In this paper, we introduce a low-complexity approximation for the discrete
Tchebichef transform (DTT). The proposed forward and inverse transforms are
multiplication-free and require a reduced number of additions and bit-shifting
operations. Numerical compression simulations demonstrate the efficiency of the
proposed transform for image and video coding. Furthermore, Xilinx Virtex-6
FPGA based hardware realization shows 44.9% reduction in dynamic power
consumption and 64.7% lower area when compared to the literature.Comment: 13 pages, 5 figures, 2 table
Enzymatic Cross-Linking of Dynamic Thiol-Norbornene Click Hydrogels
Enzyme-mediated in situ forming hydrogels are attractive for many biomedical applications because gelation afforded by enzymatic reactions can be readily controlled not only by tuning macromer compositions, but also by adjusting enzyme kinetics. For example, horseradish peroxidase (HRP) has been used extensively for in situ cross-linking of macromers containing hydroxyl-phenol groups. The use of HRP to initiate thiol-allylether polymerization has also been reported, yet no prior study has demonstrated enzymatic initiation of thiol-norbornene gelation. In this study, we discovered that HRP can generate the thiyl radicals needed for initiating thiol-norbornene hydrogelation, which has only been demonstrated previously using photopolymerization. Enzymatic thiol-norbornene gelation not only overcomes light attenuation issue commonly observed in photopolymerized hydrogels, but also preserves modularity of the cross-linking. In particular, we prepared modular hydrogels from two sets of norbornene-modified macromers, 8-arm poly(ethylene glycol)-norbornene (PEG8NB) and gelatin-norbornene (GelNB). Bis-cysteine-containing peptides or PEG-tetra-thiol (PEG4SH) was used as a cross-linker for forming enzymatically and orthogonally polymerized hydrogel. For HRP-initiated PEG-peptide hydrogel cross-linking, gelation efficiency was significantly improved via adding tyrosine residues on the peptide cross-linkers. Interestingly, these additional tyrosine residues did not form permanent dityrosine cross-links following HRP-induced gelation. As a result, they remained available for tyrosinase-mediated secondary cross-linking, which dynamically increased hydrogel stiffness. In addition to material characterizations, we also found that both PEG- and gelatin-based hydrogels exhibited excellent cytocompatibility for dynamic 3D cell culture. The enzymatic thiol-norbornene gelation scheme presented here offers a new cross-linking mechanism for preparing modularly and dynamically cross-linked hydrogels
Savers, Spenders and Fiscal Policy in a Small Open Economy
This paper analyzes the effects of fiscal policy in an open economy. We extend the savers-spenders theory of Mankiw (2000) to a small open economy with endoge- nous labor supply. We first show how the Dornbusch (1983) consumption-based real interest rate for open economies is modified when labor supply is endogenous. We then turn to the effects of fiscal policy when there are both savers and spenders. With this heterogeneity taken into account, tax cuts have a short-run contractionary effect on domestic production, and increased public spending has a short-run expan- sionary effect. Although consistent with recent empirical work, this result contrasts with those of most other theoretical models. Transitory changes in demand have per- manent real effects in our model, and we discuss the implications for real exchange- rate dynamics. We also show how "rational" savers may magnify or dampen the responses of "irrational" spenders, and show how this is related to features of the utility functions.rule-of-thumb consumers, fiscal policy, open economy
The MarR-Type Repressor MhqR Confers Quinone and Antimicrobial Resistance in Staphylococcus aureus
Aims: Quinone compounds are electron carriers and have antimicrobial and toxic properties due to their mode of actions as electrophiles and oxidants. However, the regulatory mechanism of quinone resistance is less well understood in the pathogen Staphylococcus aureus.
Results: Methylhydroquinone (MHQ) caused a thiol-specific oxidative and electrophile stress response in the S. aureus transcriptome as revealed by the induction of the PerR, QsrR, CstR, CtsR, and HrcA regulons. The SACOL2531-29 operon was most strongly upregulated by MHQ and was renamed as mhqRED operon based on its homology to the Bacillus subtilis locus. Here, we characterized the MarR-type regulator MhqR (SACOL2531) as quinone-sensing repressor of the mhqRED operon, which confers quinone and antimicrobial resistance in S. aureus. The mhqRED operon responds specifically to MHQ and less pronounced to pyocyanin and ciprofloxacin, but not to reactive oxygen species (ROS), hypochlorous acid, or aldehydes. The MhqR repressor binds specifically to a 9–9 bp inverted repeat (MhqR operator) upstream of the mhqRED operon and is inactivated by MHQ in vitro, which does not involve a thiol-based mechanism. In phenotypic assays, the mhqR deletion mutant was resistant to MHQ and quinone-like antimicrobial compounds, including pyocyanin, ciprofloxacin, norfloxacin, and rifampicin. In addition, the mhqR mutant was sensitive to sublethal ROS and 24 h post-macrophage infections but acquired an improved survival under lethal ROS stress and after long-term infections.
Innovation: Our results provide a link between quinone and antimicrobial resistance via the MhqR regulon of S. aureus.
Conclusion: The MhqR regulon was identified as a novel resistance mechanism towards quinone-like antimicrobials and contributes to virulence of S. aureus under long-term infections
Savers, Spenders and Fiscal Policy in a Small Open Economy
This paper analyzes the effects of fiscal policy in an open economy. We extend the savers-spenders theory of Mankiw (2000) to a small open economy with endogenous labor supply. We first show how the Dornbusch (1983) consumption-based real interest rate for open economies is modified when labor supply is endogenous. We then turn to the effects of fiscal policy when there are both savers and spenders. With this heterogeneity taken into account, tax cuts have a short-run contractionary effect on domestic production, and increased public spending has a short-run expansionary effect. Although consistent with recent empirical work, this result contrasts with those of most other theoretical models. Transitory changes in demand have permanent real effects in our model, and we discuss the implications for real exchange-rate dynamics. We also show how “rational” savers may magnify or dampen the responses of “irrational” spenders, and show how this is related to features of the utility functions.rule-of-thumb consumers, fiscal policy, open economy
Mitochondrial fusion and Bid-mediated mitochondrial apoptosis are perturbed by alcohol with distinct dependence on its metabolism
Environmental stressors like ethanol (EtOH) commonly target mitochondria to influence the cell’s fate. Recent literature supports that chronic EtOH exposure suppresses mitochondrial dynamics, central to quality control, and sensitizes mitochondrial permeability transition pore opening to promote cell death. EtOH-induced tissue injury is primarily attributed to its toxic metabolic products but alcoholism also impairs tissues that poorly metabolize EtOH. We embarked on studies to determine the respective roles of EtOH and its metabolites in mitochondrial fusion and tBid-induced mitochondrial apoptosis. We used HepG2 cells that do not metabolize EtOH and its engineered clone that expresses EtOH-metabolizing Cytochrome P450 E2 and alcohol dehydrogenase (VL-17A cells). We found that fusion impairment by prolonged EtOH exposure was prominent in VL-17A cells, probably owing to reactive oxygen species increase in the mitochondrial matrix. There was no change in fusion protein abundance, mitochondrial membrane potential or Ca2+ uptake. By contrast, prolonged EtOH exposure promoted tBid-induced outer mitochondrial membrane permeabilization and cell death only in HepG2 cells, owing to enhanced Bak oligomerization. Thus, mitochondrial fusion inhibition by EtOH is dependent on its metabolites, whereas sensitization to tBid-induced death is mediated by EtOH itself. This difference is of pathophysiological relevance because of the tissue-specific differences in EtOH metabolism. © 2018, The Author(s)
Complement activation and protein adsorption by carbon nanotubes
As a first step to validate the use of carbon nanotubes as novel vaccine or drug delivery devices, their interaction with a part of the human immune system, complement, has been explored. Haemolytic assays were conducted to investigate the activation of the human serum complement system via the classical and alternative pathways. Western blot and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) techniques were used to elucidate the mechanism of activation of complement via the classical pathway, and to analyse the interaction of complement and other plasma proteins with carbon nanotubes. We report for the first time that carbon nanotubes activate human complement via both classical and alternative pathways. We conclude that complement activation by nanotubes is consistent with reported adjuvant effects, and might also in various circumstances promote damaging effects of excessive complement activation, such as inflammation and granuloma formation. C1q binds directly to carbon nanotubes. Protein binding to carbon nanotubes is highly selective, since out of the many different proteins in plasma, very few bind to the carbon nanotubes. Fibrinogen and apolipoproteins (AI, AIV and CIII) were the proteins that bound to carbon nanotubes in greatest quantit
COA6 facilitates cytochrome c oxidase biogenesis as thiol-reductase for copper metallochaperones in mitochondria.
The mitochondrial cytochrome c oxidase, the terminal enzyme of the respiratory chain, contains heme and copper centers for electron transfer. The conserved COX2 subunit contains the CuA site, a binuclear copper center. The copper chaperones SCO1, SCO2, and COA6 are required for CuA center formation. Loss of function of these chaperones and the concomitant cytochrome c oxidase deficiency cause severe human disorders. Here we analyzed the molecular function of COA6 and the consequences of COA6 deficiency for mitochondria. Our analyses show that loss of COA6 causes combined complex I and complex IV deficiency and impacts membrane potential driven protein transport across the inner membrane. We demonstrate that COA6 acts as a thiol-reductase to reduce disulphide bridges of critical cysteine residues in SCO1 and SCO2. Cysteines within the CX3CXNH domain of SCO2 mediate its interaction with COA6 but are dispensable for SCO2-SCO1 interaction. Our analyses define COA6 as thiol-reductase, which is essential for CuA biogenesis
Can bio-inspired information processing steps be realized as synthetic biochemical processes?
We consider possible designs and experimental realiza-tions in synthesized
rather than naturally occurring bio-chemical systems of a selection of basic
bio-inspired information processing steps. These include feed-forward loops,
which have been identified as the most common information processing motifs in
many natural pathways in cellular functioning, and memory-involving processes,
specifically, associative memory. Such systems should not be designed to
literally mimic nature. Rather, we can be guided by nature's mechanisms for
experimenting with new information/signal processing steps which are based on
coupled biochemical reactions, but are vastly simpler than natural processes,
and which will provide tools for the long-term goal of understanding and
harnessing nature's information processing paradigm. Our biochemical processes
of choice are enzymatic cascades because of their compatibility with
physiological processes in vivo and with electronics (e.g., electrodes) in
vitro allowing for networking and interfacing of enzyme-catalyzed processes
with other chemical and biochemical reactions. In addition to designing and
realizing feed-forward loops and other processes, one has to develop approaches
to probe their response to external control of the time-dependence of the
input(s), by measuring the resulting time-dependence of the output. The goal
will be to demonstrate the expected features, for example, the delayed response
and stabilizing effect of the feed-forward loops
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