329 research outputs found

    Lowpass Filtering of Rate-Distortion Functions for Quality Smoothing in Real-Time Video Communication

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    Digital Object Identifier 10.1109/TCSVT.2005.852417In variable-bit-rate (VBR) video coding, the video is pre-processed to collect sequence-level statistics, which are used for global bit allocation in the actual encoding stage to obtain a smoothed video presentation quality. However, in real-time video recording and network streaming, this type of two-pass encoding scheme is not allowed because the access to future frames and global statistics is not available. To address this issue, we introduce the concept of low-pass filtering of rate-distortion (R-D) functions and develop a smoothed rate control (SRC) framework for real-time video recording and streaming. Theoretically, we prove that, using a geometric averaging filter, the SRC algorithm is able to maintain a smoothed video presentation quality while achieving the target bit rate automatically. We also analyze the buffer requirement of the SRC algorithm in real-time video streaming, and propose a scheme to seamlessly integrate robust buffer control into the SRC framework. The proposed SRC algorithm has very low computational complexity and implementation cost. Our extensive experimental results demonstrate that the SRC algorithm significantly reduces the picture quality variation in the encoded video clips

    Respiration driven CO2 pulses dominate Australia's flux variability

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    The Australian continent contributes substantially to the year-to-year variability of the global terrestrial carbon dioxide (CO2) sink. However, the scarcity of in-situ observations in remote areas prevents deciphering the processes that force the CO2 flux variability. Here, examining atmospheric CO2 measurements from satellites in the period 2009-2018, we find recurrent end-of-dry-season CO2 pulses over the Australian continent. These pulses largely control the year-to-year variability of Australia's CO2 balance, due to 2-3 times higher seasonal variations compared to previous top-down inversions and bottom-up estimates. The CO2 pulses occur shortly after the onset of rainfall and are driven by enhanced soil respiration preceding photosynthetic uptake in Australia's semi-arid regions. The suggested continental-scale relevance of soil rewetting processes has large implications for our understanding and modelling of global climate-carbon cycle feedbacks.Comment: 28 pages (including supplementary materials), 3 main figures, 7 supplementary figure

    Development of novel anticancer agents targeting G protein coupled receptor: GPR120

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    The G-protein coupled receptor, GPR120, has ubiquitous expression and multifaceted roles in modulating metabolic and anti-inflammatory processes. GPR120 - also known as Free Fatty Acid Receptor 4 (FFAR4) is classified as a free fatty acid receptor of the Class A GPCR family. GPR120 has recently been implicated as a novel target for cancer management. GPR120 gene knockdown in breast cancer studies revealed a role of GPR120-induced chemoresistance in epirubicin and cisplatin-induced DNA damage in tumour cells. Higher expression and activation levels of GPR120 is also reported to promote tumour angiogenesis and cell migration in colorectal cancer. A number of agonists targeting GPR120 have been reported, such as TUG891 and Compound39, but to date development of small-molecule inhibitors of GPR120 is limited. This research applied a rational drug discovery approach to discover and design novel anticancer agents targeting the GPR120 receptor. A homology model of GPR120 (short isoform) was generated to identify potential anticancer compounds using a combined in silico docking-based virtual screening (DBVS), molecular dynamics (MD) assisted pharmacophore screenings, structure–activity relationships (SAR) and in vitro screening approach. A pharmacophore hypothesis was derived from analysis of 300 ns all-atomic MD simulations on apo, TUG891-bound and Compound39-bound GPR120 (short isoform) receptor models and was used to screen for ligands interacting with Trp277 and Asn313 of GPR120. Comparative analysis of 100 ns all-atomic MD simulations of 9 selected compounds predicted the effects of ligand binding on the stability of the “ionic lock” – a characteristic of Class A GPCRs activation and inactivation. The “ionic lock” between TM3(Arg136) and TM6(Asp) is known to prevent G-protein recruitment while GPCR agonist binding is coupled to outward movement of TM6 breaking the “ionic lock” which facilitates G-protein recruitment. The MD-assisted pharmacophore hypothesis predicted Cpd 9, (2-hydroxy-N-{4-[(6-hydroxy-2-methylpyrimidin-4-yl) amino] phenyl} benzamide) to act as a GPR120S antagonist which can be evaluated and characterised in future studies. Additionally, DBVS of a small molecule database (~350,000 synthetic chemical compounds) against the developed GPR120 (short isoform) model led to selection of the 13 hit molecules which were then tested in vitro to evaluate their cytotoxic, colony forming and cell migration activities against SW480 – human CRC cell line expressing GPR120. Two of the DBVS hit molecules showed significant (\u3e 90%) inhibitory effects on cell growth with micromolar affinities (at 100 μM) - AK-968/12713190 (dihydrospiro(benzo[h]quinazoline-5,1′-cyclopentane)-4(3H)-one) and AG-690/40104520 (fluoren-9-one). SAR analysis of these two test compounds led to the identification of more active compounds in cell-based cytotoxicity assays – AL-281/36997031 (IC50 = 5.89–6.715 μM), AL-281/36997034 (IC50 = 6.789 to 7.502 μM) and AP-845/40876799 (IC50 = 14.16-18.02 μM). In addition, AL-281/36997031 and AP-845/40876799 were found to be significantly target-specific during comparative cytotoxicity profiling in GPR120-silenced and GPR120-expressing SW480 cells. In wound healing assays, AL-281/36997031 was found to be the most active at 3 μM (IC25) and prevented cell migration. As well as in the assessment of the proliferation ability of a single cell to survive and form colonies through clonogenic assays, AL-281/36997031 was found to be the most potent of all three test compounds with the survival rate of ~ 30% at 3 μM. The inter-disciplinary approach applied in this work identified potential chemical scaffolds –spiral benzo-quinazoline and fluorenone, targeting GPR120 which can be further explored for designing anti-cancer drug development studies

    Computational Protein Design and Molecular Dynamics Simulations: A Study of Membrane Proteins, Small Peptides and Molecular Systems

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    Molecular design and modeling can provide stringent assessment of our understanding of the structure and function of proteins. Due to the subtleness of the interactions that largely stabilize proteins, computational methods have been particularly valuable in establishing practical, formal and physically grounded protocols to study the structure and function of these biomolecules. Especifically, computational protein design seeks to identify sequences that fold into a desired structure and have specific structural and functional properties using computational methodologies. Among current techniques, an entropy-based formalism that efficiently determines the number and composition of sequences satisfying a predefined set of constraints seems particularly promising and powerful. Complementary to this methodology are the well-established molecular dynamics simulation techniques that have been extensively used to study structure, function and dynamics of biologically relevant systems. Herein different studies of systems using computational techniques to address particular molecular problems are described. Efforts to redesign membrane proteins to generate water-soluble variants were applied to a widely studied pentameric ligand-gated ion channel, the nicotinic acetylchoilne receptor (nAChR). NMR structures and binding studies demostrated the robustness and applicability of the computational design approach. Toward the creation of water-soluble variants of a G protein–coupled receptor (GPCR), comparative modeling and docking calculations were used to investigate the structure of the human μ opioid receptor and presented in light of previous mutagenesis studies of structure and agonist-induced activation. Candidate peptides for possible therapeutic agents were computationally analyzed. Peptide design, loop modeling and MD simulations were applied to investigate the stromal cell-derived factor-1&a; (SDF-1&a;). SDF-1&a; displays promising therapeutic benefits to treat blood-supply related heart disease and elicit growth of microvasculature. Simplified analogs of SDF-1&a; exhibit enhanced therapeutic properties in cell-based assays. MD simulations provide insights about the molecular features of this enhancement. One simplified peptide offers a potentially clinically translatable neovasculogenic therapy. Lastly, MD simulations were utilized to analyze a molecule with hindered internal rotors, a tribenzylamine hemicryptophane. The molecule was characterized by different experimental and computational techniques. The structural and dynamic features of the hemicryptophane molecule make it an attractive starting point for controlling internal rotation of aromatic rings within molecular systems

    A Rate Control Model of MPEG-4 Encoder for Video Transmission over Wireless Sensor Network

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    Recently, multimedia application has a lot of attention in the research community, especially when transmitting video over IEEE 802.15.4 standard. This is due to the capability of providing low complexity with low cost, but still maintaining the quality of video in term of packet received. However, transmitting video over Wireless Sensor Network (WSN) posed a new research challenges with high bandwidth demand and energy constrained of sensor nodes. MPEG-4 video codec is one of the compression techniques that used to decrease the amount of bandwidth required to meet WSN environment. Therefore, video encoding is a useful tool for rate control to control the video bit rate and maintaining the video quality especially in real-time communication applications. Video bit rate is affected by quantization scale, frame rate, and Group of Picture (GOP) size. A rate control model called enhanced Video Motion Classification based (e-ViMoC) model is proposed in this paper to produce the desired bit rate that complies to the IEEE 802.15.4 standard, while at the same time preserving the video quality. The analysis has shown that, the video transmission using e-ViMoC rate control achieves enhancement in delivery ratio, energy consumption and video quality (PSNR) when compared to video transmission using uncompressed video

    Inverse modelling of European CH4 emissions during 2006-2012 using different inverse models and reassessed atmospheric observations

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    We present inverse modelling (top down) estimates of European methane (CH4) emissions for 2006-2012 based on a new quality-controlled and harmonised in situ data set from 18 European atmospheric monitoring stations. We applied an ensemble of seven inverse models and performed four inversion experiments, investigating the impact of different sets of stations and the use of a priori information on emissions.The inverse models infer total CH4 emissions of 26.8 (20.2-29.7) TgCH(4) yr(-1) (mean, 10th and 90th percentiles from all inversions) for the EU-28 for 2006-2012 from the four inversion experiments. For comparison, total anthropogenic CH4 emissions reported to UNFCCC (bottom up, based on statistical data and emissions factors) amount to only 21.3 TgCH(4) yr(-1) (2006) to 18.8 TgCH(4) yr(-1) (2012). A potential explanation for the higher range of top-down estimates compared to bottom-up inventories could be the contribution from natural sources, such as peatlands, wetlands, and wet soils. Based on seven different wetland inventories from the Wetland and Wetland CH4 Inter-comparison of Models Project (WETCHIMP), total wetland emissions of 4.3 (2.3-8.2) TgCH(4) yr(-1) from the EU-28 are estimated. The hypothesis of significant natural emissions is supported by the finding that several inverse models yield significant seasonal cycles of derived CH4 emissions with maxima in summer, while anthropogenic CH4 emissions are assumed to have much lower seasonal variability. Taking into account the wetland emissions from the WETCHIMP ensemble, the top-down estimates are broadly consistent with the sum of anthropogenic and natural bottom-up inventories. However, the contribution of natural sources and their regional distribution remain rather uncertain.Furthermore, we investigate potential biases in the inverse models by comparison with regular aircraft profiles at four European sites and with vertical profiles obtained during the Infrastructure for Measurement of the European Carbon Cycle (IMECC) aircraft campaign. We present a novel approach to estimate the biases in the derived emissions, based on the comparison of simulated and measured enhancements of CH4 compared to the background, integrated over the entire boundary layer and over the lower troposphere. The estimated average regional biases range between -40 and 20% at the aircraft profile sites in France, Hungary and Poland.</p
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