Non-coding RNAs: the architects of eukaryotic complexity

Around 98% of all transcriptional output in humans is noncoding RNA. RNA-mediated gene regulation is widespread in higher eukaryotes and complex genetic phenomena like RNA interference, co-suppression, transgene silencing, imprinting, methylation, and possibly position-effect variegation and transvection, all involve intersecting pathways based on or connected to RNA signaling. I suggest that the central dogma is incomplete, and that intronic and other non-coding RNAs have evolved to comprise a second tier of gene expression in eukaryotes, which enables the integration and networking of complex suites of gene activity. Although proteins are the fundamental effectors of cellular function, the basis of eukaryotic complexity and phenotypic variation may lie primarily in a control architecture composed of a highly parallel system of trans-acting RNAs that relay state information required for the coordination and modulation of gene expression, via chromatin remodeling, RNA-DNA, RNA-RNA and RNA-protein interactions. This system has interesting and perhaps informative analogies with small world networks and dataflow computing.

Transcripts of the MHM region on the chicken Z chromosome accumulate as non-coding RNA in the nucleus of female cells adjacent to the DMRT1 locus

The male hypermethylated (MHM) region, located near the middle of the short arm of the Z chromosome of chickens, consists of approximately 210 tandem repeats of a BamHI 2.2-kb sequence unit. Cytosines of the CpG dinucleotides of this region are extensively methylated on the two Z chromosomes in the male but much less methylated on the single Z chromosome in the female. The state of methylation of the MHM region is established after fertilization by about the 1-day embryonic stage. The MHM region is transcribed only in the female from the particular strand into heterogeneous, high molecular-mass, non-coding RNA, which is accumulated at the site of transcription, adjacent to the DMRT1 locus, in the nucleus. The transcriptional silence of the MHM region in the male is most likely caused by the CpG methylation, since treatment of the male embryonic fibroblasts with 5-azacytidine results in hypo-methylation and active transcription of this region. In ZZW triploid chickens, MHM regions are hypomethylated and transcribed on the two Z chromosomes, whereas MHM regions are hypermethylated and transcriptionally inactive on the three Z chromosomes in ZZZ triploid chickens, suggesting a possible role of the W chromosome on the state of the MHM region.

A new joint coding and modulation scheme for channels with clipping

A major limitation in any high-performance digital communication system is the linearity region of the transmitting amplifier. Nonlinearities typically lead to signal clipping. Efficient communication in such conditions requires maintaining a low peak-to-average power ratio (PAR) in the transmitted signal while achieving a high throughput of data. Excessive PAR leads either to frequent clipping or to inadequate resolution in the analog-to-digital or digital-to-analog converters. Currently proposed signaling schemes for future generation wireless communications suffer from a high PAR. This paper presents a new signaling scheme for channels with clipping which achieves a PAR as low as 3. For a given linear range in the transmitter's digital-to-analog converter, this scheme achieves a lower bit-error rate than existing multicarrier schemes, owing to increased separation between constellation points. We present the theoretical basis for this new scheme, approximations for the expected bit-error rate, and simulation results. (C) 2002 Elsevier Science (USA).

DNA vaccine coding for the full-length infectious Kunjin virus RNA protects mice against the New York strain of West Nile virus

A plasmid DNA directing transcription of the infectious full-length RNA genome of Kunjin (KUN) virus in vivo from a mammalian expression promoter was used to vaccinate mice intramuscularly. The KUN viral cDNA encoded in the plasmid contained the mutation in the NS1 protein (Pro-250 to Leu) previously shown to attenuate KUN virus in weanling mice. KUN virus was isolated from the blood of immunized mice 3-4 days after DNA inoculation, demonstrating that infectious RNA was being transcribed in vivo; however, no symptoms of virus-induced disease were observed. By 19 days postimmunization, neutralizing antibody was detected in the serum of immunized animals. On challenge with lethal doses of the virulent New York strain of West Nile (WN) or wild-type KUN virus intracerebrally or intraperitoneally, mice immunized with as little as 0.1-1 mug of KUN plasmid DNA were solidly protected against disease. This finding correlated with neutralization data in vitro showing that serum from KUN DNA-immunized mice neutralized KUN and WN,viruses with similar efficiencies. The results demonstrate that delivery of an attenuated but replicating KUN virus via a plasmid DNA vector may provide an effective vaccination strategy against virulent strains of WN virus.

Development of a quality use of medicines coding system to rate clinical pharmacists' medication review recommendations

Objective: To develop a 'quality use of medicines' coding system for the assessment of pharmacists' medication reviews and to apply it to an appropriate cohort. Method: A 'quality use of medicines' coding system was developed based on findings in the literature. These codes were then applied to 216 (111 intervention, 105 control) veterans' medication profiles by an independent clinical pharmacist who was supported by a clinical pharmacologist with the aim to assess the appropriateness of pharmacy interventions. The profiles were provided for veterans participating in a randomised, controlled trial in private hospitals evaluating the effect of medication review and discharge counselling. The reliability of the coding was tested by two independent clinical pharmacists in a random sample of 23 veterans from the study population. Main outcome measure: Interrater reliability was assessed by applying Cohen's kappa score on aggregated codes. Results: The coding system based on the literature consisted of 19 codes. The results from the three clinical pharmacists suggested that the original coding system had two major problems: (a) a lack of discrimination for certain recommendations e. g. adverse drug reactions, toxicity and mortality may be seen as variations in degree of a single effect and (b) certain codes e. g. essential therapy were in low prevalence. The interrater reliability for an aggregation of all codes into positive, negative and clinically non-significant codes ranged from 0.49-0.58 (good to fair). The interrater reliability increased to 0.72-0.79 (excellent) when all negative codes were excluded. Analysis of the sample of 216 profiles showed that the most prevalent recommendations from the clinical pharmacists were a positive impact in reducing adverse responses (31.9%), an improvement in good clinical pharmacy practice (25.5%) and a positive impact in reducing drug toxicity (11.1%). Most medications were assigned the clinically non-significant code (96.6%). In fact, the interventions led to a statistically significant difference in pharmacist recommendations in the categories; adverse response, toxicity and good clinical pharmacy practice measured by the quality use of medicine coding system. Conclusion: It was possible to use the quality use of medicine coding system to rate the quality and potential health impact of pharmacists' medication reviews, and the system did pick up differences between intervention and control patients. The interrater reliability for the summarised coding system was fair, but a larger sample of medication regimens is needed to assess the non-summarised quality use of medicines coding system.

Compression Efficiency Analysis of Wyner-Ziv Video Coding with Motion Compensated Side Information Interpolation

The Wyner-Ziv video coding (WZVC) rate distortion performance is highly dependent on the quality of the side information, an estimation of the original frame, created at the decoder. This paper, characterizes the WZVC efficiency when motion compensated frame interpolation (MCFI) techniques are used to generate the side information, a difficult problem in WZVC especially because the decoder only has available some reference decoded frames. The proposed WZVC compression efficiency rate model relates the power spectral of the estimation error to the accuracy of the MCFI motion field. Then, some interesting conclusions may be derived related to the impact of the motion field smoothness and the correlation to the true motion trajectories on the compression performance.

A flexible side information generation framework for distributed video coding

One of the most efficient approaches to generate the side information (SI) in distributed video codecs is through motion compensated frame interpolation where the current frame is estimated based on past and future reference frames. However, this approach leads to significant spatial and temporal variations in the correlation noise between the source at the encoder and the SI at the decoder. In such scenario, it would be useful to design an architecture where the SI can be more robustly generated at the block level, avoiding the creation of SI frame regions with lower correlation, largely responsible for some coding efficiency losses. In this paper, a flexible framework to generate SI at the block level in two modes is presented: while the first mode corresponds to a motion compensated interpolation (MCI) technique, the second mode corresponds to a motion compensated quality enhancement (MCQE) technique where a low quality Intra block sent by the encoder is used to generate the SI by doing motion estimation with the help of the reference frames. The novel MCQE mode can be overall advantageous from the rate-distortion point of view, even if some rate has to be invested in the low quality Intra coding blocks, for blocks where the MCI produces SI with lower correlation. The overall solution is evaluated in terms of RD performance with improvements up to 2 dB, especially for high motion video sequences and long Group of Pictures (GOP) sizes.

Low Complexity Intra Mode Selection for Efficient Distributed Video Coding

Motion compensated frame interpolation (MCFI) is one of the most efficient solutions to generate side information (SI) in the context of distributed video coding. However, it creates SI with rather significant motion compensated errors for some frame regions while rather small for some other regions depending on the video content. In this paper, a low complexity Infra mode selection algorithm is proposed to select the most 'critical' blocks in the WZ frame and help the decoder with some reliable data for those blocks. For each block, the novel coding mode selection algorithm estimates the encoding rate for the Intra based and WZ coding modes and determines the best coding mode while maintaining a low encoder complexity. The proposed solution is evaluated in terms of rate-distortion performance with improvements up to 1.2 dB regarding a WZ coding mode only solution.

Adaptive deblocking filter for transform domain Wyner-Ziv video coding

Wyner-Ziv (WZ) video coding is a particular case of distributed video coding, the recent video coding paradigm based on the Slepian-Wolf and Wyner-Ziv theorems that exploits the source correlation at the decoder and not at the encoder as in predictive video coding. Although many improvements have been done over the last years, the performance of the state-of-the-art WZ video codecs still did not reach the performance of state-of-the-art predictive video codecs, especially for high and complex motion video content. This is also true in terms of subjective image quality mainly because of a considerable amount of blocking artefacts present in the decoded WZ video frames. This paper proposes an adaptive deblocking filter to improve both the subjective and objective qualities of the WZ frames in a transform domain WZ video codec. The proposed filter is an adaptation of the advanced deblocking filter defined in the H.264/AVC (advanced video coding) standard to a WZ video codec. The results obtained confirm the subjective quality improvement and objective quality gains that can go up to 0.63 dB in the overall for sequences with high motion content when large group of pictures are used.

Statistical motion learning for improved transform domain Wyner-Ziv video coding

Wyner - Ziv (WZ) video coding is a particular case of distributed video coding (DVC), the recent video coding paradigm based on the Slepian - Wolf and Wyner - Ziv theorems which exploits the source temporal correlation at the decoder and not at the encoder as in predictive video coding. Although some progress has been made in the last years, WZ video coding is still far from the compression performance of predictive video coding, especially for high and complex motion contents. The WZ video codec adopted in this study is based on a transform domain WZ video coding architecture with feedback channel-driven rate control, whose modules have been improved with some recent coding tools. This study proposes a novel motion learning approach to successively improve the rate-distortion (RD) performance of the WZ video codec as the decoding proceeds, making use of the already decoded transform bands to improve the decoding process for the remaining transform bands. The results obtained reveal gains up to 2.3 dB in the RD curves against the performance for the same codec without the proposed motion learning approach for high motion sequences and long group of pictures (GOP) sizes.

Advanced side information creation techniques and framework for Wyner-Ziv video coding

Recently, several distributed video coding (DVC) solutions based on the distributed source coding (DSC) paradigm have appeared in the literature. Wyner-Ziv (WZ) video coding, a particular case of DVC where side information is made available at the decoder, enable to achieve a flexible distribution of the computational complexity between the encoder and decoder, promising to fulfill novel requirements from applications such as video surveillance, sensor networks and mobile camera phones. The quality of the side information at the decoder has a critical role in determining the WZ video coding rate-distortion (RD) performance, notably to raise it to a level as close as possible to the RD performance of standard predictive video coding schemes. Towards this target, efficient motion search algorithms for powerful frame interpolation are much needed at the decoder. In this paper, the RD performance of a Wyner-Ziv video codec is improved by using novel, advanced motion compensated frame interpolation techniques to generate the side information. The development of these type of side information estimators is a difficult problem in WZ video coding, especially because the decoder only has available some reference, decoded frames. Based on the regularization of the motion field, novel side information creation techniques are proposed in this paper along with a new frame interpolation framework able to generate higher quality side information at the decoder. To illustrate the RD performance improvements, this novel side information creation framework has been integrated in a transform domain turbo coding based Wyner-Ziv video codec. Experimental results show that the novel side information creation solution leads to better RD performance than available state-of-the-art side information estimators, with improvements up to 2 dB: moreover, it allows outperforming H.264/AVC Intra by up to 3 dB with a lower encoding complexity.

Augmented LDPC Graph for Distributed Video Coding with Multiple Side Information

The advances made in channel-capacity codes, such as turbo codes and low-density parity-check (LDPC) codes, have played a major role in the emerging distributed source coding paradigm. LDPC codes can be easily adapted to new source coding strategies due to their natural representation as bipartite graphs and the use of quasi-optimal decoding algorithms, such as belief propagation. This paper tackles a relevant scenario in distributedvideo coding: lossy source coding when multiple side information (SI) hypotheses are available at the decoder, each one correlated with the source according to different correlation noise channels. Thus, it is proposed to exploit multiple SI hypotheses through an efficient joint decoding technique withmultiple LDPC syndrome decoders that exchange information to obtain coding efficiency improvements. At the decoder side, the multiple SI hypotheses are created with motion compensated frame interpolation and fused together in a novel iterative LDPC based Slepian-Wolf decoding algorithm. With the creation of multiple SI hypotheses and the proposed decoding algorithm, bitrate savings up to 8.0% are obtained for similar decoded quality.

Scalable Unified Transform Architecture for Advanced Video Coding Embedded Systems

A novel high throughput and scalable unified architecture for the computation of the transform operations in video codecs for advanced standards is presented in this paper. This structure can be used as a hardware accelerator in modern embedded systems to efficiently compute all the two-dimensional 4 x 4 and 2 x 2 transforms of the H.264/AVC standard. Moreover, its highly flexible design and hardware efficiency allows it to be easily scaled in terms of performance and hardware cost to meet the specific requirements of any given video coding application. Experimental results obtained using a Xilinx Virtex-5 FPGA demonstrated the superior performance and hardware efficiency levels provided by the proposed structure, which presents a throughput per unit of area relatively higher than other similar recently published designs targeting the H.264/AVC standard. Such results also showed that, when integrated in a multi-core embedded system, this architecture provides speedup factors of about 120x concerning pure software implementations of the transform algorithms, therefore allowing the computation, in real-time, of all the above mentioned transforms for Ultra High Definition Video (UHDV) sequences (4,320 x 7,680 @ 30 fps).