ATOM : a distributed system for video retrieval via ATM networks

The convergence of high speed networks, powerful personal computer processors and improved storage technology has led to the development of video-on-demand services to the desktop that provide interactive controls and deliver Client-selected video information on a Client-specified schedule. This dissertation presents the design of a video-on-demand system for Asynchronous Transfer Mode (ATM) networks, incorporating an optimised topology for the nodes in the system and an architecture for Quality of Service (QoS). The system is called ATOM which stands for Asynchronous Transfer Mode Objects. Real-time video playback over a network consumes large bandwidth and requires strict bounds on delay and error in order to satisfy the visual and auditory needs of the user. Streamed video is a fundamentally different type of traffic to conventional IP (Internet Protocol) data since files are viewed in real-time, not downloaded and then viewed. This streaming data must arrive at the Client decoder when needed or it loses its interactive value. Characteristics of multimedia data are investigated including the use of compression to reduce the excessive bit rates and storage requirements of digital video. The suitability of MPEG-1 for video-on-demand is presented. Having considered the bandwidth, delay and error requirements of real-time video, the next step in designing the system is to evaluate current models of video-on-demand. The distributed nature of four such models is considered, focusing on how Clients discover Servers and locate videos. This evaluation eliminates a centralized approach in which Servers have no logical or physical connection to any other Servers in the network and also introduces the concept of a selection strategy to find alternative Servers when Servers are fully loaded. During this investigation, it becomes clear that another entity (called a Broker) could provide a central repository for Server information. Clients have logical access to all videos on every Server simply by connecting to a Broker. The ATOM Model for distributed video-on-demand is then presented by way of a diagram of the topology showing the interconnection of Servers, Brokers and Clients; a description of each node in the system; a list of the connectivity rules; a description of the protocol; a description of the Server selection strategy and the protocol if a Broker fails. A sample network is provided with an example of video selection and design issues are raised and solved including how nodes discover each other, a justification for using a mesh topology for the Broker connections, how Connection Admission Control (CAC) is achieved, how customer billing is achieved and how information security is maintained. A calculation of the number of Servers and Brokers required to service a particular number of Clients is presented. The advantages of ATOM are described. The underlying distributed connectivity is abstracted away from the Client. Redundant Server/Broker connections are eliminated and the total number of connections in the system are minimized by the rule stating that Clients and Servers may only connect to one Broker at a time. This reduces the total number of Switched Virtual Circuits (SVCs) which are a performance hindrance in ATM. ATOM can be easily scaled by adding more Servers which increases the total system capacity in terms of storage and bandwidth. In order to transport video satisfactorily, a guaranteed end-to-end Quality of Service architecture must be in place. The design methodology for such an architecture is investigated starting with a review of current QoS architectures in the literature which highlights important definitions including a flow, a service contract and flow management. A flow is a single media source which traverses resource modules between Server and Client. The concept of a flow is important because it enables the identification of the areas requiring consideration when designing a QoS architecture. It is shown that ATOM adheres to the principles motivating the design of a QoS architecture, namely the Integration, Separation and Transparency principles. The issue of mapping human requirements to network QoS parameters is investigated and the action of a QoS framework is introduced, including several possible causes of QoS degradation. The design of the ATOM Quality of Service Architecture (AQOSA) is then presented. AQOSA consists of 11 modules which interact to provide end-to-end QoS guarantees for each stream. Several important results arise from the design. It is shown that intelligent choice of stored videos in respect of peak bandwidth can improve overall system capacity. The concept of disk striping over a disk array is introduced and a Data Placement Strategy is designed which eliminates disk hot spots (i.e. Overuse of some disks whilst others lie idle.) A novel parameter (the B-P Ratio) is presented which can be used by the Server to predict future bursts from each video stream. The use of Traffic Shaping to decrease the load on the network from each stream is presented. Having investigated four algorithms for rewind and fast-forward in the literature, a rewind and fast-forward algorithm is presented. The method produces a significant decrease in bandwidth, and the resultant stream is very constant, reducing the chance that the stream will add to network congestion. The C++ classes of the Server, Broker and Client are described emphasizing the interaction between classes. The use of ATOM in the Virtual Private Network and the multimedia teaching laboratory is considered. Conclusions and recommendations for future work are presented. It is concluded that digital video applications require high bandwidth, low error, low delay networks; a video-on-demand system to support large Client volumes must be distributed, not centralized; control and operation (transport) must be separated; the number of ATM Switched Virtual Circuits (SVCs) must be minimized; the increased connections caused by the Broker mesh is justified by the distributed information gain; a Quality of Service solution must address end-to-end issues. It is recommended that a web front-end for Brokers be developed; the system be tested in a wide area A TM network; the Broker protocol be tested by forcing failure of a Broker and that a proprietary file format for disk striping be implemented

Coordinate Descent for Mixed-norm NMF

Nonnegative matrix factorization (NMF) is widely used in a variety of machine learning tasks involving speech, documents and images. Being able to specify the structure of the matrix factors is crucial in incorporating prior information. The factors correspond to the feature matrix and the learnt representation. In particular, we allow an user-friendly specification of sparsity on the groups of features using the L1/L2 measure. Also, we propose a pairwise coordinate descent algorithm to minimize the objective. Experimental evidence of the efficacy of this approach is provided on the ORL faces dataset

Coarse-grained simulation of transmembrane peptides in the gel phase

We use Dissipative Particle Dynamics simulations, combined with parallel tempering and umbrella sampling, to investigate the potential of mean force between model transmembrane peptides in the various phases of a lipid bilayer, including the low-temperature gel phase. The observed oscillations in the effective interaction between peptides are consistent with the different structures of the surrounding lipid phases

The scale of population structure in Arabidopsis thaliana

The population structure of an organism reflects its evolutionary history and influences its evolutionary trajectory. It constrains the combination of genetic diversity and reveals patterns of past gene flow. Understanding it is a prerequisite for detecting genomic regions under selection, predicting the effect of population disturbances, or modeling gene flow. This paper examines the detailed global population structure of Arabidopsis thaliana. Using a set of 5,707 plants collected from around the globe and genotyped at 149 SNPs, we show that while A. thaliana as a species self-fertilizes 97% of the time, there is considerable variation among local groups. This level of outcrossing greatly limits observed heterozygosity but is sufficient to generate considerable local haplotypic diversity. We also find that in its native Eurasian range A. thaliana exhibits continuous isolation by distance at every geographic scale without natural breaks corresponding to classical notions of populations. By contrast, in North America, where it exists as an exotic species, A. thaliana exhibits little or no population structure at a continental scale but local isolation by distance that extends hundreds of km. This suggests a pattern for the development of isolation by distance that can establish itself shortly after an organism fills a new habitat range. It also raises questions about the general applicability of many standard population genetics models. Any model based on discrete clusters of interchangeable individuals will be an uneasy fit to organisms like A. thaliana which exhibit continuous isolation by distance on many scales

Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia

Abstract:Altered olfactory function is a common symptom of COVID-19, but its etiology is unknown. A key question is whether SARS-CoV-2 (CoV-2) – the causal agent in COVID-19 – affects olfaction directly, by infecting olfactory sensory neurons or their targets in the olfactory bulb, or indirectly, through perturbation of supporting cells. Here we identify cell types in the olfactory epithelium and olfactory bulb that express SARS-CoV-2 cell entry molecules. Bulk sequencing demonstrated that mouse, non-human primate and human olfactory mucosa expresses two key genes involved in CoV-2 entry, ACE2 and TMPRSS2. However, single cell sequencing revealed that ACE2 is expressed in support cells, stem cells, and perivascular cells, rather than in neurons. Immunostaining confirmed these results and revealed pervasive expression of ACE2 protein in dorsally-located olfactory epithelial sustentacular cells and olfactory bulb pericytes in the mouse. These findings suggest that CoV-2 infection of non-neuronal cell types leads to anosmia and related disturbances in odor perception in COVID-19 patients

Evidence for early Pliocene and late Miocene transgressions in southern Patagonia (Argentina): 87Sr/86Sr ages of the pectinid “Chlamys” actinodes (Sowerby)

AbstractNumerical ages based on 87Sr/86Sr dating of calcitic shells belonging to the pectinid “Chlamys” actinodes (Sowerby) document the only late Miocene (Tortonian) sea flooding event in the Austral Basin at Cabo Buentiempo (8.95 ± 0.82 Ma, 2 s.e.), and provide evidence of the first documented early Pliocene (Zanclean) transgression in Argentina recorded at Cañadón Darwin (5.15 ± 0.18 Ma, 2 s.e., Austral Basin) and at Terraces of Cerro Laciar (5.10 ± 0.21 Ma, 2 s.e.), southern San Jorge Basin). The sedimentary rocks deposited during the Tortonian are correlated with the youngest beds deposited by the “Entrerriense Sea” that covered northern Patagonia. The Zanclean marine episode is correlated with the long-term cycle represented in the Southern Hemisphere by the flooding events recorded in Cockburn and James Ross Islands (Antarctica) and in North-Central Chile

Genome-Wide Association Study Using Extreme Truncate Selection Identifies Novel Genes Affecting Bone Mineral Density and Fracture Risk

Osteoporotic fracture is a major cause of morbidity and mortality worldwide. Low bone mineral density (BMD) is a major predisposing factor to fracture and is known to be highly heritable. Site-, gender-, and age-specific genetic effects on BMD are thought to be significant, but have largely not been considered in the design of genome-wide association studies (GWAS) of BMD to date. We report here a GWAS using a novel study design focusing on women of a specific age (postmenopausal women, age 55–85 years), with either extreme high or low hip BMD (age- and gender-adjusted BMD z-scores of +1.5 to +4.0, n = 1055, or −4.0 to −1.5, n = 900), with replication in cohorts of women drawn from the general population (n = 20,898). The study replicates 21 of 26 known BMD–associated genes. Additionally, we report suggestive association of a further six new genetic associations in or around the genes CLCN7, GALNT3, IBSP, LTBP3, RSPO3, and SOX4, with replication in two independent datasets. A novel mouse model with a loss-of-function mutation in GALNT3 is also reported, which has high bone mass, supporting the involvement of this gene in BMD determination. In addition to identifying further genes associated with BMD, this study confirms the efficiency of extreme-truncate selection designs for quantitative trait association studies

3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

Background: Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. Methods: In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m2, or at least 27 kg/m2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. Findings: The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p<0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13–0·34). Liraglutide induced greater weight loss than placebo at week 160 (–6·1 [SD 7·3] vs −1·9% [6·3]; estimated treatment difference −4·3%, 95% CI −4·9 to −3·7, p<0·0001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. Interpretation: In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. Funding: Novo Nordisk, Denmark

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio