Application of Risk within Net Present Value Calculations for Government Projects

In January 2004, President Bush announced a new vision for space exploration. This included retirement of the current Space Shuttle fleet by 2010 and the development of new set of launch vehicles. The President's vision did not include significant increases in the NASA budget, so these development programs need to be cost conscious. Current trade study procedures address factors such as performance, reliability, safety, manufacturing, maintainability, operations, and costs. It would be desirable, however, to have increased insight into the cost factors behind each of the proposed system architectures. This paper reports on a set of component trade studies completed on the upper stage engine for the new launch vehicles. Increased insight into architecture costs was developed by including a Net Present Value (NPV) method and applying a set of associated risks to the base parametric cost data. The use of the NPV method along with the risks was found to add fidelity to the trade study and provide additional information to support the selection of a more robust design architecture

Functional asymmetry of transmembrane segments in nicotinic acetylcholine receptors

Nicotinic acetylcholine receptors are heteropentameric ion channels that open upon activation to a single conducting state. The second transmembrane segments of each subunit were identified as channel-forming elements, but their respective contribution in the gating process remains unclear. Moreover, the detailed impact of variations of the membrane potential, such as occurring during an action potential, on the transmembrane domains, is unknown. Residues at the 12' position, close to the center of each second transmembrane segment, play a key role in channel gating. We examined their functional symmetry by substituting a lysine to that position of each subunit and measuring the electrical activity of single channels. For 12' lysines in the alpha, gamma and delta subunits rapid transitions between an intermediate and large conductance appeared, which are interpreted as single lysine protonation events. From the kinetics of these transitions we calculated the pK (a) values of respective lysines and showed that they vary differently with membrane hyperpolarization. Respective mutations in beta or epsilon subunits gave receptors with openings of either intermediate or large conductance, suggesting extreme pK (a) values in two open state conformations. The results demonstrate that these parts of the highly homologous transmembrane domains, as probed by the 12' lysines, sense unequal microenvironments and are differently affected by physiologically relevant voltage changes. Moreover, observation of various gating events for mutants of alpha subunits suggests that the open channel pore exists in multiple conformations, which in turn supports the notion of functional asymmetry of the channel

Kairos: Preemptive Data Center Scheduling Without Runtime Estimates

The vast majority of data center schedulers use task runtime estimates to improve the quality of their scheduling decisions. Knowledge about runtimes allows the schedulers, among other things, to achieve better load balance and to avoid head-of-line blocking. Obtaining accurate runtime estimates is, however, far from trivial, and erroneous estimates lead to sub-optimal scheduling decisions. Techniques to mitigate the effect of inaccurate estimates have shown some success, but the fundamental problem remains. This paper presents Kairos, a novel data center scheduler that assumes no prior information on task runtimes. Kairos introduces a distributed approximation of the Least Attained Service (LAS) scheduling policy. Kairos consists of a centralized scheduler and per-node schedulers. The per-node schedulers implement LAS for tasks on their node, using preemption as necessary to avoid head-of-line blocking. The centralized scheduler distributes tasks among nodes in a manner that balances the load and imposes on each node a workload in which LAS provides favorable performance. We have implemented Kairos in YARN. We compare its performance against the YARN FIFO scheduler and Big-C, an open-source state-of-the-art YARN-based scheduler that also uses preemption. Compared to YARN FIFO, Kairos reduces the median job completion time by 73% and the 99th percentile by 30%. Compared to Big-C, the improvements are 37% for the median and 57% for the 99th percentile. We evaluate Kairos at scale by implementing it in the Eagle simulator and comparing its performance against Eagle. Kairos improves the 99th percentile of short job completion times by up to 55% for the Google trace and 85% for the Yahoo trace

Novel genetic parameters for genetic residual feed intake in dairy cattle using time series data from multiple parities and countries in North America and Europe.

Residual feed intake is viewed as an important trait in breeding programs that could be used to enhance genetic progress in feed efficiency. In particular, improving feed efficiency could improve both economic and environmental sustainability in the dairy cattle industry. However, data remain sparse, limiting the development of reliable genomic evaluations across lactation and parity for residual feed intake. Here, we estimated novel genetic parameters for genetic residual feed intake (gRFI) across the first, second, and third parity, using a random regression model. Research data on the measured feed intake, milk production, and body weight of 7,379 cows (271,080 records) from 6 countries in 2 continents were shared through the Horizon 2020 project GenTORE and Resilient Dairy Genome Project. The countries included Canada (1,053 cows with 47,130 weekly records), Denmark (1,045 cows with 72,760 weekly records), France (329 cows with 16,888 weekly records), Germany (938 cows with 32,614 weekly records), the Netherlands (2,051 cows with 57,830 weekly records), and United States (1,963 cows with 43,858 weekly records). Each trait had variance components estimated from first to third parity, using a random regression model across countries. Genetic residual feed intake was found to be heritable in all 3 parities, with first parity being predominant (range: 22-34%). Genetic residual feed intake was highly correlated across parities for mid- to late lactation; however, genetic correlation across parities was lower during early lactation, especially when comparing first and third parity. We estimated a genetic correlation of 0.77 ± 0.37 between North America and Europe for dry matter intake at first parity. Published literature on genetic correlations between high input countries/continents for dry matter intake support a high genetic correlation for dry matter intake. In conclusion, our results demonstrate the feasibility of estimating variance components for gRFI across parities, and the value of sharing data on scarce phenotypes across countries. These results can potentially be implemented in genetic evaluations for gRFI in dairy cattle

Cloud-scale VM Deflation for Running Interactive Applications On Transient Servers

Transient computing has become popular in public cloud environments for running delay-insensitive batch and data processing applications at low cost. Since transient cloud servers can be revoked at any time by the cloud provider, they are considered unsuitable for running interactive application such as web services. In this paper, we present VM deflation as an alternative mechanism to server preemption for reclaiming resources from transient cloud servers under resource pressure. Using real traces from top-tier cloud providers, we show the feasibility of using VM deflation as a resource reclamation mechanism for interactive applications in public clouds. We show how current hypervisor mechanisms can be used to implement VM deflation and present cluster deflation policies for resource management of transient and on-demand cloud VMs. Experimental evaluation of our deflation system on a Linux cluster shows that microservice-based applications can be deflated by up to 50\% with negligible performance overhead. Our cluster-level deflation policies allow overcommitment levels as high as 50\%, with less than a 1\% decrease in application throughput, and can enable cloud platforms to increase revenue by 30\%.Comment: To appear at ACM HPDC 202

Genome-wide association studies of fertility and calving traits in Brown Swiss cattle using imputed whole-genome sequences

BACKGROUND: The detection of quantitative trait loci has accelerated with recent developments in genomics. The introduction of genomic selection in combination with sequencing efforts has made a large amount of genotypic data available. Functional traits such as fertility and calving traits have been included in routine genomic estimation of breeding values making large quantities of phenotypic data available for these traits. This data was used to investigate the genetics underlying fertility and calving traits and to identify potentially causative genomic regions and variants. We performed genome-wide association studies for 13 functional traits related to female fertility as well as for direct and maternal calving ease based on imputed whole-genome sequences. Deregressed breeding values from ~1000-5000 bulls per trait were used to test for associations with approximately 10 million imputed sequence SNPs. RESULTS: We identified a QTL on BTA17 associated with non-return rate at 56 days and with interval from first to last insemination. We found two significantly associated non-synonymous SNPs within this QTL region. Two more QTL for fertility traits were identified on BTA25 and 29. A single QTL was identified for maternal calving traits on BTA13 whereas three QTL on BTA19, 21 and 25 were identified for direct calving traits. The QTL on BTA19 co-localizes with the reported BH2 haplotype. The QTL on BTA25 is concordant for fertility and calving traits and co-localizes with a QTL previously reported to influence stature and related traits in Brown Swiss dairy cattle. CONCLUSION: The detection of QTL and their causative variants remains challenging. Combining comprehensive phenotypic data with imputed whole genome sequences seems promising. We present a QTL on BTA17 for female fertility in dairy cattle with two significantly associated non-synonymous SNPs, along with five additional QTL for fertility traits and calving traits. For all of these we fine mapped the regions and suggest candidate genes and candidate variants

Towards Efficient and Scalable Data-Intensive Content Delivery: State-of-the-Art, Issues and Challenges

This chapter presents the authors’ work for the Case Study entitled “Delivering Social Media with Scalability” within the framework of High-Performance Modelling and Simulation for Big Data Applications (cHiPSet) COST Action 1406. We identify some core research areas and give an outline of the publications we came up within the framework of the aforementioned action. The ease of user content generation within social media platforms, e.g. check-in information, multimedia data, etc., along with the proliferation of Global Positioning System (GPS)-enabled, always-connected capture devices lead to data streams of unprecedented amount and a radical change in information sharing. Social data streams raise a variety of practical challenges: derivation of real-time meaningful insights from effectively gathered social information, a paradigm shift for content distribution with the leverage of contextual data associated with user preferences, geographical characteristics and devices in general, etc. In this article we present the methodology we followed, the results of our work and the outline of a comprehensive survey, that depicts the state-of-the-art situation and organizes challenges concerning social media streams and the infrastructure of the data centers supporting the efficient access to data streams in terms of content distribution, data diffusion, data replication, energy efficiency and network infrastructure. The challenges of enabling better provisioning of social media data have been identified and they were based on the context of users accessing these resources. The existing literature has been systematized and the main research points and industrial efforts in the area were identified and analyzed. In our works, in the framework of the Action, we came up with potential solutions addressing the problems of the area and described how these fit in the general ecosystem

IR laser-induced protein crystal transformation

A method and the design of instrumentation, and its preliminary practical realisation, including test experiments, with the object of inducing phase changes of biomolecular crystals by controlled dehydration through heating with infrared (IR) light are described. The aim is to generate and select crystalline phases through transformation in the solid state which have improved order (higher resolution in X-ray diffraction experiments) and reduced mosaic spread (more uniformly aligned mosaic blocks) for diffraction data collection and analysis. The crystal is heated by pulsed and/or constant IR laser irradiation. Loss of crystal water following heating and its reabsorption through equilibration with the environment is measured optically by a video system. Heating proved superior to traditional controlled dehydration by humidity change for the test cases CODH (carbon monoxide dehydrogenase) and CLK2 (a protein kinase). Heating with IR light is experimentally simple and offers an exploration of a much broader parameter space than the traditional method, as it allows the option of varying the rate of phase changes through modification of the IR pulse strength, width and repeat frequency. It impacts the crystal instantaneously, isotropically and homogeneously, and is therefore expected to cause less mechanical stress