Agent Based Simulation Seas Evaluation of DoDAF Architecture

With Department of Defense (DoD) weapon systems being deeply rooted in the command, control, communications, computers, intelligence, surveillance, and reconnaissance (C4ISR) structure, it is necessary for combat models to capture C4ISR effects in order to properly assess military worth. Unlike many DoD legacy combat models, the agent based model System Effectiveness and Analysis Simulation (SEAS) is identified as having C4ISR analysis capabilities. In lieu of requirements for all new DoD C4ISR weapon systems to be placed within a DoD Architectural Framework (DoDAF), investigation of means to export data from the Framework to the combat model SEAS began. Through operational, system, and technical views, the DoDAF provides a consistent format for new weapon systems to be compared and evaluated. Little research has been conducted to show how to create an executable model of an actual DoD weapon system described by the DoDAF. In collaboration with Systems Engineering masters student Captain Andrew Zinn, this research identified the Aerospace Operation Center (AOC) weapon system architecture, provided by the MITRE Corp., as suitable for translation into SEAS. The collaborative efforts lead to the identification and translation of architectural data products to represent the Time Critical Targeting (TCT) activities of the AOC. A comparison of the AOC weapon system employing these TCT activities with an AOC without TCT capabilities is accomplished within a Kosovo-like engagement (provided by Space and Missile Center Transformations Directorate). Results show statistically significant differences in measures of effectiveness (MOEs) chosen to compare the systems. The comparison also identified the importance of data products not available in this incomplete architecture and makes recommendations for SEAS to be more receptive to DoDAF data products

Selection of primer-template sequences that bind human immunodeficiency virus reverse transcriptase with high affinity

A SELEX (systematic evolution of ligands by exponential enrichment)-based approach was developed to determine whether HIV-RT showed preference for particular primer-template sequences. A 70 nt duplex DNA was designed with 20 nt fixed flanking sequences at the 3′ and 5′ ends and a randomized 30 nt internal sequence. The fixed sequence at the 5′ end contained a BbsI site six bases removed from the randomized region. BbsI cuts downstream of its recognition site generating four base 5′ overhangs with recessed 3′ termini. Cleavage produced a 50 nt template and 46 nt primer with the 3′ terminus within the randomized region. HIV-RT was incubated with this substrate and material that bound RT was isolated by gel-shift. The recovered material was treated to regenerate the BbsI site, amplified by PCR, cleaved with BbsI and selected with HIV-RT again. This was repeated for 12 rounds. Material from round 12 bound approximately 10-fold more tightly than starting material. All selected round 12 primer-templates had similar sequence configuration with a 6–8 base G run at the 3′ primer terminus, similar to the HIV polypurine tract. Further modifications indicate that the Gs were necessary and sufficient for strong binding

Extraction efficiency of drifting electrons in a two-phase xenon time projection chamber

We present a measurement of the extraction efficiency of quasi-free electrons from the liquid into the gas phase in a two-phase xenon time-projection chamber. The measurements span a range of electric fields from 2.4 to 7.1 kV/cm in the liquid xenon, corresponding to 4.5 to 13.1 kV/cm in the gaseous xenon. Extraction efficiency continues to increase at the highest extraction fields, implying that additional charge signal may be attained in two-phase xenon detectors through careful high-voltage engineering of the gate-anode region

Calibration of a two-phase xenon time projection chamber with a 37^{37}Ar source

We calibrate a two-phase xenon detector at 0.27 keV in the charge channel and at 2.8 keV in both the light and charge channels using a $^{37}$Ar source that is directly released into the detector. We map the light and charge yields as a function of electric drift field. For the 2.8 keV peak, we calculate the Thomas-Imel box parameter for recombination and determine its dependence on drift field. For the same peak, we achieve an energy resolution, $E_{\sigma}/E_{mean}$, between 9.8% and 10.8% for 0.1 kV/cm to 2 kV/cm electric drift fields.Comment: 12 pages, 7 figure

Analysis of 83mKr prompt scintillation signals in the PIXeY detector

Prompt scintillation signals from 83mKr calibration sources are a useful metric to calibrate the spatial variation of light collection efficiency and electric field magnitude of a two phase liquid-gas xenon time projection chamber. Because 83mKr decays in two steps, there are two prompt scintillation pulses for each calibration event, denoted S1a and S1b. We study the ratio of S1b to S1a signal sizes in the Particle Identification in Xenon at Yale (PIXeY) experiment and its dependence on the time separation between the two signals (Δ t), notably its increase at low Δ t. In PIXeY data, the Δ t dependence of S1b/S1a is observed to exhibit two exponential components: one with a time constant of 0.05 ± 0.02 μ s, which can be attributed to processing effects and pulse overlap and one with a time constant of 10.2 ± 2.2 μs that increases in amplitude with electric drift field, the origin of which is not yet understood

Pathway analysis following association study

Genome-wide association studies often emphasize single-nucleotide polymorphisms with the smallest p-values with less attention given to single-nucleotide polymorphisms not ranked near the top. We suggest that gene pathways contain valuable information that can enable identification of additional associations. We used gene set information to identify disease-related pathways using three methods: gene set enrichment analysis (GSEA), empirical enrichment p-values, and Ingenuity pathway analysis (IPA). Association tests were performed for common single-nucleotide polymorphisms and aggregated rare variants with traits Q1 and Q4. These pathway methods were evaluated by type I error, power, and the ranking of the VEGF pathway, the gene set used in the simulation model. GSEA and IPA had high power for detecting the VEGF pathway for trait Q1 (91.2% and 93%, respectively). These two methods were conservative with deflated type I errors (0.0083 and 0.0072, respectively). The VEGF pathway ranked 1 or 2 in 123 of 200 replicates using IPA and ranked among the top 5 in 114 of 200 replicates for GSEA. The empirical enrichment method had lower power and higher type I error. Thus pathway analysis approaches may be useful in identifying biological pathways that influence disease outcomes

Topoclimate effect on treeline elevation depends on the regional framework: A contrast between Southern Alps (New Zealand) and Apennines (Italy) forests

Deciphering the spatial patterns of alpine treelines is critical for understanding the ecosystem processes involved in the persistence of tree species and their altitudinal limit. Treelines are thought to be controlled by temperature, and other environmental variables but they have rarely been investigated in regions with different land-use change legacies. Here, we systematically investigated treeline elevation in the Apennines (Italy) and Southern Alps (New Zealand) with contrasting human history but similar biogeographic trajectories, intending to identify distinct drivers that affect their current elevation and highlight their respective peculiarities. Over 3622 km of Apennines, treeline elevation was assessed in 302 mountain peaks and in 294 peaks along 4504 km of Southern Alps. The major difference between the Southern Alps and Apennines treeline limit is associated with their mountain aspects. In the Southern Alps, the scarcely anthropized Nothofagus treeline elevation was higher on the warmer equator-facing slopes than on the pole-facing ones. Contrary to what would be expected based on temperature limitation, the elevation of Fagus sylvatica treelines in the Apennines was higher on colder, pole-facing slopes than on human-shaped equator-facing, warmer mountainsides. Pervasive positive correlations were found between treeline elevation and temperature in the Southern Alps but not in the Apennines. While the position of the Fagus and Nothofagus treelines converge on similar isotherms of annual average temperature, a striking isothermal difference between the temperatures of the hottest month on which the two taxonomic groups grow exists. We conclude that actual treeline elevation reflects the ecological processes driven by a combination of local-scale topoclimatic conditions, and human disturbance legacy. Predicting dynamic processes affecting current and future alpine treeline position requires further insight into the modulating influences that are currently understood at a regional scale

Growth factor release from a chemically modified elastomeric poly(1,8‐octanediol‐co‐citrate) thin film promotes angiogenesis in vivo

The ultimate success of in vivo organ formation utilizing ex vivo expanded “starter” tissues relies heavily upon the level of vascularization provided by either endogenous or artificial induction of angiogenic or vasculogenic events. To facilitate proangiogenic outcomes and promote tissue growth, an elastomeric scaffold previously shown to be instrumental in the urinary bladder regenerative process was modified to release proangiogenic growth factors. Carboxylic acid groups on poly(1,8‐octanediol‐co‐citrate) films (POCfs) were modified with heparan sulfate creating a heparan binding POCf (HBPOCf). Release of proangiogenic growth factors vascular endothelial growth factor (VEGF), fibroblast growth factor 2 (FGF2), and insulin‐like growth factor 1 (IGF‐1) from HBPOCfs demonstrated an approximate threefold increase over controls during a 30‐day time course in vitro . Atomic force microscopy demonstrated significant topological differences between films. Subcutaneous implantation of POCf alone, HBPOCf, POCf‐VEGF, and HBPOCf‐VEGF within the dorsa of nude rats yielded increased vascular growth in HBPOCf‐VEGF constructs. Vessel quantification studies revealed that POCfs alone contained 41.1 ± 4.1 vessels/mm 2 , while HBPOCf, POCf‐VEGF, and HBPOCF‐VEGF contained 41.7 ± 2.6, 76.3 ± 9.4, and 167.72 ± 15.3 vessels/mm 2 , respectively. Presence of increased vessel growth was demonstrated by CD31 and vWF immunostaining in HBPOCf‐VEGF implanted areas. Data demonstrate that elastomeric POCfs can be chemically modified and possess the ability to promote angiogenesis in vivo . © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90248/1/33306_ftp.pd

Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE Collaboration): a meta-analysis of genome-wide association studies

<p>Background - Various genome-wide association studies (GWAS) have been done in ischaemic stroke, identifying a few loci associated with the disease, but sample sizes have been 3500 cases or less. We established the METASTROKE collaboration with the aim of validating associations from previous GWAS and identifying novel genetic associations through meta-analysis of GWAS datasets for ischaemic stroke and its subtypes.</p> <p>Methods - We meta-analysed data from 15 ischaemic stroke cohorts with a total of 12 389 individuals with ischaemic stroke and 62 004 controls, all of European ancestry. For the associations reaching genome-wide significance in METASTROKE, we did a further analysis, conditioning on the lead single nucleotide polymorphism in every associated region. Replication of novel suggestive signals was done in 13 347 cases and 29 083 controls.</p> <p>Findings - We verified previous associations for cardioembolic stroke near PITX2 (p=2·8×10−16) and ZFHX3 (p=2·28×10−8), and for large-vessel stroke at a 9p21 locus (p=3·32×10−5) and HDAC9 (p=2·03×10−12). Additionally, we verified that all associations were subtype specific. Conditional analysis in the three regions for which the associations reached genome-wide significance (PITX2, ZFHX3, and HDAC9) indicated that all the signal in each region could be attributed to one risk haplotype. We also identified 12 potentially novel loci at p<5×10−6. However, we were unable to replicate any of these novel associations in the replication cohort.</p> <p>Interpretation - Our results show that, although genetic variants can be detected in patients with ischaemic stroke when compared with controls, all associations we were able to confirm are specific to a stroke subtype. This finding has two implications. First, to maximise success of genetic studies in ischaemic stroke, detailed stroke subtyping is required. Second, different genetic pathophysiological mechanisms seem to be associated with different stroke subtypes.</p&gt