Certify for success: A methodology for human-centered certification of advanced aviation systems

This position paper uses the methodology in Design for Success as a basis for a human factors certification program. The Design for Success (DFS) methodology espouses a multi-step process to designing and developing systems in a human-centered fashion. These steps are as follows: (1) naturalizing - understand stakeholders and their concerns; (2) marketing - understand market-oriented alternatives to meeting stakeholder concerns; (3) engineering - detailed design and development of the system considering tradeoffs between technology, cost, schedule, certification requirements, etc.; (4) system evaluation - determining if the system meets its goal(s); and (5) sales and service - delivering and maintaining the system. Because the main topic of this paper is certification, we will focus our attention on step 4, System Evaluation, since it is the natural precursor to certification. Evaluation involves testing the system and its parts for their correct behaviors. Certification focuses not only on ensuring that the system exhibits the correct behaviors, but ONLY the correct behaviors

Embryonic Pattern Scaling Achieved by Oppositely Directed Morphogen Gradients

Morphogens are proteins, often produced in a localised region, whose concentrations spatially demarcate regions of differing gene expression in developing embryos. The boundaries of expression must be set accurately and in proportion to the size of the one-dimensional developing field; this cannot be accomplished by a single gradient. Here, we show how a pair of morphogens produced at opposite ends of a developing field can solve the pattern-scaling problem. In the most promising scenario, the morphogens effectively interact according to the annihilation reaction $A+B\to\emptyset$ and the switch occurs according to the absolute concentration of $A$ or $B$. In this case embryonic markers across the entire developing field scale approximately with system size; this cannot be achieved with a pair of non-interacting gradients that combinatorially regulate downstream genes. This scaling occurs in a window of developing-field sizes centred at a few times the morphogen decay length.Comment: 24 pages; 11 figures; uses iopar

Cosmological Luminosity Evolution of QSO/AGN Population

We apply the observed optical/X-ray spectral states of the Galactic black hole candidates (GBHCs) to the cosmological QSO luminosity evolution under the assumptions that QSOs and GBHCs are powered by similar accretion processes and that their emission mechanisms are also similar. The QSO luminosity function (LF) evolution in various energy bands is strongly affected by the spectral evolution which is tightly correlated with the luminosity evolution. We generate a random sample of QSOs born nearly synchronously by allowing the QSOs to have redshifts in a narrow range around an initial high redshift, black hole masses according to a power-law, and mass accretion rates near Eddington rates. The QSOs evolve as a single long-lived population on the cosmological time scale. The pure luminosity evolution results in distinct luminosity evolution features due to the strong spectral evolution. Most notably, different energy bands (optical/UV, soft X-ray, and hard X-ray) show different evolutionary trends and the hard X-ray LF in particular shows an apparent reversal of the luminosity evolution (from decreasing to increasing luminosity) at low redshifts, which is not seen in the conventional pure luminosity evolution scenario without spectral evolution. The resulting mass function of black holes (BHs), which is qualitatively consistent with the observed QSO LF evolution, shows that QSO remnants are likely to be found as BHs with masses in the range 10**8-5x10**10 solar masses. The long-lived single population of QSOs are expected to leave their remnants as supermassive BHs residing in rare, giant elliptical galaxies.Comment: 9 pages, 2 figures, ApJ

QSO's from Galaxy Collisions with Naked Black Holes

In the now well established conventional view (see Rees [1] and references therein), quasi-stellar objects (QSOs) and related active galactic nuclei (AGN) phenomena are explained as the result of accretion of plasma onto giant black holes which are postulated to form via gravitational collapse of the high density regions in the centers of massive host galaxies. This model is supported by a wide variety of indirect evidence and seems quite likely to apply at least to some observed AGN phenomena. However, one surprising set of new Hubble Space Telescope (HST) observations [2-4] directly challenges the conventional model, and the well known evolution of the QSO population raises some additional, though not widely recognized, difficulties. We propose here an alternative possibility: the Universe contains a substantial independent population of super-massive black holes, and QSO's are a phenomenon that occurs due to their collisions with galaxies or gas clouds in the intergalactic medium (IGM). This hypothesis would naturally explain why the QSO population declines very rapidly towards low redshift, as well as the new HST data.Comment: plain TeX file, no figures, submitted to Natur

A Semantic Cross-Species Derived Data Management Application

Managing dynamic information in large multi-site, multi-species, and multi-discipline consortia is a challenging task for data management applications. Often in academic research studies the goals for informatics teams are to build applications that provide extract-transform-load (ETL) functionality to archive and catalog source data that has been collected by the research teams. In consortia that cross species and methodological or scientific domains, building interfaces that supply data in a usable fashion and make intuitive sense to scientists from dramatically different backgrounds increases the complexity for developers. Further, reusing source data from outside one's scientific domain is fraught with ambiguities in understanding the data types, analysis methodologies, and how to combine the data with those from other research teams. We report on the design, implementation, and performance of a semantic data management application to support the NIMH funded Conte Center at the University of California, Irvine. The Center is testing a theory of the consequences of "fragmented" (unpredictable, high entropy) early-life experiences on adolescent cognitive and emotional outcomes in both humans and rodents. It employs cross-species neuroimaging, epigenomic, molecular, and neuroanatomical approaches in humans and rodents to assess the potential consequences of fragmented unpredictable experience on brain structure and circuitry. To address this multi-technology, multi-species approach, the system uses semantic web techniques based on the Neuroimaging Data Model (NIDM) to facilitate data ETL functionality. We find this approach enables a low-cost, easy to maintain, and semantically meaningful information management system, enabling the diverse research teams to access and use the data

Activated lymphocyte recruitment into the tumor microenvironment following preoperative sipuleucel-T for localized prostate cancer.

BackgroundSipuleucel-T is a US Food and Drug Administration-approved immunotherapy for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Its mechanism of action is not fully understood. This prospective trial evaluated the direct immune effects of systemically administered sipuleucel-T on prostatic cancer tissue in the preoperative setting.MethodsPatients with untreated localized prostate cancer were treated on an open-label Phase II study of sipuleucel-T prior to planned radical prostatectomy (RP). Immune infiltrates in RP specimens (posttreatment) and in paired pretreatment biopsies were evaluated by immunohistochemistry (IHC). Correlations between circulating immune response and IHC were assessed using Spearman rank order.ResultsOf the 42 enrolled patients, 37 were evaluable. Adverse events were primarily transient, mild-to-moderate and infusion related. Patients developed T cell proliferation and interferon-γ responses detectable in the blood following treatment. Furthermore, a greater-than-three-fold increase in infiltrating CD3(+), CD4(+) FOXP3(-), and CD8(+) T cells was observed in the RP tissues compared with the pretreatment biopsy (binomial proportions: all P < .001). This level of T cell infiltration was observed at the tumor interface, and was not seen in a control group consisting of 12 concurrent patients who did not receive any neoadjuvant treatment prior to RP. The majority of infiltrating T cells were PD-1(+) and Ki-67(+), consistent with activated T cells. Importantly, the magnitude of the circulating immune response did not directly correlate with T cell infiltration within the prostate based upon Spearman's rank order correlation.ConclusionsThis study is the first to demonstrate a local immune effect from the administration of sipuleucel-T. Neoadjuvant sipuleucel-T elicits both a systemic antigen-specific T cell response and the recruitment of activated effector T cells into the prostate tumor microenvironment

Overcoming the risk of inaction from emissions uncertainty in smallholder agriculture

The potential for improving productivity and increasing the resilience of smallholder agriculture, while also contributing to climate change mitigation, has recently received considerable political attention (Beddington et al 2012). Financial support for improving smallholder agriculture could come from performance-based funding including sale of carbon credits or certified commodities, payments for ecosystem services, and nationally appropriate mitigation action (NAMA) budgets, as well as more traditional sources of development and environment finance. Monitoring the greenhouse gas fluxes associated with changes to agricultural practice is needed for performance-based mitigation funding, and efforts are underway to develop tools to quantify mitigation achieved and assess trade-offs and synergies between mitigation and other livelihood and environmental priorities (Olander 2012)

Revealing power dynamics and staging conflicts in agricultural system transitions : Case studies of innovation platforms in New Zealand

Innovation platforms (IPs) that support agricultural innovation to enable transition processes towards more sustainable agriculture provide a space where conflicts of interest among actors in the existing agricultural system (the so called incumbent regime) may play out. Sometimes these conflicts over how actors will benefit from an action are not revealed until actors are brought together. However, a barrier to change occurs when IP actors use their existing power to mobilise resources to influence if and how individual and collective interests are aligned. In the context of agricultural innovation and transitions, this paper uses the power in transitions framework (Avelino and Wittmayer, 2016), along with analytical perspectives on conflicts and role perceptions, to understand how consciously staging or revealing conflicts of interest among IP actors changed role perceptions and power relations among these actors. The paper explores this topic in two IPs addressing agricultural production and sustainability challenges in New Zealand's agricultural sector. Conflicts were staged in IPs when one group of actors mobilised resources that enabled them to move existing power relations from one-sided, to synergistic or a mutual dependency. This enabled conflicts to be acknowledged and solved. In contrast, conflicts were not staged when actors mobilised resources to maintain antagonostic power relations. Our cases demontrate that staging conflicts to change actors' role perceptions is an important intermediary step to forming new power relations in the agricultural system. Our findings highlight the need for IP theory to conceptualise power relations in IPs as context specific, dynamic and a force shaping outcomes, rather than solely a force exerted by actors in the incumbent regime over IP actors.</p

Elastic energy of polyhedral bilayer vesicles

In recent experiments [M. Dubois, B. Dem\'e, T. Gulik-Krzywicki, J.-C. Dedieu, C. Vautrin, S. D\'esert, E. Perez, and T. Zemb, Nature (London) Vol. 411, 672 (2001)] the spontaneous formation of hollow bilayer vesicles with polyhedral symmetry has been observed. On the basis of the experimental phenomenology it was suggested [M. Dubois, V. Lizunov, A. Meister, T. Gulik-Krzywicki, J. M. Verbavatz, E. Perez, J. Zimmerberg, and T. Zemb, Proc. Natl. Acad. Sci. U.S.A. Vol. 101, 15082 (2004)] that the mechanism for the formation of bilayer polyhedra is minimization of elastic bending energy. Motivated by these experiments, we study the elastic bending energy of polyhedral bilayer vesicles. In agreement with experiments, and provided that excess amphiphiles exhibiting spontaneous curvature are present in sufficient quantity, we find that polyhedral bilayer vesicles can indeed be energetically favorable compared to spherical bilayer vesicles. Consistent with experimental observations we also find that the bending energy associated with the vertices of bilayer polyhedra can be locally reduced through the formation of pores. However, the stabilization of polyhedral bilayer vesicles over spherical bilayer vesicles relies crucially on molecular segregation of excess amphiphiles along the ridges rather than the vertices of bilayer polyhedra. Furthermore, our analysis implies that, contrary to what has been suggested on the basis of experiments, the icosahedron does not minimize elastic bending energy among arbitrary polyhedral shapes and sizes. Instead, we find that, for large polyhedron sizes, the snub dodecahedron and the snub cube both have lower total bending energies than the icosahedron