The Disciplined Use of Simplifying Assumptions

Submitted to the ACM SIGSOFT Second Software Engineering Symposium: Workshop on Rapid Prototyping. Columbia, Maryland, April 19-21, 1982.Simplifying assumptions — everyone uses them but no one's programming tool explicitly supports them. In programming, as in other kinds of engineering design, simplifying assumptions are an important method for dealing with complexity. Given a complex programming problem, expert programmers typically choose simplifying assumptions which, though false, allow them to arrive rapidly at a program which addresses the important features of the problem without being distracted by all of its details. The simplifying assumptions are then incrementally retracted with corresponding modifications to the initial program. This methodology is particularly applicable to rapid prototyping because the main questions of interest can often be answered using only the initial program. Simplifying assumptions can easily be misused. In order to use them effectively two key issues must be addressed. First, simplifying assumptions should be chosen which simplify the design problems significantly without changing the essential character of the program which needs to be implemented. Second, the designer must keep track of all the assumptions he is making so that he can later retract them in an orderly manner. By explicitly dealing with these issues, a programming assistant system could directly support the use of simplifying assumptions as a disciplined part of the software development process.MIT Artificial Intelligence Laborator

Strip casting with fluxing agent applied to casting roll

A strip caster (10) for producing a continuous strip (24) includes a tundish (12) for containing a melt (14), a pair of horizontally disposed water cooled casting rolls (22) and devices (29) for electrostatically coating the outer peripheral chill surfaces (44) of the casting rolls with a powder flux material (56). The casting rolls are juxtaposed relative to one another for forming a pouting basin (18) for receiving the melt through a teeming tube (16) thereby establishing a meniscus (20) between the rolls for forming the strip. The melt is protected from the outside air by a non-oxidizing gas passed through a supply line (28) to a sealing chamber (26). A preferred flux is boron oxide having a melting point of about 550° C. The flux coating enhances wetting of the steel melt to the casting roll and dissolves any metal oxide formed on the roll

Exploitation of Other Social Amoebae by Dictyostelium caveatum

Dictyostelium amoebae faced with starvation trigger a developmental program during which many cells aggregate and form fruiting bodies that consist of a ball of spores held aloft by a thin stalk. This developmental strategy is open to several forms of exploitation, including the remarkable case of Dictyostelium caveatum, which, even when it constitutes 1/10(3) of the cells in an aggregate, can inhibit the development of the host and eventually devour it. We show that it accomplishes this feat by inhibiting a region of cells, called the tip, which organizes the development of the aggregate into a fruiting body. We use live-cell microscopy to define the D. caveatum developmental cycle and to show that D. caveatum amoebae have the capacity to ingest amoebae of other Dictyostelid species, but do not attack each other. The block in development induced by D. caveatum does not affect the expression of specific markers of prespore cell or prestalk cell differentiation, but does stop the coordinated cell movement leading to tip formation. The inhibition mechanism involves the constitutive secretion of a small molecule by D. caveatum and is reversible. Four Dictyostelid species were inhibited in their development, while D. caveatum is not inhibited by its own compound(s). D. caveatum has evolved a predation strategy to exploit other members of its genus, including mechanisms of developmental inhibition and specific phagocytosis

African Malaria Control Programs Deliver ITNs and Achieve What the Clinical Trials Predicted

Thomas Eisele and Richard Steketee discuss new research in PLoS Medicine by Stephen Lim and colleagues that examined the association of insecticide-treated nets with the reduction of P. falciparum prevalence in children under 5 and all-cause post-neonatal mortality

Wrong Turn in Cyberspace: Using ICANN to Route Around the APA and the Constitution

The Internet relies on an underlying centralized hierarchy built into the domain name system (DNS) to control the routing for the vast majority of Internet traffic. At its heart is a single data file, known as the root. Control of the root provides singular power in cyberspace. This Article first describes how the United States government found itself in control of the root. It then describes how, in an attempt to meet concerns that the United States could so dominate an Internet chokepoint, the U. S. Department of Commerce (DoC) summoned into being the Internet Corporation for Assigned Names and Numbers (ICANN), a formally private nonprofit California corporation. DoC then signed contracts with ICANN in order to clothe it with most of the U. S. government\u27s power over the DNS, and convinced other parties to recognize ICANN\u27s authority. ICANN then took regulatory actions that the U. S. Department of Commerce was unable or unwilling to make itself, including the imposition on all registrants of Internet addresses of an idiosyncratic set of arbitration rules and procedures that benefit third-party trademark holders. Professor Froomkin then argues that the use of ICANN to regulate in the stead of an executive agency violates fundamental values and policies designed to ensure democratic control over the use of government power, and sets a precedent that risks being expanded into other regulatory activities. He argues that DoC\u27s use of ICANN to make rules either violates the APA\u27s requirement for notice and comment in rulemaking and judicial review, or it violates the Constitution\u27s nondelegation doctrine. Professor Froomkin reviews possible alternatives to ICANN, and ultimately proposes a decentralized structure in which the namespace of the DNS is spread out over a transnational group of policy partners with DoC

Rituximab or Cyclosporine in the Treatment of Membranous Nephropathy

Background: B-cell anomalies play a role in the pathogenesis of membranous nephropathy. B-cell depletion with rituximab may therefore be noninferior to treatment with cyclosporine for inducing and maintaining a complete or partial remission of proteinuria in patients with this condition. Methods: We randomly assigned patients who had membranous nephropathy, proteinuria of at least 5 g per 24 hours, and a quantified creatinine clearance of at least 40 ml per minute per 1.73 m(2) of body-surface area and had been receiving angiotensin-system blockade for at least 3 months to receive intravenous rituximab (two infusions, 1000 mg each, administered 14 days apart; repeated at 6 months in case of partial response) or oral cyclosporine (starting at a dose of 3.5 mg per kilogram of body weight per day for 12 months). Patients were followed for 24 months. The primary outcome was a composite of complete or partial remission of proteinuria at 24 months. Laboratory variables and safety were also assessed. Results: A total of 130 patients underwent randomization. At 12 months, 39 of 65 patients (60%) in the rituximab group and 34 of 65 (52%) in the cyclosporine group had a complete or partial remission (risk difference, 8 percentage points; 95% confidence interval [CI], -9 to 25; P=0.004 for noninferiority). At 24 months, 39 patients (60%) in the rituximab group and 13 (20%) in the cyclosporine group had a complete or partial remission (risk difference, 40 percentage points; 95% CI, 25 to 55; P<0.001 for both noninferiority and superiority). Among patients in remission who tested positive for anti-phospholipase A(2) receptor (PLA2R) antibodies, the decline in autoantibodies to anti-PLA2R was faster and of greater magnitude and duration in the rituximab group than in the cyclosporine group. Serious adverse events occurred in 11 patients (17%) in the rituximab group and in 20 (31%) in the cyclosporine group (P=0.06). Conclusions: Rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria at 12 months and was superior in maintaining proteinuria remission up to 24 months. (Funded by Genentech and the Fulk Family Foundation; MENTOR ClinicalTrials.gov number, .) In a randomized, controlled trial involving patients with membranous nephropathy, rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria at 12 months and was superior in maintaining proteinuria remission for up to 24 months.Genentech; Fulk Family Foundation6 month embargo; published July 4, 2019This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

An intrinsically disordered proteins community for ELIXIR.

Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) are now recognised as major determinants in cellular regulation. This white paper presents a roadmap for future e-infrastructure developments in the field of IDP research within the ELIXIR framework. The goal of these developments is to drive the creation of high-quality tools and resources to support the identification, analysis and functional characterisation of IDPs. The roadmap is the result of a workshop titled "An intrinsically disordered protein user community proposal for ELIXIR" held at the University of Padua. The workshop, and further consultation with the members of the wider IDP community, identified the key priority areas for the roadmap including the development of standards for data annotation, storage and dissemination; integration of IDP data into the ELIXIR Core Data Resources; and the creation of benchmarking criteria for IDP-related software. Here, we discuss these areas of priority, how they can be implemented in cooperation with the ELIXIR platforms, and their connections to existing ELIXIR Communities and international consortia. The article provides a preliminary blueprint for an IDP Community in ELIXIR and is an appeal to identify and involve new stakeholders

Old stones' song: Use-wear experiments and analysis of the Oldowan quartz and quartzite assemblage from Kanjera South (Kenya)

Evidence of Oldowan tools by w2.6 million years ago (Ma) may signal a major adaptive shift in hominin evolution. While tool-dependent butchery of large mammals was important by at least 2.0 Ma, the use of artifacts for tasks other than faunal processing has been difficult to diagnose. Here we report on use-wear analysis ofw2.0 Ma quartz and quartzite artifacts from Kanjera South, Kenya. A use-wear framework that links processing of specific materials and tool motions to their resultant use-wear patterns was developed. A blind test was then carried out to assess and improve the efficacy of this experimental use-wear framework, which was then applied to the analysis of 62 Oldowan artifacts from Kanjera South. Usewear on a total of 23 artifact edges was attributed to the processing of specific materials. Use-wear on seven edges (30%) was attributed to animal tissue processing,corroborating zooarchaeological evidence for butchery at the site. Use-wear on 16 edges (70%)was attributed to the processing of plant tissues, including wood, grit-covered plant tissues that we interpret asunderground storage organs (USOs), and stems of grass or sedges. These results expand our knowledge of the suite of behaviours carried out in the vicinity of Kanjera South to include the processing of materials that would be ‘invisible’ using standard archaeological methods. Wood cutting and scraping may represent the production and/or maintenance of wooden tools. Use-wear related to USO processing extends the archaeological evidence for hominin acquisition and consumption of this resource by over 1.5 Ma. Cutting of grasses, sedges or reeds may be related to a subsistence task (e.g., grass seed harvesting, cutting out papyrus culm for consumption) and/or a non-subsistence related task (e.g., production of ‘twine,’ simple carrying devices, or bedding). These results highlight the adaptive significance of lithic technology for hominins at Kanjera

Introduction: new research in monetary history - A map

This handbook aims to provide a comprehensive (though obviously not exhaustive) picture of state-of-the-art international scholarship on the history of money and currency. The chapters of this handbook cover a wide selection of research topics. They span chronologically from antiquity to nowadays and are geographically stretched from Latin America to Asia, although most of them focus on Western Europe and the USA, as a large part of the existing research does. The authors of these chapters constitute, we hope, a balanced sample of various generations of scholars who contributed to what Barry Eichengreen defined as "the new monetary and financial history" &#8211; an approach that combines the analysis of monetary aggregates and policies with the structure and dynamics of the banking sector and financial markets. We have structured this handbook in ten broad thematic parts: the historical origins of money; money, coinage, and the state; trade, money markets, and international currencies; money and metals; monetary experiments; Asian monetary systems; exchange rate regimes; monetary integration; central banking and monetary policy; and aggregate price shocks. In this introduction, we offer for each part some historical context, a few key insights from the literature, and a brief analytical summary of each chapter. Our aim is to draw a map that hopefully will help readers to organize their journey through this very wide and diverse research area