Silencing disease genes in the laboratory and the clinic

Synthetic nucleic acids are commonly used laboratory tools for modulating gene expression and have the potential to be widely used in the clinic. Progress towards nucleic acid drugs, however, has been slow and many challenges remain to be overcome before their full impact on patient care can be understood. Antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) are the two most widely used strategies for silencing gene expression. We first describe these two approaches and contrast their relative strengths and weaknesses for laboratory applications. We then review the choices faced during development of clinical candidates and the current state of clinical trials. Attitudes towards clinical development of nucleic acid silencing strategies have repeatedly swung from optimism to depression during the past 20 years. Our goal is to provide the information needed to design robust studies with oligonucleotides, making use of the strengths of each oligonucleotide technology

Competency Education Series: Policy Brief One, An Emerging Federal Role for Competency Education

After two decades of standards-based reform, a new education paradigm has begun to take hold -- the rise of competency education. This new vision builds on the strong foundation of new college and career ready standards, challenging stakeholders to design an education system that emphasizes mastery of content standards and the transferable skills critical to success in college and today's workforce.A competency education system puts students at the center, replacing rigid time-based structures with flexible learning environments that ensure students receive the support and extra time they need to succeed. This highly-personalized approach provides clear, individualized pathways to student proficiency that help mobilize stakeholders around the collective goal of college and career readiness for all students. A growing number of states and districts have begun to embrace this vision for education, leading to an explosion of new policies, pilot initiatives, and tools designed to help schools implement competencybased approaches.The success of the competency movement depends heavily on the federal government's willingness to partner with states and districts as they design education systems that put students at the center. A true partnership will grant states the flexibility to innovate and develop equally ambitious accountability and assessment policies that better align with student centered education to ensure all students graduate with the knowledge and skills to succeed. This paper is the first in a series to help policymakers define the appropriate role for the federal government supporting competency education in the nation's K-12 schools

When Failure Is Not an Option: Designing Competency-Based Pathways for Next Generation Learning

Proposes an online learning-assisted model in which students advance by demonstrating mastery of subjects based on clear, measurable objectives and meaningful assessments. Examines innovation drivers, challenges, and philanthropic opportunities

NASA System Safety Handbook. Volume 2: System Safety Concepts, Guidelines, and Implementation Examples

This is the second of two volumes that collectively comprise the NASA System Safety Handbook. Volume 1 (NASASP-210-580) was prepared for the purpose of presenting the overall framework for System Safety and for providing the general concepts needed to implement the framework. Volume 2 provides guidance for implementing these concepts as an integral part of systems engineering and risk management. This guidance addresses the following functional areas: 1.The development of objectives that collectively define adequate safety for a system, and the safety requirements derived from these objectives that are levied on the system. 2.The conduct of system safety activities, performed to meet the safety requirements, with specific emphasis on the conduct of integrated safety analysis (ISA) as a fundamental means by which systems engineering and risk management decisions are risk-informed. 3.The development of a risk-informed safety case (RISC) at major milestone reviews to argue that the systems safety objectives are satisfied (and therefore that the system is adequately safe). 4.The evaluation of the RISC (including supporting evidence) using a defined set of evaluation criteria, to assess the veracity of the claims made therein in order to support risk acceptance decisions

Breaking Boundaries in Computing in Undergraduate Courses

An important question in undergraduate curricula is that of incorporating computing into STEM courses for majors and non-majors alike. What does it mean to teach “computing” in this context? What are some of the benefits and challenges for students and instructors in such courses? This paper contributes to this important dialog by describing three undergraduate courses that have been developed and taught at Harvey Mudd College and Loyola Marymount University. Each case study describes the course objectives, implementation challenges, and assessments

Lessons from an Open Source Business

Creating a successful company is difficult; but creating a successful company, a successful open source project, and a successful ecosystem all at the same time is much more difficult. This article takes a retrospective look at some of the lessons we have learned in building BigBlueButton, an open source web conferencing system for distance education, and in building Blindside Networks, a company following the traditional business model of providing support and services to paying customers. Our main message is that the focus must be on creating a successful open source project first, for without it, no company in the ecosystem can flourish

Continuity and change in a spin-off venture: the process of reimprinting

Because new entrants very often spin off from established firms, their learning and capabilities are closely linked to their organizational and technological heritage. While this may provide an initial advantage, parental influence can generate inertia and resistance to change, unless the new company is able to unlearn inappropriate practices and create its unique competitive identity. The tension between inheritance and search for novelty is the subject of the article. Building on an in-depth case study of Acorn Computers and ARM semiconductors, we present a model of intergenerational learning and spin-off performance. Early parental influence is followed by intense learning, improvisation and response to feedback from the market. This we term reimprinting, to emphasize the enduring competitive and organizational identity established early on by the spin-off, which in this case provided the basis for disruptive innovation. Focus on the parent–progeny dyad as the unit of analysis can reveal micro-processes that reconstitute past experience to make possible both continuity and innovation in the spin-off ventur

The RISC-KIT storm impact database: A new tool in support of DRR

This paper presents a new storm impact database for European coastlines that facilitates the upload, browsing and download of a broad range of physical and impact information related to historical and recent marine storm events. The database is transparent in terms of open access to raw data and metadata, makes use of version control systems through the OpenEarth repository and promotes the use of international standards. A total of 298 storm events are currently stored in the database from the ten RISC-KIT case study sites, including historical events dating back to the sixteenth century. To demonstrate the application of the tool, examples of typical event data contained within the database as well as the ability of the database to identify impacts of events across regions are presented. It is envisaged that this database will expand beyond the ten case study sites, with the aim of promoting and greatly improving the collection and reporting of extreme hydro-meteorological events across Europe into the future