Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis.

The TAR DNA-binding protein 43 (TDP-43) has been identified as the major disease protein in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U), defining a novel class of neurodegenerative conditions: the TDP-43 proteinopathies. The first pathogenic mutations in the gene encoding TDP-43 (TARDBP) were recently reported in familial and sporadic ALS patients, supporting a direct role for TDP-43 in neurodegeneration. In this study, we report the identification and functional analyses of two novel and one known mutation in TARDBP that we identified as a result of extensive mutation analyses in a cohort of 296 patients with variable neurodegenerative diseases associated with TDP-43 histopathology. Three different heterozygous missense mutations in exon 6 of TARDBP (p.M337V, p.N345K, and p.I383V) were identified in the analysis of 92 familial ALS patients (3.3%), while no mutations were detected in 24 patients with sporadic ALS or 180 patients with other TDP-43-positive neurodegenerative diseases. The presence of p.M337V, p.N345K, and p.I383V was excluded in 825 controls and 652 additional sporadic ALS patients. All three mutations affect highly conserved amino acid residues in the C-terminal part of TDP-43 known to be involved in protein-protein interactions. Biochemical analysis of TDP-43 in ALS patient cell lines revealed a substantial increase in caspase cleaved fragments, including the approximately 25 kDa fragment, compared to control cell lines. Our findings support TARDBP mutations as a cause of ALS. Based on the specific C-terminal location of the mutations and the accumulation of a smaller C-terminal fragment, we speculate that TARDBP mutations may cause a toxic gain of function through novel protein interactions or intracellular accumulation of TDP-43 fragments leading to apoptosis

Transformative Sea-level Rise Research and Planning: Establishing a University, Tribal, and Community Partnership for a Resilient California North Coast

Sea-level rise (SLR) is and will continue to be a pressing issue in the rural, North Coast region of California, especially since nearby Wigi (or Humboldt Bay) is experiencing one of the fastest rates of relative SLR on the U.S. West Coast. In this paper, we argue that SLR presents a transformative opportunity to rekindle environmental relationships and reshape the future of the California North Coast and beyond. As the preeminent higher education institution of the region, Cal Poly Humboldt has the responsibility to be a leader in education, research, and planning for climate resilience. We describe efforts of the Cal Poly Humboldt Sea Level Rise Institute to establish a university-Tribal-community partnership that braids together different approaches and ways of knowing to develop research and planning that supports a resilient California North Coast. Since Wigi is projected to experience the effects of SLR sooner than the rest of the state, the North Coast region is poised to act as an incubator for new ideas and solutions, including Indigenous knowledge systems, and to play a role in influencing equitable, resilient, and transformative SLR adaptation processes in other parts of the state and the world. This will require developing programming and expertise in specific disciplinary areas, but, more importantly, will require the development of opportunities and spaces for various disciplines, ways of knowing, and sectors (e.g. Tribal nations, academia, government, NGOs, private companies, and community groups) to converge and bring the best of what they have to address climate-induced challenges and opportunities

Place-Based Learning Communities on a Rural Campus: Turning Challenges into Assets

At Humboldt State University (HSU), location is everything. Students are as drawn to our spectacular natural setting as they are to the unique majors in the natural resource sciences that the university has to offer. However, the isolation that nurtures the pristine natural beauty of the area presents a difficult reality for students who are accustomed to more densely populated environments. With the large majority of our incoming students coming from distant cities, we set out to cultivate a “home away from home” by connecting first-year students majoring in science, technology, engineering and math (STEM) to the communities and local environment of Humboldt County. To achieve this, we designed first-year place-based learning communities (PBLCs) that integrate unique aspects and interdisciplinary themes of our location throughout multiple high impact practices, including a summer experience, blocked-enrolled courses, and a first-year experience course entitled Science 100: Becoming a STEM Professional in the 21st Century. Native American culture, traditional ways of knowing, and contemporary issues faced by tribal communities are central features of our place-based curriculum because HSU is located on the ancestral land of the Wiyot people and the university services nine federally recognized American Indian tribes. Our intention is that by providing a cross-cultural, validating environment, students will: feel and be better supported in their academic pursuits; cultivate values of personal, professional and social responsibility; and increase the likelihood that they will complete their HSU degree. As we complete the fourth year of implementation, we aim to harness our experience and reflection to improve our programming and enable promising early results to be sustained

National Hydrogen And Fuel Cell Education Program Part I: Curriculum

In 2008, the U.S. Department of Energy (DOE) made five awards to university programs seeking to develop and expand education programs in Hydrogen and Fuel Cells. The main objective of the DOE program was to train graduates who will comprise the next generation workforce needed for research, development, and demonstration activities in government, industry, and academia. Hydrogen and fuel cell technologies (HFCT) are considered strong components in the future suite of technologies enabling energy independence and a cleaner environment for stationary and transportation applications. However, HFCT are inherently complex and require contribution from most of the engineering and technology disciplines. At the same time, HFCT topics are rare in university programs and few engineering students receive adequate training. The paper will present the educational efforts and models being developed under this funding. The program is offered through California State University Los Angeles, Humboldt State University, Michigan Technological University, University of North Carolina Charlotte and University of North Dakota. With collaborations, the list of participating colleges is even larger. The authors\u27 intent is to share the wealth of approaches taken to and the challenges and accomplishments of developing HFCT curriculum, which range from designing short modules for existing courses to dedicating majors and minors to the topic. More than twenty courses are modified or developed as part of the activities. As a result, HFCT is introduced to technology and chemical, mechanical, electrical, and environmental engineering majors. The activities undertaken also include outreach to non-major student population and school programs. © American Society for Engineering Education, 2010

Final Technical Report: Hydrogen Energy in Engineering Education (H2E3)

Schatz Energy Research Center's Hydrogen Energy in Engineering Education curriculum development project delivered hydrogen energy and fuel cell learning experiences to over 1,000 undergraduate engineering students at five California universities, provided follow-on internships for students at a fuel cell company; and developed commercializable hydrogen teaching tools including a fuel cell test station and a fuel cell/electrolyzer experiment kit. Monitoring and evaluation tracked student learning and faculty and student opinions of the curriculum, showing that use of the curriculum did advance student comprehension of hydrogen fundamentals. The project web site (hydrogencurriculum.org) provides more information

National Hydrogen And Fuel Cell Education Program Part Ii: Laboratory Practicum

Hydrogen and fuel cell technologies (HFCT) hold the promise of cleaner transportation and reducing the US reliance on imported fuels. However, their introduction in technical curriculums nationwide is rather slow, while the demand for trained workforce for research, development, and demonstration activities in government, industry, and academia is growing. In 2008, the U.S. Department of Energy (DOE) made five awards to university programs seeking to develop and expand Hydrogen and Fuel Cells Education. The program is offered through California State University Los Angeles, Humboldt State University, Michigan Technological University, University of North Carolina Charlotte and University of North Dakota. The participating universities are actively developing a variety of new curricula or modifications to existing majors. A detailed account of curricular activities is given by the authors in a sister publication1. Recognizing the inherent complexity of the topic and a multitude of new concepts, the HFCT programs are integrating laboratory practicum and projects supporting student learning. Both equipment available on the market and custom-built laboratory units are discussed. Over the recent years, several manufacturers have come forward with HFCT equipment offerings. Equipment\u27s performance, integration into courses and variety of adopted applications at several institutions are being presented in a single publication. In addition, descriptions of several custom experiments addressing specific needs in their respective programs are shared. © American Society for Engineering Education, 2010

Engineering foundations for the determination of security costs

This material is presented to ensure timely dissemination of scholarly and technical work. Copyright and all rights therein are retained by authors or by other copyright holders. All persons copying this information are expected to adhere to the terms and constraints invoked by each author's copyright. In most cases, these works may not be reposted without the explicit permission of the copyright holder