Unravelling the multiple roles of FUS in RNA processing and on ALS pathogenesis

Two genes with related functions in RNA biogenesis were recently reported in patients with familial ALS: the FUS/TLS gene at the ALS6 locus and the TARDBP/TDP-43 gene at the ALS10 locus [1, 2]. FUS has been implicated to function in several steps of gene expression, including transcription regulation [3], RNA splicing [4, 5], mRNA transport in neurons [6] and, interestingly, in microRNA (miRNA) processing [7]. The goal of this project is to identify the molecular mechanisms leading to the development of FUS mutations-associated ALS. Specifically, we want to test the hypothesis that these FUS mutations misregulate miRNA levels that in turn affect the expression of genes critical for motor neuron survival. In addition we want to test whether misregulation of the miRNA profile is a common feature in ALS. We have performed immunoprecipitations from total extracts of 293T cells expressing FLAG-tagged FUS to characterize its interactome by mass spectrometry. This proteomic study not only revealed a strong interaction of FUS with splicing factors, but shows that FUS might be involved in many, quite different pathways. To map which parts of the FUS protein contribute to the interaction with splicing factors, we have performed a set of experiments with a series of missense and deletion mutants. With this approach, we will not only gain information on the binding partners of FUS along with a map of the required domains for the interactions, but it will also help to unravel whether certain ALS-associated FUS mutations lead to a loss or gain of function due to gain or loss of interactors. Additionally, we have performed quantitative interactomics using SILAC to identify interactome differences of ALS-associated FUS mutants. To this end we have performed immunoprecipitations of total extract from 293T cells, stably transduced with constructs expressing wild-type FUS-FLAG as well as three different ALS-associated mutants (G156E, R244C, P525L). First results indicate striking differences in the interactome with certain RNA binding proteins. We are now validating these candidates in order to reveal the importance of these differential interactions in the context of ALS.

Workers and respirators: What factors influence medical clearance? Experience in the petrochemical industry 2004--2008

This retrospective cohort study analyzed data from more than 2200 OSHA-mandated respirator medical evaluations performed between 2004 and 2008, with information initially obtained using an online questionnaire, to determine what factors influence medical clearance and the ability to safely wear respiratory protection in a large petrochemical company.^ The employees were mostly white males with a high school education, ranging in age from 25 to 60 years of age, who had been employed with the company an average of eight years. Their work was typically performed outdoors in a rural or offshore setting. Respirators were typically required for emergency response – escape or rescue only – and/or limited to less than four hours per month.^ Approximately 90% of the population achieved medical clearance by utilizing the online questionnaire. Of the remaining 10%, 66% were cleared after additional "hands-on" medical examination exam; 28% of the individuals' jobs were modified by their supervisor in order to not use a respirator, and 6% of the individuals (n=13) were excluded from wearing a respirator on the basis of the medical examination. The primary causes for exclusion from respirator use were cardiovascular (37.5%) and respiratory (31.3%) issues, followed by psychological (18.8%) and musculoskeletal (12.5%) concerns. Ultimately, over 99% of workers evaluated under this system were found capable of using respiratory protection safely. This questionnaire has proven to be an excellent health screening tool capable of initiating early detection and further investigation of potentially serious medical conditions within a large and diverse population in multiple locations. ^

Measuring value in cancer-related health care: A case study in head and neck cancer

In the current climate of escalating health care costs, defining value and accurately measuring it are two critical issues affecting not only the future of cancer care in particular but also the future of health care in general. Specifically, measuring and improving value in cancer-related health care are critical for continued advancements in research, management, and overall delivery of care. However, in oncology, most of this research has focused on value as it relates to insurance industry and payment reform, with little attention paid to value as the output of clinical interventions that encompass integrated clinical teams focusing on the entire cycle of care and measuring objective outcomes that are most relevant to patients. ^ In this study, patient-centered value was defined as health outcomes achieved per dollar spent, and calculated using objective functional outcomes and total care costs. The analytic sample comprised patients diagnosed with three common head and neck cancers—cancer of the larynx, oral cavity, and oropharynx—who were treated in an integrated tertiary care center over an approximately 10-year period. The results of this study provide initial empirical data that can be used to assess and ultimately to help improve the quality and value of head and neck cancer care, and more importantly they can be used by patients and clinicians to make better-informed decisions about care, particularly what therapeutic services and outcomes matter the most to patients.^

Status and constraints of costly port rejection : a case from the Vietnamese frozen seafood export industry

While the rising exports have been the source of growth for many developing countries in recent years, the rate of commodities rejected at the ports of developed countries has also been high. Yet why it has remained so despite the costs involved is mostly unknown. This paper takes a case of the frozen seafood export industry in Vietnam and examines the current status of port rejection, roles played by various stakeholders along the value chains, and the constraints faced by the Vietnamese producers and exporters. It concludes with some policy implications, including strengthening the enforcement mechanism of standards compliance particularly at the upstream of the value chain and providing public testing labs for small-scale producers.

Application of radiochemistry in food processing research. annual report /

"TID-4500."

Application of radiochemistry techniques in food processing research. progress report /

"TID-4500."

Drugs--current good manufacturing practice in manufacture, processing, packing, or holding. : regulations under the Federal Food, Drug, and Cosmetic Act, Part 133, Title 21, Code of Federal Regulations. Part 191, Hazardous substances.

Mode of access: Internet.

Report of a study of the foundry industry of North Carolina,

Mode of access: Internet.

The demand for aluminum: a case study in long-range forecasting.

"Developed from a doctoral dissertation, Long-range forecasting of the demand for aluminum (University of Illinois, 1956)"

Relationships between wages, wage payment methods, and personnel efficiency in the furniture industry : a report on management opinion in eighteen furniture factories /

Includes bibliographical references.

Designing and managing collaborative enterprises in the automotive industry

This paper presents the findings of a recently completed research project. It sheds light upon the appropriate governance of inter-firm relationships, in order to achieve competitive success for the whole partnership and its individual members. An exploratory study in the German automotive industry using inductive Grounded Theory was conducted, in order to form a set of propositions that were then validated. The research has resulted in the consolidation of these propositions into a novel concept termed Collaborative Enterprise Governance, which draws on an inter-disciplinary body of knowledge. The core of the concept is a competence based contingency framework that helps enterprise managers in selecting the most appropriate governance strategy (i.e. enterprise structure) for an inter-firm relationships within automotive supply networks (i.e. enterprises), depending on various exogenous and endogenous factors.