Learning from Engineers to Develop a Model of Disciplinary Literacy in Engineering (Year 3)

Purpose This paper will the describe the overall project goals, activities, preliminary findings, and future work on this project. The purpose of this project is to develop a model of Disciplinary Literacy Instruction (DLI) in engineering that can be used in both K-12 and undergraduate engineering settings. This model of DLI will be informed by knowledge about the ways practicing engineers across four disciplines of engineering (i.e., electrical/computer, mechanical/aerospace, civil/environmental, and chemical/biological) read, interpret, evaluate, and generate texts in the context of their work environment. This information will be translated into a model of DLI in engineering to teach students how to use authentic engineering literacy practices as they learn discipline specific engineering content. Project Activities During the first year of this project, we conducted on-site observations with two electrical engineers and two mechanical engineers. In addition, we held interviews and conducted think-aloud protocols that were informed by the observations with each engineer. From these data sources, we developed a codebook describing the types of texts that the engineers interpreted, evaluated, and generated at the workplace. worked with both mechanical and electrical engineering consultants to help refine and revise the codes and code definitions to enhance their authenticity to each discipline. To further ensure the quality of our data analysis procedures, we sought feedback on our codes from three advisory board consultants having expertise in disciplinary literacy, engineering, and K-12 engineering education. During the second year of this project, we analyzed the interview and think-aloud protocol transcripts from the electrical and mechanical engineers to generate themes that described the interpretive and evaluative frameworks the engineers used as they solved a technical problem or generated a solution for a client or customer. Similarly, we developed themes that described the socially situated activities in which the previously defined genres were embedded. Taken together, these frameworks and activities inform the development of the DLI model in engineering. We also began collecting observation, interview, and think aloud data with one civil and one environmental engineer during this year. Currently, in the third year of this project, we are analyzing the observation field notes and the interview and think-aloud protocol transcripts from the civil and environmental engineers. Simultaneously, we are generating data with the final pair of engineers: one biological and one chemical engineer. We continue to refine our codebook by adding new genres as they appear and merging any similar, existing genres to capture the range of texts with which the engineers engaged. Engineering consultants from both the civil and environmental disciplines will provide feedback on our codes. Combined data from this phase with previous phases will be used develop disciplinary specific curricular materials for K-12 and undergraduate engineering education. Future Activities The data collected and analyzed throughout the project will inform the development of a model for DLI in engineering that can be used by teachers in both undergraduate and K-12 educational settings. This model will provide a framework for teachers to instruct students on how to use the authentic reading and writing strategies that practicing engineers use while solving problems. By providing a diverse set of students with exposure to these literacy practices in school at a young age, a model of DLI in engineering has the potential to remove literacy-based barriers that may deter students from pursuing engineering pathways

Differential effects of RASA3 mutations on hematopoiesis are profoundly influenced by genetic background and molecular variant.

Studies of the severely pancytopenic scat mouse model first demonstrated the crucial role of RASA3, a dual RAS and RAP GTPase activating protein (GAP), in hematopoiesis. RASA3 is required for survival in utero; germline deletion is lethal at E12.5-13.5 due to severe hemorrhage. Here, conditional deletion in hematopoietic stem and progenitor cells (HSPCs) using Vav-iCre recapitulates the null phenotype demonstrating that RASA3 is required at the stem and progenitor level to maintain blood vessel development and integrity and effective blood production. In adults, bone marrow blood cell production and spleen stress erythropoiesis are suppressed significantly upon induction of RASA3 deficiency, leading to pancytopenia and death within two weeks. Notably, RASA3 missense mutations in two mouse models, scat (G125V) and hlb381 (H794L), show dramatically different hematopoietic consequences specific to both genetic background and molecular variant. The mutation effect is mediated at least in part by differential effects on RAS and RAP activation. In addition, we show that the role of RASA3 is conserved during human terminal erythropoiesis, highlighting a potential function for the RASA3-RAS axis in disordered erythropoiesis in humans. Finally, global transcriptomic studies in scat suggest potential targets to ameliorate disease progression

Oropouche orthobunyavirus infection is mediated by the cellular host factor Lrp1

Oropouche orthobunyavirus (OROV

Lrp1 is essential for lethal Rift Valley fever hepatic disease in mice

Rift Valley fever virus (RVFV) is an emerging arbovirus found in Africa. While RVFV is pantropic and infects many cells and tissues, viral replication and necrosis within the liver play a critical role in mediating severe disease. The low-density lipoprotein receptor-related protein 1 (Lrp1) is a recently identified host factor for cellular entry and infection by RVFV. The biological significance of Lrp1, including its role in hepatic disease in vivo, however, remains to be determined. Because Lrp1 has a high expression level in hepatocytes, we developed a mouse model in which Lrp1 is specifically deleted in hepatocytes to test how the absence of liver Lrp1 expression affects RVF pathogenesis. Mice lacking Lrp1 expression in hepatocytes showed minimal RVFV replication in the liver, longer time to death, and altered clinical signs toward neurological disease. In contrast, RVFV infection levels in other tissues showed no difference between the two genotypes. Therefore, Lrp1 is essential for RVF hepatic disease in mice

Broad Spectrum Antiviral Activity of Favipiravir (T-705): Protection from Highly Lethal Inhalational Rift Valley Fever

Background:Development of antiviral drugs that have broad-spectrum activity against a number of viral infections would be of significant benefit. Due to the evolution of resistance to currently licensed antiviral drugs, development of novel anti-influenza drugs is in progress, including Favipiravir (T-705), which is currently in human clinical trials. T-705 displays broad-spectrum in vitro activity against a number of viruses, including Rift Valley Fever virus (RVFV). RVF is an important neglected tropical disease that causes human, agricultural, and economic losses in endemic regions. RVF has the capacity to emerge in new locations and also presents a potential bioterrorism threat. In the current study, the in vivo efficacy of T-705 was evaluated in Wistar-Furth rats infected with the virulent ZH501 strain of RVFV by the aerosol route.Methodology/Principal Findings:Wistar-Furth rats are highly susceptible to a rapidly lethal disease after parenteral or inhalational exposure to the pathogenic ZH501 strain of RVFV. In the current study, two experiments were performed: a dose-determination study and a delayed-treatment study. In both experiments, all untreated control rats succumbed to disease. Out of 72 total rats infected with RVFV and treated with T-705, only 6 succumbed to disease. The remaining 66 rats (92%) survived lethal infection with no significant weight loss or fever. The 6 treated rats that succumbed survived significantly longer before succumbing to encephalitic disease.Conclusions/Significance:Currently, there are no licensed antiviral drugs for treating RVF. Here, T-705 showed remarkable efficacy in a highly lethal rat model of Rift Valley Fever, even when given up to 48 hours post-infection. This is the first study to show protection of rats infected with the pathogenic ZH501 strain of RVFV. Our data suggest that T-705 has potential to be a broad-spectrum antiviral drug. © 2014 Caroline et al

Response to second treatment after initial failed treatment in a multicenter prospective infantile spasms cohort

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135085/1/epi13557_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135085/2/epi13557.pd

Noncoding deletions reveal a gene that is critical for intestinal function.

Large-scale genome sequencing is poised to provide a substantial increase in the rate of discovery of disease-associated mutations, but the functional interpretation of such mutations remains challenging. Here we show that deletions of a sequence on human chromosome 16 that we term the intestine-critical region (ICR) cause intractable congenital diarrhoea in infants1,2. Reporter assays in transgenic mice show that the ICR contains a regulatory sequence that activates transcription during the development of the gastrointestinal system. Targeted deletion of the ICR in mice caused symptoms that recapitulated the human condition. Transcriptome analysis revealed that an unannotated open reading frame (Percc1) flanks the regulatory sequence, and the expression of this gene was lost in the developing gut of mice that lacked the ICR. Percc1-knockout mice displayed phenotypes similar to those observed upon ICR deletion in mice and patients, whereas an ICR-driven Percc1 transgene was sufficient to rescue the phenotypes found in mice that lacked the ICR. Together, our results identify a gene that is critical for intestinal function and underscore the need for targeted in vivo studies to interpret the growing number of clinical genetic findings that do not affect known protein-coding genes

Medical imaging of pulmonary disease in SARS-CoV-2-exposed non-human primates

Chest X-ray (CXR), computed tomography (CT), and positron emission tomography-computed tomography (PET-CT) are noninvasive imaging techniques widely used in human and veterinary pulmonary research and medicine. These techniques have recently been applied in studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-exposed non-human primates (NHPs) to complement virological assessments with meaningful translational readouts of lung disease. Our review of the literature indicates that medical imaging of SARS-CoV-2-exposed NHPs enables high-resolution qualitative and quantitative characterization of disease otherwise clinically invisible and potentially provides user-independent and unbiased evaluation of medical countermeasures (MCMs). However, we also found high variability in image acquisition and analysis protocols among studies. These findings uncover an urgent need to improve standardization and ensure direct comparability across studies