Large-scale behaviour of Sobolev functions in Ahlfors regular metric measure spaces

In this paper, we study the behaviour at infinity of $p$-Sobolev functions in the setting of Ahlfors $Q$-regular metric measure spaces supporting a $p$-Poincar\'e inequality. By introducing the notions of sets which are $p$-thin at infinity, we show that functions in the homogeneous space $\dot N^{1,p}(X)$ necessarily have limits at infinity outside of $p$-thin sets, when $1\le pQ$, we show by example that uniqueness of limits at infinity may fail for functions in $\dot N^{1,p}(X)$. While functions in $\dot N^{1,p}(X)$ may not have any reasonable limit at infinity when $p=Q$, we introduce the notion of a $Q$-thick set at infinity, and characterize the limits of functions in $\dot N^{1,Q}(X)$ along infinite curves in terms of limits outside $Q$-thin sets and along $Q$-thick sets. By weakening the notion of a thick set, we show that a function in $\dot N^{1,Q}(X)$ with a limit along such an almost thick set may fail to have a limit along any infinite curve. While homogeneous $p$-Sobolev functions may have infinite limits at infinity when $p\ge Q$, we provide bounds on how quickly such functions may grow: when $p=Q$, functions in $\dot N^{1,p}(X)$ have sub-logarithmic growth at infinity, whereas when $p>Q$, such functions have growth at infinity controlled by $d(\cdot, O)^{1-Q/p}$, where $O$ is a fixed base point in $X$. For the inhomogeneous spaces $N^{1,p}(X)$, the phenomenon is different. We show that for $1\le p\le Q$, the limit of a function $u\in N^{1,p}(X)$ is zero outside of a $p$-thin set, whereas $\lim_{x\to+\infty}u(x)=0$ for all $u\in N^{1,p}(X)$ when $p>Q$

Augmented Reality Glasses that Accommodate a Wide Range of Ophthalmic Prescriptions

Traditional eyewear frames are designed to accommodate a wide range of prescriptions. This includes the ability to include strong corrective lenses of significant thickness. However, augmented reality (AR) glasses with integrated displays can be much more constrained in terms of thickness, weight, and mechanical features since they have to accommodate a much larger number of components. As a result, traditional eyewear lens installation methods and features may not be feasible in AR glasses. This disclosure describes an ophthalmic lens edge profile and frame construction that minimizes mass and volume. The lens edge combined with the frame construction that includes an outer frame, an inner frame, and a step bevel, allows for a slim and compact solution that can accommodate prescription lenses

Leadership Initiatives International Public Health Internship Program

In a nine-month internship for Leadership Initiatives, our team worked together to develop and implement an international public health campaign to address major health concerns prevalent in the region of Bauchi State, Nigeria. Our topic was the issue of selfmedication and its effects among the community. We launched a campaign to collect survey data and develop an educational workshop for the project.https://scholarworks.moreheadstate.edu/celebration_posters_2023/1030/thumbnail.jp

Novel approaches to prevent and treat pertussis

Pertussis remains a significant health problem, killing up to 200,000 infants annually. We are pursuing two complementary approaches to this problem, (1) engineering the adenylate cyclase toxin as an additional antigen for inclusion in the current accellular vaccine and (2) developing a neonatal antibody therapeutic to protect infants during the most vulnerable period before they are fully vaccinated. The current vaccine confers short-term immunity and prevents the symptoms of disease but does not reduce infection or transmission rates. The adenylate cyclase toxin (ACT) is the leading candidate for inclusion in future vaccines, yet there is surprisingly little data detailing the mechanisms by which ACT confers protection or its appropriateness for manufacturing and formulation as a part of a multicomponent vaccine. We have engineered this protein for improved production and stability and have identified a panel of neutralizing and non-neutralizing antibodies to aid in further engineering efforts. We are currently using the original ACT and our engineered variant in mouse immunization experiments to dissect ACT’s role in protection. Notably, addition of our engineered protein to the current acellular vaccine results in 97% increased bacterial clearance during the early stages of disease, likely by protecting macrophages and neutrophils from toxin activites. To provide a therapeutic option before a new vaccine is lisenced, we have developed a humanized antibody, hu1B7, to both treat and prevent pertussis. This has been engineered for high affinity binding, reduced immunogenicity and extended serum half-life. We have shown hu1B7 is protective against disease in mouse and adolescent baboon models of disease. We have also characterized the antibodies’ mechanisms of action, using biochemical, structural and cellular assays. To determine if passive immunization could protect newborns from pertussis infection, hu1B7 was tested in newborn baboons. Two-day-old baboons received hu1B7 (40 mg/kg, IV) and five weeks later were infected with 108 cfu of B. pertussis. Animals were monitored for clinical signs of disease including leukocytosis, coughing, and bacterial colonization. Thu far, 7 hu1B7-treated and 6 control animals have completed the study. Antibody prophylaxis mitigated the clinical signs of pertussis, including leukocytosis (p = 0.004) and coughing, but as expected, did not prevent bacterial colonization (p = 0.15). As a step toward lowering the cost for developing world applications, we have generated and completed in vitro testing of an extended half-life version of hu1B7. Data from baboons treated with this variant will be reporte

Functional analysis of three Arabidopsis ARGONAUTES using slicer-defective mutants

[EN] In RNA-directed silencing pathways, ternary complexes result from small RNA-guided ARGONAUTE (AGO) associating with target transcripts. Target transcripts are often silenced through direct cleavage (slicing), destabilization through slicer-independent turnover mechanisms, and translational repression. Here, wild-type and active-site defective forms of several Arabidopsis thaliana AGO proteins involved in posttranscriptional silencing were used to examine several AGO functions, including small RNA binding, interaction with target RNA, slicing or destabilization of target RNA, secondary small interfering RNA formation, and antiviral activity. Complementation analyses in ago mutant plants revealed that the catalytic residues of AGO1, AGO2, and AGO7 are required to restore the defects of Arabidopsis ago1-25, ago2-1, and zip-1 (AGO7-defective) mutants, respectively. AGO2 had slicer activity in transient assays but could not trigger secondary small interfering RNA biogenesis, and catalytically active AGO2 was necessary for local and systemic antiviral activity against Turnip mosaic virus. Slicer-defective AGOs associated with miRNAs and stabilized AGO-miRNA-target RNA ternary complexes in individual target coimmunoprecipitation assays. In genome-wide AGO-miRNA-target RNA coimmunoprecipitation experiments, slicer-defective AGO1-miRNA associated with target RNA more effectively than did wild-type AGO1-miRNA. These data not only reveal functional roles for AGO1, AGO2, and AGO7 slicer activity, but also indicate an approach to capture ternary complexes more efficiently for genome-wide analyses.We thank Goretti Nguyen for excellent technical assistance. A. C. was supported by a postdoctoral fellowship from the Ministerio de Ciencia e Innovacion (BMC-2008-0188). H.G.-R. was the recipient of a Helen Hay Whitney Postdoctoral fellowship (F-972). This work was supported by grants from the National Science Foundation (MCB-1231726), the National Institutes of Health (AI043288), and Monsanto Corporation.Carbonell, A.; Fahlgren, N.; García-Ruíz, H.; Gilbert, KB.; Montgomery, TA.; Nguyen, T.; Cuperus, JT.... (2012). Functional analysis of three Arabidopsis ARGONAUTES using slicer-defective mutants. The Plant Cell. 24(9):3613-3629. https://doi.org/10.1105/tpc.112.099945S36133629249Allen, E., Xie, Z., Gustafson, A. M., & Carrington, J. C. (2005). microRNA-Directed Phasing during Trans-Acting siRNA Biogenesis in Plants. Cell, 121(2), 207-221. doi:10.1016/j.cell.2005.04.004Aukerman, M. J., & Sakai, H. (2003). Regulation of Flowering Time and Floral Organ Identity by a MicroRNA and Its APETALA2-Like Target Genes. The Plant Cell, 15(11), 2730-2741. doi:10.1105/tpc.016238Axtell, M. J., Jan, C., Rajagopalan, R., & Bartel, D. P. (2006). A Two-Hit Trigger for siRNA Biogenesis in Plants. 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Molecular Cell, 15(2), 173-183. doi:10.1016/j.molcel.2004.06.006Wang, L., Si, Y., Dedow, L. K., Shao, Y., Liu, P., & Brutnell, T. P. (2011). A Low-Cost Library Construction Protocol and Data Analysis Pipeline for Illumina-Based Strand-Specific Multiplex RNA-Seq. PLoS ONE, 6(10), e26426. doi:10.1371/journal.pone.0026426Wang, X.-B., Jovel, J., Udomporn, P., Wang, Y., Wu, Q., Li, W.-X., … Ding, S.-W. (2011). The 21-Nucleotide, but Not 22-Nucleotide, Viral Secondary Small Interfering RNAs Direct Potent Antiviral Defense by Two Cooperative Argonautes in Arabidopsis thaliana    . The Plant Cell, 23(4), 1625-1638. doi:10.1105/tpc.110.082305Wang, Y., Juranek, S., Li, H., Sheng, G., Wardle, G. S., Tuschl, T., & Patel, D. J. (2009). Nucleation, propagation and cleavage of target RNAs in Ago silencing complexes. Nature, 461(7265), 754-761. doi:10.1038/nature08434Wu, L., & Belasco, J. G. (2008). Let Me Count the Ways: Mechanisms of Gene Regulation by miRNAs and siRNAs. 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Single-cell alternative polyadenylation analysis delineates GABAergic neuron types.

BACKGROUND: Alternative polyadenylation (APA) is emerging as an important mechanism in the post-transcriptional regulation of gene expression across eukaryotic species. Recent studies have shown that APA plays key roles in biological processes, such as cell proliferation and differentiation. Single-cell RNA-seq technologies are widely used in gene expression heterogeneity studies; however, systematic studies of APA at the single-cell level are still lacking. RESULTS: Here, we described a novel computational framework, SAPAS, that utilizes 3'-tag-based scRNA-seq data to identify novel poly(A) sites and quantify APA at the single-cell level. Applying SAPAS to the scRNA-seq data of phenotype characterized GABAergic interneurons, we identified cell type-specific APA events for different GABAergic neuron types. Genes with cell type-specific APA events are enriched for synaptic architecture and communications. In further, we observed a strong enrichment of heritability for several psychiatric disorders and brain traits in altered 3' UTRs and coding sequences of cell type-specific APA events. Finally, by exploring the modalities of APA, we discovered that the bimodal APA pattern of Pak3 could classify chandelier cells into different subpopulations that are from different laminar positions. CONCLUSIONS: We established a method to characterize APA at the single-cell level. When applied to a scRNA-seq dataset of GABAergic interneurons, the single-cell APA analysis not only identified cell type-specific APA events but also revealed that the modality of APA could classify cell subpopulations. Thus, SAPAS will expand our understanding of cellular heterogeneity

Additions to Philippine Slender Skinks of the <i>Brachymeles bonitae </i>Complex (Reptilia: Squamata: Scincidae) III:a new species from Tablas Island

Davis, Drew R., Geheber, Aaron D., Watters, Jessa L., Penrod, Michelle L., Feller, Kathryn D., Ashford, Alissa, Kouri, Josh, Nguyen, Daniel, Shauberger, Kathryn, Sheatsley, Kyra, Winfrey, Claire, Wong, Rachel, Sanguila, Marites B., Brown, Rafe M., Siler, Cameron D. (2016): Additions to Philippine Slender Skinks of the Brachymeles bonitae Complex (Reptilia: Squamata: Scincidae) III: a new species from Tablas Island. Zootaxa 4132 (1), DOI: http://doi.org/10.11646/zootaxa.4132.1.