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BACKGROUND: Despite substantial illness burden and healthcare utilization conferred by pain from vaso-occlusive episodes (VOE) in children with sickle cell disease (SCD), disease-modifying therapies to effectively treat SCD-VOE are lacking. The aim of the Sickle Cell Disease Treatment with Arginine Therapy (STArT) Trial is to provide definitive evidence regarding the efficacy of intravenous arginine as a treatment for acute SCD-VOE among children, adolescents, and young adults. METHODS: STArT is a double-blind, placebo-controlled, randomized, phase 3, multicenter trial of intravenous arginine therapy in 360 children, adolescents, and young adults who present with SCD-VOE. The STArT Trial is being conducted at 10 sites in the USA through the Pediatric Emergency Care Applied Research Network (PECARN). Enrollment began in 2021 and will continue for 5 years. Within 12 h of receiving their first dose of intravenous opioids, enrolled participants are randomized 1:1 to receive either (1) a one-time loading dose of L-arginine (200 mg/kg with a maximum of 20 g) administered intravenously followed by a standard dose of 100 mg/kg (maximum 10 g) three times a day or (2) a one-time placebo loading dose of normal saline followed by normal saline three times per day at equivalent volumes and duration as the study drug. Participants, research staff, and investigators are blinded to the participant's randomization. All clinical care is provided in accordance with the institution-specific standard of care for SCD-VOE based on the 2014 National Heart, Lung, and Blood Institute guidelines. The primary outcome is time to SCD-VOE pain crisis resolution, defined as the time (in hours) from study drug delivery to the last dose of parenteral opioid delivery. Secondary outcomes include total parental opioid use and patient-reported outcomes. In addition, the trial will characterize alterations in the arginine metabolome and mitochondrial function in children with SCD-VOE. DISCUSSION: Buildin

Presents an instructional resource on Haitian art and provides historical information on Haiti. Features four artists: (1) Hector Hyppolite; (2) Edouard Duval-Carrie; (3) Paul Claude Gardere; and (4) Bien-Aime Sylvain. Includes background information on each artist, learning activities, and reproductions of their artwork. (CMK)

This dissertation examines how the aesthetic, sexual, and gendered concerns of men's highly wrought compares with contemporary women writers. While both men and women writers remain preoccupied with similar issues surrounding gender, desire, and reform, men's fiction departs from this shared project in the manner in which they focus on issues of manhood and masculinity. My dissertation calls attention to how male authors' use of the highly wrought style, a literary aesthetic traditionally associated with women's fiction, to explore heterodox masculine desire and imagination in 19th century America., Doctor of Philosophy

Surveillance of the extracellular environment by immune receptors is of central importance to eukaryotic survival. The rice receptor kinase XA21, which confers robust resistance to most strains of the Gram-negative bacterium Xanthomonas oryzae pv. oryzae (Xoo), is representative of a large class of cell surface immune receptors in plants and animals. We report the identification of a previously undescribed Xoo protein, called RaxX, which is required for activation of XA21-mediated immunity. Xoo strains that lack RaxX, or carry mutations in the single RaxX tyrosine residue (Y41), are able to evade XA21-mediated immunity. Y41 of RaxX is sulfated by the prokaryotic tyrosine sulfotransferase RaxST. Sulfated, but not nonsulfated, RaxX triggers hallmarks of the plant immune response in an XA21-dependent manner. A sulfated, 21-amino acid synthetic RaxX peptide (RaxX21-sY) is sufficient for this activity. Xoo field isolates that overcome XA21-mediated immunity encode an alternate raxX allele, suggesting that coevolutionary interactions between host and pathogen contribute to RaxX diversification. RaxX is highly conserved in many plant pathogenic Xanthomonas species. The new insights gained from the discovery and characterization of the sulfated protein, RaxX, can be applied to the development of resistant crop varieties and therapeutic reagents that have the potential to block microbial infection of both plants and animals.

We used a molecular screen to identify genes upregulated in regenerating adult rat dorsal root ganglion cells. FLRT3 mRNA and protein characterized by a fibronectin type III domain and a leucine-rich repeat motif was upregulated in damaged sensory neurons. The protein was then transported into their peripheral and central processes where the FLRT3 protein was localized to presynaptic axon terminals. In vitro, the FLRT3 protein was expressed at the cell surface, regulated neurite outgrowth in sensory neurons, but did not exhibit homophilic binding. FLRT3 was widely expressed in the developing embryo, particularly in the central nervous system and somites. However, in the adult, we found no evidence for accumulation or reexpression of the FLRT3 protein in damaged axons of the central nervous system. We conclude that FLRT3 codes for a putative cell surface receptor implicated in both the development of the nervous system and in the regeneration of the peripheral nervous system (PNS).

Writing Guide with Handbook aligns to the goals, topics, and objectives of many first-year writing and composition courses. It is organized according to relevant genres, and focuses on the writing process, effective writing practices or strategies including graphic organizers, writing frames, and word banks to support visual learning and conventions of usage and style. The text includes an editing and documentation handbook, which provides information on grammar and mechanics, common usage errors, and citation styles. Writing Guide with Handbook breaks down barriers in the field of composition by offering an inviting and inclusive approach to students of all intersectional identities. To meet this goal, the text creates a reciprocal relationship between everyday rhetoric and the evolving world of academia. Writing Guide with Handbook builds on students' life experiences and their participation in rhetorical communities within the familiar contexts of personal interaction and social media. The text seeks to extend these existing skills by showing students how to construct a variety of compelling compositions in a variety of formats, situations, and contexts. The authors conceived and developed Writing Guide with Handbook in 2020; its content and learning experiences reflect the instructional, societal, and individual challenges students have faced. The authors invite students and instructors to practice invitational discussions even as they engage in verbal and written argument. Instructors will be empowered to emphasize meaning and voice and to teach empathy as a rhetorical strategy. Students will be empowered to negotiate their identities and their cultures through language as they join us in writing, discovering, learning, and creating.