New United Center Arena (semester?), IPRO 335: United Center Replacement IPRO 335 IPRO Day Presentation Sp06

This project involves design of a multipurpose sporting arena to be located within the city of Chicago. The arena should seat a capacity of about 20,000 spectators and will house such sports as pro and college basketball, ice hockey, arena football, and also will be used for musical events. Assume the arena is to be located at the current location of United Center with the same amount of above ground area available for parking.Deliverables for IPRO 335: New United Center Arena for the Spring 2006 semeste

New United Center Arena (semester?), IPRO 335

This project involves design of a multipurpose sporting arena to be located within the city of Chicago. The arena should seat a capacity of about 20,000 spectators and will house such sports as pro and college basketball, ice hockey, arena football, and also will be used for musical events. Assume the arena is to be located at the current location of United Center with the same amount of above ground area available for parking.Deliverables for IPRO 335: New United Center Arena for the Spring 2006 semeste

New United Center Arena (semester?), IPRO 335: United Center Replacement IPRO 335 Abstract Sp06

This project involves design of a multipurpose sporting arena to be located within the city of Chicago. The arena should seat a capacity of about 20,000 spectators and will house such sports as pro and college basketball, ice hockey, arena football, and also will be used for musical events. Assume the arena is to be located at the current location of United Center with the same amount of above ground area available for parking.Deliverables for IPRO 335: New United Center Arena for the Spring 2006 semeste

New United Center Arena (semester?), IPRO 335: United Center Replacement IPRO 335 Poster Sp06

This project involves design of a multipurpose sporting arena to be located within the city of Chicago. The arena should seat a capacity of about 20,000 spectators and will house such sports as pro and college basketball, ice hockey, arena football, and also will be used for musical events. Assume the arena is to be located at the current location of United Center with the same amount of above ground area available for parking.Deliverables for IPRO 335: New United Center Arena for the Spring 2006 semeste

New United Center Arena (semester?), IPRO 335: United Center Replacement IPRO 335 Final Report Sp06

This project involves design of a multipurpose sporting arena to be located within the city of Chicago. The arena should seat a capacity of about 20,000 spectators and will house such sports as pro and college basketball, ice hockey, arena football, and also will be used for musical events. Assume the arena is to be located at the current location of United Center with the same amount of above ground area available for parking.Deliverables for IPRO 335: New United Center Arena for the Spring 2006 semeste

Errors in the Diagnosis of Visual Field Progression in Normal-tension Glaucoma

Background: Despite strictly defined criteria for visual field progression in the ongoing Normal-tension Glaucoma Study, the authors noted a surprisingly large number of patients reaching the endpoint. Traditional methods could not be used to check the diagnostic accuracy of their criteria, because no "gold standard" was established for distinguishing true change from physiologic long-term fluctuation. Methods: The authors developed a statistical method based on the results of duplicate tests for progression in their subjects. This method allowed the authors to assess the sensitivity, specificity, and predictive values of their diagnostic criterion. It also estimated the true incidence of progression and provided standard errors for the estimates. Results: The authors found that their original strict criteria for progression, based on duplicate testing, produced false calls of progression 57% of the time. By raising the requirement for deterioration and by repeating the entire sequence of duplicate testing once more, the authors have successfully reduced the rate of false calls to 2%. Conclusion: Accuracy in recognizing progression is improved by not accepting small changes as evidence of progression and by confirming the findings on repeat testing

Dominant negative variants in IKZF2 cause ICHAD syndrome, a new disorder characterised by immunodysregulation, craniofacial anomalies, hearing impairment, athelia and developmental delay

BackgroundHelios (encoded by IKZF2), a member of the Ikaros family of transcription factors, is a zinc finger protein involved in embryogenesis and immune function. Although predominantly recognised for its role in the development and function of T lymphocytes, particularly the CD4+ regulatory T cells (Tregs), the expression and function of Helios extends beyond the immune system. During embryogenesis, Helios is expressed in a wide range of tissues, making genetic variants that disrupt the function of Helios strong candidates for causing widespread immune-related and developmental abnormalities in humans.MethodsWe performed detailed phenotypic, genomic and functional investigations on two unrelated individuals with a phenotype of immune dysregulation combined with syndromic features including craniofacial differences, sensorineural hearing loss and congenital abnormalities.ResultsGenome sequencing revealed de novo heterozygous variants that alter the critical DNA-binding zinc fingers (ZFs) of Helios. Proband 1 had a tandem duplication of ZFs 2 and 3 in the DNA-binding domain of Helios (p.Gly136_Ser191dup) and Proband 2 had a missense variant impacting one of the key residues for specific base recognition and DNA interaction in ZF2 of Helios (p.Gly153Arg). Functional studies confirmed that both these variant proteins are expressed and that they interfere with the ability of the wild-type Helios protein to perform its canonical function—repressing IL2 transcription activity—in a dominant negative manner.ConclusionThis study is the first to describe dominant negative IKZF2 variants. These variants cause a novel genetic syndrome characterised by immunodysregulation, craniofacial anomalies, hearing impairment, athelia and developmental delay

Loss-of-function in RBBP5 results in a syndromic neurodevelopmental disorder associated with microcephaly

Epigenetic dysregulation has been associated with many inherited disorders. RBBP5 (HGNC:9888) encodes a core member of the protein complex that methylates histone 3 lysine-4 (H3K4) and has not been implicated in human disease. We identify five unrelated individuals with de novo heterozygous variants in RBBP5. Three nonsense/frameshift and two missense variants were identified in probands with neurodevelopmental symptoms including global developmental delay, intellectual disability, microcephaly, and short stature. Here, we investigate the pathogenicity of the variants through protein structural analysis and transgenic Drosophila models. Both missense p.(T232I) and p.(E296D) variants affect evolutionarily conserved amino acids located at the interface between RBBP5 and the nucleosome. In Drosophila, overexpression analysis identifies partial loss-of-function mechanisms when the variants are expressed using the fly Rbbp5 or human RBBP5 cDNA. Loss of Rbbp5 leads to a reduction in brain size. The human reference or variant transgenes fail to rescue this loss and expression of either missense variant in an Rbbp5 null background results in a less severe microcephaly phenotype than the human reference, indicating both missense variants are partial loss-of-function alleles. Haploinsufficiency of RBBP5 observed through de novo null and hypomorphic loss-of-function variants is associated with a syndromic neurodevelopmental disorder. Huang et al. report the first functional validation of candidate pathological variants in RBBP5. We present three truncating p.(K244Nfs*6), p.(W254*), p.(R307*) and two missense p.(T232I), p.(E296D) variants found de novo in affected individuals sharing phenotypes including microcephaly and short stature. RBBP5 is a core member of the COMPASS complex responsible for H3 lysine 4 methylation to activate developmental target genes (COMPASS complex adapted from Namitz et al., 2023). Differentiation of neural stem cells in humans and neuroblasts in Drosophila is conserved allowing for the study of neural development in the fly model organism (neural stem cell/neuroblast differentiation diagram adapted from Kim and Hirth, 2009). We used overexpression and rescue experiments to characterize the missense variants in the fly. Neural progenitor populations were evaluated in the larval brain and tissue specific phenotypes were quantified using adult eye and wing morphology studies. We identify that the truncating and missense variants are loss-of-function alleles. As additional patients are identified, the full phenotypic spectrum of RBBP5-related disorders will be elucidated. Created with Biorender.com. [Display omitted

Biallelic variants in ribonuclease inhibitor (RNH1), an inflammasome modulator, are associated with a distinctive subtype of acute, necrotizing encephalopathy

Mendelian etiologies for acute encephalopathies in previously healthy children are poorly understood, with the exception of RAN binding protein 2 (RANBP2)–associated acute necrotizing encephalopathy subtype 1 (ANE1). We provide clinical, genetic, and neuroradiological evidence that biallelic variants in ribonuclease inhibitor (RNH1) confer susceptibility to a distinctive ANE subtype. This study aimed to evaluate clinical data, neuroradiological studies, genomic sequencing, and protein immunoblotting results in 8 children from 4 families who experienced acute febrile encephalopathy. All 8 healthy children became acutely encephalopathic during a viral/febrile illness and received a variety of immune modulation treatments. Long-term outcomes varied from death to severe neurologic deficits to normal outcomes. The neuroradiological findings overlapped with ANE but had distinguishing features. All affected children had biallelic predicted damaging variants in RNH1: a subset that was studied had undetectable RNH1 protein. Incomplete penetrance of the RNH1 variants was evident in 1 family. Biallelic variants in RNH1 confer susceptibility to a subtype of ANE (ANE2) in previously healthy children. Intensive immunological treatments may alter outcomes. Genomic sequencing in children with unexplained acute febrile encephalopathy can detect underlying genetic etiologies, such as RNH1, and improve outcomes in the probands and at-risk siblings