The Challenge of Diversity

This essay addresses the role of Sacred Heart University within the community of Bridgeport, a community of great diversity of ethnic groups, races, religions and social classes. Father Fitzpatrick uses the Gospels to explain his message that there is a miracle of unity in diversity; One Church, Many Cultures. This essay was presented at the First Presidential Lecture Series at Sacred Heart University on October 8, 1988

Hydrologic and Hydraulic Modeling of the Tunnel and Reservoir Plan System in Northeastern Illinois

The Tunnel and Reservoir Plan (TARP) was adopted by the Metropolitan Sanitary District of Greater Chicago in 1972 to address combined sewer overflow (CSO) pollution and flooding problems in 970 km2 of the Chicago metropolitan area served by combined sewers. TARP consists of about 175 km of tunnels, three reservoirs, 256 drop shafts, and over 600 connecting structures, pumping stations, and other appurtenances for the capture and storage of CSOs and for conveying the stored CSOs to water reclamation plants for treatment. The TARP system is comprised of three independent systems: the Calumet system serving the south suburbs and a portion of the south side of Chicago, the Upper Des Plaines system serving the northwest suburbs, and the Mainstream/ Des Plaines system serving the remainder of Chicago and the north, west and southwest suburbs. The Metropolitan Water Reclamation District of Greater Chicago (MWRDGC) desires to develop new, updated and enhanced computer models to allow for simulation of the TARP systems. The new models will be used to optimize operation of the system as actually constructed, to determine constraints in the system, identify physical changes that may be needed to improve performance, and allow what-if analyses to be performed for potential storm scenarios and facility revisions. The modeling includes development of a Physical Inventory system, Hydraulic Modeling of the TARP systems, and Hydrologic Modeling of the TARP service areas. The Physical Inventory provides a digital description of the physical geometry of the TARP system and the related hydraulic performance of system components. Hydrologic Modeling uses data for each dropshafts service area to determine hydrographs describing the inflows to the TARP systems. A ma jor component of the Hydrologic Modeling is to develop tools and methods that allow robust simulation of the extreme heterogeneity of highly urbanized systems and that provide guidance for data compilation needed to improve the accuracy of such simulations. Hydraulic Modeling uses the information from the Physical Inventory and the Hydrologic Modeling to simulate hydraulic response of the TARP system to different inputs. The Hydraulic Modeling tools developed are capable of simulating the range of possible flows in the system, from gravity flows over a dry bed to mixed gravity/surcharged flows to shocks and hydraulic transients

Intraoperative electrocochleographic characteristics of auditory neuropathy spectrum disorder in cochlear implant subjects

Auditory neuropathy spectrum disorder (ANSD) is characterized by an apparent discrepancy between measures of cochlear and neural function based on auditory brainstem response (ABR) testing. Clinical indicators of ANSD are a present cochlear microphonic (CM) with small or absent wave V. Many identified ANSD patients have speech impairment severe enough that cochlear implantation (CI) is indicated. To better understand the cochleae identified with ANSD that lead to a CI, we performed intraoperative round window electrocochleography (ECochG) to tone bursts in children (n = 167) and adults (n = 163). Magnitudes of the responses to tones of different frequencies were summed to measure the “total response” (ECochG-TR), a metric often dominated by hair cell activity, and auditory nerve activity was estimated visually from the compound action potential (CAP) and auditory nerve neurophonic (ANN) as a ranked “Nerve Score”. Subjects identified as ANSD (45 ears in children, 3 in adults) had higher values of ECochG-TR than adult and pediatric subjects also receiving CIs not identified as ANSD. However, nerve scores of the ANSD group were similar to the other cohorts, although dominated by the ANN to low frequencies more than in the non-ANSD groups. To high frequencies, the common morphology of ANSD cases was a large CM and summating potential, and small or absent CAP. Common morphologies in other groups were either only a CM, or a combination of CM and CAP. These results indicate that responses to high frequencies, derived primarily from hair cells, are the main source of the CM used to evaluate ANSD in the clinical setting. However, the clinical tests do not capture the wide range of neural activity seen to low frequency sounds

The Effective Field Theory of Cosmological Large Scale Structures

Large scale structure surveys will likely become the next leading cosmological probe. In our universe, matter perturbations are large on short distances and small at long scales, i.e. strongly coupled in the UV and weakly coupled in the IR. To make precise analytical predictions on large scales, we develop an effective field theory formulated in terms of an IR effective fluid characterized by several parameters, such as speed of sound and viscosity. These parameters, determined by the UV physics described by the Boltzmann equation, are measured from N-body simulations. We find that the speed of sound of the effective fluid is c_s^2 10^(-6) and that the viscosity contributions are of the same order. The fluid describes all the relevant physics at long scales k and permits a manifestly convergent perturbative expansion in the size of the matter perturbations \delta(k) for all the observables. As an example, we calculate the correction to the power spectrum at order \delta(k)^4. The predictions of the effective field theory are found to be in much better agreement with observation than standard cosmological perturbation theory, already reaching percent precision at this order up to a relatively short scale k \sim 0.24 h/Mpc.Comment: v2: typos corrected, JHEP published versio

UV Absorption Lines from High-Velocity Gas in the Vela Supernova Remnant: New insights from STIS Echelle Observations of HD72089

The star HD72089 is located behind the Vela supernova remnant and shows a complex array of high and low velocity interstellar absorption features arising from shocked clouds. A spectrum of this star was recorded over the wavelength range 1196.4 to 1397.2 Angstroms at a resolving power lambda/Delta lambda = 110,000 and signal-to-noise ratio of 32 by STIS on the Hubble Space Telescope. We have identified 7 narrow components of C I and have measured their relative populations in excited fine-structure levels. Broader features at heliocentric velocities ranging from -70 to +130 km/s are seen in C II, N I, O I, Si II, S II and Ni II. In the high-velocity components, the unusually low abundances of N I and O I, relative to S II and Si II, suggest that these elements may be preferentially ionized to higher stages by radiation from hot gas immediately behind the shock fronts.Comment: 11 pages, 2 figures, Latex. Submitted for the special HST ERO issue of the Astrophysical Journal Letter

A Gerbil Model of Sloping Sensorineural Hearing Loss

The goal of the overall project is to develop knowledge about cochlear physiology during cochlear implantation and develop procedures for assessing its status during hearing preservation surgery. As a step toward this goal, for this study, we established an animal model of sloping high frequency sensorineural hearing loss that mimics the hearing condition of candidates for combined electric-acoustic stimulation

Short-read whole genome sequencing identifies causative variants in most individuals with previously unexplained aniridia

Background: Classic aniridia is a highly penetrant autosomal dominant disorder characterised by congenital absence of the iris, foveal hypoplasia, optic disc anomalies and progressive opacification of the cornea. >90% of cases of classic aniridia are caused by heterozygous, loss-of-function variants affecting the PAX6 locus. Methods Short-read whole genome sequencing was performed on 51 (39 affected) individuals from 37 different families who had screened negative for mutations in the PAX6 coding region. Results Likely causative mutations were identified in 22 out of 37 (59%) families. In 19 out of 22 families, the causative genomic changes have an interpretable deleterious impact on the PAX6 locus. Of these 19 families, 1 has a novel heterozygous PAX6 frameshift variant missed on previous screens, 4 have single nucleotide variants (SNVs) (one novel) affecting essential splice sites of PAX6 5′ non-coding exons and 2 have deep intronic SNV (one novel) resulting in gain of a donor splice site. In 12 out of 19, the causative variants are large-scale structural variants; 5 have partial or whole gene deletions of PAX6, 3 have deletions encompassing critical PAX6 cis-regulatory elements, 2 have balanced inversions with disruptive breakpoints within the PAX6 locus and 2 have complex rearrangements disrupting PAX6. The remaining 3 of 22 families have deletions encompassing FOXC1 (a known cause of atypical aniridia). Seven of the causative variants occurred de novo and one cosegregated with familial aniridia. We were unable to establish inheritance status in the remaining probands. No plausibly causative SNVs were identified in PAX6 cis-regulatory elements. Conclusion Whole genome sequencing proves to be an effective diagnostic test in most individuals with previously unexplained aniridia

Monoallelic variants resulting in substitutions of MAB21L1 Arg51 Cause Aniridia and microphthalmia

Classical aniridia is a congenital and progressive panocular disorder almost exclusively caused by heterozygous loss-of-function variants at the PAX6 locus. We report nine individuals from five families with severe aniridia and/or microphthalmia (with no detectable PAX6 mutation) with ultrarare monoallelic missense variants altering the Arg51 codon of MAB21L1. These mutations occurred de novo in 3/5 families, with the remaining families being compatible with autosomal dominant inheritance. Mice engineered to carry the p.Arg51Leu change showed a highly-penetrant optic disc anomaly in heterozygous animals with severe microphthalmia in homozygotes. Substitutions of the same codon (Arg51) in MAB21L2, a close homolog of MAB21L1, cause severe ocular and skeletal malformations in humans and mice. The predicted nucleotidyltransferase function of MAB21L1 could not be demonstrated using purified protein with a variety of nucleotide substrates and oligonucleotide activators. Induced expression of GFP-tagged wildtype and mutant MAB21L1 in human cells caused only modest transcriptional changes. Mass spectrometry of immunoprecipitated protein revealed that both mutant and wildtype MAB21L1 associate with transcription factors that are known regulators of PAX6 (MEIS1, MEIS2 and PBX1) and with poly(A) RNA binding proteins. Arg51 substitutions reduce the association of wild-type MAB21L1 with TBL1XR1, a component of the NCoR complex. We found limited evidence for mutation-specific interactions with MSI2/Musashi-2, an RNA-binding proteins with effects on many different developmental pathways. Given that biallelic loss-of-function variants in MAB21L1 result in a milder eye phenotype we suggest that Arg51-altering monoallelic variants most plausibly perturb eye development via a gain-of-function mechanism

Orally Active Adenosine A 1 Receptor Agonists with Antinociceptive Effects in Mice

Adenosine A1 receptor (A1AR) agonists have antinociceptive effects in multiple preclinical models of acute and chronic pain. Although numerous A1AR agonists have been developed, clinical applications of these agents have been hampered by their cardiovascular side effects. Herein we report a series of novel A1AR agonists, some of which are structurally related to adenosine 5′-monophosphate (5′-AMP), a naturally occurring nucleotide that itself activates A1AR. These novel compounds potently activate A1AR in several orthogonal in vitro assays and are subtype selective for A1AR over A2AAR, A2BAR, and A3AR. Among them, UNC32A (3a) is orally active and has dose-dependent antinociceptive effects in wild-type mice. The antinociceptive effects of 3a were completely abolished in A1AR knockout mice, revealing a strict dependence on A1AR for activity. The apparent lack of cardiovascular side effects when administered orally and high affinity (Ki of 36 nM for the human A1AR) make this compound potentially suitable as a therapeutic