Uncovering the Effectiveness of Post-Sandy Housing Recovery Efforts in New York City

This thesis seeks to examine the effectiveness of post-Sandy CDBG-DR-funded housing recovery efforts in New York City. Using historical precedents to understand federal disaster policy and to identify its common limitations, this research then attempts to analyze the progress of NYC’s existing housing recovery programs. In order to identify the challenges and limitations of these programs, this thesis utilized information gathered from an inspection of available housing recovery data as well as interviews with representatives of various city, state and federal agencies. By combining the quantified progress of NYC’s housing recovery with the varied perspectives of individuals implementing and guiding these efforts, this research attempted to distill the broad successes and failures of different recovery programs. Taking these lessons, several recommendations are provided with the goal of improving the effectiveness of future CDBG-DR-housing recovery efforts

High Performance Liquid Chromatography (HPLC) for Ampicillin and Cefuroxime

Appropriate levels of an active pharmaceutical ingredient (API) in medicines must be present in a medical product for the patient to receive therapeutic value. High performance liquid chromatography (HPLC) was used to develop a methodology to test for the API in Ampicillin and Cefuroxime drugs. Following the regulations of the Distributed Pharmaceutical Analysis Lab (DPAL) out of Notre Dame system sustainability requirements linearity, precision, accuracy/range, spike/degraded spike, limit of detection /quantitation, tailing factor, and number of theoretical plates were experimentally determined to meet the excepted standards

Percy Julian and the Rise in Inclusive Pedagogy in the Department of Chemistry and Biochemistry

As a research fellow at DePauw, Dr. Percy L. Julian included undergratuate students in his research to synthesize physostigmine. Building on that legacy, the Department of Chemistry and Biochemistry continues a longstanding history of supporting undergraduate research. Recongnizing tht there is inequity in who participates in research, our department recently initiated an application process open to all students in our courses to equalize the way in which stuents learn about and get started in research. Students in our structure and propterties of organiz molecules course view and reflect on the Forgotten Genius documentary and the recently awarded HHMU Inclusive Excellence Initiative grant has provided many faculty members development opportunities in inclusive pedagogy. In May, Dr. Julian was appointed posthumously to the DePauw University faculty. The Department of Chemistry and Biochemistry celebrates this appointment and continues to work toward creating a positive and inviting atmosphere for all students at DePauw

Method Development for the Analysis of Pharmaceuticals Using High Performance Liquid Chromatography

Since 2013, there have been 1500 reports of counterfeit drugs to WHO, especially from African, American, and European regions 1. Tackling the problem of poor drug quality, the Distributed Pharmaceutical Analysis Lab (DPAL) provides a quality analysis to quantify active pharmaceutical ingredient contents with a goal to trigger a report to the MRA or WHO2. With the support of DPAL, we would like to perform a series of chromatography experiments using the HPLC in order to identify and quantify the active pharmaceutical ingredients (API) of Amoxicillin and Ciprofloxacin

Lab-on-a-Bubble: Synthesis, Characterization, and Evaluation of Buoyant Gold Nanoparticle-Coated Silica Spheres

This paper describes the development and preparation of a new class of materials for surface-enhanced Raman scattering (SERS) consisting of gold nanoparticles coated onto hollow, buoyant silica microspheres. These materials allow for a new type of molecular assay designated as a lab-on-a-bubble (LoB). LoB materials serve as a convenient platform for the detection of analytes in solution and offer several advantages over traditional colloidal gold and planar SERS substrates, such as the ability to localize and concentrate analytes for detection. An example assay is presented using the LoB method and cyanide detection. Cyanide binds to SERS-active, gold-coated LoBs and is detected directly from the corresponding SERS signal. The abilities of LoBs and a gold colloid to detect cyanide are compared, and in both cases, a detection limit of ∼170 ppt was determined. Differences in measurement error using LoBs versus gold colloid are also described, as well as an assay for 5,5′-dithiobis(2-nitrobenzoic acid) that shows the benefit of using LoBs over SERS analyses in colloids, which are often plagued by particle aggregation

A first-in-class small molecule inhibitor of the COP9 signalosome subunit 5 for the treatment of cancer

The COP9 signalosome (CSN) is the platform for assembly and disassembly of cullin-RING E3 ubiquitin ligases (CRL), which comprise the largest enzyme family of the ubiquitin proteasome system (UPS) in humans1-4 . Over 200 CRL complexes are implicated in the regulation of almost all cellular processes including cell cycle progression, transcription, and apoptosis5, and aberrant CRL activity is frequently associated with cancer6-8. Since CSN functions as the protease which cleaves the ubiquitin-like protein Nedd8 from CRLs and thereby initiates their remodelling, inhibitors of the catalytic subunit CSN59 may have therapeutic potential for the treatment of tumours10,11. Here we present CSN5i- 3, a potent, selective and orally available small molecule inhibitor of CSN5. The compound traps CRLs in the neddylated, active state leading to the autoinactivation of a subset of CRLs, e.g. SCFSkp2, by inducing the degradation of their substrate recognition module (SRM). As a result, the corresponding CRL substrates are stabilized, e.g. tumour suppressors p21 and p27. Surprisingly, we also found CRLs, e.g. SCFβTrCP, whose SRMs are not degraded upon CSN5 inhibition, and their substrates remain unaffected. CSN5i-3 differentially affected tumour cell lines and suppressed growth of a human xenograft in mice. Our results provide insights into how CSN regulates CRLs and suggest that CSN5 inhibition has therapeutic potential for the treatment of cancer

Human cytomegalovirus UL40 signal peptide regulates cell surface expression of the NK cell ligands HLA-E and gpUL18

Human CMV (HCMV)-encoded NK cell-evasion functions include an MHC class I homolog (UL18) with high affinity for the leukocyte inhibitory receptor-1 (CD85j, ILT2, or LILRB1) and a signal peptide (SP(UL40)) that acts by upregulating cell surface expression of HLA-E. Detailed characterization of SP(UL40) revealed that the N-terminal 14 aa residues bestowed TAP-independent upregulation of HLA-E, whereas C region sequences delayed processing of SP(UL40) by a signal peptide peptidase-type intramembrane protease. Most significantly, the consensus HLA-E-binding epitope within SP(UL40) was shown to promote cell surface expression of both HLA-E and gpUL18. UL40 was found to possess two transcription start sites, with utilization of the downstream site resulting in translation being initiated within the HLA-E-binding epitope (P2). Remarkably, this truncated SP(UL40) was functional and retained the capacity to upregulate gpUL18 but not HLA-E. Thus, our findings identify an elegant mechanism by which an HCMV signal peptide differentially regulates two distinct NK cell-evasion pathways. Moreover, we describe a natural SP(UL40) mutant that provides a clear example of an HCMV clinical virus with a defect in an NK cell-evasion function and exemplifies issues that confront the virus when adapting to immunogenetic diversity in the host