Substrate Trafficking Within the Type VII Secretion Systems of Pathogenic Mycobacteria

Tuberculosis (TB), primarily caused by infection of Mycobacterium tuberculosis (Mtb) in the lungs, is the deadliest infectious bacterial disease killing 1.5 million people annually. A major determinant of virulence is active secretion through three specialized type VII secretion (ESX) systems; ESX-1, ESX-3, and ESX-5. A large group of substrates exported by the ESX systems is the PE (Proline-Glutamine) and PPE (Proline-Proline-Glutamate) families of proteins, which are highly expanded in the pathogenic species of Mycobacteria and encompass over 7% of Mtb’s genome coding capacity. PE and PPE proteins interact together to form PE-PPE heterodimers, and are secreted through specific ESX systems. Despite this massive expansion and the implication of a few select members in key virulence processes, most family members have still undefined functions. This can be partially attributed to previously reported difficulties of working with the purified proteins in vitro and a poor understanding of how heterodimer pairs are trafficked within the mycobacterial cell to their cognate ESX system. Each ESX system that secretes PE-PPE heterodimers encodes a unique copy of the chaperone protein, EspG. The work contained here aims to elucidate the mechanism of PE-PPE heterodimer recognition by EspG for the ESX-3 and ESX-5 systems. Structural analysis of ESX-3-specific PE5-PPE4-EspG3 heterotrimer shows that EspG3 and EspG5 employ unique binding modes to their cognate PE-PPE heterodimers, which presents unique interfaces of the highly conserved PPE proteins to each EspG. The ESX-5-specific PPE proteins are variable at the hydrophobic (hh) motif, which is shielded from solvent upon binding of EspG. Structural analysis of selected hh mutants in the context of the PE25-PPE41-EspG5 suggested plasticity within the PPE-binding region of EspG5 to allow it to bind the various ESX-5-specific PPE proteins. Taken together, these results improve our understanding of trafficking of an important group of ESX substrates, setting the stage for more targeted studies of individual PE and PPE proteins to determine the still unknown functions of most family members. This may prove to be a fruitful avenue of therapeutic development to lower the burden of the global public health emergency caused by TB

fflonk: a Fast-Fourier inspired verifier efficient version of PlonK

We present a variant of the Kate, Zaverucha and Goldberg polynomial commitment scheme [KZG] where $d$ polynomials can be opened at a point that is a $d$\u27th power, such that the amount of verifier group operations does not depend on $d$. Our method works by reducing opening multiple polynomials at a single point $x$, to opening a single polynomial at many points via an ``FFT-like identity\u27\u27. As an application we present a version of the PlonK zk-SNARK[GWC] with significantly improved verifier performance, at the cost roughly tripling the prover time. Specifically, in addition to the two pairings, the verifier only performs five scalar multiplications, rather than 16 or 18 as in the versions presented in [GWC]

plookup: A simplified polynomial protocol for lookup tables

We present a protocol for checking the values of a committed polynomial $f\in \mathbb{F}_{<n}[X]$ over a multiplicative subgroup $H\subset \mathbb{F}$ of size $n$, are contained in the values of a table $t\in \mathbb{F}^d$. Our protocol can be viewed as a simplification of one from Bootle et. al [BCGJM, ASIACRYPT 2018] for a similar problem, with potential efficiency improvements when $d\leq n$. In particular, [BCGJM]\u27s protocol requires comitting to several auxiliary polynomials of degree $d\cdot \log n$, whereas ours requires three commitments to auxiliary polynomials of degree $n$, which can be much smaller in the case $d\sim n$. One common use case of this primitive in the zk-SNARK setting is a ``batched range proof\u27\u27, where one wishes to check all of $f$\u27s values on $H$ are in a range $[0,\ldots,M]$. We present a slightly optimized protocol for this special case, and pose improving it as an open problem

PLONK: Permutations over Lagrange-bases for Oecumenical Noninteractive arguments of Knowledge

zk-SNARK constructions that utilize an updatable universal structured reference string remove one of the main obstacles in deploying zk-SNARKs [GKMMM, Crypto 2018]. The important work of Maller et al. [MBKM, CCS 2019] presented $\mathsf{Sonic}$ - the first potentially practical zk-SNARK with fully succinct verification for general arithmetic circuits with such an SRS. However, the version of $\mathsf{Sonic}$ enabling fully succinct verification still requires relatively high proof construction overheads. We present a universal SNARK construction with fully succinct verification, and significantly lower prover running time (roughly 7.5-20 less group exponentiations than [MBKM] in the fully succinct verifier mode depending on circuit structure). Similarly to [MBKM], we rely on a permutation argument based on Bayer and Groth [Eurocrypt 2012]. However, we focus on ``Evaluations on a subgroup rather than coefficients of monomials\u27\u27; which enables simplifying both the permutation argument and the artihmetization step

Where’s the EASY Button? Uncovering E-Book Usability

E-book platforms have multiplied among vendors and publishers, complicating not only acquisitions and collection development decisions, but also the user experience. Using a methodology of task-based user testing, the researchers sought to measure and compare user performance of eight common tasks on nine e-book platforms: EBSCO eBooks, ProQuest Ebook Central, Gale Virtual Reference Library (GVRL), Oxford Reference, Safari Books Online, IGI Global, CRCnetBASE, Springer Link, and JSTOR. Success and failure rates per task, average time spent per task, and user comments were evaluated to gauge the usability of each platform. Findings indicate that platforms vary widely in terms of users’ ability and speed in completing known-item searches, navigation tasks, and identification of specialized tools, with implications for library acquisition and user instruction decisions. Results also suggest several key vendor design recommendations for an optimal user experience. The study did not aim to declare a “winning” platform, and all the platforms tested demonstrated both strengths and weaknesses in different aspects, but overall performance and user preference favored ProQuest’s Ebook Central platform.Librar

Peptide Inhibitors Targeting the \u3cem\u3eNeisseria gonorrhoeae\u3c/em\u3e Pivotal Anaerobic Respiration Factor AniA

Neisseria gonorrhoeae causes the sexually transmitted infection gonorrhea, which is highly prevalent worldwide and has a major impact on reproductive and neonatal health. The superbug status of N. gonorrhoeae necessitates the development of drugs with different mechanisms of action. Here, we focused on targeting the nitrite reductase AniA, which is a pivotal component of N. gonorrhoeae anaerobic respiration and biofilm formation. Our studies showed that gonococci expressing AniA containing the altered catalytic residues D137A and H280A failed to grow under anaerobic conditions, demonstrating that the nitrite reductase function is essential. To facilitate the pharmacological targeting of AniA, new crystal structures of AniA were refined to 1.90-Å and 2.35-Å resolutions, and a phage display approach with libraries expressing randomized linear dodecameric peptides or heptameric peptides flanked by a pair of cysteine residues was utilized. Biopanning experiments led to the identification of 29 unique peptides, with 1 of them, C7-3, being identified multiple times. Evaluation of their ability to interact with AniA using enzyme-linked immunosorbent assay and computational docking studies revealed that C7-3 was the most promising inhibitor, binding near the type 2 copper site of the enzyme, which is responsible for interaction with nitrite. Subsequent enzymatic assays and biolayer interferometry with a synthetic C7-3 and its derivatives, C7-3m1 and C7-3m2, demonstrated potent inhibition of AniA. Finally, the MIC50 value of C7-3 and C7-3m2 against anaerobically grown N. gonorrhoeae was 0.6 mM. We present the first peptide inhibitors of AniA, an enzyme that should be further exploited for antigonococcal drug development

Small UAS Detect and Avoid Requirements Necessary for Limited Beyond Visual Line of Sight (BVLOS) Operations

Potential small Unmanned Aircraft Systems (sUAS) beyond visual line of sight (BVLOS) operational scenarios/use cases and Detect And Avoid (DAA) approaches were collected through a number of industry wide data calls. Every 333 Exemption holder was solicited for this same information. Summary information from more than 5,000 exemption holders is documented, and the information received had varied level of detail but has given relevant experiential information to generalize use cases. A plan was developed and testing completed to assess Radio Line Of Sight (RLOS), a potential key limiting factors for safe BVLOS ops. Details of the equipment used, flight test area, test payload, and fixtures for testing at different altitudes is presented and the resulting comparison of a simplified mathematical model, an online modeling tool, and flight data are provided. An Operational Framework that defines the environment, conditions, constraints, and limitations under which the recommended requirements will enable sUAS operations BVLOS is presented. The framework includes strategies that can build upon Federal Aviation Administration (FAA) and industry actions that should result in an increase in BVLOS flights in the near term. Evaluating approaches to sUAS DAA was accomplished through five subtasks: literature review of pilot and ground observer see and avoid performance, survey of DAA criteria and recommended baseline performance, survey of existing/developing DAA technologies and performance, assessment of risks of selected DAA approaches, and flight testing. Pilot and ground observer see and avoid performance were evaluated through a literature review. Development of DAA criteria—the emphasis here being well clear— was accomplished through working with the Science And Research Panel (SARP) and through simulations of manned and unmanned aircraft interactions. Information regarding sUAS DAA approaches was collected through a literature review, requests for information, and direct interactions. These were analyzed through delineation of system type and definition of metrics and metric values. Risks associated with sUAS DAA systems were assessed by focusing on the Safety Risk Management (SRM) pillar of the SMS (Safety Management System) process. This effort (1) identified hazards related to the operation of sUAS in BVLOS, (2) offered a preliminary risk assessment considering existing controls, and (3) recommended additional controls and mitigations to further reduce risk to the lowest practical level. Finally, flight tests were conducted to collect preliminary data regarding well clear and DAA system hazards

Volume 01

Introduction from Dean Dr. Charles Ross Three Decades of Digging: Undergraduate Archeology at Longwood by Jessica Fields and Stephanie Neeley Interactions of Allelopathy and Heat Stress in Plants by Derek W. Hambright and Mary E. Lehman Inertial Electrostatic Confinement D-D Fusion Device: Construction and Simulation by Andrew R. Grzankowski Shackled Nim by Zachary Johnson Development of GC-MS and Chemometric Methods for the Analysis of Accelerants in Arson Cases by Boone M. Prentice A Comparison of Image Analysis Methods in cDNA Microarrays by Ashley M. Swandby Perceived Sexual Activity of Short and Long-Term Relationships by Victoria Morgan and Katie Williamson Elderly Male Communication by Kristine G. Bender Three Poems: “Adam and Eve and an Orange Tree”, “The Name of Everything Before Dying”, and “The ‘Poet Voice’” by Katelyn N. Romaine There\u27s Nothing Like Dancing, After All : Marriage and Gender in the Dance Scenes of Jane Austen\u27s Novels by D. Nicole Swann Two Poems: “Age Nine with Mother” and “The Apple That Crawls Away From the Tree” by Jessica Fox Untitled by Mike McAteer Room 9 by Alex Grabiec Two Photographs: “Gracie” and “Emily” by Laura Nodtvedt Bowling Lanes Night by Nick Costa Two Paintings: “Can and Kettle” and “Scarecrow” by Rachel Wolfe Exploring Henrik Ibsen\u27s “Perr Gynt” by Zack Dalton Creative Writing Scholarship at Longwood University Music Scholarship at Longwood – Senior Recital Arianne K. Burrus Longwood University Theater – Peer Gyn

Miscellany

Art Writinghttps://digitalcommons.georgiasouthern.edu/miscell/1000/thumbnail.jp