Escherichia coli from urine of female patients with urinary tract infections is competent for intracellular bacterial community formation

Nearly 50% of women experience at least one urinary tract infection (UTI) in their lifetime. Studies with mice have revealed that uropathogenic Escherichia coli (UPEC) isolates invade superficial umbrella cells that line the bladder, allowing them to find a safe haven and subvert clearance by innate host responses. Rapid intracellular replication results in the formation of distinctive intracellular bacterial communities (IBCs). In this study, we evaluated whether UPEC strains cultured from the urine of women and classified as causing acute cystitis, recurrent cystitis, asymptomatic bacteriuria, or pyelonephritis could progress through the IBC cascade in a well-characterized mouse model of cystitis. Of 18 UPEC isolates collected from women, 15 formed IBCs. Variations in the size, number, and kinetics of IBC formation were observed with strains isolated from women with different clinical syndromes. Two of the three isolates that did not form IBCs when inoculated alone were able to do so when coinoculated with an isolate that was capable of generating IBCs. The mixed infections dramatically altered the behavior of the coinfecting bacteria relative to their behavior in a single infection. The study also showed that mice with five different genetic backgrounds can support IBC formation. Although UPEC isolates differ genetically in their virulence factors, the majority of UPEC isolates from different types of UTI proceed through the IBC pathway, confirming the generality of IBCs in UTI pathogenesis in mice

Antimyeloma Effects of the Heat Shock Protein 70 Molecular Chaperone Inhibitor MAL3-101

Multiple myeloma (MM) is the second most common hematologic malignancy and remains incurable, primarily due to the treatment-refractory/resistant nature of the disease. A rational approach to this compelling challenge is to develop new drugs that act synergistically with existing effective agents. This approach will reduce drug concentrations, avoid treatment resistance, and also improve treatment effectiveness by targeting new and nonredundant pathways in MM. Toward this goal, we examined the antimyeloma effects of MAL3-101, a member of a new class of non-ATP-site inhibitors of the heat shock protein (Hsp) 70 molecular chaperone. We discovered that MAL3-101 exhibited antimyeloma effects on MM cell lines in vitro and in vivo in a xenograft plasmacytoma model, as well as on primary tumor cells and bone marrow endothelial cells from myeloma patients. In combination with a proteasome inhibitor, MAL3-101 significantly potentiated the in vitro and in vivo antimyeloma effects. These data support a preclinical rationale for small molecule inhibition of Hsp70 function, either alone or in combination with other agents, as an effective therapeutic strategy for MM

The Grizzly, November 9, 1984

Program Board Attends Activities Conference • Fraternity Sponsors Thanksgiving Food Drive • Smith Addresses Value of Liberal Arts • Editorials: Newspaper Reflects Campus News and Views; Pulling the Big Lever • Letters to the Editor: Mock Election Coverage Questioned; Intervention Policy Must Go • College Bowl Season Underway • Ursinus in a Box • Shorts: Ec. Council Programs; Photo Exhibit in Library; Turkey Trot; UPB Trips Scheduled; Dutch Folk Songs; USGA Report • Bear Booters Win ECA Conference Bid • Runners Second in MAC\u27s • A Student\u27s View of The Training Facility • Mers Shine at Relay Carnival • Middle East Forum Scheduled • Theater Review: A Thurber Carnival • Student Teachers Hard at Work • News of Yesteryear: Judy Collins to Appear in Concert at Ursinushttps://digitalcommons.ursinus.edu/grizzlynews/1127/thumbnail.jp

The Grizzly, November 9, 1984

Program Board Attends Activities Conference • Fraternity Sponsors Thanksgiving Food Drive • Smith Addresses Value of Liberal Arts • Editorials: Newspaper Reflects Campus News and Views; Pulling the Big Lever • Letters to the Editor: Mock Election Coverage Questioned; Intervention Policy Must Go • College Bowl Season Underway • Ursinus in a Box • Shorts: Ec. Council Programs; Photo Exhibit in Library; Turkey Trot; UPB Trips Scheduled; Dutch Folk Songs; USGA Report • Bear Booters Win ECA Conference Bid • Runners Second in MAC\u27s • A Student\u27s View of The Training Facility • Mers Shine at Relay Carnival • Middle East Forum Scheduled • Theater Review: A Thurber Carnival • Student Teachers Hard at Work • News of Yesteryear: Judy Collins to Appear in Concert at Ursinushttps://digitalcommons.ursinus.edu/grizzlynews/1127/thumbnail.jp

The Grizzly, February 1, 1985

Ursinus Dodges Enrollment Drought • USGA Candidate Petitions Due • Letter: Spanish Prof Encounters Alumnus • New Fogerty Album a Hit • The Beat Goes Public • pro Theatre • Swimmin\u27 Women Boost Record to 3-2 • Grapplers Win 6, Lose 1 • Injured Matman Won\u27t Quit • Mers and Vers Compete During Break • Men\u27s B-ball Defeat Moravian • Lady Bears Trying to Pull Out of Slump • Chinese Star Talks to Bootershttps://digitalcommons.ursinus.edu/grizzlynews/1131/thumbnail.jp

The Grizzly, December 7, 1984

Campus Life Considers Alternative Housing • Meunch Proposes RA Pay Raise • French Department Plans Summer Study Aboard • Campus Enjoys Third Pub Night • Phone Jacks in Old Men\u27s by Spring Semester, Kane Says • College Bowl Enters Sixth Week • Grapplers Take Second at LVI • Men\u27s B-ball Jumps to 4-0 • Women\u27s B-ball Loses to Swarthmore • Fencing Club Co-sponsors Tourney • Mermen Win Big • Men\u27s Track Begins Indoor Season • Gymnasts Win Openerhttps://digitalcommons.ursinus.edu/grizzlynews/1130/thumbnail.jp

The Sloan Digital Sky Survey Quasar Lens Search. II. Statistical lens sample from the third data release

We report the first results of our systematic search for strongly lensed quasars using the spectroscopically confirmed quasars in the Sloan Digital Sky Survey (SDSS). Among 46,420 quasars from the SDSS Data Release 3 (~4188 deg^2), we select a subsample of 22,683 quasars that are located at redshifts between 0.6 and 2.2 and are brighter than the Galactic extinction-corrected i-band magnitude of 19.1. We identify 220 lens candidates from the quasar subsample, for which we conduct extensive and systematic follow-up observations in optical and near-infrared wavebands, in order to construct a complete lensed quasar sample at image separations between 1" and 20" and flux ratios of faint to bright lensed images larger than 10^(−0.5). We construct a statistical sample of 11 lensed quasars. Ten of these are galaxy-scale lenses with small image separations (~ 1"-2") and one is a large separation (15") system which is produced by a massive cluster of galaxies, representing the first statistical sample of lensed quasars including both galaxy- and cluster-scale lenses. The Data Release 3 spectroscopic quasars contain an additional 11 lensed quasars outside the statistical sample

The Grizzly, November 16, 1984

College Acquires New Properties • Crime and Punishment: The New System • Officials Seek Return of Missing Air Masks • Editorial: Force Feeding the Student Body • Letters: Campus Sage Defends Lever Pullers; Group Claims Silent Coup • Study Abroad: A Student\u27s Trip to Scotland • Steady GPA Increase for Math and Poli Sci • Shorts: Pops Concert Scheduled; Shyness Workshop; Three Students Receive Award • Gridders Defeat Dickinson, 45-14 • X-Country Runner Earns Trip to Nationals • Swimmin\u27 women....and the Mermen • CPA Urges Students to Consider Optionshttps://digitalcommons.ursinus.edu/grizzlynews/1128/thumbnail.jp

Before the Pandemic Ends: Making Sure This Never Happens Again

Introduction On 30 January 2020, the World Health Organization (WHO) declared a Global Health Emergency of international concern attendant to the emergence and spread of SARS-CoV-2, nearly two months after the first reported emergence of human cases in Wuhan, China. In the subsequent two months, global, national and local health personnel and infrastructures have been overwhelmed, leading to suffering and death for infected people, and the threat of socio-economic instability and potential collapse for humanity as a whole. This shows that our current and traditional mode of coping, anchored in responses after the fact, is not capable of dealing with the crisis of emerging infectious disease. Given all of our technological expertise, why is there an emerging disease crisis, and why are we losing the battle to contain and diminish emerging diseases? Part of the reason is that the prevailing paradigm explaining the biology of pathogen-host associations (coevolution, evolutionary arms races) has assumed that pathogens must evolve new capacities - special mutations – in order to colonize new hosts and produce emergent disease (e.g. Parrish and Kawaoka, 2005). In this erroneous but broadly prevalent view, the evolution of new capacities creates new opportunities for pathogens. Further, given that mutations are both rare and undirected, the highly specialized nature of pathogen-host relationships should produce an evolutionary firewall limiting dissemination; by those definitions, emergences should be rare (for a historical review see Brooks et al., 2019). Pathogens, however, have become far better at finding us than our traditional understanding predicts. We face considerable risk space for pathogens and disease that directly threaten us, our crops and livestock – through expanding interfaces bringing pathogens and hosts into increasing proximity, exacerbated by environmental disruption and urban density, fueled by globalized trade and travel. We need a new paradigm that explains what we are seeing. Additional section headers: The Stockholm Paradigm The DAMA Protocol A Sense of Urgency and Long-Term Commitment Reference

Development and testing of a pyro-driven launcher for harpoon-based comet sample acquisition

The CORSAIR (COmet Rendezvous, Sample Acquisition, Investigation, and Return) mission is a proposal for the fourth NASA New Frontiers program. It belongs to the Comet Surface Sample Return mission theme which focuses on acquiring and returning to Earth a macroscopic sample from the surface of a comet nucleus. CORSAIR uses a harpoon-based Sample Acquisition System (SAS) with the spacecraft hovering several meters above the comet surface. This stand-off strategy overcomes disadvantages of systems using drills or shovels. Since comets are low gravity objects, these techniques would require anchoring before sampling, which is not necessary here. Moreover, the harpoon-based system allows for acquiring several samples from different locations on the comet maximizing the scientifc output of the mission. Each SAS assembly consists of a pyro-driven launcher, a Sample Acquisition and Retrieval Projectile (SARP) and a retraction system using a deployable composite boom structure. In order to collect enough cometary material, the launcher has to provide the required kinetic energy to the SARP. Due to high energy densities, pyrotechnically actuated devices ultimately reduce the overall system mass and dimensions. Here, an overview of the development, design and testing of the launcher is given. Furthermore, the launcher theory is introduced explaining the entire reaction chain: initiation -> gas dynamics -> SARP motion