An Empirical Analysis of the Effect of Ballot Truncation on Ranked-Choice Electoral Outcomes

In ranked-choice elections voters cast preference ballots which provide a voter's ranking of the candidates. The method of ranked-choice voting (RCV) chooses a winner by using voter preferences to simulate a series of runoff elections. Some jurisdictions which use RCV limit the number of candidates that voters can rank on the ballot, imposing what we term a truncation level, which is the number of candidates that voters are allowed to rank. Given fixed voter preferences, the winner of the election can change if we impose different truncation levels. We use a database of 1171 real-world ranked-choice elections to empirically analyze the potential effects of imposing different truncation levels in ranked-choice elections. Our general finding is that if the truncation level is at least three then restricting the number of candidates which can be ranked on the ballot rarely affects the election winner

Lysosomal drug sequestration as a mechanism of drug resistance in vascular sarcoma cells marked by high CSF-1R expression

Human angiosarcoma and canine hemangiosarcoma are thought to arise from vascular tissue or vascular forming cells based upon their histological appearance. However, recent evidence indicates a hematopoietic or angioblastic cell of origin for these tumors. In support of this idea, we previously identified an endothelial-myeloid progenitor cell population with high expression of endothelial cell markers and the myeloid cell marker, colony stimulating factor 1 receptor (CSF-1R). Here, we further characterized these cells to better understand how their cellular characteristics may impact current therapeutic applications. We performed cell enrichment studies from canine hemangiosarcoma and human angiosarcoma cell lines to generate cell populations with high or low CSF-1R expression. We then utilized flow cytometry, side population and cell viability assays, and fluorescence based approaches to elucidate drug resistance mechanisms and to determine the expression of hematopoietic and endothelial progenitor cell markers. We demonstrated that cells with high CSF-1R expression enriched from hemangiosarcoma and angiosarcoma cell lines are more drug resistant than cells with little or no CSF-1R expression. We determined that the increased drug resistance may be due to increased ABC transporter expression in hemangiosarcoma and increased drug sequestration within cellular lysosomes in both hemangiosarcoma and angiosarcoma. We identified drug sequestration within cellular lysosomes as a shared drug resistance mechanism in human and canine vascular sarcomas marked by high CSF-1R expression. Taken together, our results demonstrate that studies in highly prevalent canine hemangiosarcoma may be especially relevant to understanding and addressing drug resistance mechanisms in both the canine and human forms of this disease

Propranolol Sensitizes Vascular Sarcoma Cells to Doxorubicin by Altering Lysosomal Drug Sequestration and Drug Efflux

Angiosarcoma is a rare cancer of blood vessel–forming cells with a high patient mortality and few treatment options. Although chemotherapy often produces initial clinical responses, outcomes remain poor, largely due to the development of drug resistance. We previously identified a subset of doxorubicin-resistant cells in human angiosarcoma and canine hemangiosarcoma cell lines that exhibit high lysosomal accumulation of doxorubicin. Hydrophobic, weak base chemotherapeutics, like doxorubicin, are known to sequester within lysosomes, promoting resistance by limiting drug accessibility to cellular targets. Drug synergy between the beta adrenergic receptor (β-AR) antagonist, propranolol, and multiple chemotherapeutics has been documented in vitro, and clinical data have corroborated the increased therapeutic potential of propranolol with chemotherapy in angiosarcoma patients. Because propranolol is also a weak base and accumulates in lysosomes, we sought to determine whether propranolol enhanced doxorubicin cytotoxicity via antagonism of β-ARs or by preventing the lysosomal accumulation of doxorubicin. β-AR-like immunoreactivities were confirmed in primary tumor tissues and cell lines; receptor function was verified by monitoring downstream signaling pathways of β-ARs in response to receptor agonists and antagonists. Mechanistically, propranolol increased cytoplasmic doxorubicin concentrations in sarcoma cells by decreasing the lysosomal accumulation and cellular efflux of this chemotherapeutic agent. Equivalent concentrations of the receptor-active S-(−) and -inactive R-(+) enantiomers of propranolol produced similar effects, supporting a β-AR-independent mechanism. Long-term exposure of hemangiosarcoma cells to propranolol expanded both lysosomal size and number, yet cells remained sensitive to doxorubicin in the presence of propranolol. In contrast, removal of propranolol increased cellular resistance to doxorubicin, underscoring lysosomal doxorubicin sequestration as a key mechanism of resistance. Our results support the repurposing of the R-(+) enantiomer of propranolol with weak base chemotherapeutics to increase cytotoxicity and reduce the development of drug-resistant cell populations without the cardiovascular and other side effects associated with antagonism of β-ARs

The Grizzly, January 24, 2002

Ursinus has Spoken: Results of the Grizzly Survey • A Tribute to Dr. Martin Luther King Jr. • Ursinus Joins the War Against Bioterrorism • Limerick Nuclear Plant Cited for Safety Violation • New Housing for Spring Semester • Laptop Initiative • Opinions: Laptop Controversy; Are the Crowds too Much for Wismer to Handle?; En Espana: One Student\u27s Experience Abroad • Ursinus and MTV: A Winning Combination • Judy Chicago on Display at Berman • Sigma Sigma Sigma to Install Newest Collegiate Chapter at Ursinus • To be Educated or not to be? • Ursinus Swimmers Reap Benefits of a Trip Down South Showing Well Against York • Bouncing into Another Season with the Gymnastics Team • Ursinus Wrestling: A Conference Powerhouse in the Making • Indoor Track Teams Place 4th and 7th at Gulden Relays • Swarthmore Proves to be too Much for our Lady Bearshttps://digitalcommons.ursinus.edu/grizzlynews/1504/thumbnail.jp

The Lantern Vol. 69, No. 2, Spring 2002

• What was Said in the Court of Riong • Bailan Pies (Dancing Feet) • Canard • Vernacular City • Saturday Night Motorcycles • The Muse • I Stuffed my Face in the Herbs • Jacob\u27s Nightingale • At Tracey\u27s • Ona Time, a Rhym-mer • For Yo Yo Ma\u27s Encore • Two Minutes from Earl\u27s Court Tube Station • For Two • Bald • This Year\u27s Love • The Dimmer Switch • Tickertape • Imaginary Highway • First Kiss and Related Terrors • Hairball • His Hobbies • Spaghetti Dinnerhttps://digitalcommons.ursinus.edu/lantern/1160/thumbnail.jp

The Grizzly, October 4, 2001

Campus-Wide Coin Drive Raises over $1,500 for Red Cross Fund • Tri Sigma Colony Established on the Ursinus Campus • Sisters of Omega Chi Organize Campus Blood Drive • Banned Book Week at UC • American Studies Major Offers Students Interdisciplinary Study • Ursinus Students Excited about Grand Opening of Local Kohls Department Store • Opinions: Exploring the Difference in Communication Between Men and Women; Student Response to Facilities in New Fitness Center; CAB Talks Back: Use it; Don\u27t Reduce it; Feeling Awkward in New Gym; Crossing and Construction Complaints on Main Street • Ghouls, Ghosts, Thrills and Chills: Area Amusement Parks Celebrate Halloween in Spooky Style • Author Lorene Cary Launches the Pew Fellow Lecture Series • Poem-palooza set to Arrive at Ursinus • Oktoberfest and Then Some • Polignano puts a new Spin on Fitness • Club Drugs: What you may not Know • Comparing Prices on Film Development • The Roaring Twenties? Perhaps not at Ursinus • Women\u27s Soccer Annihilates Washington, Shutout by Hopkins • UC Cross Country at Dickinson Invitational: Did They Just run out of Juice? • West Chester Wins Snell Cup Against UC Field Hockey, 4-1 • Volleyball Defeats Washington, but Falls to Haverford and Gettysburg • Men\u27s Soccer Takes out Washington • UC Women\u27s Rugby Kicks off Fall Seasonhttps://digitalcommons.ursinus.edu/grizzlynews/1496/thumbnail.jp

The Grizzly, October 18, 2001

Sisters of Omega Chi Sponsor Blood Drive • Taking a Hike with the Environmental Studies Classes • World Cultures Club Encourages Campus-Wide Cultural Awareness • Gil Cook and Heather Potts Named 2001 Homecoming King and Queen • Understanding the Social Norms at Ursinus College • Ursinus Bookstore Holding Coat and Blanket Drive • Ursinus Alumna Martha Kriebel Reflects on the Unexpected Turns in Life\u27s Path • The Economic Effects of Terrorism • Struggling to Survive: The Way of Life for Women in Afghanistan • From Mexico to Collegeville: International Exchange Student Enrique Cobarrubias • Sophomore Week: Helping Students Reach Academic Goals • Second Annual Take Back the Night Rally & March Planned for Next Week • Opinions: Lady Wismer Attacks Students Saying Next Time, I\u27m Gonna Nail You! ; A Student\u27s Battle with Smoking; New Gym is Great, not Awkward; Message of Tolerance and Peace; One Resident Complains: Loss of Interest in Special Interest Houses • Dr. David Releases his own CD • New Road Brewhouse Ready to Rock! • Scary Way to Have a Fun Fall Day • Chinese Food: The Staple of Every College Student\u27s Diet • Can\u27t Decide What to do after Graduation? This Online Program Will Help • Class of 2003 has a new President • Ruby\u27s Restaurant: A Tasty Time Capsule • Give the Wismer Staff a Break: They\u27re Working for You • Who is Grizzly the Bear? • Ursinus Field Hockey Takes Victory over Holy Cross • Bears Wake from Hibernation; Crush Gettysburg 31-7 • Men\u27s Soccer Meets Gettysburg • Volleyball Wins Against Bryn Mawr and U. of the Sciences • XC Cleans up at Lehigh University • Barth Becomes Record-holder for Points • Field Hockey Changing NCAA Division • Women\u27s Soccer Rocks the Househttps://digitalcommons.ursinus.edu/grizzlynews/1497/thumbnail.jp

Identification of Three Molecular and Functional Subtypes in Canine Hemangiosarcoma through Gene Expression Profiling and Progenitor Cell Characterization

Canine hemangiosarcomas have been ascribed to an endothelial origin based on histologic appearance; however, recent findings suggest that these tumors may arise instead from hematopoietic progenitor cells. To clarify this ontogenetic dilemma, we used genome-wide expression profiling of primary hemangiosarcomas and identified three distinct tumor subtypes associated with angiogenesis (group 1), inflammation (group 2), and adipogenesis (group 3). Based on these findings, we hypothesized that a common progenitor may differentiate into the three tumor subtypes observed in our gene profiling experiment. To investigate this possibility, we cultured hemangiosarcoma cell lines under normal and sphere-forming culture conditions to enrich for tumor cell progenitors. Cells from sphere-forming cultures displayed a robust self-renewal capacity and exhibited genotypic, phenotypic, and functional properties consistent with each of the three molecular subtypes seen in primary tumors, including expression of endothelial progenitor cell (CD133 and CD34) and endothelial cell (CD105, CD146, and αvβ3 integrin) markers, expression of early hematopoietic (CD133, CD117, and CD34) and myeloid (CD115 and CD14) differentiation markers in parallel with increased phagocytic capacity, and acquisition of adipogenic potential. Collectively, these results suggest that canine hemangiosarcomas arise from multipotent progenitors that differentiate into distinct subtypes. Improved understanding of the mechanisms that determine the molecular and phenotypic differentiation of tumor cells in vivo could change paradigms regarding the origin and progression of endothelial sarcomas

The Grizzly, October 11, 2000

University Students Disappointed by Rally • Ruhe\u27s \u27Athens\u27 with Ursinus Faces is a Work of Art • Homecoming 2000: Alumni Remember Collegeville Days • Food Critics Speak up at Dining Services Meeting • New Prof. has Students all Shook up...Over Shakespeare?! • Brodbeck Residents Take it to Extreme • French Officials Approve Morning-After Pill • Should Patients\u27 Drug Use be Confidential? • Nearing Fall Break, Freshmen High on UC Experience • The Wrong-Way Geese • Best Buddies: Offering Friendship, Making a Difference • Opinions: New Breed of Grizzly at Ursinus College; Abortion Pill Provides Pause for Debate; Pro-Life Sends Wrong Message; Is Bioengineering Ethical?; Ursinus Students React to Israeli-PLO Clashes; Presidential Debate Shows Just how Mediocre Politics can be; Defending Al Gore • Battle of the Bands Rocks in Reimert • Harpoon Louie\u27s a World Away from Wismer • Poetry Slam on Campus in November • Bears Maul Blue Jays • Women\u27s Rugby Roughed Up by Hawks • Binge Drinking Growing Problem on College Campuses • Roofies: Date Rape Drug More Popular, Dangerous Than Ever • Men\u27s Soccer Downs Aggies • New Coaches Bring Promise to Programs • Matty Earns McIntyre Award • Lowell\u27s Lone Goal Leads Bears to OT win Over Davidson Coll. • Lady Bears Struggle to go on Offensive • Volleyball Stomps the Sciences; Drops two CC Matches • Annual Alumni Lacrosse Match Ends in tie • Leadership in Adventure: ESS Class Molds Leaders Through Sporthttps://digitalcommons.ursinus.edu/grizzlynews/1475/thumbnail.jp

Beta Adrenergic Signaling: A Targetable Regulator of Angiosarcoma and Hemangiosarcoma

Human angiosarcomas and canine hemangiosarcomas are highly aggressive cancers thought to arise from cells of vascular origin. The pathological features, morphological organization, and clinical behavior of canine hemangiosarcomas are virtually indistinct from those of human angiosarcomas. Overall survival with current standard-of-care approaches remains dismal for both humans and dogs, and each is likely to succumb to their disease within a short duration. While angiosarcomas in humans are extremely rare, limiting their study and treatment options, canine hemangiosarcomas occur frequently. Therefore, studies of these sarcomas in dogs can be used to advance treatment approaches for both patient groups. Emerging data suggest that angiosarcomas and hemangiosarcomas utilize beta adrenergic signaling to drive their progression by regulating the tumor cell niche and fine-tuning cellular responses within the tumor microenvironment. These discoveries indicate that inhibition of beta adrenergic signaling could serve as an Achilles heel for these tumors and emphasize the need to design therapeutic strategies that target tumor cell and stromal cell constituents. In this review, we summarize recent discoveries and present new hypotheses regarding the roles of beta adrenergic signaling in angiosarcomas and hemangiosarcomas. Because the use of beta adrenergic receptor antagonists is well established in human and veterinary medicine, beta blockade could provide an immediate adjunct therapy for treatment along with a tangible opportunity to improve upon the outcomes of both humans and dogs with these diseases