The Grizzly, March 25, 1983

New Editors Elected: Romer, Hong, Pasekoff Named • Superstars Tournament Needs Participants • DuPont Gives Third Consecutive Chemistry Grant • The A\u27s Come to UC • Third Annual Special Olympics This Weekend • Summer in Japan • Folk Singers at Bomberger • Letters to the Editor: An Epilogue to Zeta Chi • USGA Holds Election • USGA Notes • Voight at Bat • 13 Spend Break in Quebec • To Hell With the USFL • College Bowl Goes to Maryland • 1983 Room Selection Procedure • Bear\u27s Den Replaces Cafe International • Cycling Marathon: Ride for Your Life • Men\u27s Lacrosse Slow Getting Started • Men\u27s and Women\u27s Track Win Openershttps://digitalcommons.ursinus.edu/grizzlynews/1097/thumbnail.jp

The Grizzly, April 15, 1983

Second Attack: Improvements Sought for Security • New Senior Fund • Seminar Planned • The A\u27s Come to Helfferich Hall • Letter to the Editor: Most Abominable Act • Faculty Promotions Approved • President\u27s Corner • Sexual Assault in Quad • Security Tips • Nuclear Freeze Concert • Ursinus Representatives at UN • Ice Cream Night at Bear\u27s Den • Final Exam Schedule • Republicans for Rock! • Escape From Ursinus • Bear Batsmen Drop Slugfest • Men\u27s Track Evens Up • Men\u27s Tennis Nets Two Wins • Girls\u27 Nets Optimistic • Men\u27s Lacrosse Victorioushttps://digitalcommons.ursinus.edu/grizzlynews/1098/thumbnail.jp

The Grizzly, September 30, 1983

Fraternities Speak Out • Media Meeting Held • Forum Series Begins • President\u27s Corner • Letters to the Editor • Student Profile: Weible on Wheels • Guitarist Plays at Ursinus • Faculty Lectures Open • Everybody\u27s Rockin\u27 • Accountants Sponsor Competition • Parsons Stars in Video • Volleyball Picks up First Win • Gone But Not Forgotten • Speech Exemption Exam to be Given • Soccer Team Seeks to Regroup for Divisional Play • Hockey Lookin\u27 Good • Bear Pack up for Strong Season • Western Maryland Bombs Bearshttps://digitalcommons.ursinus.edu/grizzlynews/1102/thumbnail.jp

The Grizzly, April 29, 1983

Three Administrators to Leave: Harris, Layne Retire • Ursinus Makes Inquirer Headlines • Housing Shortage is Imminent • J-Board Changes to be Made • Ursinus Students Win German Awards • Computer Genius is Honored at Myrin • Renninger to go to Scotland • Ursinus Professor Sees Work Published • President\u27s Corner • Letters to the Editor • Bike-A-Thon Proves Successful • Film Reveals Nuclear Horror • Zacharias Ursinus to be Honored in Fall • Award Time • College Choir Turns Comic • Holocaust Survivor Speaks at Commemoration • Women\u27s Tennis Overcomes Adversities; Wins MAC Play-off Berth • Bears\u27 Softball Team Reaches Goal • Women\u27s Lacrosse Turns in Another Strong Season • Ursinus Sluggers Gear Up for Home Stretch • Sports Profile: The Mile Relay Team • Track Teams Close Out Seasons • Men\u27s Tennis Concludes Successful Campaign • Men\u27s Lacrosse Suffers Two Defeatshttps://digitalcommons.ursinus.edu/grizzlynews/1100/thumbnail.jp

The Grizzly, February 4, 1983

Trouble at Cutillo\u27s: Frats Earn Reputation as Animals • Drinking Concerns Richter • Economics Council Sponsors Entrepreneur-Related Forum • President\u27s Corner • Wismer Tries Again • Pfacelift at Pfahler • Bear Blades Burnished Beat Wilmington Twice • Serendipity Celebration Features Films • Writing Center Welcomes Students • Who\u27s Who in Who\u27s Who? • Commentary: Speak Up for Coed Housing • Didja Ever Wonder • Wrestlers Earn Split • Lewis on Wall Street • Disruptive Fans Cause Flare-up at Widener • Top Individual Efforts Mark Gymnastics Team • Interview: Chupein Named to All-League Team • Lady Hoops Still Struggling • Men\u27s Basketball Find Road a Bit Bumpy • Swimmers Maul Terrors of Western Marylandhttps://digitalcommons.ursinus.edu/grizzlynews/1092/thumbnail.jp

Effects of Mavacamten on Measures of Cardiopulmonary Exercise Testing Beyond Peak Oxygen Consumption: A Secondary Analysis of the EXPLORER-HCM Randomized Trial

IMPORTANCE: Mavacamten, a cardiac myosin inhibitor, improved peak oxygen uptake (pVO2) in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) in the EXPLORER-HCM study. However, the full extent of mavacamten's effects on exercise performance remains unclear. OBJECTIVE: To investigate the effect of mavacamten on exercise physiology using cardiopulmonary exercise testing (CPET). DESIGN, SETTING, AND PARTICIPANTS: Exploratory analyses of the data from the EXPLORER-HCM study, a randomized, double-blind, placebo-controlled, phase 3 trial that was conducted in 68 cardiovascular centers in 13 countries. In total, 251 patients with symptomatic obstructive HCM were enrolled. INTERVENTIONS: Patients were randomly assigned in a 1:1 ratio to mavacamten or placebo. MAIN OUTCOMES AND MEASURES: The following prespecified exploratory cardiovascular and performance parameters were assessed with a standardized treadmill or bicycle ergometer test protocol at baseline and week 30: carbon dioxide output (VCO2), minute ventilation (VE), peak VE/VCO2 ratio, ventilatory efficiency (VE/VCO2 slope), peak respiratory exchange ratio (RER), peak circulatory power, ventilatory power, ventilatory threshold, peak metabolic equivalents (METs), peak exercise time, partial pressure of end-tidal carbon dioxide (PETCO2), and VO2/workload slope. RESULTS: Two hundred fifty-one patients were enrolled. The mean (SD) age was 58.5 (11.9) years and 59% of patients were male. There were significant improvements with mavacamten vs placebo in the following peak-exercise CPET parameters: peak VE/VCO2 ratio (least squares [LS] mean difference, -2.2; 95% CI, -3.05 to -1.26; P < .001), peak METs (LS mean difference, 0.4; 95% CI, 0.17-0.60; P < .001), peak circulatory power (LS mean difference, 372.9 mL/kg/min × mm Hg; 95% CI, 153.12-592.61; P = .001), and peak PETCO2 (LS mean difference, 2.0 mm Hg; 95% CI, 1.12-2.79; P < .001). Mavacamten also improved peak exercise time compared with placebo (LS mean difference, 0.7 minutes; 95% CI, 0.13-1.24; P = .02). There was a significant improvement in nonpeak-exercise CPET parameters, such as VE/VCO2 slope (LS mean difference, -2.6; 95% CI, -3.58 to -1.52; P < .001) and ventilatory power (LS mean difference, 0.6 mm Hg; 95% CI, 0.29-0.90; P < .001) favoring mavacamten vs placebo. CONCLUSIONS AND RELEVANCE: Mavacamten improved a range of CPET parameters beyond pVO2, indicating consistent and broad benefits on maximal exercise capacity. Although improvements in peak-exercise CPET parameters are clinically meaningful, the favorable effects of mavacamten on submaximal exertional tolerance provide further insights into the beneficial impact of mavacamten in patients with obstructive HCM. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03470545

Three red suns in the sky: A transiting, terrestrial planet in a triple M-dwarf system at 6.9 pc

We present the discovery from Transiting Exoplanet Survey Satellite (TESS) data of LTT 1445Ab. At a distance of 6.9 pc, it is the second nearest transiting exoplanet system found to date, and the closest one known for which the primary is an M dwarf. The host stellar system consists of three mid-to-late M dwarfs in a hierarchical configuration, which are blended in one TESS pixel. We use MEarth data and results from the Science Processing Operations Center data validation report to determine that the planet transits the primary star in the system. The planet has a radius of ${1.38}_{-0.12}^{+0.13}$ ${R}_{\oplus }$, an orbital period of ${5.35882}_{-0.00031}^{+0.00030}$ days, and an equilibrium temperature of ${433}_{-27}^{+28}$ K. With radial velocities from the High Accuracy Radial Velocity Planet Searcher, we place a 3σ upper mass limit of 8.4 ${M}_{\oplus }$ on the planet. LTT 1445Ab provides one of the best opportunities to date for the spectroscopic study of the atmosphere of a terrestrial world. We also present a detailed characterization of the host stellar system. We use high-resolution spectroscopy and imaging to rule out the presence of any other close stellar or brown dwarf companions. Nineteen years of photometric monitoring of A and BC indicate a moderate amount of variability, in agreement with that observed in the TESS light-curve data. We derive a preliminary astrometric orbit for the BC pair that reveals an edge-on and eccentric configuration. The presence of a transiting planet in this system hints that the entire system may be co-planar, implying that the system may have formed from the early fragmentation of an individual protostellar core.Accepted manuscrip

Platelets in Patients with Premature Coronary Artery Disease Exhibit Upregulation of miRNA340* and miRNA624*

Coronary artery disease (CAD) is the leading cause of human morbidity and mortality worldwide, underscoring the need to improve diagnostic strategies. Platelets play a major role, not only in the process of acute thrombosis during plaque rupture, but also in the formation of atherosclerosis itself. MicroRNAs are endogenous small non-coding RNAs that control gene expression and are expressed in a tissue and disease-specific manner. Therefore they have been proposed to be useful biomarkers. It remains unknown whether differences in miRNA expression levels in platelets can be found between patients with premature CAD and healthy controls. In this case-control study we measured relative expression levels of platelet miRNAs using microarrays from 12 patients with premature CAD and 12 age- and sex-matched healthy controls. Six platelet microRNAs were significantly upregulated (miR340*, miR451, miR454*, miR545:9.1. miR615-5p and miR624*) and one miRNA (miR1280) was significantly downregulated in patients with CAD as compared to healthy controls. To validate these results, we measured the expression levels of these candidate miRNAs by qRT-PCR in platelets of individuals from two independent cohorts; validation cohort I consisted of 40 patients with premature CAD and 40 healthy controls and validation cohort II consisted of 27 patients with artery disease and 40 healthy relatives. MiR340* and miR624* were confirmed to be upregulated in patients with CAD as compared to healthy controls in both validation cohorts. Two miRNAs in platelets are significantly upregulated in patients with CAD as compared to healthy controls. Whether the two identified miRNAs can be used as biomarkers and whether they are cause or consequence of the disease remains to be elucidated in a larger prospective stud

Toxic oligomers of the amyloidogenic HypF-N protein form pores in mitochondrial membranes

Studies on the amyloidogenic N-terminal domain of the E. coli HypF protein (HypF-N) have contributed significantly to a detailed understanding of the pathogenic mechanisms in neurodegenerative diseases characterised by the formation of misfolded oligomers, by proteins such as amyloid-β, α-synuclein and tau. Given that both cell membranes and mitochondria are increasingly recognised as key targets of oligomer toxicity, we investigated the damaging effects of aggregates of HypF-N on mitochondrial membranes. Essentially, we found that HypF-N oligomers characterised by high surface hydrophobicity (type A) were able to trigger a robust permeabilisation of mito-mimetic liposomes possessing cardiolipin-rich membranes and dysfunction of isolated mitochondria, as demonstrated by a combination of mitochondrial shrinking, lowering of mitochondrial membrane potential and cytochrome c release. Furthermore, using single-channel electrophysiology recordings we obtained evidence that the type A aggregates induced currents reflecting formation of ion-conducting pores in mito-mimetic planar phospholipid bilayers, with multi-level conductances ranging in the hundreds of pS at negative membrane voltages. Conversely, HypF-N oligomers with low surface hydrophobicity (type B) could not permeabilise or porate mitochondrial membranes. These results suggest an inherent toxicity of membrane-active aggregates of amyloid-forming proteins to mitochondria, and that targeting of oligomer-mitochondrial membrane interactions might therefore afford protection against such damage.peer-reviewe