ScholarWorks shares over 40,000 articles, working papers, chapters, presentations, posters, theses, historical documents and other items submitted by members of the IU Indianapolis campus community.
Get started! Login with your IU credentials to share freely with 2 million readers per year.
Communities in ScholarWorks
Select a community to browse its collections.
Recent Submissions
Proinflammatory cytokine signaling required for the generation of natural killer cell memory
(Rockefeller University Press, 2012) Sun, Joseph C.; Madera, Sharline; Bezman, Natalie A.; Beilke, Joshua N.; Kaplan, Mark H.; Lanier, Lewis L.; Pediatrics, School of Medicine
Although natural killer (NK) cells are classified as innate immune cells, recent studies demonstrate that NK cells can become long-lived memory cells and contribute to secondary immune responses. The precise signals that promote generation of long-lived memory NK cells are unknown. Using cytokine receptor-deficient mice, we show that interleukin-12 (IL-12) is indispensible for mouse cytomegalovirus (MCMV)-specific NK cell expansion and generation of memory NK cells. In contrast to wild-type NK cells that proliferated robustly and resided in lymphoid and nonlymphoid tissues for months after MCMV infection, IL-12 receptor-deficient NK cells failed to expand and were unable to mediate protection after MCMV challenge. We further demonstrate that a STAT4-dependent IFN-γ-independent mechanism contributes toward the generation of memory NK cells during MCMV infection. Understanding the full contribution of inflammatory cytokine signaling to the NK cell response against viral infection will be of interest for the development of vaccines and therapeutics.
Tracking Caregiver Strain Across Intervention Stages: A Data-Driven Approach to Emotional and Logistical Burden in Autism Support
(2025-05-09) Vontimitta, Mahitha; Neal , Tiffany; Devarapalli, Baby Amulya; Swiezy, Naomi
This project analyzed caregiver burden using longitudinal data from the Caregiver Strain Questionnaire (CSQ), collected across seven post-discharge timepoints as part of the Coordinated Care Team at HANDS in Autism®. Data from REDCap was cleaned and preprocessed using Python, then visualized with Power BI to uncover trends in objective, internalized, and externalized strain. Results showed peak caregiver burden during the preadmission and early post-discharge phases, with gradual improvement over time. However, emotional strain persisted longer than practical burdens. Visual dashboards allowed for real-time comparison of severity types and helped identify intervention windows. The project emphasized the value of data-driven tools in understanding healthcare challenges and reinforced the need for early support strategies, long-term emotional care, and improved caregiver retention in follow-up studies.
Protease Activated Receptor-1 (PAR-1) Mediated Platelet Aggregation is Dependant on Clopidogrel Response
(Elsevier, 2012) Kreutz, Rolf P.; Breall, Jeffrey A.; Kreutz, Yvonne; Owens, Janelle; Lu, Deshun; Bolad, Islam; von der Lohe, Elisabeth; Sinha, Anjan; Flockhart, David A.; Medicine, School of Medicine
Introduction: Clopidogrel inhibits ADP mediated platelet aggregation through inhibition of the P2Y12 receptor by its active metabolite. Thrombin induces platelet aggregation by binding to protease activated receptor-1 (PAR-1), and inhibition of PAR-1 has been evaluated in patients treated with clopidogrel to reduce ischemic events after acute coronary syndromes. Residual PAR-1 mediated platelet aggregation may be dependent on extent of clopidogrel response.
Material and methods: Platelet aggregation was measured in 55 patients undergoing elective PCI at 16-24 hours after 600 mg clopidogrel loading dose by light transmittance aggregometry using ADP 20 μM and thrombin receptor agonist peptide (TRAP) at 15 μM and 25 μM as agonists. Genomic DNA was genotyped for common CYP2C19 variants.
Results: Increasing quartiles of 20 μM ADP induced platelet aggregation after clopidogrel loading were associated with increasing levels of TRAP mediated platelet aggregation. Patients in the highest quartile (clopidogrel non-responders) of post treatment ADP aggregation had significantly higher TRAP mediated aggregation than the patients in the lowest quartile (clopidogrel responders) [TRAP 15 μM: 79.6 ± 5% vs. 69.5 ± 8%, p<0.001].
Conclusions: Non-responders to clopidogrel show increased residual platelet aggregation induced by TRAP, whereas clopidogrel responders exhibit attenuated response to TRAP. Addition of PAR-1 antiplatelet drugs may be most effective in patients with reduced clopidogrel response and high residual TRAP mediated platelet aggregation.
Prevention and Mitigation of Acute Radiation Syndrome in Mice by Synthetic Lipopeptide Agonists of Toll-Like Receptor 2 (TLR2)
(Public Library of Science, 2012) Shakhov, Alexander N.; Singh, Vijay K.; Bone, Frederick; Cheney, Alec; Kononov, Yevgeniy; Krasnov, Peter; Bratanova-Toshkova, Troitza K.; Shakhova, Vera V.; Young, Jason; Weil, Michael M.; Panoskaltsis-Mortari, Angela; Orschell, Christie M.; Baker, Patricia S.; Gudkov, Andrei; Feinstein, Elena; Medicine, School of Medicine
Bacterial lipoproteins (BLP) induce innate immune responses in mammals by activating heterodimeric receptor complexes containing Toll-like receptor 2 (TLR2). TLR2 signaling results in nuclear factor-kappaB (NF-κB)-dependent upregulation of anti-apoptotic factors, anti-oxidants and cytokines, all of which have been implicated in radiation protection. Here we demonstrate that synthetic lipopeptides (sLP) that mimic the structure of naturally occurring mycoplasmal BLP significantly increase mouse survival following lethal total body irradiation (TBI) when administered between 48 hours before and 24 hours after irradiation. The TBI dose ranges against which sLP are effective indicate that sLP primarily impact the hematopoietic (HP) component of acute radiation syndrome. Indeed, sLP treatment accelerated recovery of bone marrow (BM) and spleen cellularity and ameliorated thrombocytopenia of irradiated mice. sLP did not improve survival of irradiated TLR2-knockout mice, confirming that sLP-mediated radioprotection requires TLR2. However, sLP was radioprotective in chimeric mice containing TLR2-null BM on a wild type background, indicating that radioprotection of the HP system by sLP is, at least in part, indirect and initiated in non-BM cells. sLP injection resulted in strong transient induction of multiple cytokines with known roles in hematopoiesis, including granulocyte colony-stimulating factor (G-CSF), keratinocyte chemoattractant (KC) and interleukin-6 (IL-6). sLP-induced cytokines, particularly G-CSF, are likely mediators of the radioprotective/mitigative activity of sLP. This study illustrates the strong potential of LP-based TLR2 agonists for anti-radiation prophylaxis and therapy in defense and medical scenarios.
Effect of Escitalopram on Hot Flash Interference: A Randomized, Controlled Trial
(Elsevier, 2012) Carpenter, Janet S.; Guthrie, Katherine A.; Larson, Joseph C.; Freeman, Ellen W.; Joffe, Hadine; Reed, Susan D.; Ensrud, Kristine E.; LaCroix, Andrea Z.; School of Nursing
Objective: To estimate the effect of escitalopram (10-20 mg/d) versus placebo for reducing hot flash interference in daily life and understand correlates and predictors of reductions in hot flash interference, a key measure of quality of life.
Design: Multisite, randomized, double-blind, placebo-controlled clinical trial.
Setting: MsFLASH clinical sites in Boston, Indianapolis, Oakland, and Philadelphia.
Patient(s): A total of 205 midlife women (46% African-American) who met criteria participated.
Intervention(s): After baseline, women were randomized to one pill of escitalopram 10 mg/d (n = 104) or placebo (n = 101) with follow-up at 4 and 8 weeks. At week 4, those not achieving 50% fewer hot flashes were increased to two pills daily (20 mg/d or 2 placebo pills).
Main outcome measure(s): The Hot Flash Related Daily Interference Scale; correlates were variables from hot flash diaries; predictors were baseline demographics, clinical variables, depression, anxiety, sleep quality, and hot flashes.
Result(s): Compared to placebo, escitalopram significantly reduced hot flash interference by 6.0 points at week 4 and 3.4 points at week 8 more than placebo. Reductions in hot flash interference correlated with changes in hot flash diary variables. However, baseline variables did not significantly predict reductions in hot flash interference.
Conclusion(s): Escitalopram (10-20 mg/d) for 8 weeks improves women's quality of life and this benefit did not vary by demographic, clinical, mood, sleep, or hot flash variables.