Development of a Molecularly Imprinted Polymer for Use in Biomolecule Detection

Thesis advisor: Thomas ChilesMolecular recognition is an important area of research as it has far reaching applications in sensors, molecular separations, and medicine. Molecularly imprinted polymers offer an option for developing high resolution tools of detection that are both selective and sensitive. As a platform, carbon nanotubes offer a highly conductive surface and their growth and unique magnetic properties can be manipulated for our purposes. Such carbon-nanotube based sensors can afford high sensitivity, while molecular imprinting provides the selectivity of detection with the flexibility of fabrication. In order to fabricate a molecular imprint, monomeric compounds are polymerized in the presence of a target molecule of interest, which acts as the template. Once the template molecule has been removed an imprint capable of “recapturing” the target molecule is left behind. In this work we used cyclic voltammetry as a means of depositing polymer coatings doped with a target molecule. We fabricated a molecularly imprinted polymer sensor specific for ferritin using polyphenol as the polymer. The development of our imprint was monitored based on changes in impedance levels calculated by electrochemical impedance spectroscopy. After depositing ferritin-doped polyphenol layers we evaluated the effectiveness of different eluant solutions. Ultimately, deionized water was determined to be the developing solution of choice because it effectively removed the ferritin while not compromising the integrity of the remaining polymer coating. The sensor was capable of detecting ferritin at a concentration of 1x10-9 g/L (1 pg/mL). In parallel we evaluated the stability of the polyphenol coating.Thesis (BS) — Boston College, 2009.Submitted to: Boston College. College of Arts and Sciences.Discipline: College Honors Program.Discipline: Biology

Pilot Study of Delayed ICOS/ICOS-L Blockade With alphaCD40 to Modulate Pathogenic Alloimmunity in a Primate Cardiac Allograft Model

Background: Inducible costimulator (ICOS) is rapidly upregulated with T-cell stimulation and may represent an escape pathway for T-cell costimulation in the setting of CD40/CD154 costimulation blockade. Induction treatment exhibited no efficacy in a primate renal allograft model, but rodent transplant models suggest that the addition of delayed ICOS/ICOS-L blockade may prolong allograft survival and prevent chronic rejection. Here, we ask whether ICOS-Ig treatment, timed to anticipate ICOS upregulation, prolongs NHP cardiac allograft survival or attenuates pathogenic alloimmunity. Methods: Cynomolgus monkey heterotopic cardiac allograft recipients were treated with alphaCD40 (2C10R4, d0-90) either alone or with the addition of delayed ICOS-Ig (d63-110). Results: Median allograft survival was similar between ICOS-Ig + alphaCD40 (120 days, 120-125 days) and alphaCD40 (124 days, 89-178 days) treated animals, and delayed ICOS-Ig treatment did not prevent allograft rejection in animals with complete CD40 receptor coverage. Although CD4(+) TEM cells were decreased in peripheral blood (115 +/- 24) and mLNs (49 +/- 1.9%) during ICOS-Ig treatment compared with monotherapy (214 +/- 27%, P = 0.01; 72 +/- 9.9%, P = 0.01, respectively), acute and chronic rejection scores and kinetics of alloAb elaboration were similar between groups. Conclusions: Delayed ICOS-Ig treatment with the reagent tested is probably ineffective in modulating pathogenic primate alloimmunity in this model

Pregnancy-associated breast cancer and increased risk of pregnancy-associated recurrence: a case report

Abstract Introduction Pregnancy-associated breast cancer refers to breast cancer diagnosed during pregnancy, lactation, or within twelve months postpartum. Recent studies suggest that, when matched for age and stage, the prognosis of pregnancy-associated breast cancer is comparable to non-pregnancy-associated breast cancer. However, the risk for breast cancer recurrence associated with subsequent pregnancies in this population is not clear. Case presentation We describe the case of a Caucasian woman who was initially treated for pregnancy-associated breast cancer at age 23, three months after the birth of her third child. She underwent a total mastectomy with axillary node dissection, followed by chemotherapy and hormonal therapy. Ten years later, when the patient was 24 weeks pregnant with her fourth child, she presented with an ipsilateral chest wall recurrence of breast cancer. To the best of our knowledge, this represents the first reported case of a pregnancy-associated recurrence in a patient previously treated for pregnancy-associated breast cancer. Conclusion The case described here is the first report of a second occurrence of pregnancy-associated breast cancer. This case raises the possibility that pregnancy may represent a unique trigger for breast malignancy in a specific cohort of women. Although there is data showing no increase in the risk of recurrence for women who become pregnant after breast cancer treatment, pregnancy-associated breast cancer may be a distinct clinical category where subsequent pregnancies after treatment may confer an increased risk of recurrent disease.</p

Procurement characteristics of high- and low-performing OPOs as seen in OPTN/SRTR data

To meet new Centers for Medicare and Medicaid Services (CMS) metrics, organ procurement organizations (OPOs) will benefit from understanding performance across decedent and hospital types. We sought to determine the utility of existing data-reporting structures for this purpose by reviewing Scientific Registry of Transplant Recipient (SRTR) OPO-Specific Reports (OSRs) from 2013 to 2019. OSRs contain both the Standardized donation rate ratio (SDRR) metric and OPO-reported numbers of "eligible deaths" and donors by hospital. Donor hospitals were characterized using information from Homeland Infrastructure Foundation-Level Data, Dartmouth Atlas Hospital Service Area data, and the US Census Bureau. Hospital data reported by OPOs showed 51% higher eligible death donors and 140% higher noneligible death donors per 100 inpatient beds in CMS ranked top versus bottom-quartile OPOs. Top-quartile OPOs by the CMS metric recovered 78% more donors than those in the bottom quartile, but were indistinguishable by SDRR rankings. These differences persisted across hospital sizes, trauma case mix, and area demographics. OPOs with divergent performance were indistinguishable over time by SDRR, but showed changes to hospital-level recovery patterns in SRTR data. Contemporaneous recognition of underperformance across hospitals may provide important and actionable data for regulators and OPOs for focused quality improvement projects

Pilot Study of Delayed ICOS/ICOS-L Blockade With αCD40 to Modulate Pathogenic Alloimmunity in a Primate Cardiac Allograft Model

Background. Inducible costimulator (ICOS) is rapidly upregulated with T-cell stimulation and may represent an escape pathway for T-cell costimulation in the setting of CD40/CD154 costimulation blockade. Induction treatment exhibited no efficacy in a primate renal allograft model, but rodent transplant models suggest that the addition of delayed ICOS/ICOS-L blockade may prolong allograft survival and prevent chronic rejection. Here, we ask whether ICOS-Ig treatment, timed to anticipate ICOS upregulation, prolongs NHP cardiac allograft survival or attenuates pathogenic alloimmunity. Methods. Cynomolgus monkey heterotopic cardiac allograft recipients were treated with αCD40 (2C10R4, d0-90) either alone or with the addition of delayed ICOS-Ig (d63-110). Results. Median allograft survival was similar between ICOS-Ig + αCD40 (120 days, 120-125 days) and αCD40 (124 days, 89-178 days) treated animals, and delayed ICOS-Ig treatment did not prevent allograft rejection in animals with complete CD40 receptor coverage. Although CD4+ TEM cells were decreased in peripheral blood (115 ± 24) and mLNs (49 ± 1.9%) during ICOS-Ig treatment compared with monotherapy (214 ± 27%, P = 0.01; 72 ± 9.9%, P = 0.01, respectively), acute and chronic rejection scores and kinetics of alloAb elaboration were similar between groups. Conclusions. Delayed ICOS-Ig treatment with the reagent tested is probably ineffective in modulating pathogenic primate alloimmunity in this model