Interview with Ed Neubauer

https://digitalcommons.providence.edu/psp470_2023/1004/thumbnail.jp

MKK3 sustains cell proliferation and survival through p38DELTA MAPK activation in colorectal cancer

: Colorectal cancer (CRC) is one of the most common malignant tumors worldwide and understanding its underlying molecular mechanisms is crucial for the development of therapeutic strategies. The mitogen-activated protein kinase-kinase 3 (MKK3) is a specific activator of p38 MAP kinases (p38 MAPKs), which contributes to the regulation of several cellular functions, such as proliferation, differentiation, apoptosis as well as response to drugs. At present, the exact MKK3/p38 MAPK pathway contribution in cancer is heavily debated because of its pleiotropic function. In this work, we retrospectively explored the prognostic and pathobiologic relevance of MKK3 in a cohort of CRC patients and assessed MKK3 molecular functions in a panel of CRC lines and colonocytes primary cultures. We found increased MKK3 levels in late-stage CRC patients which correlated with shorter overall survival. Herein, we report that the MKK3 targeting by inducible RNA interference univocally exerts antitumor effects in CRC lines but not in primary colonocytes. While MKK3 depletion per se affects growth and survival by induction of sustained autophagy and death in some CRC lines, it potentiates response to chemotherapeutic drug 5-fluorouracil (5-FU) in all of the tested CRC lines in vitro. Here, we demonstrate for the first time that in CRC the MKK3 specifically activates p38delta MAPK isoform to sustain prosurvival signaling and that such effect is exacerbated upon 5-FU challenge. Indeed, p38delta MAPK silencing recapitulates MKK3 depletion effects in CRC cells in vitro and in vivo. Overall, our data identified a molecular mechanism through which MKK3 supports proliferation and survival signaling in CRC, further supporting MKK3 as a novel and extremely attractive therapeutic target for the development of promising strategies for the management of CRC patients

Evaluation of a synthetic single-crystal diamond detector for relative dosimetry on the Leksell Gamma Knife Perfexion radiosurgery system

Purpose: To evaluate the new commercial PTW-60019 synthetic single-crystal microDiamond detector (PTW, Freiburg, Germany) for relative dosimetry measurements on a clinical Leksell Gamma Knife Perfexion radiosurgery system. Methods: Detector output ratios (DORs) for 4 and 8 mm beams were measured using a micro- Diamond (PTW-60019), a stereotactic unshielded diode [IBA stereotactic field detector (SFD)], a shielded diode (IBA photon field detector), and GafChromic EBT3 films. Both parallel and transversal acquisition directions were considered for PTW-60019 measurements. Measured DORs were compared to the new output factor reference values for Gamma Knife Perfexion (0.814 and 0.900 for 4 and 8 mm, respectively). Profiles in the three directions were also measured for the 4 mm beam to evaluate full width at half maximum (FWHM) and penumbra and to compare them with the corresponding Leksell GammaPlan profiles. Results: FWHM and penumbra for PTW-60019 differed from the calculated values by less than 0.2 and 0.3 mm, for the parallel and transversal acquisitions, respectively. GafChromic films showed FWHM and penumbra within 0.1 mm. The output ratio obtained with the PTW-60019 for the 4 mm field was 1.6% greater in transverse direction compared to the nominal value. Comparable differences up to 0.8% and 1.0% for, respectively, GafChromic films and SFD were found. Conclusions: The microDiamond PTW-60019 is a suitable detector for commissioning and routine use of Gamma Knife with good agreement of both DORs and profiles in the three directions

“It's not just about the migrants.” Anti-immigrant discourse and co-opted marginality in the online public sphere

Lately, presumed dominant groups of citizens have expressed negative sentiments toward immigrants while claiming they are marginalized. I call these claims co-opted marginality. Co-opted marginality discourse put an unconventional association between individuals’ social situations and beliefs to the fore. Here, in-groups are disadvantaged, and outgroups are perceived as favored. The consideration defies traditional social principles and obscures the act of othering with concerns about ordering and questions how anti-immigrant discourse in the public sphere is traditionally analyzed. This dissertation explores the emergence of new narratives about immigrants, like co-opted marginality in the online environment, and suggests an alternative theoretical framework based on counterpublic theory to analyze anti-immigrant discourse. The research is based on a concurrent mixed-methods design based on semi-structured interviews (N=36) and a computer-aided content analysis of comments collected in online public forums of Singapore over six months (N= 399,599). The findings suggest that anti-immigrant discourse on social media is complex; the overt expression of negativity (xenophobia) competes with claims that engage the authorities’ responsibility and typify citizens’ fears of marginalization. The results also raise questions about social media offering opportunities for potentially influential alternative counterpublic discourses connecting via emotions, expressing co-opted marginality. It is essential to highlight that the study takes place within the specific context of a controlled media environment, possibly limiting its generalizability to different socio-political conditions. However, the thesis advocates investigating co-optation strategies online and evaluating their effects on attitudes and behaviors towards issues (e.g., racism) that are problematized by the dominant normative cognitive structure.  Doctor of Philosoph

Comparazione di vari modelli per la stima dell’evapotraspirazione di una coltura fuori suolo di pomodoro

La tesi si inserisce nelle attività di ricerca e di sperimentazione del progetto PRIMA iGUESS-Med (Innovative Greenhouse Support System in the Mediterranean Region efficient fertigation and pest management through IoT based climate control), il cui obiettivo è quello di sviluppare un Decision Support System (DSS) in grado di ridurre la dispersione di nutrienti e l’uso di sostanze chimiche nelle colture protette di pomodoro. Per poter aumentare l’efficienza nell’uso di acqua e nutrienti, iGUESS-Med DSS utilizza un modello di crescita del pomodoro per stimare il fabbisogno di acqua e fertilizzanti in diverse condizioni di allevamento della coltura e implementa tre modelli semplificati per la stima dell’evapotraspirazione della stessa (Radiation model-Almeria; Hargreaves model, e FAO24 Radiation model) calibrati e validati nell’areale di Almeria. Il principale scopo della presente tesi è stato quello di raccogliere dati di consumo idrico, pH ed EC di una coltura di pomodoro cv. Pisanello, una varietà locale toscana, coltivata in fuori suolo a ciclo chiuso su substrato di lana di roccia (Grodan®) e allevata in due differenti stagioni (autunno e primavera, con condizioni climatiche assai differenti da quelle di Almeria) e con 3 livelli differenti di conducibilità elettrica: 3.0, 6.0 e 9.0 mS/cm, per poter comparare la bontà dei tre modelli citati nella stima dell’evapotraspirazione di questa coltura. I risultati ottenuti hanno confermato una media-buona attendibilità della stima dell’evapotraspirazione della coltura dei tre modelli semplificati. In particolare, essendo i tre modelli composti da due sottomodelli, uno per la stima dell’evapotraspirazione potenziale (ET0) e l’altro dalla stima del coefficiente colturale (Kc), si è effettuato il confronto del valore di ET0 ottenuta dai tre modelli semplificati con il modello ufficiale di riferimento FAO56, evidenziando che parte della discrepanza fra evapotraspirazione misurata e stimata può essere attribuita anche ad un errore nella stima del coefficiente colturale, dovuto probabilmente alla differente varietà di pomodoro utilizzata e sistema colturale adottato in Italia rispetto ad Almeria

Rischio di caduta in pazienti amputati all'arto inferiore. Sviluppo di un modello di previsione e di una web application.

Il presente lavoro si pone l'obiettivo di realizzare un'applicazione web in grado di prevedere il rischio di caduta in pazienti con amputazione all'arto inferiore. La realizzazione si articola in due fasi: la prima comprende lo sviluppo di un modello di previsione e la seconda l'implementazione su web application tramite i framework Spring MVC e Bootstrap. Il lavoro comprende un'analisi del problema clinico dell'amputazione, uno studio sulla biomeccanica del cammino degli amputati e sui principali componenti delle protesi e una review dei principali fattori di rischio per la caduta. Lo scopo è quello di fornire uno strumento che possa individuare i soggetti esposti a rischi maggiori per consentire di effettuare interventi preventivi che possano evitare le gravi conseguenze che le cadute hanno su questa categoria di pazienti

Co-opted Marginality and Social Media in Singapore

Social media provide a platform for groups that are not conventionally ostracized to claim marginality. This study proposes a working definition for the phenomenon of co-opted marginality within the context of communication on social media. The phenomenon is examined in the Singaporean context; 17 Singaporean citizens were interviewed about their experiences with immigration online and offline. We find that, within constrained legal, social, and traditional media environments, social media provides a platform for a dominant group facing challenges to enact co-opted marginality