Synthesis and Characterization of Insulin Receptor Partial Agonists as a Route to Improved Diabetes Therapy

Thesis (Ph.D.) - Indiana University, Biochemistry, 2015Insulin-dependent diabetes requires the daily administration of insulin to regulate blood glucose. Unfortunately, insulin possesses a narrow therapeutic index which represents a risk for overdose and life-threatening hypoglycemia. This research investigates the synthesis and biological characterization of insulin-based analogs that activate the insulin receptor with high potency, but varying degrees of maximal activity. These analogs are dimeric peptides that consist of native insulin and a covalently bound insulin receptor antagonist. Structure-activity analysis revealed a key amino acid within the antagonist, and mutations at this single position control the maximal activity of the heterodimer. These analogs may represent a route to a safer insulin therapy, through selection of an optimized analog that has diminished activity relative to the native hormone

Design Review Report: Zero G Design Group

The purpose of this report is to describe the design, construction, and testing of an apparatus capable of testing and recording the deployment of thin film shells in a microgravity environment. The group has designed a prototype and ideal model to test a deceleration system that, in full scale, would provide sufficient deceleration without harming the testing apparatus. This project does not involve dropping the constructed apparatus and equipment. A counter weight chain and pulley system was chosen as the deceleration prototype for testing. Issues with budget and time constraints have limited aspects originally planned for completion in this phase of the project. Budgetary issues have restricted mounting of the electrical components within the fabricated apparatus and purchasing housing for the enclosure. Data from the prototype tests from the counterweight deceleration were collected and compared to an ideal model. Analysis of results determined that a counterweight system is sufficient for decelerating the load, but modifications need to be made to the model to accurately predict its behavior. Despite issues integrating the full system with the Efika, the automation timing sequence and video recording drivers have been successfully written and tested. In the face of obstacles and delays, the project is taking shape and the group feels confident with its direction and design

Arquitectura, cenografia e dança : a expressão da dança em 3 cenografias de João Mendes Ribeiro com Olga Roriz

Exame público realizado em 16 de Maio de 2022Dissertação de mestrado integrado em Arquitectura, Universidade Lusíada de Lisboa, 2022Esta dissertação procura, a relação entre a Arquitectura, a Cenografia e a Dança. Quais as suas diferenças? O que têm em comum? Onde se cruzam? A história e influências de cada uma das disciplinas. Expõe-se a ambiguidade do território cenográfico, expondo também as convergências conceptuais e até os seus processos, tal como a reciprocidade entre estas, o cruzamento das matérias e ainda de várias artes, o que faz naturalmente remeter a casos de estudo como, por exemplo, a Bauhaus e o seu Ballet-triádico de Oskar Schlemmer. Esta procura acontece através do factor comum, com que se torna o centro desta investigação, o corpo no espaço. Tanto na Arquitectura, na Cenografia e na Dança, o corpo é a base e o centro. Este corpo que constrói um discurso, uma narrativa espacial nas três disciplinas, faz questionar como as influencia e como reage. Estes três temas induzem a investigação de autores que foram pioneiros e grandes influências nestas narrativas espaciais, criando a ligação entre Arquitectura/Cenografia/Dança, encontrando Pina Bausch. Consequentemente explora-se a relação dos espaços e dos objectos com o corpo em movimento, atravessando temas como a materialidade, a funcionalidade e a multiplicidade arquitectónica, tal como o tema da noção da habitualidade do espaço cénico através da estreita relação entre o objecto cénico e o corpo, não obstante a verdade dos materiais e a evidência construtiva. Aborda-se ainda a questão da flexibilidade e multiplicidade dos objectos cénicos, em relação à experimentação em torno de cenografias dinâmicas que se modificam a si ou à paisagem, através da manipulação dos intérpretes, para tal investiga-se obras da Coreógrafa Olga Roriz com cenografias do Arquitecto e Cenógrafo João Mendes Ribeiro. A Cenografia é abordada do ponto de vista da experimentação de processos e linguagens comuns à arquitectura e cruzando um vasto e diversificado quadro disciplinar; os projectos apresentados vão convocando noções que residem em ambos através de exemplos de cenografias que tem como referência projectos de arquitectura, tal como projectos de arquitectura que tem como influencia cenografias através de casos de estudo de projectos do Arquitecto e Cenógrafo João Mendes Ribeiro. A componente humana e a vivência nos espaços, são temas centrais tanto na Arquitectura como na Cenografia e não há exemplo melhor que a dança, um bailarino como demonstração de um corpo que se movimenta num espaço, através das suas geometrias.This dissertation seeks, the relationship betweenArchitecture, Scenography and Dance. What are their differences? What do they have in common? Where do they intersect? The history and influences of each discipline. The ambiguity of the scenographic territory is exposed, also exposing the conceptual convergences and even its processes, such as the reciprocity between them, the crossing of materials and even of several arts, which naturally makes reference to case studies such as, for example, the Bauhaus and its Ballet-triadic of Oskar Schlemmer. This search happens through the common factor that becomes the center of this research, the body in space. In Architecture, in Scenography and in Dance, the body is the base and the center. This body that constructs a discourse, a spatial narrative in the three disciplines, makes one question how it influences them and how it reacts. These three themes induce the investigation of authors who were pioneers and great influences in these spatial narratives, creating the connection between Architecture/Scenography/Dance, finding Pina Bausch. Consequently, the relationship of spaces and objects with the body in movement is explored, crossing themes such as materiality, functionality and architectural multiplicity, as well as the notion of the habitualness of the scenic space through the close relationship between the scenic object and the body, despite the truth of the materials and the constructive evidence. The question of flexibility and multiplicity of the scenic objects is also approached, in relation to the experimentation around dynamic scenographies that modify themselves or the scenery, through the manipulation of the performers. For this purpose we investigate works by the Choreographer Olga Roriz with scenographies by the Architect and Scenographer João Mendes Ribeiro. Scenography is approached from the point of view of experimentation with processes and languages common to architecture and crossing a vast and diverse disciplinary framework; the presented projects will convoke notions that reside in both through examples of scenography that have architecture projects as reference, as well as architecture projects that have scenography as influence through case studies of projects by the Architect and Scenographer João Mendes Ribeiro. The human component and the experience in spaces are central themes in both Architecture and Scenography and there is no better example than dance, a dancer as a demonstration of a body that moves in a space, through its geometries

Faculty Recital Series: Ben Stiers, Percussion; Andy Rummel, Tuba; Baryl Brandt, Vibraphone; Noah Berkshier, Marimba; Sara Eckert, Marimba; October 25, 2022

Kemp Recital HallOctober 25, 2022Tuesday Evening8:00 p.m

Tapping Environmental History to Recreate America’s Colonial Hydrology

To properly remediate, improve, or predict how hydrological systems behave, it is vital to establish their histories. However, modern-style records, assembled from instrumental data and remote sensing platforms, hardly exist back more than a few decades. As centuries of data is preferable given multidecadal fluxes of both meteorology/climatology and demographics, building such a history requires resources traditionally considered only useful in the social sciences and humanities. In this Feature, Pastore et al. discuss how they have undertaken the synthesis of historical records and modern techniques to understand the hydrology of the Northeastern U.S. from Colonial times to modern day. Such approaches could aid studies in other regions that may require heavier reliance on qualitative narratives. Further, a better insight as to how historical changes unfolded could provide a “past is prologue” methodology to increase the accuracy of predictive environmental models

European Respiratory Society International Congress 2020: highlights from best-abstract awardees

During the 2020 European Respiratory Society (ERS) International Congress, the author of the best abstract (highest average score of abstract reviewers and only those who had not applied or were not eligible for a sponsored award) of every Assembly was awarded “a best-abstract certificate”. Best-abstract awardees were invited to write a short summary about their virtual Congress experience and their view on the evolving field of research in light of their respective ERS Assembly. The purpose of this article is to give the readers a quick overview of some of the Congress highlights and to give the stage to the promising best-abstract awardees as they are the future of the ERS.info:eu-repo/semantics/publishedVersio

Residual manifestations of hypercortisolemia following surgical treatment in a patient with Cushing syndrome.

CONTEXT: Cushing Syndrome is difficult to diagnose, and the comorbidities and persistent late effects of hypercortisolemia after treatment of the primary disease are challenging for the patient and the endocrinologist. OBJECTIVE: To report the case of a girl with obesity and hypertension, ultimately diagnosed with Cushing syndrome due to primary pigmented nodular adrenocortical disease. In this case, the complications of hypercortisolism persisted short term despite surgical intervention. PATIENT: A 4 year old morbidly obese African-American girl with developmental delay presented with hypertensive emergency in the ER and 18-month history of progressive weight gain. Her previous history included premature adrenarche, hypertension, seizures and a random high cortisol with suppressed ACTH. She was subsequently stabilized, and a diagnostic work-up persistently demonstrated elevated cortisol and suppressed ACTH. An abdominal MRI showed bilateral adrenal multinodular disease, consistent with multinodular hyperplasia of the adrenal glands. Based on these findings the patient underwent a bilateral adrenalectomy, which confirmed primary pigmented nodular adrenocortical disease. The patient had a complicated, protracted post-operative course requiring adjustment of therapy for persistent hypertension. Two months after surgery, she was readmitted to the Emergency Department with hyperpyrexia and hypertension and succumbed to the complications of sepsis. CONCLUSIONS AND OUTCOME: This case highlights the significant diagnostic and therapeutic challenges in treating children with Cushing syndrome. Resolution of the source of hypercortisolemia does not imply regression of hypertension or recovery of the immune system. Although the child underwent bilateral adrenalectomy, persistent consequences of prolonged severe hypercortisolism contributed to her death two months later

Metabolic Glycoengineering Enables the Ultrastructural Visualization of Sialic Acids in the Glycocalyx of the Alveolar Epithelial Cell Line hAELVi

The glycocalyx-a plethora of sugars forming a dense layer that covers the cell membrane-is commonly found on the epithelial surface of lumen forming tissue. New glycocalyx specific properties have been defined for various organs in the last decade. However, in the lung alveolar epithelium, its structure and functions remain almost completely unexplored. This is partly due to the lack of physiologically relevant, cost effective in vitro models. As the glycocalyx is an essential but neglected part of the alveolar epithelial barrier, understanding its properties holds the promise to enhance the pulmonary administration of drugs and delivery of nanoparticles. Here, using air-liquid-interface (ALI) cell culture, we focus on combining metabolic glycoengineering with glycan specific electron and confocal microscopy to visualize the glycocalyx of a recently immortalized human alveolar epithelial cell line (hAELVi). For this purpose, we applied different bioorthogonal labeling approaches to visualize sialic acid-an amino sugar that provides negative charge to the lung epithelial glycocalyx-using both fluorescence and gold-nanoparticle labeling. Further, we compared mild chemical fixing/freeze substitution and standard cytochemical electron microscopy embedding protocols for their capacity of contrasting the glycocalyx. In our study, we established hAELVi cells as a convenient model for investigating human alveolar epithelial glycocalyx. Transmission electron microscopy revealed hAELVi cells to develop ultrastructural features reminiscent of alveolar epithelial type II cells (ATII). Further, we visualized extracellular uni- and multilamellar membranous structures in direct proximity to the glycocalyx at ultrastructural level, indicating putative interactions. The lamellar membranes were able to form structures of higher organization, and we report sialic acid to be present within those. In conclusion, combining metabolite specific glycoengineering with ultrastructural localization presents an innovative method with high potential to depict the molecular distribution of individual components of the alveolar epithelial glycocalyx and its interaction partners

The Power to Resist: Mobilization and the Logic of Terrorist Attacks in Civil War

Existing research has argued that terrorism is common in civil war because it is "effective." Surprisingly, however, only some groups use terrorism during civil wars, while many refrain altogether. We also see considerable variation in the use of terrorism over time. This article presents a theory of terrorism as a mobilization strategy in civil war, taking into account benefits, costs, and temporal dynamics. We argue that the choice and the timing of terrorism arise from the interaction between conditions for effective mobilization and battlefield dynamics. Terrorism can mobilize support when it provokes indiscriminate government repression or when it radicalizes rebels' constituency by antagonizing specific societal groups. The timing of attacks, however, is in uenced by battlefield losses, which increase rebels' need to rally civilian support. The analyses of new disaggregated data on rebels' terrorist attacks during con icts (1989-2009) and of ISIS tactics in Iraq and Syria support our theoretical argument

Development of a Web-Based Clinical Decision Support System for Drug Prescription: ...

Purpose The emergence of electronic prescribing devices with clinical decision support systems (CDSS) is able to significantly improve management pharmacological treatments. We developed a web application available on smartphones in order to help clinicians monitor prescription and further propose CDSS. Method A web application (www.MEmind.net) was developed to assess patients and collect data regarding gender, age, diagnosis and treatment. We analyzed antipsychotic prescriptions in 4345 patients attended in five Psychiatric Community Mental Health Centers from June 2014 to October 2014. The web-application reported average daily dose prescribed for antipsychotics, prescribed daily dose (PDD), and the PDD to defined daily dose (DDD) ratio. Results The MEmind web-application reported that antipsychotics were used in 1116 patients out of the total sample, mostly in 486 (44%) patients with schizophrenia related disorders but also in other diagnoses. Second generation antipsychotics (quetiapine, aripiprazole and long-acting paliperidone) were preferably employed. Low doses were more frequently used than high doses. Long acting paliperidone and ziprasidone however, were the only two antipsychotics used at excessive dosing. Antipsychotic polypharmacy was used in 287 (26%) patients with classic depot drugs, clotiapine, amisulpride and clozapine. Conclusions In this study we describe the first step of the development of a web application that is able to make polypharmacy, high dose usage and off label usage of antipsychotics visible to clinicians. Current development of the MEmind web application may help to improve prescription security via momentary feedback of prescription and clinical decision support system