AN EMERGING THEORY ON THE INTERACTION BETWEEN REQUIREMENTS ENGINEERING AND SYSTEMS ARCHITECTING BASED ON A SUITE OF EXPLORATORY EMPIRICAL STUDIES

Requirements Engineering and Systems Architecting are often considered the most important phases of the software development lifecycle. Because of their close proximity in the software development lifecycle, there is a high degree of interaction between these two processes. While such interaction has been recognized and researched in terms of new technology (particularly methods and tools), there is a distinct lack of empirical understanding regarding the scientific properties of this interaction. Furthermore, in Requirements Engineering and Systems Architecting, not only technical but human aspects are considered critical for the success of these processes due to these processes lying at the front-end of the development cycle and therefore being more aligned with real-world issues. Thus, the scientific properties of the interactions between Requirements Engineering and Systems Architecting can be broken down into these two key aspects. For instance, the following example research questions relate to such scientific properties: What is the impact of an existing system’s architecture on requirements decision-making? What kinds of requirements-oriented problems are encountered during architecting? What is the impact of an existing systems architecture on new requirements being elicited? What is the impact of requirements engineering knowledge on systems architecting? There is little in the literature addressing such questions. This thesis explores such issues through a suite of six exploratory empirical studies that were conducted over the last five years. Based on the observations from these studies, an emerging theory is proposed that describes the impact of human and process factors in the interaction between Requirements Engineering and Systems Architecting. The impact of this emerging body of knowledge is deemed to be on the following: technology development for Requirements Engineering and Software Architecting (methods, tools, processes, etc.); hiring and training personnel for Requirements Engineering and Systems Architecture processes in industry; Requirements Engineering and Systems Architecture project planning; curriculum improvement in academia; and future empirical research in Requirements Engineering and Systems Architecting

Optimization of Peptides That Target Human Thymidylate Synthase to Inhibit Ovarian Cancer Cell Growth

Thymidylate synthase (TS) is a target for pemetrexed and the prodrug 5-fluorouracil (5-FU) that inhibit the protein by binding at its active site. Prolonged administration of these drugs causes TS overexpression, leading to drug resistance. The peptide lead, LR (LSCQLYQR), allosterically stabilizes the inactive form of the protein and inhibits ovarian cancer (OC) cell growth with stable TS and decreased dihydrofolate reductase (DHFR) expression. To improve TS inhibition and the anticancer effect, we have developed 35 peptides by modifying the lead. The D-glutamine-modified peptide displayed the best inhibition of cisplatin-sensitive and -resistant OC cell growth, was more active than LR and 5-FU, and showed a TS/DHFR expression pattern similar to LR. Circular dichroism spectroscopy and molecular dynamics studies provided a molecular-level rationale for the differences in structural preferences and the enzyme inhibitory activities. By combining target inhibition studies and the modulation pattern of associated proteins, this work avenues a concept to develop more specific inhibitors of OC cell growth and drug leads

Different impact of sex on baseline characteristics and major periprocedural outcomes of transcatheter and surgical aortic valve interventions: results of the multicenter Italian OBSERVANT Registry

Background: Despite the widespread use of transcatheter aortic valve implantation (TAVI), the role of sex on outcome after TAVI or surgical aortic valve replacement (AVR) has been poorly investigated. We investigated the impact of sex on outcome after TAVI or AVR. Methods: There were 2108 patients undergoing TAVI or AVR who were enrolled in the Italian Observational Multicenter Registry (OBSERVANT). Thirty-day mortality, major periprocedural morbidity, and transprosthetic gradients were stratified by sex according to interventions. Results: Female AVR patients showed a worse risk profile compared with male AVR patients, given the higher mean age, prevalence of frailty score of 2 or higher, New York Heart Association class of 3 or higher, lower body weight, and preoperative hemoglobin level (P ≤.02). Similarly, female TAVI patients had a different risk profile than male TAVI patients, given a higher age and a lower body weight and preoperative hemoglobin level (P ≤.005), but with a similar New York Heart Association class, frailty score, EuroSCORE (P = NS), a better left ventricular ejection fraction and a lower prevalence of left ventricular ejection fraction less than 30%, porcelain aorta, renal dysfunction, chronic obstructive pulmonary disease, arteriopathy, and previous cardiovascular surgery or percutaneous coronary intervention (P ≤.01). Women showed a smaller aortic annulus than men in both populations (P <.001). Female sex was an independent predictor in the AVR population for risk-Adjusted 30-day mortality (odds ratio [OR], 2.34; P =.043) and transfusions (OR, 1.47; P =.003), but not for risk-Adjusted acute myocardial infarction, stroke, vascular complications, permanent atrioventricular block (P = NS). Female sex was an independent predictor in the TAVI population for risk-Adjusted major vascular complications (OR, 2.92; P =.018) and transfusions (OR, 1.93; P =.003), but proved protective against moderate to severe postprocedural aortic insufficiency (P =.018). Conclusions: Female sex is a risk factor for mortality after aortic valve replacement, for major vascular complications after TAVI, and for transfusions after both approaches. Copyright © 2014 by The American Association for Thoracic Surgery