Many new curricular andinstructionalmodels must be developedor adapted as the nationmoves towards educational reform in science classrooms. This article describes how problem-based learning, an innovative curricular and instructionalmodel developed inmedical graduate schoolprograms, has been adapted for use in elementary and high school settings. Included in the integration of problem-based learning and science are components of allproblem-based episodes including initiating learning with an ill-structuredproblem, using the problem to structure the learning agenda, and teacher as metacognitive coach, wth important goals of a reformed science curriculum such as learning based on concepts of significance, student-designed experiments, and development of scientific reasoning skills, The community ofscience educators seems poised for action. There is widespread agreement that an understanding of science is increasingly critical to effective functioning in a democratic society, as issues

Classroom instruction in problem solving often takes the form of presenting neat, verification-style problems to students at the end of a period of learning. This practice stands in stark contrast to professional problem solving, where the problem comes first, and is a catalyst for investigation and learning. Problem-based learning provides students with an opportunity to grapple with realistic, ill-structured problems using the same kinds of techniques and habits of mind professionals use. The problem-based curriculum and instruction design puts students in the role of professional problem solvers by designing instruction around the investigation of an ill-structured problem. Teachers act as metacognitive coaches and tutors instead of “experts” who have the “right answer” to the problem. Two different applications of problem-based learning at the Illinois Mathematics and Science Academy are described in this article. One application is in an interdisciplinary senior elective course entitled Science, Society and the Future where problems investigate modern dilemmas resulting in modern advances in science and technology; the other is in a more traditional sophomore required course, American Studies, where the problems studied provide students with a feel for the critical decisions which drove the development of the Nation. A description of research projects underway to document the effectiveness of the program is also provided.

The high dose+adjuvant (100 μg antigen+AlOH) formulation administered at 0-7-30 days elicited the best immune response profile, including functional antibody responses, through Day 180 and was selected for use in subsequent clinical trials.

Hydrophobic ion pairing (HIP) can successfully increase the drug loading and control the release kinetics of ionizable hydrophilic drugs, addressing challenges that prevent these molecules from reaching the clinic. Nevertheless, polymeric nanoparticle (PNP) formulation development requires trial-and-error experimentation to meet the target product profile, which is laborious and costly. Herein, we design a preformulation framework (solid-state screening, computational approach, and solubility in PNP-forming emulsion) to understand counterion–drug–polymer interactions and accelerate the PNP formulation development for HIP systems. The HIP interactions between a small hydrophilic molecule, AZD2811, and counterions with different molecular structures were investigated. Cyclic counterions formed amorphous ion pairs with AZD2811; the 0.7 pamoic acid/1.0 AZD2811 complex had the highest glass transition temperature (T g; 162 °C) and the greatest drug loading (22%) and remained as phase-separated amorphous nanosized domains inside the polymer matrix. Palmitic acid (linear counterion) showed negligible interactions with AZD2811 (crystalline-free drug/counterion forms), leading to a significantly lower drug loading despite having similar log P and pK a with pamoic acid. Computational calculations illustrated that cyclic counterions interact more strongly with AZD2811 than linear counterions through dispersive interactions (offset π–π interactions). Solubility data indicated that the pamoic acid/AZD2811 complex has a lower organic phase solubility than AZD2811-free base; hence, it may be expected to precipitate more rapidly in the nanodroplets, thus increasing drug loading. Our work provides a generalizable preformulation framework, complementing traditional performance-indicating parameters, to identify optimal counterions rapidly and accelerate the development of hydrophilic drug PNP formulations while achieving high drug loading without laborious trial-and-error experimentation.

Since inexpensive computers possessing sophisticated graphics were introduced in the late 1970s, program development research has focused on syntax-directed editors that are based on the grammars of their underlying languages. The system presented here automatically generates object-oriented, syntax-directed editors for visual languages, which are described by a family of editing operations.