Jazz and the college curriculum.

Thesis (M.M.E.)--Boston Universit

TESTING FOR CORRECTNESS AND REBASELINING OF IMAGES

An image correctness testing system compares an expected image with an image generated at a device. The system transmits the expected image to the device. The system then analyzes the image that is generated at the device in order to determine a checksum of the image generated at the device. The system further compares the checksum of the image generated at the device with a checksum of the expected image and presents a difference to a user on a web interface. The system can then receive an input from the user to rebaseline the image generated at the device and/or the expected image. On receiving the user input, the system updates the checksum of the expected image equal to the checksum of the image generated at the device or vice versa

Primary care providers\u27 perspectives on online weight-loss programs: a big wish list

BACKGROUND: Integrating online weight-loss programs into the primary care setting could yield substantial public health benefit. Little is known about primary care providers\u27 perspectives on online weight-loss programs. OBJECTIVE: To assess primary care providers\u27 perspectives on online weight-loss programs. METHODS: We conducted focus group discussions with providers in family medicine, internal medicine, and combined internal medicine/pediatrics in Texas and Pennsylvania, USA. Open-ended questions addressed their experience with and attitudes toward online weight-loss programs; useful characteristics of existing online weight-loss programs; barriers to referring patients to online weight-loss programs; and preferred characteristics of an ideal online weight-loss program. Transcripts were analyzed with the grounded theory approach to identify major themes. RESULTS: A total of 44 primary care providers participated in 9 focus groups. The mean age was 45 (SD 9) years. Providers had limited experience with structured online weight-loss programs and were uncertain about their safety and efficacy. They thought motivated, younger patients would be more likely than others to respond to an online weight-loss program. According to primary care providers, an ideal online weight-loss program would provide-at no cost to the patient-a structured curriculum addressing motivation, psychological issues, and problem solving; tools for tracking diet, exercise, and weight loss; and peer support monitored by experts. Primary care providers were interested in receiving reports about patients from the online weight-loss programs, but were concerned about the time required to review and act on the reports. CONCLUSIONS: Primary care providers have high expectations for how online weight-loss programs should deliver services to patients and fit into the clinical workflow. Efforts to integrate online weight-loss programs into the primary care setting should address efficacy and safety of online weight-loss programs in clinic-based populations; acceptable methods of sending reports to primary care providers about their patients\u27 progress; and elimination or reduction of costs to patients

A Common Model for Cytokine Receptor Activation: Combined Scissor-Like Rotation and Self-Rotation of Receptor Dimer Induced by Class I Cytokine

The precise mechanism by which the binding of a class I cytokine to the extracellular domain of its corresponding receptor transmits a signal through the cell membrane remains unclear. Receptor activation involves a cytokine-receptor complex with a 1∶2 stoichiometry. Previously we used our transient-complex theory to calculate the rate constant of the initial cytokine-receptor binding to form a 1∶1 complex. Here we computed the binding pathway leading to the 1∶2 activation complex. Three cytokine systems (growth hormone, erythropoietin, and prolactin) were studied, and the focus was on the binding of the extracellular domain of the second receptor molecule after forming the 1∶1 complex. According to the transient-complex theory, translational and rotation diffusion of the binding entities bring them together to form a transient complex, which has near-native relative separation and orientation but not the short-range specific native interactions. Subsequently conformational rearrangement leads to the formation of the native complex. We found that the changes in relative orientations between the two receptor molecules from the transient complex to the 1∶2 native complex are similar for the three cytokine-receptor systems. We thus propose a common model for receptor activation by class I cytokines, involving combined scissor-like rotation and self-rotation of the two receptor molecules. Both types of rotations seem essential: the scissor-like rotation separates the intracellular domains of the two receptor molecules to make room for the associated Janus kinase molecules, while the self-rotation allows them to orient properly for transphosphorylation. This activation model explains a host of experimental observations. The transient-complex based approach presented here may provide a strategy for designing antagonists and prove useful for elucidating activation mechanisms of other receptors

The effect of membrane curvature on the conformation of antimicrobial peptides: implications for binding and the mechanism of action

Short cationic antimicrobial peptides (AMPs) are believed to act either by inducing transmembrane pores or disrupting membranes in a detergent-like manner. For example, the antimicrobial peptides aurein 1.2, citropin 1.1, maculatin 1.1 and caerin 1.1, despite being closely related, appear to act by fundamentally different mechanisms depending on their length. Using molecular dynamics simulations, the structural properties of these four peptides have been examined in solution as well as in a variety of membrane environments. It is shown that each of the peptides has a strong preference for binding to regions of high membrane curvature and that the structure of the peptides is dependent on the degree of local curvature. This suggests that the shorter peptides aurein 1.2 and citropin 1.1 act via a detergent-like mechanism because they can induce high local, but not long-range curvature, whereas the longer peptides maculatin 1.1 and caerin 1.1 require longer range curvature to fold and thus bind to and stabilize transmembrane pores

Molecular simulations of venom peptide-membrane interactions: Progress and challenges

Because of their wide range of biological activities venom peptides are a valuable source of lead molecules for the development of pharmaceuticals, pharmacological tools and insecticides. Many venom peptides work by modulating the activity of ion channels and receptors or by irreversibly damaging cell membranes. In many cases, the mechanism of action is intrinsically linked to the ability of the peptide to bind to or partition into membranes. Thus, understanding the biological activity of these venom peptides requires characterizing their membrane binding properties. This review presents an overview of the recent developments and challenges in using biomolecular simulations to study venom peptide‐membrane interactions. The review is focused on (i) gating modifier peptides that target voltage‐gated ion channels, (ii) venom peptides that inhibit mechanosensitive ion channels, and (iii) pore‐forming venom peptides. The methods and approaches used to study venom peptide‐membrane interactions are discussed with a particular focus on the challenges specific to these systems and the type of questions that can (and cannot) be addressed using state‐of‐the‐art simulation techniques. The review concludes with an outlook on future aims and directions in the field