Applying forces to elastic network models of large biomolecules using a haptic feedback device

Elastic network models of biomolecules have proved to be relatively good at predicting global conformational changes particularly in large systems. Software that facilitates rapid and intuitive exploration of conformational change in elastic network models of large biomolecules in response to externally applied forces would therefore be of considerable use, particularly if the forces mimic those that arise in the interaction with a functional ligand. We have developed software that enables a user to apply forces to individual atoms of an elastic network model of a biomolecule through a haptic feedback device or a mouse. With a haptic feedback device the user feels the response to the applied force whilst seeing the biomolecule deform on the screen. Prior to the interactive session normal mode analysis is performed, or pre-calculated normal mode eigenvalues and eigenvectors are loaded. For large molecules this allows the memory and number of calculations to be reduced by employing the idea of the important subspace, a relatively small space of the first M lowest frequency normal mode eigenvectors within which a large proportion of the total fluctuation occurs. Using this approach it was possible to study GroEL on a standard PC as even though only 2.3% of the total number of eigenvectors could be used, they accounted for 50% of the total fluctuation. User testing has shown that the haptic version allows for much more rapid and intuitive exploration of the molecule than the mouse version

Interacting with the biomolecular solvent accessible surface via a haptic feedback device

Background: From the 1950s computer based renderings of molecules have been produced to aid researchers in their understanding of biomolecular structure and function. A major consideration for any molecular graphics software is the ability to visualise the three dimensional structure of the molecule. Traditionally, this was accomplished via stereoscopic pairs of images and later realised with three dimensional display technologies. Using a haptic feedback device in combination with molecular graphics has the potential to enhance three dimensional visualisation. Although haptic feedback devices have been used to feel the interaction forces during molecular docking they have not been used explicitly as an aid to visualisation. Results: A haptic rendering application for biomolecular visualisation has been developed that allows the user to gain three-dimensional awareness of the shape of a biomolecule. By using a water molecule as the probe, modelled as an oxygen atom having hard-sphere interactions with the biomolecule, the process of exploration has the further benefit of being able to determine regions on the molecular surface that are accessible to the solvent. This gives insight into how awkward it is for a water molecule to gain access to or escape from channels and cavities, indicating possible entropic bottlenecks. In the case of liver alcohol dehydrogenase bound to the inhibitor SAD, it was found that there is a channel just wide enough for a single water molecule to pass through. Placing the probe coincident with crystallographic water molecules suggests that they are sometimes located within small pockets that provide a sterically stable environment irrespective of hydrogen bonding considerations. Conclusion: By using the software, named HaptiMol ISAS (available from http://​www.​haptimol.​co.​uk), one can explore the accessible surface of biomolecules using a three-dimensional input device to gain insights into the shape and water accessibility of the biomolecular surface that cannot be so easily attained using conventional molecular graphics software

Young people and ICT 2002: findings from a survey conducted in Autumn 2002

This report describes a survey that explored the attitudes and experiences of young people aged 5-18 and their parents, in relation to the use of information and communications technology (ICT) at home and at schoo

Frequency response of underwater ultrasonic transducers in the near field using polarimetric polarization maintaining fiber sensors

Near-field ultrasonic response (50-2000 kHz) of an underwater 1-3 piezocomposite transducer is experimentally investigated using a polarimetric polarization maintaining fiber sensor. Measured outputs from our sensor and a reference hydrophone are observed to be comparable

SUBSTRATE DELIVERY OF EMBEDDED LIPOSOMES

This invention relates to compositions useful for localized and sustained release of therapeutic agents, and more particularly to functionalized liposomes embedded in a poly electrolyte multilayer. Methods of preparing the compositions, methods of treating diseases, devices, and pharmaceutical compositions comprising the compositions are also provided

SUBSTRATE DELIVERY OF EMBEDDED LIPOSOMES

This invention relates to compositions useful for localized and sustained release of therapeutic agents , and more par ticularly to functionalized liposomes embedded in a poly electrolyte multilayer . Methods of preparing the composi tions , methods of treating diseases , devices , and pharmaceutical compositions comprising the compositions are also provide

A longitudinal examination of stressors, appraisals, and coping in youth swimming

Purpose Involvement in sport has the potential to cause athletes, coaches, and parents to experience stress. However, the extent to which experiences of stress are shared within the athletic triad is unknown. The purpose of this study was to examine the individual and shared stress experiences among youth swimmers, their mothers, and coach within the context of training, tapering, and competition. Design Multi-case study design. Method Four female swimmers, their mother, and one coach completed daily diaries for six weeks and up to three semi-structured interviews. Data were analyzed through within- and cross-case thematic analysis. Results The study showed evidence of shared stress experiences between all three members of the athletic triad. Participants predominately encountered organizational stressors, which they appraised in relation to movements between squad, interpersonal relationships, and overall progress towards performance goals/outcomes. Numerous coping strategies were employed by participants, with varying degrees of effectiveness, such as seeking social support, distancing, and lift sharing. The coping strategies used by coaches, swimmers, and parents were often interrelated with participants frequently seeking emotional support from one another. The majority of stressors and appraisals cited by parents and swimmers were shared, with both heavily relying on social support to help each other cope with the stressors encountered. Conclusion Athletes, parents, and coaches have the capacity to influence one another's stress experiences and as such their experiences should be considered simultaneously to maximize the impact of interventions

Protocol to engineer nanofilms embedded lipid nanoparticles for controlled and targeted drug delivery (NECTAR)

We present a protocol to engineer a substrate-mediated delivery platform comprising hyaluronic acid-coated lipid nanoparticles (HALNPs) embedded into polyelectrolyte multilayer (PEM) films. This platform allows controlled spatiotemporal release of lipid nanoparticles (LNP) by embedding them within the polyelectrolyte multilayer films matrix. HALNP conjugate with antibodies also adds the ability for targeted delivery. The use of LNP enables this platform to encapsulate both hydrophobic and hydrophilic drugs. This platform can easily be reproduced and utilized for various biomedical drug delivery applications. For complete details on the use and execution of this protocol, please refer to Hayward et al. (2015, 2016a, 2016b), Hayward and Kidambi (2018), and Kidambi and Hayward (2022)

Protocol to engineer nanofilms embedded lipid nanoparticles for controlled and targeted drug delivery (NECTAR)

We present a protocol to engineer a substrate-mediated delivery platform comprising hyaluronic acid-coated lipid nanoparticles (HALNPs) embedded into polyelectrolyte multilayer (PEM) films. This platform allows controlled spatiotemporal release of lipid nanoparticles (LNP) by embedding them within the polyelectrolyte multilayer films matrix. HALNP conjugate with antibodies also adds the ability for targeted delivery. The use of LNP enables this platform to encapsulate both hydrophobic and hydrophilic drugs. This platform can easily be reproduced and utilized for various biomedical drug delivery applications. For complete details on the use and execution of this protocol, please refer to Hayward et al. (2015, 2016a, 2016b), Hayward and Kidambi (2018), and Kidambi and Hayward (2022)

Debt, Religious Beliefs, and Life Satisfaction

The purpose of this study was to explore religious factors as a resource for coping with indebtedness. Using a sample (n = 3,174) extracted from the Health and Retirement Study (HRS), we examined the relationship between household debt and life satisfaction, and tested for stress-buffering (i.e., moderation) from religious identification, religious beliefs, and prayer frequency. Results suggest that some religious factors may play a small role in moderating the relationship between indebtedness and life satisfaction, and that such moderation is itself dependent on one’s religious identification. Implications for practice (particularly faith-based providers of financial counseling) and recommendations for future research are discussed