Use of virtual screening, flexible docking, and molecular interaction fields to design novel HMG-CoA reductase inhibitors for the treatment of hypercholesterolemia

Dietary changes associated with drug therapy can reduce high serum cholesterol levels and dramatically decrease the risk of coronary artery disease, stroke, and overall mortality. Statins are hypolipemic drugs that are effective in the reduction of cholesterol serum levels, attenuating cholesterol synthesis in liver by competitive inhibition regarding the substrate or molecular target HMG-CoA reductase. We have herewith used computer-aided molecular design tools, i.e., flexible docking, virtual screening in large data bases, molecular interaction fields to propose novel potential HMG-CoA reductase inhibitors that are promising for the treatment of hypercholesterolemia.

Molecular dynamics, flexible docking, virtual screening, ADMET predictions, and molecular interaction field studies to design novel potential MAO-B inhibitors

Monoamine oxidase is a flavoenzyme bound to the mitochondrial outer membranes of the cells, which is responsible for the oxidative deamination of neurotransmitter and dietary amines. It has two distinct isozymic forms, designated MAO-A and MAO-B, each displaying different substrate and inhibitor specificities. They are the well-known targets for antidepressant, Parkinson`s disease, and neuroprotective drugs. Elucidation of the x-ray crystallographic structure of MAO-B has opened the way for the molecular modeling studies. In this work we have used molecular modeling, density functional theory with correlation, virtual screening, flexible docking, molecular dynamics, ADMET predictions, and molecular interaction field studies in order to design new molecules with potential higher selectivity and enzymatic inhibitory activity over MAO-B.

From activity to active learning: drawing and dialogue interaction in virtual learning environments for computer-supported collaborative work in design.

Virtual learning environments (VLEs) would appear to be particular effective in computer-supported collaborative work (CSCW) for active learning. Most research studies looking at computer-supported collaborative design have focused on either synchronous or asynchronous modes of communication, but near-synchronous working has received relatively little attention. Yet it could be argued that near-synchronous communication encourages creative, rhetorical and critical exchanges of ideas, building on each other’s contributions. Furthermore, although many researchers have carried out studies on collaborative design protocol, argumentation and constructive interaction, little is known about the interaction between drawing and dialogue in near-synchronous collaborative design. The paper reports the first stage of an investigation into the requirements for the design and development of interactive systems to support the learning of collaborative design activities. The aim of the study is to understand the collaborative design processes while sketching in a shared white board and audio conferencing media. Empirical data on design processes have been obtained from observation of seven sessions with groups of design students solving an interior space-planning problem of a lounge-diner in a virtual learning environment, Lyceum, an in-house software developed by the Open University to support its students in collaborative learning.

Using objects to coordinate design activity in interaction

The coordination of design is a multi-faceted problem in construction. In design interactions in particular the real-time coordination of design activity is a persistent concern. The use of objects to coordinate the activity of design is studied as this happens in interactions between an architect and a building user group, in a setting where maintaining awareness of the design situation is important. An account of ways in which this was accomplished and how design activity is coordinated through interactional practices is provided. The empirical analyses examine design interaction from an ethnomethodological/conversation analysis (EM/CA) informed perspective to examine: ways in which mutual orientation to design issues are accomplished, how objects can provide a resource for the recognition of the activities of others and ways in which objects might be observable as momentarily intelligible. Subtle interactional practices involving talk, gesture and gaze were some of the small ways in which mutual orientation to the design actions of others became observable. The production of actions sequentially, in response to another's action, marked the real-time coordination of design moves in this setting. The relevance of accounts of micro-interaction to develop understanding of design activity and how it is coordinated are considered.

Mechatronic design of a high frequency probe for haptic interaction

Current force feedback, haptic interface devices are generally limited to the display of low frequency, high amplitude spatial data. A typical device consists of a low impedance framework of one or more degrees-of-freedom (dof), allowing a user to explore a pre-defined workspace via an end effector such as a handle, thimble, probe or stylus. The movement of the device is then constrained using high gain positional feedback, thus reducing the apparent dof of the device and conveying the illusion of hard contact to the user. Such devices are, however, limited to a narrow bandwidth of frequencies, typically below 30Hz, and are not well suited to the display of surface properties, such as object texture. This paper details a device to augment an existing force feedback haptic display with a vibrotactile display, thus providing a means of conveying low amplitude, high frequency spatial information of object surface properties. 1. Haptics and Haptic Interfaces Haptics is the study of human touch and interaction with the external environment via touch. Information from the human sense of touch can be classified in to two categories, cutaneous and kinesthetic. Cutaneous information is provided via the mechanoreceptive nerve endings in the glabrous skin of the human hand. It is primarily a means of relaying information regarding small-scale details in the form of skin stretch, compression and vibration.

Context relevant persuasive interaction and design: consideration of human factors influencing B2C persuasive interaction

The revolutions of electronic and mobile commerce have opened up unique opportunities for global marketing and business to consumer (B2C) persuasive interaction; with the aim of influencing user behavior. The success or failure of such persuasive interaction is impacted by cultural, social, and personal dimensions. Accordingly, failure to consider such dimensions risks the user forming a negative attitude towards retailer’s websites or mobile applications, which subsequently threatens customer behavior. A better understanding of human factors influencing the way people perceive B2C persuasive interaction is needed. This paper is introduces the concept of a context relevant persuasive interaction and proposes a guideline for designing relevant B2C persuasive interaction.

Design patterns for promoting peer interaction in discussion forums in MOOCs

Design patterns are a way of sharing evidence-based solutions to educational design problems. The design patterns presented in this paper were produced through a series of workshops, which aimed to identify Massive Open Online Course (MOOC) design principles from workshop participants’ experiences of designing, teaching and learning on these courses. MOOCs present a challenge for the existing pedagogy of online learning, particularly as it relates to promoting peer interaction and discussion. MOOC cohort sizes, participation patterns and diversity of learners mean that discussions can remain superficial, become difficult to navigate, or never develop beyond isolated posts. In addition, MOOC platforms may not provide sufficient tools to support moderation. This paper draws on four case studies of designing and teaching on a range of MOOCs presenting seven design narratives relating to the experience in these MOOCs. Evidence presented in the narratives is abstracted in the form of three design patterns created through a collaborative process using techniques similar to those used in collective autoethnography. The patterns: “Special Interest Discussions”, “Celebrity Touch” and “Look and Engage”, draw together shared lessons and present possible solutions to the problem of creating, managing and facilitating meaningful discussion in MOOCs through the careful use of staged learning activities and facilitation strategies.

Task design and interaction in collaborative writing: the students’ story

This article investigates student behaviour on collaborative assignments, looking at the relationship between task type and interaction, and considers the implications for task design. Students reported on interactions in a year-long workplace-focussed group communication project, comparing these with interactions on other academy based group assignments. Differences were seen in the amount of brainstorming, the criteria for dividing up work, the intensity of editing, and how conflict was managed. Contributing factors to these differences included the presence or absence of a creative element, the instrumental nature of the task, and the need for a collective approach inherent in the task design.

Design, synthesis and characterization of a hexapeptide bio-inspired by acetylcholinesterase and its interaction with pesticide dichlorvos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Design, Calibration, and Evaluation of Depth-of-Interaction-Capable PET Detector Modules

High-resolution, small-bore PET systems suffer from a tradeoff between system sensitivity, and image quality degradation. In these systems long crystals allow mispositioning of the line of response due to parallax error and this mispositioning causes resolution blurring, but long crystals are necessary for high system sensitivity. One means to allow long crystals without introducing parallax errors is to determine the depth of interaction (DOI) of the gamma ray interaction within the detector module. While DOI has been investigated previously, newly available solid state photomultipliers (SSPMs) well-suited to PET applications and allow new modules for investigation. Depth of interaction in full modules is a relatively new field, and so even if high performance DOI capable modules were available, the appropriate means to characterize and calibrate the modules are not. This work presents an investigation of DOI capable arrays and techniques for characterizing and calibrating those modules. The methods introduced here accurately and reliably characterize and calibrate energy, timing, and event interaction positioning. Additionally presented is a characterization of the spatial resolution of DOI capable modules and a measurement of DOI effects for different angles between detector modules. These arrays have been built into a prototype PET system that delivers better than 2.0 mm resolution with a single-sided-stopping-power in excess of 95% for 511 keV g's. The noise properties of SSPMs scale with the active area of the detector face, and so the best signal-to-noise ratio is possible with parallel readout of each SSPM photodetector pixel rather than multiplexing signals together. This work additionally investigates several algorithms for improving timing performance using timing information from multiple SSPM pixels when light is distributed among several photodetectors.

Seismic soil-interaction on earth retaining structures. Performance-based seismic design of a Retaining Wall

The design of containment walls suffering seismic loads traditionally has been realized with methods based on pseudoanalitic procedures such as Mononobe- Okabe's method, which it has led in certain occasions to insecure designs, that they have produced the ruin of many containment walls suffering the action of an earthquake. A method is proposed in this papers for the design of containment walls in different soils, suffering to the action of an earthquake, based on the Performance-Based Seismic Design.

Towards an Active Design. An Approach on the Body Interaction with the Built Environment.

El impacto de la tecnología en el ambiente construido y en las actividades en él desarrolladas, es una de las causas de la progresiva sedentarización de la especie humana. Desde un enfoque que analiza la interacción del cuerpo con la arquitectura, a través de distintas referencias en escalas diversas, esta investigación intenta establecer la relación entre la evolución del ambiente pasivo y la sedentarización, proponiendo frente a un espacio mecanizado y digitalizado que disminuye la actividad física humana, la búsqueda de nuevos tipos de espacios arquitectónicos que promuevan el movimiento repercutiendo en el bienestar y la salud. Esta tesis estudia por tanto el impacto de la tecnología en el espacio, intentando aproximarse a estrategias que disminuyan el efecto pasivo y estimulen la actividad motora. Estas propuestas abarcan tanto la ciudad, como la edificación y el propio espacio doméstico afectando a los sistemas de circulación, a la configuración espacial y sobre todo a la incorporación de ”espacios activos”, en donde se contempla la posibilidad de un uso alternativo de la tecnología como un elemento positivo.