[Show abstract][Hide abstract] ABSTRACT: Relatively little is understood about the practice of teaching for adaptability. Our prior research demonstrates that challenge-based instruction (CBI) can foster Adaptive Expertise (AE). AE is a combination of 1) traditional routine expertise as defined by content knowledge and its correct application and 2) the skills and habits to use that knowledge in new ways on novel problems. The experiments reported in this paper investigate the hypotheses that 1) both the nature of the learning environment (adaptive or routine) and the level of expertise of the learner (adaptive or routine) are important for understanding the development of innovation and efficiency, and 2) innovation and efficiency co-develop in the CBI environment. In Experiment 1, we examined students' exam performance, coding for both innovation and efficiency, across a complete implementation of the CBI biotransport course. We assessed students' level of innovation and efficiency on routine and adaptive problems at four time points at the grain size of exam questions. In Experiment 2, we interviewed eight students three times over the course of their biotransport class. Students solved the same heat transfer problem on each interview, talking aloud as they solved the problem. This design enabled the use of text analysis and clustering learning analytics methods to examine how students' use of innovation and efficiency changed over the course of the interviews in small time segments. Both experiments demonstrated gains in innovation and efficiency, and appropriate use of them given the context of the task. Experiment 2 additionally demonstrated the co-developing nature of the two elements of AE.
[Show abstract][Hide abstract] ABSTRACT: This study was conducted to compare the heat shock responses of cells grown in two- (2D) and three-dimensional (3D) culture environments as indicated by the level of Heat Shock Protein 70 expression and the incidence of apoptosis and necrosis of prostate cancer cell lines in response to graded thermal stress. PC3 cells were stably transduced with a dual reporter system composed of two tandem expression cassettes - a conditional heat shock protein promoter driving the expression of green fluorescent protein (HSPp-GFP) and a CMV promoter controlling the constitutive expression of a "beacon" red fluorescent protein (CMVp-RFP). Two- and three-dimensional cultures of PC3 prostate cancer cells were grown in 96-well plates for evaluation of their time-dependent response to supraphysiological temperature. To induce controlled thermal stress, culture plates were placed on a flat copper surface of a circulating water manifold that maintained the specimens within +/-0.1 degree C of a target temperature. Stress protocols included various combinations of temperature, ranging from 37-57 degree C, and exposure times of up to 2 hours. The majority of protocols were focused on temperature and time permutations where the response gradient was greatest. Post-treatment analysis by flow cytometry analysis was used to measure the incidences of apoptosis (annexin V-FITC stain), necrosis (propidium iodide (PI) stain) and HSP70 transcription (GFP expression). Cells grown in 3D compared to 2D culture showed reduced incidence of apoptosis and necrosis and a higher level of HSP70 expression in response to heat shock at the temperatures tested. Cells responded differently to thermal stress when grown in 2D and 3D cultures. Three dimensional culture appears to enhance survival plausibly by activating protective processes related to enhanced HSP70 expression. These differences highlight the importance of selecting physiologically relevant 3D models in assessing cellular thermal stress responses in experimental settings.
Journal of Biomechanical Engineering 03/2014; · 1.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This presentation will describe the design of several new classes of devices for low temperature therapeutic procedures and the results of initial tests on humans. The devices are used for cryotherapy and for induction of core temperature reduction. Their operation is based on new methods to induce targeted behaviors of the human thermoregulatory system. More than 300 human trials have been conducted that will be presented and discussed. Extensive data records include skin and core temperature measurements, and superficial and deep cutaneous blood flow. Computer simulation models for local and systemic heat transfer behavior during therapeutic cooling include integrated effects such as regional modulation of blood flow, local thermal boundary conditions, and thermoregulatory control schemes.
[Show abstract][Hide abstract] ABSTRACT: This paper presents an updated and augmented version of the Wissler human thermoregulation model that has been developed continuously over the past 50 years. The existing Fortran code is translated into C with extensive embedded commentary. A graphical user interface (GUI) has been developed in Python to facilitate convenient user designation of input and output variables and formatting of data presentation. Use of the code with the GUI is described and demonstrated. New physiological elements were added to the model to represent the hands and feet, including the unique vascular structures adapted for heat transfer associated with glabrous skin. The heat transfer function and efficacy of glabrous skin is unique within the entire body based on the capacity for a very high rate of blood perfusion and the novel capability for dynamic regulation of blood flow. The model was applied to quantify the absolute and relative contributions of glabrous skin flow to thermoregulation for varying levels of blood perfusion. The model also was used to demonstrate how the unique features of glabrous skin blood flow may be recruited to implement thermal therapeutic procedures. We have developed proprietary methods to manipulate the control of glabrous skin blood flow in conjunction with therapeutic devices and simulated the effect of these methods with the model.
Journal of Biomechanical Engineering 02/2013; 135(2):021006. · 1.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We discuss and give examples of the use of selective laser sintering to fabricate solid macroscopic models of microscopic specimens that have been imaged with a confocal microscope. The digital image processing necessary to create structurally sound models of both translucent and opaque specimens is presented. The fabricated models offer the ultimate in data visualization since they can be physically handled and manipulated to investigate the shape and features of the specimen. Such a powerful visualization tool is useful in both research and educational environments.
[Show abstract][Hide abstract] ABSTRACT: In this paper an approach for improving the quality of 3-D microscopic images obtained through optical serial sectioning is described and implemented. A serially sectioned image is composed of a sequence of 2-D images obtained by incrementing the focusing plane of the microscope through the specimen of interest; ideally, the image obtained at each focusing plane should be in focus, and should contain information lying only within that plane. In practice, however, the images obtained contain redundant information from neighbouring focusing planes and are blurred by a three-dimensional low-pass distortion. These degradations are a consequence of the limited aperture of any optical system; using principles of geometric optics and allowing for the passage of light through the specimen, we are able to demonstrate that the microscope distortion can be described as a linear system, if the absorption of the specimen is assumed to be linear and non-diffractive. The transfer function of the microscope is found to zero a biconic region of 3-D spatial frequencies orientated along the optical axis; a closed-form expression is derived for the low-pass transfer function of the microscope outside the region of missing frequencies. The planar resolution of the serial sections can be greatly improved by convolving the image obtained with the inverse of the low-pass distortion function, although the missing cone of frequencies is not recoverable. The reconstruction technique is demonstrated using both simulated images, to demonstrate more clearly the effects of the distortion and the accuracy of the subsequent reconstruction, and actual experiments with a pollen grain and a stained preparation of human cerebellum tissue.
[Show abstract][Hide abstract] ABSTRACT: Sub-lethal temperature elevations in the tumour incurred during laser cancer therapy can induce heat shock protein (HSP) expression leading to enhanced tumour survival and recurrence. Nanoshells utilised in combination with laser therapy can potentially enable selective heat deposition, greater thermal injury, and diminished HSP expression in the tumour. The study objective was to measure the distribution of temperature and HSP expression in prostate tumours in response to laser therapy alone or with nanoshells to determine if these combinatorial therapies can minimise HSP expression.
PC3 cells were inoculated in the backs of CB17-Prkd c SCID/J mice and treated with external laser irradiation (wavelength of 810 nm, irradiance of 5 W/cm(2), spot size of 5 mm, and heating duration of 3 min) alone or in combination with gold nanoshells (diameter of 55 nm and outer gold shell thickness of 10 nm) introduced into the tumour 24 h prior to laser treatment. Magnetic resonance temperature imaging was used to measure the distribution of temperature elevation in the tumours during laser treatment. Tumours were sectioned 16 h following laser treatment, stained for Hsp27 and Hsp70, imaged with a confocal microscope, and HSP expression levels were quantified as a function of depth in the tumours.
Maximum temperature elevations at the tumour surface were 28°C for laser treatment only and 50°C for laser heating in combination with gold nanoshells. Laser therapy alone caused significant induction of HSP expression in the first few millimeters of the tumour depth, whereas decreasing HSP expression occurred with greater tumour depth. Tumours treated with laser and nanoshells experienced substantial temperatures (73-78°C) at the tumour surface and temperatures greater than 53°C in the first few millimeters which eliminated HSP expression.
Inclusion of nanoshells in laser therapy can provide a mechanism for enhancing heat deposition capable of eliminating HSP expression within a larger tumour region compared to laser heating alone.
International Journal of Hyperthermia 01/2011; 27(8):791-801. · 2.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Applications of the macroscopic species conservation equation discussed in Chap. 13 are used extensively in biotransport.
However, the macroscopic approach has important practical restrictions. It is limited to predicting concentrations, fluxes,
or flows that are spatially averaged. If concentrations or fluxes have significant spatial variations, a different approach
must be applied. Rather than apply the species conservation principle to the entire system, a microscopic portion of the system
is analyzed. The resulting expression will be a differential equation that is valid at any position within the boundaries
of the system. Boundary conditions that are specific to the problem at hand must be applied to find a solution for a particular
system. Applications include axial variations of oxygen and carbon dioxide in capillaries, axial variations in salt concentration
in the Loop of Henle, radial concentration variations of urea in tissue or hemodialyzers, solute concentration variations
in porous microcapsules, etc.
[Show abstract][Hide abstract] ABSTRACT: >The flow of energy through biological materials such as blood vessels, airways, or tissue is integral to a very large array
of processes in living systems. Thus, it is interesting and important to develop a facility for describing the transport of
heat as a function of a standard set of critical parameters.
[Show abstract][Hide abstract] ABSTRACT: The irradiation of tissue by laser light results in the absorption of energy. Since this is a fully dissipative process, the
consequence is that the increment in energy is expressed entirely as a heat transfer absorbed by the tissue. In conjunction
with this absorption, there will be an increase in the energy stored locally in the tissue as a function of the geometric
pattern of absorption. Two primary mechanisms of energy storage are encountered most frequently during laser irradiation:
sensible and latent. Sensible storage results in a change in temperature and latent in a change in phase. The two mechanisms
may occur simultaneously or singularly, depending on the initial state of the tissue and the intensity of the irradiation.
A local increase in the temperature will cause a diffusion of heat to surrounding areas that are cooler. Therefore, the analysis
of heat transfer is an important and relevant component of understanding the process and consequences of laser irradiation
of tissue. Phase change and temperature elevation are often a direct source of injury to tissue.
[Show abstract][Hide abstract] ABSTRACT: Many biological and physiological mass transfer problems can be solved using a macroscopic approach. This is particularly
true for fluid systems that can be considered to be reasonably well mixed. Systems with significant spatial gradients in concentration
cannot be accurately analyzed with the macroscopic approach. In such cases, the microscopic approach to mass transfer discussed
in Chaps. 14 and 15 must be applied. The macroscopic approach is appropriate when we are not interested in the spatial variations
within the system, but instead are interested in average transient values or output values. Common objectives of the macroscopic
approach are to find the rate of accumulation of a particular species in the system, the mass flow into or out of the system,
or the rate at which a species is produced or utilized by chemical reaction within a system. Common applications include the
pharmacokinetics of drugs in the body, diagnostic tracer studies, species synthesis in bioreactors, cellular transport, and
[Show abstract][Hide abstract] ABSTRACT: When we speak of mass transfer, we are generally referring to the movement of one or more molecular species relative to the
others. Before we can describe this relative movement, we need to understand the most common ways of quantifying the presence
of each species. Consider the closed system with volume V shown in Fig.12.1 which contains three different molecular species A, B, and C, represented by three different colors.
[Show abstract][Hide abstract] ABSTRACT: Hyperthermia can induce heat shock protein (HSP) expression in tumours, which will cause enhanced tumour viability and increased resistance to additional thermal, chemotherapy, and radiation treatments. The study objective was to determine the relationship of hyperthermia protocols with HSP expression kinetics and cell death and develop corresponding computational predictive models of normal and cancerous prostate cell response.
HSP expression kinetics and cell viability were measured in PC3 prostate cancer and RWPE-1 normal prostate cells subjected to hyperthermia protocols of 44° to 60°C for 1 to 30 min. Hsp27, Hsp60, and Hsp70 expression kinetics were determined by western blotting and visualised with immunofluorescence and confocal microscopy. Based on measured HSP expression data, a mathematical model was developed for predicting thermally induced HSP expression. Cell viability was measured with propidium iodide staining and flow cytometry to quantify the injury parameters necessary for predicting cell death following hyperthermia.
Significant Hsp27 and Hsp70 levels were induced in both cell types with maximum HSP expression occurring at 16 h post-heating, and diminishing substantially after 72 h. PC3 cells were slightly more sensitive to thermal stress than RWPE-1 cells. Arrhenius analysis of injury data suggested a transition between injury mechanisms at 54°C. HSP expression and injury models were effective at predicting cellular response to hyperthermia.
Measurement of thermally induced HSP expression kinetics and cell viability associated with hyperthermia enabled development of thermal dosimetry guidelines and predictive models for HSP expression and cell injury as a function of thermal stress to investigate and design more effective hyperthermia therapies.
International Journal of Hyperthermia 01/2010; 26(8):748-64. · 2.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The healing effect of therapeutic hyperthermia induced by widely available heat wrap products is understood to be based on concomitant temperature dependent vasodilation and increase in mass transport. We hypothesize that an additional mechanism of healing associated with increased heat shock protein (HSP) expression is also a contributing factor. HSP expression is controlled by the level and duration of heating and can have a potent effect on healing. We have developed a combined thermal stress and HSP expression model for bioheat transport into the tissues of the back produced by a therapeutic heat wrap. The model predicts temperature distribution in the deep tissues of the back by a modified version of the Pennes (1948, "Analysis of Tissue and Arterial Blood Temperatures in the Resting Human Forearm," J. Appl. Physiol., 1(2), pp. 93-122) bioheat equation. The model also predicts HSP70/actin concentrations based on existing empirical expression data from our laboratory as a function of heating time and temperature. Thermal boundary conditions were input for a typical heat wrap worn for its functional duration of 8 h or more. Temperatures in the paraspinal muscles of the back increase by a minimum of 1 degrees C after 1 h of heating and persist for at least 2 h. HSP70/actin expression is increased 1.7-fold above the control. The model demonstrates that elevated HSP expression may provide an important contribution to the healing process in injured tissue when a therapeutic heat wrap is worn.
Journal of Biomechanical Engineering 08/2009; 131(7):074510. · 1.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Induced hypothermia is an acknowledged useful therapy for treating conditions that lead to cell and tissue damage caused by ischemia, including traumatic brain injury, stroke, and cardiac arrest. An accumulating body of clinical evidence, together with several decades of research, has documented that the efficacy of hypothermia is dependent on achieving a reduced temperature in the target tissue before or soon following the ischemia-precipitating event. The temperature must be lowered to within a rather small range of values to effect therapeutic benefit without introducing collateral problems. Rewarming must be much slower than cooling. Many different methods and devices have been used for cooling, with mixed results. There are existing opportunities for bioengineers to improve our understanding of the mechanisms of hypothermia and to develop more effective methods of cooling the brain following trauma.
[Show abstract][Hide abstract] ABSTRACT: An adaptive feedback control system is presented which employs a computational model of bioheat transfer in living tissue to guide, in real-time, laser treatments of prostate cancer monitored by magnetic resonance thermal imaging. The system is built on what can be referred to as cyberinfrastructure-a complex structure of high-speed network, large-scale parallel computing devices, laser optics, imaging, visualizations, inverse-analysis algorithms, mesh generation, and control systems that guide laser therapy to optimally control the ablation of cancerous tissue. The computational system has been successfully tested on in vivo, canine prostate. Over the course of an 18 min laser-induced thermal therapy performed at M.D. Anderson Cancer Center (MDACC) in Houston, Texas, the computational models were calibrated to intra-operative real-time thermal imaging treatment data and the calibrated models controlled the bioheat transfer to within 5 degrees C of the predetermined treatment plan. The computational arena is in Austin, Texas and managed at the Institute for Computational Engineering and Sciences (ICES). The system is designed to control the bioheat transfer remotely while simultaneously providing real-time remote visualization of the on-going treatment. Post-operative histology of the canine prostate reveal that the damage region was within the targeted 1.2 cm diameter treatment objective.
Annals of Biomedical Engineering 02/2009; 37(4):763-82. · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hot beverages such as tea, hot chocolate, and coffee are frequently served at temperatures between 160 degrees F (71.1 degrees C) and 185 degrees F (85 degrees C). Brief exposures to liquids in this temperature range can cause significant scald burns. However, hot beverages must be served at a temperature that is high enough to provide a satisfactory sensation to the consumer. This paper presents an analysis to quantify hot beverage temperatures that balance limiting the potential scald burn hazard and maintaining an acceptable perception of adequate product warmth. A figure of merit that can be optimized is defined that quantifies and combines both the above effects as a function of the beverage temperature. An established mathematical model for simulating burns as a function of applied surface temperature and time of exposure is used to quantify the extent of thermal injury. Recent data from the literature defines the consumer preferred drinking temperature of coffee. A metric accommodates the thermal effects of both scald hazard and product taste to identify an optimal recommended serving temperature. The burn model shows the standard exponential dependence of injury level on temperature. The preferred drinking temperature of coffee is specified in the literature as 140+/-15 degrees F (60+/-8.3 degrees C) for a population of 300 subjects. A linear (with respect to temperature) figure of merit merged the two effects to identify an optimal drinking temperature of approximately 136 degrees F (57.8 degrees C). The analysis points to a reduction in the presently recommended serving temperature of coffee to achieve the combined result of reducing the scald burn hazard and improving customer satisfaction.
[Show abstract][Hide abstract] ABSTRACT: The direct correlation between levels of heat shock protein expression and efficiency of its tissue protection function motivates this study of how thermal doses can be used for an optimal stress protocol design. Heat shock protein 70 (HSP70) expression kinetics were visualized continuously in cultured bovine aortic endothelial cells (BAECs) on a microscope heating stage using green fluorescent protein (GFP) as a reporter. BAECs were transfected with a DNA vector, HSP(p)-HSP70-GFP which expresses an HSP70-GFP fusion protein under control of the HSP70 promoter. Expression levels were validated by western blot analysis. Transfected cells were heated on a controlled temperature microscope stage at 42 degrees C for a defined period, then shifted to 37 degrees C for varied post-heating times. The expression of HSP70-GFP and its sub-cellular localization were visualized via fluorescence microscopy. The progressive expression kinetics were measured by quantitative analysis of serial fluorescence images captured during heating protocols from 1 to 2 h and post-heating times from 0 to 20 h. The results show two sequential peaks in HSP70 expression at approximately 3 and 12 h post-heat shock. A progressive translocation of HSP70 from the cytoplasm to the nucleus was observed from 6 to 16 h. We conclude that we have successfully combined molecular cloning and optical imaging to study HSP70 expression kinetics. The kinetic profile for HSP70-GFP fusion protein is consistent with the endogenous HSP70. Furthermore, information on dynamic intracellular translocation of HSP70 was extracted from the same experimental data.
Biotechnology and Bioengineering 02/2008; 99(1):146-54. · 4.16 Impact Factor