Improving the accuracy of burn-surface estimation

A user-friendly computer-assisted method of calculating total body surface area burned (TBSAB) has been developed. This method is more accurate, faster, and subject to less error than conventional methods. For comparison, the ability of 30 physicians to estimate TBSAB was tested. Parameters studied included the effect of prior burn care experience, the influence of burn size, the ability to accurately sketch the size of burns on standard burn charts, and the ability to estimate percent TBSAB from the sketches. Despite the ability for physicians of all levels of training to accurately sketch TBSAB, significant burn size over-estimation (p less than 0.01) and large interrater variability of potential consequence was noted. Direct benefits of a computerized system are many. These include the need for minimal user experience and the ability for wound-trend analysis, permanent record storage, calculation of fluid and caloric requirements, hemodynamic parameters, and the ability to compare meaningfully the different treatment protocols.     

Half-a-century of the "Körmend Growth Study"

The authors give a sketch about the "K?rmend Growth Study" which is series of cross-sectional growth studies, carried out in K?rmend, a small town in Western Hungary. The first investigation was carried out in 1958 (K-58) and it has been repeated every ten years (K-68, K-78, K-88, and K-98). All 3-18 year-old healthy boys and girls in nurseries and schools in K?rmend were involved in the study. Twenty-three body measurements were taken. This paper focuses on changes in height, weight, and BMI. Means of these two body measurements show an increase from time to time (as a phenomenon of positive secular trend), however, the secular trend for increasing height and weight is declining. BMI follows a similar pattern.     

A connectionist model of development.

We present a phenomenological modeling framework for development. Our purpose is to provide a systematic method for discovering and expressing correlations in experimental data on gene expression and other developmental processes. The modeling framework is based on a connectionist or "neural net" dynamics for biochemical regulators, coupled to "grammatical rules" which describe certain features of the birth, growth, and death of cells, synapses and other biological entities. We outline how spatial geometry can be included, although this part of the model is not complete. As an example of the application of our results to a specific biological system, we show in detail how to derive a rigorously testable model of the network of segmentation genes operating in the blastoderm of Drosophila. To further illustrate our methods, we sketch how they could be applied to two other important developmental processes: cell cycle control and cell-cell induction. We also present a simple biochemical model leading to our assumed connectionist dynamics which shows that the dynamics used is at least compatible with known chemical mechanisms.     

Simplicity and complexity in MIRROR universes

The scientific simplicity principle (OCCAM's razor) has always been strongly enforced by the available modelling tools. Moreover, the concept of simplicity itself is shaped by these (classical) tools. Computer models are less subject to simplicity constraints than other models are. It may be argued that complexity is the preeminent property for biological systems to study. In this paper we discuss our MIRROR modelling methodology in which (a concept of) simplicity is reconciled with biological complexity. Simplicity resides in the simple "TODO" ("do what there is to do") of the "individuals" (molecules, cells, organisms) which inhabit the model universe. The complexity appears in the multiple (levels of) individuals and the multiple levels of observable behavior of the universe. Examples are given of the development of complex, self-regulating social structures by simple interactions of individuals, and the adaptability of TODO based entities is compared to that of evolving entities. On the basis of these examples we sketch a slightly unconventional image of the evolution of complexity in biotic systems and discuss observations on the molecular record of biotic evolution which seem to fit this image.     

Modeling of laser coagulation of tissue with MRI temperature monitoring

Light energy from a laser source that is delivered into body tissue via a fiber-optic probe with minimal invasiveness has been used to ablate solid tumors. This thermal coagulation process can be guided and monitored accurately by continuous magnetic resonance imaging (MRI) since the laser energy delivery system does not interfere with MRI. This report deals with mathematical modeling and analysis of laser coagulation of tissue. This model is intended for "real-time" analysis of magnetic resonance images obtained during the coagulation process to guide clinical treatment. A mathematical model is developed to simulate the thermal response of tissue to a laser light heating source. For fast simulation, an approximate solution of the thermal model is used to predict the dynamics of temperature distribution and tissue damage induced by a laser energy line source. The validity of these simulations is tested by comparison with MRI-based temperature data acquired from in vivo experiments in rabbits. The model-simulated temperature distribution and predicted lesion dynamics correspond closely with MRI-based data. These results demonstrate the potential for using this combination of fast modeling and MRI technologies during laser heating of tissue for online prediction of tumor lesion size during laser heating.     

Safe touch temperatures for hot plates.

A finite difference heat transfer model has been developed to predict the Safe Touch Temperatures (STT) for plates made of different materials. SST can be defined as the highest temperature at which no pain is felt when the surface is touched for a long enough period to allow safe handling of the equipment. The criterion used to quantify damage is the "damage function" that was originally proposed by Henriques and Moritz. There are several uncertainties present in the physiological and thermal properties of the skin that give rise to a solution range rather than a single solution. Certain simplifying assumptions are made that tend to yield solutions for STT that are toward the lower or "safe" end of the solution range. The model developed is a two-dimensional axisymmetric model in cylindrical coordinates. A finite difference scheme that uses the Alternating Direction Implicit method is used to solve the problem. It is a second-order scheme in both space and time domains. A parametric analysis of the model is performed to isolate those factors that affect the STT to the greatest extent. Data are presented for a variety of cases, which cover commonly observed ranges in material and geometric properties. It is found that the material properties, namely thermal conductivity and volumetric heat capacity, and the plate thickness ratio are the three most important parameters. These three parameters account for a range of STT from 56 degrees C-100 degrees C with thick metals at the low end and thin metals and plastics in the high range. This method represents a significant improvement over existing standard practices.     

Auditory Sketches: Very Sparse Representations of Sounds Are Still Recognizable

Sounds in our environment like voices, animal calls or musical instruments are easily recognized by human listeners. Understanding the key features underlying this robust sound recognition is an important question in auditory science. Here, we studied the recognition by human listeners of new classes of sounds: acoustic and auditory sketches, sounds that are severely impoverished but still recognizable. Starting from a time-frequency representation, a sketch is obtained by keeping only sparse elements of the original signal, here, by means of a simple peak-picking algorithm. Two time-frequency representations were compared: a biologically grounded one, the auditory spectrogram, which simulates peripheral auditory filtering, and a simple acoustic spectrogram, based on a Fourier transform. Three degrees of sparsity were also investigated. Listeners were asked to recognize the category to which a sketch sound belongs: singing voices, bird calls, musical instruments, and vehicle engine noises. Results showed that, with the exception of voice sounds, very sparse representations of sounds (10 features, or energy peaks, per second) could be recognized above chance. No clear differences could be observed between the acoustic and the auditory sketches. For the voice sounds, however, a completely different pattern of results emerged, with at-chance or even below-chance recognition performances, suggesting that the important features of the voice, whatever they are, were removed by the sketch process. Overall, these perceptual results were well correlated with a model of auditory distances, based on spectro-temporal excitation patterns (STEPs). This study confirms the potential of these new classes of sounds, acoustic and auditory sketches, to study sound recognition.     

Construction of preferential cDNA microarray specialized for human colorectal carcinoma: molecular sketch of colorectal cancer

cDNA microarray analyses can be used to identify candidate genes that play important roles in human carcinogenesis. To gain insight into the molecular sketch of colorectal cancer, we have constructed cDNA microarrays specialized for colorectal cancer, which we named "Colonochip" by selecting genes that are expressed in colorectal cancer, normal colonic mucosa, and liver metastatic cancer tissues. This microarray contained 4608 nonredundant cDNA clones from over 30,000 cDNA clones derived from the three types of human cDNA libraries, as well as clones from 170 additional conventional major genes suspected to be involved in colorectal carcinogenesis, according to literatures. Using this "Colonochip," we were able to identify 59 genes showing twofold or more differential expression between primary cancer and normal colonic mucosa, potent candidates for diagnosis, and therapy of colorectal cancer for further studies.     

On the distribution of the weevil <Emphasis Type="Italic">Lixus subtilis</Emphasis> Boheman, 1835 (Coleoptera,Curculionidae: Lixinae)

Data on the distribution and host plants of Lixus (Phillixus) subtilis Boh. are given with a brief sketch of its bionomics and a distribution map.     

The transport of potassium through lipid bilayer membranes by the neutral carriers valinomycin and monactin

Summary Stationary conductance experiments on neutral and negatively charged bilayer membranes in the presence of valinomycin or monactin agree with a recently proposed carrier transport model, which is common to both carrier types. This model assumes an interface reaction between a cation from the aqueous solution and a carrier molecule from the membrane phase to establish charge transport across the interface. The transport across the membrane interior is described by some kind of Eyring model. The discussion of the current-voltage characteristic, the dependence of membrane conductance on the carrier and K⁺ concentrations, and the comparison with appropriate experiments allow correlation of the different rate constants of the transport model. The results show that the rate constants partly depend on the surface charge of the membranes. This dependency can be described by introducing the Gouy-Chapman theory for charged surfaces into the transport model.It was found that the carrier molecules could be added either to the aqueous phase or to the membrane-forming solution. The quantitative treatment of this phenomenon gives an evaluation of the partition coefficient of the carrier molecules between the membrane bulk phase and water.     

Does alpha-helix folding necessarily provide an energy source for the protein-lipid binding?

Lipid-induced alpha-helix folding, which occurs in many lipid surface-binding proteins and peptides such as apolipoproteins and synucleins, has been proposed to provide an energy source for protein-lipid interactions. We propose that in a system comprised of a phospholipid surface and a small polypeptide that is unfolded in solution and binds reversibly to lipid surface, helical folding involves expenditure of free energy as compared to a similar polypeptide that is alpha-helical in solution. This is a consequence of the entropic cost of helix folding that is illustrated in a simple thermodynamic model and exemplifies the general "key-into-lock" paradigm of protein-ligand binding. Even though this simple model does not explicitly address the protein-induced lipid re-arrangement and may not directly apply to large proteins that undergo significant tertiary structural changes upon lipid binding, it suggests that the notion of helix folding as an energy source for lipid binding should be treated with caution.     

The influence of change in the size of face elements on the perception of a woman's portrait

This research attempts to answer the question how the change of selected face elements influences the likeness between the original portrait (sketch) and its modified versions. For this purpose, several series of portraits were created into which changes to the original sizes of eyes, mouth and nose within a scope of +/-14% (every 2%) were introduced. The task for a subject consisted of indicating one portrait out of each row that was the first to be "clearly unlike the original image". In this way, two values were obtained for each feature (lesser and greater than the initial one). These values have been called "the terminal values", i.e. those which, according to the subjects, once exceeded, the portrait becomes unlike the original. The results obtained indicate that the majority of the subjects, as much as 61.7%, consider the face they observe to be "clearly different" when the change of the studied features amounts to at least 8% of the original value, or even 6% in some cases. In addition, it has been noticed that, in the process of identification, men much earlier than women (p=0.049) consider the portraits in the row with the reduction of eye size unlike the original image.     

Compartmental analysis of carcinogenic experiments: Formulation of a stochastic model

Numerous models for tumor formation and development have been proposed and analyzed. The present model is rather unique by virtue of its incorporation of casual biological theory into the chance mechanisms. This is accomplished by using the very flexible technique of compartmental modeling. An important consequence is that the present model readily lends itself to many types of generalizations and analyses, some of which are explored in this paper. The complete stochastic solution for the model is derived. Factorability of the hazard rate is established. Use of the stochastic solution for safe dose estimation is considered.     

View-Based Organization and Interplay of Spatial Working and Long-Term Memories

Space perception provides egocentric, oriented views of the environment from which working and long-term memories are constructed. “Allocentric” (i.e. position-independent) long-term memories may be organized as graphs of recognized places or views but the interaction of such cognitive graphs with egocentric working memories is unclear. Here we present a simple coherent model of view-based working and long-term memories, together with supporting evidence from behavioral experiments. The model predicts that within a given place, memories for some views may be more salient than others, that imagery of a target square should depend on the location where the recall takes place, and that recall favors views of the target square that would be obtained when approaching it from the current recall location. In two separate experiments in an outdoor urban environment, pedestrians were approached at various interview locations and asked to draw sketch maps of one of two well-known squares. Orientations of the sketch map productions depended significantly on distance and direction of the interview location from the target square, i.e. different views were recalled at different locations. Further analysis showed that location-dependent recall is related to the respective approach direction when imagining a walk from the interview location to the target square. The results are consistent with a view-based model of spatial long-term and working memories and their interplay.     

Study of chemically modified hemoglobin as an artificial oxygen carrier in the model of hemorrhagic shock in dogs]

Hemodynamic and gas-transporting properties of the chemically modified hemoglobin solution have been studied on the model of hemorrhagic shock in dog. It has been shown that the polymerized hemoglobin solution exerts the hemodynamic action just as the plasma substitute "polyglucin" does. However, in contrast to the latter, polyhemoglobin circulating in the vascular bed for a prolonged period of time increases the blood oxygen capacity and oxygen delivery to tissues with the resultant increase in body total oxygen taking-up.     

Crystal structure of an open conformation of citrate synthase from chicken heart at 2.8-A resolution

The X-ray structure of a new crystal form of chicken heart muscle citrate synthase, grown from solutions containing citrate and coenzyme A or L-malate and acetyl coenzyme A, has been determined by molecular replacement at 2.8-A resolution. The space group is P4(3) with a = 58.9 A and c = 259.2 A and contains an entire dimer of molecular weight 100,000 in the asymmetric unit. Both "closed" conformation chicken heart and "open" conformation pig heart citrate synthase models (Brookhaven Protein Data Bank designations 3CTS and 1CTS) were used in the molecular replacement solution, with crystallographic refinement being initiated with the latter. The conventional crystallographic R factor of the final refined model is 19.6% for the data between 6- and 2.8-A resolution. The model has an rms deviation from ideal values of 0.034 A for bond lengths and of 3.6 degrees for bond angles. The conformation of the enzyme is essentially identical with that of a previously determined "open" form of pig heart muscle citrate synthase which crystallizes in a different space group, with one monomer in the asymmetric unit, from either phosphate or citrate solution. The crystalline environment of each subunit of the chicken enzyme is different, yet the conformation is the same in each. The open conformation is therefore not an artifact of crystal packing or crystallization conditions and is not species dependent. Both "open" and "closed" crystal forms of the chicken heart enzyme grow from the same drop, showing that both conformations of the enzyme are present at equilibrium in solution containing reaction products or substrate analogues.     

Kinetic modeling of tumor regression incorporating the concept of cancer stem-like cells for patients with locally advanced lung cancer

Background

Personalized medicine for patients receiving radiation therapy remains an elusive goal due, in part, to the limits in our understanding of the underlying mechanisms governing tumor response to radiation. The purpose of this study was to develop a kinetic model, in the context of locally advanced lung cancer, connecting cancer cell subpopulations with tumor volumes measured during the course of radiation treatment for understanding treatment outcome for individual patients.

Methods

The kinetic model consists of three cell compartments: cancer stem-like cells (CSCs), non-stem tumor cells (TCs) and dead cells (DCs). A set of ordinary differential equations were developed to describe the time evolution of each compartment, and the analytic solution of these equations was iterated to be aligned with the day-to-day tumor volume changes during the course of radiation treatment. A least squares fitting method was used to estimate the parameters of the model that include the proportion of CSCs and their radio-sensitivities. This model was applied to five patients with stage III lung cancer, and tumor volumes were measured from 33 cone-beam computed tomography (CBCT) images for each of these patients. The analytical solution of these differential equations was compared with numerically simulated results.

Results

For the five patients with late stage lung cancer, the derived proportions of CSCs are 0.3 on average, the average probability of the symmetry division is 0.057 and the average surviving fractions of CSCs is 0.967, respectively. The derived parameters are comparable to the results from literature and our experiments. The preliminary results suggest that the CSC self-renewal rate is relatively small, compared to the proportion of CSCs for locally advanced lung cancers.

Conclusions

A novel mathematical model has been developed to connect the population of cancer stem-like cells with tumor volumes measured from a sequence of CBCT images. This model may help improve our understanding of tumor response to radiation therapy, and is valuable for development of new treatment regimens for patients with locally advanced lung cancer.