A revision of body surface area estimations

The results from the present study indicate that the equation of Dubois and Dubois (1916), now in common use for estimating body surface area, is not the most accurate of those available. Our new equation is based on the measurement of body weight and upper calf circumference only. It accounts for a large percentage of the total variance (88.9%), and has a low standard error of estimate (0.05 m2), which suggests that this equation may be more useful in the estimation of human body surface area than many of the equations previously produced. Direct comparisons of the accuracy of other workers' equations is difficult to assess due to the different methods by which the equations have been produced and expressed. We do not advocate the use of different equations for males and females because the data indicate that the present equation probably applies equally well to both sexes.     

Phylogeny and Bayesian divergence time estimations of small-headed flies (Diptera: Acroceridae) using multiple molecular markers

The first formal analysis of phylogenetic relationships among small-headed flies (Acroceridae) is presented based on DNA sequence data from two ribosomal (16S and 28S) and two protein-encoding genes: carbomoylphosphate synthase (CPS) domain of CAD (i.e., rudimentary locus) and cytochrome oxidase I (COI). DNA sequences from 40 species in 22 genera of Acroceridae (representing all three subfamilies) were compared with outgroup exemplars from Nemestrinidae, Stratiomyidae, Tabanidae, and Xylophagidae. Parsimony and Bayesian simultaneous analyses of the full data set recover a well-resolved and strongly supported hypothesis of phylogenetic relationships for major lineages within the family. Molecular evidence supports the monophyly of traditionally recognised subfamilies Philopotinae and Panopinae, but Acrocerinae are polyphyletic. Panopinae, sometimes considered "primitive" based on morphology and host-use, are always placed in a more derived position in the current study. Furthermore, these data support emerging morphological evidence that the type genus Acrocera Meigen, and its sister genus Sphaerops, are atypical acrocerids, comprising a sister lineage to all other Acroceridae. Based on the phylogeny generated in the simultaneous analysis, historical divergence times were estimated using Bayesian methodology constrained with fossil data. These estimates indicate Acroceridae likely evolved during the late Triassic but did not diversify greatly until the Cretaceous.     

Quantification of lung surface area using computed tomography

Objective

To refine the CT prediction of emphysema by comparing histology and CT for specific regions of lung. To incorporate both regional lung density measured by CT and cluster analysis of low attenuation areas for comparison with histological measurement of surface area per unit lung volume.

Methods

The histological surface area per unit lung volume was estimated for 140 samples taken from resected lung specimens of fourteen subjects. The region of the lung sampled for histology was located on the pre-operative CT scan; the regional CT median lung density and emphysematous lesion size were calculated using the X-ray attenuation values and a low attenuation cluster analysis. Linear mixed models were used to examine the relationships between histological surface area per unit lung volume and CT measures.

Results

The median CT lung density, low attenuation cluster analysis, and the combination of both were important predictors of surface area per unit lung volume measured by histology (p < 0.0001). Akaike''s information criterion showed the model incorporating both parameters provided the most accurate prediction of emphysema.

Conclusion

Combining CT measures of lung density and emphysematous lesion size provides a more accurate estimate of lung surface area per unit lung volume than either measure alone.     

A comprehensive approach to the molecular determinants of lifespan using a Boolean model of geroconversion

Altered molecular responses to insulin and growth factors (GF) are responsible for late‐life shortening diseases such as type‐2 diabetes mellitus (T2DM) and cancers. We have built a network of the signaling pathways that control S‐phase entry and a specific type of senescence called geroconversion. We have translated this network into a Boolean model to study possible cell phenotype outcomes under diverse molecular signaling conditions. In the context of insulin resistance, the model was able to reproduce the variations of the senescence level observed in tissues related to T2DM's main morbidity and mortality. Furthermore, by calibrating the pharmacodynamics of mTOR inhibitors, we have been able to reproduce the dose‐dependent effect of rapamycin on liver degeneration and lifespan expansion in wild‐type and HER2–neu mice. Using the model, we have finally performed an in silico prospective screen of the risk–benefit ratio of rapamycin dosage for healthy lifespan expansion strategies. We present here a comprehensive prognostic and predictive systems biology tool for human aging.     

Determination of body surface area and formulas to estimate body surface area using the alginate method

The purpose of this study was to determine the body surface area (BSA) based on the alginate method, to derive formulae for estimating BSA, and to compare the error of the present formula to previous formulas obtained from other countries. We directly measured the entire body surface area of 34 males (20-60 years old, 158.5-187.5 cm in height, 48.5-103.1 kg in body weight) and 31 females (20-63 years old, 140.6-173.1 cm, 36.8-106.1 kg) using alginate. The measurements showed that the BSA had a mean of 18,339 cm(2) (15,416-22,753 cm(2)) for males, and 16,452 cm(2) (12,825-22,025 cm(2)) for females. Based on these measurements, a regression model to estimate BSA was derived: Estimated BSA (cm(2))=73.31 Height (cm)(0.725) x Weight (kg)(0.425) (r(2)=0.999). The mean error of the formula was -0.1%, and did not show any significant difference by gender or body shape. When applied to the datasets (n=506) composed of various races (Caucasians, Africans, and Asians), the mean error of the formula was 0.4% and was smaller than that of DuBois & DuBois's, Gehan & George's, and Mosteller's formulas when applied to the same datasets. The errors of the three previous formulas were also within 2%. Overall, formulas based on the DuBois exponent (Weight(0.425) Height (0.725)) did not show any tendency of overestimation or underestimation by body shape, but other BSA-formulae showed differences by body shape. The present BSA formula has shown good accuracy in Korean adults of all weight categories compared to traditional formulas.     

Nanoindentation response of nickel surface using molecular dynamics simulation

The mechanisms of dislocation nucleation on a nickel (Ni) (001) surface under nanoindentation behaviours are investigated using molecular dynamics simulation. The characteristic mechanisms include the molecular models of a thermal layer (TL) and thermal with a free layer (TFL), multi-step load/unload cycles, tilt angles and shapes of the indenter, and slip vectors. The model of a TL has higher reaction force than a TFL. The maximum forces of nanoindentation decrease with increasing time of the multi-step load/unload cycle. The indenter with the tilt angle has larger force to act on the molecular model than the indenter along the normal direction. The effect of the indentation shape is presented such that the conical tip has larger load force to act on the molecular model. The defects along Shockley partials on the (111) plane are produced during nanoindentation involving nucleation, glide and slip.     

Fast approximations for accessible surface area and molecular volume of protein segments

Equations are presented that approximate the accessible surface area of a continuous protein segment using the surface area of an inertial ellipsoid and that approximate the molecular volume from the number of non-hydrogen atoms in the segment. These approximations, which are appropriate for segments of four or more residues in length, are much faster to calculate than the exact solutions, yet suffer only a 3–8% error. Included in an appendix are FORTRAN subroutines that calculate the surface area of an ellipsoid from its three principal moments of inertia.     

The molecular weights of Arthropod hemocyanin subunits: Influence of tris buffer in SDS-PAGE estimations

• 1.1. Available molecular weights data for Arthropod hemocyanin subunits as measured by polyacrylamide gel electrophoresis in the presence of dodecyl sulfate are analyzed.
• 2.2. Relationship between buffer composition and subunit mobility in SDS-PAGE is shown by studying Cancer pagurus hemocyanin.
• 3.3. Tris buffers are suspected to give erroneous molecular weight estimations for Arthropod hemocyanin subunits.

     

Searching for geometric molecular shape complementarity using bidimensional surface profiles

The study presented herein is a bidimensional approach to the complementarity of two molecular surfaces. From two chosen sections we have established a methodology of generating the optimal matching of two shapes. Our approach consists in describing two molecular surface sections by a shape vector (the angular profile), in finding their matching patterns by comparison of the two profiles, and in optimizing the relative locations of the two sections in two-dimensional space, using rotations and translations defined by geometric characteristics. The set of optimal configurations are successively displayed on a screen. Satisfying results have been obtained for the matching of the complex kallikreine Atrypsin pancreatic bovin 2. This efficient method could be used as a preprocessing for a tridimensional shape complementarity approach between two molecular surfaces.     

Phenology model from surface meteorology does not capture satellite-based greenup estimations

Seasonal temperature change in temperate forests is known to trigger the start of spring growth, and both interannual and spatial variations in spring onset have been tied to climatic variability. Satellite dates are increasingly being used in phenology studies, but to date that has been little effort to link remotely sensed phenology to surface climate records. In this research, we use a two‐parameter spring warming phenology model to explore the relationship between climate and satellite‐based phenology. We employ daily air temperature records between 2000 and 2005 for 171 National Oceanographic and Atmospheric Administration weather stations located throughout New England to construct spring warming models predicting the onset of spring, as defined by the date of half‐maximum greenness (D₅₀) in deciduous forests as detected from Moderate Resolution Imaging Spectrometer. The best spring warming model starts accumulating temperatures after March 20th and when average daily temperatures exceed 5°C. The accumulated heat sums [heating degree day (HDD)] required to reach D₅₀ range from 150 to 300 degree days over New England, with the highest requirements to the south and in coastal regions. We test the ability of the spring warming model to predict phenology against a null photoperiod model (average date of onset). The spring warming model offers little improvement on the null model when predicting D₅₀. Differences between the efficacies of the two models are expressed as the ‘climate sensitivity ratio’ (CSR), which displays coherent spatial patterns. Our results suggest that northern (beech‐maple‐birch) and central (oak‐hickory) hardwood forests respond to climate differently, particularly with disparate requirements for the minimum temperature necessary to begin spring growth (3 and 6°C, respectively). We conclude that spatial location and species composition are critical factors for predicting the phenological response to climate change: satellite observations cannot be linked directly to temperature variability if species or community compositions are unknown.     

Detection of small sequence differences using competitive PCR: molecular monitoring of genetically improved, mercury-reducing bacteria

A quantitative PCR approach is presented to detect small genomic sequence differences for molecular quantification of recombinant DNA. The only unique genetic feature of the mercury-reducing, genetically improved Pseudomonas putida KT2442::mer73 available to distinguish it from its native mercury-resistant relatives is the DNA sequence crossing the border of the insertion site of the introduced DNA fragment. The quantification assay is a combination of specific PCR amplification and temperature gradient gel electrophoresis (TGGE). Gene quantification is provided by a competitively co-amplified DNA standard constructed by point mutation PCR. After computing the denaturation behavior of the target DNA stretch, a single base difference was introduced to achieve maximum migration difference in TGGE between the original target DNA and the modified standard without altering the PCR amplification efficiency. This competitive PCR strategy is a highly specific and sensitive way to detect small sequence differences and to monitor recombinant DNA in effluxes of biotechnological plants.     

Seeing (through) masks: An exploration of masks and mask making

In the form of a collage I juxtapose my experience of mask‐making with various interpretations of the nature and meaning of masks in order to explore the questions of whether masks can have meaning for those outside the culture of origin and whether encountering cultural artifacts like masks can enhance our own self‐understanding. I conclude, with some interpreters of masks, that the answer to these questions is in the affirmative, at least as a possibility.     

Oligoglycine surface structures: molecular dynamics simulation

The full-atomic molecular dynamics (MD) simulation of adsorption mode for diantennary oligoglycines [H-Gly4-NH(CH2)5]2 onto graphite and mica surface is described. The resulting structure of adsorption layers is analyzed. The peptide second structure motives have been studied by both STRIDE (structural identification) and DSSP (dictionary of secondary structure of proteins) methods. The obtained results confirm the possibility of polyglycine II (PGII) structure formation in diantennary oligoglycine (DAOG) monolayers deposited onto graphite surface, which was earlier estimated based on atomic-force microscopy measurements.     

Genomics and medicine: an anticipation. From Boolean Mendelian genetics to multifactorial molecular medicine

The major impact of the completion of the human genome sequence will be the understanding of diseases, with deduced therapy. In the field of genetic disorders, we will complete the catalogue of monogenic diseases, also called Mendelian diseases because they obey the Boolean logic of Mendel's laws. The major challenge now is to decipher the polygenic and multifactorial etiology of common diseases, such as cancer, cardio-vascular, nutritional, allergic, auto-immune and degenerative diseases. In fact, every gene, when mutated, is a potential disease gene, and we end up with the new concept of 'reverse medicine'; i.e., deriving new diseases or pathogenic pathways from the knowledge of the structure and function of every gene. By going from sequence to function (functional genomics and proteomics) we will gain insight into basic mechanisms of major functions such as cell proliferation, differentiation and development, which are perturbed in many pathological processes. By learning the meaning of some non-coding and of regulatory sequences our understanding will gain in complexity, generating a molecular and supramolecular integrated physiology, helping to build a molecular patho-physiology of the different syndromes. Besides those cognitive advances, there are also other issues at stake, such as: progress in diagnostic and prediction (predictive medicine); progress in therapy (pharmacogenomics and gene-based therapy); ethical issues; impact on business.     

Thiol-functionalized polymeric micelles: from molecular recognition to improved mucoadhesion

Surface-modified colloids which can selectively interact with biological species or surfaces show promise as drug delivery systems. However, the preparation of such targeted devices remains challenging, especially when considering polyion complex micelles for which side reactions with the ionic core components (typically carboxylic acid or amino groups) can occur. To solve this issue, an innovative synthetic strategy is proposed and used to prepare an asymmetric poly(ethylene glycol)-block-poly(2-(N,N-dimethylamino)ethyl methacrylate) copolymer presenting a thiol group at the end of the poly(ethylene glycol) chain. Thiol groups are highly appealing given that they react almost exclusively and quantitatively with maleimides under physiological conditions, thereby facilitating the chemical functionalization of the copolymer. The simplicity of the derivatization procedure is illustrated by preparing model biotin-capped copolymers. The biotinylated copolymers are shown to self-assemble with an oligonucleotide in aqueous media to form polyion complex micelles with biotin groups at their outer surface. These micelles are capable of molecular recognition toward streptavidin. Alternatively, thiol-decorated (nonderivatized) micelles are prepared and show improved mucoadhesion through the formation of disulfide bonds with mucin. Finally, intermicellar disulfide bonds are generated under oxidative conditions to promote the formation of stimuli-responsive micellar networks.     

Determination of hand surface area by sex and body shape using alginate

Hand surface area (HSA) has been utilized for burned skin area estimation in burn therapy, heat exchange in thermal physiology, exposure assessment in occupational toxicology, and the development of manual equipment/ protective gloves in ergonomics. The purpose of this study was to determine the hand surface area to the total body surface area (BSA) and derive a formula for estimating HSA. Thirty-four Korean males (20-60 years old; 158.5-187.5 cm in height; 48.5-103.1 kg in body weight) and thirty-one Korean females (20-63 years old; 140.6-173.1 cm; 36.8-106.1 kg) participated as subjects. The HSA and BSA of 65 subjects were directly measured using alginate. The measurements showed 1) the surface area of the hand had a mean of 448 (371-540) cm(2) for males, and 392 (297-482) cm(2) for females. 2) The hand as a percentage of the total body surface area for males and females was 2.5% and 2.4% respectively, showing no significant difference. 3) The hand as a percentage of BSA by body shape was 2.5% for the lean group and 2.3% for overweight people (p=0.001). 4) When estimating the surface area of a hand, formulae based on hand length or hand circumference were more valid than formulae based on height and body weight. We obtained the following formula for estimating HSA: Estimated HSA(cm(2))=1.219 Hand length(cm) x Hand circumference(cm).     

An in silico target identification using Boolean network attractors: Avoiding pathological phenotypes

Target identification aims at identifying biomolecules whose function should be therapeutically altered to cure the considered pathology. An algorithm for in silico target identification using Boolean network attractors is proposed. It assumes that attractors correspond to phenotypes produced by the modeled biological network. It identifies target combinations which allow disturbed networks to avoid attractors associated with pathological phenotypes. The algorithm is tested on a Boolean model of the mammalian cell cycle and its applications are illustrated on a Boolean model of Fanconi anemia. Results show that the algorithm returns target combinations able to remove attractors associated with pathological phenotypes and then succeeds in performing the proposed in silico target identification. However, as with any in silico evidence, there is a bridge to cross between theory and practice. Nevertheless, it is expected that the algorithm is of interest for target identification.