A variable gap penalty function and feature weights for protein 3-D structure comparisons

We have developed a variable gap penalty function for use inthe comparison program COMPARER which aligns protein sequenceson the basis of their 3-D structures. For deletions and insertions,components are a function of structural features of individualamino acid residues (e.g. secondary structure and accessibility).We have also obtained relative weights for different featuresused in the comparison by examining the equivalent residuesin weight matrices and in alignments for pairs of 3-D structureswhere the equivalences are relatively unambiguous. We have usedthe new parameters and the varible gap penalty function in COMPARERto align protein structures in the Brookhaven Data Bank. Thevariable gap penalty function is useful especially in avoidinggaps in secondary structure elements and the new feature weightsgive improved alignments. The alignments for both azurins andplastocyanins and N- and C-terminal lobes for aspartic proteinasesare discussed     

Effect of different acids with Δ9,12-dienoic structures on Δ9 desaturation activity in rat liver microsomes

The effect of oral administration, for 24 or 48 hr, of different octadeca fatty acids containing a 9,12-dienoic structure on the fatty acid composition and Δ9 desaturation activity of liver microsomes of rat fed a fat-free diet was studied. The ethyl esters of linoelaidic and γ-linolenic acids, the methyl ester of linoleic acid and free columbinic acid were administered to rats maintained on a fat-free diet. The supplementation of the fat-free diet with linoelaidate produced no relevant changes in the fatty acid composition pattern of liver microsomes and did not modify the percentage of conversion of palmitic to palmitoleic acid. The addition of linoleate or γ-linolenate to the fat-free diet returned liver microsome Δ9 desaturation activity toward the control and partially restored the liver microsome fatty acid spectrum found in the fat-free diet. Columbinic acid (5-trans-9-cis,12-cis-18∶3), which cannot be transformed into arachidonic acid, also decreased the Δ9 desaturation activity enhanced by the fat-free diet and evoked changes in the microsomal fatty acid composition similar to those produced by the ω6 fatty acids. These results suggest that the modulation of Δ9 desaturase activity evoked by dietary administration of unsaturated acids of ω6 series would depend on thecis double bond configuration of these acids.     

Lipoprotein lipid and protein synthesis in experimental nephrosis and plasmapheresis. I: Studies in rat in vivo

The incorporation of L-4,5-[³H]leucine into the ultracentrifugally separated apolipoproteins of very low, low, and high density lipoproteins (VLDL, LDL, HDL) and into serum albumin was found three-to four-fold higher in nephrotic than in normal rats one hour after intravenous injection. Incorporation of leucine into the circulating lipids was negligible. Increases of similar magnitude were obtained in the incorporation of simultaneously injected 1,5[¹⁴C] citrate into the lipids of VLDL, LDL, and HDL of nephrotic rats. Of the citrate carbons incorporated into serum and liver lipids, the proportion in cholesterol was higher in nephrotic rats when compared to normal rats. The incorporation of both precursors into total proteins and lipids of the liver vs. the incorporation into the lipoproteins was relatively lower in nephrotic than in control rats, indicating a preferential channeling into secretable products. The occurrence of enhanced new lipid synthesis in nephrosis was corroborated by the finding of markedly enhanced synthesis of lipoprotein-borne fatty acids and cholesterol from³H₂O. These results point out that while leucine is not an efficient in vivo precursor of lipoprotein lipids in nephrosis, de novo lipogenesis proceeds from other precursors. Similar trend of changes, though of smaller magnitude, was elicited in rats after double plasmapheresis, 18 hr apart, when measured 3 hr after the second plasma withdrawal. This indicates that the loss of circulating proteins either by direct removal or through kidney lesion stimulates the compensatory hepatic response involving excessive lipoprotein synthesis. Time-course studies showed that peak incorporation of leucine and citrate into the protein and lipid components of lipoproteins, respectively, as well as into serum albumin, occurred coincidentally 3 hr after the second plasmapheresis, suggesting an interdependence of the enhanced protein and lipid synthesis.     

Incorporation and distribution of saturated and unsaturated fatty acids into nuclear lipids of hepatic cells

Liver nuclear incorporation of stearic (18∶0), linoleic (18∶2n−6), and arachidonic (20∶4n−6) acids was studied by incubation in vitro of the [1-¹⁴C] fatty acids with nuclei, with or without the cytosol fraction at different times. The [1-¹⁴C] fatty acids were incorporated into the nuclei as free fatty acids in the following order: 18∶0>20∶4n−6≫18∶2n−6, and esterified into nuclear lipids by an acyl-CoA pathway. All [1-¹⁴C] fatty acids were esterified mainly to phospholipids and triacylglycerols and in a minor proportion to diacylglycerols. Only [1-¹⁴C] 18∶2n−6-CoA was incorporated into cholesterol esters. The incorporation was not modified by cytosol addition. The incorporation of 20∶4n−6 into nuclear phosphatidylcholine (PC) pools was also studied by incubation of liver nuclei in vitro with [1-¹⁴C]20∶4n−6-CoA, and nuclear labeled PC molecular species were determined. From the 15 PC nuclear molecular species determined, five were labeled with [1-¹⁴C]20∶4n−6-CoA: 18∶0–20∶4, 16∶0–20∶4, 18∶1–20∶4, 18∶2–20∶4, and 20∶4–20∶4. The highest specific radioactivity was found in 20∶4–20∶4 PC, which is a minor species. In conclusion, liver cell nuclei possess the necessary enzymes to incorporate exogenous saturated and unsaturated fatty acids into lipids by an acyl-CoA pathway, showing specificity for each fatty acid. Liver cell nuclei also utilize exogenous 20∶4n−6-CoA to synthesize the major molecular species of PC with 20∶4n−6 at the sn-2 position. However, the most actively synthesized is 20∶4–20∶4 PC, which is a quantitatively minor component. The labeling pattern of 20∶4–20∶4 PC would indicate that this molecular species is synthesized mainly by the de novo pathway.     

Swelling and mechanical properties of cellulose hydrogels. I. Preparation,characterization, and swelling behavior

Cellulose hydrogels have been synthesized by reacting solutions of cellulose xanthate with different amounts of epichlorohydrin (0–24% w/w on cellulose) after which the cellulose was regenerated. The weight fraction of crystalline cellulose, determined by density measurements, decreases with the extent of chemical crosslinking and was estimated to vary between 30 and 42% for dry gels. The degree of equilibrium swelling in water of the prepared hydrogels varied between 3.05 and 6.33 g water/g dry gel (g/g). The degree of swelling decreases with increasing chemical crosslinking. As a result of the irreversible changes occurring during drying, the degree of swelling in water can be reduced down to 0.74 g/g. According to density gradient column measurements, the partial specific volume of water is 0.865 cm³/g at water contents below 0.13 g/g. It is suggested that water having this partial specific volume is the specific hydration water. At higher water contents, the partial specific volume of gel water equals the specific volume of bulk water. It is implicit in the interpretation of the density data in terms of a two state model of gel water that the crystallinity of cellulose is independent of the water content. Depending on the degree of swelling, heat treatment resulted in either an irreversible increase or decrease of the degree of swelling.     

Stabilised finite element methods for a bending moment formulation of the Reissner-Mindlin plate model

This work presents new stabilised finite element methods for a bending moments formulation of the Reissner-Mindlin plate model. The introduction of the bending moment as an extra unknown leads to a new weak formulation, where the symmetry of this variable is imposed strongly in the space. This weak problem is proved to be well-posed, and stabilised Galerkin schemes for its discretisation are presented and analysed. The finite element methods are such that the bending moment tensor is sought in a finite element space constituted of piecewise linear continuos and symmetric tensors. Optimal error estimates are proved, and these findings are illustrated by representative numerical experiments.     

Comparison of two scaling approaches for the development of biomechanical multi-body human models

Dimensional scaling approaches are widely used to develop multi-body human models in injury biomechanics research. Given the limited experimental data for any particular anthropometry, a validated model can be scaled to different sizes to reflect the biological variance of population and used to characterize the human response. This paper compares two scaling approaches at the whole-body level: one is the conventional mass-based scaling approach which assumes geometric similarity; the other is the structure-based approach which assumes additional structural similarity by using idealized mechanical models to account for the specific anatomy and expected loading conditions. Given the use of exterior body dimensions and a uniform Young’s modulus, the two approaches showed close values of the scaling factors for most body regions, with 1.5 % difference on force scaling factors and 13.5 % difference on moment scaling factors, on average. One exception was on the thoracic modeling, with 19.3 % difference on the scaling factor of the deflection. Two 6-year-old child models were generated from a baseline adult model as application example and were evaluated using recent biomechanical data from cadaveric pediatric experiments. The scaled models predicted similar impact responses of the thorax and lower extremity, which were within the experimental corridors; and suggested further consideration of age-specific structural change of the pelvis. Towards improved scaling methods to develop biofidelic human models, this comparative analysis suggests further investigation on interior anatomical geometry and detailed biological material properties associated with the demographic range of the population.     

Assignment Games with Conflicts: Robust Price of Anarchy and Convergence Results via Semi-Smoothness

We study assignment games in which jobs select machines, and in which certain pairs of jobs may conflict, which is to say they may incur an additional cost when they are both assigned to the same machine, beyond that associated with the increase in load. Questions regarding such interactions apply beyond allocating jobs to machines: when people in a social network choose to align themselves with a group or party, they typically do so based upon not only the inherent quality of that group, but also who amongst their friends (or enemies) chooses that group as well. We show how semi-smoothness, a recently introduced generalization of smoothness, is necessary to find tight bounds on the robust price of anarchy, and thus on the quality of correlated and Nash equilibria, for several natural job-assignment games with interacting jobs. For most cases, our bounds on the robust price of anarchy are either exactly 2 or approach 2. We also prove new convergence results implied by semi-smoothness for our games. Finally we consider coalitional deviations, and prove results about the existence and quality of strong equilibrium.