Analysis and prediction of VH/VL packing in antibodies

The packing of VH and VL domains in antibodies can vary, influencing the topography of the antigen-combining site. However, until recently, this has largely been ignored in modelling antibody structure. We present an analysis of the degree of variability observed in known structures together with a machine-learning approach to predict the packing angle. A neural network was trained on sets of interface residues and a genetic algorithm designed to perform ‘feature selection' to define which sets of interface residues could be used most successfully to perform the prediction. While this training procedure was very computationally intensive, prediction is performed in a matter of seconds. Thus, not only do we provide a rapid method for predicting the packing angle, but also we define a set of residues that may be important in antibody humanization in order to obtain the correct binding site topograph

A Comparative Analysis of Cognitive Tutoring and Constraint-Based Modeling

Numerous approaches to student modeling have been proposed since the inception of the field more than three decades ago. hat the field is lacking completely is comparative analyses of different student modeling approaches. Such analyses are sorely needed, as they can identify the most promising approaches and provide guidelines for future research. In this paper we compare Cognitive Tutoring to Constraint-Based Modeling (CBM). We present our experiences in implementing a database design tutor using both methodologies and highlight their strengths and weaknesses. We compare their characteristics and argue the differences are often more apparent than real. For specific domains, one approach may be favoured over the other, making them viable complementary methods for supporting learning

Tissue engineering for total meniscal substitution : Animal study in sheep model

Objective: The aim of the study was to investigate the use of a novel hyaluronic acid/polycaprolactone material for meniscal tissue engineering and to evaluate the tissue regeneration after the augmentation of the implant with expanded autologous chondrocytes. Two different surgical implantation techniques in a sheep model were evaluated. Methods: Twenty-four skeletally mature sheep were treated with total medial meniscus replacements, while two meniscectomies served as empty controls. The animals were divided into two groups: cell-free scaffold and scaffold seeded with autologous chondrocytes. Two different surgical techniques were compared: in 12 animals, the implant was sutured to the capsule and to the meniscal ligament; in the other 12 animals, also a transtibial fixation of the horns was used. The animals were euthanized after 4 months. The specimens were assessed by gross inspection and histology. Results: All implants showed excellent capsular ingrowth at the periphery. Macroscopically, no difference was observed between cell-seeded and cell-free groups. Better implant appearance and integrity was observed in the group without transosseous horns fixation. Using the latter implantation technique, lower joint degeneration was observed in the cell-seeded group with respect to cell-free implants. The histological analysis indicated cellular infiltration and vascularization throughout the implanted constructs. Cartilaginous tissue formation was significantly more frequent in the cell-seeded constructs. Conclusion: The current study supports the potential of a novel HYAFF/polycaprolactone scaffold for total meniscal substitution. Seeding of the scaffolds with autologous chondrocytes provides some benefit in the extent of fibrocartilaginous tissue repair

Properties of pattern formation and selection processes in nonequilibrium systems with external fluctuations

We extend the phase field crystal method for nonequilibrium patterning to stochastic systems with external source where transient dynamics is essential. It was shown that at short time scales the system manifests pattern selection processes. These processes are studied by means of the structure function dynamics analysis. Nonequilibrium pattern-forming transitions are analyzed by means of numerical simulations.Comment: 15 poages, 8 figure

Infra-red Spectroscopic Studies of GdBaCo2O5.5

This paper reports infrared spectroscopic studies on GdBaCo$_{2}$O$_{5.5}$ layered perovskite which exhibits successive magnetic transitions from paramagnetic to ferromagnetic to antiferromagnetic states as well as high temperature metal to insulator transition and a change in charge transport mechanism at low temperature. Infrared absorption spectra recorded at various temperatures in the range 80 K to 350 K reveal changes in the positions of Co-O stretching and bending frequencies which provide an explanation to the magnetic and transport behaviour of this compound.Comment: 5 figure

Exact Resummations in the Theory of Hydrodynamic Turbulence: I The Ball of Locality and Normal Scaling

This paper is the first in a series of three papers that aim at understanding the scaling behaviour of hydrodynamic turbulence. We present in this paper a perturbative theory for the structure functions and the response functions of the hydrodynamic velocity field in real space and time. Starting from the Navier-Stokes equations (at high Reynolds number Re) we show that the standard perturbative expansions that suffer from infra-red divergences can be exactly resummed using the Belinicher-L'vov transformation. After this exact (partial) resummation it is proven that the resulting perturbation theory is free of divergences, both in large and in small spatial separations. The hydrodynamic response and the correlations have contributions that arise from mediated interactions which take place at some space- time coordinates. It is shown that the main contribution arises when these coordinates lie within a shell of a "ball of locality" that is defined and discussed. We argue that the real space-time formalism developed here offers a clear and intuitive understanding of every diagram in the theory, and of every element in the diagrams. One major consequence of this theory is that none of the familiar perturbative mechanisms may ruin the classical Kolmogorov (K41) scaling solution for the structure functions. Accordingly, corrections to the K41 solutions should be sought in nonperturbative effects. These effects are the subjects of papers II and III in this series, that will propose a mechanism for anomalous scaling in turbulence, which in particular allows multiscaling of the structure functions.Comment: PRE in press, 18 pages + 6 figures, REVTeX. The Eps files of figures will be FTPed by request to [email protected]

A Framework for Decision-based Consistencies

International audienceConsistencies are properties of constraint networks that can be enforced by appropriate algorithms to reduce the size of the search space to be explored. Recently, many consistencies built upon taking decisions (most often, variable assignments) and stronger than (general- ized) arc consistency have been introduced. In this paper, our ambition is to present a clear picture of decision-based consistencies. We identify four general classes (or levels) of decision-based consistencies, denoted by S∆φ, E∆φ, B∆φ and D∆φ, study their relationships, and show that known consistencies are particular cases of these classes. Interestingly, this gen- eral framework provides us with a better insight into decision-based con- sistencies, and allows us to derive many new consistencies that can be directly integrated and compared with other ones

Stress corrosion cracking in Al-Zn-Mg-Cu aluminum alloys in saline environments

Copyright 2013 ASM International. This paper was published in Metallurgical and Materials Transactions A, 44A(3), 1230 - 1253, and is made available as an electronic reprint with the permission of ASM International. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplications of any material in this paper for a fee or for commercial purposes, or modification of the content of this paper are prohibited.Stress corrosion cracking of Al-Zn-Mg-Cu (AA7xxx) aluminum alloys exposed to saline environments at temperatures ranging from 293 K to 353 K (20 °C to 80 °C) has been reviewed with particular attention to the influences of alloy composition and temper, and bulk and local environmental conditions. Stress corrosion crack (SCC) growth rates at room temperature for peak- and over-aged tempers in saline environments are minimized for Al-Zn-Mg-Cu alloys containing less than ~8 wt pct Zn when Zn/Mg ratios are ranging from 2 to 3, excess magnesium levels are less than 1 wt pct, and copper content is either less than ~0.2 wt pct or ranging from 1.3 to 2 wt pct. A minimum chloride ion concentration of ~0.01 M is required for crack growth rates to exceed those in distilled water, which insures that the local solution pH in crack-tip regions can be maintained at less than 4. Crack growth rates in saline solution without other additions gradually increase with bulk chloride ion concentrations up to around 0.6 M NaCl, whereas in solutions with sufficiently low dichromate (or chromate), inhibitor additions are insensitive to the bulk chloride concentration and are typically at least double those observed without the additions. DCB specimens, fatigue pre-cracked in air before immersion in a saline environment, show an initial period with no detectible crack growth, followed by crack growth at the distilled water rate, and then transition to a higher crack growth rate typical of region 2 crack growth in the saline environment. Time spent in each stage depends on the type of pre-crack (“pop-in” vs fatigue), applied stress intensity factor, alloy chemistry, bulk environment, and, if applied, the external polarization. Apparent activation energies (E a) for SCC growth in Al-Zn-Mg-Cu alloys exposed to 0.6 M NaCl over the temperatures ranging from 293 K to 353 K (20 °C to 80 °C) for under-, peak-, and over-aged low-copper-containing alloys (~0.8 wt pct), they are typically ranging from 20 to 40 kJ/mol for under- and peak-aged alloys, and based on limited data, around 85 kJ/mol for over-aged tempers. This means that crack propagation in saline environments is most likely to occur by a hydrogen-related process for low-copper-containing Al-Zn-Mg-Cu alloys in under-, peak- and over-aged tempers, and for high-copper alloys in under- and peak-aged tempers. For over-aged high-copper-containing alloys, cracking is most probably under anodic dissolution control. Future stress corrosion studies should focus on understanding the factors that control crack initiation, and insuring that the next generation of higher performance Al-Zn-Mg-Cu alloys has similar longer crack initiation times and crack propagation rates to those of the incumbent alloys in an over-aged condition where crack rates are less than 1 mm/month at a high stress intensity factor

Signatures of Large Extra Dimensions

String theory suggests modifications of our spacetime such as extra dimensions and the existence of a mininal length scale. In models with addidional dimensions, the Planck scale can be lowered to values accessible by future colliders. Effective theories which extend beyond the standart-model by including extra dimensions and a minimal length allow computation of observables and can be used to make testable predictions. Expected effects that arise within these models are the production of gravitons and black holes. Furthermore, the Planck-length is a lower bound to the possible resolution of spacetime which might be reached soon.Comment: 8 pages, no figures, Talk presented at the NATO Advanced Study Institute: Structure and Dynamics of Elementary Matter, Kemer, Turkey, 22 Sep - 2 Oct 2003. Proceedings to be published by Kluwer Academic publisher

Meixner class of non-commutative generalized stochastic processes with freely independent values I. A characterization

Let $T$ be an underlying space with a non-atomic measure $\sigma$ on it (e.g. $T=\mathbb R^d$ and $\sigma$ is the Lebesgue measure). We introduce and study a class of non-commutative generalized stochastic processes, indexed by points of $T$, with freely independent values. Such a process (field), $\omega=\omega(t)$, $t\in T$, is given a rigorous meaning through smearing out with test functions on $T$, with $\int_T \sigma(dt)f(t)\omega(t)$ being a (bounded) linear operator in a full Fock space. We define a set $\mathbf{CP}$ of all continuous polynomials of $\omega$, and then define a con-commutative $L^2$-space $L^2(\tau)$ by taking the closure of $\mathbf{CP}$ in the norm $\|P\|_{L^2(\tau)}:=\|P\Omega\|$, where $\Omega$ is the vacuum in the Fock space. Through procedure of orthogonalization of polynomials, we construct a unitary isomorphism between $L^2(\tau)$ and a (Fock-space-type) Hilbert space $\mathbb F=\mathbb R\oplus\bigoplus_{n=1}^\infty L^2(T^n,\gamma_n)$, with explicitly given measures $\gamma_n$. We identify the Meixner class as those processes for which the procedure of orthogonalization leaves the set $\mathbf {CP}$ invariant. (Note that, in the general case, the projection of a continuous monomial of oder $n$ onto the $n$-th chaos need not remain a continuous polynomial.) Each element of the Meixner class is characterized by two continuous functions $\lambda$ and $\eta\ge0$ on $T$, such that, in the $\mathbb F$ space, $\omega$ has representation \omega(t)=\di_t^\dag+\lambda(t)\di_t^\dag\di_t+\di_t+\eta(t)\di_t^\dag\di^2_t, where \di_t^\dag and \di_t are the usual creation and annihilation operators at point $t$