Fourier-Space Crystallography as Group Cohomology

We reformulate Fourier-space crystallography in the language of cohomology of groups. Once the problem is understood as a classification of linear functions on the lattice, restricted by a particular group relation, and identified by gauge transformation, the cohomological description becomes natural. We review Fourier-space crystallography and group cohomology, quote the fact that cohomology is dual to homology, and exhibit several results, previously established for special cases or by intricate calculation, that fall immediately out of the formalism. In particular, we prove that {\it two phase functions are gauge equivalent if and only if they agree on all their gauge-invariant integral linear combinations} and show how to find all these linear combinations systematically.Comment: plain tex, 14 pages (replaced 5/8/01 to include archive preprint number for reference 22

Evaluation of rate law approximations in bottom-up kinetic models of metabolism.

BackgroundThe mechanistic description of enzyme kinetics in a dynamic model of metabolism requires specifying the numerical values of a large number of kinetic parameters. The parameterization challenge is often addressed through the use of simplifying approximations to form reaction rate laws with reduced numbers of parameters. Whether such simplified models can reproduce dynamic characteristics of the full system is an important question.ResultsIn this work, we compared the local transient response properties of dynamic models constructed using rate laws with varying levels of approximation. These approximate rate laws were: 1) a Michaelis-Menten rate law with measured enzyme parameters, 2) a Michaelis-Menten rate law with approximated parameters, using the convenience kinetics convention, 3) a thermodynamic rate law resulting from a metabolite saturation assumption, and 4) a pure chemical reaction mass action rate law that removes the role of the enzyme from the reaction kinetics. We utilized in vivo data for the human red blood cell to compare the effect of rate law choices against the backdrop of physiological flux and concentration differences. We found that the Michaelis-Menten rate law with measured enzyme parameters yields an excellent approximation of the full system dynamics, while other assumptions cause greater discrepancies in system dynamic behavior. However, iteratively replacing mechanistic rate laws with approximations resulted in a model that retains a high correlation with the true model behavior. Investigating this consistency, we determined that the order of magnitude differences among fluxes and concentrations in the network were greatly influential on the network dynamics. We further identified reaction features such as thermodynamic reversibility, high substrate concentration, and lack of allosteric regulation, which make certain reactions more suitable for rate law approximations.ConclusionsOverall, our work generally supports the use of approximate rate laws when building large scale kinetic models, due to the key role that physiologically meaningful flux and concentration ranges play in determining network dynamics. However, we also showed that detailed mechanistic models show a clear benefit in prediction accuracy when data is available. The work here should help to provide guidance to future kinetic modeling efforts on the choice of rate law and parameterization approaches

Symmetry of Magnetically Ordered Quasicrystals

The notion of magnetic symmetry is reexamined in light of the recent observation of long range magnetic order in icosahedral quasicrystals [Charrier et al., Phys. Rev. Lett. 78, 4637 (1997)]. The relation between the symmetry of a magnetically-ordered (periodic or quasiperiodic) crystal, given in terms of a ``spin space group,'' and its neutron diffraction diagram is established. In doing so, an outline of a symmetry classification scheme for magnetically ordered quasiperiodic crystals is provided. Predictions are given for the expected diffraction patterns of magnetically ordered icosahedral crystals, provided their symmetry is well described by icosahedral spin space groups.Comment: 5 pages. Accepted for publication in Phys. Rev. Letter

SBMLsqueezer: A CellDesigner plug-in to generate kinetic rate equations for biochemical networks

<p>Abstract</p> <p>Background</p> <p>The development of complex biochemical models has been facilitated through the standardization of machine-readable representations like SBML (Systems Biology Markup Language). This effort is accompanied by the ongoing development of the human-readable diagrammatic representation SBGN (Systems Biology Graphical Notation). The graphical SBML editor CellDesigner allows direct translation of SBGN into SBML, and vice versa. For the assignment of kinetic rate laws, however, this process is not straightforward, as it often requires manual assembly and specific knowledge of kinetic equations.</p> <p>Results</p> <p>SBMLsqueezer facilitates exactly this modeling step via automated equation generation, overcoming the highly error-prone and cumbersome process of manually assigning kinetic equations. For each reaction the kinetic equation is derived from the stoichiometry, the participating species (e.g., proteins, mRNA or simple molecules) as well as the regulatory relations (activation, inhibition or other modulations) of the SBGN diagram. Such information allows distinctions between, for example, translation, phosphorylation or state transitions. The types of kinetics considered are numerous, for instance generalized mass-action, Hill, convenience and several Michaelis-Menten-based kinetics, each including activation and inhibition. These kinetics allow SBMLsqueezer to cover metabolic, gene regulatory, signal transduction and mixed networks. Whenever multiple kinetics are applicable to one reaction, parameter settings allow for user-defined specifications. After invoking SBMLsqueezer, the kinetic formulas are generated and assigned to the model, which can then be simulated in CellDesigner or with external ODE solvers. Furthermore, the equations can be exported to SBML, LaTeX or plain text format.</p> <p>Conclusion</p> <p>SBMLsqueezer considers the annotation of all participating reactants, products and regulators when generating rate laws for reactions. Thus, for each reaction, only applicable kinetic formulas are considered. This modeling scheme creates kinetics in accordance with the diagrammatic representation. In contrast most previously published tools have relied on the stoichiometry and generic modulators of a reaction, thus ignoring and potentially conflicting with the information expressed through the process diagram. Additional material and the source code can be found at the project homepage (URL found in the Availability and requirements section).</p

On the joint residence time of N independent two-dimensional Brownian motions

We study the behavior of several joint residence times of N independent Brownian particles in a disc of radius $R$ in two dimensions. We consider: (i) the time T_N(t) spent by all N particles simultaneously in the disc within the time interval [0,t]; (ii) the time T_N^{(m)}(t) which at least m out of N particles spend together in the disc within the time interval [0,t]; and (iii) the time {\tilde T}_N^{(m)}(t) which exactly m out of N particles spend together in the disc within the time interval [0,t]. We obtain very simple exact expressions for the expectations of these three residence times in the limit t\to\infty.Comment: 8 page

Early microstructural white matter changes in patients with HIV: A diffusion tensor imaging study

Background: Previous studies have reported white matter (WM) brain alterations in asymptomatic patients with human immunodeficiency virus (HIV). Methods: We compared diffusion tensor imaging (DTI) derived WM fractional anisotropy (FA) between HIV-patients with and without mild macroscopic brain lesions determined using standard magnetic resonance imaging (MRI). We furthermore investigated whether WM alterations co-occurred with neurocognitive deficits and depression. We performed structural MRI and DTI for 19 patients and 19 age-matched healthy controls. Regionally-specific WM integrity was investigated using voxel-based statistics of whole-brain FA maps and region-of-interest analysis. Each patient underwent laboratory and neuropsychological tests. Results: Structural MRI revealed no lesions in twelve (HIV-MRN) and unspecific mild macrostructural lesions in seven patients (HIV-MRL). Both analyses revealed widespread FA-alterations in all patients. Patients with HIV-MRL had FA-alterations primarily adjacent to the observed lesions and, whilst reduced in extent, patients with HIV-MRN also exhibited FA-alterations in similar regions. Patients with evidence of depression showed FA-increase in the ventral tegmental area, pallidum and nucleus accumbens in both hemispheres, and patients with evidence of HIV-associated neurocognitive disorder showed widespread FA-reduction. Conclusion: These results show that patients with HIV-MRN have evidence of FA-alterations in similar regions that are lesioned in HIV-MRL patients, suggesting common neuropathological processes. Furthermore, they suggest a biological rather than a reactive origin of depression in HIV-patients

The unexpectedly short Holocene Humid Period in Northern Arabia

The early to middle Holocene Humid Period led to a greening of today's arid Saharo-Arabian desert belt. While this phase is well defined in North Africa and the Southern Arabian Peninsula, robust evidence from Northern Arabia is lacking. Here we fill this gap with unprecedented annually to sub-decadally resolved proxy data from Tayma, the only known varved lake sediments in Northern Arabia. Based on stable isotopes, micro-facies analyses and varve and radiocarbon dating, we distinguish five phases of lake development and show that the wet phase in Northern Arabia from 8800-7900 years BP is considerably shorter than the commonly defined Holocene Humid Period (similar to 11,000-5500 years BP). Moreover, we find a two century-long peak humidity at times when a centennial-scale dry anomaly around 8200 years BP interrupted the Holocene Humid Period in adjacent regions. The short humid phase possibly favoured Neolithic migrations into Northern Arabia representing a strong human response to environmental changes

The Family Name as Socio-Cultural Feature and Genetic Metaphor: From Concepts to Methods

A recent workshop entitled The Family Name as Socio-Cultural Feature and Genetic Metaphor: From Concepts to Methods was held in Paris in December 2010, sponsored by the French National Centre for Scientific Research (CNRS) and by the journal Human Biology. This workshop was intended to foster a debate on questions related to the family names and to compare different multidisciplinary approaches involving geneticists, historians, geographers, sociologists and social anthropologists. This collective paper presents a collection of selected communications

Human resources for health and burden of disease: an econometric approach

<p>Abstract</p> <p>Background</p> <p>The effect of health workers on health has been proven to be important for various health outcomes (e.g. mortality, coverage of immunisation or skilled birth attendants). The study aim of this paper is to assess the relationship between health workers and disability-adjusted life years (DALYs), which represents a much broader concept of health outcome, including not only mortality but also morbidity.</p> <p>Methods</p> <p>Cross-country multiple regression analyses were undertaken, with DALYs and DALYs disaggregated according to the three different groups of diseases as the dependent variable. Aggregate health workers and disaggregate physicians, nurses, and midwives were included as independent variables, as well as a variable accounting for the skill mix of professionals. The analysis also considers controlling for the effects of income, income distribution, percentage of rural population with access to improved water source, and health expenditure.</p> <p>Results</p> <p>This study presents evidence of a statistically negative relationship between the density of health workers (especially physicians) and the DALYs. An increase of one unit in the density of health workers per 1000 will decrease, on average, the total burden of disease between 1% and 3%. However, in line with previous findings in the literature, the density of nurses and midwives could not be said to be statistically associated to DALYs.</p> <p>Conclusions</p> <p>If countries increase their health worker density, they will be able to reduce significantly their burden of disease, especially the burden associated to communicable diseases. This study represents supporting evidence of the importance of health workers for health.</p

Global Health Actors Claim To Support Health System Strengthening—Is This Reality or Rhetoric?

Bruno Marchal and colleagues argue that most current strategies aimed at health systems strengthening remain selectively targeted at specific diseases