Attractor Modulation and Proliferation in 1+∞\infty Dimensional Neural Networks

We extend a recently introduced class of exactly solvable models for recurrent neural networks with competition between 1D nearest neighbour and infinite range information processing. We increase the potential for further frustration and competition in these models, as well as their biological relevance, by adding next-nearest neighbour couplings, and we allow for modulation of the attractors so that we can interpolate continuously between situations with different numbers of stored patterns. Our models are solved by combining mean field and random field techniques. They exhibit increasingly complex phase diagrams with novel phases, separated by multiple first- and second order transitions (dynamical and thermodynamic ones), and, upon modulating the attractor strengths, non-trivial scenarios of phase diagram deformation. Our predictions are in excellent agreement with numerical simulations.Comment: 16 pages, 15 postscript figures, Late

Prevalence and correlates of diphtheria toxoid antibodies in children and adults in Israel

ABSTRACTA seroepidemiological study was performed to evaluate immunity to diphtheria and to determine the correlates of diphtheria toxoid antibody levels among children and adults in Israel. In total, 3185 sera from an age-stratified sample of children and adults, obtained in 2000–2001, were tested for diphtheria toxoid antibodies by an in-house double-antigen ELISA. A level of ≤0.01 IU /mL (no immune protection or seronegativity) was found in 168 (5.3%) of the 3185 subjects, 639 (20.1%) had antibody levels of 0.011–0.099 IU /mL (basic immunity or low seropositivity), and 2378 (74.7%) had antibody levels ≥0.1 IU /mL (full protection or seropositivity). Seronegativity increased significantly in subjects aged >50 years, reaching levels of 9.7%, 12.6% and 18.9% in the groups aged 50–54, 55–59 and >60 years, respectively (p 0.001), with rates of basic immunity following a similar pattern. Subjects born abroad had higher seronegativity rates than those born in Israel (7.7%vs. 4.9%; p 0.019). No difference in diphtheria toxoid antibody levels was found according to other demographical variables, such as gender, Jewish or Arab ethnicity, urban or rural settlements, and the subjects’ place of residence. The level of immunity to diphtheria among children and adults in Israel was satisfactory, with the exception of individuals aged >50 years. The risk of diphtheria outbreaks is low, but sporadic cases may occur among individuals lacking basic immunity against the disease

Acute rejection is associated with antibodies to non-Gal antigens in baboons using Gal-knockout pig kidneys

We transplanted kidneys from α1,3-galactosyltransferase knockout (GalT-KO) pigs into six baboons using two different immunosuppressive regimens, but most of the baboons died from severe acute humoral xenograft rejection. Circulating induced antibodies to non-Gal antigens were markedly elevated at rejection, which mediated strong complement-dependent cytotoxicity against GalT-KO porcine target cells. These data suggest that antibodies to non-Gal antigens will present an additional barrier to transplantation of organs from GalT-KO pigs to humans. © 2005 Nature Publishing Group

An associative network with spatially organized connectivity

We investigate the properties of an autoassociative network of threshold-linear units whose synaptic connectivity is spatially structured and asymmetric. Since the methods of equilibrium statistical mechanics cannot be applied to such a network due to the lack of a Hamiltonian, we approach the problem through a signal-to-noise analysis, that we adapt to spatially organized networks. The conditions are analyzed for the appearance of stable, spatially non-uniform profiles of activity with large overlaps with one of the stored patterns. It is also shown, with simulations and analytic results, that the storage capacity does not decrease much when the connectivity of the network becomes short range. In addition, the method used here enables us to calculate exactly the storage capacity of a randomly connected network with arbitrary degree of dilution.Comment: 27 pages, 6 figures; Accepted for publication in JSTA

Affine differential geometry analysis of human arm movements

Humans interact with their environment through sensory information and motor actions. These interactions may be understood via the underlying geometry of both perception and action. While the motor space is typically considered by default to be Euclidean, persistent behavioral observations point to a different underlying geometric structure. These observed regularities include the “two-thirds power law” which connects path curvature with velocity, and “local isochrony” which prescribes the relation between movement time and its extent. Starting with these empirical observations, we have developed a mathematical framework based on differential geometry, Lie group theory and Cartan’s moving frame method for the analysis of human hand trajectories. We also use this method to identify possible motion primitives, i.e., elementary building blocks from which more complicated movements are constructed. We show that a natural geometric description of continuous repetitive hand trajectories is not Euclidean but equi-affine. Specifically, equi-affine velocity is piecewise constant along movement segments, and movement execution time for a given segment is proportional to its equi-affine arc-length. Using this mathematical framework, we then analyze experimentally recorded drawing movements. To examine movement segmentation and classification, the two fundamental equi-affine differential invariants—equi-affine arc-length and curvature are calculated for the recorded movements. We also discuss the possible role of conic sections, i.e., curves with constant equi-affine curvature, as motor primitives and focus in more detail on parabolas, the equi-affine geodesics. Finally, we explore possible schemes for the internal neural coding of motor commands by showing that the equi-affine framework is compatible with the common model of population coding of the hand velocity vector when combined with a simple assumption on its dynamics. We then discuss several alternative explanations for the role that the equi-affine metric may play in internal representations of motion perception and production

Regulatory module involving FGF13, miR-504, and p53 regulates ribosomal biogenesis and supports cancer cell survival

The microRNA miR-504 targets TP53 mRNA encoding the p53 tumor suppressor. miR-504 resides within the fibroblast growth factor 13 (FGF13) gene, which is overexpressed in various cancers. We report that the FGF13 locus, comprising FGF13 and miR-504, is transcriptionally repressed by p53, defining an additional negative feedback loop in the p53 network. Furthermore, we show that FGF13 1A is a nucleolar protein that represses ribosomal RNA transcription and attenuates protein synthesis. Importantly, in cancer cells expressing high levels of FGF13, the depletion of FGF13 elicits increased proteostasis stress, associated with the accumulation of reactive oxygen species and apoptosis. Notably, stepwise neoplastic transformation is accompanied by a gradual increase in FGF13 expression and increased dependence on FGF13 for survival ("nononcogene addiction"). Moreover, FGF13 overexpression enables cells to cope more effectively with the stress elicited by oncogenic Ras protein. We propose that, in cells in which activated oncogenes drive excessive protein synthesis, FGF13 may favor survival by maintaining translation rates at a level compatible with the protein quality- control capacity of the cell. Thus, FGF13 may serve as an enabler, allowing cancer cells to evade proteostasis stress triggered by oncogene activation

Zippin’ up my boots, goin’ back to my roots: Radical left parties in Southern Europe

Radical left parties actively encourage the participation of their members in internal decision-making and insist on promoting organised links to trade unions and social movements. As a party family, they deviate from what is considered to be the trend in which Western political parties have turned their backs on their social roots. Drawing on the experience of South European radical left parties from the fall of the Berlin Wall until the recent financial crisis, we argue that ideology, electoral incentives, party competition and external events explain the radical left's pronounced emphasis on linkage, while organisational trajectory explains variation within the party family in terms of the linkage strategies pursued

Stochastic Analysis of the SOS Response in Escherichia coli

BACKGROUND: DNA damage in Escherichia coli evokes a response mechanism called the SOS response. The genetic circuit of this mechanism includes the genes recA and lexA, which regulate each other via a mixed feedback loop involving transcriptional regulation and protein-protein interaction. Under normal conditions, recA is transcriptionally repressed by LexA, which also functions as an auto-repressor. In presence of DNA damage, RecA proteins recognize stalled replication forks and participate in the DNA repair process. Under these conditions, RecA marks LexA for fast degradation. Generally, such mixed feedback loops are known to exhibit either bi-stability or a single steady state. However, when the dynamics of the SOS system following DNA damage was recently studied in single cells, ordered peaks were observed in the promoter activity of both genes (Friedman et al., 2005, PLoS Biol. 3(7):e238). This surprising phenomenon was masked in previous studies of cell populations. Previous attempts to explain these results harnessed additional genes to the system and deployed complex deterministic mathematical models that were only partially successful in explaining the results. METHODOLOGY/PRINCIPAL FINDINGS: Here we apply stochastic methods, which are better suited for dynamic simulations of single cells. We show that a simple model, involving only the basic components of the circuit, is sufficient to explain the peaks in the promoter activities of recA and lexA. Notably, deterministic simulations of the same model do not produce peaks in the promoter activities. CONCLUSION/SIGNIFICANCE: We conclude that the double negative mixed feedback loop with auto-repression accounts for the experimentally observed peaks in the promoter activities. In addition to explaining the experimental results, this result shows that including additional regulations in a mixed feedback loop may dramatically change the dynamic functionality of this regulatory module. Furthermore, our results suggests that stochastic fluctuations strongly affect the qualitative behavior of important regulatory modules even under biologically relevant conditions, thus emphasizing the importance of stochastic analysis of regulatory circuits