Push is Fast on Sparse Random Graphs

We consider the classical push broadcast process on a large class of sparse random multigraphs that includes random power law graphs and multigraphs. Our analysis shows that for every $\varepsilon>0$, whp $O(\log n)$ rounds are sufficient to inform all but an $\varepsilon$-fraction of the vertices. It is not hard to see that, e.g. for random power law graphs, the push process needs whp $n^{\Omega(1)}$ rounds to inform all vertices. Fountoulakis, Panagiotou and Sauerwald proved that for random graphs that have power law degree sequences with $\beta>3$, the push-pull protocol needs $\Omega(\log n)$ to inform all but $\varepsilon n$ vertices whp. Our result demonstrates that, for such random graphs, the pull mechanism does not (asymptotically) improve the running time. This is surprising as it is known that, on random power law graphs with $2<\beta<3$, push-pull is exponentially faster than pull

Activation émotionnelle chez les troubles de personnalité

Six traitements psychothérapiques des troubles de personnalité sont brièvement présentés dans cette revue de la littérature. Ces traitements se basent sur des modèles théoriques différents, les approches cognitive-comportementale, psychodynamique et interpersonnelle et ont déjà fait leurs preuves cliniques et empiriques en termes de leur efficacité. Se centrant sur les processus de changement thérapeutique, les auteurs émettent l’hypothèse que le processus d’activation émotionnelle est l’un des ingrédients les plus intéressants de ces traitements. Les traitements sont discutés sous l’angle de cette hypothèse et de ses implications cliniques.There are at least six psychotherapeutic treatments of personality disorders having received empirical and clinical validation in terms of their efficacy. These treatments are based on different theoretical models, namely the cognitive-behavioural, psychodynamic and interpersonal models. This article briefly presents these treatments, focusing on the process of therapeutic change. It is assumed that the process of emotional activation is one of the most interesting theoretical psychotherapy ingredient in treatments of these patients. The treatments are discussed regarding this hypothesis and its clinical implications.En esta revisión de la literatura se presentan brevemente seis tratamientos psicoterapéuticos de los trastornos de la personalidad. Estos tratamientos se basan en modelos teóricos diferentes, los enfoques cognitivo-comportamentales, psicodinámicos e interpersonales, cuya eficacia ya ha sido probada clínica y empíricamente. Al centrarse en los procesos de cambio terapéutico, los autores plantean la hipótesis de que el proceso de activación emocional es uno de los componentes más interesantes de estos tratamientos. Los tratamientos se discuten bajo el punto de vista de esta hipótesis y sus implicaciones clínicas.Seis tratamentos psicoterápicos dos transtornos de personalidade são apresentados brevemente nesta revista da literatura. Estes tratamentos baseiam-se em modelos teóricos diferentes, abordagens cognitivo-comportamental, psicodinâmica e interpessoal, e já passaram por provas clínicas e empíricas com respeito à sua eficácia. Concentrando-se nos processos de mudança terapêutica, os autores levantam a hipótese de que o processo de ativação emocional é um dos ingredientes mais interessantes destes tratamentos. Os tratamentos são discutidos sob o ângulo desta hipótese e destas implicações clínicas

The relation of phase noise and luminance contrast to overt attention in complex visual stimuli

Models of attention are typically based on difference maps in low-level features but neglect higher order stimulus structure. To what extent does higher order statistics affect human attention in natural stimuli? We recorded eye movements while observers viewed unmodified and modified images of natural scenes. Modifications included contrast modulations (resulting in changes to first- and second-order statistics), as well as the addition of noise to the Fourier phase (resulting in changes to higher order statistics). We have the following findings: (1) Subjects' interpretation of a stimulus as a “natural” depiction of an outdoor scene depends on higher order statistics in a highly nonlinear, categorical fashion. (2) Confirming previous findings, contrast is elevated at fixated locations for a variety of stimulus categories. In addition, we find that the size of this elevation depends on higher order statistics and reduces with increasing phase noise. (3) Global modulations of contrast bias eye position toward high contrasts, consistent with a linear effect of contrast on fixation probability. This bias is independent of phase noise. (4) Small patches of locally decreased contrast repel eye position less than large patches of the same aggregate area, irrespective of phase noise. Our findings provide evidence that deviations from surrounding statistics, rather than contrast per se, underlie the well-established relation of contrast to fixation

Monitoring serum concentrations for once-daily netilmicin dosing regimens

A once-daily dosing regimen for aminoglycosides is less expensive, at least as effective and possibly less toxic than multiple-daily dosing regimens. Once-daily dosing might also allow the frequency of measuring the serum concentrations of these antibiotics to be reduced since two of the major objectives of monitoring, high peak and low trough concentrations, are more likely to be achieved with this regimen. A novel strategy for monitoring serum concentrations which relies on a single sample obtained 8 h after a dose, as opposed to both trough and peak samples, is evaluated here. Serum kinetics of netilmicin were studied prospectively in 51 adult patients with initial serum creatinine concentrations of 25 μmol/L was detected in 0 of 7 patients with an 8-h concentration of 6 mg/L. The results of this study suggest that adequate information about serum netilmicin concentrations in patients receiving a once-daily dose may be derived from a sample obtained 8 h after administratio

Glutathione-conjugating and membrane-remodeling activity of GDAP1 relies on amphipathic C-terminal domain

Mutations in the ganglioside-induced differentiation associated protein 1 (GDAP1) cause severe peripheral motor and sensory neuropathies called Charcot-Marie-Tooth disease. GDAP1 expression induces fission of mitochondria and peroxisomes by a currently elusive mechanism, while disease causing mutations in GDAP1 impede the protein’s role in mitochondrial dynamics. In silico analysis reveals sequence similarities of GDAP1 to glutathione S-transferases (GSTs). However, a proof of GST activity and its possible impact on membrane dynamics are lacking to date. Using recombinant protein, we demonstrate for the first time theta-class-like GST activity for GDAP1, and it’s activity being regulated by the C-terminal hydrophobic domain 1 (HD1) of GDAP1 in an autoinhibitory manner. Moreover, we show that the HD1 amphipathic pattern is required to induce membrane dynamics by GDAP1. As both, fission and GST activities of GDAP1, are critically dependent on HD1, we propose that GDAP1 undergoes a molecular switch, turning from a pro-fission active to an auto-inhibited inactive conformation.ISSN:2045-232

Mtmr13/Sbf2-deficient mice: an animal model for CMT4B2

Charcot-Marie-Tooth (CMT) disease denotes a large group of genetically heterogeneous hereditary motor and sensory neuropathies and ranks among the most common inherited neurological disorders. Mutations in the Myotubularin-Related Protein-2 (MTMR2) or MTMR13/Set-Binding Factor-2 (SBF2) genes are associated with the autosomal recessive disease subtypes CMT4B1 or CMT4B2. Both forms of CMT share similar features including a demyelinating neuropathy associated with reduced nerve conduction velocity (NCV) and focally folded myelin. Consistent with a common disease mechanism, the homodimeric MTMR2 acts as a phosphoinositide D3-phosphatase with phosphatidylinositol (PtdIns) 3-phosphate and PtdIns 3,5-bisphosphate as substrates while MTMR13/SBF2 is catalytically inactive but can form a tetrameric complex with MTMR2, resulting in a strong increase of the enzymatic activity of complexed MTMR2. To prove that MTMR13/SBF2 is the disease-causing gene in CMT4B2 and to provide a suitable animal model, we have generated Mtmr13/Sbf2-deficient mice. These animals reproduced myelin outfoldings and infoldings in motor and sensory peripheral nerves as the pathological hallmarks of CMT4B2, concomitant with decreased motor performance. The number and complexity of myelin misfoldings increased with age, associated with axonal degeneration, and decreased compound motor action potential amplitude. Prolonged F-wave latency indicated a mild NCV impairment. Loss of Mtmr13/Sbf2 did not affect the levels of its binding partner Mtmr2 and the Mtmr2-binding Dlg1/Sap97 in peripheral nerves. Mice deficient in Mtmr13/Sbf2 together with known Mtmr2-deficient animals will be of major value to unravel the disease mechanism in CMT4B and to elucidate the critical functions of protein complexes that are involved in phosphoinositide-controlled processes in peripheral nerve

An animal model for Charcot-Marie-Tooth disease type 4B1

Charcot-Marie-Tooth disease (CMT) comprises a family of clinically and genetically very heterogeneous hereditary peripheral neuropathies and is one of the most common inherited neurological disorders. We have generated a mouse model for CMT type 4B1 using embryonic stem cell technology. To this end, we introduced a stop codon into the Mtmr2 locus within exon 9, at the position encoding amino acid 276 of the MTMR2 protein (E276X). Concomitantly, we have deleted the chromosomal region immediately downstream of the stop codon up to within exon 13. The resulting allele closely mimics the mutation found in a Saudi Arabian CMT4B1 patient. Animals homozygous for the mutation showed various degrees of complex myelin infoldings and outfoldings exclusively in peripheral nerves, in agreement with CMT4B1 genetics and pathology. Mainly, paranodal regions of the myelin sheath were affected, with a high degree of quantitative and qualitative variability between individuals. This pathology was progressive with age, and axonal damage was occasionally observed. Distal nerve regions were more affected than proximal parts, in line with the distribution in CMT. However, we found no significant electrophysiological changes, even in aged (16-month-old) mice, suggesting that myelin infoldings and outfoldings per se are not invariably associated with detectable electrophysiological abnormalities. Our animal model provides a basis for future detailed molecular and cellular studies on the underlying disease mechanisms in CMT4B1. Such an analysis will reveal how the disease develops, in particular, the enigmatic myelin infoldings and outfoldings as well as axonal damage, and provide mechanistic insights that may aid in the development of potential therapeutic approache

On globally sparse Ramsey graphs

We say that a graph $G$ has the Ramsey property w.r.t.\ some graph $F$ and some integer $r\geq 2$, or $G$ is $(F,r)$-Ramsey for short, if any $r$-coloring of the edges of $G$ contains a monochromatic copy of $F$. R{\"o}dl and Ruci{\'n}ski asked how globally sparse $(F,r)$-Ramsey graphs $G$ can possibly be, where the density of $G$ is measured by the subgraph $H\subseteq G$ with the highest average degree. So far, this so-called Ramsey density is known only for cliques and some trivial graphs $F$. In this work we determine the Ramsey density up to some small error terms for several cases when $F$ is a complete bipartite graph, a cycle or a path, and $r\geq 2$ colors are available