Network Discovery by Generalized Random Walks

We investigate network exploration by random walks defined via stationary and adaptive transition probabilities on large graphs. We derive an exact formula valid for arbitrary graphs and arbitrary walks with stationary transition probabilities (STP), for the average number of discovered edges as function of time. We show that for STP walks site and edge exploration obey the same scaling $\sim n^{\lambda}$ as function of time $n$. Therefore, edge exploration on graphs with many loops is always lagging compared to site exploration, the revealed graph being sparse until almost all nodes have been discovered. We then introduce the Edge Explorer Model, which presents a novel class of adaptive walks, that perform faithful network discovery even on dense networks.Comment: 23 pages, 7 figure

The fickle Mutation of a Cytoplasmic Tyrosine Kinase Effects Sensitization but not Dishabituation in Drosophila Melanogaster

fickle is a P-element mutation identified from a screen for defects in courtship behavior and disrupts the fly homolog of Bruton's tyrosine kinase (Btk) gene (Baba et al., 1999). Here, we show that habituation of the olfactory jump reflex also is defective in fickle. Unlike, the prototypical memory mutants, rutabaga and dunce, which habituate more slowly than normal, fickle flies habituate faster than normal. fickle's faster-than-normal response decrement did not appear to be due to sensorimotor fatigue, and dishabituation of the jump response was normal. Based on a long-standing “two opponent process” theory of habituation, these data suggested that behavioral sensitization might be defective in fickle. To test this hypothesis, we designed a olfactory sensitization procedure, using the same stimuli to habituate (odor) and dishabituate (vortexing) flies. Mutant flies failed to show any sensitization with this procedure. Our study reveals a “genetic dissection” of sensitization and dishabituation and, for the first time, provides a biological confirmation of the two opponent process theory of habituation

Concentration- and time-dependent effectof aminooxyacetic acidon cortical epileptogenicity

In the present electrophysiological study the effect of aminooxyacetic acid (AOAA) on the cortical epileptogenicity, and on the basic electro-cortical activity was investigated in anesthetized rats.AOAA did not induce spontaneous epileptiform discharges but modified the somato-sensory evoked responses and the cortical epileptogenicity (induced by 4-aminopyridine) in the same manner depending on its concentration. AOAA at low concentrations increased the amplitude of evoked responses and the ipsilateral manifestation of epileptiform activity, however, at high concentrations significantly suppressed both the evoked responses and the induction and expression of seizures discharges. The anticonvulsive effect of AOAA was time-dependent (reached its maximum after 2h AOAA pre-treatment) and reversible. AOAA at low concentrations probably increases the efficacy of the NMDA excitatory system and decreases GABA-synthesis, resulting neuronal hyperexcitation. However, AOAA at high concentrations can lead to an effective cortical inhibition through intra- and extracellular accumulation of GABA. The gradual GABA accumulation - up to a certain level - at the synapses could also explain the time-dependency of the anticonvulsive effect of AOAA

Distributed flow optimization and cascading effects in weighted complex networks

We investigate the effect of a specific edge weighting scheme $\sim (k_i k_j)^{\beta}$ on distributed flow efficiency and robustness to cascading failures in scale-free networks. In particular, we analyze a simple, yet fundamental distributed flow model: current flow in random resistor networks. By the tuning of control parameter $\beta$ and by considering two general cases of relative node processing capabilities as well as the effect of bandwidth, we show the dependence of transport efficiency upon the correlations between the topology and weights. By studying the severity of cascades for different control parameter $\beta$, we find that network resilience to cascading overloads and network throughput is optimal for the same value of $\beta$ over the range of node capacities and available bandwidth

Olfactory Jump Reflex Habituation in Drosophila and Effects of Classical Conditioning Mutations

Habituation is a nonassociative learning mechanism, in which an initial response toward repeated stimuli gradually wanes. This is amongst the simplest and most widespread forms of behavioral plasticity. So far, neither the underlying molecular mechanisms nor the precise neural networks of habituation are well understood. We have developed a novel paradigm to quantify habituation of the olfactory jump reflex in Drosophila. We present data demonstrating several behavioral properties of this phenomenon, generally observed in other species. We also show that the dunce and rutabaga memory mutants behave abnormally in this assay, suggesting that this assay might be used in behavioral screens for new mutants with defects in this simpler form of behavioral plasticity

Scaling behavior in crackle sound during lung inflation

During slow inflation of lung lobes, we measure a sequence of short explosive transient sound waves called "crackles," each consisting of an initial spike followed by ringing. The crackle time series is irregular and intermittent, with the number of spikes of size s following a power law, n(s)proportional to s(-alpha), with alpha = 2.77 +/- 0.05. We develop a model of crackle wave generation and propagation in a tree structure that combines the avalanchelike opening of airway segments with the wave propagation of crackles in a tree structure. The agreement between experiments and simulations suggests that (i) the irregularities are a consequence of structural heterogeneity in the lung, (ii) the intermittent behavior is due to the avalanchelike opening, and (iii) the scaling is a result of successive attenuations acting on the sound spikes as they propagate through a cascade of bifurcations along the airway tree. [S1063-651X(99)13810-8]

Saturated Fats: A Perspective from Lactation and Milk Composition

For recommendations of specific targets for the absolute amount of saturated fat intake, we need to know what dietary intake is most appropriate? Changing agricultural production and processing to lower the relative quantities of macronutrients requires years to accomplish. Changes can have unintended consequences on diets and the health of subsets of the population. Hence, what are the appropriate absolute amounts of saturated fat in our diets? Is the scientific evidence consistent with an optimal intake of zero? If not, is it also possible that a finite intake of saturated fats is beneficial to overall health, at least to a subset of the population? Conclusive evidence from prospective human trials is not available, hence other sources of information must be considered. One approach is to examine the evolution of lactation, and the composition of milks that developed through millennia of natural selective pressure and natural selection processes. Mammalian milks, including human milk, contain 50% of their total fatty acids as saturated fatty acids. The biochemical formation of a single double bond converting a saturated to a monounsaturated fatty acid is a pathway that exists in all eukaryotic organisms and is active within the mammary gland. In the face of selective pressure, mammary lipid synthesis in all mammals continues to release a significant content of saturated fatty acids into milk. Is it possible that evolution of the mammary gland reveals benefits to saturated fatty acids that current recommendations do not consider

Molecular Evolution of Phosphoprotein Phosphatases in Drosophila

Phosphoprotein phosphatases (PPP), these ancient and important regulatory enzymes are present in all eukaryotic organisms. Based on the genome sequences of 12 Drosophila species we traced the evolution of the PPP catalytic subunits and noted a substantial expansion of the gene family. We concluded that the 18–22 PPP genes of Drosophilidae were generated from a core set of 8 indispensable phosphatases that are present in most of the insects. Retropositons followed by tandem gene duplications extended the phosphatase repertoire, and sporadic gene losses contributed to the species specific variations in the PPP complement. During the course of these studies we identified 5, up till now uncharacterized phosphatase retrogenes: PpY+, PpD5+, PpD6+, Pp4+, and Pp6+ which are found only in some ancient Drosophila. We demonstrated that all of these new PPP genes exhibit a distinct male specific expression. In addition to the changes in gene numbers, the intron-exon structure and the chromosomal localization of several PPP genes was also altered during evolution. The G−C content of the coding regions decreased when a gene moved into the heterochromatic region of chromosome Y. Thus the PPP enzymes exemplify the various types of dynamic rearrangements that accompany the molecular evolution of a gene family in Drosophilidae

CONCEPTT: Continuous Glucose Monitoring in Women with Type 1 Diabetes in Pregnancy Trial: A multi-center, multi-national, randomized controlled trial - Study protocol.

BACKGROUND: Women with type 1 diabetes strive for optimal glycemic control before and during pregnancy to avoid adverse obstetric and perinatal outcomes. For most women, optimal glycemic control is challenging to achieve and maintain. The aim of this study is to determine whether the use of real-time continuous glucose monitoring (RT-CGM) will improve glycemic control in women with type 1 diabetes who are pregnant or planning pregnancy. METHODS/DESIGN: A multi-center, open label, randomized, controlled trial of women with type 1 diabetes who are either planning pregnancy with an HbA1c of 7.0 % to ≤10.0 % (53 to ≤ 86 mmol/mol) or are in early pregnancy (<13 weeks 6 days) with an HbA1c of 6.5 % to ≤10.0 % (48 to ≤ 86 mmol/mol). Participants will be randomized to either RT-CGM alongside conventional intermittent home glucose monitoring (HGM), or HGM alone. Eligible women will wear a CGM which does not display the glucose result for 6 days during the run-in phase. To be eligible for randomization, a minimum of 4 HGM measurements per day and a minimum of 96 hours total with 24 hours overnight (11 pm-7 am) of CGM glucose values are required. Those meeting these criteria are randomized to RT- CGM or HGM. A total of 324 women will be recruited (110 planning pregnancy, 214 pregnant). This takes into account 15 and 20 % attrition rates for the planning pregnancy and pregnant cohorts and will detect a clinically relevant 0.5 % difference between groups at 90 % power with 5 % significance. Randomization will stratify for type of insulin treatment (pump or multiple daily injections) and baseline HbA1c. Analyses will be performed according to intention to treat. The primary outcome is the change in glycemic control as measured by HbA1c from baseline to 24 weeks or conception in women planning pregnancy, and from baseline to 34 weeks gestation during pregnancy. Secondary outcomes include maternal hypoglycemia, CGM time in, above and below target (3.5-7.8 mmol/l), glucose variability measures, maternal and neonatal outcomes. DISCUSSION: This will be the first international multicenter randomized controlled trial to evaluate the impact of RT- CGM before and during pregnancy in women with type 1 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01788527 Registration Date: December 19, 2012