Electrical Flows, Laplacian Systems, and Faster Approximation of Maximum Flow in Undirected Graphs

We introduce a new approach to computing an approximately maximum s-t flow in a capacitated, undirected graph. This flow is computed by solving a sequence of electrical flow problems. Each electrical flow is given by the solution of a system of linear equations in a Laplacian matrix, and thus may be approximately computed in nearly-linear time. Using this approach, we develop the fastest known algorithm for computing approximately maximum s-t flows. For a graph having n vertices and m edges, our algorithm computes a (1-\epsilon)-approximately maximum s-t flow in time \tilde{O}(mn^{1/3} \epsilon^{-11/3}). A dual version of our approach computes a (1+\epsilon)-approximately minimum s-t cut in time \tilde{O}(m+n^{4/3}\eps^{-8/3}), which is the fastest known algorithm for this problem as well. Previously, the best dependence on m and n was achieved by the algorithm of Goldberg and Rao (J. ACM 1998), which can be used to compute approximately maximum s-t flows in time \tilde{O}(m\sqrt{n}\epsilon^{-1}), and approximately minimum s-t cuts in time \tilde{O}(m+n^{3/2}\epsilon^{-3})

Hypocretin-1 receptors regulate the reinforcing and reward-enhancing effects of cocaine: pharmacological and behavioral genetics evidence.

Considerable evidence suggests that transmission at hypocretin-1 (orexin-1) receptors (Hcrt-R1) plays an important role in the reinstatement of extinguished cocaine-seeking behaviors in rodents. However, far less is known about the role for hypocretin transmission in regulating ongoing cocaine-taking behavior. Here, we investigated the effects of the selective Hcrt-R1 antagonist SB-334867 on cocaine intake, as measured by intravenous (IV) cocaine self-administration in rats. The stimulatory effects of cocaine on brain reward systems contribute to the establishment and maintenance of cocaine-taking behaviors. Therefore, we also assessed the effects of SB-334867 on the reward-enhancing properties of cocaine, as measured by cocaine-induced lowering of intracranial self-stimulation (ICSS) thresholds. Finally, to definitively establish a role for Hcrt-R1 in regulating cocaine intake, we assessed IV cocaine self-administration in Hcrt-R1 knockout mice. We found that SB-334867 (1-4 mg/kg) dose-dependently decreased cocaine (0.5 mg/kg/infusion) self-administration in rats but did not alter responding for food rewards under the same schedule of reinforcement. This suggests that SB-334867 decreased cocaine reinforcement without negatively impacting operant performance. SB-334867 (1-4 mg/kg) also dose-dependently attenuated the stimulatory effects of cocaine (10 mg/kg) on brain reward systems, as measured by reversal of cocaine-induced lowering of ICSS thresholds in rats. Finally, we found that Hcrt-R1 knockout mice self-administered far less cocaine than wildtype mice across the entire dose-response function. These data demonstrate that Hcrt-R1 play an important role in regulating the reinforcing and reward-enhancing properties of cocaine and suggest that hypocretin transmission is likely essential for establishing and maintaining the cocaine habit in human addicts

Baraminological Analysis of Devonian and Carboniferous Tetrapodomorphs

According to evolutionary theory, the origin of tetrapods (or limbed vertebrates) from a fish-like ancestor during the Devonian Period was one of the major events in the history of life. Devonian sediments have yielded several families of tetrapod-like fishes, including the elpistostegids which range from the Givetian to Frasnian of the Middle to Upper Devonian and are regarded as close to the evolutionary ancestry of tetrapods. Two of the best-known ‘early’ tetrapods are Ichthyostega and Acanthostega, first described from fossil material discovered in the Famennian (uppermost Upper Devonian) sediments of East Greenland. These taxa (and others subsequently described) display mosaic combinations of fish-like and tetrapod-like characters, along with some unique traits (such as polydactyly) not found in more ‘derived’ tetrapods. Creationists have claimed that these organisms are not evolutionary intermediates, but were rather the inhabitants of aquatic environments associated with a pre-Flood floating forest biome, with morphologically intermediate traits that equipped them for life in an environment that was itself intermediate between the sea and the land. This paper evaluates the baraminic status of a range of Devonian and Carboniferous fishes and tetrapods using the techniques of statistical baraminology. Baraminic distance correlation (BDC) and three-dimensional multidimensional scaling (MDS) are applied to six previously published character-taxon matrices. The results reveal little evidence of continuity, and significant evidence of discontinuity, between the elpistostegids and tetrapods such as Ichthyostega and Acanthostega, consistent with the creationist claim of separate ancestry. However, further work will be required to elucidate the baraminic relationships within these presumably apobaraminic groups

Platelet-mediated metabolism of the common dietary flavonoid, quercetin.

BACKGROUND: Flavonoid metabolites remain in blood for periods of time potentially long enough to allow interactions with cellular components of this tissue. It is well-established that flavonoids are metabolised within the intestine and liver into methylated, sulphated and glucuronidated counterparts, which inhibit platelet function. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate evidence suggesting platelets which contain metabolic enzymes, as an alternative location for flavonoid metabolism. Quercetin and a plasma metabolite of this compound, 4'-O-methyl quercetin (tamarixetin) were shown to gain access to the cytosolic compartment of platelets, using confocal microscopy. High performance liquid chromatography (HPLC) and mass spectrometry (MS) showed that quercetin was transformed into a compound with a mass identical to tamarixetin, suggesting that the flavonoid was methylated by catechol-O-methyl transferase (COMT) within platelets. CONCLUSIONS/SIGNIFICANCE: Platelets potentially mediate a third phase of flavonoid metabolism, which may impact on the regulation of the function of these cells by metabolites of these dietary compounds