A statistical consequence of the logical calculus of nervous nets

A formal method is derived for converting logical relations among the actions of neurons in a net into statistical relations among the frequencies of their impulses.     

Electromyographic activity from human laryngeal, pharyngeal, and submental muscles during swallowing.

The durations and temporal relationships of electromyographic activity from the submental complex, superior pharyngeal constrictor, cricopharyngeus, thyroarytenoid, and interarytenoid muscles were examined during swallowing of saliva and of 5- and 10-ml water boluses. Bipolar, hooked-wire electrodes were inserted into all muscles except for the submental complex, which was studied with bipolar surface electrodes. Eight healthy, normal, subjects produced five swallows of each of three bolus volumes for a total of 120 swallows. The total duration of electromyographic activity during the pharyngeal stage of the swallow did not alter with bolus condition; however, specific muscles did show a volume-dependent change in electromyograph duration and time of firing. Submental muscle activity was longest for saliva swallows. The interarytenoid muscle showed a significant difference in duration between the saliva and 10-ml water bolus. Finally, the interval between the onset of laryngeal muscle activity (thyroarytenoid, interarytenoid) and of pharyngeal muscle firing patterns (superior pharyngeal constrictor onset, cricopharyngeus offset) decreased as bolus volume increased. The pattern of muscle activity associated with the swallow showed a high level of intrasubject agreement; the presence of somewhat different patterns among subjects indicated a degree of population variance.     

A role for gelsolin in stress fiber-dependent cell contraction.

Gelsolin is an abundant actin binding protein that mediates the rapid remodeling of cortical actin filaments through severing, capping, and nucleating activities. Most of the attention on the intracellular function of gelsolin has focused on the remodeling of the cortical actin meshwork but the localization of gelsolin to other regions of the cell suggests that it may have other important functions elsewhere. In cultured fibroblasts, gelsolin is heavily enriched in stress fibers, where its function in these contractile organelles is unknown. To study gelsolin function during stress fiber formation and cell contraction, we first assessed gelsolin levels in stress fiber preparations from lysophosphatidic acid (LPA)-treated human fibroblasts. LPA induced a large, time-dependent, calcium-independent increase of actin, gelsolin, alpha-actinin, and tropomyosin in stress fiber preparations. A microinjected gelsolin antibody that inhibits severing by gelsolin reduced stress fibers. Anti-sense-transfected gelsolin-depleted 3T3 cell lines treated with LPA after serum starvation required approximately 6 h to form stress fibers and focal adhesions, in contrast to control lines transfected with vector only, which formed stress fibers 15 min after addition of LPA. In cells microinjected with the gelsolin antibody that inhibits severing, Mg-ATP-induced cell contraction was greatly reduced in approximately 90% of injected cells compared to cells injected with an irrelevant antibody. Gelsolin-depleted cells were incapable of collagen gel contraction and showed no apparent Mg-ATP-induced cell contraction compared to cell lines transfected with vector only. The involvement of gelsolin in cell contraction and remodeling of collagen gels suggests a novel role for gelsolin in stress fiber-dependent cell function.     

Burn‐in Free Nonfullerene‐Based Organic Solar Cells

Organic solar cells that are free of burn‐in, the commonly observed rapid performance loss under light, are presented. The solar cells are based on poly(3‐hexylthiophene) (P3HT) with varying molecular weights and a nonfullerene acceptor (rhodanine‐benzothiadiazole‐coupled indacenodithiophene, IDTBR) and are fabricated in air. P3HT:IDTBR solar cells light‐soaked over the course of 2000 h lose about 5% of power conversion efficiency (PCE), in stark contrast to [6,6]‐Phenyl C61 butyric acid methyl ester (PCBM)‐based solar cells whose PCE shows a burn‐in that extends over several hundreds of hours and levels off at a loss of ≈34%. Replacing PCBM with IDTBR prevents short‐circuit current losses due to fullerene dimerization and inhibits disorder‐induced open‐circuit voltage losses, indicating a very robust device operation that is insensitive to defect states. Small losses in fill factor over time are proposed to originate from polymer or interface defects. Finally, the combination of enhanced efficiency and stability in P3HT:IDTBR increases the lifetime energy yield by more than a factor of 10 when compared with the same type of devices using a fullerene‐based acceptor instead.     

Rap1 activation in collagen phagocytosis is dependent on nonmuscle myosin II-A

Rap1 enhances integrin-mediated adhesion but the link between Rap1 activation and integrin function in collagen phagocytosis is not defined. Mass spectrometry of Rap1 immunoprecipitates showed that the association of Rap1 with nonmuscle myosin heavy-chain II-A (NMHC II-A) was enhanced by cell attachment to collagen beads. Rap1 colocalized with NM II-A at collagen bead-binding sites. There was a transient increase in myosin light-chain phosphorylation after collagen-bead binding that was dependent on myosin light-chain kinase but not Rho kinase. Inhibition of myosin light-chain phosphorylation, but not myosin II-A motor activity inhibited collagen-bead binding and Rap activation. In vitro binding assays demonstrated binding of Rap1A to filamentous myosin rods, and in situ staining of permeabilized cells showed that NM II-A filaments colocalized with F-actin at collagen bead sites. Knockdown of NM II-A did not affect talin, actin, or β1-integrin targeting to collagen beads but targeting of Rap1 and vinculin to collagen was inhibited. Conversely, knockdown of Rap1 did not affect localization of NM II-A to beads. We conclude that MLC phosphorylation in response to initial collagen-bead binding promotes NM II-A filament assembly; binding of Rap1 to myosin filaments enables Rap1-dependent integrin activation and enhanced collagen phagocytosis.     

Search Algorithms as a Framework for the Optimization of Drug Combinations

Combination therapies are often needed for effective clinical outcomes in the management of complex diseases, but presently they are generally based on empirical clinical experience. Here we suggest a novel application of search algorithms—originally developed for digital communication—modified to optimize combinations of therapeutic interventions. In biological experiments measuring the restoration of the decline with age in heart function and exercise capacity in Drosophila melanogaster, we found that search algorithms correctly identified optimal combinations of four drugs using only one-third of the tests performed in a fully factorial search. In experiments identifying combinations of three doses of up to six drugs for selective killing of human cancer cells, search algorithms resulted in a highly significant enrichment of selective combinations compared with random searches. In simulations using a network model of cell death, we found that the search algorithms identified the optimal combinations of 6–9 interventions in 80–90% of tests, compared with 15–30% for an equivalent random search. These findings suggest that modified search algorithms from information theory have the potential to enhance the discovery of novel therapeutic drug combinations. This report also helps to frame a biomedical problem that will benefit from an interdisciplinary effort and suggests a general strategy for its solution.     

The upscaling of transpiration from individual trees to areal transpiration in tree belts

Sap flow measurements have long been used to measure transpiration in individual trees and there exist some well established methods for upscaling individual tree volumetric transpiration to areal transpiration in plantation and forest plots. However, where edge effects are significant, such as in tree belts, the area the volumetric transpiration is to be projected upon is unknown. This paper provides a methodology for estimating the area that a tree belt hydrologically occupies by using either measurements of tree root density or soil moisture distribution. An application of the proposed methodology shows that simply assuming that the area of the tree belt is the crown projected area could lead to an overestimation of the areal transpiration of 100%. The online version of the original article can be found at .     

Structure and growth rates of the high-latitude coral: <Emphasis Type="Italic">Plesiastrea versipora</Emphasis>

The high-latitude coral species Plesiastrea versipora was investigated to identify growth rates in colonies over 1 m in diameter. Six colonies from two temperate gulfs (latitudes of 33°–35°S) in Southern Australia were examined using X-ray, luminescence and ²³⁸U/²³⁰Th dating techniques. Annual density bands were present in each coral but varied in width and definition, suggesting different linear extension and calcification rates. Differences in density band width were observed at the local scale (amongst colonies on the same reef) and regional scales (between the two gulfs). Extension rates of the P. versipora colonies examined in this study varied between 1.2 and 7 mm per year, which are amongst the slowest growth rates reported for hermatypic corals. As only one of the six P. versipora colonies had obvious luminescent banding, we conclude that luminescent banding is not an accurate chronological marker in this species of temperate water coral. Coral age estimates derived from counting density bands in X-radiographs ranged from 90 to 320 years for the six colonies studied. U-Th ages from the same colonies determined by high-precision multi-collector inductively coupled plasma mass spectrometer established radiometric ages between 105 and 381 years. The chronological variation in absolute ages between the two techniques varied between 2 and 19% in different colonies, with the lowest growth rates (~1 mm) displaying the greatest variation between density band age and radiometric U-Th age. This result implies that the age of P. versipora and other slow-growing corals cannot be determined accurately from density bands alone. The outcome of this research demonstrates that P. versipora may be useful as a paleoclimate archive, recording several centuries in a single colony in high-latitude environments (corals found in latitudes greater than 30° in either hemisphere), where other well-established coral climate archives, such as Porites, do not occur.