An integrated semiconductor device enabling non-optical genome sequencing

The seminal importance of DNA sequencing to the life sciences, biotechnology and medicine has driven the search for more scalable and lower-cost solutions. Here we describe a DNA sequencing technology in which scalable, low-cost semiconductor manufacturing techniques are used to make an integrated circuit able to directly perform non-optical DNA sequencing of genomes. Sequence data are obtained by directly sensing the ions produced by template-directed DNA polymerase synthesis using all-natural nucleotides on this massively parallel semiconductor-sensing device or ion chip. The ion chip contains ion-sensitive, field-effect transistor-based sensors in perfect register with 1.2 million wells, which provide confinement and allow parallel, simultaneous detection of independent sequencing reactions. Use of the most widely used technology for constructing integrated circuits, the complementary metal-oxide semiconductor (CMOS) process, allows for low-cost, large-scale production and scaling of the device to higher densities and larger array sizes. We show the performance of the system by sequencing three bacterial genomes, its robustness and scalability by producing ion chips with up to 10 times as many sensors and sequencing a human genome.     

Transparency and coherence in human motion perception

When confronted with moving images, the visual system often must decide whether the motion signals arise from a single object or from multiple objects. A special case of this problem arises when two independently moving gratings are superimposed. The gratings tend to cohere and move unambiguously in a single direction (pattern motion) instead of moving independently (component motion). Here we report that the tendency to see pattern motion depends very strongly on the luminance of the intersections (that is, to regions where the gratings overlap) relative to that of the gratings in a way that closely parallels the physics of transparency. When the luminance of these regions is chosen appropriately, pattern motion is destroyed and replaced by the appearance of two transparent gratings moving independently. The observations imply that motion detecting mechanisms in the visual system must have access to tacit 'knowledge' of the physics of transparency and that this knowledge can be used to segment the scene into different objects. The same knowledge could, in principle, be used to avoid confusing shadows with real object boundaries.     

Neuronal synchrony does not correlate with motion coherence in cortical area MT

Natural visual scenes are cluttered with multiple objects whose individual features must somehow be selectively linked (or 'bound') if perception is to coincide with reality. Recent neurophysiological evidence supports a 'binding-by-synchrony' hypothesis: neurons excited by features of the same object fire synchronously, while neurons excited by features of different objects do not. Moving plaid patterns offer a straightforward means to test this idea. By appropriate manipulations of apparent transparency, the component gratings of a plaid pattern can be seen as parts of a single coherently moving surface or as two non-coherently moving surfaces. We examined directional tuning and synchrony of area-MT neurons in awake, fixating primates in response to perceptually coherent and non-coherent plaid patterns. Here we show that directional tuning correlated highly with perceptual coherence, which is consistent with an earlier study. Although we found stimulus-dependent synchrony, coherent plaids elicited significantly less synchrony than did non-coherent plaids. Our data therefore do not support the binding-by-synchrony hypothesis as applied to this class of motion stimuli in area MT.     

Neural correlates of perceptual motion coherence.

The motions of overlapping contours in a visual scene may arise from the physical motion(s) of either a single or multiple surface(s). A central problem facing the visual motion system is that of assigning the most likely interpretation. The rules underlying this perceptual decision can be explored using a visual stimulus formed by superimposing two moving gratings. The resultant percept is either that of a single coherently moving 'plaid pattern' (coherent motion) or of the two component gratings sliding noncoherently across one another (noncoherent motion). When plaid patterns are configured to mimic one transparent grating overlying another, the percept of noncoherent motion dominates. We now report that neurons in the visual cortex of rhesus monkeys exhibit changes in direction tuning that parallel this perceptual phenomenon: sensitivity to the motions of the component gratings is enhanced under conditions that favour the perception of noncoherent motion. These results challenge models of cortical visual processing that fail to take into account the contribution of figural image segmentation cues to the analysis of visual motion.     

Object-based attention determines dominance in binocular rivalry

A question of long-standing interest to philosophers, psychologists and neuroscientists is how the brain selects which signals enter consciousness. Binocular rivalry and attention both involve selection of visual stimuli, but affect perception quite differently. During binocular rivalry, awareness alternates between two different stimuli presented to the two eyes. In contrast, attending to one of two different stimuli impairs discrimination of the ignored stimulus, but without causing it to disappear from consciousness. Here we show that despite this difference, attention and rivalry rely on shared object-based selection mechanisms. We cued attention to one of two superimposed transparent surfaces and then deleted the image of one surface from each eye, resulting in rivalry. Observers usually reported seeing only the cued surface. They were also less accurate in judging unpredictable changes in the features of the uncued surface. Our design ensured that selection of the cued surface could not have resulted from spatial, ocular or feature-based mechanisms. Rather, attention was drawn to one surface, and this caused the other surface to be perceptually suppressed during rivalry. These results raise the question of how object representations compete during these two forms of perceptual selection, even as the features of those objects change unpredictably over time.     

Regulation and electric excitation of enzyme membranes in vitro]

Enzyme membranes can be activated or inhibited by applying continuous or alternating electrical fields. The field can modify the transport or reaction term of the transport-reaction by action on the displacement of charged species including those giving pH effects or inducing volume flows. A first experimental example is given: the progressive supression of the inhibition of hexokinase by the product when increasing alternating fields are applied. In the same way the apparent optimal pH approaches that of the soluble enzyme. In addition to its theoretical and practical implications electrical regulation can lead to the monitoring of enzyme reaction-driven mechanochemical fibers.     

Production of spinal curvatures in rats by chemically dissimilar substances

Zusammenfassung Starke Kyphoskoliosen werden in Ratten durch Fütterung von osteolathyrogenischen Substanzen wie 2-Aminopropionitril, Aminoacetonitril, 2-Mercaptoethylamin, Cystamin, Semicarbazid und Acetonsemicarbazid induziert. Kyphosen können auch durchp-Hydrazinobenzoesäure, 4,4-Diphenylsemicarbazid, 1,5-Diphenylcarbazid, 1,3-Diäthyl-2-thioharnstoff und Thiosemicarbazid hervorgerufen werden. Es wird vermutet, dass derselbe toxische Mechanismus dieser chemisch ungleichen Substanzen durch Bildung von Koordinationsverbindungen oder Chelaten bedingt ist.

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This investigation was supported in part by Research Grant A-1427 from the National Institute of Arthritis and Metabolic Diseases, National Institutes of Health, U. S. Public Health Service. The authors also gratefully acknowledge generous gifts of BAPN acid fumarate by Dr.D. V. Frost of Abbott Laboratories, North Chicago, Ill. — These results were presented in part at the annual meeting of the American Institute of Nutrition, April 1958:W. Dasler andR. V. Milliser, Fed. Proc.17, 474 (1958).