Abstract: The invention relates to an apparatus and method for monitoring cells and to a method for monitoring changes in cells upon addition of an analyte to the cell's environment, comprising a device which includes an array of microelectrodes disposed in a cell culture chamber, upon which array a portion of cells adhere to the surfaces of the microelectrodes. The diameter of the cells are larger than the diameters of the microelectrodes. A voltage signal is applied across each of the microelectrodes and a reference electrode. Detection and monitoring of the signals resulting from the application of the voltage signal provides information regarding the electrical characteristics of the individual cells, including impedance (combined cell membrane capacitance and conductance), action potential parameters, cell membrane capacitance, cell membrane conductance, and cell/substrate seal resistance. Such an invention is useful in detecting or screening a variety of biological and chemical agents.

Abstract: Recombinant mycobacterial vaccine vehicles capable of expressing DNA of interest which encodes at least one protein antigen for at least one pathogen against which an immune response is desired and which can be incorporated into the mycobacteria or stably integrated into the mycobacterial genome. The vaccine vehicles are useful for administration to mammalian hosts for purposes of immunization. A recombinant vector which replicates in E. coli but not in mycobacteria is also disclosed. The recombinant vector includes 1) a mycobacterial gene or portions thereof, necessary for recombination with homologous sequences in the genome of mycobacteria transformed with the recombinant plasmid; 2) all or a portion of a gene which encodes a polypeptide or protein whose expression is desired in mycobacteria transformed with the recombinant plasmid; 3) DNA sequences necessary for replication and selection in E. coli; and 4) DNA sequences necessary for selection in mycobacteria (e.g., drug resistance).

Abstract: An electron source includes a negative electron affinity photocathode on a light-transmissive substrate and a light beam generator for directing a light beam through the substrate at the photocathode for exciting electrons into the conduction band. The photocathode has at least one active area for emission of electrons with dimensions of less than about two micrometers. The electron source further includes electron optics for forming the electrons into an electron beam and a vacuum enclosure for maintaining the photocathode at high vacuum. The photocathode is patterned to define emission areas. A patterned mask may be located on the emission surface of the active layer, may be buried within the active layer or may be located between the active layer and the substrate.

Abstract: A deflection sensor for a microcantilever includes two sets of interdigitated fingers, one (reference) set being attached to the substrate from which the microcantilever extends and the other (movable) set being attached to the tip of the microcantilever. Together the interdigitated fingers form an optical phase grating. The deflection of the microcantilever is measured by directing a light beam against the optical phase grating and detecting the intensity of the reflected light in the first (or other) component of the resulting diffraction pattern. As the microcantilever deflects, the reference and movable fingers move relative to one another creating large variations in the intensity of the zeroth and first order components of the diffraction pattern. To eliminate "1/f" noise the deflection of the microcantilever can be measured using an AC signal.

Abstract: An electron beam source includes a cathode having an electron emission surface including an active area for emission of electrons and a cathode shield assembly including a conductive shield disposed in proximity to the electron emission surface of the cathode. The shield has an opening aligned with the active area. The electron beam source further includes a device for stimulating emission of electrons from the active area of the cathode, electron optics for forming the electrons into an electron beam and a vacuum enclosure for maintaining the cathode at high vacuum. The cathode may be a negative electron affinity photocathode formed on a light-transmissive substrate. The shield protects non-emitting areas of the emission surface from contamination and inhibits cathode materials from contaminating components of the electron beam source. The cathode may be moved relative to the opening in the shield so as to align an new active area with the opening.

Abstract: An extremely small aperture is formed using a sharp conductive tip. The aperture may be in the form of a transparent window or an open aperture. In a first embodiment, the conductive tip is positioned adjacent a layer of titanium and a voltage is applied to the tip. The intense electric field near the tip anodizes the titanium and creates a small transparent window of titanium dioxide. In a second embodiment, a titanium layer is covered with a layer of silicon, a small region of the silicon is oxidized using a conductive tip, and the silicon and then the titanium are etched. In a third embodiment, an electric field from a conductive tip creates a pit in a surface titanium oxide layer. The titanium is then etched, using the oxide layer as a mask, to form an open aperture. The conductive tip is preferably the tip of an atomic force microscope.

Abstract: A cantilever for a scanning probe microscope (SPM) includes a piezoelectric element in a thicker, less flexible section near the fixed base of the cantilever and a piezoresistor in a thinner, more flexible section near the free end of the cantilever. When the SPM operates in the constant force mode, the piezoelectric element is used to control the tip-sample separation. Since the resonant frequency of the piezoelectric element is substantially higher than that of conventional piezoelectric tube scanners, much higher scan rates can be achieved. When the SPM operates in the dynamic or intermittent contact mode, a superimposed AD-DC signal is applied to the piezoelectric element, and the latter is used to vibrate the cantilever as well as to control the tip-sample spacing. In another embodiment the cantilever is supported on a knife edge and vibrates at a third or higher order resonant frequency.

Abstract: A thick column is formed by masking and etching a substrate, and the column is thinned to a very small diameter (e.g., .ltoreq.5 nm) by oxidizing the column and removing the oxide layer. A metal layer is deposited on the surface of the substrate, and the column and substrate are etched to form a pit. The backside of the substrate is etched to form an aperture surrounded by the metal layer. Alternatively, the metal layer is removed and a dopant layer is implanted into the substrate, followed by the etching of the backside, leaving an aperture surrounded by the dopant layer. In a second alternative, the oxidized column is broken from the substrate, and the backside is etched, leaving an aperture surrounded by an oxide layer. These processes can be used to fabricate apertures of very small and reproducible dimensions for such instruments as near field scanning optical microscopes and scanning ion conductance microscopes.

Abstract: The invention provides novel polypeptides which are associated with the transcription complex NF-AT, polynucleotides encoding such polypeptides, antibodies which are reactive with such polypeptides, polynucleotide hybridization probes and PCR amplification probes for detecting polynucleotides which encode such polypeptides, transgenes which encode such polypeptides, homologous targeting constructs that encode such polypeptides and/or homologously integrate in or near endogenous genes encoding such polypeptides, nonhuman transgenic animals which comprise functionally disrupted endogenous genes that normally encode such polypeptides, and transgenic nonhuman animals which comprise transgenes encoding such polypeptides.

Abstract: Chemical and electrical poling is described, as well as an improved optical converter having a solid state body which employs the same.

Abstract: We have developed a general procedure for the regulated (inducible) dimerization or oligomerization of intracellular proteins and disclose methods and materials for using that procedure to regulatably initiate cell-specific apoptosis (programmed cell death) in genetically engineered cells.

Abstract: Methods, apparatus and computer program products for selfcalibrating two-dimensional metrology stages include using a rigid artifact plate having an N.times.N array of marks thereon to map each of a two-dimensional array of stage positions (u,v) to a corresponding position in a Cartesian coordinate grid (x,y) to determine the distortion functions G.sub.x (x,y) and G.sub.y (x,y). This mapping function is performed by a series of operations which preferably use an orthogonal Fourier series to decouple determination of a pivoting point and a rotation angle from determination of the distortion functions. These operations include, among other things, determining complete and incomplete non-four-fold rotationally symmetric distortion between the two-dimensional array of stage positions (u,v) and the Cartesian coordinate grid (x,y). Operations are then performed to decouple the determination of the pivoting point and the rotation angle from the determination of the distortion functions G.sub.x (x,y) and G.sub.

Abstract: A trellis shaper for multi-channel modulation is provided as a means for obtaining significant shaping gain in applications requiring high-performance transceivers. The trellis shaper works across the subchannels in the multi-channel system and accommodates both the variable amounts of power and the different constellation sizes associated with the various tones. This invention offers significant advantage over the more straightforward approach of shaping each subchannel independently in terms of a reduction in delay, a reduction in memory requirements, and a reduction in complexity.

Abstract: This invention relates to an improvement in promoting the rate of association for high specificity binding pairs used in a variety of industrial, research and medical applications. These pairs include enzyme/substrate, complementary polynucleotide and antibody/antigen combinations. In one specific embodiment, this invention relates to the acceleration of nucleic acid hybridization by heterogeneous nuclear ribonucleoproteins ?hnRNPs!. In another specific embodiment, this invention relates to the acceleration of nucleic acid hybridization by a cationic detergent.

Abstract: A cantilever for a scanning probe microscope (SPM) includes a piezoelectric element in a thicker, less flexible section near the fixed base of the cantilever and a piezoresistor in a thinner, more flexible section near the free end of the cantilever. When the SPM operates in the constant force mode, the piezoelectric element is used to control the tip-sample separation. Since the resonant frequency of the piezoelectric element is substantially higher than that of conventional piezoelectric tube scanners, much higher scan rates can be achieved. When the SPM operates in the dynamic or intermittent contact mode, a superimposed AD-DC signal is applied to the piezoelectric element, and the latter is used to vibrate the cantilever as well as to control the tip-sample spacing. In another embodiment the cantilever is supported on a knife edge and vibrates at a third or higher order resonant frequency.

Abstract: A method is described for increasing the temporal resolution of MR fluoroscopy procedures. A central portion of the image requiring a higher temporal resolution is updated more frequently using less-than-complete newly acquired NMR data. A running average of the signals produced by peripheral structures is used to form the periphery of the image and to remove artifact-producing data from the less-than-complete NMR data.

Abstract: An electron source includes a negative electron affinity photocathode on a light-transmissive substrate and a light beam generator for directing a light beam through the substrate at the photocathode for exciting electrons into the conduction band. The photocathode has at least one active area for emission of electrons with dimensions of less than about two micrometers. The electron source further includes electron optics for forming the electrons into an electron beam and a vacuum enclosure for maintaining the photocathode at high vacuum. In one embodiment, the active emission area of the photocathode is defined by the light beam that is incident on the photocathode. In another embodiment, the active emission area of the photocathode is predefined by surface modification of the photocathode. The source provides very high brightness from an ultra-small active emission area of the photocathode.

Abstract: A lithography system includes a plurality of cantilevers, preferably formed in a silicon wafer. Each cantilever includes a tip located near the free end of the cantilever and an electrical conduction path which extends along the length of the cantilever to the tip. A switch is included in the conduction path to control the voltage at the tip of the cantilever.The array of such cantilevers is positioned adjacent a wafer which is to be patterned, in the manner of an atomic force microscope operating in either the contact or noncontact mode. The cantilever array is scanned over the wafer, preferably in a raster pattern, and the individual switches are operated so as to control an electric current or electric field at the tip of each cantilever. The electric current or field is used to write a pattern on a layer of resist coating the wafer or on the surface of the wafer itself.

Abstract: Novel methods and microorganisms are provided, where novel genetic mammalian cell invasive capability is imparted to a microorganism by the introduction of an exogenous ail or hil gene. The resulting organisms are then capable of binding to mammalian cells and are transferred to the cytoplasm. Other novel genetic capabilities may be imparted to the unicellular microorganism, which may serve as a vaccine for one or more pathogens or may introduce genetic capabilities or foreign molecules into a mammalian host cell. The sequences may be used for an in vitro screen for pathogenicity. Mutant microorganisms having an attenuated invasive phenotype are also disclosed wherein one or more invasive genes have been modified.

Abstract: A device for detecting the presence of particles and irregularities on the surface of a semiconductor wafer or other substrate includes a plurality of cantilevers formed on a semiconductor substrate and a means of detecting the deflection of each of the cantilevers. The cantilevers may, for example, be formed in rows and separated by selected distances. The entire substrate is then scanned over the surface to be examined, in a raster pattern, for example, and the deflection of the individual cantilevers is monitored.