Abstract: Disclosed herein are methods of chemical conjugation comprising contacting a lysosomal enzyme with a first crosslinking agent to introduce aldehyde groups; contacting a lysosomal targeting peptide with a second crosslinking agent to introduce a hydrazide group at the N-terminal residue; contacting the lysosomal enzyme with aldehyde groups of step a. with the lysosomal targeting peptide with a hydrazide group at the N-terminal residue of step b; and forming a lysosomal enzyme-lysosomal targeting peptide conjugate.

Abstract: Described herein are methods of making targeting peptides conjugated to a recombinant lysosomal enzyme by modifying the amino (N)-terminus and one or more lysine residues on a recombinant human lysosomal enzyme using a first crosslinking agent to give rise to a first crosslinking agent modified recombinant human lysosomal enzyme, modifying a lysine or cysteine within a short extension linker at the carboxyl (C)-terminus on a variant IGF-2 peptide having a short extension linker using a second crosslinking agent to give rise to a second crosslinking agent modified variant IGF-2 peptide, and then conjugating the first crosslinking agent modified recombinant human lysosomal enzyme to the second crosslinking agent modified variant IGF-2 peptide containing a short extension linker. Also described herein are conjugates synthesized using the methods disclosed herein. Also described herein are treatment methods using the disclosed conjugates.

Abstract: Described herein are methods of making targeting peptides conjugated to recombinant lysosomal enzymes by modifying the amino (N)-terminus and one or more lysine residues on recombinant human lysosomal enzymes using a first crosslinking agent to give rise to first crosslinking agent modified recombinant human lysosomal enzymes, modifying the first amino acid within a short linker at the amino (N)-terminus on a variant IGF-2 peptide using a second crosslinking agent to give rise to a second crosslinking agent modified variant IGF-2 peptide, and then conjugating the first crosslinking agent modified recombinant human lysosomal enzyme to the second crosslinking agent modified variant IGF-2 peptide containing a short linker. Also described herein are conjugates synthesized characterized as having higher affinities for the IGF2/CI-MPR receptor and cellular uptake using the methods disclosed herein. Also described herein are treatment methods using the disclosed conjugates.

Abstract: A column readout amplifier and imaging array using the same method are disclosed. The column readout amplifier includes a signal amplifier having an amplifier signal output, a first filter capacitor, a buffer amplifier having a buffer amplifier input and a buffer amplifier output, and a switching network. The switching network connects the amplifier signal output to the buffer amplifier input and the buffer amplifier output to the first filter capacitor during a first time period, and connects the amplifier signal output directly to the first filter capacitor during a second time period. The time periods can be of fixed duration or determined by the difference in potential between the input and output of the buffer amplifier. The column readout amplifier can be used in an imaging array to readout columns of pixels.

Abstract: Disclosed herein are methods of chemical conjugation comprising contacting a lysosomal enzyme with a first crosslinking agent to introduce aldehyde groups; contacting a lysosomal targeting peptide with a second crosslinking agent to introduce a hydrazide group at the N-terminal residue; contacting the lysosomal enzyme with aldehyde groups of step a. with the lysosomal targeting peptide with a hydrazide group at the N-terminal residue of step b; and forming a lysosomal enzyme-lysosomal targeting peptide conjugate.

Abstract: Polypeptide signal sequences of modified fragments of human immunoglobulin heavy chain binding protein (Bip) are disclosed. Also disclosed are fusion proteins comprising a modified fragment of human immunoglobulin heavy chain binding protein (Bip) operably linked to a heterologous polypeptide. Also disclosed are protein expression vectors comprising a promoter operably linked to a first DNA sequence encoding a signal sequence comprising a modified fragment of human immunoglobulin heavy chain binding protein (Bip) and a second DNA sequence encoding a heterologous polypeptide fused in frame to the first DNA sequence. Further disclosed are methods of producing a polypeptide comprising expressing a fusion protein comprising a polypeptide signal sequences of modified fragments of human immunoglobulin heavy chain binding protein (Bip) operably linked to a heterologous polypeptide and recovering the heterologous polypeptide.

Abstract: A self-charging electric bicycle that includes a solar panel disposed upon a back plate above the rear wheel, a first dynamo operationally engaged by the rotational force of the front wheel, a second dynamo operationally engaged by the rotational force of the rear wheel, and a third dynamo operationally engaged at a high gear ratio by a second chain in operational communication with the bicycle pedal crank, wherein an electric battery disposed within a housing upon the bicycle frame is charged and recharged when the bicycle is moved and pedaled and when sunlight is incident the solar panel, whereby an electric motor is activatable to drive the bicycle, as desired.

Abstract: A column readout amplifier and imaging an-ay using the same method are disclosed. The column readout amplifier includes a signal amplifier having an amplifier signal output, a first filter capacitor, a buffer amplifier having a buffer amplifier input and a buffer amplifier output, and a switching network. The switching network connects the amplifier signal output to the buffer amplifier input and the buffer amplifier output to the first filter capacitor during a first time period, and connects the amplifier signal output directly to the first filter capacitor during a second time period. The time periods can be of fixed duration or determined by the difference in potential between the input and output of the buffer amplifier. The column readout amplifier can be used in an imaging array to readout columns of pixels.

Abstract: Described herein are variant, recombinant ?-glucocerebrosidase proteins characterized as having increased stability relative to recombinant wild-type ?-glucocerebrosidase. Also provided herein are variant, recombinant ?-glucocerebrosidase proteins characterized as retaining more catalytic activity relative to recombinant wild-type ?-glucocerebrosidase. Further described herein are variant, recombinant ?-glucocerebrosidase proteins that can have amino acid variations at one or more of the following positions: 316, 317, 321 and 145. Methods of making the variant, recombinant ?-glucocerebrosidase proteins are also described as well as methods of treating patients having lysosomal storage diseases.

Abstract: Described herein are methods of making targeting peptides conjugated to recombinant lysosomal enzymes by modifying the amino (N)-terminus and one or more lysine residues on recombinant human lysosomal enzymes using a first crosslinking agent to give rise to first crosslinking agent modified recombinant human lysosomal enzymes, modifying the first amino acid within a short linker at the amino (N)-terminus on a variant IGF-2 peptide using a second crosslinking agent to give rise to a second crosslinking agent modified variant IGF-2 peptide, and then conjugating the first crosslinking agent modified recombinant human lysosomal enzyme to the second crosslinking agent modified variant IGF-2 peptide containing a short linker. Also described herein are conjugates synthesized characterized as having higher affinities for the IGF2/CI-MPR receptor and cellular uptake using the methods disclosed herein. Also described herein are treatment methods using the disclosed conjugates.

Abstract: Polypeptide signal sequences of modified fragments of human immunoglobulin heavy chain binding protein (Bip) are disclosed. Also disclosed are fusion proteins comprising a modified fragment of human immunoglobulin heavy chain binding protein (Bip) operably linked to a heterologous polypeptide. Also disclosed are protein expression vectors comprising a promoter operably linked to a first DNA sequence encoding a signal sequence comprising a modified fragment of human immunoglobulin heavy chain binding protein (Bip) and a second DNA sequence encoding a heterologous polypeptide fused in frame to the first DNA sequence. Further disclosed are methods of producing a polypeptide comprising expressing a fusion protein comprising a polypeptide signal sequences of modified fragments of human immunoglobulin heavy chain binding protein (Bip) operably linked to a heterologous polypeptide and recovering the heterologous polypeptide.

Abstract: Described herein are variant, recombinant ?-glucocerebrosidase proteins characterized as having increased stability relative to recombinant wild-type ?-glucocerebrosidase. Also provided herein are variant, recombinant ?-glucocerebrosidase proteins characterized as retaining more catalytic activity relative to recombinant wild-type ?-glucocerebrosidase. Further described herein are variant, recombinant ?-glucocerebrosidase proteins that can have amino acid variations at one or more of the following positions: 316, 317, 321 and 145. Methods of making the variant, recombinant ?-glucocerebrosidase proteins are also described as well as methods of treating patients having lysosomal storage diseases.

Abstract: An image sensor and method for using the image sensor to capture an image are disclosed. The image sensor includes an imaging array, a first block amplifier and a controller. A first plurality of pixels in the imaging array includes pixels having a photodiode connected to a first node by a gate transistor, a reset transistor connected between the first node and a reset node, a pixel amplifier having an input connected to the first node and an output, and an output gate for connecting the pixel amplifier output to an output bus. The sensor has a monitoring mode and an image capture mode. In the monitoring mode the reset node is connected to the first block amplifier whose output is monitored and used to trigger the image capture mode when the output exceeds a predetermined threshold.

Abstract: A camera has a continuous full-resolution burst mode wherein a sequence of full-resolution images is captured, is image processed by a pipeline of dedicated hardware image processing engines, is zoomed by a zoom engine, is compressed by a compression engine, and is stored into nonvolatile storage as a sequence of discrete files. The capturing of images and the storing of files continues at a rate of at least three frames per second until the user indicates burst mode operation is to stop or until nonvolatile storage becomes filled. Although the camera has a buffer memory into which raw sensor data is placed before image processing, the number of images that can be captured in a single burst is not limited by the size of the buffer memory. The cost of a consumer market camera having continuous burst mode capability is therefore reduced by reducing the required amount of buffer memory.

Abstract: An image sensor and method for using the image sensor to capture an image are disclosed. The image sensor includes an imaging array, a first block amplifier and a controller. A first plurality of pixels in the imaging array includes pixels having a photodiode connected to a first node by a gate transistor, a reset transistor connected between the first node and a reset node, a pixel amplifier having an input connected to the first node and an output, and an output gate for connecting the pixel amplifier output to an output bus. The sensor has a monitoring mode and an image capture mode. In the monitoring mode the reset node is connected to the first block amplifier whose output is monitored and used to trigger the image capture mode when the output exceeds a predetermined threshold.

Abstract: A CCD imaging array and a charge measurement amplifier for use in such imaging arrays is disclosed. The array includes a plurality of pixels that accumulate charge when exposed to light, a readout amplifier having input and output ports. The readout amplifier has a variable gain that is set by a gain control signal. The readout amplifier also includes a reset path between the input and output ports, the path having an impedance controlled by a reset signal. A controller generates the gain control signal and the reset signal during a charge measurement cycle. Initially the gain is set to a first value after generating the reset signal. The gain is changed to a second value during the charge measurement cycle if the output signal exceeds a first threshold value. The readout amplifier can be constructed from an operational amplifier having a capacitive feedback loop.

Abstract: A CCD imaging array and a charge measurement amplifier for use in such imaging arrays is disclosed. The array includes a plurality of pixels that accumulate charge when exposed to light, a readout amplifier having input and output ports. The readout amplifier has a variable gain that is set by a gain control signal. The readout amplifier also includes a reset path between the input and output ports, the path having an impedance controlled by a reset signal. A controller generates the gain control signal and the reset signal during a charge measurement cycle. Initially the gain is set to a first value after generating the reset signal. The gain is changed to a second value during the charge measurement cycle if the output signal exceeds a first threshold value. The readout amplifier can be constructed from an operational amplifier having a capacitive feedback loop.

Abstract: There is disclosed a runner for a Francis-type hydraulic turbine where each runner blade has a outlet edge comprising a deflected edge portion. The deflected edge portion is located adjacent to the junction or attachment point of the outlet edge to the band of the runner to define a stress reducing tip extension portion of the blade adjacent the band. This tip extension portion reduces stress concentration adjacent where the outlet edge joins the runner band.

Abstract: A propeller type runner is described in which the leading edge of each blade "leans" forward from the root in the direction of rotation to reduce cavitation and increase efficiency. The "lean" provided to each blade of a five blade design is such that the leading edge of each blade obscures a large portion of the trailing edge of the preceding blade.