Abstract: Hydrophobically-modified proteins and methods of making them are described. A hydrophobic moiety is attached to a surface amino acid residue of the protein. The hydrophobic moiety can be a lipid or a peptide. Alternatively, the protein can be derivatized by a wide variety of chemical reactions that append a hydrophobic structure to the protein. The preferred protein is of mammalian origin and is selected from the group consisting of Sonic, Indian, and Desert hedgehog. The hydrophobic moiety is used as a convenient tether to which may be attached a vesicle such as a cell membrane, liposome, or micelle.

Abstract: The present invention makes availables assays and reagents inhibiting paracrine and/or autocrine signals produced by a hedgehog protein comprising contacting a cell sensitive to the hedgehog protein with a steroidal alkaloid, or other small molecule, in a sufficient amount to reduce the sensitivity of the cell to the hedgehog protein.

Abstract: The present invention sterol-modified hedgehog polypeptides and functional fragments thereof. Methods of identifying compositions which affect hedgehog activity based on inhibition of cholesterol modification of hedgehog protein are described. In one aspect of the invention, the method provides a means for affecting cholesterol biosynthesis or transport in a cell comprising contacting a cell with an effective amount of a compound that affects hedgehog, thereby affecting cholesterol biosynthesis or transport. The effect may be inhibition or stimulation of cholesterol biosynthesis or transport.

Abstract: The present invention makes availables assays and reagents inhibiting paracrine and/or autocrine signals produced by a hedgehog protein comprising contacting a cell sensitive to the hedgehog protein with a steroidal alkaloid, or other small molecule, in a sufficient amount to reduce the sensitivity of the cell to the hedgehog protein.

Abstract: The present invention sterol-modified hedgehog polypeptides and functional fragments thereof. Methods of identifying compositions which affect hedgehog activity based on inhibition of cholesterol modification of hedgehog protein are described. In one aspect of the invention, the method provides a means for affecting cholesterol biosynthesis or transport in a cell comprising contacting a cell with an effective amount of a compound that affects hedgehog, thereby affecting cholesterol biosynthesis or transport. The effect may be inhibition or stimulation of cholesterol biosynthesis or transport.

Abstract: The present invention provides two novel polypeptides, referred to as the “N” and “C” fragments of hedgehog, or N-terminal and C-terminal fragments, respectively, which are derived after specific cleavage at a Gly↓Cys Phe site recognized by the autoproteolytic domain in the native protein. Methods of identifying compositions which affect hedgehog activity based on inhibition of cholesterol modification of hedgehog protein are described. Also provided are methods of use of the N and C fragments.

Abstract: The present invention provides two novel polypeptides, referred to as the "N" and "C" fragments of hedgehog, or N-terminal and C-terminal fragments, respectively, which are derived after specific cleavage at a G.sup..dwnarw. CF site recognized by the autoproteolytic domain in the native protein. Also provided are methods of use of the N and C fragments.

Abstract: The present invention provides two novel polypeptides, referred to as the "N" and "C" fragments of hedgehog, or N-terminal and C-terminal fragments, respectively, which are derived after specific cleavage at a G.sup..dwnarw. CF site recognized by the autoproteolytic domain in the native protein. Also included are sterol-modified hedgehog polypeptides and functional fragments thereof. Methods of identifying compositions which affect hedgehog activity based on inhibition of cholesterol modification of hedgehog protein are described.

Abstract: Automatic dynamic phase alignment of digital data, skewed with respect to a local clock, is obtained over a wide range of skew and skew frequencies. The system includes (i) an edge detector (52) containing predetermined delays (e.g., D1, D2, D3), (ii) delay registers (e.g., 72, 76, 84, 86), and (iii) a controller (54) for deciding when un-delayed and delayed data D0, D1, D2, D3 have transitions (102-138) which bracket corresponding clock transitions (100, 110, 120, 130) and regulating a subsequent two-stream parallel (e.g., bi-phase) register-multiplexer (56). The controller selects from the register-multiplexer (56), whichever of in-phase data D or delayed data DD has its transition spaced away from the clock transition by at least one delay D1, D2, or D3.

Abstract: A variable clock delay circuit provides a clock output signal (CLKOUT) whose phase can be varied with respect to an incoming reference signal (REFIN). A voltage controlled ring oscillator (24) having a plurality of delay stages (26-33) locks to a predetermined factor of the frequency of the incoming reference signal. A multiplexer circuit (14) selectively provides a signal (or its inversion thereof) appearing at a selected input of any one of the plurality of delay stages to its output. A divider circuit (16) divides the signal appearing at the output of the multiplexer circuit by the predetermined factor to obtain the clock output signal whose frequency is substantially equal to the frequency of the incoming reference signal and whose phase can be adjusted with respect to the incoming reference signal.

Abstract: An improved memory utilization arrangement for a VITERBI decoder which allows the amount of memory required for storing state metrics to be minimized. Both old and new state metrics are required to be stored. This scheme utilizes memory locations for which old metrics have been previously read for storing the newly calculated metrics. In one implementation of this invention, a barrel shifter is used to calculate the address at which to store and retrieve the appropriate metrics. Another implementation employs a shift register with a shifting and inserting operation to align the metrics in the proper order and at the same time store the new metrics for subsequent calculations. As a result of the saving of memory, the amount of memory and power consumption are reduced substantially.

Abstract: A method for preparing an alcohol insoluble polymide membrane. An appropriate membrane-forming casting liquid containing the required polyamide is evaporated under conditions of high total humidity and an air flow of less than 305 m/min. (1000 ft/min) in order to form the membrane. Membranes of a single polyamide, e.g. Nylon 6,6 can be formed by the method.