Abstract: Tissue plasminogen activator (t-PA) derivatives are produced in useful quantities using recombinant DNA techniques. Specific derivatives include amino acid deletion derivatives and amino acid substitution derivatives. A deletion derivative lacking the N-terminal first 68 amino acids is specifically exemplified having requisite t-PA characteristics. The invention disclosed thus enables the production of t-PA derivatives via recombinant means. Methods, expression vehicles and various host cells useful in the production of said t-PA derivatives are also disclosed.

Abstract: Biologically active variant tissue plasminogen activators are disclosed. The disclosure focuses on position 276 variants that exhibit enhanced fibrin specificity.

Abstract: A human tissue plasminogen activator (t-PA) is produced in useful quantities using recombinant DNA techniques. The invention disclosed thus enables the production of t-PA free of contaminants with which it is ordinarily associated in its native cellular environment. Methods, expression vehicles and various host cells useful in its production are also disclosed.

Abstract: A system for safely removing even a hazardous contaminant from a substrate surface includes a light energy source whose output is controlled to selectively provide components primarily in the visible and infrared spectrum, and a power unit for energizing the light energy source at a desired energy level, pulse width and pulse repetition rate. Proper selection of these parameters permits the energy source to heat the contaminant sufficiently to cause direct carbonization without entering a melt phase, without the need for any precoat medium. Because the resultant molecular decomposition of the contaminant occurs relatively faster than heat transfer to the underlying substrate, substantially no substrate heating results. The light source energy transforms the contaminant to an ash that is removed from the substrate by a vacuum system preferably surrounding the light source. The light source is preferably a xenon flash lamp operated with a pulse repetition rate of between about 0.

Abstract: A method for selecting novel proteins such as growth hormone and antibody fragment variants having altered binding properties for their respective receptor molecules is provided. The method comprises fusing a gene encoding a protein of interest to the carboxy terminal domain of the gene III coat protein of the filamentous phage M13. The gene fusion is mutated to form a library of structurally related fusion proteins that are expressed in low quantity on the surface of a phagemid particle. Biological selection and screening are employed to identify novel ligands useful as drug candidates. Disclosed are preferred phagemid expression vectors and selected human growth hormone variants.

Abstract: Polypeptides that are cleared from the kidney and do not contain in their original form a Fc region of an IgG are altered so as to comprise a salvage receptor binding epitope of an Fc region of an IgG and thereby have increased circulatory half-life. Methods are described herein which utilize these polypeptides in treating disorders involving the LFA-1 receptor. In one of the described methods of treatment, the polypeptide includes the amino acid sequence PKNSSMISNTP (SEQ ID NO:3) and may also include the sequence selected from the group consisting of HQNLSDGK (SEQ ID NO: 1), HQNISDGK (SEQ ID NO:2), HQSLGTQ (SEQ ID NO:11) and VISSHLGQ (SEQ ID NO:31).

Abstract: The instant invention discloses the unexpected result that mutant signal sequences with reduced translational strength provided essentially complete processing and high levels of expression of a polypeptide of interest as compared to wild type signal sequences, and that many mammalian polypeptides require a narrow range of translation levels to achieve maximum secretion. A set of signal sequence vectors provides a range of translational strengths for optimizing expression of a polypeptide of interest.

Abstract: Biologically active variant tissue plasminogen activators are disclosed. The disclosure focuses on position 276 variants that exhibit enhanced fibrin specificity.

Abstract: Step conveyor comprising a primary stationary beam (1) and as secondary beam (2) being movable upwards and downwards as well as to and fro relative thereto. The secondary beam (2) is supported by restrictedly pivotable bow-shaped eccentrically journalled segments (3) resting on a stationary guideway (5). In each position the secondary beam (2) is positioned below the level of the primary beam (1). At its top the secondary beam (2) carries dogs (6) which in a nonoperative rest position are positioned below the level of the primary beam (1) and which in an operational position extend beyond the level of the primary beam (1) and can engage the objects (7) to be transported.

Abstract: Tissue plasminogen activator (t-PA) derivatives are produced in useful quantities using recombinant DNA techniques. Specific derivatives include amino acid deletion derivatives and amino acid substitution derivatives. A deletion derivative lacking the N-terminal first 68 amino acids is specifically exemplified having requisite t-PA characteristics. The invention disclosed thus enables the production of t-PA derivatives via recombinant means. Methods, expression vehicles and various host cells useful in the production of said t-PA derivatives are also disclosed.

Abstract: Tissue plasminogen activator (t-PA) derivatives are produced in useful quantifies using recombinant DNA techniques. Specific derivatives include amino acid deletion derivatives and amino acid substitution derivatives. A deletion derivative lacking the N-terminal first 68 amino acids is specifically exemplified having requisite t-PA characteristics. The invention disclosed thus enables the production of t-PA derivatives via recombinant means. Methods, expression vehicles and various host cells useful in the production of said t-PA derivatives are also disclosed.

Abstract: The invention provides a recombinant virus vector for use as an immunotherapeutic or vaccine. The recombinant virus vector comprises at least one pair of nucleotide sequences heterologous to the virus and which have sufficient sequence homology that recombination between them might be expected. The pair of nucleotide sequences are arranged in the virus vector such that they are inverted with respect to each other. The virus vector is able to infect a mammalian host cell and express as polypeptide the heterologous nucleotide sequences in the host cell. For infection thought to be caused by HPV infection, the pair of nucleotide sequences encode part or all of human papillomavirus (HPV) wild-type proteins or mutant proteins immunologically cross-reactive therewith. For an immunotherapeutic or vaccine against cervical cancer, the recombinant virus vector encodes part or all of the HPV wild-type proteins HPV16E7 and HPV18E7 or mutant proteins immunologically cross-reactive therewith.

Abstract: A method for determining whether an electrochemical cell is substantially fully charged. The determination is made by ascertaining the rate of change of the impedance of the cell with changing frequency, at low frequency. A method for determining the state of charge of an electrochemical cell by comparing the impedance of the cell at two or more frequencies or by comparing the impedance of the cell, at a medium frequency, with the impedance at high frequency. Apparatus for generating output signals representative of the magnitude of resistive and reactive components of an impedance (30). The apparatus has a signal generator (70) for passing AC current through the impedance, and a synchronous demodulator circuit (88) for demodulating AC signal appearing across the impedance pursuant to passing the current through it. A phase shift circuit (130, 132, 136, 138, 140) selectively generates control signals in phase or 90.degree.

Abstract: Novel human tissue-type plasminogen activator variant that a) retains substantially full biological activity b) has a modified carbohydrate structure and c) has an altered in vivo half-life. Means for preparation of the variants and results of assays measuring function of the activators are also disclosed.

Abstract: A method of treating injuries to or diseases of the central nervous system that predominantly effects glia and/or non-cholinergic neuronal cells characterized in that it comprises the step of increasing the active concentration(s) of insulin-like growth factor 1 and/or analogues thereof in the central nervous system of the patient. The present invention also provides therapeutic compositions comprising insulin-like growth factor 1 and/or analogues thereof for administration to a patient at or following a neural insult, which compositions are useful in minimizing damage to the central nervous system that would otherwise occur following the insult.

Abstract: Biologically active mutant tissue plasminogen activators are disclosed wherein site directed mutagenesis, for example, of a two-chain activation site renders said mutants resistant to conversion to the two-chain form. In addition, mutant tissue plasminogen activators are disclosed which have amino acid substitutions or deletions in the region of positions 274-277, which may or may not be resistant to conversion to the two-chain form, but show enhanced fibrin specificity relative to wild-type tissue plasminogen activator.

Abstract: A method of identifying a compound which interferes with the binding of MDM2 to human p53 has been determined. This method comprises forming a mixture between MDM2 and a fragment of human p53 consisting of 6 to 28 amino acids comprising TFSDLW (SEQ ID NO:2), adding a test compound to the mixture and determining the quantity of protein bound to the other before and after adding the compound. A compound which decreases the amount of binding of the two proteins to each other is a compound which interferes with the binding of MDM2 to human p53.

Abstract: Human tissue plasminogen activator (t-PA) is produced in useful quantities using recombinant DNA techniques. The invention disclosed thus enables the production of t-PA free of contaminants with which it is ordinarily associated in its native cellular environment. Methods, expression vehicles and various host cells useful in its production are also disclosed.

Abstract: A silo-like container includes an apparatus for discharging material within the container. The container interior bottom member leaves an annular opening with respect to the container walls, through which opening material may fall to be collected. A preferably toothed discharge ring is disposed above the interior bottom member and is rotated by a drive wheel. A retaining element preferably having teeth-like members is mounted adjacent the interior wall of the silo. As the discharge ring is rotated, planetary motion preferably about a silo axis occurs. The retaining element teeth-like members cooperate with the toothed portion of the discharge ring to urge rotational movement of the discharge ring about its own virtual axis. Discharge ring motion urges material within the silo radially outward toward the annular opening. The retaining element is mounted above the discharge ring such that the discharge ring is prevented from rising upward.

Abstract: Polypeptides comprising an N-terminal amino acid sequence corresponding to amino acids 107-111 of parathyroid hormone related protein (PTHrP) having bone resorption inhibitory activity are provided. The polypeptides are provided in pharmaceutical compositions for the treatment of diseases and disorders where inhibition of bone resorption is indicated.