ON UKRAINIAN LABOR MARKET NEEDS IN MARKETERS

Asymmetric Incremental Sheet Forming (AISF) has been developed as a flexible process for low-volume production of sheet metal parts. In AISF, a part is obtained as the sum of localized plastic deformations produced by a simple forming tool that moves under CNC control. In spite of about 20 years of research and development, AISF has not had much industrial take-up yet. The main reason for this is that attempts to improve, among other limitations, the accuracy, speed and range of feasible geometries of the process by adapted process strategies has not brought about general solutions. This paper presents an overview of the current state of development of hybrid asymmetric incremental sheet forming processes at RWTH Aachen University. The goal of the development of hybrid ISF processes is to allow for a quantum leap of the capabilities of AISF in order to enable a broader industrial use of AISF. Two hybrid process variations of AISF are presented: stretch forming combined with ISF and laser-assisted AISF. It is shown that the combination of stretch forming and AISF can improve the time per part, sheet thickness distribution and accuracy of the final part. Laser-assisted AISF is shown to enable the flexible forming of non cold-workable materials such as magnesium and titanium alloys when the forming conditions are adapted to the temperature and strain rate dependent formability of the sheet metal. In addition, first results of the forming of hybrid aluminum-steel sheet metal are shown

A phase I study of OncoVEX(GM-CSF), a second-generation oncolytic herpes simplex virus expressing granulocyte macrophage colony-stimulating factor

PURPOSE: To conduct a phase I clinical trial with a second-generation oncolytic herpes simplex virus (HSV) expressing granulocyte macrophage colony-stimulating factor (Onco VEXGM-CSF) to determine the safety profile of the virus, look for evidence of biological activity, and identify a dosing schedule for later studies. EXPERIMENTAL DESIGN: The virus was administered by intratumoral injection in patients with cutaneous or s.c. deposits of breast, head and neck and gastrointestinal cancers, and malignant melanoma who had failed prior therapy. Thirteen patients were in a single-dose group, where doses of 10(6), 10(7), and 10(8) plaque-forming units (pfu)/mL were tested, and 17 patients were in a multidose group testing a number of dose regimens. RESULTS: The virus was generally well tolerated with local inflammation, erythema, and febrile responses being the main side effects. The local reaction to injection was dose limiting in HSV-seronegative patients at 10(7) pfu/mL. The multidosing phase thus tested seroconverting HSV-seronegative patients with 10(6) pfu/mL followed by multiple higher doses (up to 10(8) pfu/mL), which was well tolerated by all patients. Biological activity (virus replication, local reactions, granulocyte macrophage colony-stimulating factor expression, and HSV antigen-associated tumor necrosis), was observed. The duration of local reactions and virus replication suggested that dosing every 2 to 3 weeks was appropriate. Nineteen of 26 patient posttreatment biopsies contained residual tumor of which 14 showed tumor necrosis, which in some cases was extensive, or apoptosis. In all cases, areas of necrosis also strongly stained for HSV. The overall responses to treatment were that three patients had stable disease, six patients had tumors flattened (injected and/or uninjected lesions), and four patients showed inflammation of uninjected as well as the injected tumor, which, in nearly all cases, became inflamed. CONCLUSIONS: Onco VEXGM-CSF is well tolerated and can be safely administered using the multidosing protocol described. Evidence of an antitumor effect was seen