Abstract: A conditionally replicating adenovirus were generated that can specifically replicate and express therapeutic genes in neuroendocrine tumors. The promoter-specific expression of the adenoviruses is regulated upstream by an INSM1 (insulinoma-associated-1) promoter that is silent in normal adult tissues but active in developing neuroendocrine cells and neuroendocrine tumors. By placing the I NSM 1-promoter with an insulator and two copies of neuronal restrictive silencer elements in an adenoviral vector, the construct can retain tumor specificity and drive expression of a mutated adenovirus E1A gene (?24E1A) and the herpes simplex virus thymidine kinase gene. The I NSM1-promoter-driven viruses could replicate specifically in the I NSM1-positive cells and I NSM1-specific HSV-tk expression in combination with ganciclovir treatment displayed dose-dependent tumor cell-specific killing in insulinomas.

Abstract: A conditionally replicating adenovirus were generated that can specifically replicate and express therapeutic genes in neuroendocrine tumors. The promoter-specific expression of the adenoviruses is regulated upstream by an INSM1 (insulinoma-associated-1) promoter that is silent in normal adult tissues but active in developing neuroendocrine cells and neuroendocrine tumors. By placing the INSM1-promoter with an insulator and two copies of neuronal restrictive silencer elements in an adenoviral vector, the construct can retain tumor specificity and drive expression of a mutated adenovirus E1A gene (424E1A) and the herpes simplex virus thymidine kinase gene. The INSM1-promoter-driven viruses could replicate specifically in the INSM1-positive cells and I NSM1-specific HSV-tk expression in combination with ganciclovir treatment displayed dose-dependent tumor cell-specific killing in insulinomas.

Abstract: A self-locking bolt assembly (1) includes a split bolt (2) and a screw set pin (3). The bolt includes a threaded shank (4), an axial bore (6) extending through the shank, the bore (6) including a threaded bore section (6A), a tapered end section (6C), and a bore midsection (6B) between the threaded bore section and the tapered end section. The screw set pin (3) includes a screw section (10B) having threads for engaging the threaded bore section (6A) and a pin shaft (10) having a tapered end section (10A) for engaging the tapered end section (6C) of the bore (6), the pin shaft (10) having a proximal end attached to the screw section (10B). The pin shaft (10) is sufficiently long to ensure that the screw set pin (3) further into the bore (6) without galling threads of the screw section (10B).

Abstract: A self-locking bolt assembly (1) includes a split bolt (2) and a screw set pin (3). The bolt includes a threaded shank (4), an axial bore (6) extending through the shank, the bore (6) including a threaded bore section (6A), a tapered end section (6C), and a bore midsection (6B) between the threaded bore section and the tapered end section. The screw set pin(3) includes a screw section (10B) having threads for engaging the threaded bore section (6A) and a pin shaft (10) having a tapered end section (10A) for engaging the tapered end section (6C) of the bore (6), the pin shaft (10) having a proximal end attached to the screw section (10B). The pin shaft (10) is sufficiently long to ensure that the screw set pin (3) further into the bore (6) without galling threads of the screw section (10B).

Abstract: A self-locking bolt assembly (1) includes a split bolt (2) and a screw set pin (3). The bolt includes a threaded shank (4), an axial bore (6) extending through the shank, the bore (6) including a threaded bore section (6A), a tapered end section (6C), and a bore midsection (6B) between the threaded bore section and the tapered end section. The screw set pin(3) includes a screw section (10B) having threads for engaging the threaded bore section (6A) and a pin shaft (10) having a tapered end section (10A) for engaging the tapered end section (6C) of the bore (6), the pin shaft (10) having a proximal end attached to the screw section (10B). The pin shaft (10) is sufficiently long to ensure that the screw set pin (3) further into the bore (6) without galling threads of the screw section (10B).