Abstract: The present disclosure relates to the reversal of T cell exhaustion using aplysiatoxin analogs or PKC theta agonist compounds for anti-cancer immunotherapy. The treatment with aplysiatoxin analogs or PKC theta agonist compounds improve the anti-tumour activity of a T cell, inducing a NFAT-dependent T cell activation, increasing the pool of immune-checkpoint inhibitor responsive T cells, increasing lymphocyte infiltration and increasing the population of activated CD4+ and/or CD8+ cells. The methods of the present disclosure provide treatment of tumors and infections.

Abstract: A valve assembly for high pressure applications includes a pre-charge chamber, at least one inlet for pressurized gas to enter the assembly, a system poppet and an outlet for releasing pressurized gas into a desired environment. Pressurized gas can flow through access channels into a single bellows, which expands to move a shaft connected to the system poppet to open the poppet. In another embodiment, the pre-charge chamber compresses a first bellows to expand a second bellows, and vice versa upon reciprocation. The two bellows are hydraulically connected and filled with incompressible fluid. Each bellows has an internal limiting valve to retain incompressible fluid therewithin, and to preclude the complete nesting of either of the bellows. The retained fluid within the bellows maintains an internal pressure to minimize differential pressure, thereby minimizing the risk of bellows failure.

Abstract: A valve assembly for high pressure applications includes a pre-charge chamber in fluid communication with a first bellows, at least one inlet for pressurized gas to enter the assembly, a system poppet and an outlet for releasing pressurized gas into a desired environment. The pre-charge chamber and first bellows are filled with pre-charge gas to a threshold pressure. Pressurized gas can flow through access channels into a second bellows, which expands to move a valve shaft connected to the poppet assembly to open the poppet and allow the release of gas. The expansion of the second bellows pushes incompressible fluid disposed between the two bellows against the first bellows, thus contracting the first bellows. The gas within each bellows maintains an internal pressure equal to the pressure exerted upon each bellows by the incompressible fluid, so as to minimize differential pressure across the bellows in the extended position.

Abstract: A valve assembly for high pressure applications includes a pre-charge chamber, at least one inlet for pressurized gas to enter the assembly, a system poppet and an outlet for releasing pressurized gas into a desired environment. Pressurized gas can flow through access channels into a single bellows, which expands to move a shaft connected to the system poppet to open the poppet. In another embodiment, the pre-charge chamber compresses a first bellows to expand a second bellows, and vice versa upon reciprocation. The two bellows are hydraulically connected and filled with incompressible fluid. Each bellows has an internal limiting valve to retain incompressible fluid therewithin, and to preclude the complete nesting of either of the bellows. The retained fluid within the bellows maintains an internal pressure to minimize differential pressure, thereby minimizing the risk of bellows failure.

Abstract: A valve assembly for high pressure applications includes a pre-charge chamber in fluid communication with a first bellows, at least one inlet for pressurized gas to enter the assembly, a system poppet and an outlet for releasing pressurized gas into a desired environment. The pre-charge chamber and first bellows are filled with pre-charge gas to a threshold pressure. Pressurized gas can flow through access channels into a second bellows, which expands to move a valve shaft connected to the poppet assembly to open the poppet and allow the release of gas. The expansion of the second bellows pushes incompressible fluid disposed between the two bellows against the first bellows, thus contracting the first bellows. The gas within each bellows maintains an internal pressure equal to the pressure exerted upon each bellows by the incompressible fluid, so as to minimize differential pressure across the bellows in the extended position.

Abstract: Apparatus for laying and/or retrieving elongate flexible elements, such as pipes and cables having accessories at spaced intervals, is mounted on a floating vessel such as a barge an comprises two self powered conveyors pivotally connected together through a hinge but which may be locked relative to one another for use. A trolley runs on wheels or rails on either side of the conveyor system and has an upper surface consisting of a further powered conveyor. The sides of the conveyor extend to form a chute at the outboard end. In normal operation the trolley is stored and the pipe or cable is carried by the conveyors to the chute which guides it into the water. The shape of the chute permits the pipe/cable to leave the barge at up to 45 degrees either side of the fore and aft axis of the conveyor.

Abstract: A system for offshore operations include a column 1 extending above sea level from the seabed, which is connected by a bridge 2 to a semisubmersible offshore oil production platform 3. The connection of the bridge 2 to the platform 3 is achieved by an improved joint arrangement which permits relative rotation about both substantially vertical and horizontal axes to reduce loads transmitted to the column. The column 1 is connected by a universal joint arrangement 4 to a base on the seabed. The joint 4 has radially outwardly distributed joint surfaces which provides an axial passageway through the joint for risers. The joint arrangement includes a first main joint and a second normally unloaded ball joint which takes up the column load in the event of failure of the first joint.

Abstract: A frequency modulator circuit arrangement, comprising a phase modulator (1) having a carrier signal input (2) which is fed from a carrier signal generator (18) and a modulation signal input (3) which is fed from a modulation signal input terminal (6) via an integrated circuit (7), includes a controllable frequency divider (16) in the carrier signal path through the phase modulator enabling the arrangement to operate with input modulation signals containing d.c. components without the integrator circuit output signal reaching impossibly high values. If the integrator output signal exceeds a first threshold (at terminal 26), a D-type flip-flop (27) is tripped causing a switch 28 to close, reducing the charge in the integrator capacitor (10) via a resistor (22) and hence changing the phase shift produced by the phase modulator. The division factor of the divider is simultaneously changed for one or more divisions cycles to introduce a compensating steady phase shift.