Abstract: The invention provides method of depleting endogenous T-cells or NK-cells to facilitate propagation or survival of engineered T-cells introduced into a subject for a therapeutic purpose. The depletion regime involves a co-administration of an immunotherapeutic agent against T-cells and an immunotherapeutic agent that inhibits CD47 interaction with NK-cells. The immunotherapeutic agent against T-cells or NK-cells binds to an antigen on T-cells or NK-cells effecting depletion of the T-cells or NK-cells, which depletion is promoted by the immunotherapeutic agent inhibiting CD47-SIRP? interaction. The genetically engineered T-cells or NK-cells can have a variety of genetic modifications such as a chimeric antigen receptor that targets the T-cells to a target cell.

Abstract: The invention provides genetically modified hematopoietic stem or progenitor cells (HSPCs) and methods of using the HSPCs in stem cell replacement therapy. The HSPCs are genetically modified to express a receptor conferring a selective advantage on the introduced cells relative to endogenous HSPCs or a control HSPCs without the modification. The presence of such a receptor provides resistance to an immunotherapy regime used for eliminating endogenous HSPCs.

Abstract: The invention provides co-administration regimes of immunotherapeutic agents specifically binding to c-kit or inhibiting CD47-SIRP? for ablation of endogenous HSPCs. Relatively low levels of anti-c-kit result in saturation of binding to c-kit on HSPCs without significant reduction of the levels HSPCs. Significant reduction of the level of HSPCs can be obtained when the action of anti-c-kit is promoted by an immunotherapeutic agent inhibiting CD47-SIRP?. HSPCs expressing c-kit can thus be reduced to an acceptable level an acceptable level to permit introduction of replacement HSPCs without detrimental delay during which a subject has inadequate HSPCs.

Abstract: The invention is related to phosphorus substituted anti-inflammatory compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Abstract: The invention is related to phosphorus substituted anti-inflammatory compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Abstract: The active metabolites of adefovir and tenofovir (PMEApp and PMPApp) are active against the MMTV RT. They are 25-fold more potent than 3TCppp, suggesting that tenofovir and adefovir may be effective at inhibiting the MMTV-like retroviruses, which may be the etiological agents involved in PBC and breast cancer.

Abstract: The invention is related to phosphorus substituted therapeutic agents, compositions containing such phosphorus substituted agents, and therapeutic methods that include the administration of such phosphorus substituted agents, as well as to processes and intermediates useful for preparing such agents.

Abstract: The invention is related to phosphorus substituted anti-inflammatory compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Abstract: The active metabolites of adefovir and tenofovir (PMEApp and PMPApp) are active against the MMTV RT. They are 25-fold more potent than 3TCppp, suggesting that tenofovir and adefovir may be effective at inhibiting the MMTV-like retroviruses, which may be the etiological agents involved in PBC and breast cancer.

Abstract: A shaft seal arrangement for turbochargers comprises a two piece wear washer for preventing passage of bearing lubricant into the turbocharger turbine housing. The two pieces of the wear washer seal respectively with the turbocharger shaft and with the turbocharger bearing housing. The two pieces of the wear washer further cooperate with each other to form a radially displaceable seal arrangement to accommodate radial excursions of the shaft without leakage of bearing lubricant.