Selective haematological cancer eradication with preserved haematopoiesis.

Haematopoietic stem cell (HSC) transplantation (HSCT) is the only curative treatment for a broad range of haematological malignancies, but the standard of care relies on untargeted chemotherapies and limited possibilities to treat malignant cells after HSCT without affecting the transplanted healthy cells. Antigen-specific cell-depleting therapies hold the promise of much more targeted elimination of diseased cells, as witnessed in the past decade by the revolution of clinical practice for B cell malignancies. However, target selection is complex and limited to antigens expressed on subsets of haematopoietic cells, resulting in a fragmented therapy landscape with high development costs.

Anti-CD45 PBD-based antibody-drug conjugates are effective targeted conditioning agents for gene therapy and stem cell transplant.

Stem cell gene therapy and hematopoietic stem cell transplantation (SCT) require conditioning to ablate the recipient's hematopoietic stem cells (HSCs) and create a niche for gene-corrected/donor HSCs. Conventional conditioning agents are non-specific, leading to off-target toxicities and resulting in significant morbidity and mortality. We developed tissue-specific anti-human CD45 antibody-drug conjugates (ADCs), using rat IgG2b anti-human CD45 antibody clones YTH24.

Atmospheric Chemistry of HOHgO Mimics That of a Hydroxyl Radical.

HOHgO, formed from HOHg + O, is a key intermediate in the OH-initiated oxidation of Hg in the atmosphere. As no experimental data are available for HOHgO, we use computational chemistry (CCSD(T)//M06-2X/AVTZ) to characterize its reactions with atmospheric trace gases (NO, NO, CH, CH, CHO and CO). In summary, HOHgO, like the analogous BrHgO radical, largely mimics the reactivity of OH in reactions with NO, alkanes, alkenes, and aldehydes.

Aviation Decompression Sickness in Aerospace and Hyperbaric Medicine.

The U.S. Navy experienced a series of physiological events in aircrew involving primarily the F/A-18 airframe related to rapid decompression of cabin pressures, of which aviation decompression sickness (DCS) was felt to contribute.

Structure-guided design and characterization of a clickable, covalent PARP16 inhibitor.

PARP16-the sole ER-resident PARP family member-is gaining attention as a potential therapeutic target for cancer treatment. Nevertheless, the precise function of the catalytic activity of PARP16 is poorly understood. This is primarily due to the lack of inhibitors that are selective for PARP16 over other PARP family members.