Engineering synthetic phosphorylation signaling networks in human cells.

Protein phosphorylation signaling networks have a central role in how cells sense and respond to their environment. We engineered artificial phosphorylation networks in which reversible enzymatic phosphorylation cycles were assembled from modular protein domain parts and wired together to create synthetic phosphorylation circuits in human cells. Our design scheme enabled model-guided tuning of circuit function and the ability to make diverse network connections; synthetic phosphorylation circuits can be coupled to upstream cell surface receptors to enable fast-timescale sensing of extracellular ligands, and downstream connections can regulate gene expression.

PGMweb: an online tool for visualizing the X-ray beam path through plane grating monochromators.

We present here a newly developed software tool (called PGMweb) for computing and simulating the X-ray beam path through a plane grating monochromator (PGM), a key component in soft X-ray beamlines at modern synchrotron and free-electron laser facilities. A historical overview of the development of PGMs is presented, with special attention dedicated to the collimated PGM optical scheme found at several X-ray facilities worldwide. The analytical expressions that fully describe the geometry of a PGM are derived and have been implemented as functions in a Python library (pyplanemono).

Health Outcomes 50 Years After Preterm Birth in Participants of a Trial of Antenatal Betamethasone.

Background And Objectives: Preterm birth results in neonatal and childhood morbidity and mortality. Additionally, population-based studies show poorer cardiovascular health in adult survivors, but a full range of health outcomes has not been investigated into midlife. We aimed to assess the health outcomes after preterm vs term birth at 50 years in survivors of a randomized trial of antenatal betamethasone.

Polyinosinic/Polycytidylic Lipid Nanoparticles Enhance Immune Cell Infiltration and Improve Survival in the Glioblastoma Mouse Model.

Glioblastoma (GBM) immunotherapy is particularly challenging due to the pro-tumorigenic microenvironment, marked by low levels and inactive immune cells. Toll-like receptor (TLR) agonists have emerged as potent immune adjuvants but failed to show improved outcomes in clinical trials when administered as a monotherapy. We hypothesize that a combined nanoparticulate formulation of TLR agonist and immunogenic cell death-inducing drug (doxorubicin) will synergize to induce improved GBM immunotherapy.