Rational Design and Optimization of a Potent IDO1 Proteolysis Targeting Chimera (PROTAC).

Indoleamine 2,3-dioxygenase 1 (IDO1) is a potently immunosuppressive protein that inhibits antitumor immunity through both tryptophan metabolism and non-enzymatic functions. Pharmacological therapies targeting IDO1 enzyme activity have generally failed to improve the overall survival of patients with cancer. Developing new therapeutic agents that are capable of neutralizing both enzyme-and non-enzyme-derived immunosuppressive IDO1 effects is therefore of high interest.

The translational landscape of HIV-1 infected cells reveals key gene regulatory principles.

Human immunodeficiency virus-1 (HIV-1) uses a number of strategies to modulate viral and host gene expression during its life cycle. To characterize the transcriptional and translational landscape of HIV-1 infected cells, we used a combination of ribosome profiling, disome sequencing and RNA sequencing. We show that HIV-1 messenger RNAs are efficiently translated at all stages of infection, despite evidence for a substantial decrease in the translational efficiency of host genes that are implicated in host cell translation.

In search of lost time: Discrete- versus continuous-time models of working alliance and symptom severity.

Objective: The therapeutic alliance is one of the most stable predictors of symptom burden over the course of therapy. So far, this effect has only been examined on the basis of sessions. Continuous-time models (CTM) allow this relationship to be modeled as a continuous process in which the actual time interval between measurements is considered.

A Pilot Study to Assess the Safety and Efficacy of Umbilical Cord Blood-Derived Mesenchymal Stromal Cells for the Treatment of Synovitis in Horses.

Synovitis is present before and during osteoarthritis in horses and can result in performance-limiting lameness. Twenty-four horses with lameness localized to the metacarpo-/metatarsophalangeal joint or a single joint of the carpus were enrolled in this study. We evaluated the response of intra-articular injection with 10 million activated (aMSC) or non-activated (naMSC) allogeneic equine umbilical cord blood-derived mesenchymal stromal cells (MSCs).

Rapid 3D printing of unlayered, tough epoxy-alcohol resins with late gel points dual-color curing technology.

Additive manufacturing technologies and, in particular, vat photopolymerization promise complex structures that can be made in a fast and easy fashion for highly individualized products. While the technology has upheld this promise many times already, some polymers are still out of reach or at least problematic to print reliably. High-performance epoxide-based resins, which are regulated by chain transfer multifunctional alcohols, are a typical example of resins with late gel points, which require long irradiation times and high light intensities to print.