Protein structure generation via folding diffusion.

The ability to computationally generate novel yet physically foldable protein structures could lead to new biological discoveries and new treatments targeting yet incurable diseases. Despite recent advances in protein structure prediction, directly generating diverse, novel protein structures from neural networks remains difficult. In this work, we present a diffusion-based generative model that generates protein backbone structures via a procedure inspired by the natural folding process. We describe a protein backbone structure as a sequence of angles capturing the relative orientation of the constituent backbone atoms, and generate structures by denoising from a random, unfolded state towards a stable folded structure. Not only does this mirror how proteins natively twist into energetically favorable conformations, the inherent shift and rotational invariance of this representation crucially alleviates the need for more complex equivariant networks. We train a denoising diffusion probabilistic model with a simple transformer backbone and demonstrate that our resulting model unconditionally generates highly realistic protein structures with complexity and structural patterns akin to those of naturally-occurring proteins. As a useful resource, we release an open-source codebase and trained models for protein structure diffusion.

Two for One: Diffusion Models and Force Fields for Coarse-Grained Molecular Dynamics.

Coarse-grained (CG) molecular dynamics enables the study of biological processes at temporal and spatial scales that would be intractable at an atomistic resolution. However, accurately learning a CG force field remains a challenge. In this work, we leverage connections between score-based generative models, force fields, and molecular dynamics to learn a CG force field without requiring any force inputs during training. Specifically, we train a diffusion generative model on protein structures from molecular dynamics simulations, and we show that its score function approximates a force field that can directly be used to simulate CG molecular dynamics. While having a vastly simplified training setup compared to previous work, we demonstrate that our approach leads to improved performance across several protein simulations for systems up to 56 amino acids, reproducing the CG equilibrium distribution and preserving the dynamics of all-atom simulations such as protein folding events.

Palliative and terminal care at home as portrayed in Dutch newspapers in 2009 compared to 2000.

BACKGROUND: Terminal care at home is receiving increased attention from the Dutch media, which is relevant for primary care providers. OBJECTIVES: To explore the portrayal of terminal care at home in newspapers in the Netherlands in 2000 and in 2009. METHOD: We performed a systematic analysis of documents retrieved from the LexisNexis Academic NL database. We compared data regarding the 'point of reference' (or 'frame') and the 'moral judgments' in articles appearing in the first six months of 2009 to the same period in 2000. RESULTS: In the year 2000, the framing of articles in regional newspapers appeared to be predominantly consumer-oriented (66%) and in national newspapers predominantly contextual (63%). The moral judgment in the regional articles was predominantly positive (66%), in the national newspapers predominantly negative (58%). In 2009, articles in regional and national newspapers were categorized mainly as consumer-oriented (73% and 55%, respectively), and new themes appeared, i.e. self care and medical topics. For moral judgment, again regional articles were mainly positive (76%) and national articles were mainly negative (39%) and neutral (31%). CONCLUSION: Regarding the theme 'terminal care at home' as published in Dutch newspapers in 2009 as compared to 2000, the diversity of the framing was more prominent and over all moral judgments were more positive, particularly in regional newspapers. Health care providers should realize that the portrayal of palliative and terminal care at home may differ depending on the type of newspaper--regional or national.

Non-responsiveness to hepatitis B vaccination in HIV seropositive patients; possible causes and solutions.

Hyporesponsiveness (anti-HBs 10-100 IU/l) or non-responsiveness (anti-HBs < 10 IU/l) to hepatitis B vaccines is a problem in approximately 20-70% of HIV-positive patients. Mechanisms for impaired humoral and cellular immunity related to the HIV infection are reviewed. Contributing risk factors like age, gender, CD4+ T-cell count, HIV RNA load and coinfection with hepatitis C are highlighted. New developments in improving the HBV vaccine immunogenicity are discussed and clinical recommendations are given for HBV-re-vaccination of HIV patients who failed on standard HBV vaccination.