PaLM 2 Technical Report

We introduce PaLM 2, a new state-of-the-art language model that has better multilingual and reasoning capabilities and is more compute-efficient than its predecessor PaLM. PaLM 2 is a Transformer-based model trained using a mixture of objectives. Through extensive evaluations on English and multilingual language, and reasoning tasks, we demonstrate that PaLM 2 has significantly improved quality on downstream tasks across different model sizes, while simultaneously exhibiting faster and more efficient inference compared to PaLM. This improved efficiency enables broader deployment while also allowing the model to respond faster, for a more natural pace of interaction. PaLM 2 demonstrates robust reasoning capabilities exemplified by large improvements over PaLM on BIG-Bench and other reasoning tasks. PaLM 2 exhibits stable performance on a suite of responsible AI evaluations, and enables inference-time control over toxicity without additional overhead or impact on other capabilities. Overall, PaLM 2 achieves state-of-the-art performance across a diverse set of tasks and capabilities. When discussing the PaLM 2 family, it is important to distinguish between pre-trained models (of various sizes), fine-tuned variants of these models, and the user-facing products that use these models. In particular, user-facing products typically include additional pre- and post-processing steps. Additionally, the underlying models may evolve over time. Therefore, one should not expect the performance of user-facing products to exactly match the results reported in this report

Protein Aggregation and Protein Instability Govern Familial Amyotrophic Lateral Sclerosis Patient Survival

The nature of the “toxic gain of function” that results from amyotrophic lateral sclerosis (ALS)-, Parkinson-, and Alzheimer-related mutations is a matter of debate. As a result no adequate model of any neurodegenerative disease etiology exists. We demonstrate that two synergistic properties, namely, increased protein aggregation propensity (increased likelihood that an unfolded protein will aggregate) and decreased protein stability (increased likelihood that a protein will unfold), are central to ALS etiology. Taken together these properties account for 69% of the variability in mutant Cu/Zn-superoxide-dismutase-linked familial ALS patient survival times. Aggregation is a concentration-dependent process, and spinal cord motor neurons have higher concentrations of Cu/Zn-superoxide dismutase than the surrounding cells. Protein aggregation therefore is expected to contribute to the selective vulnerability of motor neurons in familial ALS

Game Analysis Wiki

The goal of this project was to create a system that challenged conventional game analysis in order to encourage deeper thought about game design. To accomplish this goal, a game analysis wiki was created for cataloging movement-based game mechanics found across various different games. This report documents the development of this wiki from start to finish, as well the creation of a tag-based system for game analysis. Significant issues that arose during development are also discussed in this report

PyNE Progress Report

<p>Talk given to the ANS Winter Meeting 2014</p

Single-Cell Analysis of Human Mononuclear Phagocytes Reveals Subset-Defining Markers and Identifies Circulating Inflammatory Dendritic Cells

Human mononuclear phagocytes comprise phenotypically and functionally overlapping subsets of dendritic cells (DCs) and monocytes, but the extent of their heterogeneity and distinct markers for subset identification remains elusive. By integrating high-dimensional single-cell protein and RNA expression data, we identified distinct markers to delineate monocytes from conventional DC2 (cDC2s). Using CD88 and CD89 for monocytes and HLA-DQ and Fc epsilon RI alpha for cDC2s allowed for their specific identification in blood and tissues. We also showed that cDC2s could be subdivided into phenotypically and functionally distinct subsets based on CD5, CD163, and CD14 expression, including a distinct subset of circulating inflammatory CD5(-)CD163(+)CD14(+) cells related to previously defined DC3s. These inflammatory DC3s were expanded in systemic lupus erythematosus patients and correlated with disease activity. These findings further unravel the heterogeneity of DC subpopulations in health and disease and may pave the way for the identification of specific DC subset-targeting therapies

Single-Cell Analysis of Human Mononuclear Phagocytes Reveals Subset-Defining Markers and Identifies Circulating Inflammatory Dendritic Cells

Human mononuclear phagocytes comprise phenotypically and functionally overlapping subsets of dendritic cells (DCs) and monocytes, but the extent of their heterogeneity and distinct markers for subset identification remains elusive. By integrating high-dimensional single-cell protein and RNA expression data, we identified distinct markers to delineate monocytes from conventional DC2 (cDC2s). Using CD88 and CD89 for monocytes and HLA-DQ and FcεRIα for cDC2s allowed for their specific identification in blood and tissues. We also showed that cDC2s could be subdivided into phenotypically and functionally distinct subsets based on CD5, CD163, and CD14 expression, including a distinct subset of circulating inflammatory CD5−CD163+CD14+ cells related to previously defined DC3s. These inflammatory DC3s were expanded in systemic lupus erythematosus patients and correlated with disease activity. These findings further unravel the heterogeneity of DC subpopulations in health and disease and may pave the way for the identification of specific DC subset-targeting therapies. Using high-dimensional protein and RNA single-cell analyses, Dutertre et al. analyze human dendritic cell and monocyte subsets and identify markers that delineate them and unravel their heterogeneity. They also reveal the presence of inflammatory CD14+ DC3s, a subset of cDC2s, that correlate with disease progression and may be functionally involved in systemic lupus erythematosus immunopathology