Genome-wide analysis of alternative RNA splicing in children with Acute Myeloid Leukemia (AML)

The pediatric Acute Myeloid Leukemia (AML) is a high-risk and hard-to-treat childhood cancer that originates in the bone marrow from immature white blood cells. Recently, more and more evidence indicates that aberrant splicing of genes is a common characteristic for AML. Gene expression profiles have proved extremely useful for identifying genes that are associated with clinical characteristics and survival outcome of cancer patients. However, conventional gene expression profiles do not account for the differences observed in expressed isoforms when alternative RNA splicing is analyzed. Alternative RNA splicing can generate dozens of distinct transcripts from individual genes and the expressions of some transcript isoforms may correlate with the patients’ characteristics and survival outcome. Current statistical methods in detecting and analyzing differentially expressed and spliced isoforms are limited. Recently we developed a novel approach to identifying differentially expressed or spliced isoforms among different medical conditions. We used a linear mixed effects model-based approach for analyzing the complex alternative RNA sequencing regulation patterns detected by whole-transcriptome RNA-sequencing technologies. Here, we applied this approach to perform differential isoform expression/splicing analysis with 234 patients in which 153 patients who were relapsed or dead within 3 years (Cases) and 81 who achieved continuous complete remission for three or more years (Controls). As a result, we identified 1144 genes with differentially expressed or spliced isoforms and 740 genes whose isoforms are differentially spliced between pediatric AML patients with good and bad outcomes. Our analysis provided biological insight for the disease progression as well as the biomarkers and therapeutic targets for the pediatric AML

Increasing occurrence of cold and warm extremes during the recent global warming slowdown.

The recent levelling of global mean temperatures after the late 1990s, the so-called global warming hiatus or slowdown, ignited a surge of scientific interest into natural global mean surface temperature variability, observed temperature biases, and climate communication, but many questions remain about how these findings relate to variations in more societally relevant temperature extremes. Here we show that both summertime warm and wintertime cold extreme occurrences increased over land during the so-called hiatus period, and that these increases occurred for distinct reasons. The increase in cold extremes is associated with an atmospheric circulation pattern resembling the warm Arctic-cold continents pattern, whereas the increase in warm extremes is tied to a pattern of sea surface temperatures resembling the Atlantic Multidecadal Oscillation. These findings indicate that large-scale factors responsible for the most societally relevant temperature variations over continents are distinct from those of global mean surface temperature

Synthesizing Coherent Story with Auto-Regressive Latent Diffusion Models

Conditioned diffusion models have demonstrated state-of-the-art text-to-image synthesis capacity. Recently, most works focus on synthesizing independent images; While for real-world applications, it is common and necessary to generate a series of coherent images for story-stelling. In this work, we mainly focus on story visualization and continuation tasks and propose AR-LDM, a latent diffusion model auto-regressively conditioned on history captions and generated images. Moreover, AR-LDM can generalize to new characters through adaptation. To our best knowledge, this is the first work successfully leveraging diffusion models for coherent visual story synthesizing. Quantitative results show that AR-LDM achieves SoTA FID scores on PororoSV, FlintstonesSV, and the newly introduced challenging dataset VIST containing natural images. Large-scale human evaluations show that AR-LDM has superior performance in terms of quality, relevance, and consistency.Comment: Technical Repor

Theoretical EXAFS studies of a model of the oxygen-evolving complex of photosystem II obtained with the quantum cluster approach

The oxygen-evolving complex (OEC) of photosystem II is the only natural system that can form O2 from water and sunlight and it consists of a Mn4Ca cluster. In a series of publications, Siegbahn has developed a model of the OEC with the quantum mechanical (QM) cluster approach that is compatible with available crystal structures, able to form O2 with a reasonable energetic barrier, and has a significantly lower energy than alternative models. In this investigation, we present a method to restrain a QM geometry optimization toward experimental polarized extended X-ray absorption fine structure (EXAFS) data. With this method, we show that the cluster model is compatible with the EXAFS data and we obtain a refined cluster model that is an optimum compromise between QM and polarized EXAFS data. (C) 2012 Wiley Periodicals, Inc

The response of sea ice and high-salinity shelf water in the Ross Ice Shelf Polynya to cyclonic atmosphere circulations

Coastal polynyas in the Ross Sea are important source regions of high-salinity shelf water (HSSW) - the precursor of Antarctic Bottom Water thatsupplies the lower limb of the thermohaline circulation. Here, the responseof sea ice production and HSSW formation to synoptic-scale and mesoscalecyclones was investigated for the Ross Ice Shelf Polynya (RISP) using acoupled ocean-sea ice-ice shelf model targeted on the Ross Sea. Whensynoptic-scale cyclones prevailed over RISP, sea ice production (SIP)increased rapidly by 20 %-30 % over the entire RISP. During the passage of mesoscale cyclones, SIP increased by about 2 times over the western RISP but decreased over the eastern RISP, resulting respectively from enhancement inthe offshore and onshore winds. HSSW formation mainly occurred in thewestern RISP and was enhanced responding to the SIP increase under bothtypes of cyclones. Promoted HSSW formation could persist for 12-60 h after the decay of the cyclones. The HSSW exports across the DrygalskiTrough and the Glomar Challenger Trough were positively correlated with themeridional wind. Such correlations are mainly controlled by variations ingeostrophic ocean currents that result from sea surface elevation change and density differences.Peer reviewe

Local polynomial regression for pooled response data

We propose local polynomial estimators for the conditional mean of a continuous response when only pooled response data are collected under different pooling designs. Asymptotic properties of these estimators are investigated and compared. Extensive simulation studies are carried out to compare finite sample performance of the proposed estimators under various model settings and pooling strategies. We apply the proposed local polynomial regression methods to two real-life applications to illustrate practical implementation and performance of the estimators for the mean function