AVEID: Automatic Video System for Measuring Engagement In Dementia

Engagement in dementia is typically measured using behavior observational scales (BOS) that are tedious and involve intensive manual labor to annotate, and are therefore not easily scalable. We propose AVEID, a low cost and easy-to-use video-based engagement measurement tool to determine the engagement level of a person with dementia (PwD) during digital interaction. We show that the objective behavioral measures computed via AVEID correlate well with subjective expert impressions for the popular MPES and OME BOS, confirming its viability and effectiveness. Moreover, AVEID measures can be obtained for a variety of engagement designs, thereby facilitating large-scale studies with PwD populations

The Adverse Impact of Temperature on Income

Crop Production/Industries, Risk and Uncertainty,

Income and temperatures: Working paper series--10-06

The contemporaneous relationship between temperature and income is important because it enables economists to estimate the economic impact of global warming without assuming a structural model. Until recently, empirical evidence generally suggests that there is a negative relationship between temperature and income, and therefore global warming has an adverse impact on economic activity. However, recently Nordhaus (2006) finds that the temperature-income relationship depends on how income is measured. We show in this paper that the results of Nordhaus (2006) may be due to a model misspecification or an omitted-variable problem. Based on a well-motivated temperature-income model, we find that the relationship between temperature and income is not dependent on income measurement. Our regression results show that the adverse impact of an increase of 3 degrees Celsius in temperature can be as much as a 9% decrease in income for developed nations such as the United States and the United Kingdom. Therefore, our results suggest more aggressive climate mitigation policy

Amyloid β-sheet mimics that antagonize protein aggregation and reduce amyloid toxicity.

The amyloid protein aggregation associated with diseases such as Alzheimer's, Parkinson's and type II diabetes (among many others) features a bewildering variety of β-sheet-rich structures in transition from native proteins to ordered oligomers and fibres. The variation in the amino-acid sequences of the β-structures presents a challenge to developing a model system of β-sheets for the study of various amyloid aggregates. Here, we introduce a family of robust β-sheet macrocycles that can serve as a platform to display a variety of heptapeptide sequences from different amyloid proteins. We have tailored these amyloid β-sheet mimics (ABSMs) to antagonize the aggregation of various amyloid proteins, thereby reducing the toxicity of amyloid aggregates. We describe the structures and inhibitory properties of ABSMs containing amyloidogenic peptides from the amyloid-β peptide associated with Alzheimer's disease, β(2)-microglobulin associated with dialysis-related amyloidosis, α-synuclein associated with Parkinson's disease, islet amyloid polypeptide associated with type II diabetes, human and yeast prion proteins, and Tau, which forms neurofibrillary tangles

Time and regime dependence of foreign exchange exposure: Working paper series--10-11

In this paper, we extend Francis, Hasan, and Hunter (2008) and Stacks and Wei (2005) by simultaneously taking into account the time and the regime dependence of foreign exchange exposure in a reduced-form framework. Specifically, we use a random coefficient model and the quantile regression technique invented by Koenker and Bassett (1978) to examine the currency exposure of 30 US industry portfolios. We find that all 30 industry portfolios exhibit significant foreign exchange exposure. Therefore, our results support Francis, Hasan, and Hunter (2008) and Stacks and Wei (2005), and suggest that the methodological weakness, not hedging, explains the insignificance of currency risk in previous studies

A Robust Gene Expression Prognostic Signature for Overall Survival in High-Grade Serous Ovarian Cancer.

The objective of this research was to develop a robust gene expression-based prognostic signature and scoring system for predicting overall survival (OS) of patients with high-grade serous ovarian cancer (HGSOC). Transcriptomic data of HGSOC patients were obtained from six independent studies in the NCBI GEO database. Genes significantly deregulated and associated with OS in HGSOCs were selected using GEO2R and Kaplan-Meier analysis with log-rank testing, respectively. Enrichment analysis for biological processes and pathways was performed using Gene Ontology analysis. A resampling/cross-validation method with Cox regression analysis was used to identify a novel gene expression-based signature associated with OS, and a prognostic scoring system was developed and further validated in nine independent HGSOC datasets. We first identified 488 significantly deregulated genes in HGSOC patients, of which 232 were found to be significantly associated with their OS. These genes were significantly enriched for cell cycle division, epithelial cell differentiation, p53 signaling pathway, vasculature development, and other processes. A novel 11-gene prognostic signature was identified and a prognostic scoring system was developed, which robustly predicted OS in HGSOC patients in 100 sampling test sets. The scoring system was further validated successfully in nine additional HGSOC public datasets. In conclusion, our integrative bioinformatics study combining transcriptomic and clinical data established an 11-gene prognostic signature for robust and reproducible prediction of OS in HGSOC patients. This signature could be of clinical value for guiding therapeutic selection and individualized treatment

Quality assessment on Polygoni Multiflori Caulis using HPLC/UV/MS combined with principle component analysis

BACKGROUND: Polygoni Multiflori Caulis, the dried caulis of Polygonum multiflorum Thunb., is one of the commonly used traditional Chinese medicines having antioxidant, anti-obesity, anti-inflammatory and antibacterial effects. Polygoni Multiflori Caulis used clinically or circulated on market have great differences in their diameters. However, to the best of our knowledge, no study has been reported on the qualities of Polygoni Multiflori Caulis with different diameters. RESULTS: Systematic HPLC/UV/MS chromatographic fingerprinting and quantitative analytical methods combined with principal component analysis were developed and applied to analyze different Polygoni Multiflori Caulis samples. The contents of 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside, the chemical marker for quality control on Polygoni Multiflori Caulis specified in Chinese Pharmacopoeia (2010 edition), were found to have surprising relevance with the samples’ diameters for the first time. CONCLUSION: The finding provides a scientific basis for collecting Polygoni Multiflori Caulis in the best time. Moreover, the diameter can be used as the criterion for quality control on Polygoni Multiflori Caulis as a preliminary step in the future. In addition, scores plot obtained from principal component analysis shows the obvious differences between unqualified Polygoni Multiflori Caulis samples and qualified ones visually, which can be used to single out the unqualified ones with qualified ones efficiently and immediately

The role of sirtuins in epigenetic regulation

Epigenetic mechanisms regulating gene expression mainly involve DNA methylation, histone modification, and non-coding RNAs. Disruption of these mechanisms may lead to cancer, complicated disorders such as behavioral disorders, amnesia, autoimmune disease, and addiction. DNA methylation is a widespread modification found in various species, which is produced by DNA methyltransferases (DNMTs), including Dnmt1, Dnmt2, Dnmt3a, Dnmt3b and Dnmt3L, and also considered as a stable gene-silencing mechanism. Specifically, the inhibition of gene transcription occurs, either by blocking the binding of transcriptional factors or through the recruitment of methylated DNA binding domain proteins. However, DNA methylation is also linked with histone modifications. Histones undergo a series of covalent modifications, like methylation, acetylation, ubiquitination, phosphorylation, and sumoylation. Furthermore, histone modifications are determined by the substrate specificity of the enzymes as well as enzymes that remove these marks. Among these modifications, histone acetylation is regarded as one of the marks for transcriptional activation and deacetylation of histone is closely associated with gene repression. In this work, we found that the nicotine adenine dinucleotide (NAD+)-dependent deacetylase sirtuins family is involved in epigenetic regulation, and connects histone deacetylation with DNA methylation. On the one hand, Sirt1 can interact with non-histone proteins, like Dnmt1 and Uhrf1, and influence protein stability and DNA methylation. Sirt1 mediated deacetylation stabilizes Uhrf1 in combination with the deubiquitinase Usp7. Functionally, deacetylation of Uhrf1 is a prerequisite for Uhrf1 to be phosphorylated by Cdk2 and enter into S phase of the cell cycle. The expression level of Uhrf1 fluctuates in different phases of the cell cycle and plays a crucial role in the regulation of DNA methylation. On the other hand, Sirtuins have been reported to deacetylate various substrates of histones, such as H3K9ac, H3K14ac, H4K16ac, and H1K6ac (Imai et al., 2000; Vaquero et al., 2004). Not only Sirt7 is a highly selective H3K18ac deacetylase for maintaining cellular transformation, but also Sirt1, Sirt2, and Sirt6 can deacetylate H3K18ac and regulate metabolism by downregulating some target genes. Significantly, these genes are regulated via a transcriptional factor, Hif1a, which provides new insights into therapies and metabolic diseases. Specifically, these genes are downregulated via the increased DNA methylation because sirtuins-mediated H3K18 deacetylation promotes Uhrf1-associated ubiquitination of H3K18, which is essential for Dnmt1 binding and DNA methylation (Qin et al., 2015a). Taken together, our data suggest that H3K18 acetylation, as one of the common histone substrate of sirtuin proteins, is enriched at the transcription start site (TSS) of active and poised genes, offends DNA methylation and thereby promotes transcriptional activation of these genes