The structural basis of actinomycin D–bindinginduces nucleotide flipping out, a sharp bendand a left-handed twist in CGG triplet repeats

The potent anticancer drug actinomycin D (ActD)functions by intercalating into DNA at GpC sites,thereby interrupting essential biological processesincluding replication and transcription. Certainneurological diseases are correlated with the expansionof (CGG)n trinucleotide sequences, whichcontain many contiguous GpC sites separated by asingle G:G mispair. To characterize the binding ofActD to CGG triplet repeat sequences, the structuralbasis for the strong binding of ActD to neighbouringGpC sites flanking a G:G mismatch has beendetermined based on the crystal structure of ActDbound to ATGCGGCAT, which contains a CGGtriplet sequence. The binding of ActD molecules toGCGGC causes many unexpected conformationalchanges including nucleotide flipping out, a sharpbend and a left-handed twist in the DNA helix via atwo site-binding model. Heat denaturation, circulardichroism and surface plasmon resonance analysesshowed that adjacent GpC sequences flanking aG:G mismatch are preferred ActD-binding sites. Inaddition, ActD was shown to bind the hairpin conformationof (CGG)16 in a pairwise combination andwith greater stability than that of other DNAintercalators. Our results provide evidence of apossible biological consequence of ActD bindingto CGG triplet repeat sequences

Identifying And Validating Type 1 And Type 2 Diabetic Cases Using Administrative Date: A Tree-Structured Model

Background: Planning, implementing, monitoring, temporal evolution and prognosis differ between type 1 diabetes (T1DM) and type 2 diabetes (T2DM). To date, few administrative diabetes registries have distinguished T1DM from T2DM, reflecting the lack of required differential information and possible recording bias. Objective: Using a classification tree model, we developed a prediction rule to distinguish T1DM from T2DM accurately, using information from a large administrative database.Methods: The Medical Archival Retrieval System (MARS) at the University of Pittsburgh Medical Center from 1/1/2000-9/30/2009 included administrative and clinical data for 209,642 unique diabetic patients aged ≥ 18 years. We identified 10,004 T1DM and 156,712 T2DM patients as probable or possible cases, based on clinical criteria. Classification tree models were fit using TIBCO Spotfire S+ 8.1 (TIBCO Software). We used 10-fold cross-validation to choose model size. We estimated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of T1DM.Results: The main predictors that distinguished T1DM from T2DM include age < 40 vs. ≥ 40 years, ICD-9 codes of T1DM or T2DM diagnosis, oral hypoglycemic agent use, insulin use, and episode(s) of diabetic ketoacidosis diagnosis. History of hypoglycemic coma, duration in the MARS database, in-patient diagnosis of diabetes, and number of complications (including myocardial infarction, coronary artery bypass graft, dialysis, neuropathy, retinopathy, and amputation) are ancillary predictors. The tree-structured model to predict T1DM from probable cases yields sensitivity (99.63%), specificity (99.28%), PPV (89.87%) and NPV (99.71%).Conclusion: Our preliminary predictive rule to distinguish between T1DM and T2DM cases in a large administrative database appears to be promising and needs to be validated. The public health significance is that being able to distinguish between these diabetes subtypes will allow future subtype-specific analyses of cost, morbidity, and mortality. Future work will focus on ascertaining the validity and generalizability of our predictive rule, by conducting a review of medical charts (as an internal validation) and applying the rule to another MARS dataset or other administrative databases (as external validations)

Ludwigia octovalvis extract improves glycemic control and memory performance in diabetic mice

Ethnopharmacological relevance Ludwigia octovalvis (Jacq.) P.H. Raven (Onagraceae) extracts have historically been consumed as a healthful drink for treating various conditions, including edema, nephritis, hypotension and diabetes. Aim of the study We have previously shown that Ludwigia octovalvis extract (LOE) can significantly extend lifespan and improve age-related memory deficits in Drosophila melanogaster through activating AMP-activated protein kinase (AMPK). Since AMPK has become a critical target for treating diabetes, we herein investigate the anti-hyperglycemic potential of LOE. Materials and methods Differentiated C2C12 muscle cells, HepG2 hepatocellular cells, streptozotocin (STZ)-induced diabetic mice and high fat diet (HFD)-induced diabetic mice were used to investigate the anti-hyperglycemic potential of LOE. The open field test and novel object recognition test were used to evaluate spontaneous motor activity and memory performance of HFD-induced diabetic mice. Results In differentiated C2C12 muscle cells and HepG2 hepatocellular cells, treatments with LOE and its active component (β-sitosterol) induced significant AMPK phosphorylation. LOE also enhanced uptake of a fluorescent glucose derivative (2-NBDG) and inhibited glucose production in these cells. The beneficial effects of LOE were completely abolished when an AMPK inhibitor, dorsomorphin, was added to the culture system, suggesting that LOE requires AMPK activation for its action in vitro. In streptozotocin (STZ)-induced diabetic mice, we found that both LOE and β-sitosterol induced an anti-hyperglycemic effect comparable to that of metformin, a drug that is commonly prescribed to treat diabetes. Moreover, LOE also improved glycemic control and memory performance of mice fed a HFD. Conclusions These results indicate that LOE is a potent anti-diabetic intervention that may have potential for future clinical applications

物理模型試驗應用於順向坡板岩變形特性之研究

本文主要探討臺灣板岩順向坡變形特性，藉由現場調查、地形分析與物理模型試驗說明板岩不同條件下之重力變形特性，並推估板岩變形過程與潛在崩壞機制。結果顯示，坡趾侵蝕透空與降雨入滲機制為板岩變形之關鍵，其將造成板岩材料強度弱化加速發生變形。此外，板岩變形初始發生於崖頂張力區，坡體將沿著高角度葉理滑移，並於侵蝕弱化帶附近形成剪切破壞或複合型破壞。而變形範圍內具有相當多葉理張開之現象，其將有助於地表水與地下水滲入，促使板岩變形區加速變形至崩壞。This paper focuses on characterizing the deformation of consequent slate slopes in Taiwan. Onsite surveys, terrain analysis, and a physical model test are used to describe the characteristics of gravity-driven deformation under various conditions and identify the process of slate deformation as well as potential failure mechanisms. Slate deformation is shown to begin in the tension zone at cliff tops, wherein the slope body slips along the highly inclined foliation, contributing to shear failure or composite failure near the eroded zone of weakness. The phenomenon of foliation opening is widespread within the area of deformation, enabling surface water and groundwater to seep in, thereby accelerating deformation and failure in the slate deformation zone

Pharmacoepidemiologic Studies: An Interrupted-time Series Analysis on Drug Utilization and Evalution of Beneficial or Adverse Drug Effects

Background: Pharmacoepidemiologic research is a valuable tool to enable one to understand medication utilization patterns, beneficial/harmful outcomes of drug therapy, and to evaluate the impact of other interventions on outcomes of drug therapy in “real-world” settings. Objectives: This dissertation aimed to apply pharmacoepidemiologic methods to examine (1) changes in utilization patterns of cholesterol-lowering medications following the release of the guidelines and evidence-based data, (2) the associations between statin use and gait speed decline in older adults, and (3) the associations between aspirin, non-aspirin nonsteroidal anti-inflammatory drugs or acetaminophen and risk of ovarian cancer. Methods: The study samples were from two sources including (1) community-dwelling older adults in the Health, Aging and Body Composition Study, and (2) 902 women with ovarian cancer and 1,802 controls in a population-based case-control study. An interrupted time-series analysis, multivariable generalized estimating equations, and multivariable logistic regression were used to examine our three objectives, respectively. Results: First, the use of cholesterol-lowering medication increased substantially over a decade in older adults, but was not related to a change in level or trend following the release of the evidence-based guidelines. Secondly, statin use had a decreased risk of gait speed decline. Thirdly, risk reductions of ovarian cancer were observed with the use of aspirin or selective COX-2 inhibitors. Conclusion: These findings suggest that further studies are needed to investigate risk-benefit balance of cholesterol-lowering therapy and the potential benefits/barriers of the treatment among adults aged ≥ 80 years. Moreover, further investigations are warranted to confirm the risk-benefit balance of statin use and physical function decline in older adults. Future research on the associations between aspirin use and the risk of ovarian cancer should better characterize accompanying medical conditions, health and lifestyle behaviors, genetic susceptibility, and the overall risk-benefit balance. The public health relevance of these findings is that understanding the utilization patterns of cholesterol-lowering therapy and potential benefits of statins on physical function may prevent cardiovascular disease and disability in older adults. In addition, aspirin or COX-2 inhibitors may be potential agents for the prevention of ovarian cancer, the second leading gynecologic cancer in the US

IQNet: Image Quality Assessment Guided Just Noticeable Difference Prefiltering For Versatile Video Coding

Image prefiltering with just noticeable distortion (JND) improves coding efficiency in a visual lossless way by filtering the perceptually redundant information prior to compression. However, real JND cannot be well modeled with inaccurate masking equations in traditional approaches or image-level subject tests in deep learning approaches. Thus, this paper proposes a fine-grained JND prefiltering dataset guided by image quality assessment for accurate block-level JND modeling. The dataset is constructed from decoded images to include coding effects and is also perceptually enhanced with block overlap and edge preservation. Furthermore, based on this dataset, we propose a lightweight JND prefiltering network, IQNet, which can be applied directly to different quantization cases with the same model and only needs 3K parameters. The experimental results show that the proposed approach to Versatile Video Coding could yield maximum/average bitrate savings of 41\%/15\% and 53\%/19\% for all-intra and low-delay P configurations, respectively, with negligible subjective quality loss. Our method demonstrates higher perceptual quality and a model size that is an order of magnitude smaller than previous deep learning methods

The Strategy of Sedimentation Reuse Response to Dam Removal, Case Study Shihgang Dam

Source: ICHE Conference Archive - https://mdi-de.baw.de/icheArchive

Team resource management strategy on reducing unplanned extubation events rate of endotracheal tube

Session presented on Thursday, July 21, 2016 and Friday, July 22, 2016: Purpose: The purpose of this study is to reduce the rate of unplanned endotracheal tube removal in ICU. In order to learn about the process of team resources management mode and how to plan decrease the the rate of unplanned endotracheal tube removal in order to protect patient\u27s safety. Methods: After cause analyzing from the 20 cases who were suffered unplanned endotracheal tube removal in ICU in 2011. The team resources management mode was utilized to build up certain interventions in order to improve this situation, such as leadership, situational monitoring, team supporting and communication. Thus, we plan in-service education. Establish the standard unplanned endotracheal tube removal. Plan I\u27M SAFE activity. Establish the partner system in clinical care. Innovate zero extubation by patient. Interprerfessional meeting take place for effectively to communicate the patient clinical care plan. Results: After engaging interventions from January 2012 to May 2013, the rate of unplanned endotracheal tube removal has decreased from 0.27% in 2011 to 0.14% in 2012 by 12 cases. This reached the study goal. The zero extubation by patient from January 2012 to May 2013, we culculate the days no patient extubation by himself in the duration is achieve 104 days. The Interprerfessional meeting all participants attendance rate is 95%. Conclusion: The endotracheal tube safety is the way to promote patient\u27s safety and it also be serious problem for public health care system. This kind of patients care is focus on physycal restraint and protect the invasive tube. This study not only applied the team resources management mode to prevent unplanned endotracheal tube removal which had achieved significant positive result, but also increased patients\u27 safety. Besides, positive negotiation climate in working place had established through management strategy. This study obtain many special glory, and Iin our hospital that become a TRM pole with a trophy hung on it. This successful experience is expend to other hospital. We hope the team resources management mode can continue to promote patient\u27s safety in order to provide excellent medical treatment quality