Culturing human intestinal stem cells for regenerative applications in the treatment of inflammatory bowel disease

Abstract Both the incidence and prevalence of inflammatory bowel disease (IBD) is increasing globally; in the industrialized world up to 0.5% of the population are affected and around 4.2 million individuals suffer from IBD in Europe and North America combined. Successful engraftment in experimental colitis models suggests that intestinal stem cell transplantation could constitute a novel treatment strategy to re‐establish mucosal barrier function in patients with severe disease. Intestinal stem cells can be grown in vitro in organoid structures, though only a fraction of the cells contained are stem cells with regenerative capabilities. Hence, techniques to enrich stem cell populations are being pursued through the development of multiple two‐dimensional and three‐dimensional culture protocols, as well as co‐culture techniques and multiple growth medium compositions. Moreover, research in support matrices allowing for efficient clinical application is in progress. In vitro culture is accomplished by modulating the signaling pathways fundamental for the stem cell niche with a suitable culture matrix to provide additional contact‐dependent stimuli and structural support. The aim of this review was to discuss medium compositions and support matrices for optimal intestinal stem cell culture, as well as potential modifications to advance clinical use in IBD

Genetic and Functional Dissection of HTRA1 and LOC387715 in Age-Related Macular Degeneration

A common haplotype on 10q26 influences the risk of age-related macular degeneration (AMD) and encompasses two genes, LOC387715 and HTRA1. Recent data have suggested that loss of LOC387715, mediated by an insertion/deletion (in/del) that destabilizes its message, is causally related with the disorder. Here we show that loss of LOC387715 is insufficient to explain AMD susceptibility, since a nonsense mutation (R38X) in this gene that leads to loss of its message resides in a protective haplotype. At the same time, the common disease haplotype tagged by the in/del and rs11200638 has an effect on the transcriptional upregulation of the adjacent gene, HTRA1. These data implicate increased HTRA1 expression in the pathogenesis of AMD and highlight the importance of exploring multiple functional consequences of alleles in haplotypes that confer susceptibility to complex traits

Discovery of [11C]MK-6884: a positron emission tomography (PET) imaging agent for the study of M4 muscarinic receptor positive allosteric modulators (PAMs) in neurodegenerative diseases

The measurement of receptor occupancy (RO) using positron emission tomography (PET) has been instrumental in guiding discovery and development of CNS directed therapeutics. We and others have investigated muscarinic acetylcholine receptor 4 (M4) positive allosteric modulators (PAMs) for the treatment of symptoms associated with neuropsychiatric disorders. In this article, we describe the synthesis, in vitro, and in vivo characterization of a series of central pyridine-related M4 PAMs that can be conveniently radiolabeled with carbon-11 as PET tracers for the in vivo imaging of an allosteric binding site of the M4 receptor. We first demonstrated its feasibility by mapping the receptor distribution in mouse brain and confirming that a lead molecule 1 binds selectively to the receptor only in the presence of the orthosteric agonist carbachol. Through a competitive binding affinity assay and a number of physiochemical properties filters, several related compounds were identified as candidates for in vivo evaluation. These candidates were then radiolabeled with 11C and studied in vivo in rhesus monkeys. This research eventually led to the discovery of the clinical radiotracer candidate [11C]MK-6884

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

FZUImageReg: A toolbox for medical image registration and dose fusion in cervical cancer radiotherapy

The combination external-beam radiotherapy and high-dose-rate brachytherapy is a standard form of treatment for patients with locally advanced uterine cervical cancer. Personalized radiotherapy in cervical cancer requires efficient and accurate dose planning and assessment across these types of treatment. To achieve radiation dose assessment, accurate mapping of the dose distribution from HDR-BT onto EBRT is extremely important. However, few systems can achieve robust dose fusion and determine the accumulated dose distribution during the entire course of treatment. We have therefore developed a toolbox (FZUImageReg), which is a user-friendly dose fusion system based on hybrid image registration for radiation dose assessment in cervical cancer radiotherapy. The main part of the software consists of a collection of medical image registration algorithms and a modular design with a user-friendly interface, which allows users to quickly configure, test, monitor, and compare different registration methods for a specific application. Owing to the large deformation, the direct application of conventional state-of-the-art image registration methods is not sufficient for the accurate alignment of EBRT and HDR-BT images. To solve this problem, a multi-phase non-rigid registration method using local landmark-based free-form deformation is proposed for locally large deformation between EBRT and HDR-BT images, followed by intensity-based free-form deformation. With the transformation, the software also provides a dose mapping function according to the deformation field. The total dose distribution during the entire course of treatment can then be presented. Experimental results clearly show that the proposed system can achieve accurate registration between EBRT and HDR-BT images and provide radiation dose warping and fusion results for dose assessment in cervical cancer radiotherapy in terms of high accuracy and efficiency

Study on the Application of X - ray Separation Technology in Phosphate Mine Dressing

This paper introduces the present situation and problems of phosphate mine dressing, introduces the principle and application status of X-ray separation technology, and gives a detailed introduction and data analysis of the application in phosphate mine dressing. X-ray separation technology is non-water separation and simple process, it can solve the problems such as high flotation ratio of low grade phosphate ore, high consumption of heavy medium, high cost and bad influence on environment. Proposes some methods to improve the precision of X-ray separation technology of phosphate rock, and prospects the application prospect of this technology of phosphate

Thermal Radiation Shielding and Mechanical Strengthening of Mullite Fiber/SiC Nanowire Aerogels Using In Situ Synthesized SiC Nanowires

Traditional solid nanoparticle aerogels have been unable to meet the requirements of practical application due to their inherent brittleness and poor infrared shielding performance. Herein, combining vacuum impregnation and high-temperature pyrolysis, a novel micro/nano-composite fibrous aerogel was prepared via in situ synthesis of silicon carbide nanowires (SiC NWS) in mullite fiber (MF) preform. During this process, uniformly distributed SiC NWS in the MF preform serve as an enhancement phase and also act as an infrared shielding agent to reduce radiation heat transfer, which can significantly improve the mechanical properties of the mullite fiber/silicon carbide nanowire composite aerogels (MF/SiC NWS). The fabricated MF/SiC NWS exhibited excellent thermal stability (1400 °C), high compressive strength (~0.47 MPa), and outstanding infrared shielding performance (infrared transmittance reduced by ~70%). These superior properties make them appealing for their potential in practical application as high-temperature thermal insulators

CCCI Fall 2016: The Memory Project

CCCI Lecture Series: Filmmakers from The Memory Project at Caochangdi Workstation in Beijing - "Knocking on Memory's Door with a Video Camera" November 7, 2016 We are walking down Memory Lane. We are continuing to remember. CCD Workstation began the Folk Memory Documentary Project in 2010. More than twenty participants traveled back to their family villages to film and interview village elders. Their research focused on the years from 1959 to 1961, a period known as the Great Chinese Famine. A handful of people took video cameras and went back to their respective villages. They went in search of the old generation still living there in dim, stark houses. They went to uncover the memories hidden deep inside the villagers. Each filmmaker had some prior relationship to the village. Some of them were born or grew up there, some still live there, and some had never lived in the village but had parents or grandparents who had. For the old people in the village, this was the first time anyone had come with a camera to ask them to open their memory chests. Here was the younger generation, leaping over their parents’ generation-- that generation wiped clean of memory- to ask the elders about the past. This meeting may be awkward and uncomfortable but it is also an exciting adventure. Their stories are now documentary films presented in this program. Excerpts from interviews with each filmmaker shown at the beginning. Co-sponsored by the Department of Performing & Media Arts and the Internationalizing the Cornell Curriculum Grant.Cornell East Asia Program and the Department of Performing & Media Arts1_kaky17o

Multistep Wind Speed Forecasting Based on a Hybrid Model of VMD and Nonlinear Autoregressive Neural Network

Reducing the costs of wind power requires reasonable wind farm operation and maintenance strategies, and then to develop these strategies, the 24-hour ahead forecasting of wind speed is necessary. However, existing prediction work is mostly limited to 5 hours. This work developed a diurnal forecasting methodology for the regional wind farm according to real-life data of the supervisory control and data acquisition (SCADA) system of a wind farm from Jiangxi Province. The methodology used the variational mode decomposition (VMD) to extract wind characteristics, and then, the characteristics were put in the nonlinear autoregressive neural network (Narnet) and long short-term memory network (LSTM) for prediction; the forecast results of VMD-Narnet and VMD-LSTM are compared with the actual wind speed. The comparison results indicate that compared with the LSTM, the Narnet improves the accuracy by 61.90% in 24 hours on wind speed forecasting, and the predicted time horizon was improved by 6.8 hours. This work strongly supports the development of wind farm operation and maintenance strategies and provides a foundation for the reduction of wind power costs

The Measurement of Green Finance Development Index and Its Poverty Reduction Effect: Dynamic Panel Analysis Based on Improved Entropy Method

Finance contributes to poverty alleviation through economic growth, and the development of green finance is related to the sustainable development of the world economy and environment. Green finance not only helps promote sustainable economic development but also helps reduce poverty. Based on the analysis of related theories about green finance and poverty alleviation, this paper selects 18 indicators from three dimensions of economic development, financial development, and social environmental development and uses the improved entropy method to measure the green finance development index of China’s 25 provinces and municipalities from 2004 to 2017. The results show that the development level of green finance in China’s 25 provinces and municipalities is quite different. On the basis of the above analysis, make an empirical analysis of the impact of the green finance development index on poverty alleviation using multiple regression analysis and static panel and dynamic panel estimation methods. The research results show that there is a significant positive correlation between green finance and poverty alleviation; the higher the level of green finance development, the more conducive the poverty alleviation. So, this paper suggests that poverty can be better alleviated by improving the level of green finance development, financial asset level, and economic development level