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Use of gene-editing technology to introduce targeted modifications in pigs

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Journal of Animal science and Biotechnology 2018年第2期9卷 268-277页

作者： Junghyun Ryu randall s.Prather Kiho Lee Department of Animal and Poultry sciences Virginia Tech175 W.Campus DriveBlacksburgVA 24061USA Division of Animal science University of Missouri-Columbia920 East Campus DriveColumbiaMO 65211USA National swine Resource and Research Center University of Missouri-ColumbiaColumbiaMO 65211USA

Pigs are an important resource in agriculture and serve as a model for human diseases. Due to their physiological and anatomical similarities with humans, pigs can recapitulate symptoms of human diseases, making them a useful model in biomedicine. However, in the past pig models have not been widely used partially because of the difficulty in genetic modification. The lack of true embryonic stem cells in pigs forced researchers to utilize genetic modification in somatic cells and somatic cell nuclear transfer(sCNT) to generate genetically engineered(GE) pigs carrying site-specific modifications. Although possible, this approach is extremely inefficient and GE pigs born through this method often presented developmental defects associated with the cloning process. Advancement in the gene-editing systems such as Zinc-Finger Nucleases(ZFNs), Transcription activator-like effector nucleases(TALENs), and the Clustered regularly interspaced short palindromic repeat(CRIsPR)/CRIsPR-associated 9(Cas9) system have dramatically increased the efficiency of producing GE pigs. These gene-editing systems, specifically engineered endonucleases, are based on inducing double-stranded breaks(DsBs) at a specific location, and then site-specific modifications can be introduced through one of the two DNA repair pathways: non-homologous end joining(NHEJ) or homology direct repair(HDR).Random insertions or deletions(indels) can be introduced through NHEJ and specific nucleotide sequences can be introduced through HDR, if donor DNA is provided. Use of these engineered endonucleases provides a higher success in genetic modifications, multiallelic modification of the genome, and an opportunity to introduce site-specific modifications during embryogenesis, thus bypassing the need of sCNT in GE pig production. This review will provide a historical prospective of GE pig production and examples of how the gene-editing system, led by engineered endonucleases, have improved GE pig production. We wil

关键词： CRIsPR/Cas9 Gene-editing Genetic engineering Knock-in Knockout Pig TALEN ZFN

Obeticholic acid for severe bile acid diarrhea with intestinal failure:A case report and review of the literature

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World Journal of Gastroenterology 2018年第21期24卷 2320-2326页

作者： Christian Lodberg Hvas Peter ott Peter Paine simon Lal soren Peter Jorgensen Jens Frederik Dahlerup Department of Hepatology and Gastroenterology Aarhus University HospitalAarhus C 8000Denmark Department of Gastroenterology Salford Royal NHS Foundation TrustSalfordManchester M6 8HDUnited Kingdom

Bile acid diarrhea results from excessive amounts of bile acids entering the colon due to hepatic overexcretion of bile acids or bile acid malabsorption in the terminal ileum. The main therapies include bile acid sequestrants, such as colestyramine and colesevelam, which may be given in combination with the opioid receptor agonist loperamide. some patients are refractory to conventional treatments. We report the use of the farnesoid X receptor agonist obeticholic acid in a patient with refractory bile acid diarrhea and subsequent intestinal failure. A 32-year-old woman with quiescent colonic Crohn's disease and a normal terminal ileum had been diagnosed with severe bile acid malabsorption and complained of watery diarrhea and fatigue. The diarrhea resulted in hypokalemia and sodium depletion that made her dependent on twice weekly intravenous fluid and electrolyte infusions. Conventional therapies with colestyramine, colesevelam, and loperamide had no effect. second-line antisecretory therapies with pantoprazole, liraglutide, and octreotide also failed. Third-line treatment with obeticholic acid reduced the number of stools from an average of 13 to an average of 7 per 24h and improved the patient's quality of life. The fluid and electrolyte balances normalized. The effect was sustained during follow-up for 6 mo with treatment at a daily dosage of 25 mg. The diarrhea worsened shortly after cessation of obeticholic acid. This case report supports the initial report that obeticholic acid may reduce bile acid production and improve symptoms in patients with bile acid diarrhea.

关键词： Bile acid malabsorption Diarrhea Farnesoid X-activated receptor Crohn’s disease

Understanding fluorine-free electrolytes via small-angle X-ray scattering

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Journal of Energy Chemistry 2022年第7期31卷 340-346,I0009页

作者： Kun Qian Zhou Yu Yuzi Liu David J.Gosztola randall E.Winans Lei Cheng Tao Li Department of Chemistry and Biochemistry Northern Illinois UniversityDeKalbIL 60115USA Materials science Division and Joint Center for Energy storage Research Argonne National LaboratoryLemontIL 60439USA Center for Nanoscale Materials Argonne National LaboratoryLemontIL 60439USA X-ray science Division and Joint Center for Energy storage Research Argonne National LaboratoryLemontIL 60439USA

Fluorine-free electrolytes have attracted great attention because of its low-cost and environmental friendliness. However, so far, little is known about the solution structures of these electrolytes. Here,we compare the solvation phenomenon of sodium tetraphenylborate(NaBPh_(4)) salt dissolved in organic solvents of propylene carbonate(PC), 1,2-dimethoxyethane(DME), acetonitrile(ACN) and tetrahydrofuran(THF). small-angle X-ray scattering(sAXs) reveals a unique two-peak structural feature in this saltconcentrated PC electrolyte, while solutions using other solvents only have one scattering *** dynamics(MD) simulations further reveal that there are anion-based clusters in addition to the short-range charge ordering in the concentrated NaBPh4/PC electrolyte. Raman spectroscopy confirms the existence of considerable contact ion pairs(CIPs). This work emphasizes the importance of global and local structural analysis, which will provide valuable clues for understanding the structureperformance relationship of electrolytes.

关键词： Fluorine-free electrolytes sodium-ion batteries small-angle X-ray scattering solvation structures sodium tetraphenylborate

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关注养禽业中抗生素的使用及其影响

中国家禽 2006年第18期28卷 41-47页

作者： randall s singer Charles L Hofacre

在过去的十几年里,抗生素在禽类生产中的使用方式发生了很大的变化。原因之一是取消某些抗生素的使用,如美国取消氟喹诺酮在家禽的使用以及欧盟禁用抗生素促生长剂。另外,许多大型禽业公司自发减少抗生素促生长剂的使用。抗生素使用发... 详细信息

在过去的十几年里,抗生素在禽类生产中的使用方式发生了很大的变化。原因之一是取消某些抗生素的使用,如美国取消氟喹诺酮在家禽的使用以及欧盟禁用抗生素促生长剂。另外,许多大型禽业公司自发减少抗生素促生长剂的使用。抗生素使用发生变化的主要动力还是来自于与这项措施息息相关的公共健康问题。

关键词：抗生素促生长剂养禽业氟喹诺酮健康问题发生变化禽类家禽

High-throughput predictions of metal-organic framework electronic properties:theoretical challenges,graph neural networks,and data exploration

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npj Computational Materials 2022年第1期8卷 1053-1062页

作者： Andrew s.Rosen Victor Fung Patrick Huck Cody T.O’Donnell Matthew K.Horton Donald G.Truhlar Kristin A.Persson Justin M.Notestein randall Q.snurr Department of Materials science and Engineering University of CaliforniaBerkeleyCA94720USA Miller Institute for Basic Research in science University of CaliforniaBerkeleyBerkeleyCA94720USA Materials science Division Lawrence Berkeley National LaboratoryBerkeleyCA94720USA Department of Chemical and Biological Engineering Northwestern UniversityEvanstonIL60208USA Center for Nanophase Materials sciences Oak Ridge National LaboratoryOak RidgeTN37831USA Energy Technologies Area Lawrence Berkeley National LaboratoryBerkeleyCA94720USA Department of Chemistry Chemical Theory Centerand Minnesota Supercomputing InstituteUniversity of MinnesotaMinneapolisMN55455USA Molecular Foundry Lawrence Berkeley National LaboratoryBerkeleyCA94720USA

With the goal of accelerating the design and discovery of metal–organic frameworks(MOFs)for electronic,optoelectronic,and energy storage applications,we present a dataset of predicted electronic structure properties for thousands of MOFs carried out using multiple density functional *** to more accurate hybrid functionals,we find that the widely used PBE generalized gradient approximation(GGA)functional severely underpredicts MOF band gaps in a largely systematic manner for semi-conductors and insulators without magnetic ***,an even larger and less predictable disparity in the band gap prediction is present for MOFs with open-shell 3d transition metal *** regards to partial atomic charges,we find that different density functional approximations predict similar charges overall,although hybrid functionals tend to shift electron density away from the metal centers and onto the ligand environments compared to the GGA point of *** more significant differences in partial atomic charges are observed when comparing different charge partitioning *** conclude by using the dataset of computed MOF properties to train machine-learning models that can rapidly predict MOF band gaps for all four density functional approximations considered in this work,paving the way for future high-throughput screening *** encourage exploration and reuse of the theoretical calculations presented in this work,the curated data is made publicly available via an interactive and user-friendly web application on the Materials Project.

关键词： charges electronic centers

A Case Review of selected Popular Computing Games： Therapeutic and Affective Aspects of Gaming and Comparisons to Children＇s Literature

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通讯和计算机（中英文版） 2016年第6期13卷 271-280页

作者： randall Basham school of social Work the University of Texas at Arlington U.S.A.

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粉末注射成形与液相烧结科学基础的建立

粉末冶金技术 2008年第2期26卷 145-151,152页

作者： randall M. German 韩凤麟(译) CAVs Chair Professor in Mechanical Engineering Director Center for Advanced Vehicular Systems Mississipi State University P. O. Box 5405 Mississippi State MS 39762-5405 USA 不详

就固-液-孔隙系统的流变学特性而言,粉末注射成形与液相烧结具有同样特点。粉末注射成形起始于1930年代,而金属粉末的液相烧结大体上也可溯源于同一时代。这2种工艺都对粘度和固体含量与温度的关系高度敏感,但都有所不同。因此,提出了... 详细信息

就固-液-孔隙系统的流变学特性而言,粉末注射成形与液相烧结具有同样特点。粉末注射成形起始于1930年代,而金属粉末的液相烧结大体上也可溯源于同一时代。这2种工艺都对粘度和固体含量与温度的关系高度敏感,但都有所不同。因此,提出了一个包括应变速率、颗粒大小、固体含量等因素及颗粒结合程度的模型。在液相烧结中,固体在液体中的溶解度通过颗粒结合影响与时间相关的粘度。同样,在粉末注射成形中,长聚合物的缠结影响与时间相关的粘度。粉末注射成形与液相烧结二者的相似之处,在于都能够将流变学特性模型用于计算机模拟。

关键词：粉末注射成形液相烧结流变学模型粘度粘性流动烧结

Lots of Physicists Are Nervous about the speed of Light

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考试（高考英语） 2011年第11期 26-28页

作者： Eric randall 不详

[1]Physicists spent their weekends walking back media hype over an experiment that at first glance seems to disprove Einstein’s famed theory of *** preached dispassionate skepticism,but behind all that careful cynicism,there seemed a lot of hand-wringing.编者注:hype:Hype is the use of a lot of publicity and advertising to make people interested

关键词：高中英语教学教学方法阅读教学

seasonal variation in adult hip disease secondary to osteoarthritis and developmental dysplasia of the hip

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World Journal of Orthopedics 2016年第12期7卷 821-825页

作者： Tatsuya sueyoshi Merrill A Ritter Kenneth E Davis randall T Loder Department of Orthopedic surgery Kyoto University Center for Hip and Knee surgery James Whitcomb Riley Children’s Hospital

AIM To determine if there was a seasonal variation in adults undergoing total hip arthroplasty for end stage hip disease due to osteoarthritis(OA) or sequelae of developmental dysplasia of the hip(DDH).METHODs The total hip registry from the author's institution for the years 1969 to 2013 was reviewed. The month of birth,age,gender,and ethnicity was recorded. Differences between number of births observed and expected in the winter months(October through February) and non-winter mo(March through september) were analyzed with the χ2 test. Detailed temporal variation was mathematically assessed using cosinor *** There were 7792 OA patients and 60 DDH patients who underwent total hip arthroplasty. There were more births than expected in the winter months for both the DDH(P s. Cosinor analyses demonstrated a peak date of birth on 1st October. CONCLUsION These data demonstrate an increased prevalence of DDH and OA in those patients born in winter.

关键词： seasonal trend Winter Osteoarthritis Birth month Developmental hip dysplasia