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Inflammation-associated microsatellite alterations:Mechanisms and significance in the prognosis of patients with colorectal cancer

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World Journal of Gastrointestinal Oncology 2018年第1期10卷 1-14页

作者： Minoru Koi stephanie s Tseng-Rogenski john M Carethers Department of Internal Medicine and Comprehensive Cancer Center University of MichiganAnn ArborMI 48109-5368United States

Microsatellite alterations within genomic DNA frameshift as a result of defective DNA mismatch repair(MMR). About 15% of sporadic colorectal cancers(CRCs) manifest hypermethylation of the DNA MMR gene MLH1, resulting in mono-and di-nucleotide frameshifts to classify it as microsatellite instability-high(MsI-H) and hypermutated, and due to frameshifts at coding microsatellites generating neo-antigens, produce a robust protective immune response that can be enhanced with immune checkpoint blockade. More commonly, approximately 50% of sporadic nonMsI-H CRCs demonstrate frameshifts at di-and tetra-nucleotide microsatellites to classify it as MsIlow/elevated microsatellite alterations at selected tetranucleotide repeats(EMAsT) as a result of functional somatic inactivation of the DNA MMR protein MsH3 via a nuclear-to-cytosolic displacement. The trigger for MsH3 displacement appears to be inflammation and/or oxidative stress, and unlike MsI-H CRC patients, patients with MsI-L/EMAsT CRCs show poor prognosis. These inflammatory-associated microsatellite alterations are a consequence of the local tumor microenvironment, and in theory, if the microenvironment is manipulated to lower inflammation, the microsatellite alterations and MsH3 dysfunction should be corrected. Here we describe the mechanisms and significance of inflammatory-associated microsatellite alterations, and propose three areas to deeply explore the consequences and prevention of inflammation's effect upon the DNA MMR system.

关键词： Microsatellite instability Microsatellite stable Elevated microsatellite alterations at selected tetranucleotide repeats Colorectal cancer Mismatch repair Inflammation MsH3

Can an 8^(th) grade student learn point of care ultrasound?

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World Journal of Emergency Medicine 2019年第2期10卷 109-113页

作者： Alexander s.Kwon shadi Lahham john C.Fox sage Hill school Department of Emergency Medicine UC Irvine Medical Center UC Irvine School of Medicine

BACKGROUND: Point-of-care ultrasound has gained widespread use in developing countries due to decreased cost and improved telemedicine capabilities. Ultrasound training, specifi cally image acquisition skills, is occurring with more frequency in non-medical personnel with varying educational levels in these underdeveloped areas. This study evaluates if students without a high school education can be trained to acquire useful FAsT images, and to determine if an 8^(th) grade student can teach peers these ***: The 8^(th) grade students at a small middle school were divided into two groups. One group received training by a certified medical sonographer, while the other group received training by a peer 8^(th) grade student trainer who had previously received training by the sonographer. After training, each student was independently tested by scanning the four FAsT locations. A blinded ultrasound expert evaluated these images and deemed each image adequate or inadequate for clinical ***: Eighty video image clips were obtained. The overall image adequacy rate was 74%. The splenorenal window had the highest rate at 95%, followed by retrovesical at 90%, hepatorenal at 75%, and subxiphoid cardiac at 35%. The adequacy rate of the sonographer-trained group was 78%, while the adequacy rate of the student-trained group was 70%. The difference in image adequacy rate between the two groups was not signifi cant(P-value 0.459).CONCLUsION: The majority of 8^(th) graders obtained clinically adequate FAsT images after minimal training. Additionally, the student-trained group performed as well as the sonographer-trained group.

关键词： Point of care ultrasound FAsT Image acquisition Training

Immune checkpoint inhibitor-mediated colitis in gastrointestinal malignancies and inflammatory bowel disease

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World Journal of Gastrointestinal Oncology 2021年第8期13卷 772-798页

作者： Alexa R Weingarden samuel J s Rubin john Gubatan Division of Gastroenterology and Hepatology Department of MedicineStanford UniversityRedwood CityCA 94063United States stanford University school of Medicine Stanford UniversityRedwood CityCA 94063United States

Immune checkpoint inhibitors(ICI)have markedly changed the landscape of cancer *** re-invigorating the immune system against tumors,ICI provide novel therapeutic options for a broad variety of malignancies,including many gastrointestinal(GI)***,these therapies can also induce autoimmune-like side effects in healthy tissue across the *** of the most common of these side effects is ICI-mediated colitis and diarrhea(IMC).Here,we review the incidence and risk of IMC in ICI therapy,with a focus on what is known regarding IMC in patients with GI *** also discuss data available on the use of ICI and risk of IMC in patients with pre-existing inflammatory bowel disease,as these patients may have increased risk of IMC due to their underlying intestinal pathology.

关键词： Immune checkpoint inhibitors Cytotoxic T-lymphocyte antigen 4 Programmed cell death protein-1 Inflammatory bowel disease Gastrointestinal cancer

simplified seismic fatigue evaluation for rigid steel connections

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Earthquake Engineering and Engineering Vibration 2003年第2期2卷 245-253页

作者： AymanA.shama john B.Mander stuart.s.Chen Parsons Corporation 100 BroadwayNew York.NY 10005USA Ph.D.P.E Department of Civil Engineering University of CanterburyNew Zealand Professor Department of Civil Structural & Environmental EngineeringState University of New York at BuffaloBuffaloNY 14260USA Associated Professor

A simplified fatigue-life model is proposed for assessing the seismic inelastic rotational capacity of steel *** relations are developed for rigid steel connections under lateral *** this is extended to account for the effects of the welded steel moment frame(WsMF)connections of the so-called pre-Northridge *** seismic fatigue theory is validated against experimental *** experiments were conducted under increasing ductility amplitudes until the onset of ***'rule was used to convert the test results to given an equivalent constant amplitude cyclic fatigue *** agreement is obtained when comparing the experimental observations with the theoretical predictions.

关键词： fatigue cyclic load seismic pile-to-cap moment frames connections steel

Evolutionary relationship and species separation of four morphologically similar stichotrichous ciliates (Protozoa,Ciliophora)

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Progress in Natural science:Materials International 2009年第5期19卷 581-586页

作者： john Clamp Khaled A.s.Al-Rasheid Abdulaziz A.Al-Khedhairy Department of Biology North Carolina Central University Zoology Department King Saud University

Phylogenetic and taxonomic studies on ciliate protists using molecular approaches have been demonstrated to be very reliable to form strong conclusions and results. In the present work, species separation of some morphologically similar stichotrichous ciliates, two species of Pseudokeronopsis and two species of Apokeronopsis, was reexamined using amplified ribosomal DNA restriction analysis (PCR-RFLP). Five of 10 restriction enzymes revealed species-specific polymorphic patterns, of which four similar stichotrichs could be significantly separated and identified. Among them, EcoR I offered almost no significantly different restriction fragment patterns, but the four species could be separated from one another and identified with Hae Ⅲ. Distinctly different restriction digestion haplotypes and simi-larity indices separated the species, and were used to construct a phylogeny. Phylogenies based on ITs2 nucleotide sequences and ITs2 secondary structures supported the separation of Pseudokeronopsis and Apokeronopsis using RFLP analysis, although three Pseudoker-onopsis carnea populations did not cluster together. In addition, phylogenetic analyses using multiple algorithms confirmed that these two genera formed two distinct groups within the urostylids.

关键词： Ciliophora Pseudokeronopsis Apokeronopsis PCR-RFLP ITs2 secondary structures

A Damage-tolerant Bulk Metallic Glass at Liquid-nitrogen Temperature

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Journal of Materials science & Technology 2014年第6期30卷 627-630页

作者： Jun Yi s.Mohsen seifi Weihua Wang john J.Lewandowski Department of Materials science and Engineering Case Western Reserve UniversityClevelandOH 44106-7204 USA Institute of Physics Chinese Academy of Sciences

Tensile tests and notch toughness tests were conducted on Zr61Ti2Cu25Al12 glass （ZT） at room temperature and liquid-nitrogen temperature. The tensile strength of ZT was improved from 1.63 GPa at room temperature to 1.72 GPa at liquid-nitrogen temperature. Micro-notches with a root radius of 1-3μm were introduced to test the notch toughness of ZT at room temperature and liquid-nitrogen temperature. The test results revealed that the notch toughness of ZT at liquid-nitrogen temperature is comparable to that of ZT at room temperature. The combination of high yield strength and notch toughness of ZT at liquid-nitrogen temperature is comparable to that of the best cryogenic engineering materials.

关键词： Metallic glasses Yield strength Fracture toughness Liquid-nitrogen temperature

Electrical stimulation and denervated muscles after spinal cord injury

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Neural Regeneration Research 2020年第8期15卷 1397-1407页

作者： subhalakshmi Chandrasekaran john Davis Ines Bersch Gary Goldberg Ashraf s.Gorgey spinal Cord Injury and Disorders Hunter Holmes McGuire VA Medical CenterRichmondVAUSA swiss Paraplegic Centre NottwilSwitzerland Institute of Clinical sciences Department of Orthopedics at the University of GothenburgGothenburgSweden Department of Physical Medicine and Rehabilitation Virginia Commonwealth UniversityRichmondVAUSA Electrodiagnostic Center Hunter Holmes McGuire VA Medical CenterRichmondVAUSA

spinal cord injury(sCI)population with injury below T10 or injury to the cauda equina region is characterized by denervated muscles,extensive muscle atrophy,infiltration of intramuscular fat and formation of fibrous *** morphological changes may put individuals with sCI at higher risk for developing other diseases such as various cardiovascular diseases,diabetes,obesity and ***,there is no available rehabilitation intervention to rescue the muscles or restore muscle size in sCI individuals with lower motor neuron ***,hereby,performed a review of the available evidence that supports the use of electrical stimulation in restoration of denervated muscle following *** pulse width stimulation(LPWs)technique is an upcoming method of stimulating denervated *** primary objective is to explore the best stimulation paradigms(stimulation parameters,stimulation technique and stimulation wave)to achieve restoration of the denervated *** parameters,such as the pulse duration,need to be 100–1000 times longer than in innervated muscles to achieve desirable excitability and *** use of electrical stimulation in animal and human models induces muscle *** in animal models indicate that electrical stimulation,with a combination of exercise and pharmacological interventions,have proven to be effective in improving various aspects like relative muscle weight,muscle cross sectional area,number of myelinated regenerated fibers,and restoring some level of muscle *** studies have shown similar outcomes,identifying the use of LPWs as an effective strategy in increasing muscle cross sectional area,the size of muscle fibers,and improving muscle ***,displaying promise is an effective future stimulation *** summary,LPWs is a novel stimulation technique for denervated muscles in humans with *** studies on LPWs of denervated muscles will help in translating

关键词： denervation DXA electrical stimulation LMN injury LPWs MRI spinal cord injury stimulation parameters

Mixing of powders and granular materials by mechanical means——A perspective

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Particuology 2012年第4期10卷 397-427页

作者： john Bridgwater Department of Chemical Engineering and Biotechnology University of CambridgePembroke StreetCambridge CB2 3RAUK Laboratory for simulation and Modeling of Particulate systems School of Materials Science and EngineeringThe University of New South WalesSydneyNSW 2052Australia

When engineers and scientists encounter the mixing of powders, they enter a subject where it is often difficult to find bearings. This perspective seeks to address this need by setting out the state of prac- tice. It then considers the growing momentum in the area following advances in computation and in measurement that became significant in the 1990s. The mixing of powders and granular materials is of central importance for the quality and performance of a wide range of products. However, process design and operation are very difficult, being largely based on judgement rather than science. There are not even tabulated data to tell how the quality of mixtures depends on mixer selection. Design depends on experience and insight, not science. There are no sound scale-up laws for a given equipment type, largely because particle size needs to be included in any dimensional analysis. Design is not possible by applying physical principles. There is no reliable equation to describe the flow of single component powders, let alone multi-component mixtures. In most cases, measurement has been difficult because the materials are optically opaque. Work in the research literature has been questionable because the results obtained for mixture sampling are affected by sample size. Recently, modern experimental techniques and modelling work have provided a good deal of infor- mation on the behaviour of many of the pieces of equipment, though these have been small in size and often confined to materials of a single size. However, the studies have enhanced knowledge of physical behaviour. For example, for a wide range of equipment when operating at lower velocities, mixing is determined by the number of revolutions of the mixer, not the time. Observations of flow structure have led to a few specific models that should scale with equipment size. Measurement techniques are slowly becoming more effective in giving internal flow patterns and in measuring powder composition. For cohe

关键词： PerspectivePowder mixingMixing of granular materialsCurrent designMixture qualityMixing mechanismsExperiments and computationsResearch trendsOpportunities for advancesegregationCohesion

Plant xylem hydraulics:What we understand,current research,and future challenges

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Journal of Integrative Plant Biology 2017年第6期59卷 356-389页

作者： Martin D. Venturas john s. sperry Uwe G. Hacke Department of Biology University of Utah257 S 1400ESalt Lake CityUT 84112USA Department of Renewable Resources University of AlbertaEdmontonAB T6G 2E3Canada

Herein we review the current state-of-the-art of plant hydraulics in the context of plant physiology, ecology, and evolution, focusing on current and future research opportunities. We explain the physics of water transport in plants and the limits of this transport system, highlighting the relationships between xylem structure and function. We describe the great variety of techniques existing for evaluating xylem resistance to cavitation. We address several methodological issues and their connec- tion with current debates on conduit refilling and exponentially shaped vulnerability curves. We analyze the trade-offs existing between water transport safety and efficiency. We also stress how little information is available on molecular biology of cavitation and the potential role of aquaporins in conduit refilling. Finally, we draw attention to how plant hydraulic traits can be used for modeling stomatal responses to environmental variables and climate change, including drought mortality.

关键词： William J. Lucas, University of California, Davis, UsAReceived Jan. 10,2017 Accepted Mar. 9,2017 Online on Mar. 14,2017