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Updates on treatment of irritable bowel syndrome

World Journal of Gastroenterology 2008年第17期14卷 2639-2649页

作者： christopher W Hammerle Christina m Surawicz Department of medicine University of Colorado Health Sciences Center Harborview medical Center University of Washington

Irritable bowel syndrome （IBS） is a highly prevalent gastrointestinal disorder characterized by abdominal pain and discomfort in association with altered bowel habits. It is estimated tD affect 10%-15% of the Western population, and has a large impact on quality of life and （in）direct healthcare costs. IBS is a multifactorial disorder involving dysregulation within the brain-gut axis, and it is frequently associated with gastrointestinal motor and sensory dysfunction, enteric and central nervous system irregularities, neuroimmune dysregulation, and postinfectious inflammation. As with other functional medical disorders, the treatment for IBS can be challenging. Conventional therapy for those with moderate to severe symptoms is largely unsatisfactory, and the development of new and effective drugs is made difficult by the complex pathogenesis, variety of symptoms, and lack of objective clinical findings that are the hallmark of this disorder. Fortunately, research advances over the past several decades have provided insight into potential mechanisms responsible for the pathogenesis of IBS, and have led to the development of several promising pharmaceutical agents. In recent years there has been much publicity over several of these new IBS medications （alosetron and tegaserod） because of their reported association with ischemic colitis and cardiovascular disease. While these agents remain available for use under restricted prescribing programs, this highlights the need for continued development of safe and effective medication for IBS. This article provides a physiologicallybased overview of recently developed and frequently employed pharmaceutical agents used to treat IBS, and discusses some non-pharmaceutical options that may be beneficial in this disorder.

关键词： Irritable bowel syndrome Treatment Pharmacotherapy Challenges Opportunities

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CO2 degassing and melting of metasomatized mantle lithosphere during rifting-Numerical study

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Geoscience Frontiers 2019年第4期10卷 1409-1420页

作者： Weronika Gorczyk christopher m. Gonzalez University of Western Australia Centre for Exploration TargetingSchool of Earth SciencesARC Centre of Excellence for Core to Crust Fluid SystemsPerthWestern AustraliaAustralia School of Earth Atmosphere and EnvironmentMonash University ClaytonMelbourneVICAustralia

:Reactivation of metasomatized mantle lithosphere may occur during continental extension,which is an important component of plate *** lower most part of the metasomatized domains in the subcontinental mantle lithosphere can be locally enriched in ***,partial melting of these metasomatized domains may play a crucial role in the global carbon ***,little is known about this process and up until now few numerical constraints are *** we address this knowledge gap and use a 2-D high resolution petrological-thermomechanical model to assess lithospheric ***2 degassing and *** test 4 lithospheric thicknesses:90,110,130 and 200 km with a 10 km thick metasomatized layer at the base using CO2 of 2 wt.%in the bulk *** carbonate enriched layer is stable below^3 GPa(>110 km)for a temperature of 1300℃;therefore,we only observe degassing patterns for lithospheric models that are 130 km and 200 km *** metasomatized layer for the 130 km thick lithosphere mostly comprises carbonatite melting,whereas in the 200 km thick scenario propagation of melt development from kimberlites to carbonatites occurs as the metasomatic mantle is exhumed during *** numerical models fit well into natural rifting zones of the European Cenozoic Rift System for young(shallow)and of the North Atlantic Rift for old(thick)lithosphere.

关键词： Rifting mantle CO2 degassing Carbonate melting

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Glutaminase inhibition in renal cell carcinoma therapy

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Cancer Drug Resistance 2019年第2期2卷 356-364页

作者： Aleksandra m.Raczka Paul A.reynolds School of medicine University of St AndrewsSt Andrews KY169TFUK Biomedical Sciences Research Complex University of St AndrewsSt AndrewsUK.

Receptor tyrosine kinase inhibitors have been a standard first-line therapy for renal cell carcinoma(RCC)for over a *** they stabilize the disease,they are unable to remove all tumor cells,leading to ***,both intrinsic and acquired resistance to therapy are a significant health *** order to overcome resistance,several combination therapies have been recently approved by the *** approach takes advantage of altered metabolism in tumor cells,which switch to alternative metabolic pathways to sustain their rapid growth and ***-839 is a small molecule inhibitor of kidney type glutaminase(GLS).GLS is often upregulated in glutamine addicted cancers,enhancing glutamine metabolism for the production of energy and the biosynthesis of various cellular building ***-839 is currently in clinical trials for several tumors,including clear cell(cc)RCC,both as monotherapy and in combination with the approved therapeutic agents everolimus,cabozantinib and *** results of Phase 1/2 clinical trials look promising,especially for CB-839 plus cabozantinib,and all combinations seem to be well ***,cancer cells can activate compensatory pathways to overcome glutaminolysis ***,genetic and metabolomic studies are crucial for the successful implementation of CB-839 alone or in combination in subgroups of ccRCC patients.

关键词： Glutamine addiction renal cell carcinoma combination therapy metabolism

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Heat Transfer in the microlayer Under a Bubble During Nucleate Boiling

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Tsinghua Science and Technology 2010年第4期15卷 404-413页

作者： David m.christopher 张璐 Key Laboratory for Thermal Science and Power Engineering of ministry of Education Department of Thermal Engineering Tsinghua University

many studies have shown that a very thin liquid microlayer forms under vapor bubbles during nucleate boiling. The heat transfer from the surface to the bubble is then significantly affected by this mi- crolayer and the curved region leading into the microlayer. Various models have been developed to predict the microlayer shape and the heat transfer along the curved interfacial region, but they tend to have incon- sistent boundary conditions or unrealistic results. This paper presents a theoretical model to predict the mi- crolayer thickness and the heat transfer rates for a variety of conditions. The results show how the wall su- perheat, the Hamaker constant, the bubble radius, and the accommodation coefficient at the interface affect the evaporation heat transfer rates and the microlayer shape for a large range of conditions for water and FC 72. The microlayer results are then shown to compare well with predictions made by solving the Na- vier-Stokes equations in the microlayer.

关键词： nucleate boiling bubble growth heat transfer microlayer

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Experimental Study of High moisture Content Gas Flow Across a Cylinder at moderate reynolds Numbers

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Tsinghua Science and Technology 2003年第5期8卷 598-604页

作者： D.m.christopher 郭亮 Department of Thermal Engineering

The Nusselt number for cross flow of a mixture of air and vapor over a cylinder was measured at moderate reynolds numbers (30007000) for temperatures from 300℃ to 700℃ and for vapor mass fractions of 0.180.35. Results are also presented for a set of three cylinders aligned perpendicular to the flow for the same range of conditions. The effect of the vapor concentration and temperature on the convection coefficients was investigated to develop a modified Zhukauskas correlation. The results show that the Nusselt number increases as the moisture content increases and that the increase is more than could be accounted for by typical models for the property variations of mixtures. The exponent of the vapor concentration term in the modified correlation is 0.145 for the entire data set indicating the importance of the property variation due to the moisture content.

关键词： high moisture content cross flow convection coefficients heat exchangers

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Dynamic Bubble Behaviour during microscale Subcooled Boiling

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Chinese Physics Letters 2005年第11期22卷 2881-2884页

作者：王昊彭晓峰 David m. christopher Laboratory of Phase-Change and Interracial Transport Phenomena Department of Thermal Engineering Tsinghua University Beijing 100084

Bubble cycles, including initiation, growth and departure, are the physical basis of nucleate boiling. The present investigation, however, reveals unusual bubble motions during subcooled nucleate boiling on microwires 25 or 100μm in diameter. Two types of bubble motions, bubble sweeping and bubble return, are observed in the experiments. Bubble sweeping describes a bubble moving back and forth along the wire, which is motion parallel to the wire. Bubble return is the bubble moving back to the wire after it has detached or leaping above the wire. Theoretical analyses and numerical simulations are conducted to investigate the driving mechanisms for both bubble sweeping and return. marangoni flow from warm to cool regions along the bubble interface is found to produce the shear stresses needed to drive these unusual bubble movements.

关键词： subcooled boiling ELECTRIC WIRE driving mechanism bubbles Nucleate boiling Shear stress

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Strategies towards statistically robust interpretations of in situ U-Pb zircon geochronology

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Geoscience Frontiers 2016年第4期7卷 581-589页

作者： christopher J.Spencer christopher L.Kirkland Richard J.m.Taylor The Institute of Geoscience Research(TIGeR) Department of Applied GeologyWestern Australian School of MinesCurtin UniversityWA 6102Australia Centre for Exploration Targeting-Curtin Node Department of Applied GeologyWestern Australian School of MinesCurtin UniversityWA 6102Australia Australian Research Council Centre of Excellence for Core to Crust Fluid SystemsPerthWA 6102Australia

Zircon U-Pb geochronology has become a keystone tool across Earth science, arguably providing the gold standard in resolving deep geological time. The development of rapid in situ analysis of zircon （via laser ablation and secondary ionization mass spectrometry） has allowed for large amounts of data to be generated in a relatively short amount of time and such large volume datasets offer the ability to address a range of geological questions that would otherwise remain intractable （e.g. detrital zircons as a sedi- ment fingerprinting method）. The ease of acquisition, while bringing benefit to the Earth science com- munity, has also led to diverse interpretations of geochronological data. In this work we seek to refocus U -Pb zircon geochronology toward best practice by providing a robust statistically coherent workflow. We discuss a range of data filtering approaches and their inherent limitations （e.g. discordance and the reduced chi-squared; mSWD）. We evaluate appropriate mechanisms to calculate the most geologically appropriate age from both 238U/206pb and 207pb/206pb ratios and demonstrate the cross over position when chronometric power swaps between these ratios. As our in situ analytical techniques become progressively more precise, appropriate statistical handing of U-Pb datasets will become increasingly pertinent.

关键词： Zircon Geochronology U-Pb Geostatistics mSWD

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Quantifying Kinematic Tremor in an NGLY1-Deficient Individual: A Case Study

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Case Reports in Clinical medicine 2024年第1期13卷 25-36页

作者： Brock Futrell christopher Alexander malaya Dacia martinez Diaz Christian Alfaro Hannah Elizabeth Gustafson Subhalakshmi Chandrasekaran Rhea mohan Phatak Bernhard Suter Charles Shannon Layne Department of Health and Human Performance University of Houston Houston USA Center for Neuromotor and Biomechanics Research University of Houston Houston USA Department of Computer Science and Engineering Texas A&M University College Station USA Blue Bird Circle Rett Center Texas Children’s Hospital Houston USA Baylor College of medicine Houston USA Center for NeuroEngineering and Cognitive Science University of Houston Houston USA

NGLY1 Deficiency is an autosomal recessive congenital disorder that has been identified in less than 100 individuals. most individuals with NGLY1 Deficiency display hyperkinetic movement disorders, including choreiform, athetoid, dystonic myoclonic, dyskinetic, and dysmetric movements. Developing a consistent and concise consensus on the classification and evaluation of tremors is essential to forward the research and treatment of tremors. It has also been reported that some individuals with NGLY1 Deficiency demonstrate tremor, but such tremor has never been formally investigated. The primary objective of this study is to determine if an individual with NGLY1 Deficiency demonstrates an identifiable tremor during a series of arm movements and, if so, describe the frequency and power characteristics of that tremor. Arm movement kinematics were obtained using a 16-camera Vicon system, and time series trajectory waveforms for three planes of a marker placed on the hand were developed. Custom mATLAB scripts were utilized to compute Fast Fourier Transformations of the data within the identified waveform segments. A mean frequency of 2.30 Hz (SD = 1.05) with a mean power of 5.02 |P1(f)| (SD = 4.63) suggests that our participant’s kinematic data did display a persistent tremor in both hands across all tasks and movement planes. Analyses of the reaching hand and the non-reaching hand suggest the participant displayed an action tremor in both postural and intention (kinetic) tremors. Future directions should include assessing additional individuals with NGLY1 Deficiency to determine if the tremor is a distinguishable disorder behavior. Additionally, evaluating other anatomical sites, such as the elbow, head, and lower limbs, would provide further insights into the characteristics of this tremor.

关键词： Tremor NGLY Fast Fourier Transformation Reaching Hyperkinetic movement

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Protecting miners from coal bursts during development above historic mine workings in Harlan County,KY

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International Journal of mining Science and Technology 2021年第1期31卷 111-116页

作者： christopher mark mine Safety and Health Administration PittsburghPA 15236USA

In order to reach a large,untapped reserve of high-quality coal,D8 Cloverlick mine proposed to mine a corridor nearly 600 m deep beneath the Benham Spur of Black mountain,Kentucky’s highest peak.D8 Cloverlick mine was extracting the Owl seam,but the corridor’s route lay approximately 20 m above century-old mine workings in the C–(Darby)*** to the concern,three serious coal bursts had recently occurred in nearby Owl seam *** of the old workings seemed to indicate that the underlying C–seam had been fully ***,two of the coal bursts had occurred above areas where the C–Seam was also shown as mined *** Safety and Health Administration(mSHA)Technical Support therefore investigated the records of past mining to better understand the old mine *** conditions observed in current Owl seam workings were also compared with the maps of the old C–seam *** study concluded that the presence of hazardous underlying remnants could not be ruled *** mitigate the burst risk,D8 Cloverlick mine adopted a strategy of stress probe drilling.A self-propelled coal drill was used to auger 11.5-m-long,small diameter holes in advance of *** each hole was drilled,the cuttings were measured to detect the presence of highly stressed *** the crossing was successfully completed without incident.

关键词： Coal bursts Underground mining Room-and-pillar Destressing

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Bubble Coalescence Heat Transfer During Subcooled Nucleate Pool Boiling

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工程热物理学报 2012年第12期33卷 2171-2175页

作者： Abdoulaye Coulibaly LIN Xipeng Bi Jingliang David m christopher Department of Thermal Engineering Tsinghua University

Bubble coalescence during subcooled nucleate pool boiling was investigated experimentally using constant wall temperature boundary conditions while the wall heat flux was measured at a various locations to understand the effects of coalescence on the heat *** observations showed that the coalesced bubble moved and oscillated on the heater surface with significant heat transfer variations prior to *** observations also showed coalescence with no increase in the heat transfer *** heat flux for boiling with coalescence fluctuated much more than for single bubble boiling due to the vaporization of the liquid layer trapped between the bubbles.

关键词： microheater pool boiling bubble coalescence bubble dynamics

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