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Role of ion channels in gastrointestinal cancer

World j.urnal of Gastroenterology 2019年第38期25卷 5732-5772页

作者： Kyle j.Anderson Robert T Cormier Patricia M scott Department of Biomedical Sciences University of Minnesota Medical School

In their seminal papers Hanahan and Weinberg described oncogenic processes a normal cell undergoes to be transformed into a cancer *** functions of ion channels in the gastrointestinal(GI)tract influence a variety of cellular processes,many of which overlap with these hallmarks of *** this review we focus on the roles of the calcium(Ca^2+),sodium(Na^+),potassium(K^+),chloride(Cl^-)and zinc(Zn^2+)transporters in GI cancer,with a special emphasis on the roles of the KCNQ1 K+channel and CFTR Cl-channel in colorectal cancer(CRC).Ca^2+is a ubiquitous second messenger,serving as a signaling molecule for a variety of cellular processes such as control of the cell cycle,apoptosis,and *** members of the TRP superfamily,including TRPM8,TRPM7,TRPM6 and TRPM2,have been implicated in GI cancers,especially through overexpression in pancreatic adenocarcinomas and down-regulation in colon ***-gated sodium channels(VGSCs)are classically associated with the initiation and conduction of action potentials in electrically excitable cells such as neurons and muscle *** VGSC NaV1.5 is abundantly expressed in human colorectal CRC cell lines as well as being highly expressed in primary CRC *** have demonstrated that conductance through NaV1.5 contributes significantly to CRC cell invasiveness and cancer ***2+transporters of the ZIP/SLC39A and ZnT/SLC30A families are dysregulated in all maj.r GI organ cancers,in particular,ZIP4 up-regulation in pancreatic cancer(PC).More than 70 K+channel genes,clustered in four families,are found expressed in the GI tract,where they regulate a range of cellular processes,including gastrin secretion in the stomach and anion secretion and fluid balance in the intestinal *** distinct types of K+channels are found dysregulated in the GI *** are hERG1 upregulation in PC,gastric cancer(GC)and CRC,leading to enhanced cancer angiogenesis and invasion,and KCNQ1 down-regulation in CR

关键词： Ion channels Gastrointestinal cancer Colorectal cancer Gastric cancer Pancreatic cancer Esophageal cancer Hepatocellular carcinoma Prognostic biomarker Novel therapies Clinical targets

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Multiplexed cytokine detection on plasmonic gold substrates with enhanced near-infrared fluorescence

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Nano Research 2013年第2期6卷 113-120页

作者： Bo Zhang j.rdan Price Guosong Hong scott M. Tabakman Hailiang Wang j.stin A. j.rrell j. Feng Paul j. Utz Hongj.e Dai Department of Chemistry Stanford University Stanford California USA Department of Medicine Division of Immunology and Rheumatology Stanford University School of Medicine Stanford California USA Institute for Immunity Transplantation and Infection Stanford University School of Medicine Stanford California USA

Protein microarrays based on fluorescence detection have been widely utilized for high-throughput functional proteomic analysis. However, a drawback of such assays has been low sensitivity and narrow dynamic range, limiting their capabilities, especially for detecting low abundance biological molecules such as cytokines in human samples. Here, we present fluorescence-enhancing microarrays on plasmonic gold films for multiplexed cytokine detection with up to three orders of magnitude higher sensitivity than on conventional nitrocellulose and glass substrates. Cytokine detection on the gold plasmonic substrate is about one to two orders of magnitude more sensitive than enzyme-linked immunosorbent assay （ELISA） and can be multiplexed. A panel of six cytokines （Vascular endothelial growth factor （VEGF）, Interleukin 1β （IL-1β）, Interleukin 4 （IL-4）, Interleukin 6 （IL-6）, Interferon γ （IFN-γ）, and Tumor necrosis factor （TNF）） were detected in the culture media of cancer cells. This work establishes a new method of high throughput multiplexed cytokine detection with higher sensitivity and dynamic range than ELISA.

关键词： microarray cytokine plasmonic multiplex near infrared fluorescence

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Searching for new ferroelectrics and multiferroics: A user’s point of view

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npj.Computational Materials 2015年第1期1卷 47-55页

作者： j. scott School of Chemistry and School of Physics St Andrews UniversitySt AndrewsFifeScotland

A perspective on computational studies of ferroelectrics and multiferroics is given that emphasises what has yet to be done,along with some subtleties in previously studied *** with the extensive data-mining studies of Abrahams and more recently,Rabe,a survey is given of magnetostrictive effects in antiferromagnetic antiferroelectrics(after Toledano and Toledano),which has an nonmagnetic analogy in the antiferroelectric phase of tris-sarcosine calcium chloride and a reminder of the unusual spin–phonon coupling of Holden et *** systems such as KCoF3 and *** is also paid to field-temperature phase diagrams,finite non-periodic boundary conditions,and processing-dependent structures.

关键词： analogy ferroelectric phonon

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Mobility of charge carriers in mineral oil and ester fluids

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High Voltage 2021年第6期6卷 1040-1050页

作者： Qingj.ang Xue Igor Timoshkin Mark PWilson Martin Given scott j.MacGregor Department of Electronic and Electrical Engineering University of StrathclydeGlasgowUK

New,more stringent environmental requirements for electrical insulation liquids have led to the development of novel,more environment‐friendly liquid *** fluids,introduced several decades ago,provide a viable alternative to traditional mineral insu-lating *** order to expand the practical applications of these novel dielectric fluids,their dielectric and electrical parameters should be *** of the critical pa-rameters that affects and governs the development of pre‐breakdown processes in insulating liquids is the mobility of charge *** the present paper,the mobility of charge carriers in commercially available synthetic and natural insulating ester fluids and in a mineral insulating oil were obtained using two methods,the time of flight and the space charge saturation current *** mobility was obtained for a wide range of electrical field *** was found that the mobility of charge carriers is greater in the mineral oil than in both,the natural and synthetic,ester *** was also established that the mobility is higher for higher applied electric *** results of this work will help in characterizing liquid dielectrics and in optimizing high‐voltage systems in which liquid dielectrics,including natural and synthetic ester fluids,are used.

关键词： field. charge liquids

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A comparison of the relative efficiency of ICSI and extended culture with epididymal sperm versus testicular sperm in patients with obstructive azoospermia

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Asian j.urnal of Andrology 2020年第2期22卷 222-226页

作者： scott j.Morin Brent M Hanson Caroline R j.neau Shelby A Neal j.ssica N Landis Richard T scott j. j.mes M Hotaling Reproductive Medicine Associates of New j.rsey 140 Allen RoadBasking RidgeNJ 07920USA Division of Reproductive Endocrinology and Infertility Department of Obstetrics and GynecologySidney Kimmel Medical College at Thomas Jefferson University833 Chestnut StreetPhiladelphiaPA 19107USA Foundation for Embryonic Competence 140 Allen RoadBasking RidgeNJ 07920USA Division of Urology Department of SurgeryUniversity of Utah School of Medicine30 N 1900 ESalt Lake CityUT 84132USA Department of Obstetrics and Gynecology University of Utah School of Medicine30 N 1900 ESalt Lake CityUT 84132USA.An abbreviated version of this manuscript was published and presented as an abstract at the American Society for Reproductive Medicine(ASRM)2017 Scientific Congress.

This is a retrospective cohort study comparing blastocyst transfer outcomes following intracytoplasmic sperm inj.ction utilizing epididymal versus testicular sperm for men with obstructive *** cases at a single center between 2012 and 2016 were *** approach was selected at the surgeon’s discretion and included microepididymal sperm aspiration or testicular sperm *** culture was exclusively utilized prior to *** primary outcome was live birth *** outcomes included fertilization rate,blastulation rate,euploidy rate,and implantation rate.A mixed effects model was ***-six microepididymal sperm aspiration cases and 93 testicular sperm extraction cases were *** live birth rate was equivalent(48.6%vs 50.5%,P=0.77).However,on mixed effects model,epididymal sperm resulted in a greater likelihood of fertilization(adj.sted OR:1.37,95%CI:1.05–1.81,P=0.02)and produced a higher blastulation rate(adj.sted OR:1.41,95%CI:1.1–1.85,P=0.01).As a result,the epididymal sperm group had more supernumerary blastocysts available(4.3 vs 3,Pj.ction following microepididymal sperm aspiration resulted in a greater number of usable blastocysts per ***,the true benefit of epididymal sperm may only be demonstrated via a comparison of cumulative pregnancy rates after multiple transfers from one cohort.

关键词： azoospermia intracytoplasmic sperm inj.ction male infertility testicular sperm extraction

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Semen analysis in 21st century medicine： the need for sperm function testing

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Asian j.urnal of Andrology 2010年第1期12卷 64-70页

作者： Dolores j. Lamb scott Department of Urology and the Department of Molecular and Cellular Biology Baylor College of MedicineHouston TX 77030 USA

Sperm function testing, once commonly performed for the infertile couple before employing assisted reproductive technology （ART）, has fallen out of favour in many reproductive medicine centers throughout the world. Indeed, the most recent addition of the ＇World Health Organisation （WHO） Laboratory Manual for the Examination and Processing of Hu- man Semen＇ now groups many of these procedures into a section termed Research Procedures. In large part, this reflects the current clinical practice of bypassing the in-depth evaluation of the male partner, while assuming that if a spermatozoon can be found for intracytoplasmic sperm inj.ction （ICSI）, it must be a healthy cell capable of achieving fertilization. Never- theless, sperm function testing can provide valuable clinical insights into defects causing male infertility. Admittedly, in some cases, functional sperm deficiencies can be overcome using an ART. In other cases, couples will be empowered by the knowledge of the cause of their infertility, and for some couples, perhaps even the likelihood of ICSI success （relative to the spermatozoa）. The knowledge allows them to make truly informed reproductive decisions, including （perhaps） the de- cision to seek donor insemination, to adopt or to remain childless. Knowledge of the cause of their infertility may provide closure for couples and a sense of confidence regarding their choice of reproductive treatment.

关键词： semen analysis sperm function tests

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Draft Genome Sequence of Mentha Iongifolia and Development of Resources for Mint Cultivar Improvement

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Molecular Plant 2017年第2期10卷 323-339页

作者： Kelly j. Vining Sean R. j.hnson Amirhossein Ahkami Iris Lange Amber N. Parrish Susan C. Trapp rodney B. Croteau Shannon C.K. Straub Iovanna Pandelova B. Markus Lange Department of Horticulture Oregon State University Corvallis OR 97331 USA M. j. Murdock Metabolomics Laboratory Institute of Biological Chemistry Washington State University Pullman WA 99164-6340 USA Department of Biology Hobart and William Smith Colleges Geneva NY 14456 USA Present address: Pacific Northwest National Laboratory Environmental Molecular Sciences Laboratory (EMSL) Richiand WA 99354 USA Present address: Medifluidics Inc. Fort Collins. CO 80525 USA

The genus Mentha encompasses mint species cultivated for their essential oils, which are formulated into a vast array of consumer products. Desirable oil characteristics and resistance to the fungal disease Verti- cillium wilt are top priorities for the mint industry. However, cultivated mints have complex polyploid ge- homes and are sterile. Breeding efforts, therefore, require the development of genomic resources for fertile mint species. Here, we present draft de novo genome and plastome assemblies for a wilt-resistant South African accession of Mentha Iongifolia （L.） Huds., a diploid species ancestral to cultivated peppermint and spearmint. The 353 Mb genome contains 35 597 predicted protein-coding genes, including 292 disease resistance gene homologs, and nine genes determining essential oil characteristics. A genetic linkage map ordered 1397 genome scaffolds on 12 pseudochromosomes. More than two million simple sequence repeats were identified, which will facilitate molecular marker development. The M. Iongifolia genome is a valuable resource for both metabolic engineering and molecular breeding. This is exemplified by employing the genome sequence to clone and functionally characterize the promoters in a peppermint cultivar, and demonstrating the utility of a glandular trichome-specific promoter to increase expression of a biosynthetic gene, thereby modulating essential oil composition.

关键词： aromatic plant essential oil genome mint Verticillium wilt

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Experimental and Modeling Study of Forest Fire Effect on Soil Thermal Conductivity

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Pedosphere 2016年第4期26卷 462-473页

作者： Kathleen M.SMITS Elizabeth KIRBY William j.MASSMAN Larry scott BAGGETT Center for the Experimental Study of Subsurface Environmental Processes Department of Civil and Environmental EngineeringColorado School of Mines USDA Forest Service Rocky Mountain Research Station

An understanding of soil thermal conductivity after a wildfire or controlled burn is important to land management and post-fire recovery efforts. Although soil thermal conductivity has been well studied for non-fire heated soils, comprehensive data that evaluate the long-term effect of extreme heating from a fire on the soil thermal conductivity are limited. The purpose of this study was to evaluate the long-term impact of fire on the effective thermal conductivity of soils by directly comparing fire-heated and no-fire control soils through a series of laboratory studies. The thermal conductivity was measured for ten soil samples from two sites within the Manitou Experimental Forest, Colorado, USA, for a range of water contents from saturation to the residual degree of saturation. The thermal conductivity measured was compared with independent estimates made using three empirical models from literature, including the Campbell et al. （1994）, CSt~ and Konrad （2005）, and Massman et al. （2008） models. Results demonstrate that for the test soils studied, the thermal conductivity of the fire-heated soils was slightly lower than that of the control soils for all observed water contents. Modeling results show that the Campbell et al. （1994） model gave the best agreement over the full range of water contents when proper fitting parameters were employed. Further studies are needed to evaluate the significance of including the influence of fire burn on the thermal properties of soils in modeling studies.

关键词： controlled burn degree of saturation empirical model water content wildfire

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Overcoming Barriers to Uptake of Voluntary Medical Male Circumcision in a Traditionally Circumcising Community in Machinga District, Malawi

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World j.urnal of AIDS 2017年第1期7卷 40-58页

作者： rodney j. Masese j.ne L. Chimango Noel D. Mbirimtengerenj. Community and Mental Health Department Kamuzu College of Nursing University of Malawi Lilongwe Malawi Medical-Surgical Nursing Department Kamuzu College of Nursing University of Malawi Lilongwe Malawi

Introduction: Voluntary medical male circumcision (VMMC) reduces chances of contracting HIV during heterosexual intercourse in males, and risk of cervical cancer in their female sexual partners. However, its uptake among traditionally circumcising communities, where male circumcision carries a cultural significance, has not been studied. Previous research has focused on barriers to uptake of VMMC in non-circumcising communities. This study was conducted to determine socio-cultural barriers to VMMC uptake in order to identify culture-sensitive and evidence-based interventions to increase its uptake. Methodology: This exploratory mixed methods cross-sectional study generated quantitative data from 262 randomly sampled sexually active men;and qualitative data through four focus-group discussions with 58 purposely selected male participants and 10 key informants. Results: The study established that only 6.3% (n = 15) of those circumcised (90.8%, n = 238) were circumcised in clinical setting. Limited access to VMMC services, cost, pain, being attended to by female providers and cultural influences were the maj.r hindrances to uptake of VMMC. Conclusion: Although there is a paradigm shift of preference from traditional male circumcision to VMMC in this community, its uptake is low. The study recommends that besides introducing mobile VMMC services, the Ministry of Health should collaborate with traditional circumcisers and local leaders to provide gender-and-culture-sensitive safer medical male circumcision services.

关键词： VMMC Medical Circumcision Traditional Circumcision Malawi Uptake

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A Comparative Study of Closure Relations for CFD Modelling of Bubbly Flow in a Vertical Pipe

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Open j.urnal of Fluid Dynamics 2021年第2期11卷 98-134页

作者： Geoffrey S. Gray scott j. Ormiston Department of Mechanical Engineering University of Manitoba Winnipeg Canada

Commercial code CFX was used to examine the performance of a two-fluid model to predict the details of upward isothermal bubbly flow of air and water in a vertical pipe. The model equations are volume-averaged Navier-Stokes equations that require closure models for interfacial forces and bubble-induced turbulence effects. Two-equation SST and k-epsilon RANS turbulence models were also used. A parametric study of closure models included both standard options in CFX and previously published novel closure models that were implemented with user-defined functions. The CFD simulations were compared with two cases from the MTLoop experiments by Lucas et al. at the Helmholtz-Zentrum Dresden Rossendorf: one with wall-peak void fraction profile (MT039), and another with a core-peak void fraction profile (MT118). The effect of changing the drag force closures was not significant for the set examined. Poor predictions were found when the lift force and wall lubrication models were incompatible in magnitude. There was no significant effect of changing the liquid phase turbulence model. Changing the bubble-induced turbulence models, however, had a significant impact on the radial void fraction profile. The novel wall force from Lubchenko et al. at the Massachusetts Institute of Technology significantly improved the prediction of the near wall void fraction in the wall peak profile.

关键词： Two-Phase Flow Bubbly Numerical Analysis Vertical Pipe

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