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NOTUm inhibition increases endocortical bone formation and bone strength

Bone Research 2019年第1期7卷 54-65页

作者： Robert Brommage Jeff Liu Peter Voge Faika mseeh Andrea Y.Thompson David G.Potter melanie K.Shadoan gwenn m.hansen Sabrina Jeter-Jones Jie Cui Dawn Bright Jennifer P.Bardenhagen Deon D.Doree Sofia moverare-Skrtic Karin H.Nilsson Petra Henning Ulf H.Lerner Claes Ohlsson Arthur T.Sands James E.Tarver David R.Powell Brian Zambrowicz Qingyun Liu Lexicon Pharmaceuticals The WoodlandsTXUSA Wntrix HoustonTXUSA PRA Health Sciences RaleighNCUSA University of Pennsylvania PhiladelphiaPAUSA Regeneron Pharmaceuticals TarrytownNYUSA University of Texas HoustonTXUSA Centre for Bone and Arthritis Research Institute of MedicineThe Sahlgrenska Academy at University of GothenburgGothenburgSweden Centre for Bone and Arthritis Research University of GothenburgGothenburgSweden Biogen CambridgeMAUSA St.Jude Children’s Research Hospital MemphisTNUSA mD Anderson Cancer Center HoustonTXUSA Bethyl Laboratories MontgomeryTXUSA merck RahwayNJUSA Nurix San FranciscoCAUSA

The disability,mortality and costs caused by non-vertebral osteoporotic fractures are *** osteoporosis therapies are highly effective at reducing vertebral but not non-vertebral *** bone is a major determinant of non-vertebral bone *** identify novel osteoporosis drug targets,we phenotyped cortical bone of 3 366 viable mouse strains with global knockouts of druggable *** bone thickness was substantially elevated in Notum?/?*** is a secreted WNT lipase and we observed high NOTUm expression in cortical bone and osteoblasts but not *** orally active small molecules and a neutralizing antibody inhibiting NOTUm lipase activity were *** increased cortical bone thickness and strength at multiple skeletal sites in both gonadal intact and ovariectomized rodents by stimulating endocortical bone ***,inhibition of NOTUm activity is a potential novel anabolic therapy for strengthening cortical bone and preventing non-vertebral fractures.

关键词： disability osteoporosis fractures

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Effects of Aronia polyphenols on the physico-chemical properties of whey,soy,and pea protein isolate dispersions

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Food Production, Processing and Nutrition 2021年第1期3卷 391-405页

作者： mackenzie m.hansen Richard W.Hartel Yrjö H.Roos Food Technology School of Food and Nutritional SciencesUniversity College CorkCorkIreland Department of Food Science College of Agricultural and Life SciencesUniversity of WisconsinOffice A11Babcock Hall1605 Linden DriveMadisonWI 53706USA

Bioactive compounds including polyphenols(PP)have been observed to naturally form non-covalent complexation interactions with proteins under mild pH and temperature conditions,affecting protein structures and ***,addition of Aronia berry PP to liquid dispersions containing whey protein isolate(WPI)and sucrose was found to alter characteristics including viscosity,surface tension,and particle sizes,with changes being attributed to protein-PP *** this study we aimed to investigate whether Aronia PP would interact with soy and pea protein isolates(SPI and PPI,respectively)to a similar extent as with WPI in liquid protein-sucrose-PP *** hypothesized that formulations containing PPI(comprised of larger proteins)and hydrolyzed SPI(containing more carboxyl groups)may exhibit increased viscosities and decreased aggregate sizes due to enhanced protein-PP *** liquid dispersions of varied ratios of protein to sucrose contents,containing different protein isolates(WPI,SPI,and PPI),and varied Aronia PP concentrations were formulated,and physical properties were evaluated to elucidate the effects of PP *** addition altered physical characteristics differently depending on the protein isolate used,with changes attributed to protein-PP *** and PPI appeared to have higher propensities for PP interactions and exhibited more extensive shifts in physical properties than WPI *** findings may be useful for practical applications such as formulating products containing fruit and proteins to obtain desirable sensory attributes.

关键词： Whey protein Soy protein Pea protein Polyphenols Concentrated dispersions Physico-chemical properties

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Bioactives and extracts affect the physico-chemical properties of concentrated whey protein isolate dispersions

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Food Production, Processing and Nutrition 2022年第1期4卷 25-40页

作者： mackenzie m.hansen Richard W.Hartel YrjöH.Roos Food Technology School of Food and Nutritional SciencesUniversity College CorkCorkIreland Department of Food Science College of Agricultural and Life SciencesUniversity of WisconsinOffice A11Babcock Hall1605 Linden DriveMadisonWI53706USA

Non-covalent complexation interactions are known to occur between bioactive compounds and proteins. While formulating with these components can have positive outcomes such as stabilization of colors and actives, it can also result in changes to the structures and physical properties of proteins, affecting product functionality and sensory attributes. Previous experiments reported measurable changes in the physico-chemical properties of whey protein isolate (WPI) dispersions upon formulation with Aronia berry extract, ascribing changes to protein-polyphenol (PP) interactions in the systems. Pure gallotannin, beet extract, and cranberry extract, providing a diverse variety structures and sizes, were selected for further experimentation and comparison with the effects of Aronia extract. Concentrated dispersions with varying WPI:sucrose ratios, formulated with several bioactives contents from multiple different sources were analyzed to identify the effects of different bioactives on physico-chemical properties of dispersions. Dispersions formulated with cranberry extract demonstrated the largest increases in surface tensions, viscosities, and particle sizes, while those formulated with beet extract were the least affected by the presence of bioactives, suggesting that different bioactives and extracts had varying propensities for complexation interactions with WPI, despite their relatively low levels of addition (0, 0.5, and 1%).

关键词： Whey protein Concentrated dispersions Polyphenols Extracts Physico-chemical properties

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High-throughput screening of mouse gene knockouts identifies established and novel skeletal phenotypes

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Bone Research 2014年第3期2卷 152-181页

作者： Robert Brommage Jeff Liu gwenn m.hansen Laura L Kirkpatrick David G Potter Arthur T Ss Brian Zambrowicz David R Powell Peter Vogel Lexicon Pharmaceuticals The Woodlands TX USA

Screening gene function in vivo is a powerful approach to discover novel drug targets. We present high-throughput screening （HTS） data for 3 762 distinct global gene knockout （KO） mouse lines with viable adult homozygous mice generated using either gene-trap or homologous recombination technologies. Bone mass was determined from DEXA scans of male and female mice at 14 weeks of age and by microCT analyses of bones from male mice at 16 weeks of age. Wild-type （WT） cagemates/littermates were examined for each gene KO. Lethality was observed in an additional 850 KO lines. Since primary HTS are susceptible to false positive findings, additional cohorts of mice from KO lines with intriguing HTS bone data were examined. Aging, ovariectomy, histomorphometry and bone strength studies were performed and possible non-skeletal phenotypes were explored. Together, these screens identified multiple genes affecting bone mass： 23 previously reported genes （Calcr, Cebpb, Crtap, Dcstamp, Dkkl, Duoxa2, Enppl, Fgf23, Kissl/Kisslr, Kl （Klotho）, Lrp5, mstn, Neol, Npr2, Ostml, Postn, Sfrp4, S1c30a5, Sic39a13, Sost, Sumf1, Src, Wnt10b）, five novel genes extensively characterized （Cldn18, Fam20c, Lrrkl, Sgpll, Wnt16）, five novel genes with preliminary characterization （Agpat2, RassfS, Slc10a7, Stc26a7, Slc30a10） and three novel undisclosed genes coding for potential osteoporosis drug targets.

关键词： KO High-throughput screening of mouse gene knockouts identifies established and novel skeletal phenotypes BmD HTS DEXA gene

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Delivery of inert gas through a vertical borehole using inert gas generator: A theoretical study

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International Journal of mining Science and Technology 2020年第4期30卷 501-510页

作者： Rickard hansen Sustainable minerals Institute The University of QueenslandBrisbaneQueensland 4072Australia

The delivery of the inert gas through a vertical borehole using inert gas generator or IGG is *** limitations and/or transient effects are *** the analysis,the borehole diameter,borehole length,type of borehole and partial condensation prior to entering the borehole were varied.A choked flow will occur for a contraction exit or borehole of 0.3 m in diameter if no condensation prior to the contraction *** partial condensation takes place,a borehole diameter of 0.3 m will be possible if almost 50%of the water vapour ***,pressure losses along boreholes with a diameter of 0.3 or 0.4 m are significant and could pose a challenge if trying to mitigate the pressure *** a booster fan prior to the inlet of the 0.4 m lined borehole would still be a *** corresponding case with a 0.5 m borehole presents much more favourable pressure *** 0.5 m diameter lined borehole should be regarded as the lower *** rapid heating of the unlined borehole surface will increase the risk of thermal spallation and possibly imposing *** the mechanisms during gas delivery will increase the likelihood of a successful inertisation.

关键词： GAG Inert gas Condensation Pressure loss Choked flow Gas velocity Borehole Heat transfer

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Wear dependent virtual flow rate sensor for progressing cavity pumps with deformable stator

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Petroleum Science 2024年第2期21卷 1346-1353页

作者： Jens müller Sebastian Leonow Johannes Schulz Christian hansen martin monnigmann Ruhr-Universitat Bochum Universit atsstraûe 150Bochum44801Germany SEEPEX GmbH Scharnh olzstraûe 344Bottrop46240Germany

This contribution presents a novel wear dependent virtual flow rate sensor for single stage single lobe progressing cavity pumps. We study the wear-induced material loss of the pump components and the impact of this material loss on the volumetric efficiency. The results are combined with an established backflow model to implement a backflow calculation procedure that is adaptive to wear. We use a laboratory test setup with a highly abrasive fluid and operate a pump from new to worn condition to validate our approach. The obtained measurement data show that the presented virtual sensor is capable of calculating the flow rate of a pump being subject to wear during its regular operation.

关键词： Backflow Progressing cavity pump Virtual sensor Wear

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An update on hearing impairment in patients with rheumatoid arthritis

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Journal of Otology 2018年第1期13卷 1-4页

作者： A.Emamifar I.m.J.hansen Department of medicine Odense University Hospital Svendborg Hospital Svendborg Denmark Faculty of Health Sciences University of Southern Denmark Odense Denmark Section of Rheumatology Department of Medicine Odense University Hospital Svendborg Hospital Svendborg Denmark

Rheumatoid arthritis(RA) is a systemic, autoimmune disease that present with intra-articular and extra-articular manifestations. Auditory system may be involved during the course of RA disease due to numbers of pathologies. The link between hearing impairment and RA has been discussed in the previous literature. In this study we provide an update on the clinical aspect of hearing impairment in RA. We suggest to test hearing in all newly diagnosed RA patients at diagnosis as well as regularly during the course of disease.

关键词： Rheumatoid arthritis Hearing loss Hearing impairment Audiometry

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Are monitoring and evaluation systems adequate to report the programmatic coverage of HIV services among key populations in countries?

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Infectious Diseases of Poverty 2019年第4期8卷 75-81页

作者： Jinkou Zhao Sonia Arias Garcia Ed Ngoksin Jesus maria Garcia Calleja Chinelo Ogbuanu Sandra Kuzmanovska Nicholas Oliphant David Lowrance Nathalie Zorzi Peter m.hansen Keith Sabin The Global Fund to fight AIDS Tuberculosis and MalariaChemin du Pommier 40Grand-Saconnex 1218GenevaSwitzerland Center for Global Health School of Public HealthNanjing Medical UniversityNanjingChina Jiangsu Provincial Center for Disease Control and Prevention NanjingChina Strateg ic Information and Evaluation Department the Joint United Nations Programme on HIV/AIDSGenevaSwitzerland Department of HIV/AIDS World Health OrganizationGenevaSwitzerland

There was no global guidance or agreement regarding when a country has an adequate system to report on the service packages among human immunodeficiency virus(HIV)key *** article describes an approach to categorizing the system in a country for reporting the service package among HIV key *** approach consists of four dimensions,namely the epidemiological significance,comprehensiveness of the service packages,geographic coverage of services,and adequacy of the monitoring *** proposed categorization approach utilizes available information and can inform the improvement of the service delivery and monitoring systems among HIV key populations.

关键词： services among service

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Cigarette smoke-induced cell cycle arrest in spermatocytes [GC-2spd(ts)] is mediated through crosstalk between Ahr–Nrf2 pathway and mAPK signaling

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Journal of molecular Cell Biology 2015年第1期7卷 73-87页

作者： Prabagaran Esakky Deborah A.hansen Andrea m.Drury Kelle H.moley Research Department of Veterans Affairs Medical CenterSt.LouisMO 63106USA Department of Obstetrics and Gynecology Washington University School of MedicineSt.LouisMO 63110USA

Our earlier studies have demonstrated that the cigarette smoke in the form of cigarette smoke condensate(CSC)causes growth arrest of a mouse spermatocyte cell line[GC-2spd(ts)]through activation of the AHR–NRF2 *** present study demonstrates the CSC-activated p38 and ERK mAPK signaling in GC-2spd(ts)via arylhydrocarbon receptor(AHR).Pharmacological inhibition by using AHR-antagonist,or p38 mAPK and ERK(mEK1)inhibitors significantly abrogates CSC-induced growth arrest by AHR and mAPK ***-PCR,western blot,and immunofluorescence of Ahr-target of Nrf2,and stress-inducible growth suppressive Atf3 and E2f4 following treatments indicate a crosstalk among these *** of Atf3 by Nrf2 and Ahr through RNA interference suggests the existence of a cross-regulatory loop between the *** induction of E2f4 via Atf3 and its regulation by pharmacological inhibitors reveal a possible regulatory mechanism of growth inhibitory *** silencing of Ahr,Nrf2,Atf3,and E2f4 genes and downregulation of cyclins by CSC corroborate the growth inhibitory effect of cigarette ***,the data obtained suggest that the CSC-mediated mAPKs and AHR–NRF2 crosstalks lay the molecular basis for the growth arrest and cell death of spermatocytes.

关键词： spermatocytes Ahr Nrf2 CSC ATF3 E2F4 p38 mAPK and ERK

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Interferon-γ inhibits ghrelin expression and secretion via a somatostatin-mediated mechanism

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World Journal of Gastroenterology 2011年第26期17卷 3117-3125页

作者： Jesper AB Strickertsson Kristina BV DΦssing Anna Jm Aabakke Hans-Olof Nilsson Thomas VO hansen Ulrich Knigge Andreas Kjr Torkel Wadstrm Lennart Friis-hansen Genomic medicine Department of Clinical BiochemistryRigshospitaletUniversity of Copenhagen Department of Basic Animal and Veterinary Sciences Faculty of Life SciencesUniversity of Copenhagen Department of microbiology University of Lund Department of Gastro-Intestinal Surgery RigshospitaletUniversity of Copenhagen Department of Clinical Physiology RigshospitaletUniversity of Copenhagen

AIm- To investigate if and how the proinflammatory cytokine interferon γ （IFNγ） affects ghrelin expression in mice. mETHODS： The plasma concentration of ghrelin, and gastric ghrelin and somatostatin expression, were ex- amined in wild-type mice and mice infected with Helico- bacter pylori （H. pylorO. Furthermore, ghrelin expression was examined in two achlorhydric mouse models with varying degrees of gastritis due to bacterial overgrowth. To study the effect of IFNγ, alone, mice were given a subcutaneous infusion of IFNγ, for 7 d. Finally, the influ- ence of IFNγ, and somatostatin on the ghrelin promoter was characterized. RESULTS： H. py/ori infection was associated with a 50% reduction in ghrelin expression and plasma concentration. Suppression of ghrelin expression was in- versely correlated with gastric inflammation in achlorh- dyric mouse models. Subcutaneous infusion of IFNγ, suppressed fundic ghrelin mRNA expression and plasma ghrelin concentrations. Finally, we showed that the ghrelin promoter operates under the control of soma- tostatin but not under that of IFNγ. CONCLUSION： Gastric infection and inflammation is associated with increased IFNγ, expression and reduced ghrelin expression. IFNγ, does not directly control ghre- lin expression but inhibits it indirectly via somatostatin.

关键词： Ghrelin Interferon-γ Somatostatin Inflam-matory diseases He/icobacterpy/ori

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