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Mice with a heterozygous Lrp6 deletion have impaired fracture healing

Bone Research 2016年第2期4卷 101-109页

作者： Travis A Burgers juan F Vivanco juraj zahatnansky Andrew j Vander Moren james j mason Bart O Williams Center for Cancer and Cell Biology Program for Skeletal Disease and Tumor Microenvironment Van Andel Research Institute Grand Rapids MhUSA Faculfad de Ingenieria y Ciencias Adolfo Ib6fiez University Vifia del Mar Chile padnos College of Engineering and Computing Grand Valley State University Grand Rapids MI USA

Bone fracture non-unions, the failure of a fracture to heal, occur in 10%-20% of fractures and are a costly and debilitating clinical problem. The Wnt/fl-catenin pathway is critical in bone development and fracture healing. Polymorphisms of linking low-density lipoprotein receptor-related protein 6 （LRP6）, a Wnt-binding receptor, have been associated with decreased bone mineral density and fragility fractures, although this remains controversial. Mice with a homozygous deletion of Lrp6 have severe skeletal abnormalities and are not viable, whereas mice with a heterozygous deletion have a combinatory effect with Lrp5 to decrease bone mineral density. As fracture healing closely models embryonic skeletal development, we investigated the process of fracture healing in mice heterozygous for Lrp6 （Lrp6~/-） and hypothesized that the heterozygous deletion of Lrp6 would impair fracture healing. Mid-diaphyseal femur fractures were induced in Lrp6~^- mice and wild-type controls （Lrp6~/~）. Fractures were analyzed using micro-computed tomography （~CT） scans, biomechanical testing, and histological analysis. Lrp6~/- mice had significantly decreased stiffness and strength at 28 days post fracture （PF） and significantly decreased BV/TV, total density, immature bone density, and mature area within the callus on day-14 and -21 PF; they had significantly increased empty callus area at days 14 and 21 PF. Our results demonstrate that the heterozygous deletion of Lrp6 impairs fracture healing, which suggests that Lrp6 has a role in fracture healing.

关键词： bone Mice with a heterozygous Lrp6 deletion have impaired fracture healing

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Evolving landscape and novel treatments in, metastatic castrate-resistant prostate cancer

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Asian journal of Andrology 2013年第3期15卷 342-349页

作者： paul j Toren Martin E Gleave Department of Urologic Sciences Faculty of Medicine University of British Columbia Vancouver BC V5Z 1M9 Canada

Treatment options for castrate-resistant prostate cancer （CRPC） have advanced in recent years and significantly improved the Outlook for patients with this aggressive and lethal disease. Further understanding of the biology＇of CRPC has led to several new targeted therapies and continues to emphasize the importance of androgen receptor （AR） directed therapy. The treatment landscape is rapidly changing and further biologically rationale, biomarker-based ongoing clinical trials are needed. We review the recent results of major clinical trials in CRPC. New and investigational agents now in clinical evaluation are reviewed including inhibitors of angiogenesis, microtubules, chaperones, AR and intracellular kinases, as well as immunotherapy, radiopharmaceuticals and bone-targeted agents. The recent improvement in prognosis for CRPC brings continued optimism for further improvements. Thoughtful planning of clinical trials and further understanding of the mechanisms of resistance to therapies will allow for continued progress in patient care.

关键词： prostate cancer treatment resistance androgen receptor antagonists molecular targets

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Numerical Simulation of Heat Transfer in Rectangular Microchannel

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Advances in Applied Mathematics and Mechanics 2009年第2期1卷 231-241页

作者： jun Yao Yufeng Yao Peter j.mason Mayur K.Patel Faculty of Engineering Kingston University104 Friars AvenueRoehampton ValeLondon SW153DWUnited Kingdom School of Computing and Mathematical Sciences University of Greenwich30 Park RowGreenwichLondon SE109LSUnited Kingdom

Numerical simulation of heat transfer in a high aspect ratio rectangular microchannel with heat sinks has been conducted,similar to an experimental *** channel heights measuring 0.3 mm,0.6 mm and 1 mm are considered and the Reynolds number varies from 300 to 2360,based on the hydraulic ***ulation starts with the validation study on the Nusselt number and the Poiseuille number variations along the channel streamwise *** is found that the predicted Nusselt number has shown very good agreement with the theoretical estimation,but some discrepancies are noted in the Poiseuille number *** observation however is in consistent with conclusions made by other researchers for the same flow *** continues on the evaluation of heat transfer characteristics,namely the friction factor and the thermal *** is found that noticeable scaling effect happens at small channel height of 0.3 mm and the predicted friction factor agrees fairly well with an experimental based *** simulation further reveals that the thermal resistance is low at small channel height,indicating that the heat transfer performance can be enhanced with the decrease of the channel height.

关键词： Computational fluid dynamics rectangular microchannel scaling effect thermal resistance

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Surface engineering with ionic polymers on membranes for boron removal

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Frontiers of Chemical Science and Engineering 2024年第5期18卷 61-69页

作者： Xiting Zhang Chenyi Fang j paul Chen Sui Zhang Department of Chemical and Biomolecular Engineering National University of SingaporeSingapore 117576Singapore Department of Civil and Environmental Engineering National University of SingaporeSingapore 119260Singapore College of Chemistry and Environmental Engineering Shenzhen UniversityShenzhen 518060China

Removal of boric acid from seawater and wastewater using reverse osmosis membrane technologies is imperative and yet remains inadequately addressed by current commercial *** research efforts performed post-modification of reverse osmosis membranes to enhance boron rejection,which is usually accompanied by substantial sacrifice in water *** study delves into the surface engineering of low-pressure reverse osmosis membranes,aiming to elevate boron removal efficiency while maintaining optimal salt rejection and water *** were modified by the self-polymerization and co-deposition of dopamine and polystyrene sulfonate at varying ratios and *** surfaces became smoother and more hydrophilic after *** optimum membrane exhibited a water permeability of 9.2±0.1 L·m^(-2)·h^(-1)·bar^(-1),NaCl rejection of 95.8%±0.3%,and boron rejection of 49.7%±0.1% and 99.6%±0.3% at neutral and alkaline pH,*** water permeability is reduced by less than 15%,while the boron rejection is 3.7 times higher compared to the blank *** research provides a promising avenue for enhancing boron removal in reverse osmosis membranes and addressing water quality concerns in the desalination process.

关键词： membrane low-pressure reverse osmosis boron surface engineering

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Hyponatremia in cirrhosis:Pathophysiology and management

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World journal of Gastroenterology 2015年第11期21卷 3197-3205页

作者： Savio john paul j Thuluvath Division of Gastroenterology Department of MedicineSUNY Upstate Medical University University of Maryland School of Medicine and Mercy Medical Center

Hyponatremia is frequently seen in patients with ascites secondary to advanced cirrhosis and portal *** development of ascites in patients with cirrhosis is *** hypertension and the associated systemic vasodilation lead to activation of the sodium-retaining neurohumoral mechanisms which include the renin-angiotensin-aldosterone system,sympathetic nervous system and antidiuretic hormone(ADH).The net effect is the avid retention of sodium and water to compensate for the low effective circulatory volume resulting in the development of *** not apparent in the early stages of cirrhosis,the progression of cirrhosis and ascites leads to impairment of the kidneys to eliminate solutefree *** leads to additional compensatory mechanisms including non-osmotic secretion of ADH,also known as arginine vasopressin,further worsening excess water retention and thereby *** is associated with increased morbidity and mortality in patients with cirrhosis,and is an important prognostic marker both before and after liver *** management of hyponatremia in this setting is a challenge as conventional therapy for hyponatremia including fluid restriction and loop diuretics are frequently *** this review,we discuss the pathophysiology and various treatment modalities,including selective vasopressin receptor antagonists,for the management of hyponatremia in patients with cirrhosis.

关键词： Hyponatremia in cirrhosis Dilutional hypo-natremia

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Utility of droplet digital polymerase chain reaction for studying somatic mosaicism:brain malformations and beyond

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Neural Regeneration Research 2023年第11期18卷 2389-2390页

作者： Wei Shern Lee paul j.Lockhart Bruce Lefroy Centre Murdoch Children’s Research InstituteParkvilleVICAustralia Department of Paediatrics The University of MelbourneParkvilleVICAustralia

Somatic variants and how to find them:One major challenge in studying somatic mosaicism is the low abundance of potentially pathogenic somatic variant(s).Unlike inherited germline variants,which are essentially present in all cells,pathogenic somatic variants only exist in a subset of cells and may be present at very low (<1%)variant allele frequency (VAF).Despite the low VAF,these somatic variants are disease-relevant and considered *** the context of focal brain malformations,which constitute a frequent cause of drug-resistant focal epilepsy,a pathogenic somatic mammalian ta rget of rapamycin (MTOR)variant with a VAF of 0.3%has been described(Baldassari et al.,2019).The identification of pathogenic somatic variants has importa nt implications both clinically and biologically.

关键词： epilepsy beyond

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Three-dimensional simulation of liquid injection,film formation and transport,in fluidized beds

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Particuology 2009年第5期7卷 337-346页

作者： paul Zhao Peter j. O'Rourke Dale Snider CPFD Software LLCAlbuquerqueNM 87111USA CFD d'OR Software and Consulting LLCLos AlamosNM 87544USA

Liquid injection, and film formation and transport in dense-phase gas-solids fluidized beds are numerically simulated in three dimensions using a collisional exchange model that is based on the mechanism that collisions cause transfer of liquid mass, momentum, and energy between particles. In the model, each of the particles is represented by a solid core and a liquid film surrounding the core. The model is incorporated in the framework of the commercial code Barracuda developed by CPFD Software. The commercial software is an advanced CFD-based computational tool where the particles are treated as discrete entities, calculated by the MP-PIC method, and tracked using the Lagrangian method. Details of the collisional liquid transfer model have been previously presented in O＇Rourke, Zhao, and Snider （2009）; this paper presents new capabilities and proof-testing of the collision model and a new method to better quantify the penetration length. Example calculations of a fluidized bed without liquid injection show the expected effect of collisions on the reduction of granular temperature （fluctuational kinetic energy） of the bed. When applied to liquid injection into a dense-phase fluidized bed under different conditions, the model predicts liquid penetration lengths comparable to the experiments. In addition, the simulation reveals for the first time the dynamic mixing of the liquid droplets with the bed particles and the transient distribution of the droplets inside the bed.

关键词： MP-PIC Liquid injection Fluidized bed Particle collisions CPFD jet penetration

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Preserving the past or past preserving: sustaining the legacy of postmodern museum architecture

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Built Heritage 2022年第2期6卷 24-42页

作者： paul j.Armstrong paul H.Kapp Illinois School of Architecture University of Illinois at Urbana-Champaign117 Buell Hall611 Taft DriveChampaignIL 61820USA

The publication of Complexity and Contradiction in Architecture in 1964 signaled the end of *** reality was that the modern movement had already jettisoned its ideological underpinnings and had become merely another‘style.’The avant garde architects in Europe and in North America were ready to move on and saw Postmodernism as a liberating antidote to the strictures of high *** architectural styles,which had been vilified as antiquated and out of step with modern culture,were revived,reinterpreted,and ***,Postmodernism,which had burned brightly during the 1970s and 1980s,was superseded by other architectural movements,namely,Deconstructivism,Pluralism,during the waning years of the 12th *** though new building forms and design theory changed during Postmodernism,building technology remained the *** walls continued to be built as skins,comprised of either glass,masonry,metal,or synthetic cladding,which were hung of steel or concrete *** membranes covered essentially flat *** infiltration was managed in ever complex composite wall *** important,environmental systems decoupled nature from interiors and were designed to manage ever demanding humidity control *** the development of new building technology,Modernism severed design style from traditional *** re-introducing historical forms back into architecture,Postmodernism complicated ***,Postmodernism and its successors rarely developed new technological ideas by introducing more intricate building forms,which were based on theoretical ideas rather than technical ones,while continuing to employ Modernism building technology into their *** inherent paradox is the most consequential challenge in preserving ***,approximately 40 years after its inception,we must consider if,in some *** it tenable to preserve Postmodern buildings?This paper reasse

关键词： Postmodernism Modern movement Preservation Museums Materials Technology Moisture Memory Adaptation

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Stagnant lid tectonics:Perspectives from silicate planets,dwarf planets, large moons,and large asteroids

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Geoscience Frontiers 2018年第1期9卷 103-119页

作者： Robert j.Stern Taras Gerya paul j.Tackley Geosciences Department University of Texas at Dallas Department of Earth Sciences ETH-Zurich

To better understand Earth's present tectonic style-plate tectonics—and how it may have evolved from single plate(stagnant lid) tectonics, it is instructive to consider how common it is among similar bodies in the Solar System. Plate tectonics is a style of convection for an active planetoid where lid fragment(plate) motions reflect sinking of dense lithosphere in subduction zones, causing upwelling of asthenosphere at divergent plate boundaries and accompanied by focused upwellings, or mantle plumes;any other tectonic style is usefully called "stagnant lid" or "fragmented lid". In 2015 humanity completed a 50+ year effort to survey the 30 largest planets, asteroids, satellites, and inner Kuiper Belt objects,which we informally call "planetoids" and use especially images of these bodies to infer their tectonic activity. The four largest planetoids are enveloped in gas and ice(jupiter, Saturn, Uranus, and Neptune)and are not considered. The other 26 planetoids range in mass over 5 orders of magnitude and in diameter over 2 orders of magnitude, from massive Earth down to tiny Proteus; these bodies also range widely in density, from 1000 to 5500 kg/m^3. A gap separates 8 silicate planetoids with ρ = 3000 kg/m^3 or greater from 20 icy planetoids(including the gaseous and icy giant planets) with ρ = 2200 kg/m^3 or less. We define the "Tectonic Activity Index"(TAI), scoring each body from 0 to 3 based on evidence for recent volcanism, deformation, and resurfacing(inferred from impact crater density). Nine planetoids with TAI = 2 or greater are interpreted to be tectonically and convectively active whereas 17 with TAI <2 are inferred to be tectonically dead. We further infer that active planetoids have lithospheres or icy shells overlying asthenosphere or water/weak ice. TAI of silicate(rocky) planetoids positively correlates with their inferred Rayleigh number. We conclude that some type of stagnant lid tectonics is the dominant mode of heat loss and that plate tectonics

关键词： Stagnant lid Solar system Plate tectonics Planets Moons

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Clinical, cellular, microscopic, and ultrastructural studies of a case of fibrogenesis imperfecta ossium

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Bone Research 2017年第2期5卷 123-136页

作者： Melissa L Barron Mark S Rybchyn Sutharshani Ramesh Rebecca S mason S Fiona Bonar paul Stalley Sundeep Khosla Bernie Hudson Christopher Arthur Edward Kim Roderick j Clifton-Bligh Phillip B Clifton-Bligh Department of Physiology School of Medical Sciences Bosch Institute University of Sydney Sydney 2006 New South Wales Australia Douglas HanlyMoir Pathology Macquarie Park 2113 New South Wales Australia Department of Orthopaedics Royal Prince Alfred HospitalCamperdown 2050 New South Wales Australia Department of Endocrinology Mayo Clinic Rochester 55905 MN USA Department of Microbiology Royal North Shore Hospital St Leonards 2065 New South Wales Australia Department ofMicrobiology Royal North Shore Hospital St Leonards 2065 New South Wales Australia Department of Haematology Royal North Shore Hospital St Leonards 2065 New South Wales Australia Department of Endocrinology Royal North Shore Hospital St Leonards 2065 New SouthWales Australia and Faculty of Medicine University of Sydney Sydney 2006 New South Wales Australia

Fibrogenesis imperfecta ossium is a rare disorder of bone usually characterized by marked osteopenia and associated with variable osteoporosis and osteosclerosis, changing over time. Histological examination shows that newly formed collagen is abnormal, lacking birefringence when examined by polarized light. The case presented demonstrates these features and, in addition, a previously undocumented finding of a persistent marked reduction of the serum C3 and C4. Osteoblasts established in culture from a bone biopsy showed abnormal morphology on electron microscopy and increased proliferation when cultured with benzoylbenzoyl-ATP and 1,25-dihydroxyvitamin D, contrasting with findings in normal osteoblasts in culture. A gene microarray study showed marked upregulation of the messenger RNA(mRNA) for G-protein-coupled receptor 128(GPR 128), an orphan receptor of unknown function and also of osteoprotegerin in the patient's osteoblasts in culture. When normal osteoblasts were cultured with the patient's serum, there was marked upregulation of the mRNA for aquaporin 1. A single pathogenetic factor to account for the features of this disorder has not been defined, but the unique findings described here may facilitate more definitive investigation of the abnormal bone cell function.

关键词： ultrastructural cellular Clinical

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