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Notch signaling controls chondrocyte hypertrophy via indirect regulation of Sox9

Bone Research 2015年第3期3卷 140-151页

作者： Anat Kohn timothy p rutkowski Zhaoyang Liu Anthony J Mirando Michael J Zuscik Regis J O'Keefe Matthew J Hilton Department of Orthopaedics and Rehabilitation The Center for Musculoskeletal Research University of Rochester Medical Center Department of Biomedical Genetics University of Rochester Medical Center Department of Biology University of Rochester Department of Orthopaedic Surgery Duke Orthopaedic Cellular Developmental and Genome Laboratories Duke University School of Medicine Department of Orthopaedic Surgery Washington University School of Medicine

RBpjk-dependent Notch signaling regulates both the onset of chondrocyte hypertrophy and the progression to terminal chondrocyte maturation during endochondral ossification. It has been suggested that Notch signaling can regulate Sox9 transcription, although how this occurs at the molecular level in chondrocytes and whether this transcriptional regulation mediates Notch control of chondrocyte hypertrophy and cartilage development is unknown or controversial. Here we have provided conclusive genetic evidence linking RBpjk-dependent Notch signaling to the regulation of Sox9 expression and chondrocyte hypertrophy by examining tissuespecific Rbpjk mutant（prx1Cre;Rbpjkf/f）, Rbpjk mutant/Sox9 haploinsufficient（prx1Cre;Rbpjkf/f;Sox9f/1）,and control embryos for alterations in SOX9 expression and chondrocyte hypertrophy during cartilage development. These studies demonstrate that Notch signaling regulates the onset of chondrocyte maturation in a SOX9-dependent manner, while Notch-mediated regulation of terminal chondrocyte maturation likely functions independently of SOX9. Furthermore, our in vitro molecular analyses of the Sox9 promoter and Notch-mediated regulation of Sox9 gene expression in chondrogenic cells identified the ability of Notch to induce Sox9 expression directly in the acute setting, but suppresses Sox9 transcription with prolonged Notch signaling that requires protein synthesis of secondary effectors.

关键词： Figure Notch signaling controls chondrocyte hypertrophy via indirect regulation of Sox9 NICD SOX

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Tale of mitochondria and mitochondria-associated ER membrane in patient-derived neuronal models of Wolfram syndrome

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Neural Regeneration Research 2025年第9期20卷 2587-2588页

作者： Laetitia Aubry timothy Barrett Sovan Sarkar I-STEM CECSCorbeil-EssonnesFrance Universitéparis-Saclay Universitéd’EvryINSERMI-STEMUMR861Corbeil-EssonnesFrance Institute of Cancer and Genomic Sciences Institute of Biomedical ResearchCollege of Medical and Dental SciencesUniversity of BirminghamEdgbastonBirminghamUK Department of Endocrinology Birmingham Women’s and Children’s HospitalSteelhouse LaneBirminghamUK

Mitochondria and mitochondria-associated endoplasmic reticulum membrane in neurodegenerative diseases:Mitochondria generate most of the chemical energy needed to power the biochemical reactions of cells,and thus are often referred to as the"powerhouse"of the ***,this organelle is also involved in a pleth,ora of different cellular functions such as calcium(Ca^(2+))homeostasis,apoptosis,oxidative stress,and several metabolic pathways including oxidative phosphorylation,tricarboxylic acid cycle,andβ-oxidation of fatty acids.

关键词： oxidative cycle carboxylic

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An Introduction to 2-CCD Digital particle Image Velocimetry System and Its Application in Ocean Engineering

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China Ocean Engineering 1997年第3期12卷 347-356页

作者： Daichin timothy p.Dewhirst ph.D.Candidate State Key Laboratory of Coastal and Offshore EngineeringDalian University of Technology(DUT)Dalian 116023Ph.D.CandidateDepartment of PhysicsUniversity of EdinburghEdinburghUK.

The basic principle of particle image velocinmetry (pIV) is described. When a pIV image is analyzed by the method of auto-correlation, there is a direction ambiguity of 180 degrees iii velocity measurement. The problem can be solved by using 'Image Shifting Technique', but this makes devices much complicated and difficult to control. A new arrangement of 2-CCD (Charge Coupled Device) fully digitized pIV system, which can also solve the problem successfully, is introduced in the paper. As an example of application of the system, an experimental result of flow field around a horizontal cylinder in wave is presented.

关键词： particle image velocimetry CCD camera cross-correlation

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Simplified seismic performance assessment and implications for seismic design

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Earthquake Engineering and Engineering Vibration 2014年第S1期13卷 95-122页

作者： timothy J.Sullivan David p.Welch Gian Michele Calvi University of pavia Department of Civil Engineering & ArchitecturePavia 27100Italy European Centre for Training and Research in Earthquake Engineering Pavia 27100Italy UME School ROSE ProgrammeIUSS Pavia phD candidate IUSS pavia professor

The last decade or so has seen the development of refined performance-based earthquake engineering(pBEE) approaches that now provide a framework for estimation of a range of important decision variables,such as repair costs,repair time and number of casualties. This paper reviews current tools for pBEE,including the pACT software,and examines the possibility of extending the innovative displacement-based assessment approach as a simplified structural analysis option for performance assessment. Details of the displacement-based s+eismic assessment method are reviewed and a simple means of quickly assessing multiple hazard levels is proposed. Furthermore,proposals for a simple definition of collapse fragility and relations between equivalent single-degree-of-freedom characteristics and multi-degree-of-freedom story drift and floor acceleration demands are discussed,highlighting needs for future research. To illustrate the potential of the methodology,performance measures obtained from the simplified method are compared with those computed using the results of incremental dynamic analyses within the pEER performance-based earthquake engineering framework,applied to a benchmark building. The comparison illustrates that the simplified method could be a very effective conceptual seismic design tool. The advantages and disadvantages of the simplified approach are discussed and potential implications of advanced seismic performance assessments for conceptual seismic design are highlighted through examination of different case study scenarios including different structural configurations.

关键词： performance-based earthquake engineering displacement-based assessment seismic assessment

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Are hyoliths palaeozoic lophophorates?

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National Science Review 2020年第2期7卷 453-469页

作者： Fan Liu Christian B Skovsted timothy p Topper Zhifei Zhang Degan Shu State Key Laboratory of Continental Dynamics Shaanxi Key Laboratory of Early Life and Environments Department of Geology Northwest University Department of palaeobiology Swedish Museum of Natural History

The phylogenetic position of hyoliths has long been unsettled, with recent discoveries of a tentaculate feeding apparatus(‘lophophore’) and fleshy apical extensions from the shell(‘pedicle’) suggesting a lophophorate affinity. Here, we describe the first soft parts associated with the feeding apparatus of an orthothecid hyolith, Triplicatella opimus from the Chengjiang biota of South China. The tuft-like arrangement of the tentacles of T. opimus differs from that of hyolithids, suggesting they collected food directly from the substrate. A reassessment of the feeding organ in hyolithids indicates that it does not represent a lophophore and our analysis of the apical structures associated with some orthothecids show that these represent crushed portions of the shell and are not comparable to the brachiopod pedicle. The new information suggests that hyoliths are more likely to be basal members of the lophotrochozoans rather than lophophorates closely linked with the phylum Brachiopoda.

关键词： orthothecid the Chengjiang Lagerst¨atte Cambrian soft parts lophophore

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Modelling of meander migration in an incised channel

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International Journal of Sediment Research 2014年第4期29卷 441-453页

作者： Jianchun HUANG Blair p.GREIMANN timothy J.RANDLE Hydraulic Engineers Sedimentation and River Hydraulics GroupTechnical Service CenterBureau of Reclamation

An updated linear computer model for meandering rivers with incision has been *** model simulates the bed topography,flow field,and bank erosion rate in an incised meandering *** a scenario where the upstream sediment load decreases(e.g.,after dam closure or soil conservation),alluvial river experiences cross section deepening and slope *** channel migration rate might be affected in two ways:decreased channel slope and steeped bank *** proposed numerical model combines the traditional one-dimensional(1D) sediment transport model in simulating the channel erosion and the linear model for channel meandering.A non-equilibrium sediment transport model is used to update the channel bed elevation and gradations.A linear meandering model was used to calculate the channel alignment and bank erosion/accretion,which in turn was used by the 1D sediment transport *** the 1D sediment transport model,the channel bed elevation and gradations are representedin each channel cross *** the meandering model,the bed elevation and gradations are stored in two dimensional(2D) cells to represent the channel and terrain properties(elevation and gradation).A new method is proposed to exchange information regarding bed elevations and bed material fractions between 1D river geometry and 2D channel and *** ability of the model is demonstrated using the simulation of the laboratory channel migration of Friedkin in which channel incision occurs at the upstream end.

关键词： Numerical model River channel migration Meandering river Linearization analysis Sediment transport

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Theoretical simulation of T2SLs InAs/GaSb cascade photodetector for HOT condition

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Journal of Semiconductors 2018年第9期39卷 34-37页

作者： Tetiana Manyk Klaudia Hackiewicz Jaroslaw rutkowski piotr Martyniuk Institute of Applied physics Military University of Technology 2 Urbanowicza Str.

The investigation of the interband type-II superlattice In As/Ga Sb cascade photodetector in the temperature range of 320–380 K is presented. The article is devoted to the theoretical modeling of the cascade detector characteristics by the use of the Simu Apsys platform and the 4-band model（k·p 8 × 8 method）. The obtained theoretical characteristics are comparable with experimentally measured ones, suggesting that transport in the absorber is determined by the dynamics of intrinsic carriers and by their lifetime. An overlap equal to 120 me V was used in calculations and a correction term in the ＂non-common atom＂ model Hxy = 700 me V was added to the Hamiltonian. The electron and hole effective masses from dispersion curves were estimated and absorption coefficient α was calculated. Based on the simulation detectivity, D＊ characteristics in the temperature range 320–380 K were calculated. The simulated theoretical characteristics at 320 K are comparable to experimentally measured ones, however at higher temperatures, the experimental value of D＊ does not reach the theoretical values due to the low resistance of the device and short diffusion length.

关键词： interband cascade photodetectors type-II superlattice infrared detectors

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predicting Ailanthus altissima presence across a managed forest landscape in southeast Ohio

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Forest Ecosystems 2019年第4期6卷 261-273页

作者： Louis R.Iverson Joanne Rebbeck Matthew p.peters Todd Hutchinson timothy Fox Northern Research Station USDA Forest Service

Background: The negative impacts of the exotic tree, Ailanthus altissima(tree-of-heaven, stink tree), is spreading throughout much of the Eastern United States. When forests are disturbed, it can invade and expand quickly if seed sources are ***: We conducted studies at the highly dissected Tar Hollow State Forest(THSF) in southeastern Ohio USA,where Ailanthus is widely distributed within the forest, harvests have been ongoing for decades, and prescribed fire had been applied to about a quarter of the study area. Our intention was to develop models to evaluate the relationship of Ailanthus presence to prescribed fire, harvesting activity, and other landscape characteristics, using this Ohio location as a case study. Field assessments of the demography of Ailanthus and other stand attributes(e.g., fire, harvesting, stand structure) were conducted on 267 sample plots on a 400-m grid throughout THSF,supplemented by identification of Ailanthus seed-sources via digital aerial sketch mapping during the dormant season. Statistical modeling tools Random Forest(RF), Classification and Regression Trees(CART), and Maxent were used to assess relationships among attributes, then model habitats suitable for Ailanthus ***: In all, 41 variables were considered in the models, including variables related to management activities, soil characteristics, topography, and vegetation structure(derived from LiDAR). The most important predictor of Ailanthus presence was some measure of recent timber harvest, either mapped harvest history(CART) or LiDARderived canopy height(Maxent). Importantly, neither prescribed fire or soil variables appeared as important predictors of Ailanthus presence or absence in any of the models of the ***: These modeling techniques provide tools and methodologies for assessing landscapes for Ailanthus invasion, as well as those areas with higher potentials for invasion should seed sources become available. Though a case study on

关键词： Ohio Random Forest CART Maxent Landscape model Non-native invasive species

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Therapeutic modulation of the CD47-SIRpαaxis in the pediatric tumor microenvironment:working up an appetite

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Cancer Drug Resistance 2020年第3期3卷 550-562页

作者： Ajay Gupta Cenny Taslim Brian p.Tullius timothy p.Cripe Division of Hematology OncologyBlood and Marrow TransplantNationwide Children’s HospitalColumbusOH 43205USA. Center for Childhood Cancer and Blood Diseases Nationwide Children’s HospitalColumbusOH 43205USA.

Evasion of immune surveillance is one of the hallmarks of *** the adaptive immune system has been targeted via checkpoint inhibition,many patients do not sustain durable remissions due to the heterogeneity of the tumor microenvironment,so additional strategies are *** innate immune system has its own set of checkpoints,and tumors have co-opted this system by expressing surface receptors that inhibit *** of these receptors,CD47,also known as the“don’t eat me”signal,has been found to be overexpressed by most cancer histologies and has been successfully targeted by antibodies blocking the receptor or its ligand,signal regulatory proteinα(SIRpα).By enabling phagocytosis via antigen-presenting cells,interruption of CD47-SIRpαbinding leads to earlier downstream activation of the adaptive immune *** and ongoing clinical trials are demonstrating the safety and efficacy of CD47 blockade in combination with monoclonal antibodies,chemotherapy,or checkpoint inhibitors for adult cancer *** aim of this review is to highlight the current literature and research on CD47,provide an impetus for investigation of its blockade in pediatric cancer histologies,and provide a rationale for new combination therapies in these patients.

关键词： CD47 SIRpα immunotherapy tumor microenvironment pediatric cancer innate immune system checkpoint inhibitor phagocytosis

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Dietary manipulation and testosterone replacement therapy may explain changes in body composition after spinal cord injury: A retrospective case report

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World Journal of Clinical Cases 2019年第17期7卷 2427-2437页

作者： Ashraf S Gorgey Robert M Lester Mina p Ghatas Sakita N Sistrun timothy Lavis Spinal Cord Injury and Disorders Service Hunter Holmes McGuire VAMCRichmondVA 23249United States Department of physical Medicine and Rehabilitation Virginia Commonwealth UniversityRichmondVA 23249United States Bionutrition Service Center for Clinical and Translational ResearchVirginia Commonwealth UniversityRichmondVA 23249United States

BACKGROUND Reduced level of physical activity,high-fat diet and skeletal muscle atrophy are key factors that are likely to contribute to deleterious changes in body composition and metabolic following spinal cord injury (SCI).Reduced caloric intake with lowering percentage macronutrients of fat and increasing protein intake may likely to improve body composition parameters and decrease ectopic adiposity after *** To highlight the effects of dietary manipulation and testosterone replacement therapy (TRT) on body composition after SCI METHODS A 31-year-old male with T5 SCI was administered transdermal TRT daily for 16 *** intake and percentage macronutrients were analyzed using dietary *** resonance imaging and dual-energy x-ray absorptiometry were used to measure changes in body *** Caloric intake and fat percentage were reduced by 445 kcal/d and 6.5%,*** body weight decreased by 8%,body fat decreased by 29%,and lean mass increased by 7%.Thigh subcutaneous adipose tissue cross-sectional area was reduced by 31%.CONCLUSION Manipulation of caloric intake,fat percentage,and protein percentage may have influenced body composition after SCI.

关键词： Spinal cord injury Diet High-protein Low-fat Nutrients Basal metabolic rate Case report

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