Coding/decoding and reversibility of droplet trains in microfluidic networks     

Fuerstman MJ  Garstecki P  Whitesides GM 《Science (New York, N.Y.)》2007,315(5813):828-832

Droplets of one liquid suspended in a second, immiscible liquid move through a microfluidic device in which a channel splits into two branches that reconnect downstream. The droplets choose a path based on the number of droplets that occupy each branch. The interaction among droplets in the channels results in complex sequences of path selection. The linearity of the flow through the microchannels, however, ensures that the behavior of the system can be reversed. This reversibility makes it possible to encrypt and decrypt signals coded in the intervals between droplets. The encoding/decoding device is a functional microfluidic system that requires droplets to navigate a network in a precise manner without the use of valves, switches, or other means of external control.  相似文献   

PDGFRA activating mutations in gastrointestinal stromal tumors     

Heinrich MC  Corless CL  Duensing A  McGreevey L  Chen CJ  Joseph N  Singer S  Griffith DJ  Haley A  Town A  Demetri GD  Fletcher CD  Fletcher JA 《Science (New York, N.Y.)》2003,299(5607):708-710

Most gastrointestinal stromal tumors (GISTs) have activating mutations in the KIT receptor tyrosine kinase, and most patients with GISTs respond well to Gleevec, which inhibits KIT kinase activity. Here we show that approximately 35% (14 of 40) of GISTs lacking KIT mutations have intragenic activation mutations in the related receptor tyrosine kinase, platelet-derived growth factor receptor alpha (PDGFRA). Tumors expressing KIT or PDGFRA oncoproteins were indistinguishable with respect to activation of downstream signaling intermediates and cytogenetic changes associated with tumor progression. Thus, KIT and PDGFRA mutations appear to be alternative and mutually exclusive oncogenic mechanisms in GISTs.  相似文献   

Watching a protein as it functions with 150-ps time-resolved x-ray crystallography     

Schotte F  Lim M  Jackson TA  Smirnov AV  Soman J  Olson JS  Phillips GN  Wulff M  Anfinrud PA 《Science (New York, N.Y.)》2003,300(5627):1944-1947

We report picosecond time-resolved x-ray diffraction from the myoglobin (Mb) mutant in which Leu29 is replaced by Phe (L29Fmutant). The frame-by-frame structural evolution, resolved to 1.8 angstroms, allows one to literally "watch" the protein as it executes its function. Time-resolved mid-infrared spectroscopy of flash-photolyzed L29F MbCO revealed a short-lived CO intermediate whose 140-ps lifetime is shorter than that found in wild-type protein by a factor of 1000. The electron density maps of the protein unveil transient conformational changes far more dramatic than the structural differences between the carboxy and deoxy states and depict the correlated side-chain motion responsible for rapidly sweeping CO away from its primary docking site.  相似文献   

Ethics. The ISSCR guidelines for human embryonic stem cell research     

Daley GQ  Ahrlund Richter L  Auerbach JM  Benvenisty N  Charo RA  Chen G  Deng HK  Goldstein LS  Hudson KL  Hyun I  Junn SC  Love J  Lee EH  McLaren A  Mummery CL  Nakatsuji N  Racowsky C  Rooke H  Rossant J  Schöler HR  Solbakk JH  Taylor P  Trounson AO  Weissman IL  Wilmut I  Yu J  Zoloth L 《Science (New York, N.Y.)》2007,315(5812):603-604

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Contact-dependent demyelination by Mycobacterium leprae in the absence of immune cells     

Rambukkana A  Zanazzi G  Tapinos N  Salzer JL 《Science (New York, N.Y.)》2002,296(5569):927-931

Demyelination results in severe disability in many neurodegenerative diseases and nervous system infections, and it is typically mediated by inflammatory responses. Mycobacterium leprae, the causative organism of leprosy, induced rapid demyelination by a contact-dependent mechanism in the absence of immune cells in an in vitro nerve tissue culture model and in Rag1-knockout (Rag1-/-) mice, which lack mature B and T lymphocytes. Myelinated Schwann cells were resistant to M. leprae invasion but undergo demyelination upon bacterial attachment, whereas nonmyelinated Schwann cells harbor intracellular M. leprae in large numbers. During M. leprae-induced demyelination, Schwann cells proliferate significantly both in vitro and in vivo and generate a more nonmyelinated phenotype, thereby securing the intracellular niche for M. leprae.  相似文献   

Varshavsky's contributions     

Baumeister W  Bachmair A  Chau V  Cohen R  Coffino P  Demartino G  Deshaies R  Dohmen J  Emr S  Finley D  Hampton R  Hill C  Hochstrasser M  Huber R  Jackson P  Jentsch S  Johnson E  Kwon YT  Pagano M  Pickart C  Rechsteiner M  Scheffner M  Sommer T  Tansey W  Tyers M  Vierstra R  Weissman A  Wilkinson KD  Wolf D 《Science (New York, N.Y.)》2004,306(5700):1290-1292

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A family with severe insulin resistance and diabetes due to a mutation in AKT2   总被引：1，自引：0，他引：1  

George S  Rochford JJ  Wolfrum C  Gray SL  Schinner S  Wilson JC  Soos MA  Murgatroyd PR  Williams RM  Acerini CL  Dunger DB  Barford D  Umpleby AM  Wareham NJ  Davies HA  Schafer AJ  Stoffel M  O'Rahilly S  Barroso I 《Science (New York, N.Y.)》2004,304(5675):1325-1328

Inherited defects in signaling pathways downstream of the insulin receptor have long been suggested to contribute to human type 2 diabetes mellitus. Here we describe a mutation in the gene encoding the protein kinase AKT2/PKBbeta in a family that shows autosomal dominant inheritance of severe insulin resistance and diabetes mellitus. Expression of the mutant kinase in cultured cells disrupted insulin signaling to metabolic end points and inhibited the function of coexpressed, wild-type AKT. These findings demonstrate the central importance of AKT signaling to insulin sensitivity in humans.  相似文献   

Ex vivo comparison of the effect of storage temperature on canine intestinal leakage pressures     

Daniel J. Duffy BVM & S  MS  FHEA  MRCVS  DACVS-SA  DECVS  Yi-Jen Chang BVetMed  MS  Julie A. Balko VMD  DACVAA  George E. Moore DVM  PhD  ACVIM 《Veterinary surgery : VS》2020,49(3):496-501

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Biomechanical evaluation of an autologous flexor digitorum lateralis graft to augment the surgical repair of gastrocnemius tendon laceration in a canine ex vivo model     

Daniel J. Duffy BVM&S  MS  FHEA  MRCVS  DACVS-SA  DECVS  Chiara P. Curcillo VMD  Yi-Jen Chang BVetMed  MS  Lewis Gaffney BS  Matthew B. Fisher PhD  George E. Moore DVM  PhD  ACVIM 《Veterinary surgery : VS》2020,49(8):1545-1554

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Resistin concentrations in serum and stifle synovial fluid from normal and cruciate deficient dogs with osteoarthritis     

Stephanie A. Kleine DVM  DACVAA  PhD  Robert M. Gogal DVM  Thomas M. Krunkosky DVM  PhD  Sherry L. Sanderson DVM  PhD  DACVIM  DACVN  Clinton George DVM  Megan Norton MS  Steven C. Budsberg DVM  MS  DACVS 《Veterinary surgery : VS》2020,49(6):1164-1173

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