246 research outputs found

    The turbulent oscillator : a mechanism of low-frequency variability of the wind-driven ocean gyres

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    Author Posting. Β© American Meteorological Society, 2007. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography. 37 (2007): 2363-2386, doi:10.1175/jpo3118.1.Intrinsic low-frequency variability is studied in the idealized, quasigeostrophic, midlatitude, wind-driven ocean gyres operating at large Reynolds number. A robust decadal variability mode driven by the transient mesoscale eddies is found and analyzed. The variability is a turbulent phenomenon, which is driven by the competition between the eddy rectification process and the potential vorticity anomalies induced by changes of the intergyre transportFunding for Pavel Berloff was provided by NSF Grants OCE-0091836 and OCE- 0344094, by the U.K. Royal Society Fellowship, and by the Newton Trust Award, A. M. Hogg was supported by an Australian Research Council Postdoctoral Fellowship (DP0449851) during this work, and William K. Dewar was supported by NSF Grants OCE-0424227 and OCE-0550139

    Dynamical origin of low-frequency variability in a highly nonlinear midlatitude coupled model

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    Author Posting. Β© American Meteorological Society 2006. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Climate 19 (2006): 6391–6408, doi:10.1175/JCLI3976.1.A novel mechanism of decadal midlatitude coupled variability, which crucially depends on the nonlinear dynamics of both the atmosphere and the ocean, is presented. The coupled model studied involves quasigeostrophic atmospheric and oceanic components, which communicate with each other via a constant-depth oceanic mixed layer. A series of coupled and uncoupled experiments show that the decadal coupled mode is active across parameter ranges that allow the bimodality of the atmospheric zonal flow to coexist with oceanic turbulence. The latter is most intense in the regions of inertial recirculation (IR). Bimodality is associated with the existence of two distinct anomalously persistent zonal-flow modes, which are characterized by different latitudes of the atmospheric jet stream. The IR reorganizations caused by transitions of the atmosphere from its high- to low-latitude state and vice versa create sea surface temperature anomalies that tend to induce transition to the opposite atmospheric state. The decadal–interdecadal time scale of the resulting oscillation is set by the IR adjustment; the latter depends most sensitively on the oceanic bottom drag. The period T of the nonlinear oscillation is 7–25 yr for the range of parameters explored, with the most realistic parameter values yielding T β‰ˆ 20 yr. Aside from this nonlinear oscillation, an interannual Rossby wave mode is present in all coupled experiments. This coupled mode depends neither on atmospheric bimodality, nor on ocean eddy dynamics; it is analogous to the mode found previously in a channel configuration. Its time scale in the model with a closed ocean basin is set by cross-basin wave propagation and equals 3–5 yr for a basin width comparable with the North Atlantic.This research was supported by NSF Grant OCE-02-221066 (all coauthors) and DOE Grant DE-FG-03-01ER63260 (MG and SK)

    Human post-mortem synapse proteome integrity screening for proteomic studies of postsynaptic complexes

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    Background Synapses are fundamental components of brain circuits and are disrupted in over 100 neurological and psychiatric diseases. The synapse proteome is physically organized into multiprotein complexes and polygenic mutations converge on postsynaptic complexes in schizophrenia, autism and intellectual disability. Directly characterising human synapses and their multiprotein complexes from post-mortem tissue is essential to understanding disease mechanisms. However, multiprotein complexes have not been directly isolated from human synapses and the feasibility of their isolation from post-mortem tissue is unknown. Results Here we establish a screening assay and criteria to identify post-mortem brain samples containing well-preserved synapse proteomes, revealing that neocortex samples are best preserved. We also develop a rapid method for the isolation of synapse proteomes from human brain, allowing large numbers of post-mortem samples to be processed in a short time frame. We perform the first purification and proteomic mass spectrometry analysis of MAGUK Associated Signalling Complexes (MASC) from neurosurgical and post-mortem tissue and find genetic evidence for their involvement in over seventy human brain diseases. Conclusions We have demonstrated that synaptic proteome integrity can be rapidly assessed from human post-mortem brain samples prior to its analysis with sophisticated proteomic methods. We have also shown that proteomics of synapse multiprotein complexes from well preserved post-mortem tissue is possible, obtaining structures highly similar to those isolated from biopsy tissue. Finally we have shown that MASC from human synapses are involved with over seventy brain disorders. These findings should have wide application in understanding the synaptic basis of psychiatric and other mental disorders

    Association of decreased mitochondrial DNA content with ovarian cancer progression

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    Mitochondrial DNA (mtDNA) content in ovarian carcinomas was assessed by quantitative PCR. Results show that mtDNA content in tumour cell was significantly higher than that in normal ovary. Change in mtDNA content was not related with patients' age or tumour stages. However, the average mtDNA copy number in pathological low-grade tumours was over two-fold higher than that in high-grade carcinomas (P=0.012). Moreover, type I carcinomas also had a significantly higher mtDNA copy number than in type II carcinomas (P=0.019). Change in mtDNA content might be an important genetic event in the progression of ovarian carcinomas

    Multiple Redox Modes in the Reversible Lithiation of High-Capacity, Peierls-Distorted Vanadium Sulfide.

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    This is the author accepted manuscript. The final version is available from ACS via http://dx.doi.org/10.1021/jacs.5b03395Vanadium sulfide VS4 in the patronite mineral structure is a linear chain compound comprising vanadium atoms coordinated by disulfide anions [S2](2-). (51)V NMR shows that the material, despite having V formally in the d(1) configuration, is diamagnetic, suggesting potential dimerization through metal-metal bonding associated with a Peierls distortion of the linear chains. This is supported by density functional calculations, and is also consistent with the observed alternation in V-V distances of 2.8 and 3.2 Γ… along the chains. Partial lithiation results in reduction of the disulfide ions to sulfide S(2-), via an internal redox process whereby an electron from V(4+) is transferred to [S2](2-) resulting in oxidation of V(4+) to V(5+) and reduction of the [S2](2-) to S(2-) to form Li3VS4 containing tetrahedral [VS4](3-) anions. On further lithiation this is followed by reduction of the V(5+) in Li3VS4 to form Li3+xVS4 (x = 0.5-1), a mixed valent V(4+)/V(5+) compound. Eventually reduction to Li2S plus elemental V occurs. Despite the complex redox processes involving both the cation and the anion occurring in this material, the system is found to be partially reversible between 0 and 3 V. The unusual redox processes in this system are elucidated using a suite of short-range characterization tools including (51)V nuclear magnetic resonance spectroscopy (NMR), S K-edge X-ray absorption near edge spectroscopy (XANES), and pair distribution function (PDF) analysis of X-ray data.SB acknowledges Schlumberger Stichting Fund and European Research Council (EU ERC) for funding. JC thanks BK21 plus project of Korea. We thank Phoebe Allan and Andrew J. Morris, University of Cambridge, for useful discussions. We also thank Trudy Bolin and Tianpin Wu of Beamline 9-BM, Argonne National Laboratory for help with XANES measurements. The DFT calculations were performed at the UCSB Center for Scientific Computing at UC Santa Barbara, supported by the California Nanosystems Institute (NSF CNS-0960316), Hewlett-Packard, and the Materials Research Laboratory (DMR-1121053). This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357

    Cellular Model of Warburg Effect Identifies Tumor Promoting Function of UCP2 in Breast Cancer and Its Suppression by Genipin

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    The Warburg Effect is characterized by an irreversible injury to mitochondrial oxidative phosphorylation (OXPHOS) and an increased rate of aerobic glycolysis. In this study, we utilized a breast epithelial cell line lacking mitochondrial DNA (rho0) that exhibits the Warburg Effect associated with breast cancer. We developed a MitoExpress array for rapid analysis of all known nuclear genes encoding the mitochondrial proteome. The gene-expression pattern was compared among a normal breast epithelial cell line, its rho0 derivative, breast cancer cell lines and primary breast tumors. Among several genes, our study revealed that over-expression of mitochondrial uncoupling protein UCP2 in rho0 breast epithelial cells reflects gene expression changes in breast cancer cell lines and in primary breast tumors. Furthermore, over-expression of UCP2 was also found in leukemia, ovarian, bladder, esophagus, testicular, colorectal, kidney, pancreatic, lung and prostate tumors. Ectopic expression of UCP2 in MCF7 breast cancer cells led to a decreased mitochondrial membrane potential and increased tumorigenic properties as measured by cell migration, in vitro invasion and anchorage independent growth. Consistent with in vitro studies, we demonstrate that UCP2 over-expression leads to development of tumors in vivo in an orthotopic model of breast cancer. Genipin, a plant derived small molecule, suppressed the UCP2 led tumorigenic properties, which were mediated by decreased reactive oxygen species and down-regulation of UCP2. However, UCP1, 3, 4 and 5 gene expression was unaffected. UCP2 transcription was controlled by SMAD4. Together, these studies suggest a tumor-promoting function of UCP2 in breast cancer. In summary, our studies demonstrate that i) the Warburg Effect is mediated by UCP2; ii) UCP2 is over-expressed in breast and many other cancers; iii) UCP2 promotes tumorigenic properties in vitro and in vivo and iv) genipin suppresses the tumor promoting function of UCP2

    Synergism between particle-based multiplexing and microfluidics technologies may bring diagnostics closer to the patient

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    In the field of medical diagnostics there is a growing need for inexpensive, accurate, and quick high-throughput assays. On the one hand, recent progress in microfluidics technologies is expected to strongly support the development of miniaturized analytical devices, which will speed up (bio)analytical assays. On the other hand, a higher throughput can be obtained by the simultaneous screening of one sample for multiple targets (multiplexing) by means of encoded particle-based assays. Multiplexing at the macro level is now common in research labs and is expected to become part of clinical diagnostics. This review aims to debate on the β€œadded value” we can expect from (bio)analysis with particles in microfluidic devices. Technologies to (a) decode, (b) analyze, and (c) manipulate the particles are described. Special emphasis is placed on the challenges of integrating currently existing detection platforms for encoded microparticles into microdevices and on promising microtechnologies that could be used to down-scale the detection units in order to obtain compact miniaturized particle-based multiplexing platforms
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