A mechanistic model of mid-latitude decadal climate variability

Author Posting. © Elsevier B.V., 2007. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Physica D: Nonlinear Phenomena 237 (2008): 584-599, doi:10.1016/j.physd.2007.09.025.A simple heuristic model of coupled decadal ocean–atmosphere modes in middle latitudes is developed. Previous studies have treated atmospheric intrinsic variability as a linear stochastic process modified by a deterministic coupling to the ocean. The present paper takes an alternative view: based on observational, as well as process modeling results, it represents this variability in terms of irregular transitions between two anomalously persistent, high-latitude and low-latitude jet-stream states. Atmospheric behavior is thus governed by an equation analogous to that describing the trajectory of a particle in a double-well potential, subject to stochastic forcing. Oceanic adjustment to a positional shift in the atmospheric jet involves persistent circulation anomalies maintained by the action of baroclinic eddies; this process is parameterized in the model as a delayed oceanic response. The associated sea-surface temperature anomalies provide heat fluxes that affect atmospheric circulation by modifying the shape of the double-well potential. If the latter coupling is strong enough, the model’s spectrum exhibits a peak at a periodicity related to the ocean’s eddy-driven adjustment time. A nearly analytical approximation of the coupled model is used to study the sensitivity of this behavior to key model parameters.This research was supported by National Science Foundation grant OCE-02-221066 (all coauthors) and the Department of Energy grant DE-FG-03-01ER63260 (MG and SK)

A highly nonlinear coupled mode of decadal variability in a mid-latitude ocean–atmosphere model

Author Posting. © Elsevier B.V., 2007. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Dynamics of Atmospheres and Oceans 43 (2007): 123-150, doi:10.1016/j.dynatmoce.2006.08.001.This study examines mid-latitude climate variability in a model that couples turbulent oceanic and atmospheric flows through an active oceanic mixed layer. Intrinsic ocean dynamics of the inertial recirculation regions combines with nonlinear atmospheric sensitivity to sea-surface temperature (SST) anomalies to play a dominant role in the variability of the coupled system. Intrinsic low-frequency variability arises in the model atmosphere; when run in a stand-alone mode, it is characterized by irregular transitions between preferred high-latitude and less frequent low-latitude zonal-flow states. When the atmosphere is coupled to the ocean, the low-latitude state occurrences exhibit a statistically significant signal in a broad 5–15-year band. A similar signal is found in the time series of the model ocean’s energy in this coupled simulation. Accompanying uncoupled ocean-only and atmosphere-only integrations are characterized by a decrease in the decadal-band variability, relative to the coupled integration; their spectra are indistinguishable from a red spectrum. The time scale of the coupled interdecadal oscillation is set by the nonlinear adjustment of the ocean’s inertial recirculations to the high-latitude and low-latitude atmospheric forcing regimes. This adjustment involves, in turn, SST changes resulting in long-term ocean–atmosphere heat-flux anomalies that induce the atmospheric regime transitions.This research was supported by NSF grant OCE-02-221066 (all co-authors) and DOE grant DE-FG-03-01ER63260 (MG and SK)

North Atlantic climate variability in coupled models and data

© 2008 The Authors. This work is licensed under a Creative Commons Attribution License. The definitive version was published in Nonlinear Processes in Geophysics 15 (2008): 13-24, doi:10.5194/npg-15-13-2008We show that the observed zonally averaged jet in the Northern Hemisphere atmosphere exhibits two spatial patterns with broadband variability in the decadal and inter-decadal range; these patterns are consistent with an important role of local, mid-latitude ocean–atmosphere coupling. A key aspect of this behaviour is the fundamentally nonlinear bi-stability of the atmospheric jet's latitudinal position, which enables relatively small sea-surface temperature anomalies associated with ocean processes to affect the large-scale atmospheric winds. The wind anomalies induce, in turn, complex three-dimensional anomalies in the ocean's main thermocline; in particular, they may be responsible for recently reported cooling of the upper ocean. Both observed modes of variability, decadal and inter-decadal, have been found in our intermediate climate models. One mode resembles North Atlantic tri-polar sea-surface temperature (SST) patterns described elsewhere. The other mode, with mono-polar SST pattern, is novel; its key aspects include interaction of oceanic turbulence with the large-scale oceanic flow. To the extent these anomalies exist, the interpretation of observed climate variability in terms of natural and human-induced changes will be affected. Coupled mid-latitude ocean-atmosphere modes do, however, suggest some degree of predictability is possible.This research was supported by NSF grant OCE-02-221066, DOE grants DE-FG-03-01ER63260 and DE-FG02-02ER63413, as well as NASA grant NNG-06-AG66G-1 (MG & SK). PB has also been supported by the Newton Trust research grant, and SK - by the University of Wisconsin-Milwaukee Research Growth Initiative program 2006-2007

The mechanism of DNA replication termination in vertebrates

Eukaryotic DNA replication terminates when replisomes from adjacent replication origins converge. Termination involves local completion of DNA synthesis, decatenation of daughter molecules, and replisome disassembly. Termination has been difficult to study because termination events are generally asynchronous and sequence non-specific. To overcome these challenges, we paused converging replisomes with a site-specific barrier in Xenopus egg extracts. Upon removal of the barrier, forks underwent synchronous and site-specific termination, allowing mechanistic dissection of this process. We show that DNA synthesis does not slow detectably as forks approach each other and that leading strands pass each other unhindered before undergoing ligation to downstream lagging strands. Dissociation of CMG helicases occurs only after the final ligation step, and is not required for completion of DNA synthesis, strongly suggesting that converging CMGs pass one another and dissociate from double-stranded DNA. This termination mechanism allows rapid completion of DNA synthesis while avoiding premature replisome disassembl

Insect-inspired visual navigation on-board an autonomous robot: real-world routes encoded in a single layer network

Insect-Inspired models of visual navigation, that operate by scanning for familiar views of the world, have been shown to be capable of robust route navigation in simulation. These familiarity-based navigation algorithms operate by training an artificial neural network (ANN) with views from a training route, so that it can then output a familiarity score for any new view. In this paper we show that such an algorithm – with all computation performed on a small low-power robot – is capable of delivering reliable direction information along real-world outdoor routes, even when scenes contain few local landmarks and have high-levels of noise (from variable lighting and terrain). Indeed, routes can be precisely recapitulated and we show that the required computation and storage does not increase with the number of training views. Thus the ANN provides a compact representation of the knowledge needed to traverse a route. In fact, rather than losing information, there are instances where the use of an ANN ameliorates the problems of sub optimal paths caused by tortuous training routes. Our results suggest the feasibility of familiarity-based navigation for long-range autonomous visual homing

Application of the PM6 method to modeling the solid state

The applicability of the recently developed PM6 method for modeling various properties of a wide range of organic and inorganic crystalline solids has been investigated. Although the geometries of most systems examined were reproduced with good accuracy, severe errors were found in the predicted structures of a small number of solids. The origin of these errors was investigated, and a strategy for improving the method proposed

Src-Mediated Phosphorylation of the Tyrosine Phosphatase PRL-3 Is Required for PRL-3 Promotion of Rho Activation, Motility and Invasion

The metastasis-associated tyrosine phosphatase PRL-3/PTP4A is upregulated in numerous cancers, but the mechanisms modulating PRL-3 activity other than its expression levels have not been investigated. Here we report evidence for both Src-dependent tyrosine phosphorylation of PRL-3 and Src-mediated regulation of PRL-3 biological activities. We used structural mutants, pharmacological inhibitors and siRNA to demonstrate Src-dependent phosphorylation of endogenous PRL-3 in SW480 colon cancer cells. We also demonstrated that PRL-3 was not tyrosine phosphorylated in SYF mouse embryo fibroblasts deficient in Src, Yes and Fyn unless Src was re-expressed. Further, we show that platelet-derived growth factor (PDGF) can stimulate PRL-3 phosphorylation in a Src-dependent manner. Finally, we show that PRL-3-induced cell motility, Matrigel invasion and activation of the cytoskeleton-regulating small GTPase RhoC were abrogated in the presence of the phosphodeficient PRL-3 mutant Y53F, or by use of a Src inhibitor. Thus, PRL-3 requires the activity of a Src kinase, likely Src itself, to promote these cancer-associated phenotypes. Our data establish a model for the regulation of PRL-3 by Src that supports the possibility of their coordinate roles in signaling pathways promoting invasion and metastasis, and supports simultaneous use of novel molecularly targeted therapeutics directed at these proteins

Pif1- and Exo1-dependent nucleases coordinate checkpoint activation following telomere uncapping

In the absence of the telomere capping protein Cdc13, budding yeast telomeres erode, resulting in checkpoint arrest. This study shows that the helicase Pif1, known as a telomerase inhibitor, also has a direct role in the resection of uncapped telomeres, acting in parallel to the nuclease Exo1

Dependence of Peroxisome Proliferator-activated Receptor Ligand-induced Mitogen-activated Protein Kinase Signaling on Epidermal Growth Factor Receptor Transactivation

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that function as ligand-activated transcription factors regulating lipid metabolism and homeostasis. In addition to their ability to regulate PPAR-mediated gene transcription, PPARalpha and gamma ligands have recently been shown to induce activation of mitogen-activated protein kinases (MAPKs), which in turn phosphorylate PPARs, thereby affecting transcriptional activity. However, the mechanism for PPAR ligand-dependent MAPK activation is unclear. In the current study, we demonstrate that various PPARalpha (nafenopin) and gamma (ciglitazone and troglitazone) agonists rapidly induced extracellular signal-regulated kinase (Erk) and/or p38 phosphorylation in rat liver epithelial cells (GN4). The selective epidermal growth factor receptor (EGFR) kinase inhibitors, PD153035 and ZD1839 (Iressa), abolished PPARalpha and gamma agonist-dependent Erk activation. Consistent with this, PPAR agonists increased tyrosine autophosphorylation of the EGFR as well as phosphorylation at a putative Src-specific site, Tyr845. Experiments with the Src inhibitor, PP2, and the antioxidant N-acetyl-L-cysteine revealed critical roles for Src and reactive oxygen species as upstream mediators of EGFR transactivation in response to PPAR ligands. Moreover, PPARalpha and gamma ligands increased Src autophosphorylation as well as kinase activity. EGFR phosphorylation, in turn, led to Ras-dependent Erk activation. In contrast, p38 activation by PPARalpha and gamma ligands occurred independently of Src, oxidative stress, the EGFR, and Ras. Interestingly, PPARalpha and gamma agonists caused rapid activation of proline-rich tyrosine kinase or Pyk2; Pyk2 as well as p38 phosphorylation was reduced by intracellular Ca2+ chelation without an observable effect on EGFR and Erk activation, suggesting a possible role for Pyk2 as an upstream activator of p38. In summary, PPARalpha and gamma ligands activate two distinct signaling cascades in GN4 cells leading to MAPK activation

The association between serum biomarkers and disease outcome in influenza A(H1N1)pdm09 virus infection: results of two international observational cohort studies

BACKGROUND Prospective studies establishing the temporal relationship between the degree of inflammation and human influenza disease progression are scarce. To assess predictors of disease progression among patients with influenza A(H1N1)pdm09 infection, 25 inflammatory biomarkers measured at enrollment were analyzed in two international observational cohort studies. METHODS Among patients with RT-PCR-confirmed influenza A(H1N1)pdm09 virus infection, odds ratios (ORs) estimated by logistic regression were used to summarize the associations of biomarkers measured at enrollment with worsened disease outcome or death after 14 days of follow-up for those seeking outpatient care (FLU 002) or after 60 days for those hospitalized with influenza complications (FLU 003). Biomarkers that were significantly associated with progression in both studies (p<0.05) or only in one (p<0.002 after Bonferroni correction) were identified. RESULTS In FLU 002 28/528 (5.3%) outpatients had influenza A(H1N1)pdm09 virus infection that progressed to a study endpoint of complications, hospitalization or death, whereas in FLU 003 28/170 (16.5%) inpatients enrolled from the general ward and 21/39 (53.8%) inpatients enrolled directly from the ICU experienced disease progression. Higher levels of 12 of the 25 markers were significantly associated with subsequent disease progression. Of these, 7 markers (IL-6, CD163, IL-10, LBP, IL-2, MCP-1, and IP-10), all with ORs for the 3(rd) versus 1(st) tertile of 2.5 or greater, were significant (p<0.05) in both outpatients and inpatients. In contrast, five markers (sICAM-1, IL-8, TNF-α, D-dimer, and sVCAM-1), all with ORs for the 3(rd) versus 1(st) tertile greater than 3.2, were significantly (p≤.002) associated with disease progression among hospitalized patients only. CONCLUSIONS In patients presenting with varying severities of influenza A(H1N1)pdm09 virus infection, a baseline elevation in several biomarkers associated with inflammation, coagulation, or immune function strongly predicted a higher risk of disease progression. It is conceivable that interventions designed to abrogate these baseline elevations might affect disease outcome