Global Array Research Articles

Why global warming went missing since the year 2000

Over the period January 2004 to present, the seas have experienced the lack of any warming, as finally properly measured in the ARGO project where a global array of more than 3,600 free-drifting profiling floats has measured the temperature of the upper 2000 m of the sea as it was not possible before. The warming of the seas has been a negligible 1.1*10 -3 °C/year on average over the layer 0 – 2000 dbar below the accuracy of the measure. Over the period January 2000 to present, the measured land and sea temperatures of the less reliable GISS, NCDC and HADCRUT4 data sets have shown a small warming of 4.2*10 -3 °C/year on average. Same period, the climate models propose for the land and sea temperatures an unrealistic warming of 20.5*10 -3 °C/year (average of CMIP3) and 18.2*10 -3 °C/year (average of the CMIP5). The “inconvenient truth” is that climate models are predicting a warming when there is no warming rather than simply overestimating the warming as discussed so far. The paper presents the failed validation of the climate models since their introduction and suggests the reasons of their failure in the overrated effect of the changed composition of the atmosphere and the neglected natural oscillations.

Assessing equatorial surface currents in the FOAM Global and Indian Ocean models against observations from the global tropical moored buoy array

Surface currents from 2007–2008 hindcasts of the Forecast Ocean Assimilation Model (FOAM) Global and Indian Ocean models are assessed against observations at 46 global tropical moored buoy array sites. Zonal (u) currents are less challenging to model than meridional flows (v) due to their lower frequency variability. The assimilative global model has reasonable skill for zonal currents but less skill for meridional currents. The assimilative models have higher skill than the corresponding non-assimilative models. A too-strong westward bias of the order of 20cm/s is evident along the equator in all model versionsused in this study. No extra skill is evident in the high resolution (1/12°) regional model compared to the coarser resolution (1/4°) global model.

Update on the European Pulsar Timing Array

AbstractThe European Pulsar Timing Array (EPTA) is one the of three global Pulsar Timing Array communities, aiming to use the clock nature of pulsars to detect gravitational wave. In this talk, I will provide an introduction to the current status of EPTA pulsar observations and present an overview of the recent results. I will also give an update on the progress of the Large European Array for Pulsar (LEAP) project, which attempts to coherently combine the data from the five biggest single site radio telescopes in Europe and make an equivalently 200-metre diameter dish. The LEAP project is an ideal effort in performing high precision pulsar timing and studying characteristics of single pulses from millisecond pulsars.

Validation of FOAM near-surface ocean current forecasts using Lagrangian drifting buoys

Abstract. In this study, the quality of near-surface current forecasts from the FOAM ocean forecasting system is assessed using the trajectories of Lagrangian drifting buoys. A method is presented for deriving pseudo-Eulerian estimates of ocean currents from the positions of Surface Velocity Program drifters and the resulting data are compared to velocities observed by the global tropical moored buoy array. A quantitative analysis of the global FOAM velocities is performed for the period 2007 and 2008 using currents derived from over 3000 unique drifters (providing an average of 650 velocity observations per day). A potential bias is identified in the Southern Ocean which appears to be caused by wind-slip in the drifter dataset as a result of drogue loss. The drifter-derived currents are also used to show how the data assimilation scheme and a recent system upgrade impact upon the quality of FOAM current forecasts.

A New Approach Combining Surrounded-Element and Compression Methods for Analyzing Reconfigurable Reflectarray Antennas

An efficient technique to provide fast and accurate analysis of large-scale and complex reconfigurable reflectarray antennas is presented and validated. The method combines the surrounded cell approach and the compression technique to analyze the global array. It takes into account the mutual coupling effects and the numerical complexity is reduced. Only a minor electromagnetic simulation and a fast post-processing are required.

On the calibration of full-polarization 86 GHz global VLBI observations

We report the development of a semi-automatic pipeline for the calibration of 86 GHz full-polarization observations performed with the Global Millimeter-VLBI array (GMVA) and describe the calibration strategy followed in the data reduction. Our calibration pipeline involves non-standard procedures, since VLBI polarimetry at frequencies above 43 GHz is not yet well established. We also present, for the first time, a full-polarization global-VLBI image at 86 GHz (source 3C 345), as an example of the final product of our calibration pipeline, and discuss the effect of instrumental limitations on the fidelity of the polarization images. Our calibration strategy is not exclusive for the GMVA, and could be applied on other VLBI arrays at millimeter wavelengths. The use of this pipeline will allow GMVA observers to get fully-calibrated datasets shortly after the data correlation.

Abstract 5048: Global microRNA expression array analysis and potential application in discovery of promising drugs for hematologic cancer

Abstract Hematologic cancers, the third most common cause of cancer deaths, will kill ∼50,000 Americans this year. Early diagnosis and innovative treatment has been proposed to result in cure. Bendamustine (BM) is a synthetic drug which is highly effective in broad range of hematologic cancers. The efficacy of the drug is attributed to the ability of the drug to induce apoptosis as well as to inhibit cell cycle. It was highly effective in patients whose disease is refractory to other established drugs. Gambogic acid (GA) is the major active component of gambose, the resin secreted from Garcinia hanburryi which also has strong ability to induce apoptosis as well as inhibit cell cycle. microRNAs (miRNAs) are master regulators of the gene expression. Neither BM nor GA had been previously reported for their effect on miRNA expression profiles in hematologic or other cancers. We have set up an innovative global miRNA expression analysis array. Using this miRNA expression array, we analysed global expression in leukemia cells in culture treated with or without treatment of MB or GA. Our data showed comparable inhibition of cell cycle and induction of apoptosis by both GA and BM at a dose of GA several folds lower than that of BM. Our data, based on miRNA expression analysis using genome-wide miRNA expression array showed five common miRNAs, found differentially expressed (more than 3 times up or down regulated compared to untreated group with p<0.05) in both GA and BM treated groups. The data is particularly interesting, since these miRNAs have been reported to target and thus modulate expression of proteins of apoptotic pathway and senescence pathway. Out data suggest that drugs that induce apoptosis as well as inhibit cell cycle may have great therapeutic potential in hematologic cancers. Based on our data it appears that the drugs with anticancer properties may affect a common set or sets of miRNAs. To our knowledge, this constitutes the first report describing effect of both BM and GA on miRNA expression profile, not in just hematologic cancer but any cancer. Our study provides strong evidence to suggest that specific miRNA expression signature/s of hematologic cancer cells in culture following drug treatment should be further explored to screen promising drugs with higher anticancer properties. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5048. doi:1538-7445.AM2012-5048

Abstract 4658: Delta9-Tetrahydrocannabinol induces apoptosis via Cannabinol Receptor 1 and modulates methylation of oncogenes and tumorsuppressors in blasts derived from patients with acute lympoblastic or myeloid leukemia

Abstract Some cannabinol derivatives are said to possess antitumor efficacy. We have evidence that the CB1/2 cannabinoid receptor agonist Delta9-Tetrahydrocannabinol (THC), the major psychoactive component of marijuana, may have contributed to disease control in a patient with acute myeloid leukemia. We speculated that THC may induce apoptosis in native leukemic blasts and thus treated various leukemia cell lines and ex vivo blasts derived from patients with either acute lymphoblastic or myeloid leukemia in dilution series with THC. The antiproliferative effect was measured using an XTT-based assay. Induction of apoptosis was assessed by annexinV-based immunofluorescence analysis. The CB1 antagonist LY320135 or JTE-907, a selective CB2 inverse ligand agonist, were used to confirm involvement of CB1 (mainly expressed in brain tissue) or CB2 (expression in hematologic/lymphoid cells). THC was obtained with permission of the Bundesopiumstelle, Germany. Indeed, we demonstrate potent antiproliferative and proapoptotic efficacy of Delta9-THC in a dose dependent manner in leukemia cell lines of lymphoid and myeloid origin. Pretreatment with LY320135, but not with JTE-907, resulted in a dramatic abrogation of the antileukemic effect seen with THC monotherapy, arguing that THC-induced apoptosis is mediated via the cannabinoid receptor CB1. Besides a proapoptotic effect, THC was able to abrogate cellular differentiation blockage as observed in a change of morphology. Of note, THC was able to induce apoptosis in a subset of leukemia samples derived from patients with acute myeloid (mainly undifferentited AML) or lymphoblastic leukemia. Due to the patient cohort responsive to THC therapy, we speculated that epigenetic modifications might be associated with MLL (mixed lineage leukemia) methyltransferase function. In a global DNA methylation gene array, we could demonstrate that THC leads to modulation of methylation status of histone deacetylases, oncogenes and tumorsuppressors, some reported to be regulated by MLL. Ongoing work is focussing on validation whether THC treatment can be linked to MLL activity using an siRNA approach. In conclusion, while not being able to directly correlate the disease course of the above described patient to marijuana abuse, our in vitro results nevertheless demonstrate that THC mediates antileukemic activity in blasts of some patients ex vivo including that of our patient. Clinical evaluation of cannabinol receptor agonists as low-toxic agents could thus be considered in selected cases of patients with acute leukemia and this approach should further be followed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4658. doi:1538-7445.AM2012-4658

Accelerated Proliferation and Differential Global Gene Expression in Pancreatic Islets of Five-Week-Old Heterozygous Men1 Mice: Men1 Is a Haploinsufficient Suppressor

Individuals carrying heterozygous (hz) MEN1 (Multiple Endocrine Neoplasia Syndrome Type 1) germ line mutations develop endocrine tumors as a result of somatic loss of the wild-type (wt) allele. However, endocrine cell proliferation has been observed despite wt allele retention, indicating haploinsufficiency. To study downstream molecular effects of the hz haplotype, a germ line Men1 hz mouse model was used to explore differences in global endocrine pancreatic gene expression. Because islet cells of 5-wk-old hz mice express Menin from the retained wt Men1 allele, these were isolated after collagenase digestion of the pancreas, and used for global gene expression array. Wild-type littermates were used for comparison. Array findings were corroborated by quantitative PCR, Western blotting, in situ proximity ligation assay, and immunohistochemistry. The hz islets show increased proliferation: the Ki-67 index was twice as high as in wt islets (3.48 vs. 1.74%; P = 0.024). The microarray results demonstrated that several genes were differentially expressed. Some selected genes were studied on the protein level, e.g. the cytoskeletal regulator myristoylated alanine-rich protein kinase C substrate (Marcks) was significantly less expressed in hz islets, using in situ proximity ligation assay and Western blotting (P < 0.001 and P < 0.01, respectively). Further, gene ontology analysis showed that genes with higher mRNA expression in the hz endocrine pancreas were associated with e.g. chromatin maintenance and apoptosis. Lower mRNA was observed for genes involved in growth factor binding. In conclusion, despite retained Menin expression, proliferation was accelerated, and numerous genes were differentially expressed in the endocrine pancreas of 5-wk-old hz Men1 mice, corroborating the hypothesis that MEN1 is a haploinsufficient suppressor.

Model Update March 2011: Upper Mantle Heterogeneity beneath North America from Traveltime Tomography with Global and USArray Transportable Array Data

Model Update March 2011: Upper Mantle Heterogeneity beneath North America from Traveltime Tomography with Global and USArray Transportable Array Data

Evaluating Where and Why Drifters Die*

Abstract NOAA ’s Global Drifter Program (GDP) manages a global array of ~1250 active satellite-tracked surface drifting buoys (“drifters”) in collaboration with numerous national and international partners. To better manage the drifter array and to assess the performance of various drifter manufacturers, it is important to discriminate between drifters that cease transmitting because of internal failure and those that cease because of external factors such as running aground or being picked up. An accurate assessment of where drifters run aground would also allow the observations to be used to more accurately simulate the evolution of floating marine debris and to quantify globally which shores are most prone to the deposit of marine debris. While the drifter Data Assembly Center of the GDP provides a metadata file that includes cause of death, the identified cause for most drifters is simply “quit transmitting.” In this study it is shown that a significant fraction of these drifters likely ran aground or were picked up, and a statistical estimate that each drifter ran aground or was picked up is derived.

PreImplantation Factor (PIF) promoting role in embryo implantation: increases endometrial Integrin-α2β3, amphiregulin and epiregulin while reducing betacellulin expression via MAPK in decidua

BackgroundViable embryos secrete preimplantation factor (PIF), a peptide that has autocrine effects where levels correlate with cultured embryos development. sPIF (PIF synthetic analog) promotes implantation by regulating decidual-cells immunity, adhesion, apoptosis and enhances trophoblastic cell invasion. Herein sPIF priming effects on non-decidualized endometrium and decidualized-stroma are investigated, assessing elements critical for effective embryo-maternal cross-talk, prior to and at implantation.MethodsWe tested sPIF effect on human non-pregnant endometrial epithelial and non-decidualized stroma α2β3 integrin expression (IHC and flow cytometry), comparing with scrambled PIF (PIFscr-control). We examined sPIF effect on decidualized non-pregnant human endometrial stromal cells (HESC) determining pro-inflammatory mediators expression and secretion (ELISA) and growth factors (GFs) expression (Affymetrix global gene array). We tested sPIF effect on HESC Phospho-kinases (BioPlex) and isolated kinases activity (FastKinase).ResultssPIF up-regulates α2β3 integrin expression in epithelial cells, (P < 0.05) while PIFscr had no effect. In contrast, in stromal cell cultures sPIF had no effect on the same. In HESC, sPIF up-regulates pro-inflammatory cytokines; IL8, IL1β and IL6 expression. The major increase in GRO-α, ICAM-1 and MCP-3 expression is coupled with same ligands secretion (P < 0.05). sPIF modulates in HESC GFs expression: up-regulates amphiregulin and epiregulin- critical for implantation and enhances several fibroblast growth factors (FGF) relevant for decidual function. In contrast, sPIF down-regulates major pro-proliferative ligands, betacellulin and IGF1 expression. sPIF modulatory effect on GFs is exerted by down-regulating pro-proliferative phospho-activated MAPkinases, p-MEK1 and p-ERK (P < 0.01, P < 0.04, respectively). Stress-induced p-38-MAPK (P = 0.04) and c-Jun kinase signaling involved MAPK8IP2 (−2.1 fold) expression decreased which protects against reactive oxygen species. Although pro-inflammatory p-NFkB (P = 0.06) decrease was mild, its promoter TNFRS11 expression markedly (−25-fold) decreased. In contrast, anti-proliferative phosphatases PTPRZ1 and PPP2R2C expression increased.ConclusionssPIF post-fertilization primes endometrial-epithelium, while during implantation creates a beneficial pro-inflammatory milieu. PIF acts by balancing decidual pro-implantation properties while controlling excessive pro-proliferative and inflammatory signals expression. Overall, PIF influences critical peri-implantation events in a sequential coordinated fashion which facilitates embryo implantation.

A Neurocomputing Approach for Monitoring Plinian Volcanic Eruptions Using Infrasound

Plinian volcanic eruptions can inject a substantial amount of volcanic ash and gas into the stratosphere, which can present a severe hazard to commercial air traffic. A hazardous volcanic ash eruption was reported on April 14, 2010, and London's aviation authority issued an alert that an ash plume was moving from an eruption in Iceland towards northwestern Europe. This eruption resulted in the closure of large areas of European airspace. Large plinian volcanic eruptions radiate infrasonic signals that can be detected by a global infrasound array network. To reduce potential hazards for commercial aviation from volcanic ash, these infrasound sensor arrays have been used to detect infrasonic signals released by sustained volcanic eruptions that can inject ash into the stratosphere at aircraft's cruising altitudes, typically in the order of 10km. A system that is capable of near, real-time eruption detection and discrimination of plinian eruptions from other natural phenomena that can produce infrasound with overlapping spectral content (0.01 to 0.1Hz) is highly desirable to provide ash-monitoring for commercial aviation. In this initial study, cepstral features are extracted from plinian volcanic eruption and mountain associated wave infrasound signals. These feature vectors are then used to train and test a two-module neural network classifier. One module is dedicated to classifying plinian volcano eruptions, the other mountain associated waves. Using an independent validation dataset, the classifier's correct classification rate is 91.5%.

Model Update March 2011: Upper Mantle Heterogeneity beneath North America from Traveltime Tomography with Global and USArray Transportable Array Data

Online material : P -wave tomography model for the United States; scripts for plotting cross-sections. In 2011, the Transportable Array of USArray (http://www.iris.edu/USArray/), the seismological component of EarthScope (http://www.earthscope.org/), continued to extend east of the Rocky Mountains and the Great Plains and into the Midwest and Gulf Coast regions where not many routinely processed data were available for previous regional- or global-scale traveltime inversions. In previous papers (Burdick et al. 2008, 2009, 2010) we presented 3-D tomographic models of mantle P -wavespeed from global and USArrayTA traveltime data through November 2007, December 2008, and January 2010, respectively. Here we present a model update using USArrayTA data through March 2011. The new model, MITP\_USA\_2011MAR, is available as an electronic supplement. Interpretation of the 3-D tomographic images is beyond the scope of this brief research note. The method for traveltime tomography used here is described in previous papers (Li et al. 2008; Burdick et al. 2008), but for the sake of completeness we include a brief summary. We perform global (linearized) inversions of P -wave traveltime residuals using an adaptable grid with a minimum grid spacing of 0.3° × 0.3° × 45 km. The spacing of the adaptable grid is adjusted based on raypath coverage in each mantle volume. The data included in the inversion consist of ∼10 million P -wave residuals from the International Seismological Centre and the National Earthquake Information Center processed using the algorithms developed by Engdahl et al. (1998)—henceforth referred as the EHB catalog—and the database …

Intact INI1 Gene Region With Paradoxical Loss of Protein Expression in AT/RT

Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant central nervous system tumor often misdiagnosed as some other type of pediatric embryonal tumor, such as medulloblastoma (MB). Distinguishing AT/RT from primitive neuroectodermal tumor/MB is of clinical significance, as the reported survival rate of patients with AT/RT is much lower than that of patients with average-risk primitive neuroectodermal tumor/MB. The diagnosis of AT/RT currently relies primarily on the morphologic assessment and immunostaining of a few known markers, such as the lack of INI1 protein expression. Immunohistochemical staining of INI1 is considered very sensitive and is highly specific for the detection of INI1 genetic defects. Genetic studies have shown that deletion or mutation of the INI1 gene, which is located on 22q11.2, occurs in AT/RT lesions. During our gene expression microarray analysis, we unexpectedly found a subgroup of AT/RT patients still expressing INI1 mRNA, even though INI1 proteins were negative by immunohistochemistry in those cases. Direct DNA sequencing showed no INI1 sequence alternation in 3 of 4 AT/RTs. Point mutation was found in only 1 allele of the fourth case, which would result in a frameshift mutation and generate a new INI1 protein with an extra 100-aa tail. Global array comparative genomic hybridization analysis confirmed no aberration around the INI1 gene at 22q11.2. It also extended our knowledge on the chromosomal aberration situations in our series. This study reveals that a novel yet unidentified posttranscriptional regulatory mechanism(s) for INI1 protein synthesis exists in AT/RT tumor cells.

Implications of changing El Niño patterns for biological dynamics in the equatorial Pacific Ocean

[1] El Nino events are known to strongly affect biological production and ecosystem structure in the tropical Pacific. Understanding and predicting biological processes in this area are hampered because the existing in situ observing system focuses primarily on physical measurements and does not observe key biological parameters; the only high spatial and temporal resolution biology-related observations are from the global array of ocean color satellites which provide an estimate of surface chlorophyll concentrations only. Since the 1990s, an apparent shift of the El Nino maximum sea-surface temperature (SST) warm anomaly from the eastern to the central equatorial Pacific has frequently been observed. Satellite observations show significant changes in chlorophyll-a (Chl-a), new production (NP) and total primary production (PP) in the equatorial Pacific associated with these new central Pacific (CP) El Nino events (also called El Nino Modoki) relative to eastern Pacific El Ninos. During CP-El Ninos, NP, Chl-a and PP in the central basin are depressed relative to EP-El Ninos and lower values of Chl-a and PP coincide spatially with higher SST in the central Pacific. While surface Chl-a, and integrated NP and PP over the entire equatorial band, decrease during both CP and EP-El Ninos, the magnitude of this decrease seems to depend more on the intensity than type of event. The changing spatial patterns have significant implications for equatorial biological dynamics if, as has been suggested, CP-El Ninos increase in frequency in the future. Citation: Turk, D., C. S. Meinen, D. Antoine, M. J. McPhaden, and M. R. Lewis (2011), Implications of changing El Nino patterns for biological dynamicsinthe equatorial PacificOcean, Geophys. Res. Lett., 38, L23603, doi:10.1029/2011GL049674.

Signal Denoise Method Based on the Higher Order Cumulant and Local Tangent Space Mean Reconstruction

In signal denoise method to nonlinear time series based on principle manifold learning, reduction target dimension is chosen at random, which cause low efficiency. Local low dimensional manifold is obtained by the eigenvalue decomposition to the covariance matrix, but covariance belongs to the second order statistics and cannot reflect the nonlinear essential structure of signal, these reduce denoise efficiency and effect. In order to solve these problem, a new denoise algorithm based on the higher order cumulant and local tangent space mean reconstruction is proposed in this reserch. First, the signal's intrinsic dimension is obtained as dimension of reduction targets by maximum likelihood estimation. And then making use of restraining character to colored noise of high order cumulan,covariance matrix is constructed by high order cumulant function instead of second order moment function. The data outside intrinsic dimension space will be regarded as noise signal to be eliminated. Finanly the process of global array by affine transformation will be replaced by mean reconstruction,the data after denoise may be obtained in the inverse process of the phase space reconstruction. The effectiveness of the algorithm is verified through the denoise experiment in fan vibration signal with noise.

Global microRNA expression profiling of microdissected tissues identifies miR‐135b as a novel biomarker for pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is known for its poor prognosis resulting from being diagnosed at an advanced stage. Accurate early diagnosis and new therapeutic modalities are therefore urgently needed. MicroRNAs (miRNAs), considered a new class of biomarkers and therapeutic targets, may be able to fulfill those needs. Combining tissue microdissection with global miRNA array analyses, cell type-specific miRNA expression profiles were generated for normal pancreatic ductal cells, acinar cells, PDAC cells derived from xenografts and also from macrodissected chronic pancreatitis (CP) tissues. We identified 78 miRNAs differentially expressed between ND and PDAC cells providing new insights into the miRNA-driven pathophysiological mechanisms involved in PDAC development. Having filtered miRNAs which are upregulated in the three pairwise comparisons of PDAC vs. ND, PDAC vs. AZ and PDAC vs. CP, we identified 15 miRNA biomarker candidates including miR-135b. Using relative qRT-PCR to measure miR-135b normalized to miR-24 in 75 FFPE specimens (42 PDAC and 33 CP) covering a broad range of tumor content, we discriminated CP from PDAC with a sensitivity and specificity of 92.9% [95% CI=(80.5, 98.5)] and 93.4% [95% CI=(79.8, 99.3)], respectively. Furthermore, the area under the curve (AUC) value reached of 0.97 was accompanied by positive and negative predictive values of 95% and 91%, respectively. In conclusion, we report pancreatic cell-specific global miRNA profiles, which offer new candidate miRNAs to be exploited for functional studies in PDAC. Furthermore, we provide evidence that miRNAs are well-suited analytes for development of sensitive and specific aid-in-diagnosis tests for PDAC.

Systems genetics of susceptibility to obesity-induced diabetes in mice

Inbred strains of mice are strikingly different in susceptibility to obesity-driven diabetes. For instance, deficiency in leptin receptor (db/db) leads to hyperphagia and obesity in both C57BL/6 and DBA/2 mice, but only on the DBA/2 background do the mice develop beta-cell loss leading to severe diabetes, while C57BL/6 mice are relatively resistant. To further investigate the genetic factors predisposing to diabetes, we have studied leptin receptor-deficient offspring of an F2 cross between C57BL/6J (db/+) males and DBA/2J females. The results show that the genetics of diabetes susceptibility are enormously complex and a number of quantitative trait loci (QTL) contributing to diabetes-related traits were identified, notably on chromosomes 4, 6, 7, 9, 10, 11, 12, and 19. The Chr. 4 locus is likely due to a disruption of the Zfp69 gene in C57BL/6J mice. To identify candidate genes and to model coexpression networks, we performed global expression array analysis in livers of the F2 mice. Expression QTL (eQTL) were identified and used to prioritize candidate genes at clinical trait QTL. In several cases, clusters of eQTLs colocalized with clinical trait QTLs, suggesting a common genetic basis. We constructed coexpression networks for both 5 and 12 wk old mice and identified several modules significantly associated with clinical traits. One module in 12 wk old mice was associated with several measures of hepatic fat content as well as with other lipid- and diabetes-related traits. These results add to the understanding of the complex genetic interactions contributing to obesity-induced diabetes.

North Atlantic storminess and Atlantic Meridional Overturning Circulation during the last Millennium: Reconciling contradictory proxy records of NAO variability

Within the last Millennium, the transition between the Medieval Climate Anomaly (MCA; ca. 1000–1300CE) and the Little Ice Age (LIA; ca. 1400–1800CE) has been recorded in a global array of climatic and oceanographic proxies. In this study, we review proxy evidence for two alternative hypotheses for the effects of this shift in the North Atlantic region. One hypothesis postulates that the MCA/LIA transition included a weakening of the Atlantic Meridional Overturning Circulation (AMOC) and a transition to more negative North Atlantic Oscillation (NAO) conditions, resulting in a strong cooling of the North Atlantic region. The alternative hypothesis proposes a MCA/LIA shift to an increased number of storms over the North Atlantic linked to increased mid-latitude cyclogenesis and hence a pervasive positive NAO state. The two sets of proxy records and thus of the two competing hypotheses are then reconciled based on available results from climate model simulations of the last Millennium. While an increase in storm frequency implicates positive NAO, increased intensity would be consistent with negative NAO during the LIA. Such an increase in cyclone intensity could have resulted from the steepening of the meridional temperature gradient as the poles cooled more strongly than the Tropics from the MCA into the LIA.