Modes of mesoscale sea surface height and temperature variability in the East Australian

[1] Mesoscale variability where the East Australian Current (EAC) separates from the coast is studied using sea surface temperature and surface velocity streamfunction observed by satellite and a regional numerical model. The mean circulation simulated by the model (the Regional Ocean Modeling System (ROMS)) is compared to a high-resolution regional climatology, and the realism of the simulated mesoscale variability is tested by comparison to statistical analyses of the satellite data. Both ROMS and data show spectral peaks in the mesoscale energy band at periods between 90 and 180 days. Complex Empirical Orthogonal Function (EOF) analysis identifies two significant modes of mesoscale variability in the data; an Eddy Mode, for which the variability propagates southwestward along the coast, and a Wave Mode, for which phase propagation is predominantly onshore. The regional model open boundary conditions include only annual and semiannual harmonics of variability so remote mesoscale forcing is absent. The Eddy Mode is represented well in the model indicating this aspect of the circulation results from local instabilities of the flow and that its underlying dynamical process is simulated well. While the observed and modeled Wave Modes have some similarities, their differences suggest the model is deficient in representing westward propagation of mesoscale period variability in the region. Whatever the source of this energy, the orthogonality property of the EOF analysis indicates the Wave Mode does not interact significantly with eddy processes in the EAC separation

Host and viral determinants for MxB restriction of HIV-1 infection

Background: Interferon-induced cellular proteins play important roles in the host response against viral infection. The Mx family of dynamin-like GTPases, which include MxA and MxB, target a wide variety of viruses. Despite considerable evidence demonstrating the breadth of antiviral activity of MxA, human MxB was only recently discovered to specifically inhibit lentiviruses. Here we assess both host and viral determinants that underlie MxB restriction of HIV-1 infection. Results: Heterologous expression of MxB in human osteosarcoma cells potently inhibited HIV-1 infection (~12-fold), yet had little to no effect on divergent retroviruses. The anti-HIV effect manifested as a partial block in the formation of 2-long terminal repeat circle DNA and hence nuclear import, and we accordingly found evidence for an additional post-nuclear entry block. A large number of previously characterized capsid mutations, as well as mutations that abrogated integrase activity, counteracted MxB restriction. MxB expression suppressed integration into gene-enriched regions of chromosomes, similar to affects observed previously when cells were depleted for nuclear transport factors such as transportin 3. MxB activity did not require predicted GTPase active site residues or a series of unstructured loops within the stalk domain that confer functional oligomerization to related dynamin family proteins. In contrast, we observed an N-terminal stretch of residues in MxB to harbor key determinants. Protein localization conferred by a nuclear localization signal (NLS) within the N-terminal 25 residues, which was critical, was fully rescuable by a heterologous NLS. Consistent with this observation, a heterologous nuclear export sequence (NES) abolished full-length MxB activity. We additionally mapped sub-regions within amino acids 26–90 that contribute to MxB activity, finding sequences present within residues 27–50 particularly important. Conclusions: MxB inhibits HIV-1 by interfering with minimally two steps of infection, nuclear entry and post-nuclear trafficking and/or integration, without destabilizing the inherent catalytic activity of viral preintegration complexes. Putative MxB GTPase active site residues and stalk domain Loop 4 -- both previously shown to be necessary for MxA function -- were dispensable for MxB antiviral activity. Instead, we highlight subcellular localization and a yet-determined function(s) present in the unique MxB N-terminal region to be required for HIV-1 restriction. Electronic supplementary material The online version of this article (doi:10.1186/s12977-014-0090-z) contains supplementary material, which is available to authorized users

Re-channelization of turbidity currents in South China Sea abyssal plain due to seamounts and ridges

Turbidity currents can be characterized as net-erosive, net-depositional or net-bypassing. Whether a flow is erosive, depositional or bypasses depends on the flow velocity, concentration and size but these can also be impacted by external controls such as the degree of confinement, slope gradient and substrate type and erodibility. Our understanding of the relative importance of these controls comes from laboratory experiments and numerical modelling, as well as from field data due to the proliferation of high-resolution 3D seismic and bathymetric data, as well as the outcrop and rock record. In this study, based on extensive multibeam and seismic reflection surveys in combination with International Ocean Discovery Program cores from the South China Sea, we document a new mechanism of turbidity current transformation from depositional to erosive resulting in channel incision. We show how confinement by seamounts and bedrock highs of previously unconfined turbidity currents has resulted in the development of seafloor channels. These channels are inferred to be the result of confinement of flows, which have traversed the abyssal plain, leading to flow acceleration allowing them to erode the seafloor substrate. This interpretation is further supported by the coarsening of flow deposits within the area of the seamounts, indicating that confinement has increased flow competency, allowing turbidity currents to carry larger volumes of coarse sediment which has been deposited in this region. This basin-scale depositional pattern suggests that pre-established basin topography can have an important control on sedimentation which can impact characteristics such as potential hydrocarbon storage

Interannual variability of the surface summertime eastward jet in the South China Sea

Author Posting. © American Geophysical Union, 2014. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Oceans 119 (2014): 7205–7228, doi:10.1002/2014JC010206.The summertime eastward jet (SEJ) located around 12°N, 110°E–113°E, as the offshore extension of the Vietnam coastal current, is an important feature of the South China Sea (SCS) surface circulation in boreal summer. Analysis of satellite-derived sea level and sea surface wind data during 1992–2012 reveals pronounced interannual variations in its surface strength (SSEJ) and latitudinal position (YSEJ). In most of these years, the JAS (July, August, and September)-mean SSEJ fluctuates between 0.17 and 0.55 m s−1, while YSEJ shifts between 10.7°N and 14.3°N. These variations of the SEJ are predominantly contributed from the geostrophic current component that is linked to a meridional dipole pattern of sea level variations. This sea level dipole pattern is primarily induced by local wind changes within the SCS associated with the El Niño-Southern Oscillation (ENSO). Enhanced (weakened) southwest monsoon at the developing (decaying) stage of an El Niño event causes a stronger (weaker) SEJ located south (north) of its mean position. Remote wind forcing from the tropical Pacific can also affect the sea level in the SCS via energy transmission through the Philippine archipelago, but its effect on the SEJ is small. The impact of the oceanic internal variability, such as eddy-current interaction, is assessed using an ocean general circulation model (OGCM). Such impact can lead to considerable year-to-year changes of sea level and the SEJ, equivalent to ∼20% of the observed variation. This implies the complexity and prediction difficulty of the upper ocean circulation in this region.This research was supported by the ONR grant N00014-12-1-03-23 and the NSF CAREER Award 0847605.2015-04-2

Investigating knowledge management factors affecting Chinese ICT firms performance: An integrated KM framework

This is an Author's Accepted Manuscript of an article published in the Journal of Information Systems Management, 28(1), 19 - 29, 2011, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/10580530.2011.536107.This article sets out to investigate the critical factors of Knowledge Management (KM) which are considered to have an impact on the performance of Chinese information and communication technology (ICT) firms. This study confirms that the cultural environment of an enterprise is central to its success in the context of China. It shows that a collaborated, trusted, and learning environment within ICT firms will have a positive impact on their KM performance

Liposomic lubricants suppress shear-stress induced inflammatory gene regulation in the joint in vivo

Osteoarthritis (OA) is a widespread, debilitating joint disease associated with articular cartilage degradation. It is driven via mechano-inflammatory catabolic pathways, presumed up-regulated due to increased shear stress on the cartilage-embedded chondrocytes, that lead to tissue degeneration. Here we demonstrate that the up-regulation of the matrix metalloproteinase 3 (Mmp3) and interleukin-1beta (Il1b) genes upon surgical joint destabilization in a model of murine OA is completely suppressed when lipid-based lubricants are injected into the joints. At the same time, Timp1, a compression but not shear-stress sensitive gene, is unaffected by lubricant. Our results provide direct evidence that biolubrication couples to catabolic gene regulation in OA, shed strong light on the nature of the chondrocytes' response to shear stress, and have clear implications for novel OA treatments

BMP-2 Up-Regulates PTEN Expression and Induces Apoptosis of Pulmonary Artery Smooth Muscle Cells under Hypoxia

To investigate the role of bone morphogenetic protein 2 (BMP-2) in regulation of phosphatase and tensin homologue deleted on chromosome ten (PTEN) and apoptosis of pulmonary artery smooth muscle cells (PASMCs) under hypoxia.Normal human PASMCs were cultured in growth medium (GM) and treated with BMP-2 from 5-80 ng/ml under hypoxia (5% CO(2)+94% N(2)+1% O(2)) for 72 hours. Gene expression of PTEN, AKT-1 and AKT-2 were determined by quantitative RT-PCR (QRT-PCR). Protein expression levels of PTEN, AKT and phosph-AKT (pAKT) were determined. Apoptosis of PASMCs were determined by measuring activities of caspases-3, -8 and -9. siRNA-smad-4, bpV(HOpic) (PTEN inhibitor) and GW9662 (PPARγ antagonist) were used to determine the signalling pathways.Proliferation of PASMCs showed dose dependence of BMP-2, the lowest proliferation rate was achieved at 60 ng/ml concentration under hypoxia (82.2±2.8%). BMP-2 increased PTEN gene expression level, while AKT-1 and AKT-2 did not change. Consistently, the PTEN protein expression also showed dose dependence of BMP-2. AKT activity significantly reduced in BMP-2 treated PASMCs. Increased activities of caspase-3, -8 and -9 of PASMCs were found after cultured with BMP-2. PTEN expression remained unchanged when Smad-4 expression was inhibited by siRNA-Smad-4. bpV(HOpic) and GW9662 (PPARγ inhibitor) inhibited PTEN protein expression and recovered PASMCs proliferation rate.BMP-2 increased PTEN expression under hypoxia in a dose dependent pattern. BMP-2 reduced AKT activity and increased caspase activity of PASMCs under hypoxia. The increased PTEN expression may be mediated through PPARγ signalling pathway, instead of BMP/Smad signalling pathway

Effects of the MDM-2 inhibitor Nutlin-3a on PDAC cells containing and lacking WT-TP53 on sensitivity to chemotherapy, signal transduction inhibitors and nutraceuticals

Mutations at the TP53 gene are readily detected (approximately 50-75%) in pancreatic ductal adenocarcinoma (PDAC) patients. TP53 was previously thought to be a difficult target as it is often mutated, deleted or inactivated on both chromosomes in certain cancers. In the following study, the effects of restoration of wild-type (WT) TP53 activity on the sensitivities of MIA-PaCa-2 pancreatic cancer cells to the MDM2 inhibitor nutlin-3a in combination with chemotherapy, targeted therapy, as well as, nutraceuticals were examined. Upon introduction of the WT-TP53 gene into MIA-PaCa-2 cells, which contain a TP53 gain of function (GOF) mutation, the sensitivity to the MDM2 inhibitor increased. However, effects of nutlin-3a were also observed in MIA-PaCa-2 cells lacking WT-TP53, as upon co-treatment with nutlin-3a, the sensitivity to certain inhibitors, chemotherapeutic drugs and nutraceuticals increased. Interestingly, co-treatment with nutlin-3a and certain chemotherapeutic drug such as irinotecan and oxaliplatin resulted in antagonistic effects in cells both lacking and containing WT-TP53 activity. These studies indicate the sensitizing abilities that WT-TP53 activity can have in PDAC cells which normally lack WT-TP53, as well as, the effects that the MDM2 inhibitor nutlin-3a can have in both cells containing and lacking WT-TP53 to various therapeutic agents

Abilities of berberine and chemically modified berberines to interact with metformin and inhibit proliferation of pancreatic cancer cells

Pancreatic cancer is devastating cancer worldwide with few if any truly effective therapies. Pancreatic cancer has an increasing incidence and may become the second leading cause of death from cancer. Novel, more effective therapeutic approaches are needed as pancreatic cancer patients usually survive for less than a year after being diagnosed. Control of blood sugar levels by the prescription drug metformin in diseases such as diabetes mellitus has been examined in association with pancreatic cancer. While the clinical trials remain inconclusive, there is hope that certain diets and medications may affect positively the outcomes of patients with pancreatic and other cancers. Other natural compounds may share some of the effects of metformin. One "medicinal" fruit consumed by millions worldwide is berberine (BBR). Metformin and BBR both activate AMP-activated protein kinase (AMPK) which is a key mediator of glucose metabolism. Glucose metabolism has been shown to be very important in cancer and its significance is increasing. In the following studies, we have examined the effects of metformin, BBR and a panel of modified BBRs (NAX compounds) and chemotherapeutic drugs on the growth of four different human pancreatic adenocarcinoma cell lines (PDAC). Interestingly, the effects of metformin could be enhanced by BBR and certain modified BBRs. Upon restoration of WT-TP53 activity in MIA-PaCa-2 cells, an altered sensitivity to the combination of certain NAX compounds and metformin was observed compared to the parental cells which normally lack WT-TP53. Certain NAX compounds may interact with WT-TP53 and metformin treatment to alter the expression of key molecules involved in cell growth. These results suggest a therapeutic approach by combining certain pharmaceutical drugs and nutraceuticals to suppress the growth of cancer cells

Emulsion PCR: A High Efficient Way of PCR Amplification of Random DNA Libraries in Aptamer Selection

Aptamers are short RNA or DNA oligonucleotides which can bind with different targets. Typically, they are selected from a large number of random DNA sequence libraries. The main strategy to obtain aptamers is systematic evolution of ligands by exponential enrichment (SELEX). Low efficiency is one of the limitations for conventional PCR amplification of random DNA sequence library in aptamer selection because of relative low products and high by-products formation efficiency. Here, we developed emulsion PCR for aptamer selection. With this method, the by-products formation decreased tremendously to an undetectable level, while the products formation increased significantly. Our results indicated that by-products in conventional PCR amplification were from primer-product and product-product hybridization. In emulsion PCR, we can completely avoid the product-product hybridization and avoid the most of primer-product hybridization if the conditions were optimized. In addition, it also showed that the molecule ratio of template to compartment was crucial to by-product formation efficiency in emulsion PCR amplification. Furthermore, the concentration of the Taq DNA polymerase in the emulsion PCR mixture had a significant impact on product formation efficiency. So, the results of our study indicated that emulsion PCR could improve the efficiency of SELEX