bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lactate Dehydrogenase B Is Critical for Hyperactive mTOR-Mediated Tumorigenesis
Authors: Zha Xiaojun , Wang Fang , Wang Ying , He Shaozong , Jing Yanling , Wu Xueyan , Zhang Hongbing 
Published: January 2011

Abstract
Mammalian target of rapamycin (mTOR) is a major downstream effector of the receptor tyrosine kinase (RTK)–phosphoinositide 3-kinase (PI3K)–v-akt murine thymoma viral oncogene homologue 1 (AKT) signaling pathway. Although this signaling network is frequently altered in cancer, the underlying mechanisms that cause tumorigenesis as a result of activated mTOR remain largely unknown. We report here that expression of lactate dehydrogenase B (LDHB), a critical enzymatic activator of glycolysis, was upregulated in an mTOR-dependent manner in TSC1−/−, TSC2−/−, PTEN−/−, or activated AKT1-expressing mouse embryonic fibroblasts (MEF). LDHB gene expression was transactivated by signal transducer and activator of transcription 3 (STAT3), a key tumorigenic driver in many cancers, acting as a downstream mTOR effector in both mouse MEFs and human cancer cells. LDHB attenuation blunted the tumorigenic potential of oncogenic TSC2-null cells in nude mice. We concluded that LDHB is a downstream target of mTOR that is critical for oncogenic mTOR-mediated tumorigenesis. Our findings offer proof of concept for targeting LDHB as a therapeutic strategy in cancers driven by aberrant activation of the RTK-PI3K-AKT-mTOR signaling cascade. Cancer Res; 71(1); 13–8. ©2011 AACR.
Plasminogen Activator uPA Is a Direct Transcriptional Target of the JAG1-Notch Receptor Signaling Pathway in Breast Cancer
Authors: Shimizu Mamiko , Cohen Brenda , Goldvasser Pavel , Berman Hal , Virtanen Carl , Reedijk Michael 
Published: January 2011

Abstract
Aberrant activation of the Notch receptor signaling pathway and overexpression of the Notch ligand JAG1 are associated with poor outcome in breast cancer. The plasminogen activator system, which includes urokinase-type plasminogen activator (uPA), has been validated as a marker of recurrence, high metastasis risk and death in breast malignancy. By using microarray profiling of breast cancer cell lines that had undergone siRNA-mediated abrogation of Notch signaling we uncovered a link between activated Notch signaling and uPA expression. An association between elevated expression of the Notch ligand JAG1, uPA, and the basal-like breast cancer subtype was confirmed in breast cancer cell lines. The association between JAG1 and uPA expression persisted in a survey of primary carcinomas of the breast. We found that Notch knockdown reduced transcription of uPA and phenocopied uPA knockdown in breast cancer cells. Through mutational analysis we identified a CBF-1 binding site in the uPA promoter that is required for direct transcriptional regulation by Notch. These data suggest that JAG1-induced Notch activation results in breast cancer progression through upregulation of the plasminogen activator system, directly linking these 2 important pathways of poor prognosis. Cancer Res; 71(1); 277–86. ©2010 AACR.
High Basal Nuclear Levels of Nrf2 in Acute Myeloid Leukemia Reduces Sensitivity to Proteasome Inhibitors
Authors: Rushworth Stuart A. , Bowles Kristian M. , MacEwan David J. 
Published: January 2011

Abstract
Proteasome inhibitors such as bortezomib exhibit clinical efficacy in multiple myeloma, but studies in acute myeloid leukemia (AML) have been disappointing to date. The apparent failure in AML likely reflects a lack of biological understanding that might clarify applications of proteosome inhibitors in this disease. Here we show that AML cells are considerably less sensitive than control noncancerous cells to bortezomib-induced cytotoxicity, permitting most bortezomib-treated AML cells to survive treatment. We traced reduced bortezomib sensitivity to increased basal levels of nuclear Nrf2, a transcription factor that stimulates protective antioxidant enzymes. Bortezomib stimulates cytotoxicity through accumulation of reactive oxygen species (ROS) but elevated basal levels of nuclear Nrf2 present in AML cells reduced ROS levels, permitting AML cells to survive drug treatment. We further found that the Nrf2 transcriptional repressor Bach1 is rapidly inactivated by bortezomib, allowing rapid induction of Nrf2-regulated cytoprotective and detoxification genes that protect AML cells from bortezomib-induced apoptosis. By contrast, nonmalignant control cells lacked constitutive activation of Nrf2, such that bortezomib-mediated inactivation of Bach1 led to a delay in induction of Nrf2-regulated genes, effectively preventing the manifestation of apoptotic protection that is seen in AML cells. Together, our findings argue that AML might be rendered sensitive to proteasome inhibitors by cotreatment with either an Nrf2-inhibitory or Bach1-inhibitory treatment, rationalizing a targeted therapy against AML. Cancer Res; 71(5); 1999–2009. ©2011 AACR.
Detection of Circulating Tumor Cells in Human Peripheral Blood Using Surface-Enhanced Raman Scattering Nanoparticles
Authors: Wang Xu , Qian Ximei , Beitler Jonathan J. , Chen Zhuo Georgia , Khuri Fadlo R. , Lewis Melinda M. , Shin Hyung Ju C. , Nie Shuming , Shin Dong M. 
Published: January 2011

Abstract
The detection and characterization of circulating tumor cells (CTC) holds great promise for personalizing medicine and optimizing systemic therapy. However, low specificity, low sensitivity, and the time consuming nature of current approaches have impeded clinical adoption. Here we report a new method using surface-enhanced Raman spectroscopy (SERS) to directly measure targeted CTCs in the presence of white blood cells. SERS nanoparticles with epidermal growth factor peptide as a targeting ligand have successfully identified CTCs in the peripheral blood of 19 patients with squamous cell carcinoma of the head and neck (SCCHN), with a range of 1 to 720 CTCs per milliliter of whole blood. Our technique may provide an important new clinical tool for management of patients with SCCHN and other cancers. Cancer Res; 71(5); 1526–32. ©2011 AACR.
Negative Regulation of the Hippo Pathway by E3 Ubiquitin Ligase ITCH Is Sufficient to Promote Tumorigenicity
Authors: Salah Zaidoun , Melino Gerry , Aqeilan Rami I. 
Published: January 2011

AbstractThe Hippo tumor suppressor pathway, originally defined in fruit flies, regulates cellular proliferation and survival and exerts profound effects on normal mammalian cell fate and tumorigenesis. The present understanding of Hippo pathway components and mechanisms remains incomplete in cancer. WW domain-containing proteins regulate diverse biological processes through interaction with proline-tyrosine (PPxY)-containing targets. In this study, we report that the E3 ubiquitin ligase ITCH regulates stability of LATS1, a serine/threonine kinase in the Hippo pathway, through protein–protein interaction of the PPxY motifs of LATS1 with the WW domains of ITCH. Ubiquitination of LATS1 catalyzed by ITCH stimulated the proteasomal degradation of LATS1. Furthermore, ITCH-mediated degradation of LATS1 was associated with enhanced cell growth, induction of epithelial-mesenchymal transition, and increased tumorigenicity. Conversely, ITCH depletion increased LATS1 levels, enhancing FAS-induced apoptosis and reducing proliferation, survival, and migration. These phenotypes were rescued when both ITCH and LATS1 were depleted. Together, our results reveal a novel functional link between ITCH and the Hippo pathway, deepening their critical roles in tumorigenesis. Cancer Res; 71(5); 2010–20. ©2011 AACR.
A Selective Matrix Metalloproteinase-12 Inhibitor Retards Atherosclerotic Plaque Development in Apolipoprotein E–Knockout Mice
Authors: Johnson Jason L. , Devel Laurent , Czarny Bertrand , George Sarah J. , Jackson Christopher L. , Rogakos Vassilis , Beau Fabrice , Yiotakis Athanasios , Newby Andrew C. , Dive Vincent 
Published: January 2011

Objective—
Matrix metalloproteinase (MMP)-12 has been implicated in plaque progression and instability and is also amenable to selective inhibition. In this study, we investigated the influence of a greater than 10-fold selective synthetic MMP-12 inhibitor on plaque progression in the apolipoprotein E knockout mouse model of atherosclerosis.

Methods and Results—
A phosphinic peptide (RXP470.1) that is a potent, selective murine MMP-12 inhibitor significantly reduced atherosclerotic plaque cross-sectional area by approximately 50% at 4 different vascular sites in male and female apolipoprotein E knockout mice fed a Western diet. Furthermore, RXP470.1 treatment resulted in less complex plaques with increased smooth muscle cell:macrophage ratio, less macrophage apoptosis, increased cap thickness, smaller necrotic cores, and decreased incidence of calcification. Additional in vitro and in vivo findings indicate that attenuated monocyte/macrophage invasion and reduced macrophage apoptosis probably underlie the beneficial effects observed on atherosclerotic plaque progression with MMP-12 inhibitor treatment.

Conclusion—
Our data demonstrate that a selective MMP-12 inhibitor retards atherosclerosis development and results in a more fibrous plaque phenotype in mice. Our study provides proof of principle to motivate translational work on MMP-12 inhibitor therapy in humans.
Door-to-Door Capture of Incident and Prevalent Stroke Cases in Durango, Mexico
Authors: Cantu-Brito Carlos , Majersik Jennifer J. , Sánchez Brisa N. , Ruano Angel , Becerra-Mendoza Daniela , Wing Jeffrey J. , Morgenstern Lewis B. 
Published: January 2011

Background and Purpose—Stroke incidence and prevalence estimates in developing countries should include stroke cases not presenting to hospital. We performed door-to-door stroke case ascertainment in Durango Municipality, Mexico, to estimate stroke incidence and prevalence and to determine the error made by only ascertaining hospital cases.Methods—Between September 2008 and March 2009, 1996 housing units were randomly sampled to screen for stroke in Durango Municipality residents 35 years of age and older. Field workers utilized a validated screening tool. Those screening positive were referred to a neurologist for history and examination and a head CT scan. Prevalence and cumulative incidence from the door-to-door surveillance were calculated and compared with previously reported hospitalization rates during the same defined time.Results—Respondents included 2437 subjects from 1419 homes. The refusal rate was 3.8%. Twenty subjects had verified or probable stroke. The prevalence of probable or verified stroke was 7.7 per 1000 (95% CI, 4.3 per 1000–11.2 per 1000). Five patients had a stroke during the time of the hospital surveillance, yielding a cumulative incidence of 232.3 per 100 000 (95% CI, 27.8–436.9). Two of the 5 cases were captured by door-to-door surveillance but not by hospital surveillance.Conclusions—This study provides the first community-based stroke prevalence and incidence estimates in Mexico. The wide confidence intervals, despite the large number of surveyed housing units, suggest the need for more advanced sampling strategies for stroke surveillance in the developing world.
Endogenous Tissue Plasminogen Activator Mediates Bone Marrow Stromal Cell-Induced Neurite Remodeling After Stroke in Mice
Authors: Shen Li Hong , Xin Hongqi , Li Yi , Zhang Rui Lan , Cui Yisheng , Zhang Li , Lu Mei , Zhang Zheng Gang , Chopp Michael 
Published: January 2011

Background and Purpose—
Bone marrow stromal cells (BMSC) decrease neurological deficits in rodents after stroke and concomitantly induce extensive neurite remodeling in the brain, which highly correlates with the improvement of neurological function. We investigated the effects of endogenous tissue plasminogen activator (tPA) on neurite remodeling after BMSC treatment.

Methods—

Adult C57BL/6 wild-type (WT) mice and tPA knockout (tPA
−/−
) mice were subjected to middle cerebral artery occlusion, followed by an injection of 1×10
6
BMSC (n=18) or phosphate-buffered saline (n=18) into the tail vein 24 hours later. Behavioral tests were performed at 3, 7, and 14 days after middle cerebral artery occlusion. Animals were euthanized at 14 days after stroke.

Results—

The effects of BMSC on functional recovery depended on presence or absence of tPA, even after adjusting for imbalanced stroke severity. BMSC significantly improve functional recovery in WT mice compared to WT controls but show no beneficial effect in the tPA
−/−
mice compared to tPA
−/−
controls. Axonal density and synaptophysin-positive areas along the ischemic boundary zone of the cortex and striatum in WT mice are significantly higher than in the tPA
−/−
mice. BMSC treatment significantly increases tPA protein level and activity only in WT mice.

Conclusions—
Our results suggest that endogenous tPA promotes BMSC-induced neurite outgrowth and may contribute to functional recovery after stroke.
Circulation and Transport at the Southeast Tip of Greenland
Authors: Daniault Nathalie , Lherminier Pascale , Mercier Herlé 
Published: January 2011

Abstract
The circulation and related transports at the southeast tip of Greenland are determined from direct current observations of a moored current meter array. The measurements cover a time span from June 2004 to June 2006. The net mean total southwestward transport of the East Greenland–Irminger Current from the midshelf (20 km off the coast at 60°N) to the 2070-m isobath (about 100 km offshore) was estimated as 17.3 Sv (Sv ≡ 106 m3 s−1) with an uncertainty of 1 Sv. The transport variability is characterized by a standard deviation of 3.8 Sv with a peak-to-peak amplitude up to 30 Sv. The seasonal variability has an amplitude of 1.5 Sv. Frequencies around 0.1 day−1 dominate the signal, although a variability at lower frequency (∼1 month−1) also appears in winter. The coherence between the observed transport variability and the wind stress curl variability over the Irminger Sea differs significantly from 0 at the 95% confidence level for periods greater than 5 days.
Seasonal Modulation of Eddy Kinetic Energy and Its Formation Mechanism in the Southeast Indian Ocean
Authors: Jia Fan , Wu Lixin , Qiu Bo 
Published: January 2011

Abstract
Mesoscale eddy activity in the southeast Indian Ocean (15°–30°S, 60°–110°E) is investigated based on available satellite altimetry observations. The observed sea level anomaly data show that this region is the only eastern basin among the global oceans where strong eddy activity exists. Furthermore, the eddy kinetic energy (EKE) level in this region displays a distinct seasonal cycle with the maximum in austral summer and minimum in austral winter. It is found that this seasonal modulation of EKE is mediated by baroclinic instability associated with the surface-intensified South Indian Countercurrent (SICC) and the underlying South Equatorial Current (SEC) system. In austral spring and summer the enhanced flux forcing of combined meridional Ekman and geostrophic convergence strengthens the upper-ocean meridional temperature gradient, intensifying the SICC front and its vertical velocity shear. Modulation of the vertical velocity shear results in the seasonal changes in the strength of baroclinic instability, leading to the seasonal EKE variations in the southeast Indian Ocean.
Parameterizations and Algorithms for Oceanic Whitecap Coverage
Authors: Goddijn-Murphy Lonneke , Woolf David K. , Callaghan Adrian H. 
Published: January 2011

Abstract
Shipboard measurements of fractional whitecap coverage W and wind speed at 10-m height, obtained during the 2006 Marine Aerosol Production (MAP) campaign, have been combined with ECMWF wave model and Quick Scatterometer (QuikSCAT) satellite wind speed data for assessment of existing W parameterizations. The wind history trend found in an earlier study of the MAP data could be associated with wave development on whitecapping, as previously postulated. Whitecapping was shown to be mainly wind driven; for high wind speeds (&gt;9 m s−1), a minor reduction in the scatter of in situ W data points could be achieved by including sea state conditions or by using parameters related to wave breaking. The W values were slightly larger for decreasing wind/developed waves than for increasing wind/developing waves, whereas cross-swell conditions (deflection angle between wind and swell waves between ±45° and ±135°) appeared to dampen whitecapping. Tabulated curve fitting results of the different parameterizations show that the errors that could not be attributed to the propagation of the standard error in U10 remained largely unexplained. It is possible that the counteracting effects of wave development and cross swell undermine the performance of the simple parameterizations in this study.
Global Variability of the Wavenumber Spectrum of Oceanic Mesoscale Turbulence
Authors: Xu Yongsheng , Fu Lee-Lueng 
Published: January 2011

Abstract
The wavenumber spectra of sea surface height from satellite altimeter observations have revealed complex spatial variability that cannot be explained by a universal theory of mesoscale turbulence. Near the edge of the core regions of high eddy energy, agreement is observed with the prediction of the surface quasigeostrophic (SQG) turbulence theory, which has fundamental differences from that of the traditional quasigeostrophic (QG) turbulence theory. In the core regions of high eddy energy, the spectra are consistent with frontogenesis that is not fully accounted for by the SQG theory. However, the observations in the vast ocean interior of low eddy energy exhibit substantial differences from the predictions of existing theories of oceanic mesoscale turbulence. The spectra in these regions may reflect the ocean’s response to short-scale atmospheric forcing and air–sea interaction. The observations presented in this paper serve as a test bed for new theories and ocean general circulation models.
The NOAA Hydrometeorology Testbed Soil Moisture Observing Networks: Design, Instrumentation, and Preliminary Results
Authors: Zamora Robert J. , Ralph F. Martin , Clark Edward , Schneider Timothy 
Published: January 2011

Abstract
The NOAA Hydrometeorology Testbed (HMT) program has deployed soil moisture observing networks in the watersheds of the Russian River and the North Fork (NF) of the American River in northern California, and the San Pedro River in southeastern Arizona. These networks were designed to serve the combined needs of the hydrological, meteorological, agricultural, and climatological communities for observations of soil moisture on time scales that range from minutes to decades.
The networks are a major component of the HMT program that has been developed to accelerate the development and infusion of new observing technologies, modeling methods, and recent scientific research into the National Weather Service (NWS) offices and to help focus research and development efforts on key hydrological and meteorological forecast problems. These forecast problems are not only of interest to the NWS, but they also play a crucial role in providing input to water managers who work at the national, state, and local government levels to provide water for human consumption, agriculture, and other needs.
The HMT soil moisture networks have been specifically designed to capture the changes in soil moisture that are associated with heavy precipitation events and runoff from snowpack during the melt season. This paper describes the strategies used to site the networks and sensors as well as the selection, testing, and calibration of the soil moisture probes. In addition, two illustrative examples of the data gathered by the networks are shown.
The first example shows changes in soil moisture observed before and during a flood event on the Babocomari River tributary of the San Pedro River near Sierra Vista, Arizona, on 23 July 2008. The second example examines a 5-yr continuous time series of soil moisture gathered at Healdsburg, California. The time series illustrates the transition from a multiyear wet period to exceptionally dry conditions from a soil moisture perspective.
Optimal Determination of Parameters for Gamma-Type Drop Size Distributions Based on Moments
Authors: Handwerker Jan , Straub Winfried 
Published: January 2011

AbstractMeasured raindrop size distributions are often approximated by analytical functions. The parameters determining such functions are usually derived from measured data. This procedure can suffer from various uncertainties. The most important of which are (i) the limited detection range of measuring devices such as, for example, disdrometers, and (ii) poor statistics resulting from the rare appearance of relatively large drops.One way to derive the parameters is the moments method that has a degree of freedom in the choice of the moments. The aim of this study is to find an optimal choice of moments. To this end, numerical experiments are performed by calculating random samples from drop populations with gamma-shaped size distributions. These samples are evaluated as they were recorded by an ideal disdrometer whose single limitation is the cutoff with respect to very small and very large raindrops. From that data the parameters mentioned above are determined by the moments method. The truncation of the measurement is explicitly taken into account during the retrieval. Further, all possible combinations of three different moments used to derive the gamma parameters are impartially compared.It turns out that parameters derived on the basis of low-order moments are less affected by biases and noise than parameters derived by larger-order moments, that is, the sampling problem is more severe than the truncation problem, especially because the latter can be overcome much more efficiently within the retrieval algorithm. It is shown that by using very low-order moments and estimating the unmeasured fraction of the moments, optimal results from real measurements can be obtained.
Wavelet Analysis of Atmospheric Turbulence over a Coral Reef Flat
Authors: Wiebe Andrew , Sturman Andrew , McGowan Hamish 
Published: January 2011

Abstract
The world’s tropical coral reefs are at risk of severe bleaching episodes and species decline in response to global climate variability. The ecological and economic value of reef ecosystems is enormous, yet very little is known of the physical interactions that take place at the coral–ocean–atmosphere interfaces. This paper introduces and validates a novel technique for the acquisition of surface energy balance measurements over Heron Reef, part of the Capricorn Bunker Group of the southern Great Barrier Reef, Australia. Measurements of surface energy and radiation exchanges were made using a Campbell Scientific eddy covariance (EC) measurement system mounted on a floating pontoon anchored to the reef flat. A Nortek Vector velocimeter was positioned next to the pontoon to record wave motion. Wavelet analysis techniques were used to decompose the turbulent exchange of sensible heat measured by the EC unit and to compare vertical velocity measurements with wave-induced motion recorded by the velocimeter. The results indicate that although the EC system and the velocimeter share intermittent periods of high common power in their respective wavelet variance spectra, these regions are not coherent and differ in strength by more than an order of magnitude. It was concluded that over a standard averaging period of 30 min the wave-induced motion of the pontoon would not significantly interfere with the acquisition and calculation of turbulent fluxes of sensible and latent heat, thereby confirming the robustness of this method of obtaining surface energy balance measurements over coral reefs.