bluuebunny/crossref_metadata_2025_split huggingface dataset:
DYNAMICS OF MODIFIED PREDATOR-PREY MODELS
Authors: KLOEDEN P. E. , PÖTZSCHE C. 
Published: October 2010

Besides being structurally unstable, the Lotka–Volterra predator-prey model has another shortcoming due to the invalidity of the principle of mass action when the populations are very small. This leads to extremely large populations recovering from unrealistically small ones. The effects of linear modifications to structurally unstable continuous-time predator-prey models in a (small) neighbourhood of the origin are investigated here. In particular, it is shown that typically either a global attractor or repeller arises depending on the choice of coefficients.The analysis is based on Poincaré mappings, which allow an explicit representation for the classical Lotka–Volterra equations.
Acquired TNFRSF14 Mutations in Follicular Lymphoma Are Associated with Worse Prognosis
Authors: Cheung K-John J. , Johnson Nathalie A. , Affleck Joslynn G. , Severson Tesa , Steidl Christian , Ben-Neriah Susana , Schein Jacqueline , Morin Ryan D. , Moore Richard , Shah Sohrab P. , Qian Hong , Paul Jessica E. , Telenius Adele , Relander Thomas , Lam Wan , Savage Kerry , Connors Joseph M. , Brown Carolyn , Marra Marco A. , Gascoyne Randy D. , Horsman Douglas E. 
Published: October 2010

Abstract
Clinical correlative studies have linked 1p36 deletions with worse prognosis in follicular lymphoma (FL). In this study, we sought to identify the critical gene(s) in this region that is responsible for conferring inferior prognosis. BAC array technology applied to 141 FL specimens detected a minimum region of deletion (MRD) of ∼97 kb within 1p36.32 in 20% of these cases. Frequent single-nucleotide polymorphism–detected copy-neutral loss of heterozygosity was also found in this region. Analysis of promoter CpGs in the MRD did not reveal differential patterns of DNA methylation in samples that differed in 1p36 status. Exon sequencing of MRD genes identified somatic alterations in the TNFRSF14 gene in 3 of 11 selected cases with matching normal DNA. An expanded cohort consisting of 251 specimens identified 46 cases (18.3%) with nonsynonymous mutations affecting TNFRSF14. Overall survival (OS) and disease-specific survival (DSS) were associated with the presence of TNFRSF14 mutation in patients whose overall treatment included rituximab. We further showed that inferior OS and DSS were most pronounced in patients whose lymphomas contained both TNFRSF14 mutations and 1p36 deletions after adjustment for the International Prognostic Index [hazard ratios of 3.65 (95% confidence interval, 1.35–9.878, P = 0.011) and 3.19 (95% confidence interval, 1.06–9.57, P = 0.039), respectively]. Our findings identify TNFRSF14 as a candidate gene associated with a subset of FL, based on frequent occurrence of acquired mutations and their correlation with inferior clinical outcomes. Cancer Res; 70(22); 9166–74. ©2010 AACR.
Nox2 NADPH Oxidase Promotes Pathologic Cardiac Remodeling Associated with Doxorubicin Chemotherapy
Authors: Zhao Youyou , McLaughlin Declan , Robinson Emma , Harvey Adam P. , Hookham Michelle B. , Shah Ajay M. , McDermott Barbara J. , Grieve David J. 
Published: October 2010

Abstract
Doxorubicin is a highly effective cancer treatment whose use is severely limited by dose-dependent cardiotoxicity. It is well established that doxorubicin increases reactive oxygen species (ROS) production. In this study, we investigated contributions to doxorubicin cardiotoxicity from Nox2 NADPH oxidase, an important ROS source in cardiac cells, which is known to modulate several key processes underlying the myocardial response to injury. Nox2-deficient mice (Nox2−/−) and wild-type (WT) controls were injected with doxorubicin (12 mg/kg) or vehicle and studied 8 weeks later. Echocardiography indicated that doxorubicin-induced contractile dysfunction was attenuated in Nox2−/− versus WT mice (fractional shortening: 29.5 ± 1.4 versus 25.7 ± 1.0%; P &lt; 0.05). Similarly, in vivo pressure-volume analysis revealed that systolic and diastolic function was preserved in doxorubicin-treated Nox2−/− versus WT mice (ejection fraction: 52.6 ± 2.5 versus 28.5 ± 2.3%, LVdP/dtmin: −8,379 ± 416 versus −5,198 ± 527 mmHg s−1; end-diastolic pressure-volume relation: 0.051 ± 0.009 versus 0.114 ± 0.012; P &lt; 0.001). Furthermore, in response to doxorubicin, Nox2−/− mice exhibited less myocardial atrophy, cardiomyocyte apoptosis, and interstitial fibrosis, together with reduced increases in profibrotic gene expression (procollagen IIIαI, transforming growth factor-β3, and connective tissue growth factor) and matrix metalloproteinase-9 activity, versus WT controls. These alterations were associated with beneficial changes in NADPH oxidase activity, oxidative/nitrosative stress, and inflammatory cell infiltration. We found that adverse effects of doxorubicin were attenuated by acute or chronic treatment with the AT1 receptor antagonist losartan, which is commonly used to reduce blood pressure. Our findings suggest that ROS specifically derived from Nox2 NADPH oxidase make a substantial contribution to several key processes underlying development of cardiac contractile dysfunction and remodeling associated with doxorubicin chemotherapy. Cancer Res; 70(22); 9287–97. ©2010 AACR.
A dose-finding study with TAK-442, an oral factor Xa inhibitor, in patients undergoing elective total knee replacement surgery
Authors: Cao Charlie , Eriksson Bengt I. , Fisher William , Kupfer Stuart , Raskob Gary , Spaeder Jeffrey , Turpie Alexander G. G. , Weitz Jeffrey I. 
Published: October 2010

SummaryThis multicentre dose-finding study compared TAK-442, an oral factor Xa inhibitor, with enoxaparin for thromboprophylaxis after knee arthroplasty. In this parallel group study, patients were randomised to oral TAK-442 (40 or 80 mg once-daily [QD] or 10, 20, 40, or 80 mg twice-daily [BID] started 6–8 hours postoperatively), which was blinded as to dose, or to open-label subcutaneous enoxaparin (30 mg BID starting 12–24 hours postoperatively) for 10 days. Treatments were continued until bilateral venography was performed (maximum of 14 days). The primary efficacy endpoint was the composite of any deep-vein thrombosis, non-fatal pulmonary embolism or all-cause mortality, while the primary safety endpoint was major bleeding. Of 1,038 patients randomised who received at least one dose of study drug, 949 completed the study and 730 (76.9%) were evaluable for the primary efficacy analysis. Recruitment into the 10 and 20 mg BID dose groups was stopped early because the incidences of the primary efficacy endpoint were significantly higher than that with enoxaparin. The primary efficacy endpoint occurred in 22.0% of patients given enoxaparin and in 39.0%, 38.4%, 23.5%, 21.4%, 26.8%, and 14.3% of those receiving TAK-442 10 mg BID, 20 mg BID, 40 mg QD, 40 mg BID, 80 mg QD, and 80 mg BID, respectively. The incidences of major and clinically relevant non-major bleeding with TAK-442 were not dose-dependent or different from that with enoxaparin. All TAK-442 doses except 10 and 20 mg BID displayed similar efficacy and safety profiles to enoxaparin.
The dengue virus envelope protein induced PAI-1 gene expression via MEK/ERK pathways
Authors: Lin Yi-Ying , Chen Lien-Cheng , Wang Yi-Fen , Yeh Trai-Ming , Su Shu-Jem , Cheng Wei-Cheng , Chen Chang-Yu , Lin Kuan-Hua , Chou Miao-Chen , Shyu Huey-Wen 
Published: October 2010

SummaryDengue virus (DV) infections cause mild dengue fever or severe life-threatening dengue haemorrhagic fever (DHF)/ dengue shock syndrome (DSS). DV-infected patients have high plasma concentrations of plasminogen activator inhibitor type I (PAI-1). However, the mechanism to cause haemorrhage in DV infections remains poorly understood. In this study, investigation was carried out on the purified recombinant domain III of the envelope glycoprotein of DV serotypes 2 (EIII) and the signalling pathways of EIII leading to PAI-1 gene expression were measured by RT-PCR, Western blot, and immunofluorescence stain. Reporter gene constructs containing serially 5’-deleted sequences of the proximal human PAI-1 promoter region were constructed and then transfected to Huh7 cells, a human hepatoma cell line, prior to EIII treatment. EIII increased the PAI-1 mRNA and protein levels in a dose-dependent manner in Huh7 cells. Results showed that U0126, an inhibitor of extracellular signal-regulated kinase (ERK) kinase (MEK), almost completely suppressed EIII-induced PAI-1 expression. The results suggest that the MEK/ERK signalling pathways mediate the EIII-dependent induction of PAI-1 gene expression via the proximal promoter region.
The unsialylated subpopulation of recombinant activated factor VII binds to the asialo-glycoprotein receptor (ASGPR) on primary rat hepatocytes
Authors: Nielsen Hanne M. , Christensen Erik I. , Appa Rupa S. , Seested Torben 
Published: October 2010

SummaryRecombinant activated factor VII (rFVIIa; NovoSeven®) is a heterogeneously glycosylated serine protease used for treatment of haemophiliacs with inhibitors. The drug substance contains a subpopulation consisting of ~20% of rFVIIa molecules which are unsialylated and consists of carbohydrate moieties with terminally exposed galactose and N-acetyl-D-galactosamine (GalNAc). Recently, data from an in situ per-fused liver model showed that a subpopulation of rFVIIa, appearing to be unsialylated rFVIIa, was cleared by the liver, thus suggesting a carbohydrate-moiety mediated mechanism. The parenchymal cells of the liver, hepatocytes, are known to abundantly express functional carbohydrate-specific receptors and in this study we therefore used primary rat hepatocytes to study binding and intracellular fate of rFVIIa at a cellular level. Immunofluorescence microscopy showed that rFVIIa was distributed into distinct intracellular vesicles and electron microscopic autoradiography revealed that radioiodinated rFVIIa distributed only into cytoplasmic free vesicles resembling endosomes and lysosomes. These findings suggest that endocytosis of rFVIIa in hepatocytes could be partly mediated via initial membrane binding to a receptor. Quantitative binding studies showed that the presence of excess unlabelled asialo-orosomucoid, asialo-rFVIIa and GalNAc significantly decreased binding of 125I-rFVIIa. An antibody which specifically binds to the carbohydrate recognition domain of the asialoglycoprotein receptor (ASGPR) significantly decreased binding of asialo-rFVIIa by ~36% and rFVIIa by ~19%. Together our data showed that a receptor-mediated mechanism involving the ASGPR is able to bind a subpopulation of unsialylated rFVIIa, while a hepatic mechanism for binding and clearing sialylated rFVIIa is still unknown.
Cysteine residues in CUB-1 domain are critical for ADAMTS13 secretion and stability
Authors: Zhou Zhou , Yeh Hui-Chun , Jing Hua , Wang Christina , Tao Zhenyin , Choi Huiwan , Aboulfatova Khatira , Li Renhao , Dong Jing-fei 
Published: October 2010

SummaryUpon stimulation, endothelial cells release von Willebrand factor (VWF) enriched in ultra-large (UL) forms that are rapidly cleaved by ADAMTS13. The zinc metalloprotease fits in the consensus for members of the ADAMTS family, but also contains two unique C-terminal CUB domains. There are five and two cysteine residues in the CUB-1 and CUB-2 domains, respectively, instead of four as deducted from the consensus. In this study, we investigated the role of cysteine residues in the CUB-1 domain in ADAMTS13 synthesis and activity. CUB-1 and cysteine mutations were expressed in mammalian cell lines and examined for synthesis, secretion, stability, and VWF-cleaving activity. When expressed as an isolated domain, CUB-1, but not CUB-2, covalently aggregated. Converting any of the four cysteines that fit in the CUB consensus (C1192, C1213, C1236 and C1254) reduced the secretion of the mutants to the conditioned medium, but not to extracellular matrix. The mutations also resulted in a moderate increase in proteolytic degradation and decrease in cleaving VWF under static, but not flowing conditions. In contrast, replacing C1275, which was found to be in the thiol form, with a serine residue prevented covalent aggregation of CUB-1, but had no effect on secretion and VWF-cleaving activity. C1275S was also markedly resistant to proteolytic degradation. The data illustrate the importance of consensus cysteines in the secretion and proteolytic activity of ADAMTS13. They also identify an ADAMTS-13 mutant that is resistant to proteolytic degradation, while maintaining a normal VWF-cleaving activity.
Relating Passive 37-GHz Scattering to Radar Profiles in Strong Convection
Authors: Cecil Daniel J. 
Published: October 2010

Abstract
Tropical Rainfall Measuring Mission (TRMM) Microwave Imager and precipitation radar measurements are examined for strong convective systems. Storms having similar values of minimum 37-GHz polarization-corrected temperature (PCT) are grouped together, and their vertical profiles of maximum radar reflectivity are composited. Lower 37-GHz PCT corresponds to stronger radar profiles (high reflectivity through a deep layer), but characteristic profiles for a given 37-GHz PCT are different for deep tropical ocean, deep tropical land, subtropical ocean, and subtropical land regions. Tropical oceanic storms have a sharper decrease of reflectivity just above the freezing level than storms from other regions with the same brightness temperature. Storms from subtropical land regions have the slowest decrease of reflectivity with height and the greatest mixed-phase-layer ice water content (IWC). Linear fits of 37-GHz PCT versus IWC for each region are used to scale the brightness temperatures. Counts of storms with these scaled brightness temperatures below certain thresholds suggest that not as many of the strongest storms occur in central Africa as in subtropical parts of South America, the United States, and central Asia.
Spectral Analysis of Multidimensional Stochastic Geophysical Models with an Application to Decadal ENSO Variability
Authors: Kleeman Richard 
Published: October 2010

Abstract
Simple linear models with additive stochastic forcing have been rather successful in explaining the observed spectrum of important climate variables. Motivated by this, the authors analyze the spectral character of such a general stochastic system of finite dimension. The spectral matrix is derived in the case that the spectrum is a linear combination of dynamical variables and their stochastic forcings. It is found that the most convenient basis for analysis is provided by the normal modes. In general the spectrum consists of two pieces. The first “diagonal” piece is a symmetric Lorentzian curve centered on the normal mode frequencies with breadth and strength determined by the normal mode dissipation. The second cross-spectrum piece derives usually from the coherency of the stochastic forcing of two different normal modes. The cross-spectrum is smaller in magnitude than the corresponding two diagonal pieces. This relative magnitude is controlled by the Wiener coherency, which is equal to the magnitude of the correlation of the stochastic forcings of different normal modes. This new analysis framework is studied in detail for the ENSO case for which a two-dimensional stochastically forced oscillator has been previously suggested as a minimal model. It is found that the observed spectrum is rather easily reproduced given appropriate dissipation. Further, it is found that the cross-spectrum results in a phase-dependent enhancement or suppression of frequencies smaller than the dominant ENSO frequency. This therefore provides a new mechanism for decadal ENSO variability. Since the cross-spectrum is phase dependent, the decadal variability generated has a distinctive spatial character. The significance of the cross-spectrum depends on the Wiener coherency, which in turn depends on the statistics of the stochastic forcing.
Accommodation Study for an Anemometer on a Martian Lander
Authors: Lenoir Benjamin , Banfield Donald , Caughey David A. 
Published: October 2010

Abstract
Measuring the wind velocity and its turbulent fluctuations near the surface of Mars is an important component of the future exploration of Mars, not only to minimize risk in landing, but also to understand some of the most important fundamental processes that dominate Mars’ behavior today. Previous missions have included instrumentation to measure 2D mean winds, but a more sophisticated instrument has been designed that allows for fast, precise 3D measurements of the wind and its turbulent properties. These richer observations raise the question of how best to place such an instrument on a future Martian lander to minimize the flow distortions imposed by the lander, and how to correct for the perturbations that cannot be avoided. To carry out this research, computational fluid dynamic simulations in three dimensions were performed using Fluent, a commercially available software. The first step was to model the conditions at the surface of Mars and, more particularly, the quantities describing the flow in the boundary layer. Using these models, simulations were conducted with two simple shapes for the lander and with eight turbulence conditions representing neutral stability flows in the Martian boundary layer. The results are believed to be generally robust for neutral stability cases because the simulations exhibited little variability as a function of the turbulence conditions. This allowed criteria to be established that would optimize the placement of an anemometer in close proximity to a Martian lander under these conditions. The optimal position that has been derived is an elevation of 55° with a minimum distance from the lander of 0.8 times the characteristic size of the lander.
Two types of C/EBPα mutations play distinct but collaborative roles in leukemogenesis: lessons from clinical data and BMT models
Authors: Kato Naoko , Kitaura Jiro , Doki Noriko , Komeno Yukiko , Watanabe-Okochi Naoko , Togami Katsuhiro , Nakahara Fumio , Oki Toshihiko , Enomoto Yutaka , Fukuchi Yumi , Nakajima Hideaki , Harada Yuka , Harada Hironori , Kitamura Toshio 
Published: October 2010

AbstractTwo types of mutations of a transcription factor CCAAT-enhancer binding protein α (C/EBPα) are found in leukemic cells of 5%-14% of acute myeloid leukemia (AML) patients: N-terminal mutations expressing dominant negative p30 and C-terminal mutations in the basic leucine zipper domain. Our results showed that a mutation of C/EBPα in one allele was observed in AML after myelodysplastic syndrome, while the 2 alleles are mutated in de novo AML. Unlike an N-terminal frame-shift mutant (C/EBPα-Nm)–transduced cells, a C-terminal mutant (C/EBPα-Cm)–transduced cells alone induced AML with leukopenia in mice 4-12 months after bone marrow transplantation. Coexpression of both mutants induced AML with marked leukocytosis with shorter latencies. Interestingly, C/EBPα-Cm collaborated with an Flt3-activating mutant Flt3-ITD in inducing AML. Moreover, C/EBPα-Cm strongly blocked myeloid differentiation of 32Dcl3 cells, suggesting its class II mutation-like role in leukemogenesis. Although C/EBPα-Cm failed to inhibit transcriptional activity of wild-type C/EBPα, it suppressed the synergistic effect between C/EBPα and PU.1. On the other hand, C/EBPα-Nm inhibited C/EBPα activation in the absence of PU.1, despite low expression levels of p30 protein generated by C/EBPα-Nm. Thus, 2 types of C/EBPα mutations are implicated in leukemo-genesis, involving different and cooperating molecular mechanisms.
Context-dependent functions of specific microRNAs in neuronal development
Authors: Gao Fen-Biao 
Published: October 2010

AbstractMicroRNAs (miRNAs) are small noncoding RNAs that regulate multiple developmental processes at the post-transcriptional level. Recent rapid progresses have demonstrated critical roles for a number of miRNAs in neuronal development and function. In particular, miR-9 and miR-124 are specifically expressed in the mammalian nervous system, and their respective nucleotide sequences are 100% identical among many species. Yet, their expression patterns and mRNA targets are less conserved throughout evolution. As a consequence, these miRNAs exhibit diverse context-dependent functions in different aspects of neuronal development, ranging from early neurogenesis and neuronal differentiation to dendritic morphogenesis and synaptic plasticity. Some other neuronal miRNAs also exhibit context-dependent functions in development. Thus, post-transcriptional regulation of spatial and temporal expression levels of protein-coding genes by miRNAs contributes uniquely to the proper development and evolution of the complex nervous system.
Incorporation of Property-Based Testing in Coarse Aggregate Specifications for Pavement Applications
Authors: Abdelrahman Magdy , Hardy Amy 
Published: October 2010

Abstract
The demand for pavement facilities that can handle increasing loads escalates the need for high quality aggregate material. While once plentiful, quality aggregate sources are starting to diminish. When aggregates are eliminated locally by resource depletion as well as land development that prohibits mining, the cost of construction can rise significantly. The cost of transporting quality aggregate materials from other places that comply with specifications can be very expensive. Coarse aggregate specifications for pavement mixtures for many states are outdated, with some sections dating back to around the 1930s. Specifications do not reflect the current level of knowledge concerning testing methodologies of desirable aggregate properties for pavement applications, especially at the local and low volume level. There is a need to evaluate the quality of aggregates based on the suitability of property-based testing requirements. A better understanding of testing requirements used to evaluate material properties can lead to a better utilization of local aggregate materials and reduce the reliance on diminishing high quality sources. This study investigates what property-based testing requirements have been established in current specifications as well as new areas of testing that need to be developed. A questionnaire of professionals defined a set of testing requirements for different pavement applications, which were then compared to the currently specified testing requirements. The results concluded that gaps exist in how professionals define quality aggregate compared to what current specifications define as quality aggregate. This creates the need for the inclusion of more property-based testing that could better characterize aggregates based on pavement performance. This type of characterization could open up the possibility of utilizing local materials that are normally rejected for lower volume applications.