bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of sustained and intermittent paclitaxel therapy on tumor repopulation in ovarian cancer
Authors: Vassileva Vessela , Allen Christine J. , Piquette-Miller Micheline 
Published: March 2008

AbstractTumor repopulation between cycles of chemotherapy likely has a negative effect on clinical outcome in ovarian cancer patients. Thus, avoiding treatment-free periods when tumor cells proliferate by providing sustained chemotherapy regimens may improve clinical response. We investigated the effect of sustained versus intermittent paclitaxel administration on tumor repopulation in ovarian cancer. Growth, clonogenic survival, and apoptosis were followed in SKOV3 and A2780 cells after equivalent exposure to intermittent and sustained levels of paclitaxel. In vivo tumor repopulation in response to sustained and intermittent paclitaxel therapy was investigated in an i.p. xenograft model of human ovarian cancer. Tumor growth, proliferation, and apoptosis were evaluated at different intervals during and after the course of treatment using 5-bromo-2-deoxyuridine uptake, caspase-3, and terminal deoxynucleotidyl transferase–mediated dUTP nick-end labeling immunoassays. Sustained treatment significantly reduced survival in vitro in both cell lines, whereas an increase in clonogenic survival was observed in the intermittent group with each treatment gap, indicating a gradual acceleration in repopulation rates. Similarly, in vivo, sustained therapy resulted in a significant reduction of tumor growth and proliferation. Intermittent therapy resulted in increased tumor proliferation and no efficacy. The percentage of apoptotic tumor cells significantly increased in the sustained group, whereas no significant changes were seen in the control and intermittent groups. Intermittent administration of paclitaxel significantly augmented both in vitro and in vivo tumor repopulation rates, whereas sustained delivery inhibited tumor growth and repopulation. Sustained administration of paclitaxel may increase chemoresponsiveness and clinical response in ovarian cancer by attenuating tumor repopulation. [Mol Cancer Ther 2008;7(3):630–7]
Preclinical evaluation of M30 and M65 ELISAs as biomarkers of drug induced tumor cell death and antitumor activity
Authors: Cummings Jeffrey , Hodgkinson Cassandra , Odedra Rajesh , Sini Patrizia , Heaton Simon P. , Mundt Kirsten E. , Ward Tim H. , Wilkinson Robert W. , Growcott Jim , Hughes Andrew , Dive Caroline 
Published: March 2008

Abstract
M30 and M65 are ELISAs that detect different circulating forms of cytokeratin 18. Using the aurora kinase inhibitor AZD1152 and the SW620 human colon cancer xenograft, experiments were conducted to qualify preclinically both assays as serologic biomarkers of cell death. Using two different apoptotic markers, the kinetics of cell death induced by AZD1152 was first characterized in vitro in three different cell lines and shown to peak 5 to 7 days after drug addition. Treatment of non-tumor-bearing rats with AZD1152 (25 mg/kg) produced no alterations in circulating baseline values of M30 and M65 antigens. In treated, tumor-bearing animals, M30 detected a 2- to 3-fold (P &lt; 0.05) increase in plasma antigen levels by day 5 compared with controls. This correlated to a 3-fold increase in the number of apoptotic cells detected on day 5 in SW620 xenografts using immunohistochemistry. By contrast, M65 did not detect a drug-induced increase in circulating antigen levels at day 5. However, M65 plasma levels correlated to changes in tumor growth in control animals (r2 = 0.93; P &lt; 0.01) and also followed the magnitude of the temporal effect of AZD1152 on tumor growth. An intermediate but active dose of AZD1152 (12.5 mg/kg) produced a less significant increase in M30 plasma levels at day 5. It was also confirmed that the plasma profiles of M30 and M65 mirrored closely those measured in whole tumor lysates. We conclude that M30 is a pharmacodynamic biomarker of AZD1152-induced apoptosis in the SW620 xenograft model, whereas M65 is a biomarker of therapeutic response. [Mol Cancer Ther 2008;7(3):455–63]
p37 from Mycoplasma hyorhinis promotes cancer cell invasiveness and metastasis through activation of MMP-2 and followed by phosphorylation of EGFR
Authors: Gong Manman , Meng Lin , Jiang Beihai , Zhang Jianzhi , Yang Hua , Wu Jian , Shou Chengchao 
Published: March 2008

Abstract
High Mycoplasma infection in gastric cancer tissues suggests a possible association between Mycoplasma infection and tumorigenesis. By using human gastric cancer cells AGS and mouse melanoma cells B16F10 stably expressing p37, the major immunogen of Mycoplasma hyorhinis, we found that p37 enhanced cell motility, migration, and invasion in vitro. With experimental metastasis model in C57BL/6 mice, p37 adenovirus-infected B16F10 cells formed more metastasis lesions in the lung. Furthermore, p37 promoted the phosphorylation of epidermal growth factor receptor (EGFR) and extracellular signal-regulated kinase and the activity of matrix metalloproteinase-2 (MMP-2). Inhibitor of MMPs significantly blocked p37-induced EGFR but has little effect on extracellular signal-regulated kinase phosphorylation, whereas the p37-induced MMP-2 activation was only partially suppressed by inhibitor of MEK1/2 or by inhibitor of EGFR. However, all these inhibitors significantly reduced the p37-induced invasiveness of AGS cells. These results suggest that p37 may stimulate invasion by increasing the activity of MMP-2, thereby inducing EGFR phosphorylation and contributing to tumor metastasis on M. hyorhinis infection. p37 and its regulated molecules could be the potential targets for cancer therapy. [Mol Cancer Ther 2008;7(3):530–7]
Curcumin (diferuloylmethane) alters the expression profiles of microRNAs in human pancreatic cancer cells
Authors: Sun Michael , Estrov Zeev , Ji Yuan , Coombes Kevin R. , Harris David H. , Kurzrock Razelle 
Published: March 2008

Abstract
Background: A major challenge in cancer chemotherapy has been developing safe and clinically efficacious chemotherapeutic agents. With its low toxicity profile, curcumin (diferuloylmethane), a naturally occurring flavinoid derived from the rhizome of Curcuma longa, has great promise. In vitro and in vivo preclinical studies have shown its inhibitory anticancer, antioxidant, anti-inflammatory, antiproliferative, and proapoptotic activities. The multiple mechanisms of the antitumor effect of curcumin putatively include down-regulating the expression of gene products such as nuclear factor-κB, growth suppression, inducing apoptosis, and modulating various signal transduction pathways and the expression of many oncogenes. The mechanisms underlying the antitumor activity of curcumin have not, however, been completely delineated. Methods: An oligonucleotide microarray chip was developed and used to profile microRNA (miRNA) expressions in pancreatic cells treated with curcumin. Transcripts with regulated expression patterns on the arrays were validated by real-time PCRs. Additionally, potential mRNA targets were analyzed bioinformatically and confirmed with flow cytometry experiments. Results: Curcumin alters miRNA expression in human pancreatic cells, up-regulating miRNA-22 and down-regulating miRNA-199a*, as confirmed by TaqMan real-time PCR. Upregulation of miRNA-22 expression by curcumin or by transfection with miRNA-22 mimetics in the PxBC-3 pancreatic cancer cell line suppressed expression of its target genes SP1 transcription factor (SP1) and estrogen receptor 1 (ESR1), while inhibiting miRNA-22 with antisense enhanced SP1 and ESR1 expression. Conclusions: These observations suggest that modulation of miRNA expression may be an important mechanism underlying the biological effects of curcumin. [Mol Cancer Ther 2008;7(3):464–73]
Fronto-temporal Interactions during Overt Verbal Initiation and Suppression
Authors: Allen Paul , Mechelli Andrea , Stephan Klaas E. , Day Fern , Dalton Jeffery , Williams Steven , McGuire Philip K. 
Published: March 2008

Abstract
The Hayling Sentence Completion Task (HSCT) is known to activate left hemisphere frontal and temporal language regions. However, the effective connectivity between frontal and temporal language regions associated with the task has yet to be examined. The aims of the study were to examine activation and effective connectivity during the HSCT using a functional magnetic resonance imaging (fMRI) paradigm in which participants made overt verbal responses. We predicted that producing an incongruent response (response suppression), compared to a congruent one (response initiation), would be associated with greater activation in the left prefrontal cortex and an increase in the effective connectivity between temporal and frontal regions. Fifteen participants were scanned while completing 80 sentence stems. The congruency and constraint of sentences varied across trials. Dynamic Causal Modeling (DCM) and Bayesian Model Selection (BMS) were used to compare a set of alternative DCMs of fronto-temporal connectivity. The HSCT activated regions in the left temporal and prefrontal cortices, and the cuneus. Response suppression was associated with greater activation in the left middle and orbital frontal gyri and the bilateral precuneus than response initiation. Left middle temporal and frontal regions identified by the conventional fMRI analyses were entered into the DCM analysis. Using a systematic BMS procedure, the optimal DCM showed that the connection from the left middle temporal gyrus, which was driven by verbal stimuli per se, was significantly increased in strength during response suppression compared to initiation. Greater effective connectivity between left temporal and prefrontal regions during response suppression may reflect the transfer of information from posterior temporal regions where semantic and lexical information is stored to prefrontal regions where it is manipulated in preparation for an appropriate response.
The Sense of Touch: Embodied Simulation in a Visuotactile Mirroring Mechanism for Observed Animate or Inanimate Touch
Authors: Ebisch Sjoerd J. H. , Perrucci Mauro G. , Ferretti Antonio , Del Gratta Cosimo , Romani Gian Luca , Gallese Vittorio 
Published: March 2008

Abstract
Previous studies have shown a shared neural circuitry in the somatosensory cortices for the experience of one's own body being touched and the sight of intentional touch. Using functional magnetic resonance imaging (fMRI), the present study aimed to elucidate whether the activation of a visuotactile mirroring mechanism during touch observation applies to the sight of any touch, that is, whether it is independent of the intentionality of observed touching agent. During fMRI scanning, healthy participants viewed video clips depicting a touch that was intentional or accidental, and occurring between animate or inanimate objects. Analyses showed equal overlapping activation for all the touch observation conditions and the experience of one's own body being touched in the bilateral secondary somatosensory cortex (SII), left inferior parietal lobule (IPL)/supramarginal gyrus, bilateral temporal-occipital junction, and left precentral gyrus. A significant difference between the sight of an intentional touch, compared to an accidental touch, was found in the left primary somatosensory cortex (SI/Brodmann's area [BA] 2). Interestingly, activation in SI/BA 2 significantly correlated with the degree of intentionality of the observed touch stimuli as rated by participants. Our findings show that activation of a visuotactile mirroring mechanism for touch observation might underpin an abstract notion of touch, whereas activation in SI might reflect a human tendency to “resonate” more with a present or assumed intentional touching agent.
Attention Modulates Initial Stages of Visual Word Processing
Authors: Ruz María , Nobre Anna C. 
Published: March 2008

Abstract
Selective attention has the potential to enhance the initial processing of objects, their spatial locations, or their constituent features. The present study shows that this capacity to modulate initial stages of processing also applies to linguistic attributes. A cueing paradigm focused attention at different levels of word representations on a trial-by-trial basis to study the time course of attentional modulation on visual word processing by means of a high-density electrophysiology recording system. Attention to different linguistic attributes modulated components related to semantic, phonological, and orthographic stages of word processing. Crucially, the N200, associated with initial stages of orthographic decoding, was enhanced by attention to the letter pattern of words. These results suggest that top-down attention has the capacity to enhance initial perceptual stages of visual word processing and support the flexibility of attention in modulating different levels of information processing depending on task goals.
Nematodes from the Gulf of California. Part 1. The genera Ceramonema Cobb, 1920, Pselionema Cobb in Cobb, 1933 and Pterygonema Gerlach, 1954 (Nematoda: Ceramonematidae)
Authors: Mundo-Ocampo Manuel , Tandingan De Ley Irma , Rocha-Olivares Axayácatl , Baldwin James , Holovachov Oleksandr , De Ley Paul 
Published: March 2008

AbstractThe morphology and morphometry of nematodes of six species of the family Ceramonematidae is described using light and scanning electron microscopy. In this paper, we describe two new species and redescribe two known species of Ceramonema and one new species each of Pselionema and Pterygonema. Ceramonema altogolfi sp. n. is characterised by the 0.8-1.3 mm long body, 187-247 body annules, weakly developed zygapophyses, presence of intracuticular vacuoles, sexual dimorphism in amphid shape, presence of vaginal sclerotisation, complex gubernaculum and relatively uniform anal and cloacal annules, whilst C. inguinispina sp. n. has a 0.8-1.1 mm long body, 135-191 body annules, weakly developed zygapophyses, presence of intracuticular vacuoles, sexual dimorphism in amphid shape, absence of vaginal sclerotisation, thorn-shaped precloacal projection, plate-like gubernaculum and double cloacal annule. Pselionema psednum sp. n. is distinguished by 1.4-1.7 mm long body, 251-292 body annules, weakly developed zygapophyses, absence of intracuticular vacuoles, sexual dimorphism in amphid shape and Pterygonema mexicanum sp. n. is characterised by having amphids lacking a central thorn-like projection and pharynx with a distinct posterior glandular bulb. Populations of Ceramonema rectum and Ceramonema cf. yunfengi are also described. The male cloacal region of the species examined appears to be a rich potential source of taxonomic characters that have as yet received insufficient attention for this family.
Stochastic Nature of Physical Parameterizations in Ensemble Prediction: A Stochastic Convection Approach
Authors: Teixeira João , Reynolds Carolyn A. 
Published: March 2008

Abstract
In this paper it is argued that ensemble prediction systems can be devised in such a way that physical parameterizations of subgrid-scale motions are utilized in a stochastic manner, rather than in a deterministic way as is typically done. This can be achieved within the context of current physical parameterization schemes in weather and climate prediction models. Parameterizations are typically used to predict the evolution of grid-mean quantities because of unresolved subgrid-scale processes. However, parameterizations can also provide estimates of higher moments that could be used to constrain the random determination of the future state of a certain variable. The general equations used to estimate the variance of a generic variable are briefly discussed, and a simplified algorithm for a stochastic moist convection parameterization is proposed as a preliminary attempt. Results from the implementation of this stochastic convection scheme in the Navy Operational Global Atmospheric Prediction System (NOGAPS) ensemble are presented. It is shown that this method is able to generate substantial tropical perturbations that grow and “migrate” to the midlatitudes as forecast time progresses while moving from the small scales where the perturbations are forced to the larger synoptic scales. This stochastic convection method is able to produce substantial ensemble spread in the Tropics when compared with results from ensembles created from initial-condition perturbations. Although smaller, there is still a sizeable impact of the stochastic convection method in terms of ensemble spread in the extratropics. Preliminary simulations with initial-condition and stochastic convection perturbations together in the same ensemble system show a promising increase in ensemble spread and a decrease in the number of outliers in the Tropics.
Ensemble Data Assimilation with the NCEP Global Forecast System
Authors: Whitaker Jeffrey S. , Hamill Thomas M. , Wei Xue , Song Yucheng , Toth Zoltan 
Published: March 2008

Abstract
Real-data experiments with an ensemble data assimilation system using the NCEP Global Forecast System model were performed and compared with the NCEP Global Data Assimilation System (GDAS). All observations in the operational data stream were assimilated for the period 1 January–10 February 2004, except satellite radiances. Because of computational resource limitations, the comparison was done at lower resolution (triangular truncation at wavenumber 62 with 28 levels) than the GDAS real-time NCEP operational runs (triangular truncation at wavenumber 254 with 64 levels). The ensemble data assimilation system outperformed the reduced-resolution version of the NCEP three-dimensional variational data assimilation system (3DVAR), with the biggest improvement in data-sparse regions. Ensemble data assimilation analyses yielded a 24-h improvement in forecast skill in the Southern Hemisphere extratropics relative to the NCEP 3DVAR system (the 48-h forecast from the ensemble data assimilation system was as accurate as the 24-h forecast from the 3DVAR system). Improvements in the data-rich Northern Hemisphere, while still statistically significant, were more modest. It remains to be seen whether the improvements seen in the Southern Hemisphere will be retained when satellite radiances are assimilated. Three different parameterizations of background errors unaccounted for in the data assimilation system (including model error) were tested. Adding scaled random differences between adjacent 6-hourly analyses from the NCEP–NCAR reanalysis to each ensemble member (additive inflation) performed slightly better than the other two methods (multiplicative inflation and relaxation-to-prior).
Evolving Complex Electrical Structures of the STEPS 25 June 2000 Multicell Storm
Authors: Weiss Stephanie A. , Rust W. David , MacGorman Donald R. , Bruning Eric C. , Krehbiel Paul R. 
Published: March 2008

Abstract
Data from a three-dimensional lightning mapping array (LMA) and from two soundings by balloon-borne electric field meters (EFMs) were used to analyze the electrical structures of a multicell storm observed on 25 June 2000 during the Severe Thunderstorm Electrification and Precipitation Study (STEPS). This storm had a complex, multicell structure with four sections, each of whose electrical structure differed from that of the others during all or part of the analyzed period. The number of vertically stacked charge regions in any given section of the storm ranged from two to six. The most complex charge and lightning structures occurred in regions with the highest reflectivity values and the deepest reflectivity cores. Intracloud flashes tended to concentrate in areas with large radar reflectivity values, though some propagated across more than one core of high reflectivity or into the low-reflectivity anvil. Intracloud lightning flash rates decreased as the vertical extent and maximum value of reflectivity cores decreased. Cloud-to-ground flash rates increased as cores of high reflectivity descended to low altitudes. Most cloud-to-ground flashes were positive. All observed positive ground flashes initiated between the lowest-altitude negative charge region and a positive charge region just above it. The storm’s complexity makes it hard to classify the vertical polarity of its overall charge structure, but most of the storm had a different vertical polarity than what is typically observed outside the Great Plains. The electrical structure can vary considerably from storm to storm, or even within the same storm, as in the present case.
An Ensemble Multiscale Filter for Large Nonlinear Data Assimilation Problems
Authors: Zhou Yuhua , McLaughlin Dennis , Entekhabi Dara , Ng Gene-Hua Crystal 
Published: March 2008

Abstract
Operational data assimilation problems tend to be very large, both in terms of the number of unknowns to be estimated and the number of measurements to be processed. This poses significant computational challenges, especially for ensemble methods, which are critically dependent on the number of replicates used to derive sample covariances and other statistics. Most efforts to deal with the related problems of computational effort and sampling error in ensemble estimation have focused on spatial localization. The ensemble multiscale Kalman filter described here offers an alternative approach that effectively replaces, at each update time, the prior (or background) sample covariance with a multiscale tree. The tree is composed of nodes distributed over a relatively small number of discrete scales. Global correlations between variables at different locations are described in terms of local relationships between nodes at adjacent scales (parents and children). The Kalman updating process can be carried out very efficiently on such a tree, especially if the update calculations exploit the tree’s parallel structure. In fact, the resulting savings in effort far exceeds the additional work required to construct the tree. The tree-identification process offers possibilities for introducing localization in scale, which can be used instead of or in addition to localization in space. The multiscale filter is able to continually adapt to changing problem scales through associated changes in the tree structure. This is illustrated with a large (106) unknown turbulent fluid flow example that generates dynamic features that span a wide range of time and space scales. This filter is able to track changing features over long distances without any spatial localization, using a moderate ensemble size of 54. The computational savings provided by the multiscale approach, combined with opportunities for hybrid localization over both space and scale, offer significant practical benefits for large data assimilation applications.
Moving Vortices on the Sphere: A Test Case for Horizontal Advection Problems
Authors: Nair Ramachandran D. , Jablonowski Christiane 
Published: March 2008

Abstract
A new two-dimensional advection test on the surface of the sphere is proposed. The test combines a solid-body rotation and a deformational flow field to form moving vortices over the surface of the sphere. The resulting time-dependent deforming vortex centers are located on diametrically opposite sides of the sphere and move along a predetermined great circle trajectory. The horizontal wind field is deformational and nondivergent, and the analytic solution is known at any time. During one revolution around the sphere the initially smooth transported scalar develops strong gradients. Such an approach is therefore more challenging than existing advection test cases on the sphere. To demonstrate the effectiveness and versatility of the proposed test, three different advection schemes are employed, such as a discontinuous Galerkin method on a cubed-sphere mesh, a classical semi-Lagrangian method, and a finite-volume algorithm with adaptive mesh refinement (AMR) on a regular latitude–longitude grid. The numerical results are compared with the analytic solution for different flow orientation angles on the sphere.