bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of p53-Specific Immunity by a p53 Synthetic Long Peptide Vaccine in Patients Treated for Metastatic Colorectal Cancer
Authors: Speetjens Frank M. , Kuppen Peter J.K. , Welters Marij J.P. , Essahsah Farah , Voet van den Brink Anne Marie E.G. , Lantrua M. Graziella Kallenberg , Valentijn A. Rob P.M. , Oostendorp Jaap , Fathers Lorraine M. , Nijman Hans W. , Drijfhout Jan W. , van de Velde Cornelis J.H. , Melief Cornelis J.M. , van der Burg Sjoerd H. 
Published: February 2009

Abstract
Purpose: The tumor-associated self-antigen p53 is commonly overexpressed in cancer, including colorectal cancer, and can serve as a target for immunotherapy. The safety and immunogenicity of a p53 synthetic long peptide (p53-SLP) vaccine were investigated in patients treated for metastatic colorectal cancer.
Experimental Design: Ten patients were vaccinated twice with a set of 10 overlapping p53-SLP in a phase I/II trial. Both the safety and the breadth, magnitude, and polarization of vaccine-induced p53-specific T cells was evaluated in blood samples drawn before and after vaccination by IFN-γ enzyme-linked immunospot, proliferation, cytokine secretion, and multiparameter flow cytometry. The migratory capacity of p53-specific T cells was evaluated by assessing their presence in a biopsy of the second vaccination site.
Results: Toxicity was limited to grade 1/2, mostly at the vaccination site. p53-specific T-cell responses were induced in 9 of 10 colorectal cancer patients as measured by IFN-γ enzyme-linked immunospot, proliferation, and cytokine bead array. In 6 of 9 tested patients, p53-specific T-cell reactivity persisted at least 6 months. Furthermore, p53-specific T cells isolated from the vaccination site were characterized as CD4+ T cells producing both T-helper types 1 and 2 cytokines on stimulation with p53 peptide and p53 protein. Multiparameter flow cytometry revealed that only a minor population of the p53-specific CD4+ T cells was optimally polarized.
Conclusions: The p53-SLP vaccine is safe and capable to induce p53-specific T-cell responses in patients treated for colorectal cancer. New trials should focus on improving the polarization of the p53-SLP vaccine-induced T-cell response.
Combination Chemoprevention for Colon Cancer Targeting Polyamine Synthesis and Inflammation
Authors: Gerner Eugene W. , Meyskens Frank L. 
Published: February 2009

Abstract
Increased polyamine synthesis and inflammation have long been associated with colon carcinogenesis in both preclinical models and in humans. Recent experimental studies suggest that polyamines may be mechanistically involved in colonic inflammatory processes. Genetic epidemiology results indicate that a single nucleotide polymorphism influencing the expression of a polyamine biosynthetic gene is associated with both risk of colon polyp occurrence and recurrence, and the response to aspirin as a polyp preventive agent. A prospective, randomized, placebo-controlled clinical trial of combination difluoromethylornithine, a selective inhibitor of polyamine synthesis, and sulindac, a nonsteroidal anti-inflammatory drug, found that the 3-year treatment was associated with a 70% reduction of recurrence of all adenomas, and over a 90% reduction of recurrence of advanced and/or multiple adenomas, without evidence of serious toxicities. This proof-of-principle trial indicates that targeting polyamine synthesis and inflammation can be an effective strategy for preventing the occurrence of the advanced and/or multiple adenomas that are most closely associated with the development of colon cancers in humans.
Expression of Sorafenib Targets in Melanoma Patients Treated with Carboplatin, Paclitaxel and Sorafenib
Authors: Jilaveanu Lucia , Zito Christopher , Lee Sandra J. , Nathanson Katherine L. , Camp Robert L. , Rimm David L. , Flaherty Keith T. , Kluger Harriet M. 
Published: February 2009

Abstract
Background: Sorafenib, a multitarget kinase inhibitor, inhibits members of the mitogen-activated protein kinase (MAPK) pathway and receptor tyrosine kinases, including vascular endothelial growth factor receptor 2 (VEGF-R2). Sorafenib, carboplatin, and paclitaxel (SCP) has antitumor activity in melanoma patients, but no association was found between response and activating B-Raf V600E mutations. We assessed the expression of sorafenib targets in SCP-treated patient specimens and evaluated the association with response and progression-free survival.
Experimental Design: Using automated quantitative analysis, we quantified the expression of VEGF-R1, VEGF-R2, VEGF-R3, fibroblast growth factor receptor 1, platelet-derived growth factor receptor β, c-Kit, B-Raf, C-Raf, meiosis-specific serine/threonine protein kinase 1, and extracellular regulated kinase 1/2 (ERK1/2) in pretreatment specimens from 46 patients. Furthermore, we assessed ERK1/2 expression in 429 archival melanomas.
Results: VEGF-R2 expression was significantly higher in patients with a complete or partial response (P = 0.0435), whereas ERK1/2 was higher in patients who did not respond (P = 0.0417). High ERK1/2 was an independent predictor of poor survival. High ERK1/2 was associated with decreased survival in the archival melanoma cohort, suggesting that high ERK1/2-expressing tumors are biologically more aggressive. All of the six patients with both high VEGF-R2 and low ERK1/2 responded to SCP.
Conclusions: High VEGF-R2 expression is associated with response to SCP in melanoma, whereas high ERK1/2 is associated with resistance. Collection of specimens from SCP-treated melanoma patients in a cooperative group phase III trial comparing this regimen with the chemotherapy alone is ongoing, and confirmation of these findings is necessary. These markers might be useful for predicting response to sorafenib when given with other chemotherapies and in other diseases, resulting in the possible elimination of unnecessary treatment of patients unlikely to respond.
Sexual dimorphism in the performance of chemosensory investigatory behaviours by African elephants (Loxodonta africana)
Authors: Loizi Helen , Goodwin Thomas , Rasmussen  , Whitehouse Anna , Schulte Bruce 
Published: February 2009

AbstractSexual dimorphism in morphology can be accompanied by behavioural differences between the sexes. We examined if investigatory behaviour involving the trunk of African elephants showed sexual dimorphism. Males compete and search for females, but they have a lengthy period of development before they are socially viable mates. Receptive females are relatively rare. We hypothesized that males would display higher rates of chemosensory behaviour following puberty than females. Because males disperse, they were hypothesized to be more likely to contact elephants outside their kinship group. We observed the trunk tip, chemosensory behaviours of African elephants at Addo Elephant National Park, South Africa. For 208 elephants, we found no significant differences in state behaviours around waterholes by age or sex. Yet, older elephants were more likely to investigate the environment and elephant excrement than younger animals. Males were more likely to investigate urine and faeces than females. Only post-puberty animals contacted non-family with males investigating both sexes, while investigations by and to females only involved post-puberty males. Overall, the probability of performing chemosensory behaviours depended on age and sex. Male elephants appear more reliant than females on signals in urine and faeces with ensuing inspections of individuals through trunk tip contacts.
Impacts of vehicle traffic on the distribution and behaviour of rutting elk, Cervus elaphus
Authors: St. Clair Colleen , Forrest Andrew 
Published: February 2009

AbstractEven within protected areas, human disturbance has the potential to influence the distribution, behaviour and, ultimately, abundance of other species. We studied the potential disturbance caused by the presence and movement of vehicle traffic on the distribution and behaviour of elk (Cervus elaphus) during the fall rut in a Canadian National Park where people congregate on a single road to observe elk. To determine the effect of vehicle traffic on elk, we subjected the road to alternating open and closed treatments of 3 or 4 days in duration. We then used a global positioning system (GPS)-linked laser range finder and a computer programmed as an event recorder to collect information on the distribution and behaviour of elk. These methods made it possible to link the precise positions of both elk and vehicles with behavioural states, which we measured with a combination of focal animal, all-occurrence, and scan sampling. We detected no effects of road closure on the distribution of elk herds or the size, cohesion, or position of separate elk groups, but elk were more likely to cross the road when it was closed. In addition, higher proportions of female elk were vigilant in the vicinity of moving vehicles and elk of both sexes, but particularly males, spent more time in vigilance postures when the road was open. Males spent less time exhibiting reproductive behaviour (sparring and mating) when the road was open and tended to spar farther from the road. Together, these results suggest that vehicle traffic exerted a measurable effect on the behaviour, but not distribution, of elk at this site. These behavioural effects are probably biologically slight, but they could easily be lessened at this site, and potentially others, by limiting the frequency and extent of vehicle movement on the road.
Characterization of the Martian Convective Boundary Layer
Authors: Martínez Germán , Valero Francisco , Vázquez Luis 
Published: February 2009

Abstract
The authors have carried out an extensive characterization of the Martian mixed layer formed under convective conditions. The values of the mixed layer height, convective velocity scale, convective temperature scale, mean temperature standard deviation, mean horizontal and vertical velocity standard deviations, and mean turbulent viscous dissipation rate have been obtained during the strongest convective hours for the mixed layer. In addition, the existing database of the surface layer has been improved by recalculating some parameters (e.g., Monin–Obukhov length, friction velocity, or scale temperature) that had already been obtained in previous papers by other means and also by calculating new ones, such as the standard deviation of the vertical wind speed velocity, the turbulent viscous dissipation rate, and eddy transfer coefficients for momentum and heat. The Earth counterparts of all these magnitudes are also shown. In this paper, a comprehensive database concerning the whole convective planetary boundary layer on Mars is displayed, and a detailed terrestrial comparison is established.
The inputs of this work are hourly in situ temperature, hourly in situ horizontal wind speed, and hourly simulated ground temperature for specific selected Sols of the Viking and Pathfinder landers. These data correspond to typical low and midlatitude northern summertime conditions, with weak prevailing winds. To handle this set of data, surface layer and mixed layer similarity theory have been used at the strongest convective hours. In addition, the inclusion of a parameterization of a molecular sublayer and prescribed values of the surface roughness has been considered.
On the Relationship between SST Gradients, Boundary Layer Winds, and Convergence over the Tropical Oceans
Authors: Back Larissa E. , Bretherton Christopher S. 
Published: February 2009

Abstract
A linear mixed layer model that skillfully reproduces observed surface winds and convergence over the tropical oceans is used to examine the relative influence of boundary layer and free-tropospheric processes on the distribution of climatological surface winds and convergence. The semiempirical model assumes a subcloud-layer momentum force balance between pressure gradients, Coriolis acceleration, linearized friction, and downward momentum mixing, and it utilizes boundary conditions from the 40-yr ECMWF Re-Analysis (ERA-40). Observed pressure gradients are linearly decomposed into boundary layer (defined as the region below 850 hPa) and free-tropospheric components, and the surface winds and convergence associated with these components are computed. Results show that surface zonal winds are predominantly associated with a combination of free-tropospheric pressure gradients and downward momentum mixing, whereas the distribution of convergence is primarily due to boundary layer temperature gradients, which are closely related to SST gradients. The authors conclude that the climatological distribution of boundary layer convergence is primarily a function of the pattern of SST gradients and is better regarded as a cause rather than a consequence of deep convection.
The Effect of Ocean Dynamics and Orography on Atmospheric Storm Tracks
Authors: Wilson Chris , Sinha Bablu , Williams Richard G. 
Published: February 2009

AbstractThe control of atmospheric storm tracks by ocean dynamics, orography, and their interaction is investigated using idealized experiments with a simplified coupled atmosphere–ocean climate model. The study focuses on the quasi–steady state for the storm tracks in the Northern Hemisphere winter mean. The experiments start with a background state without mountains and ocean dynamics, and in separate stages include orography and a dynamic ocean to obtain a more realistic control simulation. The separate effects of ocean dynamics, orography, and their nonlinear interaction are identified for the storm tracks and the surface thermodynamic forcing over the ocean.The model study suggests that atmospheric storm tracks are a robust feature of the climate system, occurring at midlatitudes even if there is no orographic forcing or ocean heat transport. Ocean dynamics generally lead to a poleward shift in both the storm track and the maximum in atmospheric northward heat transport and induce a northeastward tilt over the Atlantic. This poleward shift is linked to the extra heat transport by the ocean and the tightening of sea surface temperature gradients on the western side of ocean basins. Orographic forcing causes along-track variability with a weakening of the storm track over the continents and induces a northeastward tilt over the western Pacific, which is associated with a stationary planetary wave train generated by the Tibetan Plateau. The interaction between ocean dynamics and orographic forcing plays a localized role, enhancing the contrast between the Atlantic and Pacific. Much of the response to the forcing is eddy mediated and transient eddies help to spread the influence of orographic and ocean forcing.
The Hadley and Walker Circulation Changes in Global Warming Conditions Described by Idealized Atmospheric Simulations
Authors: Gastineau Guillaume , Li Laurent , Le Treut Hervé 
Published: February 2009

Abstract
Sea surface temperature (SST) changes constitute a major indicator and driver of climate changes induced by greenhouse gas increases. The objective of the present study is to investigate the role played by the detailed structure of the SST change on the large-scale atmospheric circulation and the distribution of precipitation. For that purpose, simulations from the Institut Pierre-Simon Laplace Coupled Model, version 4 (IPSL-CM4) are used where the carbon dioxide (CO2) concentration is doubled. The response of IPSL-CM4 is characterized by the same robust mechanisms affecting the other coupled models in global warming simulations, that is, an increase of the hydrological cycle accompanied by a global weakening of the large-scale circulation. First, purely atmospheric simulations are performed to mimic the results of the coupled model. Then, specific simulations are set up to further study the underlying atmospheric mechanisms. These simulations use different prescribed SST anomalies, which correspond to a linear decomposition of the IPSL-CM4 SST changes in global, longitudinal, and latitudinal components. The simulation using a globally uniform increase of the SST is able to reproduce the modifications in the intensity of the hydrological cycle or in the mean upward mass flux, which also characterize the double CO2 simulation with the coupled model. But it is necessary (and largely sufficient) to also take into account the zonal-mean meridional structure of the SST changes to represent correctly the changes in the Hadley circulation strength or the zonal-mean precipitation changes simulated by the coupled model, even if these meridional changes by themselves do not change the mean thermodynamical state of the tropical atmosphere. The longitudinal SST anomalies of IPSL-CM4 also have an impact on the precipitation and large-scale tropical circulation and tend to introduce different changes over the Pacific and Atlantic Oceans. The longitudinal SST changes are demonstrated to have a smaller but opposite effect from that of the meridional anomalies on the Hadley cell circulations. Results indicate that the uncertainties in the simulated meridional patterns of the SST warming may have major consequences on the assessment of the changes of the Hadley circulation and zonal-mean precipitation in future climate projections.
Use of Remotely Sensed Actual Evapotranspiration to Improve Rainfall–Runoff Modeling in Southeast Australia
Authors: Zhang Yongqiang , Chiew Francis H. S. , Zhang Lu , Li Hongxia 
Published: February 2009

Abstract
This paper explores the use of the Moderate Resolution Imaging Spectroradiometer (MODIS), mounted on the polar-orbiting Terra satellite, to determine leaf area index (LAI), and use actual evapotranspiration estimated using MODIS LAI data combined with the Penman–Monteith equation [remote sensing evapotranspiration (ERS)] in a lumped conceptual daily rainfall–runoff model. The model is a simplified version of the HYDROLOG (SIMHYD) model, which is used to estimate runoff in ungauged catchments. Two applications were explored: (i) the calibration of SIMHYD against both the observed streamflow and ERS, and (ii) the modification of SIMHYD to use MODIS LAI data directly. Data from 2001 to 2005 from 120 catchments in southeast Australia were used for the study. To assess the modeling results for ungauged catchments, optimized parameter values from the geographically nearest gauged catchment were used to model runoff in the ungauged catchment. The results indicate that the SIMHYD calibration against both the observed streamflow and ERS produced better simulations of daily and monthly runoff in ungauged catchments compared to the SIMHYD calibration against only the observed streamflow data, despite the modeling results being assessed solely against the observed streamflow data. The runoff simulations were even better for the modified SIMHYD model that used the MODIS LAI directly. It is likely that the use of other remotely sensed data (such as soil moisture) and smarter modification of rainfall–runoff models to use remotely sensed data directly can further improve the prediction of runoff in ungauged catchments.
Divergent versus Nondivergent Instabilities of Piecewise Uniform Shear Flows on the f Plane
Authors: Paldor Nathan , Dvorkin Yona , Heifetz Eyal 
Published: February 2009

Abstract
The linear instability of a piecewise uniform shear flow is classically formulated for nondivergent perturbations on a 2D barotropic mean flow with linear shear, bounded on both sides by semi-infinite half-planes where the mean flows are uniform. The problem remains unchanged on the f plane because for nondivergent perturbations the instability is driven by vorticity gradient at the edges of the inner, linear shear region, whereas the vorticity itself does not affect it. The instability of the unbounded case is recovered when the outer regions of uniform velocity are bounded, provided that these regions are at least twice as wide as the inner region of nonzero shear. The numerical calculations demonstrate that this simple scenario is greatly modified when the perturbations’ divergence and the variation of the mean height (which geostrophically balances the mean flow) are retained in the governing equations. Although a finite deformation radius exists on the shallow water f plane, the mean vorticity gradient that governs the instability in the nondivergent case remains unchanged, so it is not obvious how the instability is modified by the inclusion of divergence in the numerical solutions of the equations. The results here show that the longwave instability of nondivergent flows is recovered by the numerical solution for divergent flows only when the radius of deformation is at least one order of magnitude larger than the width of the inner uniform shear region. Nevertheless, even at this large radius of deformation both the amplitude of the velocity eigenfunction and the distribution of vorticity and divergence differ significantly from those of nondivergent perturbations and vary strongly in the cross-stream direction. Whereas for nondivergent flows the vorticity and divergence both have a delta-function structure located at the boundaries of the inner region, in divergent flows they are spread out and attain their maximum away from the boundaries (either in the inner region or in the outer regions) in some range of the mean shear. In contrast to nondivergent flows for which the mean shear is merely a multiplicative factor of the growth rates, in divergent flows new unstable modes exist for sufficiently large mean shear with no shortwave cutoff. This unstable mode is strongly affected by the sign of the mean shear (i.e., the sign of the mean relative vorticity).
Characteristics of Langmuir Turbulence in the Ocean Mixed Layer
Authors: Grant Alan L. M. , Belcher Stephen E. 
Published: February 2009

Abstract
This study uses large-eddy simulation (LES) to investigate the characteristics of Langmuir turbulence through the turbulent kinetic energy (TKE) budget. Based on an analysis of the TKE budget a velocity scale for Langmuir turbulence is proposed. The velocity scale depends on both the friction velocity and the surface Stokes drift associated with the wave field. The scaling leads to unique profiles of nondimensional dissipation rate and velocity component variances when the Stokes drift of the wave field is sufficiently large compared to the surface friction velocity. The existence of such a scaling shows that Langmuir turbulence can be considered as a turbulence regime in its own right, rather than a modification of shear-driven turbulence.
Comparisons are made between the LES results and observations, but the lack of information concerning the wave field means these are mainly restricted to comparing profile shapes. The shapes of the LES profiles are consistent with observed profiles. The dissipation length scale for Langmuir turbulence is found to be similar to the dissipation length scale in the shear-driven boundary layer. Beyond this it is not possible to test the proposed scaling directly using available data. Entrainment at the base of the mixed layer is shown to be significantly enhanced over that due to normal shear turbulence.