bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ratiometric dosing of anticancer drug combinations: Controlling drug ratios after systemic administration regulates therapeutic activity in tumor-bearing mice
Authors: Mayer Lawrence D. , Harasym Troy O. , Tardi Paul G. , Harasym Natashia L. , Shew Clifford R. , Johnstone Sharon A. , Ramsay Euan C. , Bally Marcel B. , Janoff Andrew S. 
Published: August 2006

AbstractAnticancer drug combinations can act synergistically or antagonistically against tumor cells in vitro depending on the ratios of the individual agents comprising the combination. The importance of drug ratios in vivo, however, has heretofore not been investigated, and combination chemotherapy treatment regimens continue to be developed based on the maximum tolerated dose of the individual agents. We systematically examined three different drug combinations representing a range of anticancer drug classes with distinct molecular mechanisms (irinotecan/floxuridine, cytarabine/daunorubicin, and cisplatin/daunorubicin) for drug ratio–dependent synergy. In each case, synergistic interactions were observed in vitro at certain drug/drug molar ratio ranges (1:1, 5:1, and 10:1, respectively), whereas other ratios were additive or antagonistic. We were able to maintain fixed drug ratios in plasma of mice for 24 hours after i.v. injection for all three combinations by controlling and overcoming the inherent dissimilar pharmacokinetics of individual drugs through encapsulation in liposomal carrier systems. The liposomes not only maintained drug ratios in the plasma after injection, but also delivered the formulated drug ratio directly to tumor tissue. In vivo maintenance of drug ratios shown to be synergistic in vitro provided increased efficacy in preclinical tumor models, whereas attenuated antitumor activity was observed when antagonistic drug ratios were maintained. Fixing synergistic drug ratios in pharmaceutical carriers provides an avenue by which anticancer drug combinations can be optimized prospectively for maximum therapeutic activity during preclinical development and differs from current practice in which dosing regimens are developed empirically in late-stage clinical trials based on tolerability. [Mol Cancer Ther 2006;5(7):1854–63]
A new generation of anticancer, drug-loaded, colloidal vectors reverses multidrug resistance in glioma and reduces tumor progression in rats
Authors: Garcion Emmanuel , Lamprecht Alf , Heurtault Béatrice , Paillard Archibald , Aubert-Pouessel Anne , Denizot Benoît , Menei Philippe , Benoît Jean-Pierre 
Published: August 2006

AbstractBy focusing on rat glioma, we elucidated whether new lipid nanocapsules (LNC) were able to improve anticancer hydrophobic drug bioavailability while also overcoming multidrug resistance. Blank LNCs and LNCs loaded with the antineoplastic agent paclitaxel were formulated by an emulsion inversion phase process. Expression of efflux pumps by rat glioma cells was assessed by reverse transcription-PCR, Western blot, and immunohistochemistry, and their activity was followed using the tracer 99Tcm-methoxyisobutylisonitrile. Modalities of LNC action were addressed by using confocal microscopy detection of fluorescently labeled LNCs, fluorescence-activated cell sorting, high-performance liquid chromatography measurement of paclitaxel release, and analysis of tumor cell growth. This revealed an interaction between LNCs and efflux pumps that resulted in an inhibition of multidrug resistance in glioma cells, both in culture and in cell implants in animals. LNCs were able to target the intracellular compartment of glioma cells, a mechanism that was abrogated by using intracellular cholesterol inhibitors but not by clathrin-coated pit or caveolae uptake inhibitors. This result can be correlated to the LNC inhibitory effects on efflux pump activity that is itself known to be stimulated by intracellular cholesterol. In parallel, we showed that paclitaxel-loaded LNCs were active reservoirs from which paclitaxel could be released. Finally, we established that paclitaxel-loaded LNCs were more efficient than the commercially available paclitaxel formulation (Taxol) for clinical use, thus reducing tumor expansion in vitro and in vivo. Considering the physiologically compatible nature of LNC excipients, these data may represent an important step towards the development of new clinical therapeutic strategies against cancers. [Mol Cancer Ther 2006;5(7):1710–22]
Termites and mites – adaptive behavioural responses to infestation?
Authors: Fuchs Alexander , Korb Judith 
Published: August 2006

AbstractRapid adaptation to their hosts' defence systems usually allows parasites to keep the upper hand in the co-evolutionary arms race between hosts and parasites. However, although morphological and physiological adaptations are generally far slower in hosts than in their parasites, the former can rapidly respond to a parasite challenge by dispersal-related, adaptive changes in their behaviour. We investigated whether the drywood termite Cryptotermes secundus altered its behaviour in response to an infestation with parasitic, astigmatic mites. The frequency of the vital, dispersal-related behaviours allogrooming and proctodeal trophallaxis did not differ between colonies or between individuals with mites compared to without mites. However, activity levels were lower in mite-infested colonies and individuals spent more time resting and feeding when mites were present in the colony, irrespective of whether they were infested themselves or not. This behavioural pattern shown by individuals from infested mite-colonies is known to be associated with a development of C. secundus workers into winged dispersing sexuals. As dispersing individuals were less likely to have mites, this behavioural response to the mites' infestation might be an adaptive response to escape the deteriorating nest conditions.
Nest-mate recognition and the effect of distance from the nest on the aggressive behaviour of Camponotus chilensis (Hymenoptera: Formicidae)
Authors: Velásquez Nelson , Gómez María , González Jorge , Vásquez Rodrigo A. 
Published: August 2006

AbstractNest-mate recognition and territorial behaviour in ants are widely studied phenomena. However, few studies have analysed, under field conditions, how nest-mate recognition varies with distance from the resident's colony. In a natural population of Camponotus chilensis in central Chile, we studied nest-mate recognition and spatial variation in aggressive behaviour. C. chilensis individuals were able to discriminate nest-mates from intruders, showing no aggression toward nest companions, while aggressiveness toward allo-colonial con-specifics decreased significantly with distance. Further, the overall number of interactions and the aggressiveness of the resident ants were significantly greater at 25 cm from their colony than at further distances. Given that antennation behaviour is regularly present at all distances from the nest, it seems to entail information acquisition. Biting and intruder-dragging, the most conspicuous aggressive displays, were mainly observed at distances close to the resident colony. Other behaviours such as threatening with open mandibles, ventral bending of the gaster, and backward-movement, were observed at all distances, and they seem to represent the first signs of intruder rejection.
Innovation in wild Bornean orangutans (Pongo pygmaeus wurmbii)
Authors: van Noordwijk Maria A. , van Schaik Carel P. , Wich Serge A. 
Published: August 2006

AbstractIn most studies to date, innovations were studied if their origination was witnessed or if they arose in response to a pronounced environmental change, making it difficult to generalize. In this study, we use an operational definition developed by Ramsey et al. (MS) to design a procedure for recognizing the standing repertoire of innovations (in the sense of behaviors) in a natural population. The data were derived from an intensive field study of orangutans at Tuanan, Borneo. The main recognition criteria are (1) the incomplete geographic prevalence of the behavior, (2) identified causes of its absence in a population or an individual, and (3) comparison with the incidence of the behavior among captive orangutans. Using this procedure, we recognized 19 innovations at Tuanan and 43 for orangutans in general. Cumulative curves of number of innovations indicated that the total number of innovations observed at Tuanan remained stable after some 3,000 hours of observation, and is thus adequate for comparison with other studies. Additionally, an individual's repertoire size remained stable after ca 1,000 hours. The results showed that innovations are found in multiple domains (subsistence, comfort, and social communication), and that innovations that are performed more often are more likely to reach cultural status in a population. Across populations, innovations that increase comfort are less likely to become cultural than those that serve subsistence or are used in communication. Orangutan and chimpanzee innovation repertoires do not show significant differences across the three domains. Systematic comparisons across sites and with captivity will make it possible to validate the approach.
A likely ranking interpolation for resolving dominance orders in systems with unknown relationships
Authors: Wittemyer G. , Getz W.M. 
Published: August 2006

AbstractIn many animal systems agonistic interactions may be rare or not overt, particularly where such interactions are costly or of high risk as is common for large mammals. We present a technique developed specifically for resolving an optimized dominance order of individuals in systems with transitive (i.e. linear) dominance relationships, but where not all relationships are known. Our method augments the widely used I&SI method (de Vries, 1998) with an interpolation function for resolving the relative ranks of individuals with unknown relationships. Our method offers several advantages over other dominance methods by enabling the incorporation of any proportion of unknown relationships, resolving a unique solution to any dominance matrix, and calculating cardinal dominance strengths for each individual. As such, this method enables novel insight into difficult to study behavioural systems.
Love for sale and its fitness benefits: nuptial gifts in the scorpionfly Panorpa vulgaris represent paternal investment
Authors: Engels Sierk , Peter Sauer Klaus 
Published: August 2006

AbstractNuptial feeding is a very common strategy shown by males of various insect taxa in order to obtain copulations. In the majority of cases these gifts presented during or after courtship and/or copulation can be considered as mating effort. In this study we present data which indicate that nuptial feeding in Panorpa vulgaris (Mecoptera: Panorpidae) represents paternal investment. During copulations males produce salivary secretions which are consumed by the females. The more salivary masses a male produces the longer the copulation will last. Since sperm are transferred continuously during copulation and fertilization of eggs follows the fair raffle principle, females allocate paternity in accordance to copulation duration and therefore to the amount of nuptial gifts they receive from a certain male. In the present study we are able to show that the number of salivary masses consumed significantly affects the number of eggs a female produces. Thus, in P. vulgaris the nuptial gift increases the reproductive output of females and hence must not only be considered as mating effort but also as paternal investment. The mechanism by which salivary masses increase female fecundity is yet unknown. We hypothesize that the secretions may not only transfer nutrients but may possibly operate as carriers for an allohormone that manipulates the females' physiology in terms of increasing egg production.
Distinct Modes of the East Asian Winter Monsoon
Authors: Wu Bingyi , Zhang Renhe , D’Arrigo Rosanne 
Published: August 2006

Abstract
Two distinct modes of the East Asian winter monsoon (EAWM) have been identified, and they correspond to real and imaginary parts of the leading mode of the EAWM, respectively. Analyses of these modes used the National Centers for Environment Prediction (NCEP) and National Center for Atmospheric Research (NCAR) monthly mean reanalysis datasets for the period 1968–2003, as well as the Southern Oscillation index (SOI), North Atlantic Oscillation index, and eastern equatorial Pacific sea surface temperature (SST) data. Results were obtained by resolving a complex Hermite matrix derived from 850-hPa anomalous wind fields, and determining the resulting modes’ associations with several climate variables. The first distinct mode (M1) is characterized by an anomalous meridional wind pattern over East Asia and the western North Pacific. Mode M1 is closely related to several features of the atmospheric circulation, including the Siberian high, East Asian trough, East Asian upper-tropospheric jet, and local Hadley circulation over East Asia. Thus, M1 reflects the traditional EAWM pattern revealed in previous studies. The second distinct EAWM mode (M2), which was not identified previously, displays dominant zonal wind anomalies over the same area. Mode M2 exhibits a closer relation than M1 to sea level pressure anomalies over the northwestern Pacific southeast of Japan and with the SOI and equatorial eastern Pacific SST. Unlike M1, M2 does not show coherent relationships with the Siberian high, East Asian trough, and East Asian upper-tropospheric jet. Since atmospheric circulation anomalies relevant to M2 exhibit a quasi-barotropic structure, its existence cannot simply be attributed to differential land–sea heating. El Niño events tend to occur in the negative phase of M1 and the positive phase of M2, both corresponding to a weakened EAWM. The Arctic Oscillation does not appear to impact the EAWM on interannual time scales. Although the spatial patterns for the two modes are very different, the two distinct modes are complementary, with the leading EAWM mode being a linear combination of the two. The results herein therefore demonstrate that a single EAWM index may be inappropriate for investigating and predicting the EAWM.
Serial Clustering of Extratropical Cyclones
Authors: Mailier Pascal J. , Stephenson David B. , Ferro Christopher A. T. , Hodges Kevin I. 
Published: August 2006

Abstract
The clustering in time (seriality) of extratropical cyclones is responsible for large cumulative insured losses in western Europe, though surprisingly little scientific attention has been given to this important property. This study investigates and quantifies the seriality of extratropical cyclones in the Northern Hemisphere using a point-process approach. A possible mechanism for serial clustering is the time-varying effect of the large-scale flow on individual cyclone tracks. Another mechanism is the generation by one “parent” cyclone of one or more “offspring” through secondary cyclogenesis. A long cyclone-track database was constructed for extended October–March winters from 1950 to 2003 using 6-h analyses of 850-mb relative vorticity derived from the NCEP–NCAR reanalysis. A dispersion statistic based on the variance-to-mean ratio of monthly cyclone counts was used as a measure of clustering. It reveals extensive regions of statistically significant clustering in the European exit region of the North Atlantic storm track and over the central North Pacific. Monthly cyclone counts were regressed on time-varying teleconnection indices with a log-linear Poisson model. Five independent teleconnection patterns were found to be significant factors over Europe: the North Atlantic Oscillation (NAO), the east Atlantic pattern, the Scandinavian pattern, the east Atlantic–western Russian pattern, and the polar–Eurasian pattern. The NAO alone is not sufficient for explaining the variability of cyclone counts in the North Atlantic region and western Europe. Rate dependence on time-varying teleconnection indices accounts for the variability in monthly cyclone counts, and a cluster process did not need to be invoked.
Synoptic and Topographic Variability of Northern California Precipitation Characteristics in Landfalling Winter Storms Observed during CALJET
Authors: Kingsmill David E. , Neiman Paul J. , Ralph F. Martin , White Allen B. 
Published: August 2006

Abstract
Observations from northern California during the California Landfalling Jets (CALJET) experiment are used to examine the mean characteristics of precipitation and their variances as functions of synoptic and topographic regimes. Ten cases involving the landfall of extratropical cyclones are analyzed with radar and rain gauge data collected at two sites: one in the coastal mountains north of San Francisco (CZD) and the other in the Central Valley just west of Sacramento (KDAX). Aside from the melting-layer bright band, the most striking feature in the 10-case composite vertical profile of radar reflectivity at CZD was a distinct change in slope about 2.5 km above the bright band. This “shoulder” is thought to represent a change in the growth rate of hydrometeors. Although the bright band was quite distinct, about one-third of the profiles in the composite did not exhibit this feature. These nonbrightband (NBB) profiles had a low-level slope where reflectivity increased with decreasing altitude, a structure suggesting that collision–coalescence was the primary growth process. The relationship between surface rainfall rate and low-level radar reflectivity implies that all profiles were composed of larger numbers of small drops than expected from a Marshall–Palmer drop size distribution, a trend that was especially apparent for NBB profiles.
Synoptic variability of precipitation characteristics at CZD were examined by identifying five distinct regimes (cold sector, warm front, warm sector, cold front, and cool sector) based on a simplified conceptual model. The shoulder remained approximately 2.5 km above the bright band in each regime. Rainfall intensity was highest during the cold-frontal regime and NBB rainfall was most common during the warm-frontal, warm-sector, and cool-sector regimes. Topographic variability of precipitation characteristics was investigated by comparing results at CZD and KDAX. A shoulder structure located about 2.5 km above the bright band was also evident in the KDAX profiles, suggesting that this feature is related to large-scale dynamic, thermodynamic, and microphysical processes rather than orographic effects. The relationship between surface rainfall rate and low-level radar reflectivity near KDAX closely followed a trend expected for a Marshall–Palmer drop size distribution, implying the presence of relatively larger raindrops than observed at CZD and indicating that NBB rainfall occurs less frequently near KDAX.
Multiply Nested Regional Climate Simulation for Southern South America: Sensitivity to Model Resolution
Authors: Rojas Maisa 
Published: August 2006

Abstract
Results are reported from two 5-month-long simulations for southern South America using the fifth-generation Pennsylvania State University–NCAR Mesoscale Model (MM5). The periods of simulation correspond to May–September 1997 and 1998, which were anomalously wet and dry winters for central Chile, respectively. The model setup includes triply nested, two-way-interacting domains centered over the eastern South Pacific and the western coast of southern South America, with horizontal grid intervals of 135, 45, and 15 km. Boundary conditions are provided from NCEP–NCAR reanalyzed fields. The analysis focuses on two subregions of central Chile (30°–41°S). Region 1 (32°–35°S), which is where the observed interannual precipitation differences are largest, is topographically very complex, with a mean height of the Andes Cordillera around 4500 m. Region 2 (35°–39°S) has relatively smooth terrain, as the mean height of the Andes drops to 3000 m. Station precipitation and temperature data are used for model validation. The model exhibits a negative temperature bias (from 2° to 5°C), as well as a positive precipitation bias (40%–80%). This precipitation bias can be partially explained by a positive moisture bias over the ocean in the model. In addition, these biases are highly correlated to the representation of terrain and station elevation in the model. The highest-resolution domain has the smallest precipitation bias for low-elevation stations, but a large positive bias at high altitudes (up to 300%). It also has a better representation of the spatial distribution of the precipitation, especially in region 1, where topography has a larger impact on the precipitation. Overall, the model domain with highest resolution best reproduces the observed precipitation and temperature, as well as the interannual differences. However, this study also shows that large improvements in the simulations of the surface variables are obtained when downscaling from 135 to 45 km, but much smaller improvements are found when downscaling from 45 to 15 km. These simulations represent the first effort in simulating seasonal precipitation in this topographically complex region of the Southern Hemisphere.
Positive-Definite and Monotonic Limiters for Unrestricted-Time-Step Transport Schemes
Authors: Skamarock William C. 
Published: August 2006

Abstract
General positive-definite and monotonic limiters are described for use with unrestricted-Courant-number flux-form transport schemes. These limiters are tested using a time-split multidimensional transport scheme. The importance of minimizing the splitting errors associated with the time-split operator and of the consistency between the transport scheme and the discrete continuity equation is demonstrated.
Mechanisms of the Northward Movement of Submonthly Scale Vortices over the Bay of Bengal during the Boreal Summer
Authors: Yokoi Satoru , Satomura Takehiko 
Published: August 2006

Abstract
Mechanisms of the northward movement of submonthly scale vortices over the Bay of Bengal during the boreal summer (May–September) are studied with the use of a vorticity budget analysis applied to the ECMWF 40-yr Re-Analysis (ERA-40) data. To quantitatively evaluate the contribution from each term that constitutes the vorticity anomaly equation to the movement of the vortices, a vector measure, termed the forcing vector (FV), is used in the present study. Because the axis of the submonthly scale relative vorticity anomaly does not tilt meridionally below the 200-hPa level, the mechanisms of the northward movement of a composite submonthly scale vortex integrated from the surface to the 100-hPa level [the barotropic component (BTC)] are studied. The barotropic vortex moves northwestward, with northward speeds of 0.9° day−1. The meridional component of the FV (MFV), which represents the contribution to the meridional component of the movement, reveals that the primary and secondary terms that contribute to the northward movement are the advection of the vortex by the environmental meridional wind, and the tilting effect of the environmental horizontal vorticity vector by the vertical pressure velocity anomaly associated with the vortex, respectively. The former term works mainly in the lower troposphere, while the latter operates in the middle and upper troposphere. The first baroclinic component (FBCC) of the vortex in the troposphere also moves northwestward with almost the same northward speed as the BTC. Mechanisms of the northward movement of the FBCC are also clarified in the present study through examination of the MFV. The primary contributing term is the same as that of the BTC, while the tilting term hinders the northward movement of the FBCC. For the FBCC, the secondary contributing term is the advection of the planetary vorticity by the meridional wind anomaly associated with the horizontal convergence and divergence anomalies in the lower and upper troposphere, respectively. The present study also discusses the phase relation between the BTC and the FBCC from the viewpoint of their northward movement in an environment of easterly vertical shear.