bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global-Scale Energy and Freshwater Balance in Glacial Climate: A Comparison of Three PMIP2 LGM Simulations
Authors: Murakami Shigenori , Ohgaito Rumi , Abe-Ouchi Ayako , Crucifix Michel , Otto-Bliesner Bette L. 
Published: February 2008

Abstract
Three coupled atmosphere–ocean general circulation model (AOGCM) simulations of the Last Glacial Maximum (LGM: about 21 000 yr before present), conducted under the protocol of the second phase of the Paleoclimate Modelling Intercomparison Project (PMIP2), have been analyzed from a viewpoint of large-scale energy and freshwater balance. Atmospheric latent heat (LH) transport decreases at most latitudes due to reduced water vapor content in the lower troposphere, and dry static energy (DSE) transport in northern midlatitudes increases and changes the intensity contrast between the Pacific and Atlantic regions due to enhanced stationary waves over the North American ice sheets. In low latitudes, even with an intensified Hadley circulation in the Northern Hemisphere (NH), reduced DSE transport by the mean zonal circulation as well as a reduced equatorward LH transport is observed. The oceanic heat transport at NH midlatitudes increases owing to intensified subpolar gyres, and the Atlantic heat transport at low latitudes increases in all models whether or not meridional overturning circulation (MOC) intensifies. As a result, total poleward energy transport at the LGM increases in NH mid- and low latitudes in all models. Oceanic freshwater transport decreases, compensating for the response of the atmospheric water vapor transport. These responses in the atmosphere and ocean make the northern North Atlantic Ocean cold and relatively fresh, and the Southern Ocean relatively warm and saline. This is a common and robust feature in all models. The resultant ocean densities and ocean MOC response, however, show model dependency.
Can molecular dynamics simulations help in discriminating correct from erroneous protein 3D models?
Authors: Taly Jean-François , Marin Antoine , Gibrat Jean-François 
Published: February 2008

Abstract

Background
Recent approaches for predicting the three-dimensional (3D) structure of proteins such as de novo or fold recognition methods mostly rely on simplified energy potential functions and a reduced representation of the polypeptide chain. These simplifications facilitate the exploration of the protein conformational space but do not permit to capture entirely the subtle relationship that exists between the amino acid sequence and its native structure. It has been proposed that physics-based energy functions together with techniques for sampling the conformational space, e.g., Monte Carlo or molecular dynamics (MD) simulations, are better suited to the task of modelling proteins at higher resolutions than those of models obtained with the former type of methods. In this study we monitor different protein structural properties along MD trajectories to discriminate correct from erroneous models. These models are based on the sequence-structure alignments provided by our fold recognition method, FROST. We define correct models as being built from alignments of sequences with structures similar to their native structures and erroneous models from alignments of sequences with structures unrelated to their native structures.

Results
For three test sequences whose native structures belong to the all-α, all-β and αβ classes we built a set of models intended to cover the whole spectrum: from a perfect model, i.e., the native structure, to a very poor model, i.e., a random alignment of the test sequence with a structure belonging to another structural class, including several intermediate models based on fold recognition alignments. We submitted these models to 11 ns of MD simulations at three different temperatures. We monitored along the corresponding trajectories the mean of the Root-Mean-Square deviations (RMSd) with respect to the initial conformation, the RMSd fluctuations, the number of conformation clusters, the evolution of secondary structures and the surface area of residues. None of these criteria alone is 100% efficient in discriminating correct from erroneous models. The mean RMSd, RMSd fluctuations, secondary structure and clustering of conformations show some false positives whereas the residue surface area criterion shows false negatives. However if we consider these criteria in combination it is straightforward to discriminate the two types of models.

Conclusion
The ability of discriminating correct from erroneous models allows us to improve the specificity and sensitivity of our fold recognition method for a number of ambiguous cases.
The differentiation/retrodifferentiation program of human U937 leukemia cells is accompanied by changes of VCP/p97
Authors: Bertram Catharina , von Neuhoff Nils , Skawran Britta , Steinemann Doris , Schlegelberger Brigitte , Hass Ralf 
Published: February 2008

Abstract

Background
Retrodifferentiation and regained proliferative capacity of growth-arrested human leukemic cells after monocyte-like differentiation requires proteolytic activities together with distinct regulatory factors. The AAA ATPase valosin-containing protein (VCP/p97) contributes to protein degradation and cell cycle regulation, respectively, and it was of interest to study a possible role of VCP/p97 during this myelomonocytic differentiation and retrodifferentiation.

Results
Separation of autonomously proliferating human U937 myeloid leukemia cells by centrifugal elutriation demonstrated unaltered VCP/p97 expression levels throughout distinct phases of the cell cycle. However, phorbol ester-induced G0/G1 cell cycle arrest in differentiating human U937 leukemia cells was associated with a significantly increased protein and mRNA amount of this AAA ATPase. These elevated VCP/p97 levels progressively decreased again when growth-arrested U937 cells entered a retrodifferentiation program and returned to the tumorigenic phenotype. Whereas VCP/p97 was observed predominantly in the cytosol of U937 tumor and retrodifferentiated cells, a significant nuclear accumulation appeared during differentiation and G0/G1 growth arrest. Analysis of subcellular compartments by immunoprecipitations and 2D Western blots substantiated these findings and revealed furthermore a tyrosine-specific phosphorylation of VCP/p97 in the cytosolic but not in the nuclear fractions. These altered tyrosine phosphorylation levels, according to distinct subcellular distributions, indicated a possible functional involvement of VCP/p97 in the leukemic differentiation process. Indeed, a down-modulation of VCP/p97 protein by siRNA revealed a reduced expression of differentiation-associated genes in subsequent DNA microarray analysis. Moreover, DNA-binding and proliferation-associated genes, which are down-regulated during differentiation of the leukemic cells, demonstrated elevated levels in the VCP/p97 siRNA transfectants.

Conclusion
The findings demonstrated that monocytic differentiation and G0/G1 growth arrest in human U937 leukemia cells was accompanied by an increase in VCP/p97 expression and a distinct subcellular distribution to be reverted during retrodifferentiation. Together with a down-modulation of VCP/p97 by siRNA, these results suggested an association of this AAA ATPase in the differentiation/retrodifferentiation program.
Comparison of different pain scoring systems in critically ill patients in a general ICU
Authors: Ahlers Sabine JGM , van Gulik Laura , van der Veen Aletta M , van Dongen Hendricus PA , Bruins Peter , Belitser Svetlana V , de Boer Anthonius , Tibboel Dick , Knibbe Catherijne AJ 
Published: February 2008

Abstract
Background
Pain in critically ill patients in the intensive care unit (ICU) is common. However, pain assessment in critically ill patients often is complicated because these patients are unable to communicate effectively. Therefore, we designed a study (a) to determine the inter-rater reliability of the Numerical Rating Scale (NRS) and the Behavioral Pain Scale (BPS), (b) to compare pain scores of different observers and the patient, and (c) to compare NRS, BPS, and the Visual Analog Scale (VAS) for measuring pain in patients in the ICU.

Methods
We performed a prospective observational study in 113 non-paralyzed critically ill patients. The attending nurses, two researchers, and the patient (when possible) obtained 371 independent observation series of NRS, BPS, and VAS. Data analyses were performed on the sample size of patients (n = 113).

Results
Inter-rater reliability of the NRS and BPS proved to be adequate (kappa = 0.71 and 0.67, respectively). The level of agreement within one scale point between NRS rated by the patient and NRS scored by attending nurses was 73%. However, high patient scores (NRS ≥4) were underestimated by nurses (patients 33% versus nurses 18%). In responsive patients, a high correlation between NRS and VAS was found (rs = 0.84, P < 0.001). In ventilated patients, a moderate positive correlation was found between the NRS and the BPS (rs = 0.55, P < 0.001). However, whereas 6% of the observations were NRS of greater than or equal to 4, BPS scores were all very low (median 3.0, range 3.0 to 5.0).

Conclusion
The different scales show a high reliability, but observer-based evaluation often underestimates the pain, particularly in the case of high NRS values (≥4) rated by the patient. Therefore, whenever this is possible, ICU patients should rate their pain. In unresponsive patients, primarily the attending nurse involved in daily care should score the patient's pain. In ventilated patients, the BPS should be used only in conjunction with the NRS nurse to measure pain levels in the absence of painful stimuli.
Phase III Trial of Gemcitabine Compared With Pegylated Liposomal Doxorubicin in Progressive or Recurrent Ovarian Cancer
Authors: Ferrandina Gabriella , Ludovisi Manuela , Lorusso Domenica , Pignata Sandro , Breda Enrico , Savarese Antonella , Del Medico Pietro , Scaltriti Laura , Katsaros Dionyssios , Priolo Domenico , Scambia Giovanni 
Published: February 2008

Purpose We aimed at investigating the efficacy, tolerability, and quality of life (QOL) of gemcitabine (GEM) compared with pegylated liposomal doxorubicin (PLD) in the salvage treatment of recurrent ovarian cancer. Patients and Methods A phase III randomized multicenter trial was planned to compare GEM (1,000 mg/m2 on days 1, 8, and 15 every 28 days) with PLD (40 mg/m2 every 28 days) in ovarian cancer patients who experienced treatment failure with only one platinum/paclitaxel regimen and who experienced recurrence or progression within 12 months after completion of primary treatment. Results One hundred fifty-three patients were randomly assigned to PLD (n = 76) or GEM (n = 77). Treatment arms were well balanced for clinicopathologic characteristics. Grade 3 or 4 neutropenia was more frequent in GEM-treated patients versus PLD-treated patients (P = .007). Grade 3 or 4 palmar-plantar erythrodysesthesia was documented in a higher proportion of PLD patients (6%) versus GEM patients (0%; P = .061). The overall response rate was 16% in the PLD arm compared with 29% in the GEM arm (P = .056). No statistically significant difference in time to progression (TTP) curves according to treatment allocation was documented (P = .411). However, a trend for more favorable overall survival was documented in the PLD arm compared with the GEM arm, although the P value was of borderline statistical significance (P = .048). Statistically significantly higher global QOL scores were found in PLD-treated patients at the first and second postbaseline QOL assessments. Conclusion GEM does not provide an advantage compared with PLD in terms of TTP in ovarian cancer patients who experience recurrence within 12 months after primary treatment but should be considered in the spectrum of drugs to be possibly used in the salvage setting.
Inherited Variation in the Androgen Pathway Is Associated With the Efficacy of Androgen-Deprivation Therapy in Men With Prostate Cancer
Authors: Ross Robert W. , Oh William K. , Xie Wanling , Pomerantz Mark , Nakabayashi Mari , Sartor Oliver , Taplin Mary-Ellen , Regan Meredith M. , Kantoff Philip W. , Freedman Matthew 
Published: February 2008

Purpose Androgen-deprivation therapy (ADT) is the most common and effective systemic therapy for advanced prostate cancer. We hypothesized that germline genetic variation in the androgen axis would improve the efficacy of ADT. Patients and Methods A cohort of 529 men with advanced prostate cancer treated with ADT was genotyped for 129 DNA polymorphisms distributed across 20 genes involved in androgen metabolism. Results Three polymorphisms in separate genes (CYP19A1, HSD3B1, and HSD17B4) were significantly (P < .01) associated with time to progression (TTP) during ADT, remaining so in multivariate analyses and after correcting for the number of hypotheses tested. Individuals carrying more than one of the polymorphisms associated with improved TTP demonstrated a better response to therapy than individuals carrying zero or one (P < .0001). Conclusion This report is the first to examine the influence of inherited variation in the androgen metabolic pathway on the efficacy of ADT, establishing the importance of pharmacogenomics on individual's response to this therapy. At least two potential clinical benefits may be realized from this study. The first is prognostic –genotyping patients at these loci may yield important information that could improve efficacy prediction. The second is therapeutic –these results shed light on the pathways that govern response to ADT. Drugs could be developed (or may already exist) to inhibit or augment these targets to improve ADT efficacy.
A medication assessment tool to evaluate adherence to medication guideline criteria in cancer pain management
Authors: Håkonsen Gro Dahlseng , Torbergsen Ann Lisbeth , Strelec Petra , Campbell Derna , Hudson Steve , Loennechen Thrina 
Published: February 2008

AbstractObjectiveThe medication assessment tool for cancer pain management (MAT-CP) is a novel tool for measuring quality of drug use in chronic pain management in relation to guideline standards, and has been developed and tested in Norway with UK collaboration. The present paper describes the revision of the assessment tool for use in the UK, and its subsequent validation.SettingThree hospitals and one hospice in Scotland, UK.MethodThe MAT-CP was field-tested to produce preliminary data on its applicability in a UK clinical setting. The tool was then modified by peer review among clinical specialists before and after a pilot. The revised tool was further validated by wider application to a study sample of cancer inpatients. The outcome was the evaluation of the tool's utility in relation to clinical documentation in terms of applicability, clarity, reliability and perceived relevance of each criterion. The findings also included a quantification of adherence to the guideline criteria.Key findingsThe revised tool comprised 37 criteria covering six different aspects of cancer pain management. The field testing and pilot informed the modification of the MAT-CP to optimise its clarity and utility when applied to patients' clinical documentation. The revised tool was tested on 101 cancer patients experiencing pain (56 males), mean (standard deviation) age 68.9 (13.5) years. Overall guideline adherence was 68% (n = 1850 applicable criteria). Good inter-rater reliability (Cohen's kappa κ = 0.92) was demonstrated in the application. The preliminary application of the tool during validation and field-testing has highlighted several issues for further study.ConclusionA clinical tool to examine prescribing in cancer pain management that was designed for use in Norway has been revised for use in UK clinical settings. Reliability, face and content validity have been informed by applying the tool to patient data in clinical settings.
Intracellular pH homeostasis and serotonin-induced pH changes inCalliphorasalivary glands: the contribution of V-ATPase and carbonic anhydrase
Authors: Schewe Bettina , Schmälzlin Elmar , Walz Bernd 
Published: February 2008

SUMMARYBlowfly salivary gland cells have a vacuolar-type H+-ATPase(V-ATPase) in their apical membrane that energizes secretion of a KCl-rich saliva upon stimulation with serotonin (5-hydroxytryptamine, 5-HT). We have used BCECF to study microfluometrically whether V-ATPase and carbonic anhydrase (CA) are involved in intracellular pH (pHi) regulation,and we have localized CA activity by histochemistry. We show: (1) mean pHi in salivary gland cells is 7.5±0.3 pH units(N=96), higher than that expected from passive H+distribution; (2) low 5-HT concentrations (0.3–3 nmol l–1) induce a dose-dependent acidification of up to 0.2 pH units, with 5-HT concentrations &gt;10 nmol l–1, causing monophasic or multiphasic pH changes; (3) the acidifying effect of 5-HT is mimicked by bath application of cAMP, forskolin or IBMX; (4) salivary gland cells exhibit CA activity; (5) CA inhibition with acetazolamide and V-ATPase inhibition with concanamycin A lead to a slow acidification of steady-state pHi; (6) 5-HT stimuli in the presence of acetazolamide induce an alkalinization that can be decreased by simultaneous application of the V-ATPase inhibitor concanamycin A; (7) concanamycin A removes alkali-going components from multiphasic 5-HT-induced pH changes; (8) NHE activity and a Cl–-dependent process are involved in generating 5-HT-induced pH changes; (9) the salivary glands probably contain a Na+-driven amino acid transporter. We conclude that V-ATPase and CA contribute to steady-state pHi regulation and 5-HT-induced outward H+pumping does not cause an alkalinization of pHi because of cytosolic H+ accumulation attributable to stimulated cellular respiration and AE activity, masking the alkalizing effect of V-ATPase-mediated acid extrusion.
Vortex wake and flight kinematics of a swift in cruising flight in a wind tunnel
Authors: Henningsson P. , Spedding G. R. , Hedenström A. 
Published: February 2008

SUMMARYIn this paper we describe the flight characteristics of a swift (Apus apus) in cruising flight at three different flight speeds (8.0, 8.4 and 9.2 m s–1) in a low turbulence wind tunnel. The wingbeat kinematics were recorded by high-speed filming and the wake of the bird was visualized by digital particle image velocimetry (DPIV). Certain flight characteristics of the swift differ from those of previously studied species. As the flight speed increases, the angular velocity of the wingbeat remains constant, and so as the wingbeat amplitude increases, the frequency decreases accordingly, as though the flight muscles were contracting at a fixed rate. The wings are also comparatively inflexible and are flexed or retracted rather little during the upstroke. The upstroke is always aerodynamically active and this is reflected in the wake, where shedding of spanwise vorticity occurs throughout the wingbeat. Although the wake superficially resembles those of other birds in cruising flight, with a pair of trailing wingtip vortices connected by spanwise vortices, the continuous shedding of first positive vorticity during the downstroke and then negative vorticity during the upstroke suggests a wing whose circulation is gradually increasing and then decreasing during the wingbeat cycle. The wake (and implied wing aerodynamics)are not well described by discrete vortex loop models, but a new wake-based model, where incremental spanwise and streamwise variations of the wake impulse are integrated over the wingbeat, shows good agreement of the vertical momentum flux with the required weight support. The total drag was also estimated from the wake alone, and the calculated lift:drag ratio of approximately 13 for flapping flight is the highest measured yet for birds.
Larvae of the fall webworm, Hyphantria cunea, inhibit cyanogenesis in Prunus serotina
Authors: Fitzgerald T. D. 
Published: February 2008

SUMMARY
The larvae of the fall webworm, Hyphantria cunea (Dru.), though vulnerable to cyanide poisoning, consume the cyanogenic leaves of black cherry, Prunus serotina, without apparent harm. The cyanide contents of leaves, defensive regurgitant, the bolus, and frass were assayed by ion chromatography to determine the fate of the toxin in the caterpillar. Leaves collected in September, when the caterpillars were feeding, contained 1592±276 p.p.m. cyanide. Samples of dried frass obtained from caterpillars fed these leaves yielded 2868±552 p.p.m. cyanide. Frass extracted directly in NaOH yielded approximately five percent of the cyanide obtained from frass ground in buffer and distilled in Warburg flasks,indicating that cyanogenesis is largely inhibited as the bolus traverses the gut. This inhibition is attributable to the ability of the caterpillar to maintain a foregut environment in the presence of the bolus that is sufficiently alkaline to suppress the conversion of the plant cyanogen to cyanide. Although a number of caterpillars feed without harm on cyanogenic plants, this it the first shown to inhibit cyanogenesis in this manner.
Thermoregulation in pronghorn antelope (Antilocapra americana,Ord) in winter
Authors: Hébert J. , Lust A. , Fuller A. , Maloney S. K. , Mitchell D. , Mitchell G. 
Published: February 2008

SUMMARY
Conservation of energy is a prerequisite thermoregulatory strategy for survival in northern hemisphere winters. We have used thermistor/data logger assemblies to measure temperatures in the brain, carotid artery, jugular vein and abdominal cavity, in pronghorn antelope to determine their winter body temperature and to investigate whether the carotid rete has a survival role. Over the study period mean black globe and air temperature were–0.5±3.2°C and –2.0±3.4°C, respectively, and mean daytime solar radiation was ∼186 W m–2. Brain temperature (Tbrain, 39.3±0.3°C) was higher than carotid blood temperature (Tcarotid,38.5±0.4°C), and higher than jugular temperature(Tjugular, 37.9±0.7°C). Minimum Tbrain (38.5±0.4°C) and Tcarotid (37.8±0.2°C) in winter were higher than the minimum Tbrain (37.7±0.5°C) and Tcarotid (36.4±0.8°C) in summer that we have reported previously. Compared with summer, winter body temperature patterns were characterized by an absence of selective brain cooling (SBC), a higher range of Tbrain, a range of Tcarotidthat was significantly narrower (1.8°C) than in summer (3.1°C), and changes in Tcarotid and Tbrain that were more highly correlated (r=0.99 in winter vs r=0.83 in summer). These findings suggest that in winter the effects of the carotid rete are reduced, which eliminates SBC and prevents independent regulation of Tbrain, thus coupling Tbrain to Tcarotid. The net effect is that Tcarotid varies little. A possible consequence is depression of metabolism, with the survival advantage of conservation of energy. These findings also suggest that the carotid rete has wider thermoregulatory effects than its traditional SBC function.