bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimization of a Sea Ice Model Using Basinwide Observations of Arctic Sea Ice Thickness, Extent, and Velocity
Authors: Miller Paul A. , Laxon Seymour W. , Feltham Daniel L. , Cresswell Douglas J. 
Published: April 2006

Abstract
A stand-alone sea ice model is tuned and validated using satellite-derived, basinwide observations of sea ice thickness, extent, and velocity from the years 1993 to 2001. This is the first time that basin-scale measurements of sea ice thickness have been used for this purpose. The model is based on the CICE sea ice model code developed at the Los Alamos National Laboratory, with some minor modifications, and forcing consists of 40-yr ECMWF Re-Analysis (ERA-40) and Polar Exchange at the Sea Surface (POLES) data. Three parameters are varied in the tuning process: Ca, the air–ice drag coefficient; P*, the ice strength parameter; and α, the broadband albedo of cold bare ice, with the aim being to determine the subset of this three-dimensional parameter space that gives the best simultaneous agreement with observations with this forcing set. It is found that observations of sea ice extent and velocity alone are not sufficient to unambiguously tune the model, and that sea ice thickness measurements are necessary to locate a unique subset of parameter space in which simultaneous agreement is achieved with all three observational datasets.
Interannual to Decadal Climate Predictability in the North Atlantic: A Multimodel-Ensemble Study
Authors: Collins M. , Botzet M. , Carril A. F. , Drange H. , Jouzeau A. , Latif M. , Masina S. , Otteraa O. H. , Pohlmann H. , Sorteberg A. , Sutton R. , Terray L. 
Published: April 2006

Abstract
Ensemble experiments are performed with five coupled atmosphere–ocean models to investigate the potential for initial-value climate forecasts on interannual to decadal time scales. Experiments are started from similar model-generated initial states, and common diagnostics of predictability are used. We find that variations in the ocean meridional overturning circulation (MOC) are potentially predictable on interannual to decadal time scales, a more consistent picture of the surface temperature impact of decadal variations in the MOC is now apparent, and variations of surface air temperatures in the North Atlantic Ocean are also potentially predictable on interannual to decadal time scales, albeit with potential skill levels that are less than those seen for MOC variations. This intercomparison represents a step forward in assessing the robustness of model estimates of potential skill and is a prerequisite for the development of any operational forecasting system.
Changes in Low Cloudiness over China between 1971 and 1996
Authors: Endo Nobuhiko , Yasunari Tetsuzo 
Published: April 2006

Abstract
The climatology and long-term trends of low-cloud conditions over China were examined using the Extended Edited Cloud Report Archive data from 1971 to 1996. Linear regression analysis was applied to time series of clear-sky frequencies and low-cloud frequencies, and low-cloud amounts when present. Over the 26-yr study period, the clear-sky frequency increased over northern China. During summer, the frequency of cumuliform clouds decreased over almost all of China. A significant decrease characterized the trend in cumulonimbus (Cb) frequency; however, the Cb cloud amount when present increased over the Yangtze River basin and southern China. Increasing trends in stratocumulus (Sc) cloud amount when present were also observed over much of China.
Unique efficacy of Toll-like receptor 8 agonists in activating human neonatal antigen-presenting cells
Authors: Levy Ofer , Suter Eugénie E. , Miller Richard L. , Wessels Michael R. 
Published: April 2006

AbstractNewborns are prone to microbial infection and have poor memory responses to multiple antigens. We have previously shown that human neonatal blood monocytes exhibit impaired TNF-α responses to most known TLR agonists, including the pure TLR7 agonist imiquimod. Surprisingly, however, neonatal TNF-α responses to the imiquimod congener R-848 (TLR 7/8) were fully intact. We now show that TLR8 agonists, including R-848 (TLR7/8), the imidazoquinoline congeners 3M-003 (TLR7/8) and 3M-002 (TLR8), as well as single-stranded viral RNAs (TLR8) induced robust production of the Th1-polarizing cytokines TNF-α and IL-12 from neonatal antigen-presenting cells (APCs) that substantially exceeds responses induced by TLR-2, -4, or -7 (alone) agonists. TLR8 agonists also effectively induced up-regulation of the costimulatory molecule CD40 on neonatal and adult myeloid dendritic cells (DCs). The strong activity of TLR8 agonists correlates with their induction of p38 MAP kinase phosphorylation and with degradation of IκB-α in both neonatal and adult monocytes. We conclude that TLR8 agonists are uniquely efficacious in activating costimulatory responses in neonatal APCs and suggest that these agents are promising candidate adjuvants for enhancing immune responses in human newborns.
Transcriptomes of human prostate cells
Authors: Oudes Asa J , Campbell Dave S , Sorensen Carrie M , Walashek Laura S , True Lawrence D , Liu Alvin Y 
Published: April 2006

Abstract

Background
The gene expression profiles of most human tissues have been studied by determining the transcriptome of whole tissue homogenates. Due to the solid composition of tissues it is difficult to study the transcriptomes of individual cell types that compose a tissue. To overcome the problem of heterogeneity we have developed a method to isolate individual cell types from whole tissue that are a source of RNA suitable for transcriptome profiling.

Results
Using monoclonal antibodies specific for basal (integrin β4), luminal secretory (dipeptidyl peptidase IV), stromal fibromuscular (integrin α 1), and endothelial (PECAM-1) cells, respectively, we separated the cell types of the prostate with magnetic cell sorting (MACS). Gene expression of MACS-sorted cell populations was assessed with Affymetrix GeneChips. Analysis of the data provided insight into gene expression patterns at the level of individual cell populations in the prostate.

Conclusion
In this study, we have determined the transcriptome profile of a solid tissue at the level of individual cell types. Our data will be useful for studying prostate development and cancer progression in the context of single cell populations within the organ.
Differential expression of a new isoform of DLG2 in renal oncocytoma
Authors: Zubakov Dmitry , Stupar Zorica , Kovacs Gyula 
Published: April 2006

Abstract

Background
Renal oncocytoma, a benign tumour of the kidney, may pose a differential diagnostic problem due to overlapping phenotype with chromophobe renal cell carcinoma or other types of renal cell tumours. Therefore, identification of molecular markers would be of great value for molecular diagnostics of this tumour type.

Methods
In the current study we applied various techniques, including Affymetrix microarray hybridization and semiquantitative RT-PCR, to identify genes expressed differentially in renal oncocytomas. Subsequently, we used RACE and Northern blot hybridization to characterize the potential candidates for molecular diagnosis.

Results
We have identified new isoform of DLG2 gene, which contains 3'-end exons of the known DLG2 gene along with the hypothetical gene FLJ37266. The new isoform is specifically upregulated in renal oncocytoma, whereas the known DLG2 gene is downregulated in this type of kidney tumour.

Conclusion
The new isoform of DLG2 is the promising candidate gene for molecular differential diagnostics of renal oncocytoma.
Accelerated discharge of patients in the event of a major incident: observational study of a teaching hospital
Authors: Challen Kirsty , Walter Darren 
Published: April 2006

Abstract

Background
Since October 2002 in the UK Primary Care Trusts (PCTs) have had statutory responsibility for having and maintaining a Major Incident plan and since 2005 they have been obliged to co-operate with other responders to an incident. We aimed to establish the number of beds in our Trust which could be freed up over set periods of time in the event of a major incident and the nature and quantity of support which might be required from PCTs in order to achieve this.

Methods
Repeated survey over 12 days in 3 months of hospital bed occupancy by type of condition and discharge capacity in an 855-bed UK tertiary teaching hospital also providing secondary care services. Outcome measures were bed spaces which could be generated, timescale over which this could happen and level and type of PCT support which would be required to achieve this.

Results
Mean beds available were 78 immediately, a further 69 in 1–4 hours and a further 155 in 4–12 hours, generating a total of 302 beds (36% of hospital capacity) within 12 hours of an incident. This would require support from a PCT of 150,000 population of 10 nursing care beds, 20 therapy-supported intermediate care beds, and 25 care packages in patients' own homes.

Conclusion
In order to fulfill the requirements of the Civil Contingencies Act 2004, PCTs should plan to have surge capacity in the order of 30 residential placements and 25 community support packages per 150,000 population to support Acute Trusts in the event of a major incident.
A modular interface of IL-4 allows for scalable affinity without affecting specificity for the IL-4 receptor
Authors: Kraich Michael , Klein Markus , Patiño Edwin , Harrer Henning , Nickel Joachim , Sebald Walter , Mueller Thomas D 
Published: April 2006

AbstractBackgroundInterleukin 4 (IL-4) is a key regulator of the immune system and an important factor in the development of allergic hypersensitivity. Together with interleukin 13 (IL-13), IL-4 plays an important role in exacerbating allergic and asthmatic symptoms. For signal transduction, both cytokines can utilise the same receptor, consisting of the IL-4Rα and the IL-13Rα1 chain, offering an explanation for their overlapping biological functions. Since both cytokine ligands share only moderate similarity on the amino acid sequence level, molecular recognition of the ligands by both receptor subunits is of great interest. IL-4 and IL-13 are interesting targets for allergy and asthma therapies. Knowledge of the binding mechanism will be important for the generation of either IL-4 or IL-13 specific drugs.ResultsWe present a structure/function analysis of the IL-4 ligand-receptor interaction. Structural determination of a number of IL-4 variants together within vitrobinding studies show that IL-4 and its high-affinity receptor subunit IL-4Rα interact via a modular protein-protein interface consisting of three independently-acting interaction clusters. For high-affinity binding of wild-type IL-4 to its receptor IL-4Rα, only two of these clusters (i.e. cluster 1 centered around Glu9 and cluster 2 around Arg88) contribute significantly to the free binding energy. Mutating residues Thr13 or Phe82 located in cluster 3 to aspartate results in super-agonistic IL-4 variants. All three clusters are fully engaged in these variants, generating a three-fold higher binding affinity for IL-4Rα. Mutagenesis studies reveal that IL-13 utilizes the same main binding determinants,i.e. Glu11 (cluster 1) and Arg64 (cluster 2), suggesting that IL-13 also uses this modular protein interface architecture.ConclusionThe modular architecture of the IL-4-IL-4Rα interface suggests a possible mechanism by which proteins might be able to generate binding affinity and specificity independently. So far, affinity and specificity are often considered to co-vary,i.e. high specificity requires high affinity and vice versa. Although the binding affinities of IL-4 and IL-13 to IL-4Rα differ by a factor of more than 1000, the specificity remains high because the receptor subunit IL-4Rα binds exclusively to IL-4 and IL-13. An interface formed by several interaction clusters/binding hot-spots allows for a broad range of affinities by selecting how many of these interaction clusters will contribute to the overall binding free energy. Understanding how proteins generate affinity and specificity is essential as more and more growth factor receptor families show promiscuous binding to their respective ligands. This limited specificity is, however, not accompanied by low binding affinities.
Modulation of apoptosis in intestinal lymphocytes by a probiotic bacteria in Crohn's disease
Authors: Carol Monica , Borruel Natalia , Antolin Maria , Llopis Marta , Casellas Francesc , Guarner Francisco , Malagelada Juan R 
Published: April 2006

Abstract
Apoptosis of active T lymphocytes constitutes a maor control mechanism of immune homeostasis and tolerance. In Crohn's disease, abnormal activation of mucosal T lymphocytes against enteric bacteria is the key event triggering intestinal inflammation. Resistance of lymphocytes to apoptosis has been proposed as the pathogenetic defect. We examined the influence of bacteria-mucosa interactions on apoptosis of mucosal T lymphocytes. Ileal specimens were obtained at surgery from 12 patients with Crohn's disease. Mucosal explants from each specimen were cultured with nonpathogenic Escherichia coli ATCC 35345, Lactobacillus casei DN-114 001, or no bacteria. Cytokine release was measured in supernatant, and mononuclear cells were isolated for phenotypic characterization and Bcl-2 family protein expression. Coculture of inflamed tissue with L. casei significantly reduced the release of interleukin (IL)-6 and tumor necrosis factor α (P&lt;0.05). In addition, coculture with L. casei significantly reduced the number of T cells displaying the IL-2 receptor in the lamina propria. Expression of the antiapoptotic protein Bcl-2 in lamina propria lymphocytes was also reduced after coculture with L. casei, and the percentage of deoxyuridine triphosphate nick-end labeling positive lymphocytes increased. The nonpathogenic E. coli strain had no significant effect. In conclusion, L. casei reduces the number of activated T lymphocytes in the lamina propria of Crohn's disease mucosa. A balanced, local microecology may restore immune homeostasis.
Ischemia-induced angiogenesis: role of inflammatory response mediated by P-selectin
Authors: Egami Kimiyasu , Murohara Toyoaki , Aoki Mika , Matsuishi Toyojiro 
Published: April 2006

Abstract
P-selectin is a 140-kDa glycoprotein expressed on endothelial cells and platelets. P-selectin mediates the tethering and rolling of leukocytes along the endothelium, an early step of leukocyte extravasation. Although inflammation is a requisite process for ischemia-induced angiogenesis, little is known regarding the role of P-selectin in angiogenesis in the setting of tissue ischemia. We examined whether ischemia-induced angiogenesis is altered in P-selectin knockout (P-selectin−/−) mice. Angiogenesis was evaluated n a surgically induced hind-limb ischemia model using laser Doppler blood flowmetry (LDBF) and histological capillary density (CD). After left hind-limb ischemia, the ischemic/normal limb LDBF ratio was persistently lower in P-selectin−/− mice compared with wild-type (WT) mice. CD was also significantly lower in P-selectin−/− mice than in WT mice on Postoperative Day 14. Fewer numbers of total CD45+ inflammatory leukocytes infiltrated into the ischemic tissues in P-selectin−/− mice than in WT mice, and immunohistochemical analysis revealed the number of infiltrated leukocytes expressing vascular endothelial growth factor was also decreased in P-selectin−/− mice. P-selectin mRNA expression was augmented after hind-limb ischemia in WT mice. In conclusion, P-selectin may play an important role in ischemia-induced angiogenesis by promoting early inflammatory mononuclear cell infiltration. P-selectin would become one possible target molecule for modulating inflammatory angiogenesis.
Recognition ligands on apoptotic cells: a perspective
Authors: Gardai Shyra J , Bratton Donna L , Ogden Carole Anne , Henson Peter M 
Published: April 2006

Abstract
The process of apoptosis includes critically important changes on the cell surface that lead to its recognition and removal. The recognition also generates a number of other local tissue responses including suppression of iflammation and immunity. It is surprising that the ligands generated on the apoptotic cell, which mediates these effects, have received relatively little attention. Some of these candidate molecules and possible mechanisms for their surface expression are addressed herein, with particular emphasis on phosphatidylserine and calreticulin. However, exposure of such ligands is exclusive to apoptosis and may, in fact, occur on viable cells. To partially explain the lack of response to such potential stimuli, the presence on viable cells of “don't eat me” signals, in this case, CD47 is suggested to prevent such unwarranted actions. Loss or inactivation of the don't eat me CD47 effects accompanies apoptosis and now allow the cells to be recognized and cleared.
Adhesion of thrombotic components to the surface of a clinically used oxygenator is not affected by Trillium coating
Authors: van den Goor Jeanette M , van Oeveren Willem , Rutten Peter M , Tijssen Jan G , Eijsman León 
Published: April 2006

The Trillium® coating is designed to minimize adsorption of protein and the attachment of cells and other particles. The present study was undertaken to investigate the effect of surface coating on the adhesion of thrombotic components (activated platelets, white blood cells and fibrin) to the surface of a clinically used oxygenator. Twenty patients undergoing elective coronary artery bypass grafting (CABG) were randomized to one of the two oxygenator groups: non-coated (NC, n=10) or Trillium®-coated (TC, n=10). Platelet and white blood cell counts and factor XIIa concentrations were determined prior to the induction of anesthesia and at the end of cardiopulmonary bypass (CPB). Binding of activated platelets, white blood cells and fibrin to the artificial surfaces was quantified by means of antibody binding and histological validation was achieved by scanning electron microscopy. Patient demographic and CPB data were similar for the two groups. No significant differences between the groups were found for any of the tested thrombotic components. However, observations from our scanning electron microscopy suggested a release of formed particles from the Trillium®-coated surface. Primary adhesion of activated platelets, white blood cells and fibrin to the artificial surface of the venous blood inlet from an oxygenator is not affected by the Trillium® surface coating under conditions of full systemic heparinization.
Is body surface area still the best way to determine pump flow rate during cardiopulmonary bypass?
Authors: Alston R Peter , Anderson Anna , Sanger Keith 
Published: April 2006

For over four decades, pump flow rate during cardio-pulmonary bypass (CPB) has been estimated using body surface area (BSA). As patients presenting for heart surgery are increasingly obese, this approach may no longer be appropriate and other estimates of systemic metabolism should be used, such as body mass index and lean body mass. Mixed venous oxygen saturation (SvO2) is a robust and independent estimate of the global efficacy of CPB. The aim of this study was to determine which factors, including body surface area, body mass index and lean body mass, best predict SvO2 during CPB. Forty-eight patients undergoing elective cardiac surgery requiring CPB were studied. Patients’ height, weight and skinfold thickness at four sites (biceps, triceps, subscapularis and suprailiac) were measured. Body surface area, lean body mass and body mass index were then calculated. Pump flow rate was maintained at 2.4 L/min/m2 during CPB as per standard unit protocol. Arterial and mixed venous blood samples were taken during the cooling, stable hypothermia and rewarming phases of CPB. Nasopharyngeal temperatures and flow rates were recorded contemporaneously. The blood samples were analysed for oxygen saturation, haemoglobin concentration and partial pressures of oxygen and carbon dioxide. The values of the three time points were meaned. All potential predictor variables were then univariately correlated with mixed venous oxygen saturation (SvO2). Those correlating significantly ( p < 0.1) were entered into a multivariate linear regression model. Nasopharyngeal temperature (β=0.615, p < 0.001) and lean body mass (β=0.256, p < 0.028) were the only significant predictors of SvO2 ( r2= 0.433, p < 0.001). Pump flow rates maintained at 2.4 L/min/m2 throughout CPB results in relative over-perfusion during hypothermia. Lean body mass may be a more sensitive estimate of systemic metabolism and, therefore, may provide a more accurate means of determining pump flow rate than body surface area in patients undergoing heart surgery.
Pro-Change adult smokers program: Northumberland pilot
Authors: Anderson Claire , Mair Alpana 
Published: April 2006

Abstract

Objective
To pilot and evaluate the Pro-Change adult smokers program in primary care settings. This interactive, multimedia computer program for adult smokers was backed up with a self-help manual and support from trained health care professionals. The program assesses individuals' readiness to change their smoking behaviour using the transtheoretical model. Key objectives of the pilot were to widen access to support for smoking cessation and to engage low income and unemployed smokers in smoking cessation attempts.

Methods
Quantitative analysis of use of the computer program supplemented by qualitative research. In-depth interviews, focus groups and telephone interviews were performed with stakeholders (six), Pro-Change advisers (10) and a self-selected sample of clients (20).

Setting
The pilot was conducted in one area of England in the settings of one community pharmacy and three general medical practices between October 1999 and March 2000.

Key findings
Of the 258 people who accessed the program during the six-month pilot, 159 did so in the community pharmacy and 99 in the general medical practices. Program users included a large proportion of people on low incomes and without work. Pro-Change was well-received by clients and stakeholders. There were some issues in accessing the system in the general medical practices, where an appointment was necessary and the service was only available for part of the time. One hundred and twenty-four of the system users set a quit date, 92 (74 per cent) of whom were followed up at four weeks post quit date and 51 (41 per cent) reported that they had stopped smoking.

Conclusions
Pro-Change reached the target audience of low-income smokers. Most stakeholders, advisers and clients valued the computer program; it brought a new dimension to local smoking cessation services. Siting Pro-Change in the community pharmacy widened access compared with provision in general practices alone. Self-reported quit rates were comparable to other reported studies.