bluuebunny/crossref_metadata_2025_split huggingface dataset:
NY-ESO-1 DNA Vaccine Induces T-Cell Responses That Are Suppressed by Regulatory T Cells
Authors: Gnjatic Sacha , Altorki Nasser K. , Tang Derek Ng , Tu Shi-Ming , Kundra Vikas , Ritter Gerd , Old Lloyd J. , Logothetis Christopher J. , Sharma Padmanee 
Published: March 2009

AbstractPurpose: Different vaccination strategies against the NY-ESO-1 antigen have been employed in an attempt to induce antitumor immune responses. Antigen-specific effector T-cell responses have been reported in a subset of vaccinated patients; however, these responses have not consistently correlated with disease regression. Here, we report for the first time clinical and immune responses generated by the NY-ESO-1 DNA vaccine administered by particle-mediated epidermal delivery to cancer patients.Experimental Design: Eligible patients received treatment with the NY-ESO-1 DNA vaccine. Clinical outcomes and immune responses were assessed.Results: The NY-ESO-1 DNA vaccine was safely administered and induced both antigen-specific effector CD4 and/or CD8 T-cell responses in 93% (14 of 15) of patients who did not have detectable pre-vaccine immune responses. Despite the induction of antigen-specific T-cell responses, clinical outcomes consisted predominantly of progressive disease. Detectable effector T-cell responses were inconsistent and did not persist in all patients after completion of the scheduled vaccinations. However, high-avidity CD4 T-cell responses that were either undetectable pre-vaccine or found to be diminished at a later time during the clinical trial were detected in certain patients' samples after in vitro depletion of regulatory T cells.Conclusions: Regulatory T cells play a role in diminishing vaccine-induced antigen-specific effector T-cell responses in cancer patients. The NY-ESO-1 DNA vaccine represents a feasible immunotherapeutic strategy to induce antigen-specific T-cell responses. Counteracting regulatory T-cell activity before vaccination may lead to prolonged effector T-cell responses and possibly antitumor responses in cancer patients.
A Six-Nucleotide Insertion-Deletion Polymorphism in the CASP8 Promoter Associated with Risk and Progression of Bladder Cancer
Authors: Wang Meilin , Zhang Zhizhong , Tian Yuanyuan , Shao Jianfeng , Zhang Zhengdong 
Published: March 2009

Abstract
Purpose: Caspase-8 (CASP8) is a key regulator of apoptosis or programmed cell death, an essential defense mechanism against hyperproliferation and malignancy. We hypothesized that the variants in the CASP8 gene are associated with risk of bladder cancer.
Experimental Design: In a hospital-based case-control study of 365 case patients with newly diagnosed bladder transitional cell carcinoma and 368 cancer-free controls frequency-matched by age and sex, we genotyped the functional -652 6N ins/del polymorphism (rs3834129) in the promoter of CASP8 and assessed its associations with risk of bladder cancer and interaction with tobacco smoking.
Results: A significant decreased risk of bladder cancer was found for the CASP8 -652 6N ins/del (adjusted odds ratio, 0.72; 95% confidence interval, 0.53-0.99) and del/del (odds ratio, 0.37; 95% confidence interval, 0.18-0.77) genotypes. Furthermore, a significant additive interaction between CASP8 polymorphism and tobacco smoking on bladder cancer risk was observed.
Conclusions: These results suggested that the CASP8 -652 6N ins/del polymorphism is involved in etiology of bladder cancer and thus may be a marker for genetic susceptibility to bladder cancer in Chinese populations. Larger studies are warranted to validate our findings.
Molecular determinants of melanoma malignancy: selecting targets for improved efficacy of chemotherapy
Authors: Yang Jinming , Zaja-Milatovic Snjezana , Thu Yee-Mon , Lee Francis , Smykla Richard , Richmond Ann 
Published: March 2009

Abstract
The BRAFV600E mutation is common in human melanoma. This mutation enhances IκB kinase (IKK)/nuclear factor-κB (NF-κB) and extracellular signal-regulated kinase/activator protein signaling cascades. In this study, we evaluated the efficacy of targeting either B-Raf or IKKβ in combination with the DNA alkylating agent temozolomide for treatment of advanced metastatic melanoma. Xenografts of Hs294T human metastatic melanoma cells exhibiting the BRAFV600E mutation were treated with inhibitors of IKKβ (BMS-345541), B-Raf (BAY 54-9085), and/or temozolomide. Drug response was mechanistically analyzed in vitro and in vivo. In this study, we determined that the antitumor activity of all three drugs depends on inhibition of NF-κB. BMS-345541 inhibits IKKβ-mediated phosphorylation of IκBα and thus blocks the nuclear localization of NF-κB, whereas BAY 54-9085 inhibits activation of NF-κB through a mechanism that does not involve stabilization of IκBα. Moreover, BMS-345541, but not BAY 54-9085, activates the death pathways of p53 and c-Jun-NH2-kinase, contributing to the killing of melanoma cells. Temozolomide inhibits both NF-κB and extracellular signal-regulated kinase activity, conferring effective in vivo antitumor activity. Thus, temozolomide, but not BAY 54-9085, has a synergistic in vivo antitumor effect with BMS-345541. We conclude that the efficacy of antimelanoma therapy depends on inhibition of expression of antiapoptotic genes transcriptionally regulated by NF-κB. In contrast, drug targeting of the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway alone in melanoma cells is ineffective for melanoma therapy in cases where NF-κB is not also targeted. [Mol Cancer Ther 2009;8(3):OF636–12]
Aldehyde Dehydrogenase 1 Is a Tumor Stem Cell-Associated Marker in Lung Cancer
Authors: Jiang Feng , Qiu Qi , Khanna Abha , Todd Nevins W. , Deepak Janaki , Xing Lingxiao , Wang Huijun , Liu Zhenqiu , Su Yun , Stass Sanford A. , Katz Ruth L. 
Published: March 2009

Abstract
Tumor contains small population of cancer stem cells (CSC) that are responsible for its maintenance and relapse. Analysis of these CSCs may lead to effective prognostic and therapeutic strategies for the treatment of cancer patients. We report here the identification of CSCs from human lung cancer cells using Aldefluor assay followed by fluorescence-activated cell sorting analysis. Isolated cancer cells with relatively high aldehyde dehydrogenase 1 (ALDH1) activity display in vitro features of CSCs, including capacities for proliferation, self-renewal, and differentiation, resistance to chemotherapy, and expressing CSC surface marker CD133. In vivo experiments show that the ALDH1-positive cells could generate tumors that recapitulate the heterogeneity of the parental cancer cells. Immunohistochemical analysis of 303 clinical specimens from three independent cohorts of lung cancer patients and controls show that expression of ALDH1 is positively correlated with the stage and grade of lung tumors and related to a poor prognosis for the patients with early-stage lung cancer. ALDH1 is therefore a lung tumor stem cell-associated marker. These findings offer an important new tool for the study of lung CSCs and provide a potential prognostic factor and therapeutic target for treatment of the patients with lung cancer. (Mol Cancer Res 2009;7(3):330–8)
Tropical Cyclone Activity in the Fiji Region: Spatial Patterns and Relationship to Large-Scale Circulation
Authors: Chand Savin S. , Walsh Kevin J. E. 
Published: March 2009

AbstractThis study examines the variations in tropical cyclone (TC) genesis positions and their subsequent tracks for different phases of the El Niño–Southern Oscillation (ENSO) phenomenon in the Fiji, Samoa, and Tonga region (FST region) using Joint Typhoon Warning Center best-track data. Over the 36-yr period from 1970/71 to 2005/06, 122 cyclones are observed in the FST region. A large spread in the genesis positions is noted. During El Niño years, genesis is enhanced east of the date line, extending from north of Fiji to over Samoa, with the highest density centered around 10°S, 180°. During neutral years, maximum genesis occurs immediately north of Fiji with enhanced genesis south of Samoa. In La Niña years, there are fewer cyclones forming in the region than during El Niño and neutral years. During La Niña years, the genesis positions are displaced poleward of 12°S, with maximum density centered around 15°S, 170°E and south of Fiji. The cyclone tracks over the FST region are also investigated using cluster analysis. Tracks during the period 1970/71–2005/06 are conveniently described using three separate clusters, with distinct characteristics associated with different ENSO phases. Finally, the role of large-scale environmental factors affecting interannual variability of TC genesis positions and their subsequent tracks in the FST region are investigated. Favorable genesis positions are observed where large-scale environments have the following seasonal average thresholds: (i) 850-hPa cyclonic relative vorticity between −16 and −4 (×10−6 s−1), (ii) 200-hPa divergence between 2 and 8 (×10−6 s−1), and (iii) environmental vertical wind shear between 0 and 8 m s−1. The subsequent TC tracks are observed to be steered by mean 700–500-hPa winds.
Dynamics of the Northern Tsuchiya Jet*
Authors: Furue Ryo , McCreary Julian P. , Yu Zuojun 
Published: March 2009

Abstract
The Tsuchiya jets (TJs) are narrow eastward currents located along thermal fronts at the poleward edges of thermostad water in the Pacific Ocean. In this study, an oceanic general circulation model (OGCM) is used to explore the dynamics of the northern TJ. Solutions are found in a rectangular basin, extending 100° zonally and from 40°S to 40°N. They are forced by three idealized forcings: several patches of idealized wind fields, including one that simulates the strong Ekman pumping region in the vicinity of the Costa Rica Dome (CRD); surface heating that warms the ocean in the tropics; and a prescribed interocean circulation (IOC) that enters the basin through the southern boundary and exits through the western boundary from 2° to 6°N (the model’s Indonesian passages).
Solutions forced by all the aforementioned processes and with minimal diffusion resemble the observed flow field in the tropical North Pacific. A narrow eastward current, the model’s northern TJ, flows across the basin along the northern edge of a thick equatorial thermostad. Part of the TJ water upwells at the CRD upwelling region and the rest returns westward in the lower part of the North Equatorial Current. The deeper part of the TJ is supplied by water that leaves the western boundary current somewhat north of the equator. Its shallower part originates from water that diverges from the deep portion of the Equatorial Undercurrent (EUC); as a result, the TJ transport increases to the east and the TJ warms as it flows across the basin. These and other properties suggest that the dynamics of the model’s TJ are those of an arrested front, which in a 2½-layer model are generated when characteristics of the flow converge strongly or intersect.
Eddy form stress, due to instability waves generated at the CRD region, extends the TJ circulation to deeper levels. When diffusivity is increased to commonly used values, the thermostad is less well defined and the TJ is weak. In a solution without the IOC, the TJ is shifted to higher temperatures with its water supplied by the subtropical cell. When horizontal viscosity is reduced, the TJ becomes narrower and is flanked by a westward current on its equatorward side.
Assessment of Value Added for Surface Marine Wind Speed Obtained from Two Regional Climate Models
Authors: Winterfeldt Jörg , Weisse Ralf 
Published: March 2009

Abstract
Hindcasts with reanalysis-driven regional climate models (RCMs) are a common tool to assess weather statistics (i.e., climate) and recent changes and trends. The capability of different state-of-the-art RCMs (with and without spectral nudging applied) to add value for surface marine wind speed in comparison to the reanalysis wind speed forcing is assessed by the comparison with observations in the eastern North Atlantic in 1998. Added value is elaborated on instantaneous wind speeds and their frequency distribution. The observations are discriminated into groups according to their proximity to land and assimilation status, meaning whether they are assimilated into the reanalysis or not. For instantaneous wind speeds RCMs do not show added value both in “open ocean” areas and the German Bight. However, in the English Channel, where local topography and associated local wind regimes become important, the regional models show an added value for instantaneous wind speeds. Concerning the wind speed distribution there is a clear indication for an added value of the RCMs in coastal regions, especially for higher wind speed percentiles, while in open-ocean areas no added value is found. In comparison to the unnudged simulation, the spectrally nudged simulations better represent both instantaneous wind speeds and their frequency distribution. These results hold independently of the measurements’ assimilation status. Strictly the findings of this study only hold for hindcast studies, the results may differ for other areas and years.
Evaluation of Scalar Advection Schemes in the Advanced Research WRF Model Using Large-Eddy Simulations of Aerosol–Cloud Interactions
Authors: Wang Hailong , Skamarock William C. , Feingold Graham 
Published: March 2009

Abstract
In the Advanced Research Weather Research and Forecasting Model (ARW), versions 3.0 and earlier, advection of scalars was performed using the Runge–Kutta time-integration scheme with an option of using a positive-definite (PD) flux limiter. Large-eddy simulations of aerosol–cloud interactions using the ARW model are performed to evaluate the advection schemes. The basic Runge–Kutta scheme alone produces spurious oscillations and negative values in scalar mixing ratios because of numerical dispersion errors. The PD flux limiter assures positive definiteness but retains the oscillations with an amplification of local maxima by up to 20% in the tests. These numerical dispersion errors contaminate active scalars directly through the advection process and indirectly through physical and dynamical feedbacks, leading to a misrepresentation of cloud physical and dynamical processes. A monotonic flux limiter is introduced to correct the generally accurate but dispersive solutions given by high-order Runge–Kutta scheme. The monotonic limiter effectively minimizes the dispersion errors with little significant enhancement of numerical diffusion errors. The improvement in scalar advection using the monotonic limiter is discussed in the context of how the different advection schemes impact the quantification of aerosol–cloud interactions. The PD limiter results in 20% (10%) fewer cloud droplets and 22% (5%) smaller cloud albedo than the monotonic limiter under clean (polluted) conditions. Underprediction of cloud droplet number concentration by the PD limiter tends to trigger the early formation of precipitation in the clean case, leading to a potentially large impact on cloud albedo change.
The clinical usefulness of spirometric information
Authors: Calverley P.M.A. 
Published: March 2009

SummarySpirometry is a remarkably versatile and informative measurement with known between-test reproducibility. It can be used reliably by a range of practitioners and technologists and changes in spirometry indicate important changes in the patient's clinical condition, although the significance of a given change has to be calibrated against the disease context in which it occurs. Community-based spirometry can identify a range of diseases and exclude others while promoting significant changes in treatment.Spirometry is a key part of bronchial challenge testing, which can be said to diagnose and monitor progress in asthma. Reductions in forced expiratory volume in one second (FEV1) are prognostically relevant in chronic obstructive pulmonary disease (COPD) as are decreases in vital capacity in neuromuscular disease. Determining disease progression as the rate of decline in FEV1 is not practical at an individual patient level, but documenting the loss of lung function over time is still a valuable outcome to monitor. Used together with other clinical features, spirometry can substantially improve our assessment of the patient and their long-term management [1].
Scientific highlights from the European Sleep Research Society Congress, 2008
Authors: Goff E.A. , Jackson M.L. , Shaikh Z.F. , Atalla A. , Hill C.M. , Morrell M.J. 
Published: March 2009

SummaryYou simply cannot go to Glasgow in Scotland and be a shrinking violet. Or at least this is what we were told when we attended the European Sleep Research Society (ESRS) Congress in Glasgow in 2008. This report aims to illustrate how collaboration and communication between specialists can help to facilitate breakthroughs in clinical practice. We leave it up to the reader to decide whether those who attended also made breakthroughs in learning local customs.
Heat shock proteins and immune system
Authors: Tsan Min-Fu , Gao Baochong 
Published: March 2009

AbstractHeat shock proteins (HSPs) such as HSP 60 (Hsp60), Hsp70, Hsp90, and gp96, have been reported to play important roles in antigen presentation and cross-presentation, activation of macrophages and lymphocytes, and activation and maturation of dendritic cells. HSPs contain peptide-binding domains that bind exposed hydrophobic residues of substrate proteins. As part of their molecular chaperone functions, HSPs bind and deliver chaperoned, antigenic peptides to MHC class I molecules at the cell surface for presentation to lymphocytes. HSPs also bind nonprotein molecules with exposed hydrophobic residues including lipid-based TLR ligands. Recombinant HSP products may be contaminated with pathogen-associated molecules that contain exposed hydrophobic residues such as LPS (a TLR4 ligand), lipoprotein (a TLR2 ligand), and flagellin (a TLR5 ligand). These contaminants appear to be responsible for most, if not all, reported in vitro cytokine effects of HSPs, as highly purified HSPs do not show any cytokine effects. We propose that HSPs are molecular chaperones that bind protein and nonprotein molecules with exposed hydrophobic residues. The reported antigen presentation and cross-presentation and in vitro HSP cytokine functions are a result of molecules bound to or chaperoned by HSPs but not a result of HSPs themselves.
Exogenous Glucose–Dependent Insulinotropic Polypeptide Worsens Post prandial Hyperglycemia in T ype 2 Diabetes
Authors: Chia Chee W. , Carlson Olga D. , Kim Wook , Shin Yu-Kyong , Charles Cornelia P. , Kim Hee Seung , Melvin Denise L. , Egan Josephine M. 
Published: March 2009

OBJECTIVE
Glucose-dependent insulinotropic polypeptide (GIP), unlike glucagon-like peptide (GLP)-1, lacks glucose-lowering properties in patients with type 2 diabetes. We designed this study to elucidate the underlying pathophysiology.

RESEARCH DESIGN AND METHODS
Twenty-two insulin-naïve subjects with type 2 diabetes were given either synthetic human GIP (20 ng · kg−1 · min−1) or placebo (normal saline) over 180 min, starting with the first bite of a mixed meal (plus 1 g of acetaminophen) on two separate occasions. Frequent blood samples were obtained over 6 h to determine plasma GIP, GLP-1, glucose, insulin, glucagon, resistin, and acetaminophen levels.

RESULTS
Compared with placebo, GIP induced an early postprandial increase in insulin levels. Intriguingly, GIP also induced an early postprandial augmentation in glucagon, a significant elevation in late postprandial glucose, and a decrease in late postprandial GLP-1 levels. Resistin and acetaminophen levels were comparable in both interventions. By immunocytochemistry, GIP receptors were present on human and mouse α-cells. In αTC1 cell line, GIP induced an increase in intracellular cAMP and glucagon secretion.

CONCLUSIONS
GIP, given to achieve supraphysiological plasma levels, still had an early, short-lived insulinotropic effect in type 2 diabetes. However, with a concomitant increase in glucagon, the glucose-lowering effect was lost. GIP infusion further worsened hyperglycemia postprandially, most likely through its suppressive effect on GLP-1. These findings make it unlikely that GIP or GIP receptor agonists will be useful in treating the hyperglycemia of patients with type 2 diabetes.
Obstructive Sleep Apnea Among Obese Patients With Type 2 Diabetes
Authors: Foster Gary D. , Sanders Mark H. , Millman Richard , Zammit Gary , Borradaile Kelley E. , Newman Anne B. , Wadden Thomas A. , Kelley David , Wing Rena R. , Pi Sunyer F. Xavier , Darcey Valerie , Kuna Samuel T. ,   for the Sleep AHEAD Research Group
Published: March 2009

OBJECTIVE
To assess the risk factors for the presence and severity of obstructive sleep apnea (OSA) among obese patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS
Unattended polysomnography was performed in 306 participants.

RESULTS
Over 86% of participants had OSA with an apnea-hypopnea index (AHI) ≥5 events/h. The mean AHI was 20.5 ± 16.8 events/h. A total of 30.5% of the participants had moderate OSA (15 ≤ AHI &lt;30), and 22.6% had severe OSA (AHI ≥30). Waist circumference (odds ratio 1.1; 95% CI 1.0–1.1; P = 0.03) was significantly related to the presence of OSA. Severe OSA was most likely in individuals with a higher BMI (odds ratio 1.1; 95% CI 1.0–1.2; P = 0.03).

CONCLUSIONS
Physicians should be particularly cognizant of the likelihood of OSA in obese patients with type 2 diabetes, especially among individuals with higher waist circumference and BMI.
The emplacement mode of Upper Cretaceous plutons from the southwestern part of the Sredna Gora Zone (Bulgaria): structural and AMS study
Authors: Georgiev Neven , Henry Bernard , Jordanova Neli , Froitzheim Nikolaus , Jordanova Diana , Ivanov Zivko , Dimov Dimo 
Published: March 2009

The emplacement mode of Upper Cretaceous plutons from the southwestern part of the Sredna Gora Zone (Bulgaria): structural and AMS study
Several plutons located in the southwestern part of the Sredna Gora Zone — Bulgaria are examples of the Apuseni-Banat-Timok-Sredna Gora type of granites emplaced during Late Cretaceous (86-75 Ma) times. The studied intrusive bodies are spatially related to and deformed by the dextral Iskar-Yavoritsa shear zone. The deformation along the shear zone ceased at the time of emplacement of the undeformed Upper Cretaceous Gutsal pluton, which has intruded the Iskar-Yavoritsa mylonites. A clear transition from magmatic foliation to high-, moderate- and low-temperature superimposed foliation and lineation in the vicinity of the Iskar-Yavoritsa and related shear zones gives evidence for simultaneous tectonics and plutonism. Away from the shear zones, the granitoids appear macroscopically isotropic and were investigated using measurements of anisotropy of magnetic susceptibility at 113 stations. The studied samples show magnetic lineation and foliation, in agreement with the magmatic structures observed at a few sites. Typical features of the internal structure of the plutons are several sheet-like mafic bodies accompanied by swarms of mafic microgranular enclaves. Field observations indicate spatial relationships between mafic bodies and shear zones as well as mingling processes in the magma chamber which suggest simultaneous shearing and magma emplacement. Structural investigations as well as anisotropy of magnetic susceptibility (AMS) data attest to the controlling role of the NWSE trending Iskar-Yavoritsa shear zone and to the syntectonic emplacement of the plutons with deformation in both igneous rocks and their hosts. The tectonic situation may be explained by partitioning of oblique plate convergence into plate-boundary-normal thrusting in the Rhodopes and plate-boundary-parallel transcurrent shearing in the hinterland (Sredna Gora).