bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Phase I Clinical Trial of Single-Dose Intrapleural IFN-β Gene Transfer for Malignant Pleural Mesothelioma and Metastatic Pleural Effusions: High Rate of Antitumor Immune Responses
Authors: Sterman Daniel H. , Recio Adri , Carroll Richard G. , Gillespie Colin T. , Haas Andrew , Vachani Anil , Kapoor Veena , Sun Jing , Hodinka Richard , Brown Jennifer L. , Corbley Michael J. , Parr Michael , Ho Mitchell , Pastan Ira , Machuzak Michael , Benedict William , Zhang Xin-qiao , Lord Elaina M. , Litzky Leslie A. , Heitjan Daniel F. , June Carl H. , Kaiser Larry R. , Vonderheide Robert H. , Albelda Steven M. 
Published: August 2007

Abstract
Purpose: This phase 1 dose escalation study evaluated the safety and feasibility of single-dose intrapleural IFN-β gene transfer using an adenoviral vector (Ad.IFN-β) in patients with malignant pleural mesothelioma (MPM) and metastatic pleural effusions (MPE).
Experimental Design: Ad.IFN-β was administered through an indwelling pleural catheter in doses ranging from 9 × 1011 to 3 × 1012 viral particles (vp) in two cohorts of patients with MPM (7 patients) and MPE (3 patients). Subjects were evaluated for (a) toxicity, (b) gene transfer, (c) humoral, cellular, and cytokine-mediated immune responses, and (d) tumor responses via 18-fluorodeoxyglucose-positron emission tomography scans and chest computed tomography scans.
Results: Intrapleural Ad.IFN-β was generally well tolerated with transient lymphopenia as the most common side effect. The maximally tolerated dose achieved was 9 × 1011 vp secondary to idiosyncratic dose-limiting toxicities (hypoxia and liver function abnormalities) in two patients treated at 3 × 1012 vp. The presence of the vector did not elicit a marked cellular infiltrate in the pleural space. Intrapleural levels of cytokines were highly variable at baseline and after response to gene transfer. Gene transfer was documented in 7 of the 10 patients by demonstration of IFN-β message or protein. Antitumor immune responses were elicited in 7 of the 10 patients and included the detection of cytotoxic T cells (1 patient), activation of circulating natural killer cells (2 patients), and humoral responses to known (Simian virus 40 large T antigen and mesothelin) and unknown tumor antigens (7 patients). Four of 10 patients showed meaningful clinical responses defined as disease stability and/or regression on 18-fluorodeoxyglucose-positron emission tomography and computed tomography scans at day 60 after vector infusion.
Conclusions: Intrapleural instillation of Ad.IFN-β is a potentially useful approach for the generation of antitumor immune responses in MPM and MPE patients and should be investigated further for overall clinical efficacy.
Genetic Alterations of the ATBF1 Gene in Gastric Cancer
Authors: Cho Yong Gu , Song Jae Hwi , Kim Chang Jae , Lee Youn Soo , Kim Su Young , Nam Suk Woo , Lee Jung Young , Park Won Sang 
Published: August 2007

Abstract
Purpose: α-Fetoprotein (AFP)–producing gastric cancers are aggressive tumors with venous and lymphatic invasion and hepatic metastasis. The goal of the present study was to investigate whether somatic changes of the AFP-negative regulator AT motif binding factor-1 (ATBF1) gene are involved in the development or progression of gastric cancers and the production of AFP in gastric cancer cells.
Experimental Design: We searched for genetic alterations of the ATBF1 gene by single-strand conformational polymorphism and sequencing methods as well as allelic loss analysis with the microsatellite markers D16S3066 and D16S3139. Immunochemistry for AFP expression in gastric cancer cells was also done.
Results: In 81 sporadic gastric cancers, four mutations were detected in seven cases: one was a missense mutation and three were deletions; loss of heterozygosity at the ATBF1 locus was detected in 52.9% of informative samples. Five of the eight cancers with AFP expression showed ATBF1 genetic alterations.
Conclusions: These results suggest that genetic alteration of the ATBF1 gene may contribute to the aggressive nature of gastric cancers and the production of AFP in gastric cancer cells.
The Role of Phosphoinositide 3-Kinase Pathway Inhibitors in the Treatment of Lung Cancer
Authors: Engelman Jeffrey A. 
Published: August 2007

Abstract
The phosphoinositide 3-kinase signaling network is widely implicated in the pathogenesis of human cancer. This pathway is commandeered by cancer cells to promote unrestrained cellular growth and survival. In this brief review, we speculate about the uses of inhibitors of phosphoinositide 3-kinase signaling as treatments for human cancers, with an emphasis on non–small cell lung cancer.
Vaccination of Colorectal Cancer Patients with Modified Vaccinia Ankara Encoding the Tumor Antigen 5T4 (TroVax) Given Alongside Chemotherapy Induces Potent Immune Responses
Authors: Harrop Richard , Drury Noel , Shingler William , Chikoti Priscilla , Redchenko Irina , Carroll Miles W. , Kingsman Susan M. , Naylor Stuart , Melcher Alan , Nicholls Joanna , Wassan Harpreet , Habib Nagy , Anthoney Alan 
Published: August 2007

AbstractPurpose: The attenuated strain of vaccinia virus, modified vaccinia Ankara (MVA) encoding the tumor antigen 5T4 (TroVax), has been evaluated in an open-label phase II study in metastatic colorectal cancer patients. The primary objective was to assess the safety and immunogenicity of TroVax injected before, during, and after treatment with cycles of 5-fluorouracil, folinic acid, and oxaliplatin.Experimental Design: TroVax was administered to 17 patients with metastatic colorectal cancer. In total, 11 patients were considered to be evaluable for assessment of immunologic responses having received a total of six injections of TroVax, administered before, during, and following completion of chemotherapy. Antibody and cellular responses specific for 5T4 and MVA were monitored throughout the study.Results: Administration of TroVax alongside 5-fluorouracil, folinic acid, and oxaliplatin was safe and well tolerated with no serious adverse events attributed to TroVax. Ten of the 11 evaluable patients mounted 5T4-specific antibody responses with titers ranging from 10 to &gt;1,000. IFNγ enzyme-linked immunospot responses specific for 5T4 were detected in 10 patients with precursor frequencies exceeding 1 in 1,000 peripheral blood mononuclear cells in 4 patients. Of the 11 evaluable patients, 6 had complete or partial responses. 5T4-specific immune responses, but not MVA-specific immune responses, correlated with clinical benefit.Conclusions: Potent 5T4-specific cellular and/or antibody responses were induced in all evaluable patients and were still detectable during the period in which chemotherapy was administered. These results suggest that TroVax can be added to chemotherapy regimens without any evidence of enhanced toxicity or reduced immunologic efficacy and may provide additional clinical benefit.
Novel Agents in the Treatment of Lung Cancer: Fourth Cambridge Conference
Authors: Lynch Thomas J. , Bonomi Philip D. , Butts Charles , Davies Angela M. , Engelman Jeffrey , Govindan Ramaswamy , Herbst Roy S. , Heymach John V. , Johnson Bruce E. , Martins Renato G. , Perez-Soler Roman , Riely Gregory J. , Sandler Alan B. , Sequist Lecia V. , Socinski Mark A. , Wong Kwok-Kin , Hart Carol S. 
Published: August 2007

Abstract
The Fourth Cambridge Conference on Novel Agents in the Treatment of Lung Cancer was held in Cambridge, Massachusetts on September 29 to 30, 2006, to discuss ongoing clinical research of novel targeted agents for the treatment of non–small cell lung cancer, along with supportive basic and translational research into the molecular pathways implicated in cancer growth and resistance. New information, conclusions, and recommendations considered significant for the field by the program faculty are summarized below and presented at greater length in the individual articles and accompanying discussions that comprise the full conference proceedings.
Monthly Changes in Atmospheric Carbon Dioxide at Mauna Loa: Possible Asymmetric Effects of Warming
Authors: Kaufmann Robert K. 
Published: August 2007

Abstract
Changes in the intra-annual cycle of atmospheric CO2 at Mauna Loa, Hawaii, are investigated by comparing monthly observations to the mean value of each year’s waxing and waning phase of the cycle. Results identify a previously unnoticed change between 1965 and 2004 during October in which October concentrations declined relative to the cycle’s mean value. Results confirm a previously noted change in spring (April), but unlike previous analyses, this result indicates that between 1965 and 2004 April concentrations rose relative to the cycle’s mean value. The timing of these changes is not caused by commonly recognized patterns of atmospheric circulation, such as ENSO events. Instead, these changes may be generated by asymmetric effects of warming. Warming in early spring may increase heterotrophic respiration relative to net primary production while warming in late summer/early fall may enhance net primary production relative to heterotrophic respiration.
Extreme Value Statistics of the Total Energy in an Intermediate-Complexity Model of the Midlatitude Atmospheric Jet. Part I: Stationary Case
Authors: Felici Mara , Lucarini Valerio , Speranza Antonio , Vitolo Renato 
Published: August 2007

AbstractA baroclinic model of intermediate complexity for the atmospheric jet at middle latitudes is used as a stochastic generator of atmosphere-like time series. In this case, time series of the total energy of the system are considered. Statistical inference of extreme values is applied to sequences of yearly maxima extracted from the time series in the rigorous setting provided by extreme value theory. The generalized extreme value (GEV) family of distributions is used here as a basic model, both for its qualities of simplicity and its generality. Several physically plausible values of the parameter TE, which represents the forced equator-to-pole temperature gradient and is responsible for setting the average baroclinicity in the atmospheric model, are used to generate stationary time series of the total energy. Estimates of the three GEV parameters—location, scale, and shape—are inferred by maximum likelihood methods. Standard statistical diagnostics, such as return level and quantile–quantile plots, are systematically applied to assess goodness-of-fit. The GEV parameters of location and scale are found to have a piecewise smooth, monotonically increasing dependence on TE. The shape parameter also increases with TE but is always negative, as is required a priori by the boundedness of the total energy. The sensitivity of the statistical inferences is studied with respect to the selection procedure of the maxima: the roles occupied by the length of the sequences of maxima and by the length of data blocks over which the maxima are computed are critically analyzed. Issues related to model sensitivity are also explored by varying the resolution of the system. The method used in this paper is put forward as a rigorous framework for the statistical analysis of extremes of observed data, to study the past and present climate and to characterize its variations.
Tropical Stationary Waves in a Nonlinear Shallow-Water Model with Realistic Basic States
Authors: Kraucunas Ian , Hartmann Dennis L. 
Published: August 2007

Abstract
The nonlinear shallow-water equations are used to study the tropical stationary wave response to steady thermal forcing near the equator in earthlike zonally symmetric basic states. A thin (200 m) fluid layer is superimposed over a large (1500 m) zonally symmetric topography distribution that decreases smoothly from the Tropics to the Poles, thus providing the large meridional height gradients required to maintain realistic zonal-mean zonal winds without introducing unrealistically large tropical wave speeds. A mean meridional circulation is maintained by relaxing the fluid toward its initial, global-mean depth. Both hemispherically symmetric (equinoctial) and hemispherically asymmetric (solstitial) basic states are considered. Stationary waves are generated by adding a fixed mass source/sink distribution near the equator.
The presence of westerly zonal-mean winds in the subtropics amplifies the steady eddy response to the tropical mass forcing and shifts the Rossby gyres poleward and eastward, relative to their position in a resting basic state. When either the mass forcing or the center of the topography distribution is moved off the equator, the eddy response develops considerable hemispheric asymmetry. When the eddy forcing is centered in the “summer” hemisphere of the solstitial basic state, the eddy response exhibits a similar amplitude in both hemispheres, which suggests that the considerable hemispheric symmetry of the observed seasonally varying eddy circulations in the tropical upper troposphere may be attributed to the tendency for the maximum zonal-mean and eddy diabatic heating to occur in the same latitude band throughout the seasonal cycle. Hemispheric asymmetry in either the basic state or the eddy forcing also leads to cross-equatorial eddy momentum fluxes. Experiments performed using a balanced basic state with zero-mean meridional flow indicate that the cross-equatorial mean meridional winds play a significant role in promoting the propagation of wave activity across the equator under solstitial conditions.
Sources and Sinks of Available Potential Energy in a Moist Atmosphere
Authors: Pauluis Olivier 
Published: August 2007

Abstract
Available potential energy (APE) is defined as the difference between the total static energy of the atmosphere and that of a reference state that minimizes the total static energy after a sequence of reversible adiabatic transformations. Determining the rate at which APE is generated in the atmosphere allows one to estimate the amount of kinetic energy that can be generated by atmosphere flows. Previous expressions for the sources and sinks of APE rely on a dry framework and are limited by the fact that they require prior knowledge of the distribution of latent heat release by atmospheric motion. In contrast, this paper uses a moist APE framework to derive a general formula for the sources and sinks of APE that can be equally applied to dry and moist circulations.
Two key problems are addressed here. First, it is shown that any reorganization of the reference state due to diabatic heating or addition of water does not change its total static energy. This property makes it possible to determine the rate of change in APE even in the absence of an analytic formula for the reference state, as is the case in a moist atmosphere. Second, the effects of changing the total water content of an air parcel are also considered in order to evaluate the changes of APE due to precipitation, evaporation, and diffusion of water vapor. Based on these new findings, one can obtain the rate of change of APE from that of atmospheric entropy, water content, and pressure.
This result is used to determine the sources and sinks of APE due to different processes such as external energy sources, frictional dissipation, diffusion of sensible heat and water vapor, surface evaporation, precipitation, and reevaporation. These sources and sinks are then discussed in the context of an idealized atmosphere in radiative–convective equilibrium. For a moist atmosphere, the production of APE by the surface energy flux is much larger than any observational or theoretical estimates of frictional dissipation, and, as is argued here, must be balanced by a comparable sink of APE due to the diffusion of water vapor from unstable to stable air parcels.
Heating Structures of the TRMM Field Campaigns
Authors: Schumacher Courtney , Zhang Minghua H. , Ciesielski Paul E. 
Published: August 2007

Abstract
Heating profiles calculated from sounding networks and other observations during three Tropical Rainfall Measuring Mission (TRMM) field campaigns [the Kwajalein Experiment (KWAJEX), TRMM Large-Scale Biosphere–Atmosphere Experiment in Amazonia (LBA), and South China Sea Monsoon Experiment (SCSMEX)] show distinct geographical differences between oceanic, continental, and monsoon regimes. Differing cloud types (both precipitating and nonprecipitating) play an important role in determining the total diabatic heating profile. Variations in the vertical structure of the apparent heat source, Q1, can be related to the diurnal cycle, large-scale forcings such as atmospheric waves, and rain thresholds at each location. For example, TRMM-LBA, which occurred in the Brazilian Amazon, had mostly deep convection during the day while KWAJEX, which occurred in the western portion of the Pacific intertropical convergence zone, had more shallow and moderately deep daytime convection. Therefore, the afternoon height of maximum heating was more bottom heavy (i.e., heating below 600 hPa) during KWAJEX compared to TRMM-LBA. More organized convective systems with extensive stratiform rain areas and upper-level cloud decks tended to occur in the early and late morning hours during TRMM-LBA and KWAJEX, respectively, thereby causing Q1 profiles to be top heavy (i.e., maxima from 600 to 400 hPa) at those times. SCSMEX, which occurred in the South China Sea during the monsoon season, had top-heavy daytime and nighttime heating profiles suggesting that mesoscale convective systems occurred throughout the diurnal cycle, although more precipitation and upper-level cloud in the afternoon caused the daytime heating maximum to be larger. A tendency toward bottom- and top-heavy heating profile variations is also associated with the different cloud types that occurred before and after the passage of easterly wave troughs during KWAJEX, the easterly and westerly regimes during TRMM-LBA, and the monsoon onset and postonset active periods during SCSMEX. Rain thresholds based on heavy, moderate, and light/no-rain amounts can further differentiate top-heavy heating, bottom-heavy heating, and tropospheric cooling. These budget studies suggest that model calculations and satellite retrievals of Q1 must account for a large number of factors in order to accurately determine the vertical structure of diabatic heating associated with tropical cloud systems.
Wave Activity on the Tropical Easterly Jet
Authors: Nicholson S. E. , Barcilon A. I. , Challa M. , Baum J. 
Published: August 2007

Abstract
This article examines the question of the existence of waves on the tropical easterly jet (TEJ) over West Africa. The TEJ is a well-known feature of the Asian monsoon and waves on the jet have been implicated in various weather phenomena. Its role in West African meteorology has received little attention. A model simulation of wet and dry years over West Africa predicted wave development on the TEJ. NCEP reanalysis data confirmed the existence of these waves, using case studies in the dry year 1983 and the wet year 1950. Both the simulated and observed waves are of planetary scale, with a period of 5–6 days. Potential vorticity (PV) theory suggests that they develop via interactions between the surface and the TEJ. Overall, the results suggest that interactions between the TEJ and African easterly jet play an important role in the development of wave disturbances over West Africa.
Anisotropies and Universality of Buoyancy-Dominated Turbulent Fluctuations: A Large-Eddy Simulation Study
Authors: Antonelli Marta , Lanotte Alessandra , Mazzino Andrea 
Published: August 2007

Abstract
Turbulent fluctuations of both velocity and temperature fields, issuing from high-resolution large-eddy simulations, have been analyzed in convective boundary layers. The numerically simulated flows are strongly anisotropic at large scales: this is due both to the action of buoyancy and to the imposed geostrophic wind. Their relative weight is varied so that one experiment’s results are much more convective than the other. To properly disentangle anisotropic properties, the authors exploit both standard statistical indicators, like skewness coefficients, and the three-dimensional rotational group decomposition SO(3). Two main conclusions can be drawn. First, despite the strong anisotropies at large scales, isotropy is statistically recovered at scales much smaller than the large ones. Second, relevant statistical indicators of turbulence such as the scaling exponents, of both velocity and temperature fields, are remarkably close for the two experiments. Implications of these findings for the problem of subgrid-scale modeling are discussed.
Momentum Flux Spectrum of Convectively Forced Internal Gravity Waves and Its Application to Gravity Wave Drag Parameterization. Part II: Impacts in a GCM (WACCM)
Authors: Song In-Sun , Chun Hye-Yeong , Garcia Rolando R. , Boville Byron A. 
Published: August 2007

Abstract
Impacts of a spectral parameterization of gravity wave drag (GWD) induced by cumulus convection (GWDC) in the NCAR Whole Atmosphere Community Climate Model (WACCM1b) are investigated. In the spectral GWDC parameterization, reference wave momentum flux spectrum is launched at cloud top and analytically calculated based on the physical properties of convection and the large-scale flow. The cloud-top wave momentum flux is strong mainly in the Tropics and midlatitude storm-track regions, and exhibits anisotropy and spatiotemporal variability. The anisotropy and variability are determined by the distributions and variations of convective activities, the moving speed of convection, and horizontal wind and stability in convection regions. Zonal-mean zonal GWDC has a maximum of 13–27 (37–50) m s−1 day−1 in the mesosphere in January (July). Impacts of GWDC on zonal wind appear mainly in the low to midlatitudes of the upper stratosphere and mesosphere. In these regions, biases of zonal wind with respect to observation are reduced more than 50% through the GWDC process. In contrast to zonal wind, impacts of GWDC on temperature occur mainly in the mid- to high latitudes. Through the analysis of forcing terms in the zonal wind and temperature equations, it is found that impacts of GWDC result from interaction among wave forcing terms (resolved wave forcing, parameterized background GWD, and GWDC) and meridional circulations induced by the wave forcing terms. With regard to tropical variability, when GWDC is included, the model produces the stratospheric semiannual oscillation with more realistic amplitude and structure and stronger interannual variabilities in the lower stratosphere. These enhanced variabilities are caused by resolved wave forcing and meridional circulations.