bluuebunny/crossref_metadata_2025_split huggingface dataset:
Opposing Roles for IL-23 and IL-12 in Maintaining Occult Cancer in an Equilibrium State
Authors: Teng Michele W. L. , Vesely Matthew D. , Duret Helene , McLaughlin Nicole , Towne Jennifer E. , Schreiber Robert D. , Smyth Mark J. 
Published: August 2012

Abstract
Cancer immunoediting, the process by which the immune system controls tumor growth and shapes tumor immunogenicity, consists of 3 stages: elimination, equilibrium, and escape. The molecular mechanisms that underlie the equilibrium phase, during which the immune system maintains tumor dormancy, remain incompletely defined. Here, we investigated the length of the equilibrium phase during immune control of methycholanthrene (MCA)-induced or p53 mutant cancers and showed the critical and opposing roles of interleukin (IL)-23 and IL-12 in maintaining cancer cells in a state of immune-mediated dormancy. Inhibition of IL-23p19 was shown to reduce the malignant potential of lesions established by MCA inoculation, whereas inhibition of IL-12/23p40 enhanced tumor outgrowth. Furthermore, agonistic anti-CD40 antibody treatment mimicked the effects of anti-IL-23p19 monoclonal antibody treatment. Other cytokines such as IL-4, IL-17, TNF, and IFNαβ, which are known to play important roles either in MCA tumorigenesis or in the elimination phase of cancer immunoediting, did not play critical roles in maintaining the equilibrium phase. Taken together, our findings show opposing roles for IL-23 and IL-12 in determining the outgrowth versus dormancy of occult neoplasia and suggest a potential long-term danger in using IL-12/23p40 antibodies for treating human autoimmune inflammatory disorders. Cancer Res; 72(16); 3987–96. ©2012 AACR.
Hidden Dangers: A Cryptic Exon Disrupts BRCA2 mRNA
Authors: Fackenthal James D. , Lee Younghee , Olopade Olufunmilayo I. 
Published: August 2012

Abstract
The first mutation that disrupts BRCA2 mRNA by including a novel, cryptic exon is reported in this issue. The mutation lies deep within an intron and would not have been detected by conventional screening methods. In the future, more mutations may be discovered by direct mRNA analysis. Clin Cancer Res; 18(18); 4865–7. ©2012 AACR.
Aflibercept in Pediatric Solid Tumors: Moving Beyond the Trap
Authors: Chau Cindy H. , Figg William D. 
Published: August 2012

Abstract
Angiogenesis plays a pivotal role in the growth and metastasis of adult and pediatric solid tumors. Clinical investigation of angiogenesis inhibitors is currently under way for childhood cancers. While the pediatric study of aflibercept provides a proof-of-principle, challenges remain in developing clinical endpoints and biomarkers of angiogenesis for pediatric trials. Clin Cancer Res; 18(18); 4868–71. ©2012 AACR.
Humanization of an Anti-CCR4 Antibody That Kills Cutaneous T-Cell Lymphoma Cells and Abrogates Suppression by T-Regulatory Cells
Authors: Chang De-Kuan , Sui Jianhua , Geng Shusheng , Muvaffak Asli , Bai Mei , Fuhlbrigge Robert C. , Lo Agnes , Yammanuru Anuradha , Hubbard Luke , Sheehan Jared , Campbell James J. , Zhu Quan , Kupper Thomas S. , Marasco Wayne A. 
Published: August 2012

Abstract
Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of neoplastic disorders characterized by clonally derived and skin-homing malignant T cells that express high level of chemokine receptor CCR4, which is associated with their skin-homing capacity. CCR4 is also highly expressed on T-regulatory cells (Tregs) that can migrate to several different types of chemotactic ligand CCL17- and CCL22-secreting tumors to facilitate tumor cell evasion from immune surveillance. Thus, its high-level expression on CTCL cells and Tregs makes CCR4 a potential ideal target for antibody-based immunotherapy for CTCL and other types of solid tumors. Here, we conducted humanization and affinity optimization of a murine anti-CCR4 monoclonal antibody (mAb), mAb1567, that recognizes both the N-terminal and extracellular domains of CCR4 with high affinity and inhibits chemotaxis of CCR4+ CTCL cells. In a mouse CTCL tumor model, mAb1567 exhibited a potent antitumor effect and in vitro mechanistic studies showed that both complement-dependent cytotoxicity (CDC) and neutrophil-mediated antibody-dependent cellular cytotoxicity (ADCC) likely mediated this effect. mAb1567 also exerts human NK cell–mediated ADCC activity in vitro. Moreover, mAb1567 also effectively inhibits chemotaxis of CD4+CD25high Tregs via CCL22 and abrogates Treg suppression activity in vitro. An affinity-optimized variant of humanized mAb1567, mAb2-3, was selected for further preclinical development based on its higher binding affinity and more potent ADCC and CDC activities. Taken together, this high-affinity humanized mAb2-3 with potent antitumor effect and a broad range of mechanisms of action may provide a novel immunotherapy for CTCL and other solid tumors. Mol Cancer Ther; 11(11); 2451–61. ©2012 AACR.
Global Strain in Severe Aortic Valve Stenosis
Authors: Dahl Jordi S. , Videbæk Lars , Poulsen Mikael K. , Rudbæk Torsten R. , Pellikka Patricia A. , Møller Jacob E. 
Published: August 2012

Background—
Global longitudinal systolic strain (GLS) is often reduced in aortic stenosis despite normal ejection fraction. The importance of reduced preoperative GLS on long-term outcome after aortic valve replacement is unknown.

Methods and Results—

A total of 125 patients with severe aortic stenosis and ejection fraction >40% scheduled for aortic valve replacement were evaluated preoperatively and divided into 4 groups according to GLS quartiles. Patients were followed up for 4 years. The primary end points were major adverse cardiac events (MACEs) defined as cardiovascular mortality and cardiac hospitalization because of worsening of heart failure; the secondary end point was cardiovascular mortality. MACE and cardiac mortality were significantly increased in patients with lower GLS. Estimated 5-year MACE was increased: first quartile 19% (n=6) / second quartile 20% (n=6) / third quartile 35% (n=11) / fourth quartile 49% (n=15);
P
=0.04. Patients with increased age, left ventricular hypertrophy, and left atrial dilatation were at increased risk. In Cox regression analysis, after correcting for standard risk factors and ejection fraction, GLS was found to be significantly associated with cardiac morbidity and mortality. In a stepwise Cox model with forward selection, GLS was the sole independent predictor: hazard ratio=1.13 (95% confidence interval, 1.02–1.25),
P
=0.04. Comparing the overall log likelihood χ
2
of the predictive power of the multivariable model containing GLS was statistically superior to models based on EuroScore, history with ischemic heart disease, and ejection fraction.

Conclusions—
In patients with symptomatic severe aortic stenosis undergoing aortic valve replacement, reduced GLS provides important prognostic information beyond standard risk factors.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00294775.
Bleeding After Initiation of Multiple Antithrombotic Drugs, Including Triple Therapy, in Atrial Fibrillation Patients Following Myocardial Infarction and Coronary Intervention
Authors: Lamberts Morten , Olesen Jonas Bjerring , Ruwald Martin Huth , Hansen Carolina Malta , Karasoy Deniz , Kristensen Søren Lund , Køber Lars , Torp-Pedersen Christian , Gislason Gunnar Hilmar , Hansen Morten Lock 
Published: August 2012

Background—
Uncertainty remains over optimal antithrombotic treatment of patients with atrial fibrillation presenting with myocardial infarction and/or undergoing percutaneous coronary intervention. We investigated the risk and time frame for bleeding following myocardial infarction/percutaneous coronary intervention in patients with atrial fibrillation according to antithrombotic treatment.

Methods and Results—
Patients with atrial fibrillation and admitted with myocardial infarction or for percutaneous coronary intervention between 2000 and 2009 (11 480 subjects, mean age 75.6 years [SD ±10.3], males 60.9%) were identified by individual level linkage of nationwide registries in Denmark. Fatal or nonfatal (requiring hospitalization) bleeding was determined according to antithrombotic treatment regimen: triple therapy (TT) with vitamin K antagonist (VKA)+aspirin+clopidogrel, VKA+antiplatelet, and dual antiplatelet therapy with aspirin+clopidogrel. We calculated crude incidence rates and adjusted hazard ratios by Cox regression models. Within 1 year, 728 bleeding events were recorded (6.3%); 79 were fatal (0.7%). Within 30 days, rates were 22.6, 20.3, and 14.3 bleeding events per 100 person-years for TT, VKA+antiplatelet, and dual antiplatelet therapy, respectively. Both early (within 90 days) and delayed (90–360 days) bleeding risk with TT exposure in relation to VKA+antiplatelet was increased; hazard ratio 1.47 (1.04;2.08) and 1.36 (0.95;1.95), respectively. No significant difference in thromboembolic risk was observed for TT versus VKA+antiplatelet; hazard ratio, 1.15 (0.95;1.40).

Conclusions—
High risk of bleeding is immediately evident with TT after myocardial infarction/percutaneous coronary intervention in patients with atrial fibrillation. A continually elevated risk associated with TT indicates no safe therapeutic window, and TT should only be prescribed after thorough bleeding risk assessment of patients.
White Matter Lesion Progression in LADIS
Authors: Schmidt Reinhold , Berghold Andrea , Jokinen Hanna , Gouw Alida A. , van der Flier Wiesje M. , Barkhof Frederik , Scheltens Philip , Petrovic Katja , Madureira Sofia , Verdelho Ana , Ferro Jose M. , Waldemar Gunhild , Wallin Anders , Wahlund Lars-Olof , Poggesi Anna , Pantoni Leonardo , Inzitari Domenico , Fazekas Franz , Erkinjuntti Timo 
Published: August 2012

Background and Purpose—
White matter lesion (WML) progression has been advocated as a surrogate marker in intervention trials on cerebral small vessel disease. We assessed the rate of visually rated WML progression, studied correlations between lesion progression and cognition, and estimated sample sizes for clinical trials with pure WML progression vs combined WML progression-cognitive outcomes.

Methods—
Those 394 participants of the Leukoaraiosis and Disability Study (LADIS) study with magnetic resonance imaging scanning at baseline and 3-year follow-up were analyzed. WML progression rating relied on the modified Rotterdam Progression Scale. The Vascular Dementia Assessment Scale global score and a composite score of specific executive function tests assessed longitudinal change in cognition. Sample size calculations were based on the assumption that treatment reduces WML progression by 1 grade on the Rotterdam Progression Scale.

Results—
WML progression related to deterioration in cognitive functioning. This relationship was less pronounced in subjects with early confluent and confluent lesions. Consequently, studies in which the outcome is cognitive change resulting from treatment effects on lesion progression will need between 1809 subjects per treatment arm when using executive tests and up to 18 853 subjects when using the Vascular Dementia Assessment Scale score. Studies having WML progression as the sole outcome will need only 58 or 70 individuals per treatment arm.

Conclusions—
WML progression is an interesting outcome for proof-of-concept studies in cerebral small vessel disease. If cognitive outcome measures are added to protocols, then sample size estimates increase substantially. Our data support the use of an executive test battery rather than the Vascular Dementia Assessment Scale as the primary cognitive outcome measure.
Characteristics of Drought and Persistent Wet Spells over the United States in the Atmosphere–Land–Ocean Coupled Model Experiments
Authors: Mo Kingtse C. , Long Lindsey N. , Schemm Jae-Kyung E. 
Published: August 2012

Abstract
Atmosphere–land–ocean coupled model simulations are examined to diagnose the ability of models to simulate drought and persistent wet spells over the United States. A total of seven models are selected for this study. They are three versions of the NCEP Climate Forecast System (CFS) coupled general circulation model (CGCM) with a T382, T126, and T62 horizontal resolution; GFDL Climate Model version 2.0 (CM2.0); GFDL CM2.1; Max Planck Institute (MPI) ECHAM5; and third climate configuration of the Met Office Unified Model (HadCM3) simulations from the World Climate Research Programme (WCRP) Coupled Model Intercomparison Project phase 3 (CMIP3) experiments.
Over the United States, drought and persistent wet spells are more likely to occur over the western interior region, while extreme events are less likely to persist over the eastern United States and the West Coast. For meteorological drought, which is defined by precipitation (P) deficit, the east–west contrast is well simulated by the CFS T382 and the T126 models. The HadCM3 captures the pattern but not the magnitudes of the frequency of occurrence of persistent extreme events. For agricultural drought, which is defined by soil moisture (SM) deficit, the CFS T382, CFS T126, MPI ECHAM5, and HadCM3 models capture the east–west contrast.
The models that capture the west–east contrast also have a realistic P climatology and seasonal cycle. ENSO is the dominant mode that modulates P over the United States. A model needs to have the ENSO mode and capture the mean P responses to ENSO in order to simulate realistic drought. To simulate realistic agricultural drought, the model needs to capture the persistence of SM anomalies over the western region.
Estimation of Mixed-Phase Cloud Optical Depth and Position Using In Situ Radiation and Cloud Microphysical Measurements Obtained from a Tethered-Balloon Platform
Authors: Sikand M. , Koskulics J. , Stamnes K. , Hamre B. , Stamnes J. J. , Lawson R. P. 
Published: August 2012

AbstractMicrophysical and radiative measurements in boundary layer mixed-phase clouds (MPCs), consisting of ice crystals and liquid droplets, have been analyzed. These cloud measurements were collected during a May–June 2008 tethered-balloon campaign in Ny-Ålesund, Norway, located at 78.9°N, 11.9°E in the High Arctic. The instruments deployed on the tethered-balloon platform included a radiometer, a cloud particle imager (CPI), and a meteorological package. To analyze the data, a radiative transfer model (RTM) was constructed with two cloud layers—consistent with the CPI data—embedded in a background Rayleigh scattering atmosphere. The mean intensities estimated from the radiometer measurements on the balloon were used in conjunction with the RTM to quantify the vertical structure of the MPC system, while the downward irradiances measured by an upward-looking ground-based radiometer were used to constrain the total cloud optical depth. The time series of radiometer and CPI data obtained while profiling the cloud system was used to estimate the time evolution of the liquid water and ice particle optical depths as well as the vertical location of the two cloud layers.
Self-Organized Criticality and Homeostasis in Atmospheric Convective Organization
Authors: Yano Jun-Ichi , Liu Changhai , Moncrieff Mitchell W. 
Published: August 2012

AbstractAtmospheric convection has a tendency to organize on a hierarchy of scales ranging from the mesoscale to the planetary scales, with the latter especially manifested by the Madden–Julian oscillation. The present paper examines two major competing mechanisms of self-organization in a cloud-resolving model (CRM) simulation from a phenomenological thermodynamic point of view.The first mechanism is self-organized criticality. A saturation tendency of precipitation rate with increasing column-integrated water, reminiscent of critical phenomena, indicates self-organized criticality. The second is a self-regulation mechanism that is known as homeostasis in biology. A thermodynamic argument suggests that such self-regulation maintains the column-integrated water below a threshold by increasing the precipitation rate. Previous analyses of both observational data as well as CRM experiments give mixed results.In this study, a CRM experiment over a large-scale domain with a constant sea surface temperature is analyzed. This analysis shows that the relation between the column-integrated total water and precipitation suggests self-organized criticality, whereas the one between the column-integrated water vapor and precipitation suggests homeostasis. The concurrent presence of these two mechanisms is further elaborated by detailed statistical and budget analyses. These statistics are scale invariant, reflecting a spatial scaling of precipitation processes.
Latent Heating and Cooling Rates in Developing and Nondeveloping Tropical Disturbances during TCS-08: TRMM PR versus ELDORA Retrievals*
Authors: Park Myung-Sook , Elsberry Russell L. 
Published: August 2012

Abstract
Unique sets of Electra Doppler Radar (ELDORA) observations in both developing and nondeveloping tropical disturbances in the western North Pacific are used to retrieve latent heating and cooling rates. During the reintensification of Sinlaku, maximum heating rates of about 80 K h−1 are diagnosed in the upper troposphere in the region of a strong updraft and maximum cooling rates of about −45 K h−1 are diagnosed in the lower troposphere in the region of a strong convective-scale downdraft. The southern convective burst in the pre-Nuri mission had a lower-tropospheric maximum in latent heating that was a more favorable condition for tropical cyclone formation than was the upper-tropospheric maximum in heating and the lower-tropospheric maximum in cooling in the northern convective burst. Two nondeveloping tropical disturbances had deeper layers of more uniform heating and of cooling rates, and some evidence of more shallow cloud tops, that distinguished them from the developing cases.
Although the Shige et al. Tropical Rainfall Measuring Mission (TRMM) precipitation radar (PR) algorithm was only intended to be applied over large areas on longer time scales, the PR-derived latent heating profiles were compared with the ELDORA-derived profiles to reveal important mesoscale effects. Because all six cases indicated near-zero cooling rates, a new TRMM PR algorithm should be developed that would include the effects of saturated convective-scale downdrafts in tropical mesoscale convective systems (MCSs). Production of a legacy TRMM PR dataset with this improvement would be useful for diagnosing tropical cyclone formation dating back to 1998, and for specifying initial and validation conditions for numerical models in the tropics.
Influences of ENSO on Western North Pacific Tropical Cyclone Kinetic Energy and Its Meridional Transport
Authors: Ha Yao , Zhong Zhong , Hu Yijia , Yang Xiuqun 
Published: August 2012

Abstract
This study investigates the influences of ENSO on tropical cyclone (TC) kinetic energy and its meridional transport in the western North Pacific (WNP) using the TC wind field obtained after a method for removing TC vortices from reanalysis data is applied. Results show that ENSO strongly modulates TC kinetic energy and its meridional transport in the WNP, but their effects and regions differ. The TC kinetic energy is positively correlated with the Niño-3.4 index in the entire WNP, and its poleward transport is positively (negatively) correlated with the Niño-3.4 index in the eastern WNP (the western WNP and the South China Sea); these correlations are statistically significant. The maximum TC kinetic energy is located around 25°N, 135°E (25°N, 125°E) in the warm (cold) year, showing an east–west pattern during different ENSO phases. The meridional transport of TC kinetic energy exhibits a dipole pattern over the WNP, with the poleward (equatorward) transport in the eastern (western) WNP. Both poleward and equatorward transports strengthen (weaken) and shift eastward (westward) in El Niño (La Niña) years. Therefore, El Niño has strong influences on TC kinetic energy and its meridional transport.
Environmental Factors Contributing to Tropical Cyclone Genesis over the Western North Pacific
Authors: Yoshida Ryuji , Ishikawa Hirohiko 
Published: August 2012

Abstract
The flow environment associated with tropical cyclone genesis (TCG) over the western North Pacific was assessed via categorization into five flow patterns: monsoon shear line (SL), monsoon confluence region (CR), monsoon gyre (GY), easterly wave (EW), and preexisting tropical cyclone (PTC). Using reanalysis data and an objective algorithm, the authors defined “contribution scores” for the five flow patterns. Each score represents the contribution to TCG from each flow pattern, and scores were calculated for 908 TCG cases from 1979 to 2008 (30 yr). Of the major contribution flow patterns, SL accounted for 42% of TCGs, EW for 18%, CR for 16%, PTC for 11%, and GY for 6%. Seasonal variations in the occurrence frequency of these five patterns were clear, but interannual variations were not as apparent. Tropical cyclones often appear to be generated in conditions with multiple flow patterns. Thus, relationships between multiple flow patterns were investigated by comparing contribution scores. The SL and CR patterns were strongly correlated to each other, which can be explained by the monsoon southwesterly that organizes both patterns. The EW pattern tends to be independent of the other flow patterns. The PTC pattern has a relatively high correlation with CR, but does not have a correlation with SL or EW. Thus, the characteristics of flow patterns for the occurrence frequency of TCG are derived for a longer period than in previous studies, and correlations among flow patterns are also investigated.
Theorizing Gender, Race, and Cultural Tourism in Latin America
Authors: Babb Florence E. 
Published: August 2012

Theorizations of gender and race in Latin America have led to wide-ranging views concerning women and men in subaltern groups, whether indigenous or Afro-descendant, rural or urban. Views are similarly wide-ranging when theorizing turns to the implications of tourism development for subaltern peoples in the region. Just as it is customary to emphasize the historically subordinate status of women and racial minorities in Latin America, so too it is customary to show that tourism in the neoliberal era has particularly harsh consequences for these marginalized social sectors. At a time of indigenous mobilization, increasing migration, and urbanization, we must recognize the complex and often surprising ways in which gender, race, and tourism intertwine. Ethnographic cases from Andean Peru and Chiapas, Mexico, suggest that indigenous women play more or less prominent roles in tourism depending on several factors, with women who are active in the wider society holding more substantial positions in community-based cultural tourism. Las teorizaciones de género y raza en América Latina han conducido a una gran gama de perspectivas en lo que concierne a las mujeres y los hombres en grupos subalternos, sean estos indígenas o afro-descendientes, rurales or urbanos. Tal como es costumbre enfatizar el papel subordinado de la mujer y el indígena en América Latina, también es costumbre demostrar que el turismo en la era del neoliberalismo tiene consecuencias duras para estos sectores marginados. En un tiempo de movilización indígena, aumento en la migración, y urbanización, tenemos que reconocer las maneras complejas y a menudo sorprendentes en que el género, la raza, y el turismo se entrelacen. Casos etnográficos del Perú Andino y Chiapas, México, sugieren que las mujeres indígenas toman un papel mas o menos prominente en el turismo dependiendo de varios factores, con las mujeres mas activas en la sociedad en general consiguiendo posiciones mas substanciales en el turismo cultural basado en la comunidad.