bluuebunny/crossref_metadata_2025_split huggingface dataset:
The BH3 Mimetic ABT-737 Induces Cancer Cell Senescence
Authors: Song Jin H. , Kandasamy Karthikeyan , Zemskova Marina , Lin Ying-Wei , Kraft Andrew S. 
Published: November 2010

Abstract
ABT-737, a small molecule cell-permeable Bcl-2 antagonist that acts by mimicking BH3 proteins, induces apoptotic cell death in multiple cancer types. However, when incubated with this agent many solid tumor cell lines do not undergo apoptosis. The current study reveals a novel mechanism whereby ABT-737 when added to apoptosis-resistant cancer cells has profound biologic effects. In PV-10 cells, a renal cell carcinoma that does not die after ABT-737 treatment, this agent induces a two-fold change in the transcription of nearly 430 genes. Many of these induced mRNA changes are in secreted proteins, IL-6, IL-8, and IL-11 and chemokines CXCL2 and CXCL5, or genes associated with an “inflammatory” phenotype. Strikingly, these gene changes are highly similar to those changes previously identified in cellular senescence. Brief exposure of apoptosis-resistant renal, lung and prostate cancer cell lines to ABT-737, although not capable of inducing cell death, causes the induction of senescence-associated β-galactosidase and inhibition of cell growth consistent with the induction of cellular senescence. Evidence indicates that the induction of senescence occurs as a result of reactive oxygen species elevation followed by low-level activation of the caspase cascade, insufficient to induce apoptosis, but sufficient to lead to minor DNA damage and increases in p53, p21, IL-6 and 8 proteins. By overexpression of a dominant-negative p53 protein, we show that ABT-737-induced cellular senescence is p53-dependent. Thus, in multiple cancer types in which ABT-737 is incapable of causing cell death, ABT-737 may have additional cellular activities that make its use as an anticancer agent highly attractive. Cancer Res; 71(2); 506–15. ©2010 AACR.
Autophagic Survival in Resistance to Histone Deacetylase Inhibitors: Novel Strategies to Treat Malignant Peripheral Nerve Sheath Tumors
Authors: Lopez Gonzalo , Torres Keila , Liu Juehui , Hernandez Belinda , Young Eric , Belousov Roman , Bolshakov Svetlana , Lazar Alexander J. , Slopis John M. , McCutcheon Ian E. , McConkey David , Lev Dina 
Published: November 2010

Abstract
Histone deacetylase inhibitors (HDACi) show promise as cancer therapeutics; however, the full scope of their utility remains unknown. Here we report findings that strongly rationalize clinical evaluation of HDACis in malignant peripheral nerve sheath tumors (MPNST), a class of highly aggressive, therapeutically resistant, and commonly fatal malignancies that occur sporadically or in patients with the inherited neurofibromatosis type-1 (NF1) syndrome. We evaluated the effects of the chemical HDACis PCI-24781, suberoylanilide hydroxamic acid, and MS-275 on a panel of human NF1-associated and sporadic MPNSTs in vitro and in vivo. A subset of MPNSTs was found to be highly sensitive to HDACis, especially to PCI-24781. All cell lines in this group were NF1-associated. Significant proapoptotic effects were noted in vitro and in vivo and were independent of p53 mutational status. In contrast, as a group the sporadic–MPNST cells were markedly resistant to HDACi treatment. HDACis were found to induce productive autophagy in MPNST cells. Genetic and/or pharmacologic autophagy blockade resulted in significant HDACi-induced apoptosis in cells defined as resistant or sensitive, leading to abrogated growth of primary tumors and lung metastases in tumor xenograft assays. Among autophagy-associated genes expressed in response to HDACi, the immunity-related GTPase family, M was validated as a critical target in mediating HDACi-induced autophagy and enhanced apoptosis. Taken together, our findings strongly support the evaluation of HDACi currently in clinical trials as an important new therapeutic strategy to treat MPNST, including in combination with autophagy blocking combination regimens in particular for patients with sporadic MPNST. Cancer Res; 71(1); 185–96. ©2010 AACR.
In vivoAntitumor Activity of a Recombinant IL-7/HGFβ Hybrid Cytokine in Mice
Authors: Lai Laijun , Jin Jingjun , Goldschneider Irving 
Published: November 2010

AbstractThe immune cytokine interleukin (IL)-7 and the β-chain of hepatocyte growth factor (HGF) aggregate to form a naturally occurring heterodimer that stimulates the growth of common lymphoid progenitors and immature B and T lymphoid cells. We have cloned and expressed the heterodimer as a single-chain hybrid cytokine [recombinant (r) IL-7/HGFβ], which stimulates short-term hematopoietic stem cells as well as lymphoid precursors. Inasmuch as IL-7 and HGF are known to have antitumor and protumor activities, respectively, we determined here whether either of these activities is exhibited by rIL-7/HGFβ. We show that the in vivo administration of rIL-7/HGFβ markedly inhibits the growth of newly initiated and established tumors and the formation of pulmonary metastases in murine models of colon cancer and melanoma. The antitumor effect of rIL-7/HGFβ correlated with a marked increase in the number of tumor-infiltrating CD4+ and CD8+ T cells and activated dendritic cells. A major role for these immune cells in tumor suppression was indicated by the inability of rIL-7/HGFβ to inhibit the growth of tumor cells in vitro and in congenitally athymic mice. Analysis of interferon-γ–secreting T cells showed that the immune response was tumor specific. Our findings justify further evaluation of rIL-7/HGFβ as a novel experimental cancer therapy. Cancer Res; 71(1); 61–7. ©2011 AACR.
Erasmus and the Natural History of Friendship
Authors: Lobis Seth 
Published: November 2010

AbstractIn his colloquy Amicitia, Erasmus uses Pliny's Historia naturalis as the primary source for an energetic and inventive exploration of the topic of friendship. Like certain animals and objects in the natural world, friends share a natural affinity, but Erasmus goes further than this natural-historical observation, concluding that the moral life requires from us a more active relationship to our instincts and inclinations. Apposing two senses of the word amicitia, natural affinity and personal friendship, Erasmus ultimately suggests an intimate relationship between natural history and moral philosophy.
The Erasmian Adage in the Controversy with Luther
Authors: Rowe Asia 
Published: November 2010

AbstractDespite the absence of allusions to Luther in the Adagia, Erasmus' use of particular adages in his apologiae and letters helps to clarify his shifting strategies in debating not only Luther but his Catholic opponents. Initially interested in distinguishing between Luther and his Catholic critics and intent on bringing his fellow reformer back into the fold with adages softened by explicit framing, Erasmus eventually makes less conspicuous and more offensive use of proverbs, deploying them to conflate his enemies and represent himself as trapped between their partisan agendas.
Clouds at Arctic Atmospheric Observatories. Part I: Occurrence and Macrophysical Properties
Authors: Shupe Matthew D. , Walden Von P. , Eloranta Edwin , Uttal Taneil , Campbell James R. , Starkweather Sandra M. , Shiobara Masataka 
Published: November 2010

Abstract
Cloud observations over the past decade from six Arctic atmospheric observatories are investigated to derive estimates of cloud occurrence fraction, vertical distribution, persistence in time, diurnal cycle, and boundary statistics. Each observatory has some combination of cloud lidar, radar, ceilometer, and/or interferometer for identifying and characterizing clouds. By optimally combining measurements from these instruments, it is found that annual cloud occurrence fractions are 58%–83% at the Arctic observatories. There is a clear annual cycle wherein clouds are least frequent in the winter and most frequent in the late summer and autumn. Only in Eureka, Nunavut, Canada, is the annual cycle shifted such that the annual minimum is in the spring with the maximum in the winter. Intersite monthly variability is typically within 10%–15% of the all-site average. Interannual variability at specific sites is less than 13% for any given month and, typically, is less than 3% for annual total cloud fractions. Low-level clouds are most persistent at the observatories. The median cloud persistence for all observatories is 3–5 h; however, 5% of cloud systems at far western Arctic sites are observed to occur for longer than 100 consecutive hours. Weak diurnal variability in cloudiness is observed at some sites, with a daily minimum in cloud occurrence near solar noon for those seasons for which the sun is above the horizon for at least part of the day.
Clouds at Arctic Atmospheric Observatories. Part II: Thermodynamic Phase Characteristics
Authors: Shupe Matthew D. 
Published: November 2010

Abstract
Cloud phase defines many cloud properties and determines the ways in which clouds interact with other aspects of the climate system. The occurrence fraction and characteristics of clouds distinguished by their phase are examined at three Arctic atmospheric observatories. Each observatory has the basic suite of instruments that are necessary to identify cloud phase, namely, cloud radar, depolarization lidar, microwave radiometer, and twice-daily radiosondes. At these observatories, ice clouds are more prevalent than mixed-phase clouds, which are more prevalent than liquid-only clouds. Cloud ice occurs 60%–70% of the time over a typical year, at heights up to 11 km. Liquid water occurs at temperatures above −40°C and is increasingly more likely as temperatures increase. Within the temperature range from −40° to −30°C, liquid water occurs in 3%–5% of the observed cloudiness. Liquid water is found higher in the atmosphere when accompanied by ice; there are few liquid-only clouds above 3 km, although liquid in mixed-phase clouds occurs at heights up to about 7–8 km. Regardless of temperature or height, liquid water occurs 56% of the time at Barrow, Alaska, and at a western Arctic Ocean site, but only 32% of the time at Eureka, Nunavut, Canada. This significant difference in liquid occurrence is due to a relatively dry lower troposphere during summer at Eureka in addition to warmer cloud temperatures with more persistent liquid water layers at the far western locations. The most persistent liquid clouds at these locations occur continuously for more than 70 h in the autumn and more than 30 h in the winter. Ice clouds persist for much longer than do liquid clouds at Eureka and occur more frequently in the winter season, leading to a total cloud occurrence annual cycle that is distinct from the other observatories.
Diurnal Cycle of Thermally Driven Cross-Basin Winds in Arizona’s Meteor Crater
Authors: Lehner Manuela , Whiteman C. David , Hoch Sebastian W. 
Published: November 2010

Abstract
Cross-basin winds produced by asymmetric insolation of the crater sidewalls occur in Arizona’s Meteor Crater on days with weak background winds. The diurnal cycle of the cross-basin winds is analyzed together with radiation, temperature, and pressure measurements at the crater sidewalls for a 1-month period. The asymmetric irradiation causes horizontal temperature and pressure gradients across the crater basin that drive the cross-basin winds near the crater floor. The horizontal temperature and pressure gradients and wind directions change as the sun moves across the sky, with easterly winds in the morning and westerly winds in the evening. A case study of 12 October 2006 further illustrates the obtained relation between these parameters for an individual day. The occurrence of an elevated cross-basin flow on 23 October 2006 is shown to relate to the presence of an elevated inversion layer.
A Mass Flux Model of Nocturnal Cold-Air Intrusions into a Closed Basin
Authors: Haiden Thomas , Whiteman C. David , Hoch Sebastian W. , Lehner Manuela 
Published: November 2010

AbstractObservations made during the Meteor Crater Experiment (METCRAX) field campaign revealed unexpected nighttime cooling characteristics in Arizona’s Meteor Crater. Unlike in other natural closed basins, a near-isothermal temperature profile regularly develops over most of the crater depth, with only a shallow stable layer near the crater floor. A conceptual model proposed by Whiteman et al. attributes the near-isothermal stratification to the intrusion, and subsequent detrainment, of near-surface air from outside the crater into the crater atmosphere. To quantify and test the hypothesis, a mass flux model of the intrusion process is developed. It is found that the observed temperature profile can be reproduced, providing confirmation of the conceptual model. The near-isothermal stratification can be explained as a result of progressively cooler air entering the crater and detraining into the atmosphere, combined with the finite time of ascent in the compensating rising motion. The strength of detrainment largely determines the characteristics of the cooling process. With weak detrainment, most of the cooling arises from an adiabatic rising motion (“filling-up” mode). Stronger detrainment leads to reduced rising motion and enhanced cooling at upper levels in the crater (“destabilization” mode). Of interest is that the detrainment also reduces the total cooling, which, for a given intrusion mass flux, is determined by the temperature difference between the intruding air and the crater atmosphere at rim height.
Synoptically Driven Arctic Winter States
Authors: Stramler Kirstie , Del Genio Anthony D. , Rossow William B. 
Published: November 2010

Abstract
The dense network of the Surface Heat Budget of the Arctic (SHEBA) observations is used to assess relationships between winter surface and atmospheric variables as the SHEBA site came under the influence of cyclonic and anticyclonic atmospheric circulation systems. Two distinct and preferred states of subsurface, surface, atmosphere, and clouds occur during the SHEBA winter, extending from the oceanic mixed layer through the troposphere and preceded by same-sign variations in the stratosphere. These states are apparent in distributions of surface temperature, sensible heat and longwave radiation fluxes, ocean heat conduction, cloud-base height and temperature, and in the atmospheric humidity and temperature structure.
Surface and atmosphere are in radiative–turbulent–conductive near-equilibrium during a warm opaquely cloudy-sky state, which persists up to 10 days and usually occurs during the low surface pressure phase of a baroclinic wave, although occasionally occurs during the high surface pressure phase because of low, scattered clouds. Clouds occurring in this state have near-unity emissivity and the lowest bases in the vicinity of, or below, the temperature inversion peak. A cold radiatively clear-sky state persists up to two weeks, and occurs only in the high surface pressure phase of a baroclinic wave. The radiatively clear state has clouds that are too tenuous when surface based or, irrespective of opacity, located too far aloft to contribute significantly to the surface energy budget. There is a 13-K surface temperature difference between the two states, and atmospheric inversion peak temperatures are linearly related to the surface temperature in both states. The snow–sea ice interface temperature oscillates over the course of the winter season, as it cools during the radiatively clear state and is warmed from atmospheric emission above and ocean heat conduction from below during the opaquely cloudy state.
Analysis of satellite data over the Arctic from 70°–90°N indicates that the radiatively clear and opaquely cloudy states observed at SHEBA may be representative of the entire Arctic basin. The results suggest that model formulation inadequacies should be easier to diagnose if modeled energy transfers are compared with observations using process-based metrics that acknowledge the bimodal nature of the Arctic ocean–ice–snow–atmosphere column, rather than monthly and regionally averaged quantities. Climate change projections of thinner Arctic sea ice and larger advective water vapor influxes into the Arctic could yield different frequencies of occupation of the radiatively clear and opaquely cloudy states and higher wintertime temperatures of SHEBA ocean, ice, snow, atmosphere, and clouds—in particular, a wintertime warming of the snow–sea ice interface temperature.
Loop Current Cycle: Coupled Response of the Loop Current with Deep Flows
Authors: Chang Y.-L. , Oey L.-Y. 
Published: November 2010

Abstract
Although the upper-layer dynamics of the Loop Current and eddies in the Gulf of Mexico are well studied, the understanding of how they are coupled to the deep flows is limited. In this work, results from a numerical model are analyzed to classify the expansion, shedding, retraction, and deep-coupling cycle (the Loop Current cycle) according to the vertical mass flux across the base of the Loop. Stage A is the “Loop reforming” period, with downward flux and deep divergence under the Loop Current. Stage B is the “incipient shedding,” with strong upward flux and deep convergence. Stage C is the “eddy migration,” with waning upward flux and deep throughflow from the western Gulf into the Yucatan Channel. Because of the strong deep coupling between the eastern and western Gulf, the Loop’s expansion is poorly correlated with deep flows through the Yucatan Channel. Stage A is longest and the mean vertical flux under the Loop Current is downward. Therefore, because the net circulation around the abyssal basin is zero, the abyssal gyre in the western Gulf is cyclonic. The gyre’s strength is strongest when the Loop Current is reforming and weakest after an eddy is shed. The result suggests that the Loop Current cycle can force a low-frequency [time scales ∼ shedding periods; O(months)] abyssal oscillation in the Gulf of Mexico.
Ensemble Tropical Rainfall Potential (eTRaP) Forecasts
Authors: Ebert Elizabeth E. , Turk Michael , Kusselson Sheldon J. , Yang Jianbin , Seybold Matthew , Keehn Peter R. , Kuligowski Robert J. 
Published: November 2010

Abstract
Ensemble tropical rainfall potential (eTRaP) has been developed to improve short-range forecasts of heavy rainfall in tropical cyclones. Evolving from the tropical rainfall potential (TRaP), a 24-h rain forecast based on estimated rain rates from microwave sensors aboard polar-orbiting satellites, eTRaP combines all single-pass TRaPs generated within ±3 h of 0000, 0600, 1200, and 1800 UTC to form a simple ensemble. This approach addresses uncertainties in satellite-derived rain rates and spatial rain structures by using estimates from different sensors observing the cyclone at different times. Quantitative precipitation forecasts (QPFs) are produced from the ensemble mean field using a probability matching approach to recalibrate the rain-rate distribution against the ensemble members (e.g., input TRaP forecasts) themselves. ETRaPs also provide probabilistic forecasts of heavy rain, which are potentially of enormous benefit to decision makers. Verification of eTRaP forecasts for 16 Atlantic hurricanes making landfall in the United States between 2004 and 2008 shows that the eTRaP rain amounts are more accurate than single-sensor TRaPs. The probabilistic forecasts have useful skill, but the probabilities should be interpreted within a spatial context. A novel concept of a “radius of uncertainty” compensates for the influence of location error in the probability forecasts. The eTRaPs are produced in near–real time for all named tropical storms and cyclones around the globe. They can be viewed online (http://www.ssd.noaa.gov/PS/TROP/etrap.html) and are available in digital form to users.
The Prognosis and Predictors of Sports Function and Activity at Minimum 6 Years After Anterior Cruciate Ligament Reconstruction
Authors: Spindler Kurt P. , Huston Laura J. , Wright Rick W. , Kaeding Christopher C. , Marx Robert G. , Amendola Annunziato , Parker Richard D. , Andrish Jack T. , Reinke Emily K. , Harrell Frank E. , Dunn Warren R. ,   MOON Group, Pedroza Angela , An Angel Q. , Schmitz Leah , McCarty Eric C. , Wolf Brian R. , Jones Morgan H. , Matava Matthew J. , Flanigan David C. , Brophy Robert H. , Vidal Armando F. 
Published: November 2010

Background: The predictors of anterior cruciate ligament reconstruction (ACLR) outcome at 6 years as measured by validated patient-based outcome instruments are unknown. Hypothesis: Certain variables evaluated at the time of ACLR will predict return to sports function (as measured by the International Knee Documentation Committee [IKDC] questionnaire and the Knee injury and Osteoarthritis Outcome Score [KOOS] Sports and Recreation subscale), knee-related quality of life (KOOS Knee Related Quality of Life subscale), and activity level (Marx Activity Scale). Potential predictor variables include demographic factors, surgical technique and graft choice for ACLR, and intra-articular injuries and treatment. Study Design: Cohort study; Level of evidence, 2. Methods: All patients with unilateral ACLRs from 2002 currently enrolled in the MOON (Multicenter Orthopaedic Outcomes Network) cohort were evaluated. Patients completed the validated outcome instruments preoperatively. Physicians documented intra-articular pathologic abnormalities, treatment, and surgical techniques used at the time of surgery. At 2 and 6 years postoperatively, patients completed the same validated outcome instruments. Results: Follow-up was obtained at 2 years (88%) and at 6 years (84%). The cohort was 57% male with a median age of 23 years at enrollment. The ability to perform sports function was maintained at 6 years, but the Marx activity level continued to decline from baseline. Revision ACLR and use of allograft predicted worse outcomes on the IKDC and both KOOS subscales. Lateral meniscus treatment, smoking status, and body mass index at baseline were each predictors on 2 of 3 scales. The predictors of lower activity level were revision ACLR and female sex. Conclusion: Six years after ACLR, patients could perform sports-related functions and maintain a high knee-related quality of life similar to their 2-year level, although their physical activity level (Marx) dropped over time. Choosing autograft rather than allograft, not smoking, and having normal body mass index are advised to improve long-term outcomes.