bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resistance Emerges to Second-Generation Antiandrogens in Prostate Cancer
Authors: Nelson William G. , Yegnasubramanian Srinivasan 
Published: September 2013

Abstract
Summary: The appearance of a mutant androgen receptor, ARF876L, in prostate cancer cells chronically exposed to enzalutamide or ARN-509 promotes a switch from antagonist to agonist receptor function, undermining the potential long-term effectiveness of these second-generation antiandrogen drugs. Cancer Discov; 3(9); 971–4. ©2013 AACR.
See related article by Joseph et al., p. 1020
See related article by Korpal et al., p. 1030
Dendritic Cells: Master Regulators of the Immune Response
Authors: Mellman Ira 
Published: September 2013

Abstract
Dendritic cells (DC) are responsible for initiating all antigen-specific immune responses. As such, they are the master regulators of the immune response and serve this function by linking the microbial sensing features of the innate immune system to the exquisite specificity of the adaptive response. They are exceptionally efficient at antigen presentation and also adept at generating just the right type of T cells in response to a given pathogen. Importantly, DCs also help guide the immune system to respond to foreign antigens while avoiding the generation of autoimmune responses to self. DCs are thus paradoxically important in cancer, generating both immunity and tolerance. Given their central role in controlling the immune response in patients with cancer, DCs are emerging as a critical cell type that must be considered as we come to understand basic cancer immunobiology. They should also be considered as potential targets or at least as key players in any effort intended to generate therapeutic vaccines. Cancer Immunol Res; 1(3); 145–9. ©2013 AACR.
A Framework for Evaluating Model Credibility for Warm-Season Precipitation in Northeastern North America: A Case Study of CMIP5 Simulations and Projections
Authors: Thibeault Jeanne M. , Seth Anji 
Published: September 2013

AbstractFuture projections of northeastern North American warm-season precipitation [June–August (JJA)] indicate substantial uncertainty. Atmospheric processes important to the northeast-region JJA precipitation are identified and a first evaluation of the ability of five phase 5 of the Coupled Model Intercomparison Project (CMIP5) models to simulate these processes is performed. In this case study, the authors develop a set of process-based analyses forming a framework for evaluating model credibility in the northeast region. This framework includes evaluation of models’ ability to simulate observed spatial patterns and amounts of mean precipitation; dynamical atmospheric circulation features, moisture transport, and moisture divergence important to interannual precipitation variability; long-term trends; and SST patterns important to northeast-region summer precipitation.Wet summers in the northeast region are associated with 1) negative 500-hPa geopotential height anomalies centered near the Great Lakes; 2) positive 500-hPa geopotential height anomalies over the western Atlantic east of the Mid-Atlantic states; 3) northeastward moisture flow and increased moisture convergence along the Eastern Seaboard; 4) increased moisture divergence off the U.S. Southeast coast; and 5) positive sea level pressure (SLP) anomalies in the western Atlantic, possibly related to cold tropical Atlantic SSTs and southwest ridging of the North Atlantic anticyclone. Models are generally able to simulate these features but vary compared to observations. Models capture regional moisture transport and convergence anomalies associated with wet summers reasonably well, despite errors in simulating the climatology. Identifying sources of intermodel differences in future projections is important, determining processes relevant for model credibility. In particular, changes in moisture divergence control the sign of northeast-region summer precipitation changes, making it a critical component of process-level analyses for the region.
Interannual Variability of Arctic Landfast Ice between 1976 and 2007
Authors: Yu Yanling , Stern Harry , Fowler Charles , Fetterer Florence , Maslanik James 
Published: September 2013

Abstract
Analysis of weekly sea ice charts produced by the U.S. National Ice Center from 1976 to 2007 indicates large interannual variations in the averaged winter landfast ice extent around the Arctic Basin. During the 32-yr period of the record, landfast ice cover was relatively extensive from the early to mid-1980s but since then has declined in many coastal regions of the Arctic, particularly after the early 1990s. While the Barents, Baltic, and Bering Seas show increases in landfast ice area, the overall change for the Northern Hemisphere is negative, about −12.27 (±2.8) × 103 km2 yr−1, or −7 (±1.5)% decade−1 relative to the long-term mean. Except in a few coastal regions, the seasonal duration of landfast ice is shorter overall, particularly in the Laptev, East Siberian, and Chukchi Seas. The decreased winter landfast ice extent is associated with some notable changes in ice growth and melt patterns, in particular the slowed landfast ice expansion during fall and early winter since 1990. The observed changes in Arctic landfast ice could have profound impacts on the Arctic coasts. The challenge is to understand and project the responses of the whole coastal ecosystem to changing ice cover and Arctic warming.
Evaluation of Model Parameter Convergence when Using Data Assimilation for Soil Moisture Estimation
Authors: Dumedah Gift , Walker Jeffrey P. 
Published: September 2013

Abstract
Data assimilation (DA) methods are commonly used for finding a compromise between imperfect observations and uncertain model predictions. The estimation of model states and parameters has been widely recognized, but the convergence of estimated parameters has not been thoroughly investigated. The distribution of model state and parameter values is closely linked to convergence, which in turn impacts the ultimate estimation accuracy of DA methods. This demonstration study examines the robustness and convergence of model parameters for the ensemble Kalman filter (EnKF) and the evolutionary data assimilation (EDA) in the context of the Soil Moisture and Ocean Salinity (SMOS) soil moisture assimilation into the Joint UK Land Environment Simulator in the Yanco area in southeast Australia. The results show high soil moisture estimation accuracy for the EnKF and EDA methods when compared with the open loop estimates during evaluation and validation stages. The level of convergence was quantified for each model parameter in the EDA approach to illustrate its potential in the retrieval of variables that were not directly observed. The EDA was found to have a higher estimation accuracy than the EnKF when its updated members were evaluated against the SMOS level 2 soil moisture. However, the EnKF and EDA estimations are comparable when their forward soil moisture estimates were validated against SMOS soil moisture outside the assimilation time period. This suggests that parameter convergence does not significantly influence soil moisture estimation accuracy for the EnKF. However, the EDA has the advantage of simultaneously determining the convergence of model parameters while providing comparably higher accuracy for soil moisture estimates.
Quantitative Assessment of Operational Weather Radar Rainfall Estimates over California’s Northern Sonoma County Using HMT-West Data
Authors: Matrosov Sergey Y. , Ralph F. Martin , Neiman Paul J. , White Allen B. 
Published: September 2013

Abstract
An evaluation of Weather Surveillance Radar-1988 Doppler (WSR-88D) KMUX and KDAX radar quantitative precipitation estimation (QPE) over a site in California’s northern Sonoma County is performed and rain type climatology is presented. This site is next to the flood-prone Russian River basin and, because of the mountainous terrain and remoteness from operational radars, is generally believed to lack adequate coverage. QPE comparisons were conducted for multiyear observations with concurrent classification of rainfall structure using measurements from a gauge and an S-band profiler deployed at the location of interest. The radars were able to detect most of the brightband (BB) rain, which contributed over half of the total precipitation. For this rain type hourly radar-based QPE obtained with a default vertical profile of reflectivity correction provided results with errors of about 50%–60%. The operational radars did not detect precipitation during about 30% of the total rainy hours with mostly shallow nonbrightband (NBB) rain, which, depending on the radar, provided ~(12%–15%) of the total precipitation. The accuracy of radar-based QPE for the detected fraction of NBB rain was rather poor with large negative biases and characteristic errors of around 80%. On some occasions, radars falsely detected precipitation when observing high clouds, which did not precipitate or coexisted with shallow rain (less than 10% of total accumulation). For heavier rain with a significant fraction of BB hourly periods, radar QPE for event totals showed relatively good agreement with gauge data. Cancelation of errors of opposite signs contributed, in part, to such agreement. On average, KDAX-based QPE was biased low compared to KMUX.
A New Method to Produce Sea Surface Temperature Using Satellite Data Assimilation into an Atmosphere–Ocean Mixed Layer Coupled Model
Authors: Lee Eunjeong , Noh Yign , Hirose Naoki 
Published: September 2013

AbstractA new method of producing sea surface temperature (SST) data for numerical weather prediction is suggested, which is obtained from the assimilation of satellite-derived SST into an atmosphere–ocean mixed layer coupled model. The Weather Research and Forecasting (WRF) Model and the Noh mixed layer model are used for the atmosphere and ocean mixed layer models, respectively. Data assimilation (DA) is carried out in two steps, based on the estimation from the covariance matching method that the daily mean SST of satellite data is more accurate than the model data, if the number of data in a grid per day is sufficiently large—that is, the daily mean SST bias correction in the first DA and the sequential SST anomaly correction in the second DA. For the second DA, the model restarts from the initial condition corrected by the first DA, and DA is applied every 30 min using the nudging method. The daily mean and the diurnal variation of satellite SST are assimilated to the bulk and skin SST, respectively. The modeled results with the new data assimilation scheme are validated by statistical comparison with independent satellite and buoy data such as correlation coefficient, root-mean-square difference, and bias. Furthermore, the sensitivity and seasonal variation of the weighting factor in the second DA are examined. The new approach illustrates the possibility of applying the atmosphere–ocean mixed layer coupled model for the production of SST data combined with the assimilation of satellite data.
Initial Condition Sensitivity and Predictability of a Severe Extratropical Cyclone Using a Moist Adjoint
Authors: Doyle James D. , Amerault Clark , Reynolds Carolyn A. , Reinecke P. Alex 
Published: September 2013

AbstractThe sensitivity and predictability of a rapidly developing extratropical cyclone, Xynthia, that had a severe impact on Europe is explored using a high-resolution moist adjoint modeling system. The adjoint diagnostics indicate that the intensity of severe winds associated with the front just prior to landfall was particularly sensitive to perturbations in the moisture and temperature fields and to a lesser degree the wind fields. The sensitivity maxima are found in the low- and midlevels, oriented in a sloped region along the warm front, and maximized within the warm conveyor belt. The moisture sensitivity indicates that only a relatively small filament of moisture within an atmospheric river present at the initial time was critically important for the development of Xynthia. Adjoint-based optimal perturbations introduced into the tangent linear and nonlinear models exhibit rapid growth over 36 h, while initial perturbations of the opposite sign show substantial weakening of the low-level jet and a marked reduction in the spatial extent of the strong low-level winds. The sensitivity fields exhibit an upshear tilt along the sloping warm conveyor belt and front, and the perturbations extract energy from the mean flow as they are untilted by the shear, consistent with the PV unshielding mechanism. The results of this study underscore the need for accurate moisture observations and data assimilation systems that can adequately assimilate these observations in order to reduce the forecast uncertainties for these severe extratropical cyclones. However, given the nature of the sensitivities and the potential for rapid perturbation and error growth, the intrinsic predictability of severe cyclones such as Xynthia is likely limited.
Perspectives On Reproductive and Developmental Toxicity
Authors: Johnson E. Marshall 
Published: September 2013

Human reproduction and development is a cycle of interdependent events. Virtually all of its phases have been shown to be the primary target of one or more non-mutagenic exogenous agents (Table 1). Such agents interfere with certain of the countless epigenetic or ontogenic events essential for normal completion of the cycle. Mutagens disrupt this cycle at some points, but the overwhelming majority of reproduc tive and developmental toxins are not mutagenic. As in all aspects of toxicology, the reproductive and developmental effects of chemicals are determined by the intrinsic nature of the chemical, the quantity of the chemical exposure, the duration of exposure and the stage of the cycle at which it occurs. Signs of repro ductive toxicity range from reduced fertility to spontaneous abortion. Adverse effects on the conceptus are categorized as functional deficits, developmental retardation, structural abnormality and death. One or more of these is anticipated to occur as a result of excess exposure to most chemicals. Although the degree of hazard and risk potential can be calculated in each instance, chemicals differ markedly in their ability to interfere with reproduction (Amann, 1982) and/or develop ment (Johnson, 1984). Standardized methods for reproductive and developmental toxicity safety evaluation are available for detecting adverse effects upon any
Modern Biotechnology: a Review of Current Regulatory Status and Identification of Research and Regulatory Needs
Authors: Franklin Claire A. 
Published: September 2013

Modern biotechnology encompasses many technologies. The one that has generated the most public interest is that of genetic engineering. The field has advanced dramatically since the early 1970's, when concern was so high that a moratorium was declared on research using recombinant DNA. Today there are numerous products such as human growth hormone, interferon and monoclonal antibody diagnostic kits on the market. Despite the obvious benefits of these products, there are still concerns over the environmental application of genetically engineered organisms. Many countries have assessed their existing legislation to ascertain its adequacy to regulate such intended releases. Numerous international organizations are becoming involved as well, and optimistically, regulations that are being developed in various countries may be harmonized. These activities have identified several areas where more information is required, including microbial taxonomy and classification, pathogenicity in target and non-target species, environmental behavior and risk assessment processes. Consensus at this time appears to be that our predictive capabilities are still developing and that new organisms should be evaluated on a case-by-case basis. In contrast to chemicals, where our risk assessment procedures have developed over the years, there are still questions as to whether these procedures are suitable for assessing the risk of genetically engineered organisms. A brief overview of the technologies involved, the regulatory strategies that are evolving and the areas where research is needed to enable appropriate regulations to be developed are presented.
Health Assessment of Environmental Pollutants: Proliferative and Degenerative Diseases
Authors: Stuart Bruce O. 
Published: September 2013

In order to achieve a balanced approach to risk assessment between carcinogenic and non-carcinogenic health effects one must examine the risk of disease or death in the general population exposed to a particular air pollutant that can be related quantitatively to intensity and duration of exposures (National Academy of Sciences, 1983). Such risk assessment should be based upon careful evaluation of scientific findings of dose-response relationships in the chronically exposed population. Quantitative assessment of environmentally produced disease in man has proven to be complex and demanding. A variety of factors play important roles in this task. As an example, there are induction-latency periods for chronic diseases, including cancer, which may range from five to twenty-five years. The diseases themselves, whether proliferative or degenerative, may follow several stages of progression. There is only sparse epidemiological data on serious health effects that may be due to environmental as compared to occupational exposures. Exposures to chemical or radiological air contaminants do not occur singly but to a multiplicity of agents, and disease processes are frequently markedly affected by the interaction of a variety of factors, particularly that of cigarette smoking. There is growing recognition of potentially sensitive subpopulations, including the elderly and the very young, but adequate techniques for assessing the magnitude of increased risks to these groups have not yet been developed. The health assessments of environmental air contaminants are at present frequently based upon probability of cancer, if this has been identified as a potential result of prolonged exposure to the particular inhalation hazard. However, for many airborne hazards chronic inhalation exposure may result in morbidity or mortality risks due to chronic degenerative diseases such as emphysema, fibrosis, or chronic obstructive pulmonary disease that may be nearly as great or greater than those of more widely recognized neoplastic or proliferative disease. The relative hazards of environmentally released radioactive and chemical air contaminants, i.e., radon daughters and diesel engine exhaust, will be discussed as examples.
An Overview of Structure-Activity Relationships as an Alternative To Testing in Animals for Carcinogenicity, Mutagenicity, Dermal and Eye Irritation, and Acute Oral Toxicity
Authors: Enslein Kurt 
Published: September 2013

The use of structure-activity relationships (SAR) has proven practical for the development of equations which can be used to estimate the above-listed endpoints for a large variety of chemicals. The SAR models predict these endpoints correctly in 85 to 97% of the cases and often surpass in their predictive ability the results obtainable from the equivalent biological assays. These SAR models are being used at several levels: drug, or more generally, chemical discovery; prioritization for testing; regulatory affairs; investigation of detoxification mechanisms; and risk estimation. In the new compound (discovery) use, potential toxic effects of a set of related compounds are investigated before synthesis to select those chemicals with the lesser probabilities of producing toxic effects for further investigation, at considerable savings in research expenditure since fewer compounds need to be synthesized, and the avoidance of blind alleys. Prioritization for testing is used in numerous instances, such as selecting those chemicals in an environment which are most likely to have toxic effects for priority attention. SAR models are used by regulatory agencies to determine the possible toxic effects of chemicals for which data insufficient to render decisions have been submitted, and to gain insight into possible toxicity problems. SAR models are also used to investigate possible metabolites, and toxicity mechanisms due to the ability of making computer-based structural modifications and observing the effects on the modelled toxic endpoints. Risk analysis is a natural outgrowth of several of the above applications, and is particularly useful for SAR models of carcinogenicity. SAR models as alternatives to animal bioassays should be used in the context of other information for the chemicals of concern. Just as bioassays and in vitro methods have their limitations, so do SAR models. These include the sometimes limited data base on which to base an SAR model, the temptation to extrapolate beyond the confines of the model, and the noise inherent in the bioassays on which the models are based. Within these constraints SAR models have a considerable potential in reducing the number of animals used in toxicity testing.
The Further Development of a Mammalian DNA Alkaline Unwinding Bioassay With Potential Application to Hazard Identification for Contaminants from Environmental Samples
Authors: Daniel F. Bernard , Chang Lina W. , Schenck Kathleen M. , Deangelo Anthony B. , Skelly Michael F. 
Published: September 2013

Recently, we have detailed a DNA alkaline unwinding assay (DA UA) that can be used to rapidly measure chemically induced strand breaks in mammalian cells (Daniel et al., 1985). In this paper we present further development of this assay, including: (1) studies on the relationship between DNA adducts and DNA strand breaks; (2) evaluation of the role of cytotoxicity in DNA strand breaks; and (3) application of the DA UA to cell preparations from the liver of mice dosed with methylating agents. The level of DNA adducts produced in human CCRF-CEM cells by treatment with benzo(a)pyrene diol-epoxide (BPDE), N-acetoxy-2-acetyl amino fluorene (AAAF), and various methylating agents was linear with concentration over several orders of magnitude. Likewise, the level of strand breaks increased with the concentration over the same dose range. The strand breaks/adduct ratio ranged from 0.05 for the methyl adducts to 0.001 for the BPDE adducts. Using these values and the inherent sensitivity of the DA UA (circa 100 to 1000 breaks/ cell), (Daniel et al., 1985), the ability of the assay to detect DNA damage induced by various classes of chemical carcinogens can be calculated. The DA UA appears to be useful for assessing the relative potency of various environmental genotoxic effects on mammalian cells. In addition, it can be conducted on cells isolated from target organs of whole animals.
Risk Assessment Initiatives for Noncancer Endpoints: Implications for Risk Characterization of Chemical Mixtures
Authors: Derosa C.T. , Dourson M.L. , Osborne R. 
Published: September 2013

Current methods employed in risk assessment for noncarcinogens are associated with the estimation of reference doses (RfDs). These strategies reflect (appropriately) a protective philosophy in both theory and practice. The approaches are limited, however, in terms of the ability to project the likelihood of specific hazard above the reference dose and to integrate the health hazards of exposure to chemical mixtures (including both cancer and noncancer endpoints). Ongoing efforts that address guidelines for risk assessment of non carcinogens, both singly and as components of mixtures, are pres ented. Included is a description of the range of potential biological response categories and associated parallel issues of adversity and severity. For example, the progression of histopathological change, organ system dysfunction and organismal disability is examined as it may affect risk characterization of mixtures. Mechanistic princi ples are suggested as an appropriate focus to systematically evalu ate this progression. Once established, these principles may provide a reasonable framework in which to more accurately characterize risks associated with chemical mixtures.