bluuebunny/crossref_metadata_2025 huggingface dataset:
A Biosurfactant-Sophorolipid Acts in Synergy with Antibiotics to Enhance Their Efficiency
Authors: Joshi-Navare Kasturi , Prabhune Asmita
Published: September 2013

Sophorolipids (SLs), biosurfactants with antimicrobial properties, have been tried to address the problem of antibiotic resistance. The synergistic action of SL and antibiotics was checked using standard microdilution and spread plate methods. WithStaphylococcus aureus, SL-tetracycline combination achieved total inhibition before 4 h of exposure while tetracycline alone couldnot achieve total inhibition till the end of 6 h. The inhibition caused by exposure of bacterium to SL-tetracycline mixture was~25% more as compared to SL alone. In spite of known robustness of gram-negative bacteria, SL-cefaclor mixture proved to be efficient againstEscherichia coliwhich showed~48% more inhibition within 2 h of exposure as compared to cefaclor alone. Scanning electron microscopy of the cells treated with mixture revealed bacterial cell membrane damage and pore formation. Moreover, SLs being a type of asymmetric bola, they are expected to form self-assemblies with unique functionality. This led to the speculation that SLs being amphiphilic in nature can span through the structurally alike cell membrane and facilitate the entry of drug molecules.
The Effects of Rural-Urban Migration on Rural Communities of Southeastern Nigeria
Authors: Ajaero Chukwuedozie K. , Onokala Patience C.
Published: September 2013

This paper examined the effects of rural-urban migration on the rural communities of Southeastern Nigeria. Data were obtained using mixed methods approach comprising questionnaire surveys and key informant interviews. Six rural local government areas (LGAs) were selected based on population size and spatial equity from two states of Southeastern Nigeria. From each of the rural LGAs, fifty migrant-sending households were sampled for the study. Multiple regression and hierarchical cluster analyses were used to estimate and categorize the effects of rural-urban migration due to remittances and community projects executed by the rural-urban migrants, respectively. In addition, the Chi-square and Kruskal-Wallis tests were utilized in prioritizing areas for development interventions in the rural communities. The regression analysis shows that rural-urban migration contributes significantly towards the development of their rural communities through monetary remittances and the involvement of the rural-urban migrants in community development projects. Based on the findings, recommendations such as initiation of development projects based on the identified needs of each of the rural communities to augment the effects of migration in the study area are made.
Waldenström Macroglobulinemia: Clinical and Immunological Aspects, Natural History, Cell of Origin, and Emerging Mouse Models
Authors: Janz Siegfried
Published: September 2013

Waldenström macroglobulinemia (WM) is a rare and currently incurable neoplasm of IgM-expressing B-lymphocytes that is characterized by the occurrence of a monoclonal IgM (mIgM) paraprotein in blood serum and the infiltration of the hematopoietic bone marrow with malignant lymphoplasmacytic cells. The symptoms of patients with WM can be attributed to the extent and tissue sites of tumor cell infiltration and the magnitude and immunological specificity of the paraprotein. WM presents fascinating clues on neoplastic B-cell development, including the recent discovery of a specific gain-of-function mutation in the MYD88 adapter protein. This not only provides an intriguing link to new findings that natural effector IgM+IgD+memory B-cells are dependent on MYD88 signaling, but also supports the hypothesis that WM derives from primitive, innate-like B-cells, such as marginal zone and B1 B-cells. Following a brief review of the clinical aspects and natural history of WM, this review discusses the thorny issue of WM’s cell of origin in greater depth. Also included are emerging, genetically engineered mouse models of human WM that may enhance our understanding of the biologic and genetic underpinnings of the disease and facilitate the design and testing of new approaches to treat and prevent WM more effectively.
Transforaminal Lumbar Interbody Fusion Using a Modified Distractor Handle: A Midterm Clinicoradiological Follow-Up Study
Authors: Rewuti Abuduaini , Chen Zixian , Feng Zhenzhou , Cao Yuanwu , Jiang Xiaoxing , Jiang Chun
Published: September 2013

In current TLIF practice, the choice of the cage size is empirical and primarily depends on the case volume and experience of the surgeon. We used a self-made modified distractor handle in TLIF procedure with the goal of standardizing the intervertebral space tension and determining the proper cage size.
Visible Light Photoelectrochemical Properties of N‐Doped TiO2 Nanorod Arrays from TiN
Authors: Xie Zheng , Zhang Yongbin , Liu Xiangxuan , Wang Weipeng , Zhan Peng , Li Zhengcao , Zhang Zhengjun
Published: September 2013

N‐doped TiO2 nanorod arrays (NRAs) were prepared by annealing the TiN nanorod arrays (NRAs) which were deposited by using oblique angle deposition (OAD) technique. The TiN NRAs were annealed at 330°C for different times (5, 15, 30, 60, and 120 min). The band gaps of annealed TiN NRAs (i.e., N‐doped TiO2 NRAs) show a significant variance with annealing time, and can be controlled readily by varying annealing time. All of the N‐doped TiO2 NRAs exhibit an enhancement in photocurrent intensity in visible light compared with that of pure TiO2 and TiN, and the one annealed for 15 min shows the maximum photocurrent intensity owning to the optimal N dopant concentration. The results show that the N‐doped TiO2 NRAs, of which the band gap can be tuned easily, are a very promising material for application in photocatalysis.
A Novel Method for Recognition of Bioradiolocation Signal Breathing Patterns for Noncontact Screening of Sleep Apnea Syndrome
Authors: Alekhin Maksim , Anishchenko Lesya , Tataraidze Alexander , Ivashov Sergey , Parashin Vladimir , Korostovtseva Lyudmila , Sviryaev Yurii , Bogomolov Alexey
Published: September 2013

A novel method for recognition of breathing patterns of bioradiolocation signals breathing patterns (BSBP) in the task of noncontact screening of sleep apnea syndrome (SAS) is proposed and implemented on the base of wavelet transform (WT) and neural network (NNW) applications. Selection of the optimal parameters of WT includes determination of the proper level of wavelet decomposition and the best basis for feature extraction using modified entropy criterion. Selection of the optimal properties of NNW includes defining the best number of hidden neurons and learning algorithm for the chosen NNW topology. The effectiveness of the proposed approach is tested on clinically verified database of BRL signals corresponding to the three classes of breathing patterns: obstructive sleep apnea (OSA); central sleep apnea (CSA); normal calm sleeping (NCS) without sleep-disordered breathing (SDB) episodes.
Epigenetic Approaches for Chemosensitization of Refractory Diffuse Large B-Cell Lymphomas
Authors: Steinhardt James J. , Gartenhaus Ronald B.
Published: September 2013

Summary: Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma, with the greatest challenge for improving patient survival being the management of chemorefractory disease upon relapse. Epigenetic dysregulation has been correlated with more-aggressive malignancies and chemoresistance. In this issue of Cancer Discovery, Clozel and colleagues show the potential for low-dose DNA methyltransferase inhibitors as both a rational and an effective neoadjuvant approach for chemosensitization in DLBCL. Cancer Discov; 3(9); 968–70. ©2013 AACR.

See related article by Clozel et al., p. 1002
Resistance Emerges to Second-Generation Antiandrogens in Prostate Cancer
Authors: Nelson William G. , Yegnasubramanian Srinivasan
Published: September 2013

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

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.
Genetic Association between Neurotrophin-3 Polymorphisms and Alzheimer's Disease in Japanese Patients
Authors: Nagata Tomoyuki , Shibata Nobuto , Shinagawa Shunichiro , Nakayama Ritsuko , Kuerban Bolati , Ohnuma Tohru , Arai Heii , Nakayama Kazuhiko , Yamada Hisashi
Published: September 2013

Background: Some polymorphisms of the neurotrophin family have previously been investigated as candidate genes for Alzheimer's disease (AD). In the present study, we examined whether neurotrophin-3 (NTF-3) polymorphisms are genetic risk factors in patients with AD. Methods: From a sample of 507 subjects, we recruited 248 age-matched subjects divided into 2 groups: AD patients (n = 143) and normal controls (NCs) (n = 105). We identified 3 representative NTF-3 single nucleotide polymorphisms (SNPs): rs6332, rs6489630, and rs4930767. Next, we statistically compared the allele frequencies of each SNP between the AD and NC groups in the early-onset (<65 years) cases under a more limited age-matched condition. Results: We found a significant association between rs6332 and the total group of AD patients (p = 0.013) and significant associations between both rs6332 (p = 0.033) and rs6489630 (p = 0.035) and early-onset AD patients. Conclusion: These results suggest that NTF-3 SNPs may not only be associated with AD itself, but also with early-onset AD in Japanese patients, assuming that the NTF-3 gene may have age-related effects on neurodegenerative diseases.
Aradidae from Vietnam II. Longitergus, a new genus and two new species of micropterous Mezirinae (Hemiptera: Heteroptera: Aradidae)
Authors: PHAM MINHLAN , BAI XIAOSHUAN , HEISS ERNST , CAI WANZHI
Published: September 2013

A new micropterous flat bug genus, Longitergus n.gen. with the species productus n.sp. and similis n.sp. from Vietnam, is described. A key to related Oriental genera is given and the diagnostic morphological characters of the new genus and species are illustrated.
A review of the genus Sinodorcadion Gressitt, 1939 with description of three new species from China (Coleoptera: Cerambycidae: Lamiinae)
Authors: XIE GUANG-LIN , SHI FU-MING , WANG WEN-KAI
Published: September 2013

The genus Sinodorcadion Gressitt, 1939 is reviewed. Three new species, S. jiangi sp. nov., S. magnispinicolle sp. nov. and S. punctuscapum sp. nov., are described. A key to all known Sinodorcadion species (five) is presented.
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

Future 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

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

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

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

A 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

The 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.
Custodians and Custodianship in Urban Neighborhoods
Authors: O’Brien Daniel Tumminelli
Published: September 2013

The paper introduces a methodology for using a city’s administrative data to study custodianship, or those behaviors aimed at preventing physical disorder in the public space. Custodianship was operationalized through requests for city services regarding public maintenance (e.g., potholes), provided by the database generated by Boston, MA’s hotline for requesting city services (i.e., 311). Users can register with the system, permitting analysis of individual differences in custodianship ( N = 12,361), including frequency of reports, variety of issues reported, and geographical range of reports. Home location (available for N = 7,433) was combined with Census statistics to infer demographic characteristics. Most (76%) reported one case. There was no evidence that individuals specialize on a single type of issue. Most reported issues over a narrow geographic range (80% within 2 blocks of home). Homeowners were three times more likely than renters to report public issues. A technique for estimating the home locations of users is also tested.
Prophylactic and Antidotal Effects of Hexamethylenetetramine Against Phosgene Poisoning in Rabbits
Authors: Frosolono M.F.
Published: September 2013

New Zealand white rabbits were exposed to phosgene doses, expressed as Ct factors, of 125-3120 ppm·min. Hexamethylenetetramine (HMT), 0.3 gm/kg as a 40% aqueous solution, was injected via an ear vein into separate groups of animals at 5-10 min pre-exposure or at 15 min post-exposure to the gas. Non-exposed and exposed, non-HMT-treated animals served as controls. As assessed by survival times, gross morphology of the lungs, percent lung water measurements, serum LDH values, and respiratory gas parameters, pre-exposure administration of HMT at Ct factors as high as 3120 ppm·min provided significant prophylaxis against the effects of phosgene. Post-exposure administration of HMT, however, provided no antidotal effect even when administered as soon as 15 min after exposure to 125 ppm·min phosgene.
Improving the Use of Epidemiologic Data in Health Risk Assessment
Authors: Erdreich Linda S. , Burnett Carol
Published: September 2013

Epidemiologic data with quantitative exposure measures is infrequently available for specific environmental agents. This lack of exposure measures creates confusion in interpreting epidemiologic data and therefore has impeded its efficient use in health risk analysis. This paper discusses screening and evaluating epidemiologic studies for use in assessing health risk. It also describes the larger role of epidemiology in reducing uncertainties in risk analysis. The approach recognizes that the various designs used to increase statistical power and to control for covariables have different functions in contemporary risk assessment as practiced by regulatory agencies. Each of these study designs is categorized for its role in risk analysis as useful for hazard identification or for dose-response assessment. Studies presenting geographic correlations are construed to be not directly useful in health risk assessment. The numerical level of the exposure data is a deciding factor in using valid epidemiologic studies. However, data measured on an ordinal scale can be used in qualitative assessments and can demonstrate the strength of the relationship. The application of this procedure is illustrated using epidemiologic studies on the carcinogenicity of chemicals contaminated with dioxins.
Implications for Risk Assessment of Host Factors Causing Large Pharmacokinetic Variations
Authors: Vesell Elliot S.
Published: September 2013

Normal human subjects vary widely in their capacity to eliminate many drugs and environmental chemicals. These variations range in magnitude from fourfold to fortyfold depending on the drug and the population studied. Pharmacogenetics deals with only one of many host factors responsible for these large pharmacokinetic differences. Age, sex, diet and exposure to other drugs and chemicals, including oral contraceptives, ethanol and cigarette smoking, can alter the genetically determined rate at which a particular subject eliminates drugs and environmental chemicals. These elimination rates, therefore, are dynamic and change even in the same subject with time and condition. Regulatory legislation has only recently begun to recognize this very broad spectrum of human susceptibility and the existence of multiple special subgroups of particularly sensitive subjects. In setting standards for environmental chemicals, EPA and NIOSH have attempted to protect the most sensitive humans and should be encouraged to continue this policy. For some drugs and environmental chemicals, the commonly used safety factor of 100 may be too low; for these chemicals large, interindividual pharmacokinetic variations produced by pharmacogenetic and other host factors may make a safety factor of 400 or 500 more adequate.
The Effects of Nitrous Oxide After Exposure During Middle and Late Gestation
Authors: Tassinari Melissa S. , Mullenix Phyllis J. , Moore Paul A.
Published: September 2013

Recent evidence has indicated that the anesthetic gas nitrous oxide (N20) is teratogenic to rats if exposed during the organogenesis phase of gestation. Little is known, however, of the anatomical or functional consequences of exposures occurring later in gestation when the brain is developing. Timed pregnant Sprague-Dawley rats were exposed to 75% N2O/25% O2 using one of the following pro tocols: 24 hr exposures on gestational days 11-15 or 16-20; or 8 hr exposures on gestational days 9-13, 11-15, 14-15 or day 1 5 only. Both 24 hr exposure protocols significantly reduced fetal and ma ternal body weight, an effect not observed after the 8 hr exposures. No N20 exposure resulted in gross morphological or skeletal changes. Likewise, no significant effects on total protein and DNA levels in fetal liver and brain tissues could be found subsequent to 24 hr exposures on days 16-20; or on one, three or six days follow ing an 8 hr exposure on day 15. Evaluations of postnatal growth and neurological development in pups prenatally exposed for 8 hr on days 14 and 15 revealed two noteworthy effects. Their rate of growth in body weight was greater with respect to controls between the ages of 14 and 21 days, especially in the males. Also, reflex sus pension was reduced, significantly so in the females. In conclusion, unlike 24 hr exposures, multiple 8 hr exposures to nitrous oxide during the middle to late stages of gestation did not produce effects detectable with standard teratological measures. Subtle differences in growth rate and reflex suspension, however, indicated that nor mal development had been interrupted, but its clear distinction as a lasting effect requires additional measures of function.
Airway Sensitivity of Asthmatics To Sulfur Dioxide
Authors: Horstman Donald , Roger L. Jack , Kehrl Howard , Hazucha Milan
Published: September 2013

The purpose of this study was to describe for asthmatic subjects the distribution of individual bronchial sensitivity to sulfur dioxide (SO2). Subjects were nonsmoking male asthmatics (n = 27) who were sensitive to inhaled methacholine. None of the subjects used corticosteroids or cromolyn sodium. Oral medications were with held for 48 hr, inhaled medications for 12 hr prior to all testing. Each subject participated in four separate randomly ordered 10 min exposures to 0.00, 0.25, 0.50 and 1.00 ppm SO2 at 26° C, 70% relative humidity. During exposures, subjects breathed naturally and performed moderate exercise (VE, normalized for body surface area = 21 l/m2 x min). Before and 3 min after exposure, specific airway resistance (SRaw) was measured by body plethysmography. Those subjects whose SRaw was not doubled by exposure to 1.00 ppm were also exposed to 2.00 ppm S02. Dose response curves (relative change in SRaw, corrected for change in clean air vs S02 concentration) were constructed for each subject. Bronchial sensi tivity to SO2 [PC(SO2)], defined as the concentration of S02 which provoked an increase in SRaw 100% greater than the response to clean air, was determined. Substantial variability in sensitivity was observed: for 23 subjects, PC(SO2) ranged between 0.28 and 1.90 ppm, while for the remaining 4 subjects, it was greater than 2.00- ppm S02. The median PC(SO2) was 0.75 ppm SO2, and 6 subjects had a PC(SO2) of less than 0.50 ppm. PC(SO2) was not related (r = 0.31) to airway sensitivity to methacholine.
Percutaneous Absorption of Benzo[a]Pyrene in the Rat: Comparison of in Vivo and in Vitro Results
Authors: Yang Joseph J. , Roy Timothy A. , Mackerer Carl R.
Published: September 2013

Percutaneous absorption of 14C-labeled benzo[a]pyrene (BaP) was studied in five-day in vivo and in vitro experiments with female Sprague- Dawley rats following single topical doses of 9-10 μ g/cm2. The in vivo percutaneous absorption was measured by the presence of 14C radioactivity in urine, feces and tissues. In vitro percutaneous absorp tion was measured with excised (non-viable) skin in Franz-type diffusion cells. Several modifications of standard diffusion cell techniques which are known to enhance the transport of lipophilic compounds were evaluated. In vitro penetration was determined by directly measuring the level of 14C radioactivity in the receptorfluid. BaP was observed to readily penetrate in vivo with a total of 46.2% (n = 4, SD = 3.4%) of the applied dose being absorbed over five days. In in vitro experi ments using a ∼350 μm-thick skin section and normal saline receptor solution, only 2.1 % of the applied BaP diffused into the receptor fluid over five days. In in vitro experiments usingfull-thickness skin and a 6% solution ofnonionic surfactant receptor fluid, 28.0% of the applied BaP diffused into the receptor fluid over five days. When both a ∼350 μm-thick skin section and a 6% surfactant receptor solution were used in vitro, 49.9% (n = 4, SD = 3.1%) of the BaP dose was found in the receptor fluid after five days. The results show that the modified in vitro method is suitable for studying percutaneous absorption of lipophilic compounds such as BaP.
Alteration of the Redox State of Nadph and Glutathione in Perfused Rabbit Lung By Paraquat
Authors: Brigelius Regina , Dostal Lori A. , Horton Julie K. , Bend John R.
Published: September 2013

The glutathione and NADP + status of perfused rabbit lung was deter mined both before and after perfusion with 1 mM paraquat. The pul monary glutathione redox state was similar to that of liver, having a glutathione/glutathione disulfide ratio of about 240. This ratio was lower in lungs perfused with glucose-free medium, a condition in which NADPH probably becomes limiting. Perfusion with paraquat signifi cantly increased the pulmonary glutathione disulfide content, particu larly in the absence of glucose, resulting in a glutathionelglutathione disulfide ratio of <100. NADP+ levels in rabbit lung were increased approximately two-fold by perfusion with paraquat in medium con taining glucose and three-fold in the absence of glucose.
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
Evaluation of Immunotoxicity in a Subchronic Feeding Study of Triphenyl Phosphate
Authors: Hinton Dennis M. , Jessop John J. , Arnold Alphonso , Albert Richard H. , Hines Fred A.
Published: September 2013

Triphenyl phosphate (TPP), a potential food contaminant, was fed to weanling Spartan Sprague-Dawley rats at dose levels of 0, 0.25, 0.5, 0.75, and 1.0%for 120 days. The immunotoxicity evaluation, planned as a minimum testing model in a subchronic study design as well as to provide information on TPP, was performed along with the routine testing of a separate group of animals. Traditional measures were made of growth and food consumption, total pro tein analysis, electrophoretic analyses of serum proteins, lymphoid organ weights in relation to growth, and histopathology, with expanded immunohistochemical evaluation of B- and T- lymphocyte regions in spleen, thymus, and lymph nodes, using immunoperoxidase staining. Assessment was made of the humoral response to a T-lymphocyte-dependent antigen, sheep red blood cells, and was begun at midterm of the feeding period for the pri mary response followed by secondary and teritary booster immuni zations at 3-week intervals. The kinetics of the responses were measured by hemolysin assay of relative antibody titers at days 3, 4, 5, and 6 postinjection. No significant effects on the responses were noted for either sex at any of the dose levels tested. The only effects noted were a decreased rate of growth at high levels of TPP and increases in the levels of a- and β-globulins suggestive of increased hepatic activity.
Percutaneous and Oral Absorption of Chlorinated Paraffins in the Rat
Authors: Yang J.J. , Roy T.A. , Neil W. , Krueger A.J. , Mackerer C.R.
Published: September 2013

Parallel percutaneous absorption studies of two14 C-labelled chlori nated paraffins (C18, 50-53% chlorination; C28, 47% chlorination) were carried out in the Sprague-Dawley rat. The dermally applied dose (66 mg/cm2) was approximately equivalent to 2.0 g/kg of body weight. An oral absorption study with the C18-chlorinated paraffin (0.5 g/kg) was carried out in rats for comparison. Less than 1% of the dermally applied dose of [1- 14 C]polychloro octadecane (50-53% chlorination) and less than 0.1% of the applied dose of [14,15-14 C]polychlorooctacosane (47% chlorination) were recovered in excreta, expired air and tissues after 96 hours. In con trast, approximately 86% of the orally administered dose of [1-14 C] polychlorooctadecane (0.5 g/kg) was recovered. These results indi cate that rat skin acts as an effective barrier to chlorinated paraffins containing eighteen or more carbons and more than 40% chlorine by weight. The oral absorption of the C18 chlorinated paraffin can be estimated to be nearly 100 times greater than its dermal absorp tion. Based on current toxicity results from rodent experiments and these present findings, chlorinated paraffins of the type tested would be expected to have little or no effect in animals as a result of dermal exposure. It is reasonable to assume that such chlori nated paraffins are unlikely to be systemically toxic to humans by skin contact under normal conditions of production and use.
Hyalin Droplet Nephrosis in Male Fischer-344 Rats Following Inhalation of Diisobutyl Ketone
Authors: Dodd Darol E. , Losco Patricia E. , Troup Catherine M. , Pritts Irvin M. , Tyler Tipton R.
Published: September 2013

Four groups, each consisting of 10 male and 10 female Fischer-344 rats, were exposed 6 h/day, 5 days/week, for 9 days to diisobutyl ketone (DIBK) vapor at concentrations of 905, 300, 98, or 0 (con trol) ppm. An additional 10 rats/sex were assigned to the 905 and 0 ppm groups and allowed two weeks recovery prior to sacrifice. Rats exposed to 905 ppm had mild ocular irritation (lacrimation) and evidence of kidney toxicity, manifested as: 1) an increase in absolute and relative (as a percentage of body weight) kidney weights, 2) an increase in urine volume (and water intake) with a concomitant decrease in urine osmolality (males only), and 3) an increase in severity of hyalin droplet nephrosis in the proximal tubules (males only). Absolute and relative liver weights were also increased in both male and female rats of the 905 and 300 ppm groups. These effects either disappeared or lessened in severity fol lowing the 2-week recovery period. Male rats exposed to 300 ppm had similar renal alterations to the males of the 905 ppm group, although the alterations were fewer in number and smaller in mag nitude. Kidney weights and renal histology of the males of the 98 ppm group were similar to the control male rats, although an increase in urine volume with a decrease in urine osmolality was observed. The kidney findings in this study were not surprising because of the chemical relationship of DIBK with other aliphatic ketones (e.g., methyl isobutyl ketone, methyl isoamyl ketone) which, after repeated inhalation exposure, cause hyalin droplet nephropathy in male rats. The significance of this male rat nephro sis with regard to human exposure is unknown.
Automated High Performance Liquid Chromatography and Liquid Scintillation Counting Determination of Pesticide Mixture Octanol/Water Partition Rates
Authors: Moody Richard P. , Carroll Jeannette M. , Kresta Anne M.E.
Published: September 2013

Two novel methods are reported for measuring octanol/water par tition rates of pesticides. A liquid scintillation counting (LSC) method was developed for automated monitoring of14 C-labeled pesticides partitioning in biphasic water/octanol cocktail systems with limited success. A high performance liquid chromatography (HPLC) method was developed for automated partition rate moni toring of several constituents in a pesticide mixture, simultane ously. The mean log Kow ± SD determined from triplicate experi mental runs were for: 2,4-D-DMA (2,4-dichlorophenoxyacetic acid dimethylamine), 0.65 ± .17; Deet (N,N-diethyl-m-toluamide), 2.02 ± .01; Guthion (O,O-dimethyl-S-(4-oxo-1,2,3-benzotriazin- 3(4H)-ylmethyl)phosphorodithioate), 2.43 ± .03; Methyl- Parathion (O,O-dimethyl-O-(p-nitrophenyl)phosphorothioate), 2.68 ± .05; and Fenitrothion (O,O-dimethyl O-(4-nitro-m-tolyl) phosphorothioate), 3.16 ± .03. A strong positive linear correlation (r = .9979) was obtained between log Kow and log k' (log Kow = 2.35 (log k') + 0.63). The advantages that this automated procedure has in comparison with the standard manual shake-flask procedure are discussed.
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.