bluuebunny/crossref_metadata_2025 huggingface dataset:
Land use and climate change impacts on the hydrology of the upper Mara River Basin, Kenya: results of a modeling study to support better resource management
Authors: Mango L. M. , Melesse A. M. , McClain M. E. , Gann D. , Setegn S. G.
Published: July 2011

Abstract. Some of the most valued natural and cultural landscapes on Earth lie in river basins that are poorly gauged and have incomplete historical climate and runoff records. The Mara River Basin of East Africa is such a basin. It hosts the internationally renowned Mara-Serengeti landscape as well as a rich mixture of indigenous cultures. The Mara River is the sole source of surface water to the landscape during the dry season and periods of drought. During recent years, the flow of the Mara River has become increasingly erratic, especially in the upper reaches, and resource managers are hampered by a lack of understanding of the relative influence of different sources of flow alteration. Uncertainties about the impacts of future climate change compound the challenges. We applied the Soil Water Assessment Tool (SWAT) to investigate the response of the headwater hydrology of the Mara River to scenarios of continued land use change and projected climate change. Under the data-scarce conditions of the basin, model performance was improved using satellite-based estimated rainfall data, which may also improve the usefulness of runoff models in other parts of East Africa. The results of the analysis indicate that any further conversion of forests to agriculture and grassland in the basin headwaters is likely to reduce dry season flows and increase peak flows, leading to greater water scarcity at critical times of the year and exacerbating erosion on hillslopes. Most climate change projections for the region call for modest and seasonally variable increases in precipitation (5–10 %) accompanied by increases in temperature (2.5–3.5 °C). Simulated runoff responses to climate change scenarios were non-linear and suggest the basin is highly vulnerable under low (−3 %) and high (+25 %) extremes of projected precipitation changes, but under median projections (+7 %) there is little impact on annual water yields or mean discharge. Modest increases in precipitation are partitioned largely to increased evapotranspiration. Overall, model results support the existing efforts of Mara water resource managers to protect headwater forests and indicate that additional emphasis should be placed on improving land management practices that enhance infiltration and aquifer recharge as part of a wider program of climate change adaptation.
The "tipping" temperature within Subglacial Lake Ellsworth, West Antarctica and its implications for lake access
Authors: Thoma M. , Grosfeld K. , Mayer C. , Smith A. M. , Woodward J. , Ross N.
Published: July 2011

Abstract. We present results from new geophysical data allowing modelling of the water flow within Subglacial Lake Ellsworth (SLE), West Antarctica. Our simulations indicate that this lake has a novel temperature distribution due to significantly thinner ice than other surveyed subglacial lakes. The critical pressure boundary (tipping depth), established from the semi-empirical Equation of State, defines whether the lake's flow regime is convective or stratified. It passes through SLE and separates different temperature (and flow) regimes on either side of the lake. Our results have implications for the location of proposed access holes into SLE, the choice of which will depend on scientific or operational priorities. If an understanding of subglacial lake water properties and dynamics is the priority, holes are required in a basal freezing area at the North end of the lake. This would be the preferred priority suggested by this paper, requiring temperature and salinity profiles in the water column. A location near the Southern end, where bottom currents are lowest, is optimum for detecting the record of life in the bed sediments; to minimise operational risk and maximise the time span of a bed sediment core, a location close to the middle of the lake, where the basal interface is melting and the lake bed is at its deepest, remains the best choice. Considering potential lake-water salinity and ice-density variations, we estimate the critical tipping depth, separating different temperature regimes within subglacial lakes, to be in about 2900 to 3045 m depth.
Getting around Antarctica: new high-resolution mappings of the grounded and freely-floating boundaries of the Antarctic ice sheet created for the International Polar Year
Authors: Bindschadler R. , Choi H. , Wichlacz A. , Bingham R. , Bohlander J. , Brunt K. , Corr H. , Drews R. , Fricker H. , Hall M. , Hindmarsh R. , Kohler J. , Padman L. , Rack W. , Rotschky G. , Urbini S. , Vornberger P. , Young N.
Published: July 2011

Abstract. Two ice-dynamic transitions of the Antarctic ice sheet – the boundary of grounded ice features and the freely-floating boundary – are mapped at 15-m resolution by participants of the International Polar Year project ASAID using customized software combining Landsat-7 imagery and ICESat/GLAS laser altimetry. The grounded ice boundary is 53 610 km long; 74 % abuts to floating ice shelves or outlet glaciers, 19 % is adjacent to open or sea-ice covered ocean, and 7 % of the boundary ice terminates on land. The freely-floating boundary, called here the hydrostatic line, is the most landward position on ice shelves that expresses the full amplitude of oscillating ocean tides. It extends 27 521 km and is discontinuous. Positional (one-sigma) accuracies of the grounded ice boundary vary an order of magnitude ranging from ±52 m for the land and open-ocean terminating segments to ±502 m for the outlet glaciers. The hydrostatic line is less well positioned with errors over 2 km. Elevations along each line are selected from 6 candidate digital elevation models based on their agreement with ICESat elevation values and surface shape inferred from the Landsat imagery. Elevations along the hydrostatic line are converted to ice thicknesses by applying a firn-correction factor and a flotation criterion. BEDMAP-compiled data and other airborne data are compared to the ASAID elevations and ice thicknesses to arrive at quantitative (one-sigma) uncertainties of surface elevations of ±3.6, ±9.6, ±11.4, ±30 and ±100 m for five ASAID-assigned confidence levels. Over one-half of the surface elevations along the grounded ice boundary and over one-third of the hydrostatic line elevations are ranked in the highest two confidence categories. A comparison between ASAID-calculated ice shelf thicknesses and BEDMAP-compiled data indicate a thin-ice bias of 41.2 ± 71.3 m for the ASAID ice thicknesses. The relationship between the seaward offset of the hydrostatic line from the grounded ice boundary only weakly matches a prediction based on beam theory. The mapped products along with the customized software to generate them and a variety of intermediate products are available from the National Snow and Ice Data Center.
The Moderating Effect of Ecphoric Experience on Post‐identification Feedback: A Critical Test of the Cues‐based Inference Conceptualization
Authors: Charman Steve D. , Wells Gary L.
Published: July 2011

Confidence inflation from confirming post‐identification feedback is greater when the eyewitness is inaccurate than when the eyewitness is accurate, which is evidence that witnesses infer their confidence from feedback only to the extent that their internal cues are weak. But the accurate/inaccurate asymmetry has alternative interpretations. A critical test between these interpretations was conducted by including disconfirming feedback conditions. Student participants (n = 404) witnessed a mock crime, had either a strong or weak ecphoric experience when making their line‐up identifications, and subsequently received no feedback, confirming feedback, or disconfirming feedback. Consistent with a cues‐based conceptualization of the feedback effect, disconfirming feedback influenced witnesses with weak ecphoric experiences more than witnesses with strong ecphoric experiences, ironically increasing the confidence‐accuracy relation. Copyright © 2011 John Wiley & Sons, Ltd.
Investigation of Stress Induced Phase Transformation in TRIP‐Steel/Mg‐PSZ Composites Using EBSD
Authors: Berek Harry , Aneziris Christos Georgios , Hasterok Manuel , Biermann Horst , Wolf Steffen , Krüger Lutz
Published: July 2011

Failure tolerant metal matrix composites (MMCs) can be created by combining ceramics with ductile metals. In the frame of the present work open cell foam structures were produced. They contain 95 vol% TRIP‐steel (transformation induced plasticity) and 5 vol% zirconia. The goal was to show the effect of transformation toughening within the zirconia particles embedded in the steel matrix during compressive deformation. Deformation induced phase transformation could be shown by using electron backscatter diffraction (EBSD) in combination with energy dispersive X‐ray spectroscopy (EDX).
Local State‐of‐Charge Mapping of Lithium‐Ion Battery Electrodes
Authors: Nanda Jagjit , Remillard Jeffrey , O'Neill Ann , Bernardi Dawn , Ro Tina , Nietering Kenneth E. , Go Joo‐Young , Miller Ted J.
Published: July 2011

Current lithium‐ion battery technology is gearing towards meeting the robust demand of power and energy requirements for all‐electric transportation without compromising on the safety, performance, and cycle life. The state‐of‐charge (SOC) of a Li‐ion cell can be a macroscopic indicator of the state‐of‐health of the battery. The microscopic origin of the SOC relates to the local lithium content in individual electrode particles and the effective ability of Li‐ions to transport or shuttle between the redox couples through the cell geometric boundaries. Herein, micrometer‐resolved Raman mapping of a transition‐metal‐based oxide positive electrode, Li1‐x(NiyCozAl1‐y‐z)O2, maintained at different SOCs, is shown. An attempt has been made to link the underlying changes to the composition and structural integrity at the individual particle level. Furthermore, an SOC distribution at macroscopic length scale of the electrodes is presented.
Solvent‐Induced Morphology in Polymer‐Based Systems for Organic Photovoltaics
Authors: Ruderer Matthias A. , Guo Shuai , Meier Robert , Chiang Hsin‐Yin , Körstgens Volker , Wiedersich Johannes , Perlich Jan , Roth Stephan V. , Müller‐Buschbaum Peter
Published: July 2011

Studies on the influence of four different solvents on the morphology and photovoltaic performance of bulk‐heterojunction films made of poly(3‐hexylthiophene) (P3HT) and [6,6]‐phenyl‐C61 butyric acid methyl ester (PCBM) via spin‐coating for photovoltaic applications are reported. Solvent‐dependent PCBM cluster formation and P3HT crystallization during thermal annealing are investigated with optical microscopy and grazing‐incidence wide‐angle X‐ray scattering (GIWAXS) and are found to be insufficient to explain the differences in device performance. A combination of atomic force microscopy (AFM), X‐ray reflectivity (XRR), and grazing‐incidence small‐angle X‐ray scattering (GISAXS) investigations results in detailed knowledge of the inner film morphology of P3HT:PCBM films. Vertical and lateral phase separation occurs during spin‐coating and annealing, depending on the solvent used. The findings are summarized in schematics and compared with the IV characteristics. The main influence on the photovoltaic performance arises from the vertical material composition and the existence of lateral phase separation fitting to the exciton diffusion length. Absorption and photoluminescence measurements complement the structural analysis.
Enhanced Efficiency in Plastic Solar Cells via Energy Matched Solution Processed NiOx Interlayers
Authors: Steirer K. Xerxes , Ndione Paul F. , Widjonarko N. Edwin , Lloyd Matthew T. , Meyer Jens , Ratcliff Erin L. , Kahn Antoine , Armstrong Neal R. , Curtis Calvin J. , Ginley David S. , Berry Joseph J. , Olson Dana C.
Published: July 2011

We show enhanced efficiency and stability of a high performance organic solar cell (OPV) when the work‐function of the hole collecting indium‐tin oxide (ITO) contact, modified with a solution‐processed nickel oxide (NiOx) hole‐transport layer (HTL), is matched to the ionization potential of the donor material in a bulk‐heterojunction solar cell. Addition of the NiOx HTL to the hole collecting contact results in a power conversion efficiency (PCE) of 6.7%, which is a 17.3% net increase in performance over the 5.7% PCE achieved with a poly(3,4‐ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) HTL on ITO. The impact of these NiOx films is evaluated through optical and electronic measurements as well as device modeling. The valence and conduction band energies for the NiOx HTL are characterized in detail through photoelectron spectroscopy studies while spectroscopic ellipsometry is used to characterize the optical properties. Oxygen plasma treatment of the NiOx HTL is shown to provide superior contact properties by increasing the ITO/NiOx contact work‐function by 500 meV. Enhancement of device performance is attributed to reduction of the band edge energy offset at the ITO/NiOx interface with the poly(N‐9′‐heptadecanyl‐2,7‐carbazole‐alt‐5,5‐(4′,7′‐di‐2‐thienyl‐2′,1′,3′‐benzothidiazole) (PCDTBT):[6,6]‐phenyl‐C61 butyric acid methyl ester PCBM and [6,6]‐phenyl‐C71 butyric acid methyl ester (PC70BM) active layer. A high work‐function hole collecting contact is therefore the appropriate choice for high ionization potential donor materials in order to maximize OPV performance.
A comparison of the home range sizes of mainland and island populations of black‐faced lion tamarins (Leontopithecus caissara) using different spatial analysis
Authors: Nascimento Alexandre T. Amaral , Schmidlin Lucia A.J. , Valladares‐Padua Claudio B. , Matushima Eliana R. , Verdade Luciano M.
Published: July 2011

The critically endangered black‐faced lion tamarin,Leontopithecus caissara, has a restricted geographical distribution consisting of small mainland and island populations, each with distinct habitats in coastal southeastern Brazil. Necessary conservation management actions require an assessment of whether differences in habitats are reflected in use of space by the species. We studied two tamarin groups on the mainland at São Paulo state between August 2005 and March 2007, and compared the results with data from Superagui Island. Three home range estimators were used: minimum convex polygon (MCP), Kernel, and the new technique presented dissolved monthly polygons (DMP). These resulted, respectively, in home ranges of 345, 297, and 282ha for the 12‐month duration of the study. Spatial overlap of mainland groups was extensive, whereas temporal overlap was not, a pattern that indicates resource partitioning is an important strategy to avoid intraspecific competition.L. caissaralarge home ranges seem to be dynamic, with constant incorporation of new areas and abandonment of others through time. The main difference between mainland and island groups is the amount and variety of sleeping sites. A better understanding of the home range sizes, day range lengths, and territorial behavior of this species will aid in developing better management strategies for its protection. Additionally, the presented DMP protocol is a useful improvement over the MCP method as it results in more realistic home range sizes for wildlife species. Am. J. Primatol. 73:1114–1126, 2011. © 2011 Wiley Periodicals, Inc.
Seasonality of group size, feeding, and breeding in wild red‐shanked douc langurs (Lao PDR)
Authors: Phiapalath Phaivanh , Borries Carola , Suwanwaree Pongthep
Published: July 2011

In Asian colobines, small one‐male groups (OMG) seem to predominate alongside all‐male groups (AMG), while larger multimale groups (MMG) are rare, but are reported for Hanuman langurs and red‐shanked douc langurs. Recently, however, it has been speculated that the genus Pygathrix could have multilevel societies based on (1) a theoretical extension of the multilevel societies found in Rhinopithecus to all odd‐nosed colobines and (2) first data for black‐shanked douc langurs. This assumes bands composed of small OMG with a skewed adult sex ratio. Band size may vary with seasonal food availability resulting in smaller bands when feeding competition is increased. To investigate the social organization of red‐shanked douc langurs and potential seasonal influences, we observed 2 unhabituated groups at Hin Namno National Protected Area, Lao PDR from March 2007 to August 2008 for 803 hr. We recorded births and performed group counts and scan sampling of feeding behavior. Most births (79% of N = 15) occurred from June–September, indicating a 4‐month peak conception season from November to February. Group size averaged 24.5 individuals (range 17–45) with 2.45 adult males (range 1–4). Although the smaller group remained at a stable size (about 18 individuals), the larger group reduced from about 45 to 25 individuals during the 7‐months long lean season, when less than 50% of the feeding time was spent on fruits. This suggests feeding competition as a potential cause of seasonal variation in group size. With 1.9 females per male the skew in adult sex ratio was much lower compared with Rhinopithecus, indicating MMG rather than multilevel societies. However, data on the spacing and interaction patterns between recognized individuals need to be collected and analyzed before the social organization can be determined. Detailed ecological data are furthermore required to investigate the basis for the seasonal changes in group size found. Am. J. Primatol. 73:1134–1144, 2011. © 2011 Wiley Periodicals, Inc.
The role of TRAIL in mediating autophagy in myositis skeletal muscle: A potential nonimmune mechanism of muscle damage
Authors: Alger Heather M. , Raben Nina , Pistilli Emidio , Francia Dwight L. , Rawat Rashmi , Getnet Derese , Ghimbovschi Svetlana , Chen Yi‐Wen , Lundberg Ingrid E. , Nagaraju Kanneboyina
Published: July 2011

Objective

Multinucleated cells are relatively resistant to classic apoptosis, and the factors initiating cell death and damage in myositis are not well defined. We hypothesized that nonimmune autophagic cell death may play a role in muscle fiber damage. Recent reports indicate that TRAIL may induce both NF‐κB activation and autophagic cell death in other systems. We undertook this study to investigate the role of TRAIL in cell death and pathogenesis in vitro and in vivo, using myositis muscle tissues from humans and mice.

Methods

Gene expression profiling was performed in myositis patient and control muscle specimens. Immunohistochemistry analysis was performed to confirm the gene array findings. We also analyzed TRAIL‐induced cell death (apoptosis and autophagy) and NF‐κB activation in vitro in cultured cells.

Results

TRAIL was expressed predominantly in myositis muscle fibers, but not in biopsy specimens from normal or other dystrophic‐diseased muscle. Autophagy markers were up‐regulated in humans with myositis and in mouse models of myositis. TRAIL expression was restricted to regenerating/atrophic areas of muscle fascicles, blood vessels, and infiltrating lymphocytes. TRAIL induced NF‐κB activation and IκB degradation in cultured cells that are resistant to TRAIL‐induced apoptosis but that undergo autophagic cell death.

Conclusion

Our data demonstrate that TRAIL is expressed in myositis muscle and may mediate both activation of NF‐κB and autophagic cell death in myositis. Thus, this nonimmune pathway may be an attractive target for therapeutic intervention in myositis.
A one‐year, phase I/IIa, open‐label pilot trial of imatinib mesylate in the treatment of systemic sclerosis–associated active interstitial lung disease
Authors: Khanna Dinesh , Saggar Rajeev , Mayes Maureen D. , Abtin Fereidoun , Clements Philip J. , Maranian Paul , Assassi Shervin , Saggar Rajan , Singh Ram R. , Furst Daniel E.
Published: July 2011

Objective

Transforming growth factor β (TGFβ) and platelet‐derived growth factor (PDGF) may play a critical role in systemic sclerosis (SSc)–related interstitial lung disease (ILD), and imatinib is a potent inhibitor of TGFβ and PDGF production. In this 1‐year, phase I/IIa open‐label pilot study of imatinib in patients with SSc‐related active ILD, our primary aim was to assess the safety of imatinib; we also explored its efficacy.

Methods

We recruited 20 SSc patients with a forced vital capacity (FVC) of <85% predicted, dyspnea on exertion, and presence of a ground‐glass appearance on high‐resolution computed tomography. Patients received oral therapy with imatinib (up to 600 mg/day) for a period of 1 year. Adverse events were recorded, pulmonary function was tested, and the modified Rodnan skin thickness score (MRSS) was assessed every 3 months. The course of changes in lung function, the Health Assessment Questionnaire (HAQ) disability index (DI), and the MRSS were modeled over the period of study to explore treatment efficacy.

Results

The majority of patients were female (65%), Caucasian (75%), and had diffuse cutaneous SSc (70%). At baseline, the mean ± SD FVC % predicted was 65.2 ± 14.0 and the mean ± SD MRSS was 18.7 ± 10.1. The mean ± SD dosage of imatinib was 445 ± 125 mg/day. Of the 20 SSc patients, 12 completed the study, 7 discontinued because of adverse events (AEs), and 1 patient was lost to followup. Common AEs (≥20%) included fatigue, facial/lower extremity edema, nausea and vomiting, diarrhea, generalized rash, and new‐onset proteinuria. Treatment with imatinib showed a trend toward improvement in the FVC % predicted (1.74%; P not significant) and the MRSS (3.9 units; P < 0.001).

Conclusion

Use of high‐dose daily therapy with imatinib (600 mg/day) in SSc patients with ILD was associated with a large number of AEs. Our experience with AEs suggests that dosages of imatinib lower than 600 mg/day may be appropriate and that further dose ranging analysis is needed in order to understand the therapeutic index of imatinib in SSc.
Imatinib in active diffuse cutaneous systemic sclerosis: Results of a six‐month, randomized, double‐blind, placebo‐controlled, proof‐of‐concept pilot study at a single center
Authors: Pope Janet , McBain Donna , Petrlich Lisa , Watson Sharon , Vanderhoek Louise , de Leon Faye , Seney Shannon , Summers Kelly
Published: July 2011

Objective

To better understand the feasibility of using imatinib, a tyrosine kinase inhibitor, to treat active diffuse cutaneous systemic sclerosis (dcSSc).

Methods

We performed a 6‐month, randomized, double‐blind, placebo‐controlled, proof‐of‐concept pilot study of imatinib in patients with active dcSSc. Data on safety, modified Rodnan skin thickness scores (MRSS), Health Assessment Questionnaire (HAQ) scores, patient's and physician's global assessments (100‐mm visual analog scale), and biomarkers in serum and skin biopsy samples were collected. We used a 4:1 randomization strategy (imatinib 200 mg administered twice a day versus placebo), stratifying according to current use of methotrexate. The plan was to enroll 20 dcSSc patients.

Results

After enrolling 10 patients (9 receiving active drug and 1 receiving placebo), we found poor tolerability and high rates of adverse events with imatinib, and study enrollment was discontinued. There was no significant difference in the mean MRSS in all patients who took imatinib (31.1 at baseline versus 29.4 at 6 months) or in only those who completed 6 months of imatinib (31.0 at baseline versus 30.3 at 6 months), and there was no difference in the C‐reactive protein level, erythrocyte sedimentation rate, physician's global assessment, patient's global assessment, response to the Health Transition query, or the HAQ scores between those who did and those who did not complete 6 months of therapy. Side effects were edema, fluid retention, fatigue, nausea, cramps/myalgias, diarrhea, alopecia, and anemia. Most side effects occurred within the first week of treatment, and even when imatinib was reintroduced at a lower dosage (200 mg daily), it was poorly tolerated. Two patients were hospitalized because of side effects of the medication. In general, biomarker levels in plasma and skin did not change.

Conclusion

Imatinib was poorly tolerated, and this could limit its application in SSc. The study was too small to form conclusions about the efficacy of imatinib in SSc.
MicroRNA gene expression signatures in the developing neural tube
Authors: Mukhopadhyay Partha , Brock Guy , Appana Savitri , Webb Cynthia , Greene Robert M. , Pisano M. Michele
Published: July 2011

BACKGROUND:Neurulation requires precise, spatio‐temporal expression of numerous genes and coordinated interaction of signal transduction and gene regulatory networks, disruption of which may contribute to the etiology of neural tube defects (NTDs). MicroRNAs (miRNAs) are key modulators of cell and tissue differentiation. To define potential roles of miRNAs in development of the murine neural tube (NT), miRNA microarray analysis was conducted to establish expression profiles, and identify miRNA target genes and functional gene networks. METHODS:The miRNA expression profiles in murine embryonic NTs derived from gestational days 8.5, 9.0, and 9.5 were defined and compared utilizing miRXplore microarrays from Miltenyi Biotec GmbH, Bergisch Gladbach, Germany. Gene expression changes were verified by TaqMan quantitative Real‐Time PCR. The clValid R package and the UPGMA (hierarchical) clustering method were utilized for cluster analysis of the microarray data. Functional associations among selected miRNAs were examined via Ingenuity Pathway Analysis. RESULTS:The miRXplore chips enabled examination of 609 murine miRNAs. Expression of approximately 12% of these was detected in murine embryonic NTs. Clustering analysis revealed several developmentally regulated expression clusters among these expressed genes. Target analysis of differentially expressed miRNAs enabled identification of numerous target genes associated with cellular processes essential for normal NT development. Utilization of Ingenuity Pathway Analysis revealed interactive biologic networks which connected differentially expressed miRNAs with their target genes, and highlighted functional relationships. CONCLUSIONS: The present study defined unique gene expression signatures of a range of miRNAs in the developing NT during the critical period of NT morphogenesis. Analysis of miRNA target genes and gene interaction pathways revealed that specific miRNAs might direct expression of numerous genes encoding proteins, which have been shown to be indispensable for normal neurulation. This study is the first to identify miRNA expression profiles and their potential regulatory networks in the developing mammalian NT. Birth Defects Research (Part A) 2011. © 2011 Wiley‐Liss, Inc.
Maternal one‐carbon metabolism, MTHFR and TCN2 genotypes and neural tube defects in India
Authors: Godbole Koumudi , Gayathri Panjalingam , Ghule Smita , Sasirekha Batchu Venkatanaga , Kanitkar‐Damle Amruta , Memane Nilam , Suresh Seshadri , Sheth Jayesh , Chandak Giriraj Ratan , Yajnik Chittaranjan S.
Published: July 2011

BACKGROUND

Neural tube defects (NTDs) are among the most common severe congenital malformations, representing a long‐term public health burden in India. A deranged one‐carbon metabolism and genes regulating this metabolism have been linked to NTDs. Vitamin B12 deficiency is reported to be more prevalent than folate deficiency in the Indian population. We investigated the role of maternal nutritional and genetic markers related to one‐carbon metabolism in the etiology of NTDs.

METHODS

We conducted a multicenter case‐control study to compare plasma folate, vitamin B12, homocysteine and holo‐transcobalamin levels, and polymorphisms in methylenetetrahydrofolate reductase (MTHFR, 677C>T, 1298A>C, 1781G>A and 236+724A>G) and transcobalamin (TCN2, 776C>G) genes, in 318 women with NTD‐affected offspring (cases) and 702 women with apparently healthy offspring (controls). The samples were collected at diagnosis in cases and at delivery in controls.

RESULTS

We observed a significant association of high maternal plasma homocysteine concentrations with NTDs in the offspring (p = 0.026). There was no association of maternal folate or B12 levels with NTDs (p > 0.05) but low maternal holo‐transcobalamin predicted strong risk of NTDs in the offspring (p = 0.003). The commonly associated maternal polymorphism 677C>T in the MTHFR gene did not predict risk of NTDs in the offspring (p > 0.05) and 1298A>C and 1781G>A polymorphisms in MTHFR were protective (p = 0.024 and 0.0004 respectively). Maternal 776C>G polymorphism in TCN2 was strongly predictive of NTD in the offspring (p = 0.006).

CONCLUSION

Our study has demonstrated a possible role for maternal B12 deficiency in the etiology of NTDs in India over and above the well‐established role of folate deficiency. Birth Defects Research (Part A), 2011. © 2011 Wiley‐Liss, Inc.
Overview: developmental toxicology—new directions
Authors: Shuey Dana , Kim James H.
Published: July 2011

Since regulatory agencies began implementing the use of standardized developmental toxicology protocols in the mid‐1960s, our knowledge base of embryo‐fetal development and technologies for experimentation has grown exponentially. These developmental toxicology protocols were a direct result of the thalidomide tragedy from earlier that decade, when large numbers of women were exposed to the drug and over 10,000 cases of phocomelia resulted. In preventing a recurrence of such tragedies, the testing protocols are immensely successful and the field of toxicology has been dedicated to using them to advance safety and risk assessment of chemicals and pharmaceuticals. Recently, our perspectives on toxicity testing have been challenged by a growing awareness that while we have excelled in hazard identification, we are in dire need of improved methodologies for human health risk assessment, particularly with respect to the large numbers of environmental chemicals for which we have little toxicology data and to the growing sentiment that better alternatives to whole animals tests are needed. To provide a forum for scientists, researchers, and regulators, the Developmental and Reproductive Toxicology Technical Committee of the Health and Environmental Sciences Institute organized a 2‐day workshop titled “Developmental Toxicology—New Directions” to evaluate lessons learned over the past 30 years and discuss the future of toxicology testing. The following four articles describe different presentations and discussions that were held over the course of those 2 days. Birth Defects Res (Part B) 92:381–383, 2011. © 2011 Wiley Periodicals, Inc.
Developmental toxicity testing for safety assessment: new approaches and technologies
Authors: Knudsen Thomas B. , Kavlock Robert J. , Daston George P. , Stedman Donald , Hixon Mary , Kim James H.
Published: July 2011

The ILSI Health and Environmental Sciences Institute's Developmental and Reproductive Toxicology Technical Committee held a 2‐day workshop entitled “Developmental Toxicology—New Directions” in April 2009. The fourth session of this workshop focused on new approaches and technologies for the assessment of developmental toxicology. This session provided an overview of the application of genomics technologies for developmental safety assessment, the use of mouse embryonic stem cells to capture data on developmental toxicity pathways, dynamical cell imaging of zebrafish embryos, the use of computation models of development pathways and systems, and finally, high‐throughput in vitro approaches being utilized by the EPA ToxCast program. Issues discussed include the challenges of anchoring in vitro predictions to relevant in vivo endpoints and the need to validate pathway‐based predictions with targeted studies in whole animals. Currently, there are 10,000 to 30,000 chemicals in world‐wide commerce in need of hazard data for assessing potential health risks. The traditional animal study designs for assessing developmental toxicity cannot accommodate the evaluation of this large number of chemicals, requiring that alternative technologies be utilized. Though a daunting task, technologies are being developed and utilized to make that goal reachable. Birth Defects Res (Part B) 92:413–420, 2011. © 2011 Wiley Periodicals, Inc.
Lack of teratological effects in rats exposed to 20 or 60 kHz magnetic fields
Authors: Nishimura Izumi , Oshima Atsushi , Shibuya Kazumoto , Negishi Tadashi
Published: July 2011

BACKGROUND: A risk assessment of magnetic field (MF) exposure conducted by the World Health Organization indicated the need for biological studies on primary hazard identification and quantitative risk evaluation of intermediate frequency (300 Hz–100 kHz) MFs. Because induction heating cookers generate such MFs for cooking, reproductive and developmental effects are a concern due to the close proximity of the fields' source to a cook's abdomen. METHODS: Pregnant Crl:CD(SD) rats (25/group) were exposed to a 20 kHz, 0.2 mT(rms) or 60 kHz, 0.1 mT(rms) sinusoidal MF or sham‐exposed for 22 hr/day during organogenesis, and their fetuses were examined for malformations on gestation day 20. All teratological evaluations were conducted in a blind fashion, and experiments were duplicated for each frequency to confirm consistency of experimental outcomes. RESULTS: No exposure‐related changes were found in clinical signs, gross pathology, or number of implantation losses. The number of live fetuses and low‐body‐weight fetuses as well as the incidence of external, visceral, and skeletal malformations in the fetuses did not indicate significant differences between MF‐exposed and sham‐exposed groups. Although some fetuses showed isolated changes in sex ratio and skeletal variation and ossification, such changes were neither reproduced in duplicate experiments nor were they common to specific field frequencies. CONCLUSIONS: Exposure of rats to MFs during organogenesis did not show significant reproducible teratogenicity under experimental conditions. Present findings do not support the hypothesis that intermediate frequency MF exposure after implantation carries a significant risk for developing mammalian fetuses. Birth Defects Res (Part B) 92:469–477, 2011. © 2011 Wiley Periodicals, Inc.
Critical evaluation of current developmental toxicity testing strategies: a case of babies and their bathwater
Authors: Carney Edward W. , Ellis Amy L. , Tyl Rochelle W. , Foster Paul M.D. , Scialli Anthony R. , Thompson Kary , Kim James
Published: July 2011

This review is the second in a series of four papers emanating from a workshop entitled “Developmental Toxicology—New Directions,” which was sponsored by the ILSI Health and Environmental Sciences Institute's (HESI) Developmental and Reproductive Toxicology Technical Committee. The present review analyzes the strengths and weaknesses of current developmental safety testing approaches in an effort to identify those strengths that should be retained in the future versus the weaknesses that should be eliminated. Workshop participants considered the following to be key strengths of current testing approaches: the integrated biology of pregnant animal models including pharmacokinetic and pharmacodynamic processes, the ability to detect low incidence malformations as well as maternally mediated toxicity, and the long history of use coupled with extensive historical data. A number of weaknesses were related to the resource‐intensive nature of developmental toxicity testing (e.g., large number of animals, high costs, low throughput, the inability to keep pace with the demand for more toxicity data). Other weaknesses included the use of very high dose levels that often far exceed human exposure levels, the confounding influence of maternal toxicity, sparse understanding of basic developmental mechanisms and genetics of standard animal models relative to mouse or lower organisms, difficulties interpreting low incidence findings, and issues surrounding the interpretation of minor skeletal variations. An appreciation of these strengths and weaknesses is critical for the design of new approaches to developmental toxicity testing in the 21st century. Birth Defects Res (Part B) 92:395–403, 2011. © 2011 Wiley Periodicals, Inc.
Arrangement of type IV collagen on NH2 and COOH functionalized surfaces
Authors: Coelho Nuno Miranda , González‐García Cristina , Salmerón‐Sánchez Manuel , Altankov George
Published: July 2011

Apart from the paradigm that cell–biomaterials interaction depends on the adsorption of soluble adhesive proteins we anticipate that upon distinct conditions also other, less soluble ECM proteins such as collagens, associate with the biomaterials interface with consequences for cellular response that might be of significant bioengineering interest. Using atomic force microscopy (AFM) we seek to follow the nanoscale behavior of adsorbed type IV collagen (Col IV)—a unique multifunctional matrix protein involved in the organization of basement membranes (BMs) including vascular ones. We have previously shown that substratum wettability significantly affects Col IV adsorption pattern, and in turn alters endothelial cells interaction. Here we introduce two new model surfaces based on self‐assembled monolayers (SAMs), a positively charged –NH2, and negatively charged –COOH surface, to learn more about their particular effect on Col IV behavior. AFM studies revealed distinct pattern of Col IV assembly onto the two SAMs resembling different aspects of network‐like structure or aggregates (suggesting altered protein conformation). Moreover, the amount of adsorbed FITC‐labeled Col IV was quantified and showed about twice more protein on NH2 substrata. Human umbilical vein endothelial cells attached less efficiently to Col IV adsorbed on negatively charged COOH surface judged by altered cell spreading, focal adhesions formation, and actin cytoskeleton development. Immunofluorescence studies also revealed better Col IV recognition by both α1 and α2 integrins on positively charged NH2 substrata resulting in higher phosphorylated focal adhesion kinase recruitment in the focal adhesion complexes. On COOH surface, no integrin clustering was observed. Taken altogether these results, point to the possibility that combined NH2 and Col IV functionalization may support endothelization of cardiovascular implants. Biotechnol. Bioeng. 2011;108: 3009–3018. © 2011 Wiley Periodicals, Inc.
Facile pretreatment of lignocellulosic biomass at high loadings in room temperature ionic liquids
Authors: Wu Hong , Mora‐Pale Mauricio , Miao Jianjun , Doherty Thomas V. , Linhardt Robert J. , Dordick Jonathan S.
Published: July 2011

Ionic liquids (ILs) have emerged as attractive solvents for lignocellulosic biomass pretreatment in the production of biofuels and chemical feedstocks. However, the high cost of ILs is a key deterrent to their practical application. Here, we show that acetate based ILs are effective in dramatically reducing the recalcitrance of corn stover toward enzymatic polysaccharide hydrolysis even at loadings of biomass as high as 50% by weight. Under these conditions, the IL serves more as a pretreatment additive rather than a true solvent. Pretreatment of corn stover with 1‐ethyl‐3‐methylimidizolium acetate ([Emim] [OAc]) at 125 ± 5°C for 1 h resulted in a dramatic reduction of cellulose crystallinity (up to 52%) and extraction of lignin (up to 44%). Enzymatic hydrolysis of the IL‐treated biomass was performed with a common commercial cellulase/xylanase from Trichoderma reesei and a commercial β‐glucosidase, and resulted in fermentable sugar yields of ∼80% for glucose and ∼50% for xylose at corn stover loadings up to 33% (w/w) and 55% and 34% for glucose and xylose, respectively, at 50% (w/w) biomass loading. Similar results were observed for the IL‐facilitated pretreatment of switchgrass, poplar, and the highly recalcitrant hardwood, maple. At 4.8% (w/w) corn stover, [Emim][OAc] can be readily reused up to 10 times without removal of extracted components, such as lignin, with no effect on subsequent fermentable sugar yields. A significant reduction in the amount of IL combined with facile recycling has the potential to enable ILs to be used in large‐scale biomass pretreatment. Biotechnol. Bioeng. 2011;108: 2865–2875. © 2011 Wiley Periodicals, Inc.
Metabolite profiling of recombinant CHO cells: Designing tailored feeding regimes that enhance recombinant antibody production
Authors: Sellick Christopher A. , Croxford Alexandra S. , Maqsood Arfa R. , Stephens Gill , Westerhoff Hans V. , Goodacre Royston , Dickson Alan J.
Published: July 2011

Chinese hamster ovary (CHO) cells are the primary platform for commercial expression of recombinant therapeutic proteins. Obtaining maximum production from the expression platform requires optimal cell culture medium (and associated nutrient feeds). We have used metabolite profiling to define the balance of intracellular and extracellular metabolites during the production process of a CHO cell line expressing a recombinant IgG4 antibody. Using this metabolite profiling approach, it was possible to identify nutrient limitations, which acted as bottlenecks for antibody production, and subsequently develop a simple feeding regime to relieve these metabolic bottlenecks. This metabolite profiling‐based strategy was used to design a targeted, low cost nutrient feed that increased cell biomass by 35% and doubled the antibody titer. This approach, with the potential for utilization in non‐specialized laboratories, can be applied universally to the optimization of production of commercially important biopharmaceuticals. Biotechnol. Bioeng. 2011;108: 3025–3031. © 2011 Wiley Periodicals, Inc.
Working to Ensure Safety, Belonging and Success for Unaccompanied Asylum‐seeking Children
Authors: Kohli Ravi K. S.
Published: July 2011

This paper considers what safety, belonging and success mean to children and young people who seek asylum alone within richer nations. These three elements are conceptualised, taking account of journeys away from their countries of origin towards a sense of ‘home’ in a new country. The conceptual map is then used to frame existing research to establish what is known, and what needs to be further examined in understanding the ways in which the three elements are manifest when permanent resettlement, temporary admission and enforced return are all possible outcomes of an asylum claim. The paper concludes that the state of knowledge is currently uncertain in relation to each element, with some good evidence of safety and belonging in the context of permanent resettlement and relatively poor understanding of success when children and young people are forced to return away from the country of asylum. Copyright © 2011 John Wiley & Sons, Ltd.

‘Home is the place where, when you have to go there,

They have to take you in.’

The Death of the Hired Man by Robert Frost, 1915 (Frost, 1973)

‘permanent resettlement, temporary admission and enforced return are all possible outcomes of an asylum claim’
Synthesis of a New Series of 1H‐Imidazol‐1‐yl Substituted 8‐Phenylxanthines as Adenosine Receptor Ligands
Authors: Bansal Ranju , Kumar Gulshan , Gandhi Deepika , Young Louise C. , Harvey Alan L.
Published: July 2011

A new series of 1H‐imidazol‐1‐yl substituted 8‐phenylxanthine analogs has been synthesized to study the effects of the imidazole group on the binding affinity of compounds for adenosine receptors. Competition binding studies of these compounds were carried out in vitro with human cloned receptors using [3H]DPCPX and [3H]ZM 241385 as radioligands at A1 and A2A adenosine receptors, respectively. The effect of the substitution pattern of the (imidazolyl)alkoxy group on various positions of the phenyl ring at C(8) was also studied. The xanthine derivatives displayed varying degrees of affinity and selectivity towards A1 and A2A receptor subtypes despite a common but variedly substituted ArC(8).
Novel 3‐Oxo‐ and 3,24‐Dinor‐2,4‐secooleanane‐Type Triterpenes from Terminalia ivorensis A. Chev.
Authors: Ponou Beaudelaire Kemvoufo , Teponno Rémy Bertrand , Ricciutelli Massimo , Nguelefack Télesphore Bénoit , Quassinti Luana , Bramucci Massimo , Lupidi Giulio , Barboni Luciano , Tapondjou Léon Azefack
Published: July 2011

Two new oleanane‐type triterpenes named ivorengenin A (=3‐oxo‐2α,19α,24‐trihydroxyolean‐12‐en‐28‐oic acid; 1) and ivorengenin B (=4‐oxo‐19α‐hydroxy‐3,24‐dinor‐2,4‐secoolean‐12‐ene‐2,28‐dioic acid; 2), together with five known compounds, arjungenin, arjunic acid, betulinic acid, sericic acid, and oleanolic acid, were isolated from the barks of Terminalia ivorensis A. Chev. (Combretaceae). Their structures were established on the basis of 1D‐ and 2D‐NMR data, and mass spectrometry. A biogenetic pathway to the formation of these compounds from sericic acid, isolated as the major compound from this plant, was proposed. The antioxidant activities of different compounds were investigated by means of the 2,2‐azinobis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS) and 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) assays, and IC50 values were calculated and compared with Trolox activity. Antiproliferative activities of the isolated compounds were also evaluated against MDA‐MB‐231, PC3, HCT116, and T98G human cancer cell lines, against which the compounds showed significant cytotoxic activities.
Synthesis, Characterization, and DNA‐Binding and ‐Cleavage Properties of Dinuclear CuIISalophen/Salen Complexes
Authors: Rabindra Reddy Pulimamidi , Shilpa Addla
Published: July 2011

Dinuclear CuII complexes, [Cu2(salophen)2] (1) and [Cu2(salen)2] (2), with Schiff bases derived from salicylaldehyde and o‐phenylenediamine (ophen) or ethylenediamine (en) were synthesized and characterized. They exhibit square‐planar geometry with CuN2O2 coordination, where the dianionic Schiff base acts as a tetradentate N2O2 donor ligand. Calf thymus (CT)‐DNA Binding studies revealed that the complexes possess good binding propensities (Kb=3.13×105 for 1 and Kb=2.99×105 M−1 for 2). They show good DNA‐cleavage abilities under oxidative and hydrolytic conditions. Complex 1 binds and cleaves DNA more efficiently as compared to 2 due to the presence of an extended aromatic phenyl ring which might be involved in an additional stacking interaction with DNA bases. From the kinetic experiments, hydrolytic DNA‐cleavage rate constants were determined as 1.54 for 1 and 0.72 h−1 for 2. The nuclease activities of 1 and 2 are significant, giving rise to (2.03–2.88)×107‐fold rate enhancement compared to non‐catalyzed DNA cleavage.
Huperzine A as Potential Treatment of Alzheimer's Disease: An Assessment on Chemistry, Pharmacology, and Clinical Studies
Authors: Ha Giang T. , Wong Ryan K. , Zhang Yan
Published: July 2011

Alzheimer's disease (AD) is the fourth leading cause of death in adults, characterized by hallmark neuritic plaques and neurofibrillary tangles. Current treatments focus only on symptom relief. As a possible new treatment option for AD, huperzine A's chemistry, pharmacology, and clinical effectiveness are assessed. The chemical synthesis of huperzine A has been optimized, while an in vitro technique has provided a renewable plant source. Pharmacological studies showed that the drug inhibits the enzyme acetylcholinesterase reversibly and selectively. Huperzine A also displayed good pharmacokinetics with a rapid absorption and a wide distribution in the body at a low to moderate rate of elimination. Presently, inadequate toxicity data in human have been reported, yet animal studies demonstrated mild to moderate cholinergic side effects at therapeutic doses. Previous clinical trials have shown improvement in memory function using MMSE, MQ, ADAS‐COG, and ADL tests. In an unpublished phase II clinical trial, the ADAS‐COG and MMSE tests indicated cognitive enhancement at a dose of 0.4 mg, yet no improvement was observed at a dose of 0.2 mg. The MMSE scores indicated cognitive enhancement at 0.4 mg. Promising data suggested that huperzine A is well tolerated at doses up to 0.4 mg for 24 weeks. Therefore, huperzine A seems to be a potential treatment option for AD.