bluuebunny/crossref_metadata_2025 huggingface dataset:
Creation of a composite solar ultraviolet irradiance data set
Authors: DeLand Matthew T. , Cebula Richard P.
Published: November 2008

Characterization of long‐term solar ultraviolet (UV) irradiance variations is important for understanding the radiative forcing of Earth's atmosphere. Extending such a characterization to multidecadal timescales requires the merging of multiple satellite data sets. Currently available irradiance data sets show both absolute offsets and time‐dependent differences that vary between spectral ranges. We have created a composite spectral UV irradiance data set with daily spectra covering the wavelength range 120–400 nm for the time period November 1978 to August 2005. A reference irradiance spectrum is used for normalization to remove absolute biases between instruments. We selected the best irradiance data set for each spectral and temporal interval based on intercomparisons between overlapping data sets and comparisons with proxy model predictions. The long‐term behavior of the merged composite irradiance data set is consistent with expectations based on other solar activity indicators. There is no difference between the minimum values for solar cycles 21 and 22 within the uncertainty of the data, and the maximum irradiance values for cycle 23 are slightly lower than those observed for cycles 21 and 22. We also compare our composite data set with published synthetic irradiance data. These two data sets generally agree within ±2% over most spectral and temporal ranges. We hope to extend this data set in the future using measurements from the SORCE satellite.
Continuous penetration of the interplanetary electric field to the equatorial ionosphere over eight hours during intense geomagnetic storms
Authors: Huang Chao‐Song
Published: November 2008

The interplanetary electric field penetrates to the low‐latitude ionosphere and has significant influence on the ionospheric electrodynamics during intense geomagnetic storms. It is critical to understand how much of the interplanetary electric field can penetrate to the ionosphere and how long penetration electric fields can exist. In this study, we present the Defense Meteorological Satellite Program (DMSP) satellite measurements of the equatorial ionospheric ion vertical velocity in the dusk sector during two intense geomagnetic storms. We find that the equatorial ionospheric electric field at dusk is approximately proportional to the interplanetary electric field for 8–10 hours during the storm main phase. The penetration efficiency is relatively constant over the entire interval and is 5% at dusk in one storm case. The long‐lasting storm‐time penetration electric field causes significant redistribution of the ionospheric plasma. This study reveals that penetration electric fields can last for 8–10 hours without effective shielding when the magnetic storm activity is strengthening during continuous southward interplanetary magnetic field. The result implies that the interplanetary electric field is linearly coupled with the dusk equatorial ionosphere during the entire main phase of intense magnetic storms, which is very important for understanding the storm‐time ionospheric electric field and electrodynamics.
Observed sea ice extent in the Russian Arctic, 1933–2006
Authors: Mahoney Andrew R. , Barry Roger G. , Smolyanitsky Vasily , Fetterer Florence
Published: November 2008

We present a time series of sea ice extent in the Russian Arctic based on observational sea ice charts compiled by the Arctic and Antarctic Research Institute (AARI). These charts are perhaps the oldest operational sea ice data in existence and show that sea ice extent in the Russian Arctic has generally decreased since the beginning of the chart series in 1933. This retreat has not been continuous, however. For the Russian Arctic as a whole in summer, there have been two periods of retreat separated by a partial recovery between the mid‐1950s and mid‐1980s. The AARI charts, combined with air temperature records, suggest that the retreat in recent decades is pan‐Arctic and year‐round in some regions, whereas the early twentieth century retreat was only observed in summer in the Russian Arctic. The AARI ice charts indicate that a significant transition occurred in the Russian Arctic in the mid‐1980s, when its sea ice cover began to retreat along with that of the rest of the Arctic. Summertime sea ice extents derived from the AARI data set agree with those derived from passive microwave, including the Hadley Centre's global sea ice coverage and sea surface temperature (HadISST) data set. The HadISST results do not indicate the 1980s transition or the partial recovery that took place before it. The AARI charts therefore add significantly to our understanding of the variability of Arctic sea ice over the last 8 decades, and we recommend their inclusion in future historical data sets of Arctic sea ice.
Steric height variability in the Northern Atlantic on seasonal and interannual scales
Authors: Ivchenko V. O. , Danilov S. , Sidorenko D. , Schröter J. , Wenzel M. , Aleynik D. L.
Published: November 2008

Steric height (SH) variability computed from Argo profiling buoys data for the North Atlantic and period 1999–2006 is analyzed and compared to the variability computed from the satellite altimetry data. It is demonstrated that although the contribution from halosteric contraction is smaller than that from the thermal expansion, it is not negligible in wide areas in the North Atlantic and cannot be discarded (the regression of trends in full steric and thermosteric heights is 0.73). It is found that the SH variability is not really sensitive to increasing the reference level from 1000 to 1500 m. Differences in trend reach several mm/year locally, which is estimated to be below sampling errors (about 1.4 mm/year). The SH trends are between ±1 cm/year locally. The comparison of SH and altimetric height variability shows qualitative agreement of both for the amplitude of the annual harmonics and trend but reveals significant local differences which cannot be explained by bottom pressure variability. The main modes of variability seen in yearly mean patterns of SH and satellite altimetry are also different. It is suggested that sampling/interpolation errors are still too high to reveal a balance between the SH and altimetric height variability at the local level.
Arctic land hydrothermal sensitivity under warming: Idealized off‐line evaluation of a physical terrestrial scheme in a global climate model
Authors: Saito Kazuyuki
Published: November 2008

A series of idealized one‐dimensional off‐line sensitivity experiments for the Arctic hydroclimate under a transitional warming environment were conducted to investigate the impact of different internal mechanisms and external forcing (excessive water input) in a physical terrestrial scheme, Minimal Advanced Treatments of Surface Interaction and Runoff (MATSIRO), used in a global climate model. The scheme has freeze/thaw processes and was run with the column depth greater than 50 m. The inclusion of the top organic layers and the physically based parameterization of soil hydrothermal properties led to a realistic seasonal amplitude of a subsurface thermal regime and mitigated the warming and deepening of the maximum active layer thickness (ALT). After a 6‐K warming over 100 years, ALT increases by 67% (from 9.6 to 16 cm) with the top organic layers and increases by more than a factor of 2 for the default mineral layers (122% from 45 cm to 1.0 m). With the more realistic thermal property profile, the physically based parameterizations projected ALT after the 100‐year warming to be about a half of what the original parameterization did (2.0 against 3.5 m). Finer soil layer thickness near the surface had impacts on the near‐surface wetness and the energy and water exchange between the atmosphere and also showed greater tolerance to the misconfiguration of porosity profile, whose global‐scale distribution is poorly known for global climate model applications. With much wetter forcing, water infiltration kept the soil close to the saturation, degradation of the frozen state proceeded faster, and the adaptation back to a drier condition occurred on a decadal time scale.
Frost flower chemical composition during growth and its implications for aerosol production and bromine activation
Authors: Alvarez‐Aviles Laura , Simpson William R. , Douglas Thomas A. , Sturm Matthew , Perovich Donald , Domine Florent
Published: November 2008

Frost flowers have been proposed to be the major source of sea‐salt aerosol to the atmosphere during polar winter and a source of reactive bromine during polar springtime. However little is known about their bulk chemical composition or microstructure, two important factors that may affect their ability to produce aerosols and provide chemically reactive surfaces for exchange with the atmosphere. Therefore, we chemically analyzed 28 samples of frost flowers and parts of frost flowers collected from sea ice off of northern Alaska. Our results support the proposed mechanism for frost flower growth that suggests water vapor deposition forms an ice skeleton that wicks brine present on newly grown sea ice. We measured a high variability in sulfate enrichment factors (with respect to chloride) in frost flowers and seawater from the vicinity of freezing sea ice. The variability in sulfate indicates that mirabilite precipitation (Na2SO4 · 10 H2O) occurs during frost flower growth. Brine wicked up by frost flowers is typically sulfate depleted, in agreement with the theory that frost flowers are related to sulfate‐depleted aerosol observed in Antarctica. The bromide enrichment factors we measured in frost flowers are within error of seawater composition, constraining the direct reactive losses of bromide from frost flowers. We combined the chemical composition measurements with temperature observations to create a conceptual model of possible scenarios for frost flower microstructure development.
Wine ethanol 14C as a tracer for fossil fuel CO2 emissions in Europe: Measurements and model comparison
Authors: Palstra Sanne W. L. , Karstens Ute , Streurman Harm‐Jan , Meijer Harro A. J.
Published: November 2008

14C (radiocarbon) in atmospheric CO2 is the most direct tracer for the presence of fossil‐fuel‐derived CO2 (CO2‐ff). We demonstrate the 14C measurement of wine ethanol as a way to determine the relative regional atmospheric CO2‐ff concentration compared to a background site (“regional CO2‐ff excess”) for specific harvest years. The carbon in wine ethanol is directly back traceable to the atmospheric CO2 that the plants assimilate. An important advantage of using wine is that the atmosphere can be monitored annually back in time. We have analyzed a total of 165 wines, mainly from harvest years 1990–1993 and 2003–2004, among which is a semicontinuous series (1973–2004) of wines from one vineyard in southwest Germany. The results show clear spatial and temporal variations in the regional CO2‐ff excess values. We have compared our measured regional CO2‐ff excess values of 2003 and 2004 with those simulated by the REgional MOdel (REMO). The model results show a bias of almost +3 parts per million (ppm) CO2‐ff compared with those of the observations. The modeled differences between 2003 and 2004, however, which can be used as a measure for the variability in atmospheric mixing and transport processes, show good agreement with those of the observations all over Europe. Correcting for interannual variations using modeled data produces a regional CO2‐ff excess signal that is potentially useful for the verification of trends in regional fossil fuel consumption. In this fashion, analyzing 14C from wine ethanol offers the possibility to observe fossil fuel emissions back in time on many places in Europe and elsewhere.
Morphology of the dayside ionosphere of Venus: Implications for ion outflows
Authors: Fox J. L.
Published: November 2008

The nightside ionosphere of Venus is formed mostly by day‐to‐night transport of ions below the ionopause, with a small contribution from precipitation of energetic electrons from the wake. This nightward flux of ions should result in dayside ionospheres that are characterized by smaller electron density scale heights at high altitudes than those that are characteristic of diffusive equilibrium. In order to determine both the maximum possible values of the upward fluxes and the upward fluxes implied by comparison of our computed ion and electron density profiles to measurements, we have constructed more than 60 models of the high solar activity Venus ionosphere for upward velocity boundary conditions ranging from 0 to 3 × 105 cm s−1. We show that as the upward velocity at the top of the model is increased, the high‐altitude densities of the atomic ions decrease, as do the total ion and electron densities. The maximum upward O+ flux that we derive is ∼5.3 × 108 cm−2 s−1. By comparing our model electron or total ion density profiles to those from Pioneer Venus data, we have derived upward fluxes of O+ that range from 1.8 × 108 to 2.5 × 108 cm−2 s−1 with an average of 2.1 × 108 cm−2 s−1. This value is roughly equal to estimates of the transterminator ion flux and to estimates of the downward fluxes of ions over the nightside. From this, we infer that the escape flux due to ion outflow is small. We conclude that the upward fluxes of ions that we have inferred from the morphology of the ionosphere contribute mostly to the day‐to‐night flow and to the formation of the nightside ionosphere and are much less than their source‐limited values.
Infinite slope stability under steady unsaturated seepage conditions
Authors: Lu Ning , Godt Jonathan
Published: November 2008

We present a generalized framework for the stability of infinite slopes under steady unsaturated seepage conditions. The analytical framework allows the water table to be located at any depth below the ground surface and variation of soil suction and moisture content above the water table under steady infiltration conditions. The framework also explicitly considers the effect of weathering and porosity increase near the ground surface on changes in the friction angle of the soil. The factor of safety is conceptualized as a function of the depth within the vadose zone and can be reduced to the classical analytical solution for subaerial infinite slopes in the saturated zone. Slope stability analyses with hypothetical sandy and silty soils are conducted to illustrate the effectiveness of the framework. These analyses indicate that for hillslopes of both sandy and silty soils, failure can occur above the water table under steady infiltration conditions, which is consistent with some field observations that cannot be predicted by the classical infinite slope theory. A case study of shallow slope failures of sandy colluvium on steep coastal hillslopes near Seattle, Washington, is presented to examine the predictive utility of the proposed framework.
Erratum: Microbial ecology of the equine hindgut during oligofructose-induced laminitis
Authors: Milinovich Gabriel J , Burrell Paul C , Pollitt Christopher C , Klieve Athol V , Blackall Linda L , Ouwerkerk Diane , Woodland Erika , Trott Darren J
Published: November 2008

Correction to: The ISMEJ Journal (2008) 2, 1089–1100; doi: 10.1038/ismej.2008.67 The authors of the above noted an error in the publication of this paper (AOP and in this issue) in the y axis to Figure 3. The right hand y axis title for horse 4 should read: ‘Fructose (mg/gram of caecal fluid DM).’ The corrected figure for horse 4 is shown below.
Multidimensional Analysis of Snow Cover Data in South Dakota Diversity of Landscapes
Authors: Shmagin Boris , Johnston Carol
Published: November 2008

Snow distribution in SD was studied with Factor Analysis (FA) of monthly total snowfall [in]. The long-term data obtained from the High Plains Regional Climate Center were used for the territory of South Dakota. The perspective for creating an Atlas of Climate and Water Resources for SD directed this study of total monthly snowfall with connection to landscape diversity.The initial matrix {Xn*p} where n is number of stations and p is number of variables of monthly average for period of observations. The maximum number of stations n with mutual interval of observations for SD is equal 93 (n=93). These stations have mutual time interval of 18 years observations (1952-53 – 1969-70). Total monthly snowfall has data for p=10 is number of months with observation and p=11 is number of months with observations with total snowfall for the winter season. The second matrix contains proportions of total monthly snowfall to total annual (proportion is the monthly total snowfall divided on total seasonal snowfall); the number of rows n and the number of variable are the same as in the first case: n=93 and p=10, 11.The average annual sum of total monthly snowfall (September-June) for SD 34.64 in obtained on 93 stations for 1952-1970, the median is 31.84 from the same data; ranged from 10.21 to 152.27 from the same data. The most variable month is April with average4.89 [in], median 3.67, min 0.75 and max 33.18; the average proportion for April is 0.13, min 0.03 and max 0.24. The averages for November to April grow as sequence: 3.60, 5.70, 4.88, 7.25, 7.46 and 4.89 the variability of those months has sequence: 2.49 2.52 2.25 3.33 3.53 and 4.87. The Pearson coefficient of correlation for the monthly snowfall averages from September to June with annual sum has sequence: 0.83, 0.92, 0.96, 0.92, 0.93, 0.93, 0.94, 0.92, 0.90, and 0.82; the correlation for the monthly proportions from September to June with annual sum has sequence: 0.38, 0.45, -0.01, -0.32, -0.33, -0.21, -0.15, 0.27, 0.36, and 0.35.The FA of both initial matrixes had extracted two factors for monthly observations with incorporation of 93 % of total variability of the data in the model; and three factors model with 70% variability of data for monthly proportions. The two factor groups in model of observed snowfall contain winter months (Dec – Mar) and all other. The model of monthly proportions with tree factor groups include winter months in two group and combination of spring and fall months in third. The factor scores presented as maps for SD allow trace distribution of factor groups of monthly snowfall patterns for two models through the territory of SD. The combination of factor scores distribution for two models is in a good agreement with main landscape regions and subregions of SD.
Genome-wide transcription analysis of interaction between the human macrophage and Mycobacterium tuberculosis during concurrent drug administration by conventional and novel methods
Authors: Yadav Awadh Bihari , Singh Amit K. , Misra Amit
Published: November 2008

Targeted drug delivery to alveolar macrophages harboring Mycobacterium tuberculosis (Mtb) holds promise of high efficacy against pulmonary tuberculosis (TB). It was investigated whether inhalable microparticles (MP) can rescue macrophages from ‘alternative’ activation induced by pathogenic Mtb in addition to achieving targeted drug delivery. A genome-wide transcription analysis (Affymetrix HG-U133 Plus 2.0 DNA microarray) of THP-1 cell line derived macrophages was undertaken after exposing them to infection with 10 MOI of MTB H37Rv at 0, 12 and 24 hours post infection. The Molecular markers of macrophage bactericidal activity were assayed in THP-1- and primary human peripheral blood mononuclear cell (PBMC)-derived macrophages, in the presence or absence of soluble anti-tuberculosis drugs, drug-containing MP and blank MP. About 1,500 genes were differentially upregulated and about 500 genes differentially downregulated in response to various modes of treatment. Variations were also observed in the kinetics of gene expression. Cluster analysis indicated activation of several pathways related to innate immune response (cytokines, chemokines, receptors and ligands), apoptosis, cytoskeleton and membrane remodeling, general metabolism and general housekeeping. Some of these results were validated at the functional level, by studying caspase activities, concentrations and time-courses of effector molecules , rates/extents of apoptosis and nitrite oxide induction. Production of cytokines and NO, apoptosis, and bacterial survival were studied as pharmacodynamic outcomes. Cytokine responses of THP-1 derived macrophages were estimated. MP reversed suppression of tumor necrosis factor (TNF) induced by infection, and transiently upregulated γ-interferon (IFN-γ). Drug-free MP surprisingly induced IFN-γ, but not TNF. Primary cells responded to MP, regardless of drug content, by upregulation of NO; but THP-1-derived cells did not respond to blank MP. About 19% of infected cells exposed to MP underwent apoptosis as compared to ~11% cells treated with soluble drugs or blank MP. Cell death induced by blank MP was caspase-independent. Only drug-containing MP induced apoptosis through caspase-8 and caspase-9. Bacterial survival after different treatments varied between individuals. In the best case, while untreated infection resulted in survival of 900±141 colony forming units (CFU), treatment with soluble drugs, drug-containing MP and blank MP respectively, reduced CFU counts to 8.5± 0.7, 3±1.4 and 102±138.6. The results suggest a role of the drug delivery system in macrophage activation as a component of therapeutic strategy against TB.
Parallel RNAi and compound screens identify the PDK1 pathway as a target for tamoxifen sensitization
Authors: Iorns Elizabeth , Lord Christopher J. , Ashworth Alan
Published: November 2008

Tamoxifen is the most commonly used drug to treat breast cancer and acts by blocking ERα (oestrogen receptor α) signalling. Although highly effective, its usefulness is limited by the development of resistance. Given this, strategies that limit resistance by sensitizing cells to tamoxifen may be of use in the clinic. To gain insight into how this might be achieved, we used chemical and genetic screens to identify targets and small-molecule inhibitors that cause tamoxifen sensitization. A high-throughput genetic screen, using an RNA interference library targeting 779 kinases and related proteins, identified the PDK1 (phosphoinositide-dependent kinase 1) signalling pathway as a strong determinant of sensitivity to multiple ERα antagonists, including tamoxifen. A chemical screen using existing drugs and known kinase inhibitors also identified inhibitors of the PDK1 pathway, including triciribine and tetrandrine. Aside from identifying novel agents and targets for tamoxifen sensitization, this approach also provides evidence that performing chemical and genetic screens in parallel may be useful.
Molecular and functional characterization of VDAC2 purified from mammal spermatozoa
Authors: Menzel Viviana A. , Cassará M. Carolina , Benz Roland , De Pinto Vito , Messina Angela , Cunsolo Vincenzo , Saletti Rosaria , Hinsch Klaus-Dieter , Hinsch Elvira
Published: November 2008

VDAC (voltage-dependent anion channel) is the pore-forming protein located in the outer mitochondrial membrane. In higher eukaryotes, three genes encode VDAC. Nevertheless, the knowledge of VDAC isoforms is mainly restricted to VDAC1, the only isoform that has been characterized from living tissues to date. We have highly enriched the isoform VDAC2 using as starting material bovine spermatozoa. VDAC2 was obtained in the hydroxyapatite/celite pass-through of sperm proteins solubilized with Triton X-100. This fraction showed in SDS/PAGE two major bands and one faint band in the molecular mass range of 30–35 kDa. Two-dimensional electrophoresis resolved these bands in ten spots with various Coomassie Blue staining intensities. Western-blot analysis with antibodies monospecific for each isoform and MS peptide sequencing showed that the main protein resolved in electrophoresis was VDAC2 with minor contaminations of the other isoforms. Proteomic analysis of the higher molecular mass VDAC2 protein allowed the coverage of the whole protein with the exception of the tripeptide A24AR26. In the same material, the presence of two possible amino acid substitutions (T88 to L88 and A97 to Q97) was revealed. Reconstitution of VDAC2 pores in planar lipid bilayers showed typical features of mitochondrial porins. Stepwise increases in membrane conductance were observed with a predominant conductance of approx. 3.5 nS (nanoSiemens) in 1 M KCl. Very often, small short-lived fluctuations were observed with single-channel conductance of approx. 1.5 nS. Bovine spermatozoa VDAC2 was anion selective and showed voltage dependence. The present study is the first work to report the purification and characterization of VDAC2 from a mammalian tissue.
Immuno-inflammatory predictors of stroke at follow-up in patients with chronic non-valvular atrial fibrillation (NVAF)
Authors: Pinto Antonio , Tuttolomondo Antonino , Casuccio Alessandra , Di Raimondo Domenico , Di Sciacca Riccardo , Arnao Valentina , Licata Giuseppe
Published: November 2008

The aim of the present study was to determine the rates of stroke in patients with chronic NVAF (non-valvular atrial fibrillation), evaluating the relationship between plasma levels of inflammatory variables at admission and the occurrence of stroke during a 3-year follow-up. A total of 373 consecutive patients with chronic NVAF were enrolled. Blood samples were drawn within 72 h of admission, and we evaluated plasma levels of IL (interleukin)-1β, TNF-α (tumour necrosis factor-α), IL-6, IL-10, E-selectin, P-selectin, ICAM-1 (intercellular adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule-1) and vWF (von Willebrand Factor). Subsequent patient events (stroke at follow-up) were monitored over a 3 year period. By multivariate analysis, only age, hypertension and high levels of IL-6, TNF-α and vWF remained significant predictors of a higher risk of experiencing ischaemic stroke at follow-up. Moreover, plasma values of TNF-α, IL-6 and vWF had a significant area under the ROC (receiver operating characteristic) curve. In conclusion, baseline plasma levels of TNF-α, IL-6 and vWF are predictors of new-onset ischaemic stroke at follow-up in patients with chronic NVAF.
Innovation through Generic Medicines: Is it Time for a Pan-European Policy?
Authors: Simoens Steven
Published: November 2008

This paper aims to report on the ‘Innovation through generics’ roundtable, which was convened at the European Parliament in April 2008 to discuss the role of generic medicines in stimulating innovation in the pharmaceutical sector. The roundtable identified a number of factors that hamper generic market entry in Europe and, thus, inhibit competition and innovation in the pharmaceutical sector. These factors include the decline in true innovation in the pharmaceutical sector; shortcomings in current patent and registration systems; pricing and reimbursement delays for generic medicines; greater intellectual property protection and market exclusivity for originator medicines than in the United States; price linkage between generic and originator medicines in some member states; and a lack of demand-side measures that encourage physicians, pharmacists and patients to use generic medicines. There is a need for a pan-European policy relating to patents, registration, pricing and reimbursement, prescribing and dispensing of medicines. In particular, the creation of an internal market will benefit European healthcare by helping to drive down costs. The overall goal should be to support competition and true innovation and, thus, provide sustainable healthcare for patients throughout Europe.
‘Multifunctionality’: Trade Protectionism or a New Way Forward?
Authors: Dibden Jacqui , Cocklin Chris
Published: November 2008

The concept of ‘multifunctionality’ has developed partly in response to the threat which trade liberalisation presents to European agriculture. In this paper we outline different approaches to multifunctionality and consider whether, and to what extent, the concept may be applied more widely outside its home of origin in Western Europe, and specifically whether it is relevant to liberalised agricultural economies, such as Australia. The focus is on government agricultural and rural policies which contribute to the maintenance or enhancement of the multifunctional characteristics of agriculture and other land uses. We suggest that, despite differences in views of the importance of farming and rural areas, a convergence is appearing between Australia and European countries in the development of policies aimed at the promotion of multiple outcomes from agriculture.
Patchwork Neighborhood: Children's Urban Geographies in Buffalo, New York
Authors: Cope Meghan
Published: November 2008

The West Side of the City of Buffalo, New York, is a neighborhood in racial and ethnic transition, demographically. However, at any given time it represents a snapshot of a geographic area that is diverse economically, ethnically, and racially, and in terms of its built environment. I use the notion of ‘patchwork’ first as a literal interpretation based on a quilting project I facilitated with children from an after-school program in this location. Second, ‘patchwork’ is used as a metaphor capturing results of neighborhood explorations led by the children over three years (2003–06). Specifically, as I explore children's perceptions of ‘neighborhood’, the notion of ‘patchwork’ seems to accommodate their varied understandings, views, and perspectives of their neighborhoods well. Simultaneously, the notion also contributes to the fluid and active construction of the term in urban geography.
Complementarity and Substitutability among Adjacent Gateway Ports
Authors: Notteboom Theo E
Published: November 2008

The author considers complementarity and substitutability among container ports located in a single gateway region. The level of substitutability from a shipping line's perspective is assessed by means of an analysis of revealed preferences in the port-calling pattern of vessels deployed on different trade routes. The author also identifies and analyzes the factors contributing to levels of port substitutability as perceived by shipping lines. The methodology is applied to the Rhine–Scheldt Delta, a major European multiport gateway region. It is demonstrated that the large load centres in the Delta are increasingly acting as substitutes, while each of the smaller container ports functions more as a complement to one of the large load centres.
The Sackler Colloquium on promises and perils in nanotechnology for medicine
Authors: Austin Robert H. , Lim Shuang-fang
Published: November 2008

The Sackler Colloquium entitled “Nanomaterials in Biology and Medicine: Promises and Perils” was held on April 10–11, 2007. We have been able to assemble a representative sampling of 17 of the invited talks ranging over the topics presented. Any new technology carries with it both a promise of transforming the way we do things and the possibility that there are unforeseen consequences. The papers collected here represent a cross-section of these issues. As an example, we present our own work on nano-upconversion phosphors as an example of this new class of nanomaterials with potential use in medicine and biology.
Catalytic antibody degradation of ghrelin increases whole-body metabolic rate and reduces refeeding in fasting mice
Authors: Mayorov Alexander V. , Amara Neri , Chang Jason Y. , Moss Jason A. , Hixon Mark S. , Ruiz Diana I. , Meijler Michael M. , Zorrilla Eric P. , Janda Kim D.
Published: November 2008

Obesity is a chronic, costly, and globally prevalent condition, with excess caloric intake a suspected etiologic factor. Nonsurgical treatments are modestly efficacious, and weight loss maintenance is hampered by anti-famine homeostatic mechanisms. Ghrelin, a gastric hormone linked to meal initiation, energy expenditure, and fuel partitioning, is hypothesized to facilitate weight gain and impede weight loss. Unique among known animal peptides, the serine-3 residue of ghrelin is posttranslationally acylated with an
n
-octanoic acid, a modification important for the peptide's active blood-brain transport and growth hormone secretagogue receptor-1 agonist activity. Pharmacological degradation of ghrelin would be hypothesized to reduce ghrelin's biological effects. To study endogenous ghrelin's role in appetite and energy expenditure, we generated antibodies that hydrolyze the octanoyl moiety of ghrelin to form
des
-acyl ghrelin. The most proficient antibody catalyst, GHR-11E11, was found to display a second-order rate constant of 18 M
−
1·s
−1
for the hydrolysis of ghrelin to
des
-acyl ghrelin. I.v. administration of GHR-11E11 (50 mg/kg) maintained a greater metabolic rate in fasting C57BL/6J mice as compared with mice receiving a control antibody and suppressed 6-h refeeding after 24 h of food deprivation. Indirect respiratory measures of metabolism after refeeding and relative fuel substrate utilization were unaffected. The results support the hypothesis that acylated ghrelin stimulates appetite and curbs energy expenditure during deficient energy intake, whereas
des
-acyl ghrelin does not potently share these functions. Catalytic anti-ghrelin antibodies might thereby adjunctively aid consolidation of caloric restriction-induced weight loss and might also be therapeutically relevant to Prader–Willi syndrome, characterized after infancy by hyperghrelinemia, hyperphagia, and obesity.
Identification of a BK channel auxiliary protein controlling molecular and behavioral tolerance to alcohol
Authors: Martin Gilles E. , Hendrickson Linzy M. , Penta Krista L. , Friesen Ryan M. , Pietrzykowski Andrzej Z. , Tapper Andrew R. , Treistman Steven N.
Published: November 2008

Tolerance, described as the loss of drug effectiveness over time, is an important component of addiction. The degree of acute behavioral tolerance to alcohol exhibited by a naïve subject can predict the likelihood of alcohol abuse. Thus, the determinants of acute tolerance are important to understand. Calcium- and voltage-gated (BK) potassium channels, consisting of pore forming α and modulatory β subunits, are targets of ethanol (EtOH) action. Here, we examine the role, at the molecular, cellular, and behavioral levels, of the BK β4 subunit in acute tolerance. Single channel recordings in HEK-293 cells show that, in the absence of β4, EtOH potentiation of activity exhibits acute tolerance, which is blocked by coexpressing the β4 subunit. BK channels in acutely isolated medium spiny neurons
from
WT mice (in which the β4 subunit is well-represented) exhibit little tolerance. In contrast, neuronal BK channels from β4 knockout (KO) mice do display acute tolerance. Brain slice recordings showed tolerance to EtOH's effects on spike patterning in KO but not in WT mice. In addition, β4 KO mice develop rapid tolerance to EtOH's locomotor effects, whereas WT mice do not. Finally, in a restricted access ethanol self-administration assay, β4 KO mice drink more than their WT counterparts. Taken together, these data indicate that the β4 subunit controls ethanol tolerance at the molecular, cellular, and behavioral levels, and could determine individual differences in alcohol abuse and alcoholism, as well as represent a therapeutic target for alcoholism.
Ceramide starves cells to death by downregulating nutrient transporter proteins
Authors: Guenther Garret G. , Peralta Eigen R. , Rosales Kimberly Romero , Wong Susan Y. , Siskind Leah J. , Edinger Aimee L.
Published: November 2008

Ceramide induces cell death in response to many stimuli. Its mechanism of action, however, is not completely understood. Ceramide induces autophagy in mammalian cells maintained in rich media and nutrient permease downregulation in yeast. These observations suggested to us that ceramide might kill mammalian cells by limiting cellular access to extracellular nutrients. Consistent with this proposal, physiologically relevant concentrations of ceramide produced a profound and specific downregulation of nutrient transporter proteins in mammalian cells. Blocking ceramide-induced nutrient transporter loss or supplementation with the cell-permeable nutrient, methyl pyruvate, reversed ceramide-dependent toxicity. Conversely, cells became more sensitive to ceramide when nutrient stress was increased by acutely limiting extracellular nutrients, inhibiting autophagy, or deleting AMP-activated protein kinase (AMPK). Observations that ceramide can trigger either apoptosis or caspase-independent cell death may be explained by this model. We found that methyl pyruvate (MP) also protected cells from ceramide-induced, nonapoptotic death consistent with the idea that severe bioenergetic stress was responsible. Taken together, these studies suggest that the cellular metabolic state is an important arbiter of the cellular response to ceramide. In fact, increasing nutrient demand by incubating cells in high levels of growth factor sensitized cells to ceramide. On the other hand, gradually adapting cells to tolerate low levels of extracellular nutrients completely blocked ceramide-induced death. In sum, these results support a model where ceramide kills cells by inducing intracellular nutrient limitation subsequent to nutrient transporter downregulation.
p21
Cip1
restrains pituitary tumor growth
Authors: Chesnokova Vera , Zonis Svetlana , Kovacs Kalman , Ben-Shlomo Anat , Wawrowsky Kolja , Bannykh Serguei , Melmed Shlomo
Published: November 2008

As commonly encountered, pituitary adenomas are invariably benign. We therefore studied protective pituitary proliferative mechanisms. Pituitary tumor transforming gene (
Pttg
) deletion results in pituitary p21 induction and abrogates tumor development in
Rb
+/−
Pttg
−/−
mice. p21 disruption restores attenuated
Rb
+/−
Pttg
−/−
pituitary proliferation rates and enables high penetrance of pituitary, but not thyroid, tumor growth in triple mutant animals (88% of
Rb
+/−
and 72% of
Rb
+/−
Pttg
−/−
p21
−/−
vs. 30% of
Rb
+/−
Pttg
−/−
mice developed pituitary tumors,
P
< 0.001). p21 deletion also accelerated S-phase entry and enhanced transformation rates in triple mutant MEFs. Intranuclear p21 accumulates in
Pttg
-null aneuploid GH-secreting cells, and GH
3
rat pituitary tumor cells overexpressing PTTG also exhibited increased levels of mRNA for both p21 (18-fold,
P
< 0.01) and ATM (9-fold,
P
< 0.01). PTTG is abundantly expressed in human pituitary tumors, and in 23 of 26 GH-producing pituitary adenomas with high PTTG levels, senescence was evidenced by increased p21 and SA-β-galactosidase. Thus, either deletion or overexpression of
Pttg
promotes pituitary cell aneuploidy and p53/p21-dependent senescence, particularly in GH-secreting cells. Aneuploid pituitary cell p21 may constrain pituitary tumor growth, thus accounting for the very low incidence of pituitary carcinomas.
Evidence for marine microfossils from amber
Authors: Girard Vincent , Schmidt Alexander R. , Saint Martin Simona , Struwe Steffi , Perrichot Vincent , Saint Martin Jean-Paul , Grosheny Danièle , Breton Gérard , Néraudeau Didier
Published: November 2008

Amber usually contains inclusions of terrestrial and rarely limnetic organisms that were embedded in the places were they lived in the amber forests. Therefore, it has been supposed that amber could not have preserved marine organisms. Here, we report the discovery amber-preserved marine microfossils. Diverse marine diatoms as well as radiolarians, sponge spicules, a foraminifer, and a spine of a larval echinoderm were found in Late Albian and Early Cenomanian amber samples of southwestern France. The highly fossiliferous resin samples solidified ≈100 million years ago on the floor of coastal mixed forests dominated by conifers. The amber forests of southwestern France grew directly along the coast of the Atlantic Ocean and were influenced by the nearby sea: shells and remnants of marine organisms were probably introduced by wind, spray, or high tide from the beach or the sea onto the resin flows.
In situ carbonation of peridotite for CO2storage
Authors: Kelemen Peter B. , Matter Jürg
Published: November 2008

The rate of natural carbonation of tectonically exposed mantle peridotite during weathering and low-temperature alteration can be enhanced to develop a significant sink for atmospheric CO2. Natural carbonation of peridotite in the Samail ophiolite, an uplifted slice of oceanic crust and upper mantle in the Sultanate of Oman, is surprisingly rapid. Carbonate veins in mantle peridotite in Oman have an average14C age of ≈26,000 years, and are not 30–95 million years old as previously believed. These data and reconnaissance mapping show that ≈104to 105tons per year of atmospheric CO2are converted to solid carbonate minerals via peridotite weathering in Oman. Peridotite carbonation can be accelerated via drilling, hydraulic fracture, input of purified CO2at elevated pressure, and, in particular, increased temperature at depth. After an initial heating step, CO2pumped at 25 or 30 °C can be heated by exothermic carbonation reactions that sustain high temperature and rapid reaction rates at depth with little expenditure of energy. In situ carbonation of peridotite could consume >1 billion tons of CO2per year in Oman alone, affording a low-cost, safe, and permanent method to capture and store atmospheric CO2.
Striatum and pre-SMA facilitate decision-making under time pressure
Authors: Forstmann Birte U. , Dutilh Gilles , Brown Scott , Neumann Jane , von Cramon D. Yves , Ridderinkhof K. Richard , Wagenmakers Eric-Jan
Published: November 2008

Human decision-making almost always takes place under time pressure. When people are engaged in activities such as shopping, driving, or playing chess, they have to continually balance the demands for fast decisions against the demands for accurate decisions. In the cognitive sciences, this balance is thought to be modulated by a response threshold, the neural substrate of which is currently subject to speculation. In a speed decision-making experiment, we presented participants with cues that indicated different requirements for response speed. Application of a mathematical model for the behavioral data confirmed that cueing for speed lowered the response threshold. Functional neuroimaging showed that cueing for speed activates the striatum and the pre-supplementary motor area (pre-SMA), brain structures that are part of a closed-loop motor circuit involved in the preparation of voluntary action plans. Moreover, activation in the striatum is known to release the motor system from global inhibition, thereby facilitating faster but possibly premature actions. Finally, the data show that individual variation in the activation of striatum and pre-SMA is selectively associated with individual variation in the amplitude of the adjustments in the response threshold estimated by the mathematical model. These results demonstrate that when people have to make decisions under time pressure their striatum and pre-SMA show increased levels of activation.
A 12,000-year-old Shaman burial from the southern Levant (Israel)
Authors: Grosman Leore , Munro Natalie D. , Belfer-Cohen Anna
Published: November 2008

The Natufians of the southern Levant (15,000–11,500 cal BP) underwent pronounced socioeconomic changes associated with the onset of sedentism and the shift from a foraging to farming lifestyle. Excavations at the 12,000-year-old Natufian cave site, Hilazon Tachtit (Israel), have revealed a grave that provides a rare opportunity to investigate the ideological shifts that must have accompanied these socioeconomic changes. The grave was constructed and specifically arranged for a petite, elderly, and disabled woman, who was accompanied by exceptional grave offerings. The grave goods comprised 50 complete tortoise shells and select body-parts of a wild boar, an eagle, a cow, a leopard, and two martens, as well as a complete human foot. The interment rituals and the method used to construct and seal the grave suggest that this is the burial of a shaman, one of the earliest known from the archaeological record. Several attributes of this burial later become central in the spiritual arena of human cultures worldwide.
Orthogonal dipolar interactions between amide carbonyl groups
Authors: Fischer Felix R. , Wood Peter A. , Allen Frank H. , Diederich François
Published: November 2008

Orthogonal dipolar interactions between amide C=O bond dipoles are commonly found in crystal structures of small molecules, proteins, and protein–ligand complexes. We herein present the experimental quantification of such interactions by employing a model system based on a molecular torsion balance. Application of a thermodynamic double-mutant cycle allows for the determination of the incremental energetic contributions attributed to the dipolar contact between 2 amide C=O groups. The stabilizing free interaction enthalpies in various apolar and polar solvents amount to −2.73 kJ mol−1and lie in the same range as aromatic-aromatic C–H⋯π and π–π interactions. High-level intermolecular perturbation theory (IMPT) calculations on an orthogonal acetamide/N-acetylpyrrole complex in the gas phase at optimized contact distance predict a favorable interaction energy of −9.71 kJ mol−1. The attractive dipolar contacts reported herein provide a promising tool for small-molecule crystal design and the enhancement of ligand–protein interactions during lead optimization in medicinal chemistry.
Production of healthy cloned mice from bodies frozen at −20°C for 16 years
Authors: Wakayama Sayaka , Ohta Hiroshi , Hikichi Takafusa , Mizutani Eiji , Iwaki Takamasa , Kanagawa Osami , Wakayama Teruhiko
Published: November 2008

Cloning animals by nuclear transfer provides an opportunity to preserve endangered mammalian species. However, it has been suggested that the “resurrection” of frozen extinct species (such as the woolly mammoth) is impracticable, as no live cells are available, and the genomic material that remains is inevitably degraded. Here we report production of cloned mice from bodies kept frozen at −20 °C for up to 16 years without any cryoprotection. As all of the cells were ruptured after thawing, we used a modified cloning method and examined nuclei from several organs for use in nuclear transfer attempts. Using brain nuclei as nuclear donors, we established embryonic stem cell lines from the cloned embryos. Healthy cloned mice were then produced from these nuclear transferred embryonic stem cells by serial nuclear transfer. Thus, nuclear transfer techniques could be used to “resurrect” animals or maintain valuable genomic stocks from tissues frozen for prolonged periods without any cryopreservation.