bluuebunny/crossref_metadata_2025 huggingface dataset:
A CASE STUDY OF ARTHROPODS PRESERVED ON ARCHAEOLOGICAL BRONZES—MICRO‐ARCHAEOLOGICAL INVESTIGATION HELPS RECONSTRUCTING PAST ENVIRONMENTS
Authors: ROBBIOLA L. , MORET P. , LEJARS T.
Published: May 2011

This paper offers new perspectives for improving our knowledge of arthropods in wet and aerobic archaeological contexts. The very‐near environment of uncleaned buried bronze artefacts, two ronde‐bosse ornaments of a Celtic grave from the Iron Age (275 to 250 bc, La Fosse‐Cotheret, Roissy‐en‐France), was studied by means of optical and scanning electron microscopies. Taking into account recent knowledge on bronze corrosion (decuprification), this micro‐investigation (micro‐archaeology) allowed identification of two fossilized arthropods—Cryptophagus sp. (Insecta, Coleoptera, Cryptophagidae) and Coccotydaeolus sp. (Acari, Tydaeoidea, Iolinidae)—which sheds some light upon the complex taphonomic process that occurred after the burial of a Celtic chariot. These first results support the idea that the local corroded metal/soil system has to be investigated for a better understanding of archaeological microenvironments. Efficient minute investigation of soiled bronzes could be performed prior to systematic cleaning of artefacts.
ELECTROCHEMISTRY AND AUTHENTICATION OF ARCHAEOLOGICAL LEAD USING VOLTAMMETRY OF MICROPARTICLES: APPLICATION TO THE TOSSAL DE SANT MIQUEL IBERIAN PLATE
Authors: DOMÉNECH‐CARBÓ A. , DOMÉNECH‐CARBÓ M. T. , PEIRÓ‐RONDA M. A. , OSETE‐CORTINA L.
Published: May 2011

An essentially non‐invasive electrochemical methodology addressed to the authentication of archaeological lead is described. The method is based on the record of the voltammetric response of nanosamples from the archaeological artefact mechanically transferred to a graphite ‘pencil’ electrode in contact with aqueous buffers. Three diagnostic criteria for authentication are described based on the appearance of: (i) oxidative dissolution signals for trace metals like copper, arsenic, antimony and, often, tin and silver accompanying stripping peaks for lead, (ii) peak potential shifts for reduction peaks for patination products, and (iii) the presence of reduction peaks for PbO2. The method is applied to the authentication of an Iberian lead plate from the Tossal de Sant Miquel (Llíria, Spain) site using a series of genuine and false pieces from different provenances in the Valencian region (Spain).
Intention to Smoke Tobacco Using a Waterpipe Among Students in a Southeastern U.S. College
Authors: Noonan Devon , Kulbok Pamela , Yan Guofen
Published: May 2011

ABSTRACT Objective: Guided by the Theory of Reasoned Action, this study examined the association of behavioral beliefs, attitudes, normative beliefs, and subjective norms with waterpipe tobacco smoking intention in college students.

Design and Sample: A cross‐sectional design was used. A Web‐based survey was sent to a random sample of 1,000 undergraduate students from a public institution in the southeast to recruit participants.

Measures: The Theory of Reasoned Action Waterpipe Questionnaire, a modified version of the Fishbein‐Ajzen‐Hanson Questionnaire, was used to capture modal constructs of the Theory of Reasoned Action related to waterpipe use. Cronbach's α coefficients for the scales of the Theory of Reasoned Action Waterpipe Questionnaire ranged from .76 to .95.

Results: Of the sample (n=223), 13.5% currently smoked a waterpipe and 61% had ever done so. Using multiple regression, attitudes, behavioral beliefs, and subjective norms were associated with intention to smoke a waterpipe in the next 3 months and collectively explained 35% of the variance in intention. The full model, which included all the constructs of the Theory of Reasoned Action, demographic variables, and tobacco use variables, explained 83% of the variance in intention to smoke a waterpipe in the next 3 months.

Conclusions: This study provides valuable information that may be used to target students at risk for waterpipe smoking and serves as a starting point in developing theoretically driven interventions to prevent waterpipe smoking.
Early Ultrasound‐Guided Neurolysis for Pain Management in Gastrointestinal and Pelvic Malignancies: An Observational Study in a Tertiary Care Center of Urban India
Authors: Bhatnagar Sushma , Khanna Sandeep , Roshni S. , Goyal Gaurav N. , Mishra Seema , Rana Shiv P. S. , Thulkar Sanjay
Published: May 2011

Abstract:  Patients with advanced gastrointestinal and pelvic malignancies commonly present with pain of varying severity. In a majority of these patients, pain can be effectively managed using an integrated systemic pharmacological approach with oral morphine being the cornerstone of treatment. However, with escalating doses, intolerable side effects of oral morphine may lead to patient dissatisfaction. When oral pharmacotherapy fails to adequately address the issue of pain or leads to insufferable side effects, neurolytic blocks of the sympathetic axis are usually used for pain alleviation. As these blocks may reduce oral analgesic requirement, a reevaluation of their timing is merited. This article presents our hospital‐based in‐patient palliative care unit experience with early ultrasonography‐guided neurolysis of celiac plexus, superior hypogastric plexus and ganglion impar. Of the 44 patients we studied, 20 underwent celiac plexus neurolysis, 18 superior hypogastric plexus neurolysis, and 6 ganglion impar neurolysis. Their pain was being managed with oral morphine before neurolysis, but only 11.4% patients required oral morphine for satisfactory pain control, 2 months after neurolysis. The mean Visual Analog Scale score before block placement was 5.64 ± 0.69 and fell to 2.25 ± 1.33 at 2 months post neurolysis (P < 0.001). We suggest that bedside ultrasonography‐guided sympathetic axis neurolysis may be employed early in patients with incurable abdominal or pelvic cancer. Its use as a first‐line intervention for achieving pain control with minimal complications warrants further consideration and investigation. ▪
Municipal Debt and Marginal Tax Rates: Is There a Tax Premium in Asset Prices?
Authors: LONGSTAFF FRANCIS A.
Published: May 2011

We study the marginal tax rate incorporated into short‐term municipal rates using municipal swap market data. Using an affine model, we identify the marginal tax rate and the credit/liquidity spread in 1‐week tax‐exempt rates, as well as their associated risk premia. The marginal tax rate averages 38.0% and is related to stock, bond, and commodity returns. The tax risk premium is negative, consistent with the strong countercyclical nature of after‐tax fixed‐income cash flows. These results demonstrate that tax risk is a systematic asset pricing factor and help resolve the muni‐bond puzzle.
Watch What I Do, Not What I Say: The Unintended Consequences of the Homeland Investment Act
Authors: DHARMAPALA DHAMMIKA , FOLEY C. FRITZ , FORBES KRISTIN J.
Published: May 2011

The Homeland Investment Act provided a tax holiday for the repatriation of foreign earnings. Advocates argued the Act would alleviate financial constraints by reducing the cost to U.S. multinationals of accessing internal capital. This paper shows that repatriations did not increase domestic investment, employment, or R&D—even for firms that appeared to be financially constrained or lobbied for the holiday. Instead, a $1 increase in repatriations was associated with a $0.60 to $0.92 increase in shareholder payouts. Regulations intended to restrict such payouts were undermined by the fungibility of money. Results indicate that U.S. multinationals were not financially constrained and were well‐governed.
The Illiquidity of Corporate Bonds
Authors: BAO JACK , PAN JUN , WANG JIANG
Published: May 2011

This paper examines the illiquidity of corporate bonds and its asset‐pricing implications. Using transactions data from 2003 to 2009, we show that the illiquidity in corporate bonds is substantial, significantly greater than what can be explained by bid–ask spreads. We establish a strong link between bond illiquidity and bond prices. In aggregate, changes in market‐level illiquidity explain a substantial part of the time variation in yield spreads of high‐rated (AAA through A) bonds, overshadowing the credit risk component. In the cross‐section, the bond‐level illiquidity measure explains individual bond yield spreads with large economic significance.
Do Individual Investors Have Asymmetric Information Based on Work Experience?
Authors: DØSKELAND TROND M. , HVIDE HANS K.
Published: May 2011

Using a novel data set covering all individual investors' stock market transactions in Norway over 10 years, we analyze whether individual investors have a preference for professionally close stocks, and whether they make excess returns on such investments. After excluding own‐company stock holdings, investors hold 11% of their portfolio in stocks within their two‐digit industry of employment. Given the poor hedging properties of such investments, one would expect abnormally high returns. In contrast, all estimates of abnormal returns are negative, in many cases statistically significant. Overconfidence seems the most likely explanation for the excessive trading in professionally close stocks.
The Expanding Boundaries of Linguistic Anthropology: 2010 in Perspective
Authors: Monaghan Leila
Published: May 2011

ABSTRACT  In 2010, scholars of language and culture developed broader and more dynamic ways to understand traditional approaches in the anthropological study of language, reframed our analyses of communicative events, created new ways to understand the co‐construction of languages and social organizations from the family to the nation‐state, and forged activist partnerships with the communities we worked with on issues including social justice, language revitalization, and education. In this review article, I reflect on 2010 work in journals, books, and conference papers within the field of linguistic anthropology and in associated disciplines.
Anthropology Becoming … ? The 2010 Sociocultural Anthropology Year in Review
Authors: Hamilton Jennifer A. , Placas Aimee J.
Published: May 2011

ABSTRACT  In this article, we seek to outline some of the key impulses, both substantive and methodological, in cultural anthropology in 2010 as represented in the four main peer‐reviewed journals: American Anthropologist, American Ethnologist, Cultural Anthropology, and Current Anthropology. We identify four main themes of particular significance in terms of theoretical intervention and methodological innovation: Gilles Deleuze, indigeneity, natureculture (multispecies ethnography), and security.
Making Class and Gender: (Market) Socialist Enframing of Traders in Ho Chi Minh City
Authors: Leshkowich Ann Marie
Published: May 2011

ABSTRACT Over the past four decades, petty traders in Bến Thành market (Ho Chi Minh City) and Vietnamese officials have experienced and propelled rapid economic, political, and social transformations entailing reconfigurations of class and gender. Exploring the co‐construction of class and gender through state and individual narratives and performances, I here make three contributions to anthropological scholarship on socialism and late, post‐, and market socialism. First, I highlight the importance of associative gendered logics to government efforts to deploy new, morally compelling notions of class. Second, I demonstrate that socialist constructions of gender and class are not simply imposed on resistant subjects but also internalized as meaningful structures of sentiment, even among those otherwise ambivalent toward state authority. Third, I reveal that state socialist logics provide fertile ground for those enframed to exercise strategic essentialism (Spivak 1995) that affords symbolic or material advantage, even as it might also reproduce marginality.
Cultivating an Ecological and Social Balance: Elite Demands and Commoner Knowledge in Ancient Ma‘ohi Agriculture, Society Islands
Authors: Lepofsky Dana , Kahn Jennifer
Published: May 2011

ABSTRACT  Anthropological views of past human–environmental interactions are influenced by the data sets used and the subjects of study. In this article, we seek a balanced view of ancient human–environmental interactions in the Society Islands. We explore the social and ecological contexts of agricultural production by incorporating archaeological and ethnographic data as well as the motivations and actions of Ma‘ohi elites and commoners. Both elites and commoners contributed to long‐term agricultural productivity. The elite did so through periodic restrictions on harvesting; the farmers contributed ecological knowledge acquired through generations of on‐the‐ground experience. Our fine‐scale examination of the archaeological remains of three agricultural systems in the ‘Opunohu Valley indicates that the roles of elite and commoner played out differently depending on their social‐spatial proximity. By refocusing our analyses on all players in the production system, a more nuanced understanding of the range of ancient environmental and social interactions emerges.
Assessment of pain in women randomly allocated to speculum or digital insertion of the Foley catheter for induction of labor
Authors: JONSSON MARIA , HELLGREN CHARLOTTE , WIBERG‐ITZEL EVA , ÅKERUD HELENA
Published: May 2011

Objective. The primary aim was to assess pain subjectively and objectively in women during insertion of a Foley catheter for induction of labor. A secondary aim was to assess pain during cervical ripening and to evaluate maternal satisfaction. Design. Randomized controlled trial. Setting. University hospital, Sweden. Population. Forty‐two women undergoing induction of labor and cervical ripening with a Foley catheter. Methods. Women were randomly allocated to digital (n=21) or to speculum (n=21) placement of a Foley catheter. A visual analogue scale (VAS) was used for subjective assessment of pain and, for objective measurements, a skin conductance algesimeter was used and the area under the curve (AUC) was calculated (μSs). Maternal satisfaction was evaluated in a questionnaire. Main outcome measures. Pain sensation during placement of the Foley catheter. Results. There was a significant difference between groups in pain measurements during insertion of the Foley catheter. The speculum group had higher median pain scores than the digital group, VAS=5 vs. = 3 (p=0.03) and greater median AUC measurements: 1840 vs. 823μSs (p=0.04). There was no difference in pain assessments during cervical ripening. Overall satisfaction scores were high and comparable between groups. Conclusion. Digital placement of the Foley catheter is subjectively and objectively less painful compared to the use of a speculum. Digital placement should therefore be considered as an alternative in the management of these patients. Ripening of the cervix with the Foley catheter is well tolerated and the overall satisfaction rate among patients induced with this method is high.
Insights into the Rrf2 repressor family – the structure of CymR, the global cysteine regulator of Bacillus subtilis
Authors: Shepard William , Soutourina Olga , Courtois Emmanuelle , England Patrick , Haouz Ahmed , Martin‐Verstraete Isabelle
Published: May 2011

The global regulator CymR represses the transcription of a large set of genes involved in cystine uptake and cysteine biosynthesis in Bacillus subtilis and Staphylococcus aureus. This repressor belongs to the widespread and poorly characterized Rrf2 family of regulators. The crystal structure of CymR from B. subtilis reveals a biologically active dimer, where each monomer folds into two tightly packed domains: a DNA‐binding domain, which houses a winged helix–turn–helix (wHTH) motif; and a long dimerization domain, which places the wHTH motifs at the extremes. This architecture explains how these small regulators can span 23–27‐bp DNA targets. The wHTH motif of CymR resembles those of the GntR superfamily of regulators, such as FadR and HutC. Superimposing the FadR wHTH motifs bound to their DNA fragments onto the wHTH motifs of the CymR dimer structure suggests that the DNA target and/or the protein must undergo some conformational changes upon binding. The CymR structure also hints at a possible location of the Fe–S centre associated with several Rrf2‐type regulators.

Structured digital abstract

CymR
 binds to CymR by x‐ray crystallography (View Interaction 1, 2)
The Population Policy Debate from a Natural Resource Perspective: Reflections from the Wentworth Group
Authors: THOM BRUCE , MCKENZIE FIONA
Published: May 2011

Generations of Australians, especially those who live in rural or remote areas, have struggled to better understand, manage, and adapt to Australia's unique environmental conditions. Increased awareness of pressures and impacts of population growth has renewed the long‐standing debate on the nation's capacity to sustainably manage natural resources. Since 2002, the Wentworth Group of Concerned Scientists has been active in debates linking science and public policy with a declared intent to inform decision‐makers on ways to adapt to changing Australian environmental conditions, assuming a growing population. The purpose of this paper is to reflect on the population policy debate from the perspective of an entity that has as its prime objective to improve the nation's capacity to adapt to these changing conditions by influencing public policy on natural resource management.
Evaluation of MODFLOW‐LGR in Connection with a Synthetic Regional‐Scale Model
Authors: Vilhelmsen Troels N. , Christensen Steen , Mehl Steffen W.
Published: May 2011

This work studies costs and benefits of utilizing local‐grid refinement (LGR) as implemented in MODFLOW‐LGR to simulate groundwater flow in a buried tunnel valley interacting with a regional aquifer. Two alternative LGR methods were used: the shared‐node (SN) method and the ghost‐node (GN) method. To conserve flows the SN method requires correction of sources and sinks in cells at the refined/coarse‐grid interface. We found that the optimal correction method is case dependent and difficult to identify in practice. However, the results showed little difference and suggest that identifying the optimal method was of minor importance in our case. The GN method does not require corrections at the models' interface, and it uses a simpler head interpolation scheme than the SN method. The simpler scheme is faster but less accurate so that more iterations may be necessary. However, the GN method solved our flow problem more efficiently than the SN method. The MODFLOW‐LGR results were compared with the results obtained using a globally coarse (GC) grid. The LGR simulations required one to two orders of magnitude longer run times than the GC model. However, the improvements of the numerical resolution around the buried valley substantially increased the accuracy of simulated heads and flows compared with the GC simulation. Accuracy further increased locally around the valley flanks when improving the geological resolution using the refined grid. Finally, comparing MODFLOW‐LGR simulation with a globally refined (GR) grid showed that the refinement proportion of the model should not exceed 10% to 15% in order to secure method efficiency.
Changes in Quality, Liking, and Purchase Intent of Irradiated Fresh‐Cut Spinach during Storage
Authors: Fan Xuetong , Sokorai Kimberly J.B.
Published: May 2011

Abstract:  The use of ionizing radiation to enhance microbial safety of fresh spinach at a maximum dose of 4 kGy has been approved by the U.S. Food and Drug Administration (FDA). However, whether spinach can tolerate those high doses of radiation is unclear. Therefore, this study was conducted to investigate the effects of irradiation and storage on quality, liking, and purchase intent of fresh‐cut spinach. The oxygen radical absorbance capacity values and total phenolic content were not consistently affected by irradiation. However, the ascorbic acid content of irradiated sample decreased rapidly during storage, resulting in these samples being lower in ascorbic acid content than controls after 7 and 14 d of storage at 4 °C. Sensory evaluation by a 50‐member panel revealed that purchase intent and ratings for liking of appearance, aroma, texture, flavor, and overall were not affected by irradiation at doses up to 2 kGy. Therefore, irradiation at doses up to 2 kGy may be used to enhance microbial safety without affecting consumer acceptance or overall antioxidant values of irradiated spinach.
Effects of Roasting Conditions on the Physicochemical Properties and Volatile Distribution in Perilla Oils (Perilla frutescens var. japonica)
Authors: Park Min Hee , Seol Nam Gyu , Chang Pahn‐Shick , Yoon Suk Hoo , Lee Jae Hwan
Published: May 2011

Abstract:  Perilla seeds have more than 60% of α‐linolenic acid, one of omega‐3 essential fatty acids. Headspace volatiles and physicochemical properties including color, fluorescence intensity, and the oxidation products in perilla oil (PO) from perilla seeds roasted at different conditions were analyzed. Roasting temperature was 150, 170, 190, and 210 °C, and roasting time was 15 and 30 min at each roasting temperature. PO from higher roasting temperature and longer roasting time had lower L* values, higher a*, b*, and chroma values, more brown pigments and fluorescence intensity, and more conjugated dienoic acids. Pyrazines were major volatiles in PO, and furans, sulfur‐containing compounds, and hydrocarbons were also detected by a solid phase microextraction gas chromatography/mass spectrometry. In PO, 2,5‐Dimethylpyrazine and 2‐furancarboxaldehyde were 2 major volatiles. The principal component analysis of volatiles showed the 1st principal component (PC1) and the 2nd principal component (PC2) express 56.64% and 22.72% of the volatile variability in PO, respectively, which can differentiate PO prepared from roasting conditions clearly. Some physicochemical properties especially brown pigment and volatiles were positively correlated with each other in PO.

Practical Application:  Perilla oil (PO) from perilla seeds possesses more than 60% of α‐linolenic acid, one of omega‐3 fatty acids. Roasting process has been used to extract oil from perilla seeds. Understanding physicochemical properties of PO from diverse roasting conditions are important steps to produce PO in food industry. Roasting process induces darkening of color, increase of fluorescence intensity, and brown pigments in PO. Pyrazines and furans are major headspace volatiles in PO roasted above 170 °C. The results of this study can help to produce PO in industrial scales with desired headspace volatiles, colors, and oxidative state.
Correlating Changes That Occur in Chemical Properties with the Generation of Antioxidant Capacity in Different Sugar‐Amino Acid Maillard Reaction Models
Authors: Chen Xiu‐Min , Kitts David D.
Published: May 2011

Abstract:  We investigated the development of antioxidant activity relative to the change of pH, fluorescent intensity, ultraviolet (UV) absorbance (A294), browning (A420), and alpha‐dicarbonyl compounds in sugar‐amino acid Maillard reaction (MR) model systems comprising fructose, glucose, or ribose each with glycine (Fru‐Gly, Glu‐Gly, and Rib‐Gly) or lysine (Fru‐Lys, Glu‐Lys, and Rib‐Lys), respectively, which were heated at 121 °C for 5 to 90 min. For hexose models, the change in pH was shown to fit a second‐order polynomial regression with A294 and A420. Antioxidant activity was significantly and positively correlated with UV absorbance (r = 0.905, P < 0.001) and browning products (r = 0.893, P < 0.001) rather than with fluorescent products or the alpha‐dicarbonyl compounds. Type of sugar was most important in evoking a change in UV absorbance, browning, alpha‐dicarbonyl compounds, and antioxidant activity of MR products (MRPs). In conclusion, the antioxidant activity of MRPs in six model systems was more closely associated with products derived at the intermediate‐to‐late stages of the reaction and influenced mostly by the type of sugar.

Practical Application:  We report on the different factors and their interactions that are important for understanding the functional attributes of food components that comprise the generation of Maillard browning products and the associated antioxidant activities generated during high‐temperature food processing.
Temperature Predictions and Comparison With Measurements for the Blade Leading Edge and Platform of a 1 1/2 Stage Transonic HP Turbine
Authors: Mathison Randall M. , Wishart Mark B. , Haldeman Charles W. , Dunn Michael G.
Published: May 2011

A series of computational predictions generated using FINE/TURBO are compared with data to investigate implementation techniques available for predicting temperature migration through a turbine stage. The experimental results used for comparison are from a one-and-one-half stage turbine operating at design-corrected conditions in a short-duration facility. Measurements of the boundary conditions are used to set up the computational models, and the predicted temperatures are compared with measured fluid temperatures at the blade leading edge and just above the blade platform. Fluid temperature measurements have not previously been available for these locations in a transonic turbine operating at design-corrected conditions, so this represents a novel comparison. Accurate predictions for this short-duration turbine experiment require use of the isothermal wall boundary condition instead of an adiabatic boundary condition and accurate specification of the inlet temperature profile all the way to the wall. Predictions using the harmonic method agree with the temperatures measured for the blade leading edge from 65% to 95% span to within 1% normalized temperature data. Agreement over much of the rest of the leading edge is within 5% of the measured value. Comparisons at 5–10% span and for the blade platform show larger differences up to 10%, which indicates that the flow in this region is not fully captured by the prediction. This is not surprising since the purge cavity and platform leading-edge features present in the experiment are treated as a smooth hub wall in the current simulation. This work represents a step toward the larger goal of accurately predicting surface heat-flux for the complicated environment of an operational engine as it is reproduced in a laboratory setting. The experiment upon which these computations are based includes realistic complications such as one-dimensional and two-dimensional inlet temperature profiles, a heavily film-cooled vane, and purge cooling. While the ultimate goal is to accurately handle all of these features, the current model focuses on the treatment of a subset of experiments performed for a one-dimensional radial inlet temperature profile and no cooling.
Influence of Chord Length and Inlet Boundary Layer on the Secondary Losses of Turbine Blades
Authors: Sauer Helmut , Schmidt Robin , Vogeler Konrad
Published: May 2011

In this paper, results concerning the influence of chord length and inlet boundary layer thickness on the endwall loss of a linear turbine cascade are discussed. The investigations were performed in a low speed cascade tunnel using the turbine profile T40. The turning of 90 deg and 70 deg, the velocity ratio in the cascade from 1.0 to 3.5 as well as the chord length of 100 mm, 200 mm, and 300 mm were specified. In a measurement distance of one chord behind the cascade in main flow direction, an approximate proportionality of endwall loss and chord was observed in a wide range of velocity ratios. At small measurement distances (e.g., s2/l=0.4), this proportionality does not exist. If a part of the flow path within the cascade is approximately incorporated, a proportionality to the chord at small measurement distances can be obtained, too. Then, the magnitude of the endwall loss mainly depends on the distance in main flow direction. At velocity ratios near 1.0, the influence of the chord decreases rapidly, while at a velocity ratio of 1.0, the endwall loss is independent of the chord. By varying the inlet boundary layer thickness, no correlation of displacement thickness and endwall loss was achieved. A calculation method according to the modified integral equation by van Driest delivers the wall shear stress. Its influence on the endwall loss was analyzed.
Simple self-gettering differential-pump for minimizing source oxidation in oxide-MBE environment
Authors: Kim Yong-Seung , Bansal Namrata , Oh Seongshik
Published: May 2011

Source oxidation of easily oxidizing elements such as Ca, Sr, Ba, and Ti in an oxidizing ambient leads to their flux instability and is one of the biggest problems in the multielemental oxide molecular beam epitaxy technique. Here, the authors report a new scheme that can completely eliminate the source oxidation problem: a self-gettering differential pump using the source itself as the pumping medium. The pump simply comprises a long collimator mounted in front of the source in extended port geometry. With this arrangement, the oxygen partial pressure near the source was easily maintained well below the source oxidation regime, resulting in a stabilized flux, comparable to that of an ultrahigh-vacuum environment. Moreover, this pump has a self-feedback mechanism that allows a stronger pumping effectiveness for more easily oxidizing elements, which is a desired property for eliminating the source oxidation problem.
PCR-based tissue identification: the UCLH experience
Authors: Amin Sepideh , Freeman Alex , Arora Rupali , Diss Tim C
Published: May 2011

The need to accurately identify tissue of an individual can arise in a variety of settings including mislabelled slides or sample carryover. Reported rates of carryover range from 0.6% to 2.9% of slides depending on the methods of evaluation. Carryover becomes particularity clinically important when malignant tissue is found in an otherwise benign sample. The suspicion of malignancy causes immense psychological stress to the patient and results in additional management costs due to the additional investigations required to rule out malignancy. Proving a negative can be difficult and many cases result in lifelong follow-up for the patient. Molecular techniques such as PCR amplification of simple tandem repeat (STR) sequences can be used to identify tissue and hence its provenance. At University College London Hospital, STR PCR analysis has been used since 2003. Here the authors report their experience with regard to the clinical scenarios, the technique used and the outcomes.
Specific epidermal growth factor receptor autophosphorylation sites promote mouse colon epithelial cell chemotaxis and restitution
Authors: Yamaoka Toshimitsu , Frey Mark R. , Dise Rebecca S. , Bernard Jessica K. , Polk D. Brent
Published: May 2011

Upon ligand binding, epidermal growth factor (EGF) receptor (R) autophosphorylates on COOH-terminal tyrosines, generating docking sites for signaling partners that stimulate proliferation, restitution, and chemotaxis. Specificity for individual EGFR tyrosines in cellular responses has been hypothesized but not well documented. Here we tested the requirement for particular tyrosines, and associated downstream pathways, in mouse colon epithelial cell chemotactic migration. We compared these requirements to those for the phenotypically distinct restitution (wound healing) migration. Wild-type, Y992/1173F, Y1045F, Y1068F, and Y1086F EGFR constructs were expressed in EGFR−/−cells; EGF-induced chemotaxis or restitution were determined by Boyden chamber or modified scratch wound assay, respectively. Pharmacological inhibitors of p38, phospholipase C (PLC), Src, MEK, JNK/SAPK, phosphatidylinositol 3-kinase (PI 3-kinase), and protein kinase C (PKC) were used to block EGF-stimulated signaling. Pathway activation was determined by immunoblot analysis. Unlike wild-type EGFR, Y992/1173F and Y1086F EGFR did not stimulate colon epithelial cell chemotaxis toward EGF; Y1045F and Y1068F EGFR partially stimulated chemotaxis. Only wild-type EGFR promoted colonocyte restitution. Inhibition of p38, PLC, and Src, or Grb2 knockdown, blocked chemotaxis; JNK, PI 3-kinase, and PKC inhibitors or c-Cbl knockdown blocked restitution but not chemotaxis. All four EGFR mutants stimulated downstream signaling in response to EGF, but Y992/1173F EGFR was partially defective in PLCγ activation whereas both Y1068F and Y1086F EGFR failed to activate Src. We conclude that specific EGFR tyrosines play key roles in determining cellular responses to ligand. Chemotaxis and restitution, which have different migration phenotypes and physiological consequences, have overlapping but not identical EGFR signaling requirements.
Histamine receptor H1 in the nucleus tractus solitarii regulates arterial pressure and heart rate in rats
Authors: Bhuiyan Mohammad E. , Waki Hidefumi , Gouraud Sabine S. , Takagishi Miwa , Kohsaka Akira , Maeda Masanobu
Published: May 2011

Axons of histamine (HA)-containing neurons are known to project from the posterior hypothalamus to many areas of the brain, including the nucleus tractus solitarii (NTS), a central brain structure that plays an important role in regulating arterial pressure. However, the functional significance of NTS HA is still not fully established. In this study, we microinjected HA or 2-pyridylethylamine, a HA-receptor H1-specific agonist, into the NTS of urethane-anesthetized Wister rats to identify the potential functions of NTS HA on cardiovascular regulation. When HA or H1-receptor-specific agonist was bilaterally microinjected into the NTS, mean arterial pressure (MAP) and heart rate (HR) were significantly increased, whereas pretreatment with the H1-receptor-specific antagonist cetirizine into the NTS significantly inhibited the cardiovascular responses. The maximal responses of MAP and HR changes induced by HA or H1-receptor-specific agonist were dose dependent. We also confirmed gene expression of HA receptors in the NTS and that the expression level of H1 mRNA was higher than that of the other subtypes. In addition, we found that H1 receptors are mainly expressed in neurons of the NTS. These findings suggested that HA within the NTS may play a role in regulating cardiovascular homeostasis via activation of H1 receptors expressed in the NTS neurons.
Effects of carbenoxolone on flow-mediated vasodilatation in healthy adults
Authors: Lan Wei-Ren , Hou Charles Jia-Yin , Yen Chih-Hsuan , Shih Bing-Fu , Wang An-Mei , Lee Tzung-Yi , Tsai Cheng-Ho , Yeh Hung-I
Published: May 2011

Gap junctions play a key role in maintaining the functional integrity of the vascular wall. Using carbenoxolone (CBX) as a gap junction blocker, we aimed to assess the contribution of gap junctions in the vascular wall to flow-mediated vasodilatation (FMD) in healthy adults. Percentage FMD (%FMD) and circulating vasoactive molecules/activity, including atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), aldosterone, cortisol, plasma renin activity (PRA), and endothelin (ET-1), were measured in 25 healthy volunteers (mean age: 30.1 ± 5.4 yr; 14 males) before and after oral administration of CBX (100 mg). %FMD decreased after ingestion of CBX (9.71 ± 3.1 vs. 3.40 ± 2.0%; P < 0.0001). The levels of ANP, BNP, cortisol, and ET-1 remained stationary, while both PRA and aldosterone decreased ( P < 0.005) after CBX ingestion. Blood pressure and heart rate were minimally changed by CBX. Inhibition of gap junctional communication by CBX impairs FMD in healthy persons, suggesting that physiologically, vascular gap junctions participate in the maintenance of FMD. CBX does not induce the release of vasoconstricting molecules or enhance vasoconstriction, suggesting that inhibition of gap junctional communication by CBX underlies the impairment of FMD. Therefore, administering CBX in FMD examination can be a way to follow the effect of gap junctions on endothelial function, but further work remains to verify the specificity of CBX effect.
Increases in cerebrovascular impedance in older adults
Authors: Zhu Yong-Sheng , Tseng Benjamin Y. , Shibata Shigeki , Levine Benjamin D. , Zhang Rong
Published: May 2011

This study explored a novel method for measuring cerebrovascular impedance to quantify the relationship between pulsatile changes in cerebral blood flow (CBF) and arterial pressure. Arterial pressure in the internal or common carotid artery (applanation tonometry), CBF velocity in the middle cerebral artery (transcranial Doppler), and end-tidal CO2 (capnography) were measured in six young (28 ± 4 yr) and nine elderly subjects (70 ± 6 yr). Transfer function method was used to estimate cerebrovascular impedance. Under supine resting conditions, CBF velocity was reduced in the elderly despite the fact that they had higher arterial pressure than young subjects. As expected, cerebrovascular resistance index was increased in the elderly. In both young and elderly subjects, impedance modulus was reduced gradually in the frequency range of 0.78–8 Hz. Phase was negative in the range of 0.78–4.3 Hz and fluctuated at high frequencies. Compared with the young, impedance modulus increased by 38% in the elderly in the range of 0.78–2 Hz and by 39% in the range of 2–4 Hz ( P < 0.05). Moreover, increases in impedance were correlated with reductions in CBF velocity. Collectively, these findings demonstrate the feasibility of assessing cerebrovascular impedance using the noninvasive method developed in this study. The estimated impedance modulus and phase are similar to those observed in the systemic circulation and other vascular beds. Moreover, increases in impedance in the elderly suggest that arterial stiffening, besides changes in cerebrovascular resistance, contributes to reduction in CBF with age.
Preconditioned Endothelial Progenitor Cells Reduce Formation of Melanoma Metastases through SPARC-Driven Cell–Cell Interactions and Endocytosis
Authors: Defresne Florence , Bouzin Caroline , Grandjean Marie , Dieu Marc , Raes Martine , Hatzopoulos Antonis K. , Kupatt Christian , Feron Olivier
Published: May 2011

Tumor progression is associated with the release of signaling substances from the primary tumor into the bloodstream. Tumor-derived cytokines are known to promote the mobilization and the recruitment of cells from the bone marrow, including endothelial progenitor cells (EPC). Here, we examined whether such paracrine influence could also influence the capacity of EPC to interfere with circulating metastatic cells. We therefore consecutively injected EPC prestimulated by tumor-conditioned medium (EPC-CM) and luciferase-expressing B16 melanoma cells to mice. A net decrease in metastases spreading (vs. nonstimulated EPC) led us to carry out a 2-dimensional difference gel electrophoresis (2D-DIGE) proteomic study to identify possible mediators of EPC-driven protection. Among 33 proteins exhibiting significant changes in expression, secreted protein, acidic and rich in cysteine (SPARC) presented the highest induction after EPC exposure to CM. We then showed that contrary to control EPC, SPARC-silenced EPC were not able to reduce the extent of metastases when injected with B16 melanoma cells. Using adhesion tests and the hanging drop assay, we further documented that cell–cell interactions between EPC-CM and melanoma cells were promoted in a SPARC-dependent manner. This interaction led to the engulfment of melanoma cells by EPC-CM, a process prevented by SPARC silencing and mimicked by recombinant SPARC. Finally, we showed that contrary to melanoma cells, the prometastatic human breast cancer cell line MDA-MB231-D3H2 reduced SPARC expression in human EPC and stimulated metastases spreading. Our findings unravel the influence of tumor cells on EPC phenotypes through a SPARC-driven accentuation of macrophagic capacity associated with limitations to metastatic spread. Cancer Res; 71(14); 4748–57. ©2011 AACR.
The Mef/Elf4 Transcription Factor Fine Tunes the DNA Damage Response
Authors: Sashida Goro , Bae Narae , Di Giandomenico Silvana , Asai Takashi , Gurvich Nadia , Bazzoli Elena , Liu Yan , Huang Gang , Zhao Xinyang , Menendez Silvia , Nimer Stephen D.
Published: May 2011

The ATM kinase plays a critical role in initiating the DNA damage response that is triggered by genotoxic stresses capable of inducing DNA double-strand breaks. Here, we show that ELF4/MEF, a member of the ETS family of transcription factors, contributes to the persistence of γH2AX DNA damage foci and promotes the DNA damage response leading to the induction of apoptosis. Conversely, the absence of ELF4 promotes the faster repair of damaged DNA and more rapid disappearance of γH2AX foci in response to γ-irradiation, leading to a radio-resistant phenotype despite normal ATM phosphorylation. Following γ-irradiation, ATM phosphorylates ELF4, leading to its degradation; a mutant form of ELF4 that cannot be phosphorylated by ATM persists following γ-irradiation, delaying the resolution of γH2AX foci and triggering an excessive DNA damage response. Thus, although ELF4 promotes the phosphorylation of H2AX by ATM, its activity must be dampened by ATM-dependent phosphorylation and degradation to avoid an excessive DNA damage response. Cancer Res; 71(14); 4857–65. ©2011 AACR.
HDAC1 Inhibition by Maspin Abrogates Epigenetic Silencing of GlutathioneS-Transferase Pi in Prostate Carcinoma Cells
Authors: Li Xiaohua , Kaplun Alexander , Lonardo Fulvio , Heath Elisabeth , Sarkar Fazlul H. , Irish Jonathan , Sakr Wael , Sheng Shijie
Published: May 2011

Both maspin and glutathione S-transferase pi (GSTp) are implicated as tumor suppressors and downregulated in human prostate cancer. It is well established that GSTp downregulation is through DNA methylation–based silencing. We report here that maspin expression in prostate cancer cell line DU145 reversed GSTp DNA methylation, as measured by methylation- specific PCR, MethyLight assay, and bisulfite sequencing. The effect of maspin on GSTp expression was similar to that of the combination of a synthetic histone deacetylase (HDAC) inhibitor and DNA methylation inhibitor 5-aza-2′-deoxycytidine. Maspin expression also led to an increased level of acetylated histone 3, decreased level of methyl transferase, and methyl-CpG–binding domain proteins at the site of demethylated GSTp promoter DNA. Earlier, we have shown that maspin inhibits HDAC1. In PC3 cells, where both maspin and GSTp are expressed at a reduced level, maspin knockdown led to a significant reduction in GSTp expression, whereas dual knockdown of maspin and HDAC1 barely increased the level of GSTp expression. Thus, HDAC1 may play an essential role in cellular response to maspin-mediated GSTp desilencing. Maspin has been shown to increase tumor cell sensitivity to drug-induced apoptosis. Interestingly, GSTp reexpression in the absence of maspin expression perturbation blocked the phosphorylation of histone 2A.X, the induction of hypoxia-induced factor 1α (HIF-1α), and cell death of LNCaP cells under oxidative stress. Because DNA hypermethylation–based silencing may couple with and depend on histone deacetylation, our study suggests that endogenous HDAC inhibition by maspin may prevent pathologic gene silencing in prostate tumor progression. Mol Cancer Res; 9(6); 733–45. ©2011 AACR.
Transcriptional Regulation of Msx1 Natural Antisense Transcript
Authors: Babajko Sylvie , Méary Fleur , Petit Stéphane , Fernandes Isabelle , Berdal Ariane
Published: May 2011

Msx homeogenes play an important role in the epithelial-mesenchymal interactions leading development. Msx1 is relevant for dental and craniofacial morphogenesis, as suggested by phenotypes of Msx1 mutations in human and Msx1 KO mice. Our group showed that Msx1 gene expression can be regulated by a bidirectional transcription generating long noncoding antisense (AS) RNA the expression which is linked to the Msx1 sense (S) RNA level. Thus, the aim of the present study was to analyze the synthesis of Msx1 (AS) RNA. In vivo Msx1 AS expression analysis showed that (i) the putative promoter sequence but not the transcribed sequence was important and necessary for its expression, (ii) 2 different areas of alveolar bone can be distinguished depending on Msx1 S and AS expression, and (iii) Msx1 presence was necessary for Msx1 AS RNA full expression. In silico analysis of the Msx1 AS putative promoter region showed the presence of 4 Msx response elements possibly involved in Msx1 regulation. Msx1 constitutes an example of a bidirectionally transcribed gene giving rise to an S/AS RNA pair included in the big and growing family of AS noncoding RNAs. Our results contribute to defining a link between Msx1 S and AS RNAs resulting in a fine-tuned regulatory loop of Msx1 expression. The significance of this finding is that disturbance of the balance between Msx1 S and AS RNA status may be associated with tooth agenesis and bone loss.
Polyphosphates Affect Biological Apatite Nucleation
Authors: Omelon Sidney , Grynpas Marc
Published: May 2011

While biological apatite (bone mineral) resorption is understood, from the perspective of crystallization theory, nucleation is not. The degree of saturation (Ω) describes the chemical driving force for mineral dissolution (Ω <1) or formation (Ω > 1). Ω is the ratio of the ion activity product (IAP) of free apatite (available for reaction) component ion concentrations (predominately [Ca2+] and [PO43–] for apatite) and its solubility product (Ksp). Free ion concentrations can be less than total ion concentrations if the ions form complexes, or if the ion speciation changes. Within the acidic bone resorption pit, free [PO43–] is reduced due to speciation into H2PO4_. This reduces IAPbio-Ap, and Ωbio-Ap; at Ωbio-Ap <1, apatite dissolves. Apatite nucleation requires Ωbio-Ap >1, and bioaccumulation of molar total [Ca2+] and [PO43–] to form the 60–70 weight percent mineral in bone tissue. This is possible with the polymerization of PO43– into polyphosphate [polyP: (PO3–)n] which reduces free [PO43–] while leaving total [P] unchanged. polyP forms neutral complexes by chelation with Ca2+, which further reduces free [Ca2+] and Ωbio-Ap, yet total [Ca2+] is unchanged. In vitro experiments demonstrate reduction in free [Ca2+], free [PO43–], and Ωbio-Ap by Ca-polyP formation, while total [Ca2+] and total [P] are constant. polyP depolymerization restores free [Ca2+] and [PO43–] to total [Ca] and [P], and increases Ωbio-Ap, favouring apatite nucleation.
Diagnosis of Glucocorticoid-Remediable Aldosteronism in Hypertensive Children
Authors: Kamrath Clemens , Maser-Gluth Christiane , Haag Christine , Schulze Egbert
Published: May 2011

Objective: Glucocorticoid-remediable aldosteronism (GRA) is caused by the presence of a chimeric gene originating from an unequal cross-over between the CYP11B1 and CYP11B2 genes. Aldosterone suppression by dexamethasone and high 18-hydroxycortisol (18-OHF) levels have been used to differentiate GRA from the other forms of primary aldosteronism. Methods: A dexamethasone suppression test including serum 18-OHF determination and the measurement of urinary excretion of aldosterone, its metabolites and 18-OHF were performed in 3 children of a family with primary aldosteronism. Polymerase chain reactions were performed to identify the chimeric gene. Results: The chimeric gene was identified in 2 children, their mother and grandmother. The affected children had an aldosterone-to-plasma renin activity ratio >30, elevated serum 18-OHF concentration and increased urinary excretion of aldosterone, its metabolites, and 18-OHF. Post-dexamethasone concentrations of serum aldosterone and 18-OHF concentrations were suppressed. Conclusion: Although very rare, the possible diagnosis of GRA should be considered in all children or young adults with low-renin hypertension. Since genetic testing is more specific than biochemical testing, a definitive diagnosis can only be obtained by identification of the CYP11B1/CYP11B2 chimeric gene.