bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of the Shuswap Metamorphic Complex in Cordilleran tectonism: a review
Authors: Okulitch Andrew V.
Published: November 2010

The Shuswap Metamorphic Complex consists of three parts, each with unique stratigraphy and orogenic evolution, separated by major faults of diverse nature and having in common only a post-late Mesozoic tectonic history. The first part, the Monashee Complex, is a possible extension of the Precambrian Shield that contains limited evidence of Mesozoic orogenesis and that was rapidly uplifted during the Cretaceous to Paleogene. The Monashee Décollement, a warped mylonite zone interpreted as a regional thrust fault active through the Middle Jurassic, separates this complex from the second part, which contains rocks correlative with Hadrynian to late Paleozoic strata of the pericratonic prism. The third part, the Okanagan Complex, straddling the 49th Parallel from the Okanagan Valley to Kootenay Lake, contains the probable exhumed roots of a Mesozoic magmatic arc built upon possible North American continental and transitional crust and includes late Paleozoic and early Mesozoic suspect terranes.The Columbian Orogen formed during westward drift of the craton into a continent of accreted elements. Response of the craton, attenuated during at least two episodes of Proterozoic rifting, and its overlying sedimentary prism to underthrusting from the east and simultaneous collision with an accreting collage from the west took place in two stages. First, attenuated crust was telescoped and thickened to its approximate original configuration while westernmost parts of the bordering prism were deformed and metamorphosed (the Jura-Cretaceous Columbian Orogeny that affected the Okanagan Complex and strata above the Monashee Décollement). Second, the thickened crust, the deformed prism, and platformal strata were thrust eastward (the Late Cretaceous – Paleocene Laramide Orogeny that formed the Rocky Mountains Thrust Belt). Waning convergent tectonism led to ascendancy of crustal extension (primarily in the Okanagan Complex) and final uplift of cratonic massifs.
The dentition and relationships of the Paleocene primate Micromomys Szalay, with description of a new species
Authors: Fox Richard C.
Published: November 2010

Nearly complete lower dentitions (with c?, p2–4, m1–3) and the first discovered upper dentitions (with P2–4, M1–3) are described and illustrated for the late Paleocene primate Micromomys Szalay. These fossils, from the Paskapoo Formation of central Alberta, Canada, represent a new species, the geologically earliest known species of the genus. Micromomys appears to have been a primitive microsyopid most closely related to the early Paleocene Purgatorius Van Valen and Sloan and the middle Paleocene Palenochtha Gidley; a relationship between Micromomys and the early Eocene Tinimomys Szalay may not be as near as previous workers had supposed.Micromomys is the smallest primate known and was probably insectivorous. Its occurrence with the rare European primate Saxonella Russell, a new, primitive carpolestid, and an unusual mammal possibly related to palaeanodonts documents a facies not yet encountered in other Paleocene mammal local faunas, in Canada or elsewhere.
Petrology of the Archean Pontiac and Kewagama sediments and implications for the stratigraphy of the southern Abitibi belt
Authors: Lajoie Jean , Ludden John
Published: November 2010

We present an interpretation of the petrology of two Archean sedimentary groups in the southeastern portion of the Abitibi greenstone belt: (1) the Pontiac sediments, which represent an assemblage of quartz-rich sandstones, and (2) the Kewagama sediments, which are quartz poor and rich in volcanic fragments. The Pontiac sediments display a north–south decrease in bed thickness, sand/shale ratio, and grain size, suggesting derivation from a northern source relative to their present position. Petrographic and rare earth element (REE) analysis indicates that three provenances contributed to the Pontiac: (1) a mature craton, (2) light/heavy REE fractionated igneous rocks probably of tonalite–trondhjemite composition, and (3) ultramafic–mafic volcanics.In contrast to the Pontiac sediments, the Kewagama sediments were derived from acid to mafic volcanic rocks (ratio of 3:1), with minor contributions from plutonic rocks and from graded sedimentary rocks (possibly the Pontiac). The REE data indicate a source fractionated in light/heavy REE relative to the adjacent Blake River Group volcanic rocks, and it is suggested that a suitable source may be the upper Skead volcanics 60 km to the west or a volcanic assemblage similar to the upper Skead that has been eroded from a location above the Blake River Group.The Pontiac Group has characteristics similar to Phanerozoic sedimentary sequences that have accumulated at a passive continental margin, whilst the Kewagama sediments were derived from uplifted volcamc terrane.Our study indicates that the Pontiac Group is stratigraphically below the Blake River Group and that it is not a lateral deep-water facies of the Timiskaming Group. In addition, we consider the possibility that the Kewagama is younger than the Pontiac.
Devonian conodonts from Jones Island, northwest Washington
Authors: Savage Norman M.
Published: November 2010

Two small outcrops of limestone on Jones Island, northwest Washington, have yielded Devonian conodonts. Conodonts from locality 1, on the northern shore of the island, include Icriodus cf. I. brevis Stauffer, Icriodus cf. I. expansus Branson and Mehl, Polygnathus xylus Stauffer, and Ozarkodina semialternans Wirth, indicating a late Givetian to early Frasnian (hermanni–cristatus zone) age. Conodonts from locality 2, on the eastern shore, include Amydrotaxis n. sp. and Ozarkodina remscheidensis (Ziegler), indicating a probable Lochkovian age within the eurekaensis to pesavis zones. The species are mostly cosmopolitan. The exception may be Amydrotaxis n. sp., which belongs to a genus known as yet only from Cordilleran North America and eastern Australia.
Thermoluminescence dating studies of glacial silts from Ontario
Authors: Berger Glenn W.
Published: November 2010

To develop procedures for the direct dating of glacially related silts by thermoluminescence (TL), I have applied previously proposed techniques to three polymineralic 4–11 μm samples from the Toronto area. Furthermore, one of these samples was studied in detail by isolating some mineral fractions. The principal conclusion is that the TL of the lodgment Halton Till (from Woodbridge) was not significantly reset during deposition, whereas the TL of the waterlaid upper Thorncliffe silt (from the Scarborough Bluffs) was reset, as was the TL of the third sample (WC-ST), a massive silt from Woodbridge that has been generally correlated with the glaciolacustrine Sunnybrook diamict at the Bluffs. This conclusion follows from the observation of feldspar TL apparent ages of >140 ka for the ~12 ka BP Halton Till and of 36 and 66 ka for the upper Thorncliffe and WC-ST samples, respectively.The four laboratory factors that contributed most to inaccuracies in the TL apparent ages were: (1) anomalous fading in the feldspar-dominant fractions, (2) nonlinearity in TL growth curves, (3) "overbleaching" of the TL, and (4) radon loss during alpha particle counting of dry powders. The effects of each of these have been circumvented or minimized. As expected, uncertainty in the past pore-water content represented the single largest source of imprecision for such TL apparent ages after correction for the other effects.
The continental and oceanic crust and lithosphere in the Archaean: isostatic, thermal, and tectonic models
Authors: Nisbet E. G.
Published: November 2010

Simple isostatic models of the development of selected Archaean basins and greenstone belts can be used to constrain models of the Archaean lithosphere. Geophysical, geochemical, and thermal data imply that in southern Africa the late Archaean crust was probably comparable in thickness to the modern continental crust, and the whole lithosphere was perhaps over 80–100 km thick. Two Archaean belts studied may have developed by stretching of the order of 1.3–1.6:1. Isostatic and thermal data and petrological assumptions allow the construction of simple models of the Archaean oceanic lithosphere. Oceans were probably deep: mid-ocean ridges were probably subaqueous and fed by komatiitic liquids. Calc-alkaline volcanism in the Archaean may have been produced as a consequence of the subduction of hydrated komatiitic oceanic crust into a hot, low-viscosity asthensophere.
Glacigenic deposits at the Edmonton Convention Centre, Edmonton, Alberta
Authors: Catto N. R.
Published: November 2010

Four main stratigraphic units are present at the Edmonton Convention Centre site in downtown Edmonton. The lowermost sediment exposed is Cretaceous sandstone of the Horseshoe Canyon Formation. This is overlain by preglacial sands and gravels of uncertain age, which contain recumbent drag folds developed by glacial overriding of previously existing periglacial involutions. These sediments are surmounted by a glacigenic complex, consisting of subglacially modified sand and four till facies formed through passive melt out. The uppermost Quaternary sediment present is a proglacial lacustrine unit dominated by silts and clays with interbedded diamictons.A single glacial episode is recorded in the sediments. Stratigraphic relationships with other exposures throughout the Edmonton region indicate that the glacigenic complex formed during the final ice advance. Variation in the orientation of glacially induced deformations in the preglacial sands and gravels and the basal glacigenic sand indicate that the direction of ice advance was not consistent throughout the final glacial event.
Chitosanase fromStreptomyces coelicolorA3(2): biochemical properties and role in protection against antibacterial effect of chitosan
Authors: Ghinet Mariana Gabriela , Roy Sébastien , Poulin-Laprade Dominic , Lacombe-Harvey Marie-Ève , Morosoli Rolf , Brzezinski Ryszard
Published: November 2010

Chitosan, an N-deacetylated derivative of chitin, has attracted much attention as an antimicrobial agent against fungi, bacteria, and viruses. Chitosanases, the glycoside hydrolases responsible for chitosan depolymerisation, are intensively studied as tools for biotechnological transformation of chitosan. The chitosanase CsnA (SCO0677) from Streptomyces coelicolor A3(2) was purified and characterized. CsnA belongs to the GH46 family of glycoside hydrolases. However, it is secreted efficiently by the Tat translocation pathway despite its similarity to the well-studied chitosanase from Streptomyces sp. N174 (CsnN174), which is preferentially secreted through the Sec pathway. Melting point determination, however, revealed substantial differences between these chitosanases, both in the absence and in the presence of chitosan. We further assessed the role of CsnA as a potential protective enzyme against the antimicrobial effect of chitosan. A Streptomyces lividans TK24 strain in which the csnA gene was inactivated by gene disruption was more sensitive to chitosan than the wild-type strain or a chitosanase-overproducing strain. This is the first genetic evidence for the involvement of chitosanases in the protection of bacteria against the antimicrobial effect of chitosan.
New nuclear partners for nucleosome assembly protein 1: unexpected associations
Authors: Seebart Corrine , Prenni Jessica , Tomschik Miroslav , Zlatanova Jordanka
Published: November 2010

Histone chaperones are important players in chromatin dynamics. They are instrumental in nucleosome assembly and disassembly and in histone variant exchange reactions that occur during DNA transactions. The molecular mechanisms of their action are not well understood and may involve interactions with various protein partners in the context of the nucleus. In an attempt to further elucidate nuclear roles of histone chaperones, we performed a proteomic search for nuclear partners of a particular histone chaperone, nucleosome assembly protein 1 (Nap1). Proteins recognized as Nap1 partners by immuno-affinity capture and Far Western blots were identified by mass spectrometry. The identified partners are known to participate in a number of nuclear processes, including DNA replication, recombination, and repair as well as RNA transcription and splicing. Finding nuclear actin among the Nap1 partners may be of particular significance, in view of actin’s role in transcription, transcription regulation, and RNA splicing. We are proposing a model of how actin–Nap1 interaction may be involved in transcription elongation through chromatin. In addition, awareness of the interactions between Nap1 and Hsp70, another identified partner, may help to understand nucleosome dynamics around sites of single-strand DNA break repair. These studies represent a starting point for further investigation of Nap1 associations in human cells.
Importance of Arg-599 of β-galactosidase (Escherichia coli) as an anchor for the open conformations of Phe-601 and the active-site loop
Authors: Dugdale Megan L. , Vance Michael L. , Wheatley Robert W. , Driedger Michael R. , Nibber Anjan , Tran Angela , Huber Reuben E.
Published: November 2010

Structural and kinetic data show that Arg-599 of β-galactosidase plays an important role in anchoring the “open” conformations of both Phe-601 and an active-site loop (residues 794–803). When alanine was substituted for Arg-599, the conformations of Phe-601 and the loop shifted towards the “closed” positions because interactions with the guanidinium side chain were lost. Also, Phe-601, the loop, and Na+, which is ligated by the backbone carbonyl of Phe-601, lost structural order, as indicated by large B-factors. IPTG, a substrate analog, restored the conformations of Phe-601 and the loop of R599A-β-galactosidase to the open state found with IPTG-complexed native enzyme and partially reinstated order. d-Galactonolactone, a transition state analog, restored the closed conformations of R599A-β-galactosidase to those found with d-galactonolactone–complexed native enzyme and completely re-established the order. Substrates and substrate analogs bound R599A-β-galactosidase with less affinity because the closed conformation does not allow substrate binding and extra energy is required for Phe-601 and the loop to open. In contrast, transition state analog binding, which occurs best when the loop is closed, was several-fold better. The higher energy level of the enzyme•substrate complex and the lower energy level of the first transition state means that less activation energy is needed to form the first transition state and thus the rate of the first catalytic step (k2) increased substantially. The rate of the second catalytic step (k3) decreased, likely because the covalent form is more stabilized than the second transition state when Phe-601 and the loop are closed. The importance of the guanidinium group of Arg-599 was confirmed by restoration of conformation, order, and activity by guanidinium ions.
Regulation of liver fatty acid binding protein expression by clofibrate in hepatoma cells
Authors: Yan Jing , Gong Yuewen , Wang Guqi , Gong Yu , Burczynski Frank J.
Published: November 2010

Peroxisome proliferator-activated receptor (PPAR) agonists such as clofibrate are known to affect liver fatty acid binding protein (L-FABP) levels, which in turn influence hepatocellular oxidant status. The mechanism of clofibrate’s modulation of L-FABP levels is not clear. In this study we used clofibrate (PPARα agonist), MK886 (PPARα antagonist), and GW9662 (PPARγ antagonist) in determining the regulating mechanism of L-FABP expression and its antioxidant activity in CRL-1548 hepatoma cells. Antioxidant activity was assessed by determining intracellular reactive oxygen species (ROS) using dichlorofluorescein (DCF) fluorescence. The effect of clofibrate on cytosolic activity of the intracellular antioxidant enzymes was also assessed. RT-PCR and mRNA stability assay showed that clofibrate treatment enhanced L-FABP mRNA stability, which resulted in increased L-FABP levels. A nuclear run-off assay and RT-PCR measurements of L-FABP mRNA revealed that clofibrate increased the L-FABP gene transcription rate. The increased L-FABP was associated with reduced cytosolic ROS. Levels of superoxide dismutase, glutathione peroxidase, and catalase were not affected by clofibrate treatment. L-FABP siRNA knockdown studies showed that a reduction in L-FABP expression was associated with increased DCF fluorescence. We conclude that clofibrate enhanced L-FABP gene transcription and mRNA stability, thus affecting L-FABP expression and ultimately cellular antioxidant activity.
IMAGE SEGMENTATION BASED ON EDGE DETECTION AND REGION GROWING FOR THINPREP-CERVICAL SMEAR
Authors: LIN CHUEN-HORNG , CHEN CHUN-CHIEH
Published: November 2010

This study has developed an object detection and segmentation technique for processing cytoplasm and cell nucleus on ThinPrep-cervical smear images at various magnifications. Both edge detection techniques and region growing for adaptive threshold were applied to a segment cell nucleus, a cytoplasm, and backgrounds using a cervical cell image.

To validate the accuracy and feasibility of the proposed method, we took a variety of cervical cell images to perform a series of experiments. The images were of superficial cells, intermediate cells, and abnormal cells, with each taken from ThinPrep smears at various magnifications. The results indicate that the proposed method can automatically segment cell nucleus and cytoplasm regions while accurately extracting object contours. These results can serve as a reference for examiners of cell pathologies.
PHONETIC SEGMENTATION OF EMOTIONAL SPEECH WITH HMM-BASED METHODS
Authors: MPORAS IOSIF , GANCHEV TODOR , FAKOTAKIS NIKOS
Published: November 2010

In the present work we address the problem of phonetic segmentation of emotional speech. Investigating various traditional and recent HMM-based methods for speech segmentation, which we elaborated for the specifics of emotional speech segmentation, we demonstrate that the HMM-based method with hybrid embedded-isolated training offers advantageous segmentation accuracy, when compared to other HMM-based models used so far. The increased precision of the segmentation is a consequence of the iterative training process employed in the hybrid-training method, which refines the model parameters and the estimated phonetic boundaries taking advantage of the estimations made at previous iterations. Furthermore, we demonstrate the benefits of using purposely-built models for each target category of emotional speech, when compared to the case of one common model built solely from neutral speech. This advantage, in terms of segmentation accuracy, justifies the effort for creating and employing the purposely-built segmentation models per emotion category, since it significantly improves the overall segmentation accuracy.
EMPIRICAL INVESTIGATIONS INTO FIRM TECHNOLOGY ORIENTATION AND ENTREPRENEURIAL ORIENTATION
Authors: URBAN BORIS , BARRERIA JOSE
Published: November 2010

Entrepreneurship and its relation with technology is studied extensively within organizations and often conceptualized as entrepreneurial orientation (EO) and technology orientation (TO). This paper empirically tests the relationship between these orientations and firm performance by measuring how environmental dynamism and hostility may influence the EO–TO relationship. After providing an overview of the relevant variables, data are collected from 229 firms in Johannesburg, South Africa. Statistical analyses are employed to test the hypothesized associations. Findings reveal robust reliability and validity of scales used, and significant correlations between EO and environment hostility and dynamism are reported.
AN INDIAN EXPERIENCE OF THE ENVIRONMENTAL MANAGEMENT SYSTEM
Authors: KHANNA V. K.
Published: November 2010

The last two decades have seen a remarkable increase in both interest and reactions to the concept of preserving the environment. This can be attributed to the increasing statutory and regulatory requirements of government and the pressure from consumers and the life-threatening of global ecosystem deterioration. Therefore, organizations are constantly under pressure to develop and implement Environmental Management System (EMS). While some sincere efforts have been made by the Indian organizations to implement EMS and their performance have been very good, still countrywide efforts are not adequate. This paper presents the adoption of EMS in Indian organizations, extent of EMS elements used and the status of implementation of cleaner production activities by the industries. This paper also presents the benefits accrued by the Indian industries based on 56 industries feedback who are either ISO 14001 certified companies or in the advance stage of ISO 14001 implementation. This has been supplemented by some case studies of the leading Indian organizations. Most of the Indian organizations feel that EMS has a positive effect in their performance. It is observed that Indian organizations are more inclined towards getting ISO 14001 certification rather than taking full advantage of EMS However, it is evident from the statistical analysis that overall adoption of cleaner production activities are at the low level. The majority of the organizations seem to be implementing EMS out of pressure from competition, customer, government, domestic and export market. The paper concludes that though environmental awareness is on the increase in India, and commitment as well as compliance levels are far higher than before, India still lags behind in the implementation and has to go a long way. The investigation and research findings are still exploratory. Future research can focus on the organizations that are at the initial stage of EMS implementation and comparison can be drawn. Future research can focus on sector wise performance. Broadly based and larger sample size would provide better picture of EMS implementation status in Indian organizations. Analysis is based on questionnaire based feedback. The study has been able to identify the extent of the usage of key EMS elements, implementation of cleaner production activities and drivers for the implementation of EMS. The findings have been supported by the select Indian case studies.
INTERPARADIGMATIC HYBRIDS: A NEW THEORETICAL CONCEPT WHEN ADDRESSING PARADIGMATIC SHIFTS IN TECHNOLOGY
Authors: POHL HANS
Published: November 2010

Paradigmatic shifts are challenging and consequently considerable efforts have been made to find concepts relating to the innovation process which lead from one paradigm to the next. This paper takes its inspiration from previous literature and studies of more than incremental innovations in the automotive industry. It outlines the concept of an interparadigmatic hybrid as a temporary combination (in one product or service) of technologies from an existing and a future paradigm in a way that facilitates the development toward the future paradigm. The proposed concept is tested on the product level using empirical data from the automotive industry, where it is assumed that hybrid electric vehicle technologies have the role of an interparadigmatic hybrid in the potential shift from the internal combustion engine to the paradigm of "pure" electric propulsion. The conclusions include an argument for the usefulness of the proposed concept for corporate managers, and perhaps even more so for policymakers and researchers, as it provides long-term strategic guidance and a (techno)logical order.
Effects of acute Rho kinase inhibition on chronic hypoxia-induced changes in proximal and distal pulmonary arterial structure and function
Authors: Vanderpool Rebecca R. , Kim Ah Ram , Molthen Robert , Chesler Naomi C.
Published: November 2010

Hypoxic pulmonary hypertension (HPH) is initially a disease of the small pulmonary arteries. Its severity is usually quantified by pulmonary vascular resistance (PVR). Acute Rho kinase inhibition has been found to reduce PVR toward control values in animal models, suggesting that persistent pulmonary vasoconstriction is the dominant mechanism for increased PVR. However, HPH may also cause proximal arterial changes, which are relevant to right ventricular (RV) afterload. RV afterload can be quantified by pulmonary vascular impedance, which is obtained via spectral analysis of pulsatile pressure-flow relationships. To determine the effects of HPH independent of persistent pulmonary vasoconstriction in proximal and distal arteries, we quantified pulsatile pressure-flow relationships before and after acute Rho kinase inhibition and measured pulmonary arterial structure with microcomputed tomography. In control lungs, Rho kinase inhibition decreased 0 Hz impedance (Z0), which is equivalent to PVR, from 2.1 ± 0.4 to 1.5 ± 0.2 mmHg·min·ml−1( P < 0.05) and tended to increase characteristic impedance (ZC) from 0.21 ± 0.01 to 0.22 ± 0.01 mmHg·min·ml−1. In HPH lungs, Rho kinase inhibition decreased Z0( P < 0.05) without affecting ZC. Microcomputed tomography measurements performed on lungs after acute Rho kinase inhibition demonstrated that HPH significantly decreased the unstressed diameter of the main pulmonary artery (760 ± 60 vs. 650 ± 80 μm; P < 0.05), decreased right pulmonary artery compliance, and reduced the frequency of arteries of diameter 50–100 μm (both P < 0.05). These results demonstrate that acute Rho kinase inhibition reverses many but not all HPH-induced changes in distal pulmonary arteries but does not affect HPH-induced changes in the conduit arteries that impact RV afterload.
Reduced hyperthermia-induced cutaneous vasodilation and enhanced exercise-induced plasma water loss at simulated high altitude (3,200 m) in humans
Authors: Miyagawa Ken , Kamijo Yoshi-ichiro , Ikegawa Shigeki , Goto Masaki , Nose Hiroshi
Published: November 2010

We examined whether less convective heat loss during exercise at high altitude than at sea level was partially caused by reduced cutaneous vasodilation due to enhanced plasma water loss into contracting muscles and whether it was caused by hypoxia rather than by hypobaria. Seven young men performed cycling exercise for 40 min at 50% peak aerobic power in normoxia at (710 mmHg) 610 m, determined before the experiments, in three trials: 1) normobaric normoxia at 610 m (CNT), 2) hypobaric hypoxia [low pressure and low oxygen (LPLO)] at 3,200 m (510 mmHg), 3) normobaric hypoxia [normal pressure and low oxygen (NPLO)] at 610 m, in an artificial climate chamber where atmospheric temperature and relative humidity were maintained at 30°C and 50%, respectively. Subjects in CNT and LPLO breathed room air, whereas those in NPLO breathed a mixed gas of 14% O2 balanced N2, equivalent to the gas composition in LPLO. We measured change in PV (ΔPV), oxygen consumption rate (V̇o2), mean arterial blood pressure (MBP), esophageal temperature (Tes), mean skin temperature (Tsk), forearm skin blood flow (FBF), and sweat rate (SR) during exercise. Although V̇o2, MBP, Tsk, and SR responses during exercise were similar between trials ( P > 0.05), the sensitivity of forearm vascular conductance (FBF/MBP) in response to increased Tes was lower in LPLO and NPLO than in CNT ( P < 0.05), whereas that of SR was not, resulting in a greater increase in Tes from minute 5 to 40 of exercise in LPLO and NPLO than in CNT ( P = 0.026 and P = 0.011, respectively). ΔPV during exercise was twofold greater in LPLO and NPLO than in CNT. These variables were not significantly different between LPLO and NPLO. Thus reduced convective heat loss during exercise at 3,200 m was partially caused by reduced cutaneous vasodilation due to enhanced PV loss. Moreover, this may be caused by hypoxia rather than by hypobaria.
β-Catenin Activation Is Associated with Specific Clinical and Pathologic Characteristics and a Poor Outcome in Adrenocortical Carcinoma
Authors: Gaujoux Sébastien , Grabar Sophie , Fassnacht Martin , Ragazzon Bruno , Launay Pierre , Libé Rossella , Chokri Ilham , Audebourg Anne , Royer Benedict , Sbiera Silviu , Vacher-Lavenu Marie-Cécile , Dousset Bertrand , Bertagna Xavier , Allolio Bruno , Bertherat Jérôme , Tissier Frédérique
Published: November 2010

Purpose: Activation of the Wnt/β-catenin signaling pathway is frequent in adrenocortical carcinoma (ACC) and might be associated with a more aggressive phenotype. The objective of this study was to assess the prognostic value of β-catenin immunohistochemistry and CTNNB1 (β-catenin gene)/APC (adenomatous polyposis coli gene) mutations in patients with resected primary ACC.

Experimental design: In 79 patients with resected primary ACC from a French cohort (Cochin-COMETE), β-catenin expression was assessed on tumor specimens by immunohistochemistry. For patients with available DNA (n = 49), CTNNB1, and APC hotspot (mutation cluster region), were sequenced. Association between these results and the clinicopathologic characteristics of the ACC and overall and disease-free survival were studied. Results were confirmed on a tissue microarray from an independent multicentric cohort of 92 ACC from Germany (German-ENSAT cohort).

Results: In the Cochin-COMETE cohort, the presence of a β-catenin nuclear staining was significantly associated with a higher ENSAT tumor stage (i.e., stages III and IV), higher Weiss score, more frequent necrosis, mitoses, and CTNNB1/APC mutations. β-Catenin nuclear staining and the presence of CTNNB1/APC mutations were both associated with decreased overall and disease-free survival, and were independent predictive factors of survival in multivariate analysis. The same results were observed in the German-ENSAT cohort.

Conclusions: Wnt/β-catenin activation, confirmed by the presence of β-catenin nuclear staining, is an independent prognostic factor of overall and disease-free survival in patients with resected primary ACC. Clin Cancer Res; 17(2); 206–11. ©2010 AACR. Clin Cancer Res; 17(2); 328–36. ©2010 AACR.
Carbon Nanotubes Enhance CpG Uptake and Potentiate Antiglioma Immunity
Authors: Zhao Dongchang , Alizadeh Darya , Zhang Leying , Liu Wei , Farrukh Omar , Manuel Edwin , Diamond Don J. , Badie Behnam
Published: November 2010

Purpose: Stimulation of toll-like receptor-9 (TLR9) by CpG oligodeoxynucleotides (CpG) has been shown to counteract the immunosuppressive microenvironment and to inhibit tumor growth in glioma models. Because TLR9 is located intracellularly, we hypothesized that methods that enhance its internalization may also potentiate its immunostimulatory response. The goal of this study was to evaluate carbon nanotubes (CNT) as a CpG delivery vehicle in brain tumor models.

Experimental Design: Functionalized single-walled CNTs were conjugated with CpG (CNT–CpG) and evaluated in vitro and in mice bearing intracranial GL261 gliomas. Flow cytometry was used to assess CNT–CpG uptake and antiglioma immune response. Tumor growth was measured by bioluminescent imaging, histology, and animal survival.

Results: CNT–CpG was nontoxic and enhanced CpG uptake both in vitro and intracranial gliomas. CNT-mediated CpG delivery also potentiated proinflammatory cytokine production by primary monocytes. Interestingly, a single intracranial injection of low-dose CNT–CpG (but not free CpG or blank CNT) eradicated intracranial GL261 gliomas in half of tumor-bearing mice. Moreover, surviving animals exhibited durable tumor-free remission (>3 months), and were protected from intracranial tumor rechallenge, demonstrating induction of long-term antitumor immunity.

Conclusions: These findings suggest that CNTs can potentiate CpG immunopotency by enhancing its delivery into tumor-associated inflammatory cells. Clin Cancer Res; 17(4); 1–12. ©2010 AACR.
Health Benefits and Cost-Effectiveness of Primary Genetic Screening for Lynch Syndrome in the General Population
Authors: Dinh Tuan A. , Rosner Benjamin I. , Atwood James C. , Boland C. Richard , Syngal Sapna , Vasen Hans F. A. , Gruber Stephen B. , Burt Randall W.
Published: November 2010

In current clinical practice, genetic testing to detect Lynch syndrome mutations ideally begins with diagnostic testing of an individual affected with cancer before offering predictive testing to at-risk relatives. An alternative strategy that warrants exploration involves screening unaffected individuals via demographic and family histories, and offering genetic testing to those individuals whose risks for carrying a mutation exceed a selected threshold. Whether this approach would improve health outcomes in a manner that is cost-effective relative to current standards of care has yet to be demonstrated. To do so, we developed a simulation framework that integrated models of colorectal and endometrial cancers with a 5-generation family history model to predict health and economic outcomes of 20 primary screening strategies (at a wide range of compliance levels) aimed at detecting individuals with mismatch repair gene mutations and their at-risk relatives. These strategies were characterized by (i) different screening ages for starting risk assessment and (ii) different risk thresholds above which to implement genetic testing. For each strategy, 100,000 simulated individuals, representative of the U.S. population, were followed from the age of 20, and the outcomes were compared with current practice. Findings indicated that risk assessment starting at ages 25, 30, or 35, followed by genetic testing of those with mutation risks exceeding 5%, reduced colorectal and endometrial cancer incidence in mutation carriers by approximately 12.4% and 8.8%, respectively. For a population of 100,000 individuals containing 392 mutation carriers, this strategy increased quality-adjusted life-years (QALY) by approximately 135 with an average cost-effectiveness ratio of $26,000 per QALY. The cost-effectiveness of screening for mismatch repair gene mutations is comparable to that of accepted cancer screening activities in the general population such as colorectal cancer screening, cervical cancer screening, and breast cancer screening. These results suggest that primary screening of individuals for mismatch repair gene mutations, starting with risk assessment between the ages of 25 and 35, followed by genetic testing of those whose risk exceeds 5%, is a strategy that could improve health outcomes in a cost-effective manner relative to current practice. Cancer Prev Res; 4(1): 9–22. ©2010 AACR. Cancer Prev Res; 4(1); 9–22. ©2010 AACR.
Sickle Cell Disease and Transcranial Doppler Imaging
Authors: Krejza Jaroslaw , Chen Rong , Romanowicz Grzegorz , Kwiatkowski Janet L. , Ichord Rebecca , Arkuszewski Michal , Zimmerman Robert , Ohene-Frempong Kwaku , Desiderio Lisa , Melhem Elias R.
Published: November 2010

Background and Purpose—

To establish reference values of interhemispheric differences and ratios of blood flow Doppler parameters in the terminal internal carotid artery, middle cerebral artery, and anterior cerebral artery in children with sickle cell anemia.

Methods—

Fifty-seven out of 74 recruited children (mean age, 7.8±3.4 years; range limits, 3–14 years), who were free of neurological deficits and intracranial narrowing detectable by MRA and had flow velocities <170 cm/s by conventional transcranial Doppler ultrasound, underwent transcranial color-coded duplex ultrasonography. Reference limits of flow parameters corrected and uncorrected for the angle of insonation were estimated using tolerance intervals, with
P
=0.90 for all possible data values from 95% of a population.

Results—

Reference limits for left-to-right differences in cm/s in the mean angle-corrected and uncorrected flow velocities were −56 to 53 and −72 to 75 for middle cerebral artery, −49 to 57 and −81 to 91 for anterior cerebral artery, and −55 to 64 and −73 to 78 for terminal internal carotid artery, respectively. Respective reference limits for left-to-right velocity ratios were 0.31 to 1.84 and 0.38 to 1.75 for middle cerebral artery, 0.48 to 2.99 and 0.46 to 2.89 for anterior cerebral artery, and 0.61 to 2.56 and 0.56 to 2.23 for terminal internal carotid artery.

Conclusions—

The study provides reference limits of interhemispheric differences and ratios of blood flow Doppler parameters that may be helpful in identification of intracranial arterial narrowing in children with sickle cell disease undergoing ultrasound screening for stroke prevention.
Effect of Baseline CT Scan Appearance and Time to Recanalization on Clinical Outcomes in Endovascular Thrombectomy of Acute Ischemic Strokes
Authors: Goyal Mayank , Menon Bijoy K. , Coutts Shelagh B. , Hill Michael D. , Demchuk Andrew M.
Published: November 2010

Background and Purpose—

The Penumbra Pivotal Stroke Trial reported a 25% good outcome (modified Rankin scale score ≤2) despite an 81% recanalization rate. We evaluated the association of a favorable initial noncontrast CT and a short time to recanalization in predicting good outcome.

Methods—

Data were from the Penumbra Pivotal Stroke Trial. Baseline scans were evaluated by 2 experienced readers blinded to outcomes using ASPECTS. ASPECTS scores were dichotomized into >7 and ≤7 for primary analysis. Data on degree of recanalization based on thrombolysis in myocardial infarction scores, stroke onset to recanalization, and CT to recanalization times were obtained. Primary outcome was modified Rankin scale score ≤2 at 3 months.

Results—

Median baseline NIHSS was 18 (range, 8–34) and median baseline ASPECTS score was 6 (range, 0–10); 81.2% achieved recanalization (thrombolysis in myocardial infarction, 2–3) and (27.7%) achieved good outcome. Good outcome was significantly higher in the ASPECTS score >7 group when compared to the ASPECTS score ≤7 group (50% vs 15%; RR, 3.3; 95% CI, 1.6–6.8;
P
=0.0001). No patient with an ASPECTS score ≤4 (n=28) or without recanalization (n=16) had a good outcome. There was an interaction between baseline ASPECTS score (>7 and ≤7) and onset to recanalization time (≤300 minutes and >300 minutes) in predicting good outcome (
P
=0.06).

Conclusion—

Patients with baseline CT ASPECTS score ≤4 do not benefit from recanalization. Fast recanalization may benefit patients with evident damage on the CT scan (ASPECTS score >4). Overall, patients benefit the most with early recanalization and a favorable baseline CT scan (ASPECTS score >7).
Overweight, obesity, and strong attitudes
Authors: Magoc Dejan , Tomaka Joe , Thompson Sharon
Published: November 2010

Background: Obesity is the leading cause of preventable death and conveys risk for diabetes, hypertension, heart disease, and stroke. Overweight and obesity are common among college students with surveys showing 35 per cent of college students to be overweight (National College Health Risk Behavioral Survey (NCHRBS), 1995). Unhealthy diets and low physical activity are the major causes.

Objective: To examine rates of obesity, participation in exercise, and predictors of exercise among a predominantly Hispanic (72 per cent) college student sample.

Methods: Three hundred and ninety two students completed questionnaires as part of a general health screening.

Results: General participation in exercise is high (61 per cent), but the majority (69 per cent) do not meet the Centers for Disease Control and Prevention (CDC) recommendations for physical activity (PA). Also, exercise importance and gender were strong predictors of participation in physical activity and exercise in this sample.

Conclusion: Strong attitudes are an important determinant of participation in PA in this sample. Future studies might explore these relationships among other ethnic/demographic groups, as well as test the effectiveness of attitude change interventions for increasing PA.
Examining differences in the stigma of depression and schizophrenia
Authors: Norman Ross M.G. , Windell Deborah , Manchanda Rahul
Published: November 2010

Background: Although there is evidence of greater stigmatization of schizophrenia in comparison to depression, there has been little investigation of the reasons for this difference.

Aims: To examine the role of beliefs about depression and schizophrenia in mediating the difference in preferred social distance towards individuals with these two disorders.

Methods: In Study I, 200 undergraduates completed questionnaires concerning beliefs about depression or schizophrenia and willingness to interact with an individual who has one of the two disorders. In Study II, 103 members of a community service club completed similar measures.

Results: For both samples, beliefs about likely appropriateness of social behaviour showed evidence of mediating differences in preferred level of social distance. In addition, differences in perceived danger may have been a mediator for the undergraduate sample and perceived prognosis for the service club respondents.

Conclusions: Beliefs about social appropriateness, danger and prognosis, which have implications for likely costs and benefits of interaction, are more likely to mediate differences in social distance towards the disorders than beliefs concerning causation or continuity with normal experience.
Pōwhiri process in mental health research
Authors: McClintock Kahu , Mellsop Graham , Moeke-Maxwell Tess , Merry Sally
Published: November 2010

Within the health research context, indigenous people globally have a commitment to provide their own solutions. Māori, the indigenous people of Aotearoa (New Zealand) value the traditional Pōwhiri process of engagement and participation in mental health research. The practices and protocols within the Pōwhiri process (use in the Doctorate of Philosophy (2010) and Auckland University) are premised on the notion of respect and positive relationships between the tangata whenua (hosts or research participants) and manuwhiri (guests or researchers). This paper briefly describes the Pōwhiri process, which may be a model applicable to research with other indigenous cultures.
Burden of care among relatives of patients with schizophrenia in midwestern Nigeria
Authors: Igberase Osayi O. , Morakinyo Olufemi , Lawani Ambrose O. , James Bawo O. , Omoaregba Joyce O.
Published: November 2010

Background: Schizophrenia is a devastating mental disorder which places immense burden on family members. There are few studies that have explored the enormity of burden experienced by caregivers in sub-Saharan Africa.

Method: Two hundred caregivers who were relatives of 200 consecutive outpatients with a diagnosis of schizophrenia and undergoing treatment at the Federal Psychiatric Hospital, Uselu, Benin, between August and November 2008, were studied. The degree of burden experienced by the caregivers was assessed using the Burden Questionnaire (BQ). The patients’ symptomatology was assessed using the Positive and Negative Syndrome Scale (PANSS).

Results: Mean financial burden score was significantly greater than the mean scores for burden of disruption of family routine and interaction, social stigma and subjective distress. Caregivers of unemployed patients had significantly higher mean burden scores compared to those of employed patients. Level of burden showed significant associations with caregivers’ educational level, age of patient, employment status of patients and global rating of difficulty in coping with caregiving.

Conclusion: Caregivers of patients with schizophrenia experience immense burden. Public health education as well as targeted interventions in the area of employment, financial and other support for persons with mental disorders would help to ameliorate this burden.
N-Acetyl Cysteine Protects TMJ Chondrocytes from Oxidative Stress
Authors: Ueno T. , Yamada M. , Sugita Y. , Ogawa T.
Published: November 2010

Temporomandibular joint (TMJ) inflammation is closely associated with oxidative stress. This study tested the potential of N-acetyl cysteine (NAC), an anti-oxidant amino-acid derivative, in alleviating oxidative stress-related damage in TMJ chondrocytes. The inflammatory condition was simulated by the addition of hydrogen peroxide (H2O2) to TMJ-derived chondrocyte cultures. Exposure to H2O2 decreased the cell population by half within 2 days as a result of induced apoptosis and reduced proliferation. Gene expression of aggrecan and collagen II, as well as glycosaminoglycan production, were reduced by more than 70%. These compromised chondrocyte viability and function were fully restored by the addition of NAC to the cultures. NAC reduced the H2O2-elevated intracellular reactive oxygen species to the normal level and increased cellular glutathione reserves. These results indicate that NAC restores oxidative stress-induced cell death and severe functional impairment in TMJ chondrocytes, and warrant in vivo testing to explore its therapeutic potential as an anti-inflammatory agent.
Existential Dimensions of Surviving HIV
Authors: Machado Silvio
Published: November 2010

With the development of effective antiretroviral medications, long-term survivors of HIV/AIDS are confronted with life, a surprising reality many never expected. In this article, the author draws from his clinical experience to explore the existential dimensions of the experience of gay long-term survivors. In particular, the existential givens, as advanced by James Bugental, Tom Greening, and Irvin Yalom, are used as a framework in which to understand the challenges many long-term survivors face. Drawing from his clinical work with this enduring population, the author elaborates the profound nature of these challenges and the way in which the givens shed light on their ontological roots. The article concludes with an examination of survivor guilt, existential guilt, and their interplay in the lives of long-term survivors.
Housing Estates in the Czech Republic after Socialism
Authors: Temelová Jana , Novák Jakub , Ouředníček Martin , Puldová Petra
Published: November 2010

Growing income differentiation in society, diversification of housing supply and selective population mobility are resulting in increasing socio-spatial differentiation in Czech cities and neighbourhoods during the post-socialist transition. Housing estates are no exception to the processes of urban change. The paper shows that development trajectories of housing estates vary in different parts of the country, in various locations within each city and also within particular housing estates. As segregation in Czech cities takes place mainly within very small areas, statistical analyses usually fail to detect the seeds of social and physical degradation emerging in neighbourhoods and a micro survey is essential. In order to understand the patterns and factors of differentiation, the paper presents case studies from housing estates located in different cities of the Czech Republic.
Blood Quantum and Perceptions of Black-White Biracial Targets: The Black Ancestry Prototype Model of Affirmative Action
Authors: Sanchez Diana T. , Good Jessica J. , Chavez George
Published: November 2010

The present study examined the causal role of amount of Black ancestry in targets’ perceived fit with Black prototypes and perceivers’ categorization of biracial targets. Greater Black ancestry increased the likelihood that perceivers categorized biracial targets as Black and perceived targets as fitting Black prototypes (e.g., experiencing racial discrimination, possessing stereotypic traits). These results persisted, controlling for perceptions of phenotype that stem from ancestry information. Perceivers’ beliefs about how society would categorize the biracial targets predicted perceptions of discrimination, whereas perceivers’ beliefs about the targets’ self-categorization predicted trait perceptions. The results of this study support the Black ancestry prototype model of affirmative action, which reveals the downstream consequences of Black ancestry for the distribution of minority resources (e.g., affirmative action) to biracial targets.