bluuebunny/crossref_metadata_2025_split huggingface dataset:
GARUMELE, VILLE MÉDIÉVALE DU KANEM-BORNO? UNE CONTRIBUTION ARCHÉOLOGIQUE*
Authors: HAOUR ANNE , GADO BOUBE 
Published: January 2010

ABSTRACTCette contribution reconsidère le site de Garumele (Niger) à la lumière de récents travaux archéologiques. Garumele est dit dans les sources historiques avoir été la capitale de l'empire de Kanem-Borno peu avant la fondation de Birnin Gazargamo (deuxième moitié du quinzième siècle). Cet article reconcilie sources archéologiques et historiques pour évaluer la véracité de cette tradition – mais aussi pour considérer les facteurs méthodologiques et théoriques qui contribuent au mystère des origines du Kanem-Borno.
WHAT WAS THEINDIGÉNAT? THE ‘EMPIRE OF LAW’ IN FRENCH WEST AFRICA
Authors: MANN GREGORY 
Published: January 2010

ABSTRACTWhat was theindigénat? This article approaches this question via three arguments. First, a study of theindigénat(the regime of administrative sanctions applied to colonial subjects) challenges the idea that French West Africa formed part of an ‘empire of law’. Second, a dynamic spectrum of political statuses developed around theindigénatuntil its abolition in 1946. This spectrum is no less significant than one of its poles alone, that of colonial citizens. Third, theindigénat, its narrative of reform, and its relationship to law, bureaucracy, and authority illuminate the tensions between imperial rhetoric and colonial governance.
KHAT IN COLONIAL KENYA: A HISTORY OF PROHIBITION AND CONTROL
Authors: ANDERSON DAVID , CARRIER NEIL 
Published: January 2010

ABSTRACTEfforts to institute a system for the control and prohibition of khat in Kenya are examined in this article. Prohibition was introduced in the 1940s after an advocacy campaign led by prominent colonial officials. The legislation imposed a racialized view of the effect of khat, seeking to protect an allegedly ‘vulnerable’ community in the north of the country while allowing khat to be consumed and traded in other areas, including Meru where ‘traditional’ production and consumption was permitted. Colonial policy took little account of African opinion, although African agency was evident in the failure and ultimate collapse of the prohibition in the face of widespread smuggling and general infringement. Trade in khat became ever more lucrative, and in the final years of colonial rule economic arguments overcame the prohibition lobby. The imposition of prohibition and control indicates the extent to which colonial attitudes towards and beliefs about cultural behaviour among Africans shaped policies, but the story also illustrates the fundamental weakness of the colonial state in its failure to uphold the legislation.
Recovery of the Alpine lynxLynx lynxmetapopulation
Authors: Molinari-Jobin Anja , Marboutin Eric , Wölfl Sybille , Wölfl Manfred , Molinari Paolo , Fasel Michael , Kos Ivan , Blažič Mateja , Breitenmoser Christine , Fuxjäger Christian , Huber Thomas , Koren Iztok , Breitenmoser Urs 
Published: January 2010

AbstractWe use the case of the Eurasian lynxLynx lynxin the Alps to discuss how to implement existing directives and recommendations, as well as how to integrate biological concepts, into practical conservation and wildlife management. Since 1995 the occurrence of lynx in the Alpine countries has been monitored and reported by the Status and Conservation of the Alpine Lynx Population expert group. Both the area of occupancy and the estimated number of individuals increased from 1995–1999 to 2000–2004. The estimated number of lynx is 120–150 across the Alps and the area of occupancy 27,800 km2, in six distinct sub-areas. In the highly fragmented Alpine habitat lynx populations expand slowly, even in situations of high local density and when suitable habitat is available. Thus, almost 40 years after the first reintroduction, < 20% of the Alps have been recolonized by lynx. In addition to biological and ecological factors, the persistent disagreements about the return of the lynx between conservationists and other land-users, including livestock breeders and hunters, and the political fragmentation of the Alps (with different regional priorities and large carnivore policies), has prevented the creation of a consensus regarding pan-Alpine conservation goals for the lynx and the implementation of conservation measures such as translocations and reintroductions. We discuss possible approaches in the light of new guidelines for population level management plans for large carnivores recently developed on behalf of the European Commission.
Does a Famous Economist Deserve Special Standards? A Critical Note on Adam Smith Scholarship
Authors: Rashid Salim 
Published: January 2010

Matters are not very much improved when we come to the historian who qualifies all this [oversimplification of Luther] by some such phrase as that “Luther, however, was of an essentially medieval cast of mind;” for this parenthetical homage to research is precisely the vice and the delusion of the whig historian.Herbert Butterfield, The Whig Interpretation of History
Lipid-like materials for low-dose, in vivo gene silencing
Authors: Love Kevin T. , Mahon Kerry P. , Levins Christopher G. , Whitehead Kathryn A. , Querbes William , Dorkin J. Robert , Qin June , Cantley William , Qin Liu Liang , Racie Timothy , Frank-Kamenetsky Maria , Yip Ka Ning , Alvarez Rene , Sah Dinah W. Y. , de Fougerolles Antonin , Fitzgerald Kevin , Koteliansky Victor , Akinc Akin , Langer Robert , Anderson Daniel G. 
Published: January 2010

Significant effort has been applied to discover and develop vehicles which can guide small interfering RNAs (siRNA) through the many barriers guarding the interior of target cells. While studies have demonstrated the potential of gene silencing in vivo, improvements in delivery efficacy are required to fulfill the broadest potential of RNA interference therapeutics. Through the combinatorial synthesis and screening of a different class of materials, a formulation has been identified that enables siRNA-directed liver gene silencing in mice at doses below 0.01 mg/kg. This formulation was also shown to specifically inhibit expression of five hepatic genes simultaneously, after a single injection. The potential of this formulation was further validated in nonhuman primates, where high levels of knockdown of the clinically relevant gene transthyretin was observed at doses as low as 0.03 mg/kg. To our knowledge, this formulation facilitates gene silencing at orders-of-magnitude lower doses than required by any previously described siRNA liver delivery system.
Experimental and computational study on the phase stability of Al-containing cubic transition metal nitrides
Authors: Rovere Florian , Music Denis , Ershov Sergey , Baben Moritz to , Fuss Hans-Gerd , Mayrhofer Paul H , Schneider Jochen M 
Published: January 2010

The phase stability of Al-containing cubic transition metal (TM) nitrides, where Al substitutes for TM (i.e. TM1−x
Al
x
N), is studied as a function of the TM valence electron concentration (VEC). X-ray diffraction and thermal analyses data of magnetron sputtered Ti1−x
Al
x
N, V1−x
Al
x
N and Cr1−x
Al
x
N films indicate increasing phase stability of cubic TM1−x
Al
x
N at larger Al contents and higher temperatures with increasing TM VEC. These experimental findings can be understood based on first principle investigations of ternary cubic TM1−x
Al
x
N with TM = Sc, Ti, V, Cr, Y, Zr and Nb where the TM VEC and the lattice strain are systematically varied.
However, our experimental data indicate that, in addition to the decomposition energetics (cubic TM1−x
Al
x
N → cubic TMN + hexagonal AlN), future stability models have to include nitrogen release as one of the mechanisms that critically determine the overall phase stability of TM1−x
Al
x
N.
The necessity for response indicators in fisheries management
Authors: Piet G. J. , van Overzee H. M. J. , Pastoors M. A. 
Published: January 2010

Abstract
Piet, G. J., van Overzee, H. M. J., and Pastoors, M. A. 2010. The necessity for response indicators in fisheries management. – ICES Journal of Marine Science, 67: 559–566. Results are used from traditional fisheries management to explore two potential response indicators: (i) the extent to which scientific advice is incorporated in decision-making, and (ii) the compliance of industry and the relevant authorities to these decisions. Based on the most comprehensive set of data on the management process of 125 stocks for which ICES provided advice over the period 1987–2006, we explored these response indicators and found that for just 8% of the stocks, the official total allowable catch (TAC) equalled the scientific advice, and that in recent years the official TAC overshot scientific advice by >50%. Compliance levels appear to be reflected in the percentage of stocks for which landings exceeded the official TAC, decreasing from ∼8 to 2%. However, because the TAC appears not to be limiting, compliance may not be the most appropriate indicator. Without transparent decision-making that takes scientific advice into account, or the compliance of industry as reflected by the type of response indicators explored, the effectiveness of new developments in fisheries management, such as the application of an ecosystem approach, will be compromised, as has been the case with conventional fisheries management measures.
Toll‐like receptor 9 expression in breast and ovarian cancer is associated with poorly differentiated tumors
Authors: Berger Regina , Fiegl Heidi , Goebel Georg , Obexer Petra , Ausserlechner Michael , Doppler Wolfgang , Hauser‐Kronberger Cornelia , Reitsamer Roland , Egle Daniel , Reimer Daniel , Müller‐Holzner Elisabeth , Jones Allison , Widschwendter Martin 
Published: January 2010

Toll‐like receptor 9 (TLR9) activates the innate immune response when exposed to non‐methylated CpG‐DNA. TLR9 was recently shown to be expressed by cancer cells which have been previously characterized by global hypomethylation. We set out to examine the expression and molecular activity of TLR9 in breast and ovarian cancer cells. Firstly, we confirmed higher levels of hypomethylated DNA in the serum of patients with metastatic breast cancer (n = 18) versus age‐matched tumor‐free women (n = 18). In breast cancer cell lines and tissues, TLR9 mRNA expression was associated with estrogen‐receptor (ER) status (n = 124, P = 0.005). Expression also correlated with increasing tumor grade in both breast (P = 0.03) and ovarian cancer specimens (n = 138, P = 0.04). Immunohistochemical analysis of formalin‐fixed paraffin‐embedded (FFPE) breast cancer tissues revealed higher TLR9 protein expression in hormone‐receptor (HR)‐negative specimens (n = 116, P < 0.001). Using an in vitro scratch assay, we observed that cell lines transfected to overexpress TLR9 demonstrated increased cellular migration when stimulated with CpG‐DNA. When assessing the molecular activity of TLR9 in breast cancer, we found a strong positive correlation of nuclear factor‐kappa B (NF‐κB) activity with TLR9 mRNA expression (correlation coefficient r = 0.7, P < 0.001). Finally, immunofluorescence analysis of BT‐20 and Hs578T breast cancer cell lines showed partial colocalizations of CpG‐DNA with TLR9, which diminished when the cells were exposed to methylated CpG‐DNA (mCpG‐DNA) or control GpC‐DNA. In summary we demonstrate that TLR9 expression is associated with poor differentiation in breast and ovarian cancer specimens, and that TLR9 overexpression and stimulation with hypomethylated DNA augments the migratory capacity of cancer cell lines.(Cancer Sci 2010; 101: 1059–1066)
Up‐regulation of pro‐inflammatory genes as adaptation to hypoxia in MCF‐7 cells and in human mammary invasive carcinoma microenvironment
Authors: Tafani Marco , Russo Andrea , Di Vito Maura , Sale Patrizio , Pellegrini Laura , Schito Luana , Gentileschi Stefano , Bracaglia Roberto , Marandino Ferdinando , Garaci Enrico , Russo Matteo A 
Published: January 2010

The role of tumor cells in synthesizing pro‐inflammatory molecules is still controversial. Here we report that hypoxic treatment of the MCF‐7 human mammary adenocarcinoma cell line induced activation of hypoxia‐inducible factor 1α (HIF‐1α) and nuclear factor‐kappa B (NF‐κB). Importantly, hypoxia regulated expression of alarmin receptors such as the receptor for advanced glycation end products (RAGE) and the purinoreceptor (P2X7R), and up‐regulated inflammatory response (IR) genes such as the inducible enzymes nitric oxide synthase (NOS2), cycloxygenase (COX2), and the acute‐phase protein pentraxin‐3 (PTX3). Hypoxia also stimulated chemokine (C‐X‐C motif) receptor 4 (CXCR4) mRNA synthesis. In fact, the CXCR4 ligand stromal‐derived factor‐1α (SDF‐1α) increased invasion and migration of hypoxic MCF‐7 cells. Inhibition of HIF‐1α by chetomin and NF‐κB by parthenolide reduced mRNA and protein expression of the studied molecules and prevented invasion of hypoxic MCF‐7 cells. Moreover, solid invasive mammary tumor microenvironment was analyzed after laser‐capture microdissection (LCMD) comparing tumor versus host normal tissue. Nuclear translocation of HIF‐1α and NF‐κB and up‐regulation of IR, CXCR4, estrogen receptor α (ERα), and epithelial growth factor receptor (EGFR) was observed in tumor but not in host normal tissue in the absence of a local inflammatory leukocyte infiltrate. We conclude that under hypoxic conditions MCF‐7 cells acquire a pro‐inflammatory phenotype, and that solid human mammary carcinoma evidenced a similar activation of HIF‐1α, NF‐κB, and IR genes in malignant tumor cells as compared to the normal host tissues. We suggest a role for IR activation in the malignant progression of transformed cells.(Cancer Sci 2010; 101: 1014–1023)
Pigpen, a nuclear coiled body component protein, is involved in angiogenesis
Authors: Yoshida Tomoko , Sato Yasufumi , Morita Ikuo , Abe Mayumi 
Published: January 2010

We previously reported that puromycin‐insensitive leucyl‐specific aminopeptidase (PILSAP) is required for vascular endothelial growth factor (VEGF)‐ and basic fibroblast growth factor (bFGF)‐induced angiogenesis and for endothelial differentiation from embryonic stem (ES) cells via the aminopeptidase activity of PILSAP. In this study, we searched for molecules that function during angiogenesis with PILSAP. We performed proteome analysis of nuclear extracts from embryoid bodies (EBs) made from ES cells transfected with mutant PILSAP lacking aminopeptidase activity and mock EBs. We identified pigpen, a 67‐kDa nuclear coiled body component protein. Immunoprecipitation and western blotting demonstrated the binding of PILSAP and pigpen in endothelial cells (ECs), and this interaction was enhanced by VEGF and bFGF. Pigpen was reported to be expressed in actively growing ECs such as those in embryos and tumors. However, whether Pigpen is involved in angiogenesis is not known. Therefore, we examined the effect of pigpen on angiogenesis by silencing pigpen with siRNA (siPigpen). Compared with scrambled RNA (scrPigpen), transfection of siPigpen into mouse ECs inhibited proliferation, migration, and network formation. These results were confirmed with other two siRNAs. Moreover, siPigpen suppressed bFGF‐induced angiogenesis in a Matrigel plug assay, and injection of siPigpen into Lewis lung carcinoma cell tumors implanted subcutaneously into 5‐week‐old C57/BL male mice prevented tumor growth and tumor angiogenesis. These data indicate that Pigpen is involved in angiogenesis and that pigpen may be a target for blocking tumor angiogenesis.(Cancer Sci 2010; 101: 1170–1176)
The arms race between tomato and Fusarium oxysporum
Authors: TAKKEN FRANK , REP MARTIJN 
Published: January 2010

SUMMARYThe interaction between tomato and Fusarium oxysporum f. sp. lycopersici has become a model system for the study of the molecular basis of disease resistance and susceptibility. Gene‐for‐gene interactions in this system have provided the basis for the development of tomato cultivars resistant to Fusarium wilt disease. Over the last 6 years, new insights into the molecular basis of these gene‐for‐gene interactions have been obtained. Highlights are the identification of three avirulence genes in F. oxysporum f. sp. lycopersici and the development of a molecular switch model for I‐2, a nucleotide‐binding and leucine‐rich repeat‐type resistance protein which mediates the recognition of the Avr2 protein. We summarize these findings here and present possible scenarios for the ongoing molecular arms race between tomato and F. oxysporum f. sp. lycopersici in both nature and agriculture.
Changes in quality of life and sexual health are associated with low‐dose peginterferon therapy and disease progression in patients with chronic hepatitis C
Authors: SNOW K. K. , BONKOVSKY H. L. , FONTANA R. J. , KIM H.‐Y. , STERLING R. K. , DI BISCEGLIE A. M. , MORGAN T. R. , DIENSTAG J. L. , GHANY M. G. ,   The HALT‐C Trial Group
Published: January 2010

Aliment Pharmacol Ther 31, 719–734SummaryBackground  Primary analysis of the Hepatitis C Antiviral Long‐Term Treatment against Cirrhosis (HALT‐C) Trial showed long‐term peginterferon therapy did not reduce complications in patients with chronic hepatitis C and advanced fibrosis or cirrhosis.Aim  To assess the effects of long‐term peginterferon therapy and disease progression on health‐related quality of life (HRQOL), symptoms and sexual health in HALT‐C patients.Methods  A total of 517 HALT‐C patients received peginterferon alfa‐2a (90 μg/week); 532 received no additional treatment for 3.5 years. Patients were followed up for outcomes of death, hepatocellular carcinoma and hepatic decompensation. Sexual health, SF‐36 scores and symptoms were serially assessed by repeated‐measures analyses of covariance.Results  Patients with cirrhosis (n = 427) reported lower general well‐being and more fatigue (P < 0.001) than patients with fibrosis (n = 622). Physical scores declined significantly over time, independent of treatment, and patients with cirrhosis reported lower scores. Vitality scores were lower in those with cirrhosis, and treated patients experienced a greater decline over time than untreated patients; HRQOL rebounded after treatment ended. Patients with a clinical outcome had significantly greater declines in all SF‐36 and symptom scores. Among men, Sexual Health scores were significantly worse in treated patients and in those with a clinical outcome.Conclusion  Clinical progression of chronic hepatitis C and maintenance peginterferon therapy led to worsening of symptoms, HRQOL and, in men, sexual health in a large patient cohort followed up over 4 years (NCT00006164).
Pharmacokinetics and pharmacodynamics of nasally delivered midazolam
Authors: Haschke Manuel , Suter Katja , Hofmann Sarah , Witschi Robert , Fröhlich Johannes , Imanidis Georgios , Drewe Jürgen , Briellmann Thomas A. , Dussy Franz E. , Krähenbühl Stephan , Surber Christian 
Published: January 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Nasal application of midazolam has been studied for a variety of indications. Due to the limited application volume, highly concentrated formulations are required to reach clinically relevant concentrations in adult patients. No data on the pharmacokinetics and pharmacodynamics of nasal midazolam formulations based on cyclodextrin and chitosan are available. WHAT THIS STUDY ADDS • Clinically effective midazolam concentrations can be reached within less than 10 min after nasal administration of highly concentrated formulations containing an equimolar amount of the solubilizer randomly methylated‐β‐cyclodextrin combined with the absorption enhancer chitosan. Immediate non‐invasive application of such formulations in emergency treatment of seizure patients by lay persons could offer clinical benefits in situations where intravenous access cannot be quickly established.AIMS To investigate the pharmacokinetics and pharmacodynamics of nasal formulations containing midazolam (5–30 mg ml−1) complexed with cyclodextrin.METHODS An open‐label sequential trial was conducted in eight healthy subjects receiving single doses of 1 mg and 3 mg intranasally and 1 mg midazolam intravenously. Pharmacokinetic parameters were obtained by non‐compartmental and two‐compartmental models. Pharmacodynamic effects of midazolam were assessed using VAS and a reaction time test.RESULTS Mean bioavailability of midazolam after nasal administration ranged from 76 ± 12% to 92 ± 15%. With formulations delivering 1 mg midazolam, mean Cmax values between 28.1 ± 9.1 and 30.1 ± 6.6 ng ml−1 were reached after 9.4 ± 3.2–11.3 ± 4.4 min. With formulations delivering 3 mg midazolam, mean Cmax values were between 68.9 ± 19.8 and 80.6 ± 15.2 ng ml−1 after 7.2 ± 0.7–13.0 ± 4.3 min. Chitosan significantly increased Cmax and reduced tmax of midazolam in the high‐dose formulation. Mean ratios of dose‐adjusted AUC after intranasal and intravenous application for 1′‐hydroxymidazolam were between 0.97 ± 0.15 and 1.06 ± 0.24, excluding relevant gastrointestinal absorption of intranasal midazolam. The pharmacodynamic effects after the low‐dose nasal formulations were comparable with those after 1 mg intravenous midazolam. The maximum increase in reaction time by the chitosan‐containing formulation delivering 3 mg midazolam was greater compared with 1 mg midazolam i.v. (95 ± 78 ms and 19 ± 22 ms, mean difference 75.5 ms, 95% CI 15.5, 135.5, P < 0.01). Intranasal midazolam was well tolerated but caused reversible irritation of the nasal mucosa.CONCLUSIONS Effective midazolam serum concentrations were reached within less than 10 min after nasal application of a highly concentrated midazolam formulation containing an equimolar amount of the solubilizer RMβCD combined with the absorption enhancer chitosan.
Platelet von Willebrand factor – structure, function and biological importance
Authors: McGrath Rachel T. , McRae Emily , Smith Owen P. , O’Donnell James S. 
Published: January 2010

SummaryBesides circulating in normal plasma, von Willebrand factor (VWF) is also stored at relatively high concentration within the α‐granules of platelets. This pool of platelet VWF exists distinct from plasma VWF, and is enriched in haemostatically‐active high molecular weight multimers. Interestingly, the glycosylation profile of platelet VWF differs significantly from that of plasma VWF. Total sialic acid and galactose expression are reduced twofold on platelet VWF, and ABO blood group carbohydrate determinants are not present on the N‐linked glycans of platelet VWF. Consequently, in view of the critical role played by VWF glycans in modulating its activity, it is not surprising that the functional properties of platelet VWF differ markedly compared to those of plasma VWF. Nevertheless, animal model studies suggest that both plasma and platelet VWF play important roles in securing primary haemostasis. In addition, platelet VWF antigen and activity levels vary markedly between patients with different types of von Willebrand disease (VWD). Future studies to define the biochemical mechanisms responsible for these differences between plasma and platelet VWF are thus not only of basic scientific interest, but also of direct translational importance.