bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diabetes resolution and hyperinsulinaemia after metabolic Roux‐en‐Y gastric bypass
Authors: Ashrafian H. , Athanasiou T. , Li J. V. , Bueter M. , Ahmed K. , Nagpal K. , Holmes E. , Darzi A. , Bloom S. R. 
Published: September 2010

SummaryThe global prevalence of type 2 diabetes mellitus and impaired glucose metabolism continues to rise in conjunction with the pandemic of obesity. The metabolic Roux‐en‐Y gastric bypass operation offers the successful resolution of diabetes in addition to sustained weight loss and excellent long‐term outcomes in morbidly obese individuals. The procedure consists of the physiological BRAVE effects: (i) Bile flow alteration; (ii) Reduction of gastric size; (iii) Anatomical gut rearrangement and altered flow of nutrients; (iv) Vagal manipulation and (v) Enteric gut hormone modulation. This operation provides anti‐diabetic effects through decreasing insulin resistance and increasing the efficiency of insulin secretion. These metabolic outcomes are achieved through weight‐independent and weight‐dependent mechanisms. These include the foregut, midgut and hindgut mechanisms, decreased inflammation, fat, adipokine and bile metabolism, metabolic modulation, shifts in gut microbial composition and intestinal gluconeogenesis. In a small minority of patients, gastric bypass results in hyperinsulinaemic hypoglycaemia that may lead to nesidioblastosis (pancreatic beta‐cell hypertrophy with islet hyperplasia). Elucidating the precise metabolic mechanisms of diabetes resolution and hyperinsulinaemia after surgery can lead to improved operations and disease‐specific procedures including ‘diabetes surgery’. It can also improve our understanding of diabetes pathogenesis that may provide novel strategies for the management of metabolic syndrome and impaired glucose metabolism.
ENTREPRENEURIALISM IN THE GLOBALISING CITY‐REGION OF TANGIER, MOROCCO
Authors: KANAI MIGUEL , KUTZ WILLIAM 
Published: September 2010

ABSTRACTThis paper inspects the territorial and state restructuring of the globalising city‐region of Tangier. It argues that recent economic growth and transnational connections follow new forms of entrepreneurial development that aggravate social and spatial inequalities. The analysis shows that these forms of urban and regional management are embedded in the neoliberalised, yet monarch‐centric Moroccan state. Analysis of local governance arrangements demonstrates the pivotal importance of an elite cadre of urban managers within the monarchic power structure. Fieldwork evidence documents the emergence of megaprojects as preferred vehicles for entrepreneurial development through site observations, indepth interviews and archival research. The Tanger City Center project presents a case that illustrates the social and spatial implications of a restructuring territorial economy and the effects of new polarities being overlaid on existing urban and regional geographies. The paper concludes with a reflection on the comparative and relational lessons that can be drawn from Tangier's restructuring.
How Historians Begin: Openings in Historical Discourse
Authors: DEAN TREVOR 
Published: September 2010

AbstractWhy is the problem of beginning – much discussed in literary scholarship – not dealt with in similar depth by historians? This article attempts an answer to this question, and does so in three ways. First, it examines literary scholarship on textual openings, showing the various ways in which the beginning is given significance. Then, it examines and challenges the common presentation of historical discourse as distinct from fiction. Finally, it examines two sets of data: the openings of 100 historical monographs are analysed for their ‘fictionality’, and the openings of 200 research articles are analysed for their rhetorical structures.
Evangelicalism and Scandal in Victorian England: The Case of the Pearsall Smiths
Authors: ROBERTS M. J. D. 
Published: September 2010

AbstractContemporary, sociology‐assisted, enthusiasm for the study of ‘scandal’ has opened a rich field of possibilities for historians of Victorian England including historians of Victorian religious thought and practice. While exploration of this field has so far focused on the scandals of the culturally marginalized (notably Roman Catholics), the role of scandal in shaping mainstream Protestant evangelical culture in an age of ‘media‐generated celebrity’ remains largely unmapped. This article aims to demonstrate the power of scandal to shape the culture of the Victorian Protestant mainstream by an investigation and appraisal of the unfolding, contemporary interpretation, management, and ultimate resolution of a scandal which enveloped the American evangelist couple, Robert and Hannah Pearsall Smith, on their visits to England between 1873 and 1875. The outcome of these events, it is argued, was a triumph for those opposed to the ‘Americanization’ of English religious practice and cultural values, especially values linked to the regulation of sexual desire.
Estimation of methane flux offshore SW Taiwan and the influence of tectonics on gas hydrate accumulation
Authors: CHUANG P.‐C. , YANG T. F. , HONG W.‐L. , LIN S. , SUN C.‐H. , LIN A. T.‐S. , CHEN J.‐C. , WANG Y. , CHUNG S.‐H. 
Published: September 2010

AbstractWidely distributed bottom simulating reflectors (BSRs) imply the potential existence of gas hydrates offshore southwestern Taiwan. To compare the distribution of methane concentrations along passive and active margins in the region, bottom waters and cored sediments were collected during four cruises from 2005 to 2006. The results reveal that sites with high methane concentrations are predominantly distributed in the active margin and site GS5 is the only site that contains very high methane concentrations in the passive margin of studied area. Anomalously high methane fluxes still can be obtained from the calculation of diffusive methane flux, although there might be some gas leakage during or after sampling procedures. The profiles of methane and sulfate concentration reveal very shallow depths of the sulfate–methane interface (SMI) at some sites. There is evidence that sulfate reduction is mainly driven by the process of anaerobic methane oxidation. Thus, sulfate fluxes can be used as a proxy for methane fluxes through the use of diffusion equations; and the results show that the fluxes are very high in offshore southwestern Taiwan. The depths of the SMI are different at sites GH6 and C; however, both methane profiles reveal parallel methane gradients below the SMI. This might be because of methane migration to surface sediments from the same reservoir with the same diffusion rates. Although BSRs are widely distributed both in the active margin and in the passive margin, most sites with high methane concentrations have been found in the active margin. Therefore, the specific tectonic settings in offshore SW Taiwan might strongly control the stability of gas hydrates, and thus affect the methane concentrations and fluxes of the sediments and sea waters. Furthermore, the carbon isotopic composition of methane shows that a biogenic gas source is dominant at shallower depth; however, some thermogenic gases might be introduced through the fracture/fault zones from deeper source in the active region of studied area.
Macrophages increase microparticle uptake by enterocyte‐like Caco‐2 cell monolayers
Authors: Moyes Siobhan M. , Morris John F. , Carr Katharine E. 
Published: September 2010

AbstractCaco‐2 cells form an enterocyte‐like monolayer that has been used to explore small intestinal microparticle uptake. They are a useful functional model for the investigation of in vivo drug delivery systems and the uptake of particulate environmental pollutants. The aim of this paper was to determine if the previously reported decrease in Caco‐2 transepithelial resistance following exposure to macrophages was matched by increased microparticle uptake, especially as macrophage phagocytosis simulates removal of particles from the subepithelial compartment. Caco‐2 cells were grown as a monoculture for 21 days on insert membranes. A compartmentalised model involved Caco‐2 cells in the upper compartment, with THP‐1‐derived macrophages adhering to the base of the underlying well, the two cell populations communicating only through the shared culture medium. Caco‐2 cells were also cultured in macrophage‐conditioned medium and all groups were exposed apically to 2 μm latex particles for 5 or 60 min. Parameters measured were: transepithelial resistance; cytokine levels; cell dimensions and the distribution of nuclei, actin and junctional proteins. Subepithelial particle numbers, defined as those located below the insert membrane, were also counted and were significantly increased in the Caco‐2/macrophage model, with over 90% associated with the macrophages. Other changes induced by the presence of macrophages included decreased transepithelial resistance levels, diffuse localisation of some junctional proteins, higher proinflammatory cytokine levels, disorganisation of cell shape and decreased cell height associated with actin reorganisation. Macrophage‐conditioned medium produced a smaller transepithelial resistance decrease than the Caco‐2/macrophage model and there were few other changes. In conclusion, culture of Caco‐2 cells with underlying macrophages produced a lower, less organised epithelium and greater microparticle uptake.
The age‐related failure of adaptive responses to contractile activity in skeletal muscle is mimicked in young mice by deletion of Cu,Zn superoxide dismutase
Authors: Vasilaki Aphrodite , van der Meulen Jack H. , Larkin Lisa , Harrison Dawn C. , Pearson Timothy , Van Remmen Holly , Richardson Arlan , Brooks Susan V. , Jackson Malcolm J. , McArdle Anne 
Published: September 2010

SummaryIn muscle, aging is associated with a failure of adaptive responses to contractile activity, and this is hypothesized to play an important role in age‐related loss of muscle mass and function. Mice lacking the Cu,Zn superoxide dismutase (Cu,ZnSOD, SOD1) show an accelerated, age‐related loss of muscle mass and function. This work determined whether adult mice lacking Cu,ZnSOD (Sod1−/− mice) show a premature failure of adaptive responses to contractions in a similar manner to old wild‐type (WT) mice. Adult Sod1−/− mice (6–8 months of age) had a ∼ 30% reduction in gastrocnemius muscle mass compared with age‐matched WT mice. This lower muscle mass was associated with an activation of DNA binding by NFκB and AP‐1 at rest. Measurements of the activity of reactive oxygen species (ROS) in single fibres from the muscles of Sod1−/− mice at rest indicated an elevation in activity compared with fibres from WT mice. Following 15 min of isometric contractions, muscle fibres from WT mice showed an increase in the intracellular ROS activities and activation of NFκB and AP‐1, but no changes in either ROS activity or NFκB and AP‐1 activation were seen in the muscles of Sod1−/− mice following contractions. This pattern of changes mimics that seen in the muscles of old WT mice, suggesting that the attenuated responses to contractile activity seen in old mice result from chronic exposure to increased oxidant activity. Data support the use of the Sod1−/− mouse model to evaluate potential mechanisms that contribute to the loss of muscle mass and function in the elderly.
Global gene expression profiles in skeletal muscle of monozygotic female twins discordant for hormone replacement therapy
Authors: Ronkainen Paula H. A. , Pöllänen Eija , Alén Markku , Pitkänen Reino , Puolakka Jukka , Kujala Urho M. , Kaprio Jaakko , Sipilä Sarianna , Kovanen Vuokko 
Published: September 2010

SummaryAging is accompanied by inexorable loss of muscle tissue. One of the underlying causes for this is the massive change in the hormonal milieu of the body. The role of a female sex steroid – estrogen – in these processes is frequently neglected, although the rapid decline in its production coincides with a steep deterioration in muscle performance. We recruited 54‐ to 62‐year‐old monozygotic female twin pairs discordant for postmenopausal hormone replacement therapy (HRT, n = 11 pairs; HRT use 7.3 ± 3.7 years) from the Finnish Twin Cohort to investigate the association of long‐term, estrogen‐based HRT with skeletal muscle transcriptome. Pathway analysis of muscle transcript profiles revealed significant HRT‐induced up‐regulation of a biological process related to regulation of cell structure and down‐regulation of processes concerning, for example, cell–matrix interactions, energy metabolism and utilization of nutrients (false discovery rate < 0.15). Lending clinical relevance to the findings, these processes explained a significant fraction of the differences observed in relative proportion of muscle within thigh and in muscle performance (R2 = 0.180–0.257, P = 0.001–0.023). Although energy metabolism was affected through down‐regulation of the transcripts related to succinate dehydrogenase complex in mitochondria, no differences were observed in mtDNA copy number or oxidative capacity per muscle cross section. In conclusion, long‐term use of HRT was associated with subtle, but significant, differences in muscle transcript profiles. The better muscle composition and performance among the HRT users appeared to be orchestrated by improved regulatory actions on cytoskeleton, preservation of muscle quality via regulation of intramuscular extracellular matrix and a switch from glucose‐oriented metabolism to utilization of fatty acids.
KB‐R7943, an inhibitor of the reverse Na+/Ca2+exchanger, blocks N‐methyl‐D‐aspartate receptor and inhibits mitochondrial complex I
Authors: Brustovetsky Tatiana , Brittain Matthew K. , Sheets Patrick L. , Cummins Theodore R. , Pinelis Vsevolod , Brustovetsky Nickolay 
Published: September 2010

BACKGROUND AND PURPOSEAn isothiourea derivative (2‐[2‐[4‐(4‐nitrobenzyloxy)phenyl]ethyl]isothiourea methane sulfonate (KB‐R7943), a widely used inhibitor of the reverse Na+/Ca2+exchanger (NCXrev), was instrumental in establishing the role of NCXrevin glutamate‐induced Ca2+deregulation in neurons. Here, the effects of KB‐R7943 on N‐methyl‐D‐aspartate (NMDA) receptors and mitochondrial complex I were tested.EXPERIMENTAL APPROACHFluorescence microscopy, electrophysiological patch‐clamp techniques and cellular respirometry with Seahorse XF24 analyzer were used with cultured hippocampal neurons; membrane potential imaging, respirometry and Ca2+flux measurements were made in isolated rat brain mitochondria.KEY RESULTSKB‐R7943 inhibited NCXrevwith IC50= 5.7 ± 2.1 µM, blocked NMDAR‐mediated ion currents, and inhibited NMDA‐induced increase in cytosolic Ca2+with IC50= 13.4 ± 3.6 µM but accelerated calcium deregulation and mitochondrial depolarization in glutamate‐treated neurons. KB‐R7943 depolarized mitochondria in a Ca2+‐independent manner. Stimulation of NMDA receptors caused NAD(P)H oxidation that was coupled or uncoupled from ATP synthesis depending on the presence of Ca2+in the bath solution. KB‐R7943, or rotenone, increased NAD(P)H autofluorescence under resting conditions and suppressed NAD(P)H oxidation following glutamate application. KB‐R7943 inhibited 2,4‐dinitrophenol‐stimulated respiration of cultured neurons with IC50= 11.4 ± 2.4 µM. With isolated brain mitochondria, KB‐R7943 inhibited respiration, depolarized organelles and suppressed Ca2+uptake when mitochondria oxidized complex I substrates but was ineffective when mitochondria were supplied with succinate, a complex II substrate.CONCLUSIONS AND IMPLICATIONSKB‐R7943, in addition to NCXrev, blocked NMDA receptors in cultured hippocampal neurons and inhibited complex I in the mitochondrial respiratory chain. These findings are critical for the correct interpretation of experimental results obtained with KB‐R7943 and a better understanding of its neuroprotective action.
Effects of 15d‐PGJ2‐loaded poly(D,L‐lactide‐co‐glycolide) nanocapsules on inflammation
Authors: Alves CF , de Melo NFS , Fraceto LF , de Araújo DR , Napimoga MH 
Published: September 2010

BACKGROUND AND PURPOSEThe PPAR‐γ agonist 15d‐PGJ2 is a potent anti‐inflammatory agent but only at high doses. To improve the efficiency of 15d‐PGJ2, we used poly(D,L‐lactide‐co‐glycolide) nanocapsules to encapsulate it, and function as a drug carrier system. The effects of these loaded nanocapsules (15d‐PGJ2‐NC) on inflammation induced by different stimuli were compared with those of free 15d‐PGJ2.EXPERIMENTAL APPROACHMice were pretreated (s.c.) with either 15d‐PGJ2‐NC or unloaded 15d‐PGJ2 (3, 10 or 30 µg·kg−1), before induction of an inflammatory response by i.p. injection of either endotoxin (LPS), carrageenan (Cg) or mBSA (immune response).KEY RESULTSThe 15d‐PGJ2‐NC complex did not display changes in physico‐chemical parameters or drug association efficiency over time, and was stable for up to 60 days of storage. Neutrophil migration induced by i.p. administration of LPS, Cg or mBSA was inhibited by 15d‐PGJ2‐NC, but not by unloaded 15d‐PGJ2. In the Cg model, 15d‐PGJ2‐NC markedly inhibited serum levels of the pro‐inflammatory cytokines TNF‐α, IL‐1β and IL‐12p70. Importantly, 15d‐PGJ2‐NC released high amounts of 15d‐PGJ2, reaching a peak between 2 and 8 h after administration. 15d‐PGJ2 was detected in mouse serum after 24 h, indicating sustained release from the carrier. When the same concentration of unloaded 15d‐PGJ2 was administered, only small amounts of 15d‐PGJ2 were found in the serum after a few hours.CONCLUSIONS AND IMPLICATIONSThe present findings clearly indicate the potential of the novel anti‐inflammatory 15d‐PGJ2 carrier formulation, administered systemically. The formulation enables the use of a much smaller drug dose, and is significantly more effective compared with unloaded 15d‐PGJ2.
Decomposing Changes in Agricultural Producer Prices
Authors: Liefert William M. 
Published: September 2010

Abstract This article develops a method for decomposing changes in agricultural producer prices. The method builds on a procedure used by the World Bank, with the main variables in the decomposition being trade prices, exchange rates and trade policies. We expand on the World Bank decomposition procedure by broadening the analysis of policy effects, adding the effect from incomplete transmission of changes in trade prices and exchange rates to producer prices, and handling the effect on prices from interactions between variables as they change simultaneously. Decomposition results are presented for various commodities for the major emerging markets of Brazil, China and South Africa.
Incomplete Credit Markets and Commodity Marketing Behaviour
Authors: Stephens Emma C. , Barrett Christopher B. 
Published: September 2010

AbstractWe use a simple theoretical model of seasonal market participation in the presence of liquidity constraints and transaction costs to explain the ‘sell low, buy high’ puzzle in which some households do not take advantage of inter‐temporal price arbitrage through storage and sell output postharvest at prices lower than observed prices for purchases in the subsequent lean season. We test our model with data from western Kenya using maximum likelihood estimation of a multivariate sample selection model of market participation. Access to off‐farm income and credit indeed seem to influence crop sales and purchase behaviours in a manner consistent with the hypothesised patterns.
A Compact Mock Circulation Loop for the In Vitro Testing of Cardiovascular Devices
Authors: Timms Daniel L. , Gregory Shaun D. , Greatrex Nicholas A. , Pearcy Mark J. , Fraser John F. , Steinseifer Ulrich 
Published: September 2010

AbstractIn vitro cardiovascular device performance evaluation in a mock circulation loop (MCL) is a necessary step prior to in vivo testing. A MCL that accurately represents the physiology of the cardiovascular system accelerates the assessment of the device's ability to treat pathological conditions. To serve this purpose, a compact MCL measuring 600 × 600 × 600 mm (L × W × H) was constructed in conjunction with a computer mathematical simulation. This approach allowed the effective selection of physical loop characteristics, such as pneumatic drive parameters, to create pressure and flow, and pipe dimensions to replicate the resistance, compliance, and fluid inertia of the native cardiovascular system. The resulting five‐element MCL reproduced the physiological hemodynamics of a healthy and failing heart by altering ventricle contractility, vascular resistance/compliance, heart rate, and vascular volume. The effects of interpatient anatomical variability, such as septal defects and valvular disease, were also assessed. Cardiovascular hemodynamic pressures (arterial, venous, atrial, ventricular), flows (systemic, bronchial, pulmonary), and volumes (ventricular, stroke) were analyzed in real time. The objective of this study is to describe the developmental stages of the compact MCL and demonstrate its value as a research tool for the accelerated development of cardiovascular devices.
A randomized, double‐blind, placebo‐controlled, parallel‐group study of rufinamide as adjunctive therapy for refractory partial‐onset seizures
Authors: Biton Victor , Krauss Gregory , Vasquez‐Santana Blanca , Bibbiani Francesco , Mann Allison , Perdomo Carlos , Narurkar Milind 
Published: September 2010

SummaryPurpose:  Efficacy and safety of adjunctive rufinamide (3,200 mg/day) was assessed in adolescents and adults with inadequately controlled partial‐onset seizures receiving maintenance therapy with up to three antiepileptic drugs (AEDs).Methods:  This randomized, double‐blind, placebo‐controlled, parallel‐group, multicenter study comprised a 56‐day baseline phase (BP), 12‐day titration phase, and 84‐day maintenance phase (MP). The primary efficacy variable was percentage change in total partial seizure frequency per 28 days (MP vs. BP). Secondary efficacy outcome measures included ≥50% responder rate and reduction in mean total partial seizure frequency during the MP. Safety and tolerability evaluation included adverse events (AEs), physical and neurologic examinations, and laboratory values. Pharmacokinetic and pharmacodynamic assessments were conducted.Results:  Three hundred fifty‐seven patients were randomized: 176 to rufinamide and 181 to placebo. Patients had a median of 13.3 seizures per 28 days during BP; 86% were receiving ≥2 AEDs. For the intent‐to‐treat population, the median percentage reduction in total partial seizure frequency per 28 days was 23.25 for rufinamide versus 9.80 for placebo (p = 0.007). Rufinamide‐treated patients were more than twice as likely to have had a ≥50% reduction in partial seizure frequency (32.5% vs. 14.3%; p < 0.001) and had a greater reduction in median total partial seizure rate per 28 days during the MP (13.2 vs. 5.2; p < 0.001). Treatment‐emergent AEs occurring at ≥5% higher incidence in the rufinamide group compared with placebo were dizziness, fatigue, nausea, somnolence, and diplopia.Conclusions:  Adjunctive treatment with rufinamide reduced total partial seizures in refractory patients. AEs reported were consistent with the known tolerability profile of rufinamide.