bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of high temperatures on cause-specific mortality in England and Wales
Authors: Gasparrini Antonio , Armstrong Ben , Kovats Sari , Wilkinson Paul 
Published: March 2011

ObjectivesSeveral observational studies have suggested an association between high temperatures and all-cause mortality. However, estimates on more specific mortality outcomes are sparse, and frequently assessed in studies using different analytical methods.MethodsA time series analysis was performed on 10 regions in England and Wales during the summers (June–September) of 1993–2006. Average percentage linear increases in risk for a 1°C increase in temperature above region-specific thresholds and attributable deaths were computed by cause-specific mortality and age groups (0–64, 65–74, 75–84, 85+).ResultsThere was evidence of increased mortality with heat for almost all cause-of-death groups examined, with an overall increase in all-cause mortality of 2.1% (95% CI 1.6% to 2.6%) for a 1°C rise above the regional heat threshold. Among main causes, the steepest increase in risk was for respiratory mortality (+4.1% (3.5% to 4.8%) per 1°C). It was much smaller for cardiovascular causes (+1.8% (1.2% to 2.5%)) and myocardial infarction (+1.1% (0.7% to 1.5%)), but comparatively high for arrhythmias (+5.0% (3.2% to 6.9%)) and pulmonary heart disease (+8.3% (2.7% to 14.3%)). Among non- cardiorespiratory causes, the strongest effects were for genitourinary (+3.8% (2.9% to 4.7%)) and nervous system (+4.6% (3.7% to 5.4%)) disorders. 33.9% of heat deaths were attributable to cardiovascular causes, 24.7% to respiratory causes and 41.3% to all other causes combined.ConclusionsThese results suggest that the risk of heat-related mortality is distributed across a wide range of different causes, and that targeting of preventative actions based on pre-existing disease is unlikely to be efficient.
CALCULUS ON FRACTAL CURVES IN Rn
Authors: PARVATE ABHAY , SATIN SEEMA , GANGAL A. D. 
Published: March 2011

A new calculus on fractal curves, such as the von Koch curve, is formulated. We define a Riemann-like integral along a fractal curve F, called Fα-integral, where α is the dimension of F. A derivative along the fractal curve called Fα-derivative, is also defined. The mass function, a measure-like algorithmic quantity on the curves, plays a central role in the formulation. An appropriate algorithm to calculate the mass function is presented to emphasize its algorithmic aspect. Several aspects of this calculus retain much of the simplicity of ordinary calculus. We establish a conjugacy between this calculus and ordinary calculus on the real line. The Fα-integral and Fα-derivative are shown to be conjugate to the Riemann integral and ordinary derivative respectively. In fact, they can thus be evalutated using the corresponding operators in ordinary calculus and conjugacy. Sobolev Spaces are constructed on F, and Fα-differentiability is generalized. Finally we touch upon an example of absorption along fractal paths, to illustrate the utility of the framework in model making.
Incision rate of the Yellow River in Northeastern Tibet constrained by
10
Be and
26
Al cosmogenic isotope dating of fluvial terraces: implications for catchment evolution and plateau building
Authors: Perrineau A. , Woerd J. Van Der , Gaudemer Y. , Liu-Zeng Jing , Pik R. , Tapponnier P. , Thuizat R. , Rongzhang Zheng 
Published: March 2011

Abstract

Unlike other large rivers flowing out of Tibet, the Yellow River escapes from the plateau towards the NE crossing no less than five NW–SE striking, actively growing ranges and intervening basins. Thick Plio-Quaternary deposits and fluvial terraces testify to a phase of aggradation and sediment infill up to the average surface elevation (3200–3250 m a.s.l.) of the Gonghe, Guide and Qinghai Lake basins. A set of seven main terraces across the Gonghe Basin suggests progressive down-cutting of the Yellow River carving the 500 m deep Longyang gorge at the basin exit.
10
Be and
26
Al concentrations in quartz of surface and sub-surface samples of four terraces constrain the timing of incision by determining the burial age of the deposit and the exposure age of its surface. Modelling the depth dependence of the
10
Be concentration and the
26
Al/
10
Be ratio allows us to constrain the onset of the ongoing phase of incision to 120–250 ka. These ages suggest long-term incision rates between 2–6 mm a
−1
. Together with the present morphology of the Yellow River terraces across the Gonghe basin and the Longyang gorge, our results imply rapid river catchment evolution and interaction between river dynamics, tectonic and climate in northeastern Tibet.
Discontinuous low-velocity zones in southern Tibet question the viability of the channel flow model
Authors: Hetényi György , Vergne Jérôme , Bollinger Laurent , Cattin Rodolphe 
Published: March 2011

Abstract

Low-velocity zones (‘bright spots’) imaged by the INDEPTH seismic experiment in southern Tibet are extensively interpreted as widespread partial melt within the crust, which has given a strong support for the channel flow model. These suggest that a continuous seismic low-velocity zone underlies Tibet on the large scale. Here we take advantage of the Hi-CLIMB seismic experiment which includes a dense south–north profile and a lateral 2D seismic network to assess the vertical and the horizontal extension of low-velocity zones in southern Tibet. Several approaches including migration, amplitude analysis and waveform inversion of receiver functions are performed to detect crustal low-velocity zones using this new seismological dataset. Our results reveal localized and discontinuous low-velocity zones in Tibet. They indicate that the vertical extension of the low-velocity zones is about 10 km, and their maximum horizontal length appears to be
c
. 50 km. Our study suggests a partial correlation between the location of these low-velocity zones and the spatial distribution of Tibetan grabens. These results, especially the non-continuity of low-velocity zones, together with the observed regular value of mean crustal V
P
/V
S
ratio, question the existence of widespread partial melt of the southern Tibetan crust and, therefore, the viability of the channel flow model.
The seismological structure of the Tibetan Plateau crust and mantle down to 700 km depth
Authors: Mechie J. , Kind R. , Saul J. 
Published: March 2011

Abstract

A seismic velocity cross-section down to 700 km depth beneath the Tibetan Plateau has been constructed. Beneath the cover layer, felsic rocks rich in α quartz exist down to 15–25 km depth. Beneath these depths, temperatures are probably high enough for ductile flow and partial melting to occur. The velocity increase across the boundary at 30–40 km depth marks the interface between felsic upper crust and more mafic lower crust. Crustal thickness is greatest (
c
. 74 km) south of
c
. 31.5°N, where Indian lower crust forms the basal layer. Northwards, crustal thickness decreases to
c
. 66 km around 33°N, before increasing to
c
. 70 km beneath northern Tibet. Crossing the Kunlun, the crust thins to
c
. 54 km beneath the Qaidam basin. High-velocity, dense, cold Indian lithospheric mantle extends northwards until about the Banggong-Nujiang suture, where it downwells to 350–400 km depth. The lithosphere–asthenosphere boundary occurs at 160–225 km depth. The apparent northwards deepening of the 410 and 660 km discontinuities implies that the upper mantle beneath northern Tibet is slower, less dense and warmer than under southern Tibet which, in turn, could provide some of the isostatic support for the high elevations in northern Tibet where the crust is thinner than under southern Tibet.
Phosphoglucose Isomerase/Autocrine Motility Factor Mediates Epithelial-Mesenchymal Transition Regulated by miR-200 in Breast Cancer Cells
Authors: Ahmad Aamir , Aboukameel Amro , Kong Dejuan , Wang Zhiwei , Sethi Seema , Chen Wei , Sarkar Fazlul H. , Raz Avraham 
Published: March 2011

Abstract
Phosphoglucose isomerase/autocrine motility factor (PGI/AMF) plays an important role in glycolysis and gluconeogenesis and is associated with invasion and metastasis of cancer cells. We have previously shown its role in the induction of epithelial-mesenchymal transition (EMT) in breast cancer cells, which led to increased aggressiveness; however, the molecular mechanism by which PGI/AMF regulates EMT is not known. Here we show, for the first time, that PGI/AMF overexpression led to an increase in the DNA-binding activity of NF-κB, which, in turn, led to increased expression of ZEB1/ZEB2. The microRNA-200s (miR-200s) miR-200a, miR-200b, and miR-200c are known to negatively regulate the expression of ZEB1/ZEB2, and we found that the expression of miR-200s was lost in PGI/AMF overexpressing MCF-10A cells and in highly invasive MDA-MB-231 cells, which was consistent with increased expression of ZEB1/ZEB2. Moreover, silencing of PGI/AMF expression in MDA-MB-231 cells led to overexpression of miR-200s, which was associated with reversal of EMT phenotype (i.e., mesenchymal-epithelial transition), and these findings were consistent with alterations in the relative expression of epithelial (E-cadherin) and mesenchymal (vimentin, ZEB1, ZEB2) markers and decreased aggressiveness as judged by clonogenic, motility, and invasion assays. Moreover, either reexpression of miR-200 or silencing of PGI/AMF suppressed pulmonary metastases of MDA-MB-231 cells in vivo, and anti-miR-200 treatment in vivo resulted in increased metastases. Collectively, these results suggest a role of miR-200s in PGI/AMF-induced EMT and thus approaches for upregulation of miR-200s could be a novel therapeutic strategy for the treatment of highly invasive breast cancer. Cancer Res; 71(9); 3400–9. ©2011 AACR.
Combined Promoter Methylation Analysis of CADM1 and MAL: An Objective Triage Tool for High-Risk Human Papillomavirus DNA–Positive Women
Authors: Hesselink Albertus T. , Heideman Daniëlle AM , Steenbergen Renske DM , Coupé Veerle M.H. , Overmeer Renee M. , Rijkaart Dorien , Berkhof Johannes , Meijer Chris J.L.M. , Snijders Peter J.F. 
Published: March 2011

Abstract
Purpose: Screening women for high-grade cervical intraepithelial neoplasia or cervical cancer (CIN3+) by high-risk human papillomavirus (hrHPV) testing has as side-effect the detection of hrHPV-positive women without clinically relevant lesions. Here, we developed an objective assay assessing the methylation status of the promoter regions of CADM1 and MAL to triage hrHPV-positive women for CIN3+.
Experimental Design: In a training set (51 women with CIN3+ and 224 without CIN2+), panels consisting of one to four quantitative methylation-specific PCR (qMSP) assays (CADM1-m12,CADM1-m18,MAL-m1,MAL-m2) were analyzed. Cross-validated receiver-operating characteristics (ROC) curves were constructed and the panel with highest partial cross-validated area under the curve (AUC) was used for validation in an independent set of 236 consecutive hrHPV-positive women from a screening cohort. In the validation set, the ROC curve of the panel was compared with CIN3+ sensitivity and specificity of cytology and of cytology combined with HPV16/18 genotyping.
Results: In the training set, CADM1-m18 combined with MAL-m1 was the best panel (cross-validated partial AUC = 0.719). In the validation set, this panel revealed CIN3+ sensitivities ranging from 100% (95% CI: 92.4–100) to 60.5% (95% CI: 47.1–74.6), with corresponding specificities ranging from 22.7% (95% CI: 20.2–25.2) to 83.3% (95% CI: 78.4–87.4). For cytology these were 65.8% (95% CI: 52.3–79.0) and 78.8% (95% CI: 73.7–83.1) and for cytology/HPV16/18, these were 84.2% (95% CI: 72.0–92.7) and 54.0% (95% CI: 49.2–58.7), respectively. The point estimates of both cytology and cytology/HPV16/18 were equal to the values of the ROC curve of CADM1-m18/MAL-m1.
Conclusions: We developed an objective methylation marker panel that was equally discriminatory for CIN3+ as cytology or cytology with HPV16/18 genotyping in hrHPV-positive women. This opens the possibility for complete cervical screening by objective, nonmorphological molecular methods. Clin Cancer Res; 17(8); 2459–65. ©2011 AACR.
Local Activation of CD8 T Cells and Systemic Tumor Eradication without Toxicity via Slow Release and Local Delivery of Agonistic CD40 Antibody
Authors: Fransen Marieke F. , Sluijter Marjolein , Morreau Hans , Arens Ramon , Melief Cornelis J.M. 
Published: March 2011

AbstractPurpose: Immunotherapy against tumors with anti-CD40 agonistic antibodies has been extensively studied in preclinical animal models and recently also in clinical trials. Although promising results have been obtained, antibody (Ab)-related toxicity has been a limiting factor. We reasoned that strict local activation of tumor-specific CD8 T cells through stimulation of CD40 on the dendritic cells (DC) in the tumor area while excluding systemic stimulation might be sufficient for effective tumor eradication and can limit systemic toxicity.Experimental Design: Preclinical in vivo models for immunogenic tumors were used to investigate the potential of delivering a nontoxic dose of agonistic anti-CD40 Ab to the tumor region, including draining lymph node, in a slow-release formulation (montanide).Results: The delivery of anti-CD40 monoclonal Ab, formulated in slow-release Montanide ISA-51, reprograms CTLs by inducing local but not systemic DC activation, resulting in effective tumor-specific CTL responses that eradicate local and distant tumors. Adverse side effects, assayed by organ histology and liver enzymes in the blood, were much lower after local anti-CD40 Ab delivery than systemic administration. The local delivery of anti-CD40 Ab activates only CTLs against antigens presented in the tumor-draining area, because unrelated distant tumors expressing different tumor antigens were not eradicated.Conclusions: These results establish a novel therapeutic principle that local delivery and slow release of agonistic anti-CD40 Ab to the tumor-draining area effectively activates local tumor-specific CD8 T cells to become systemic effectors without causing systemic toxicity or nonspecific CTL activation. These findings have important implications for the use of anti-CD40 therapies in patients. Clin Cancer Res; 17(8); 2270–80. ©2011 AACR.
Internalization of Oncolytic Reovirus by Human Dendritic Cell Carriers Protects the Virus from Neutralization
Authors: Ilett Elizabeth J. , Bárcena Montserrat , Errington-Mais Fiona , Griffin Stephen , Harrington Kevin J. , Pandha Hardev S. , Coffey Matthew , Selby Peter J. , Limpens Ronald W.A.L. , Mommaas Mieke , Hoeben Rob C. , Vile Richard G. , Melcher Alan A. 
Published: March 2011

Abstract
Purpose: Dendritic cells (DC) may be the most effective way of delivering oncolytic viruses to patients. Reovirus, a naturally occurring oncolytic virus, is currently undergoing early clinical trials; however, intravenous delivery of the virus is hampered by pre-existing antiviral immunity. Systemic delivery via cell carriage is a novel approach currently under investigation and initial studies have indicated its feasibility by using a variety of cell types and viruses. This study addressed the efficacy of human DC to transport virus in the presence of human neutralizing serum.
Experimental Design: Following reovirus-loading, DC or T cells were cocultured with melanoma cells with or without neutralizing serum; the melanoma cells were then analyzed for cell death. Following reovirus loading, cells were examined by electron microscopy to identify mechanisms of delivery. The phagocytic function of reovirus-loaded DC was investigated by using labeled tumor cells and the ability of reovirus-loaded DC to prime T cells was also investigated.
Results: In the presence of human neutralizing serum DC, but not T cells, were able to deliver reovirus for melanoma cell killing in vitro. Electron microscopy suggested that DC protected the virus by internalization, whereas with T cells it remained bound to the surface and hence accessible to neutralizing antibodies. Furthermore, DC loaded with reovirus were fully functional with regard to phagocytosis and priming of specific antitumor immune responses.
Conclusions: The delivery of reovirus via DC could be a promising new approach offering the possibility of combining systemic viral therapy for metastatic disease with induction of an antitumor immune response. Clin Cancer Res; 17(9); 2767–76. ©2011 AACR.
Curcumin Inhibition of the Functional Interaction between Integrin α6β4 and the Epidermal Growth Factor Receptor
Authors: Soung Young Hwa , Chung Jun 
Published: March 2011

Abstract
The functional interaction between integrin α6β4 and growth factor receptors has been implicated in key signaling pathways important for cancer cell function. However, few attempts have been made to selectively target this interaction for therapeutic intervention. Previous studies showed that curcumin, a yellow pigment isolated from turmeric, inhibits integrin α6β4 signaling important for breast carcinoma cell motility and invasion, but the mechanism is not currently known. To address this issue, we tested the hypothesis that curcumin inhibits the functional interaction between α6β4 and the epidermal growth factor receptor (EGFR). In this study, we found that curcumin disrupts functional and physical interactions between α6β4 and EGFR, and blocks α6β4/EGFR-dependent functions of carcinoma cells expressing the signaling competent form of α6β4. We further showed that curcumin inhibits EGF-dependent mobilization of α6β4 from hemidesmosomes to the leading edges of migrating cells such as lammelipodia and filopodia, and thereby prevents α6β4 distribution to lipid rafts where functional interactions between α6β4 and EGFR occur. These data suggest a novel paradigm in which curcumin inhibits α6β4 signaling and functions by altering intracellular localization of α6β4, thus preventing its association with signaling receptors such as EGFR. Mol Cancer Ther; 10(5); 883–91. ©2011 AACR.
Suppression of the uPAR–uPA System Retards Angiogenesis, Invasion, and In Vivo Tumor Development in Pancreatic Cancer Cells
Authors: Gorantla Bharathi , Asuthkar Swapna , Rao Jasti S. , Patel Jitendra , Gondi Christopher S. 
Published: March 2011

Abstract
Despite existing chemotherapy and surgical resection strategies, pancreatic cancer is one of the major causes of mortality in the United States with a 5-year mean survival rate of less than 5%. The activation of the urokinase-type plasminogen activator receptor–urokinase-type plasminogen activator (uPAR–uPA) system in the development of pancreatic ductal adenocarcinoma has been well established. In the present study, we used 2 pancreatic cancer cell lines, MIA PaCa-2 and PANC-1 to show the effects of uPAR and uPA downregulation. From the results, we observed that RNAi expressing plasmids efficiently downregulated mRNA and protein expression of uPAR and uPA. In vitro and in vivo angiogenic assays revealed a significant decrease in the angiogenic potential of MIA PaCa-2 and PANC-1 cells that were downregulated for both uPAR and uPA. From the angiogenesis antibody array analysis, we observed that the simultaneous downregulation of uPAR and uPA resulted in the downregulation of angiogenin and overexpression of RANTES. Further, FACS analysis showed that the simultaneous downregulation of uPAR and uPA caused the accumulation of cells in the sub-G0/1 phase in both MIA PaCa-2 and PANC-1 cells. In addition, Western blot analysis revealed that downregulation of uPAR and uPA caused the activation of caspase 8 and CAD, which is indicative of apoptosis, and in vivo TUNEL assay confirmed these results. Finally, we observed the nuclear localization of uPA and that uPA interacts with the transcription factor Lhx-2. Taken together, the results of the present study show that the targeting of the uPAR–uPA system has therapeutic potential. Mol Cancer Res; 9(4); 377–89. ©2011 AACR.
Word Learning in 6-Month-Olds: Fast Encoding–Weak Retention
Authors: Friedrich Manuela , Friederici Angela D. 
Published: March 2011

AbstractThere has been general consensus that initial word learning during early infancy is a slow and time-consuming process that requires very frequent exposure, whereas later in development, infants are able to quickly learn a novel word for a novel meaning. From the perspective of memory maturation, this shift in behavioral development might represent a shift from slow procedural to fast declarative memory formation. Alternatively, it might be caused by the maturation of specific brain structures within the declarative memory system that may support lexical mapping from the very first. Here, we used the neurophysiological method of ERPs to watch the brain activity of 6-month-old infants, when repeatedly presented with object–word pairs in a cross-modal learning paradigm. We report first evidence that infants as young as 6 months are able to associate objects and words after only very few exposures. A memory test 1 day later showed that infants did not fully forget this newly acquired knowledge, although the ERP effects indicated it to be less stable than immediately after encoding. The combined results suggest that already at 6 months the encoding process of word learning is based on fast declarative memory formation, but limitations in the consolidation of declarative memory diminish the long lasting effect in lexical-semantic memory at that age.
Fronto-parietal Areas Necessary for a Multisensory Representation of Peripersonal Space in Humans: An rTMS Study
Authors: Serino Andrea , Canzoneri Elisa , Avenanti Alessio 
Published: March 2011

Abstract
A network of brain regions including the ventral premotor cortex (vPMc) and the posterior parietal cortex (PPc) is consistently recruited during processing of multisensory stimuli within peripersonal space (PPS). However, to date, information on the causal role of these fronto-parietal areas in multisensory PPS representation is lacking. Using low-frequency repetitive TMS (rTMS; 1 Hz), we induced transient virtual lesions to the left vPMc, PPc, and visual cortex (V1, control site) and tested whether rTMS affected audio–tactile interaction in the PPS around the hand. Subjects performed a timed response task to a tactile stimulus on their right (contralateral to rTMS) hand while concurrent task-irrelevant sounds were presented either close to the hand or 1 m far from the hand. When no rTMS was delivered, a sound close to the hand reduced RT-to-tactile targets as compared with when a far sound was presented. This space-dependent, auditory modulation of tactile perception was specific to a hand-centered reference frame. Such a specific form of multisensory interaction near the hand can be taken as a behavioral hallmark of PPS representation. Crucially, virtual lesions to vPMc and PPc, but not to V1, eliminated the speeding effect due to near sounds, showing a disruption of audio–tactile interactions around the hand. These findings indicate that multisensory interaction around the hand depends on the functions of vPMc and PPc, thus pointing to the necessity of this human fronto-parietal network in multisensory representation of PPS.