bluuebunny/crossref_metadata_2025_split huggingface dataset:
Magma flow within dykes in submarine hyaloclastite environments: an AMS study of the Miocene Cabo de Gata volcanic units
Authors: Porreca M. , Cifelli F. , Soriano C. , Giordano G. , Mattei M. 
Published: September 2014

Abstract
The Miocene Cabo de Gata volcanic arc in SE Spain comprises a wide variety of volcanic facies and eruptive styles in subaqueous to subaerial environments. In the SW sector of the area, 5–100 m-thick, NNW–SSE-orientated dykes feed and intrude submarine hyaloclastite deposits. We analysed the anisotropy of magnetic susceptibility (AMS) of six dykes and five hyaloclastite sites from three volcanic units: the Cerro Cañadillas, Los Frailes, and El Barronal formations. The main magnetic minerals are primary low-Ti titanomagnetite and magnetite. The AMS ellipsoids in the dykes are generally oblate-triaxial in shape, with magnetic foliations subparallel to the dyke walls. Kinematic field evidence supports the inferred flow directions deduced from magnetic lineation and imbrication of magnetic foliation. The geometric relationships between dyke margins and AMS axes indicate that dykes at El Barronal were emplaced via prevalent subvertical upward magma flow. The inferred flow directions are reproduced well by analogue models of AMS simulating magma migration in dykes with a diapiric geometry. The other dykes were emplaced by lateral magma propagation. Conversely, hyaloclastite shows a large scatter of the AMS axes reflecting different degrees of fragmentation. We observe a gradual increase in scatter in the AMS from confined dykes to fragmented hyaloclastite.
Volcanic glass and its suitability to recover the ancient geomagnetic field strength
Authors: Ferk A. , Leonhardt R. , Hess K.-U. , Dingwell D. B. 
Published: September 2014

Abstract
The determination of the past ancient magnetic field intensity is typically very difficult and error prone. Fresh volcanic glass has been suggested to be an ideal material for obtaining direction and strength of the magnetic field. Domain state bias is generally absent, thermal alteration is normally negligible and, as demonstrated in this study, cooling-rate differences can be corrected for. Major issues remaining include alteration and the origin of the remanence: that is, whether it is a true thermo-, a thermochemical or, for altered samples, a chemical remanence. Hydration, devitrification and perlitization lead to incorrect estimates of the palaeointensity, which are very difficult to recognize as the palaeointensity analysis does not easily expose these biasing effects and points towards ‘reliable’ results. Particular care on sampling and/or volatile measurements are necessary to overcome these drawbacks.
Percolation of the interacting elastic stress fields of aligned cracks as an alternative explanation of critical crack densities
Authors: Heffer Kes 
Published: September 2014

Abstract
The concept that the lithosphere is in a general critical, or near-critical, mechanical state has previously assumed spatial intersection of fractures at the critical point. This paper provides an initial basis for an alternative mechanism in which elastic interactions between aligned, open, spatially separated (micro-)cracks in rock can, by themselves, lead to a continuous phase change at a critical threshold of crack density lower than that required for crack coalescence. The existence of a critical density of aligned cracks is first demonstrated on a regular 2D hexagonal grid when subjected to a central stress perturbation; at this critical density the elastic tensile stress interactions have a long-range effect. From the results of those calculations an approximation of the tensile stress field around a crack in 3D is provided. The percolation behaviour of such 3D bodies is discussed and a critical crack density in 3D for elastic interaction of 0.035 is deduced. This falls within the range of crack densities (0.015–0.045) interpreted from observations of shear-wave splitting in many different rocks. The possibility that critical crack interactions can be mostly elastic provides one explanation of the long-range nature of correlations in flowrate fluctuations in oilfields without large-scale seismicity.
Upregulation of IGF1R by Mutant RAS in Leukemia and Potentiation of RAS Signaling Inhibitors by Small-Molecule Inhibition of IGF1R
Authors: Weisberg Ellen , Nonami Atsushi , Chen Zhao , Nelson Erik , Chen Yongfei , Liu Feiyang , Cho HaeYeon , Zhang Jianming , Sattler Martin , Mitsiades Constantine , Wong Kwok-Kin , Liu Qingsong , Gray Nathanael S. , Griffin James D. 
Published: September 2014

Abstract
Purpose: Activating mutations in the RAS oncogene occur frequently in human leukemias. Direct targeting of RAS has proven to be challenging, although targeting of downstream RAS mediators, such as MEK, is currently being tested clinically. Given the complexity of RAS signaling, it is likely that combinations of targeted agents will be more effective than single agents.
Experimental Design: A chemical screen using RAS-dependent leukemia cells was developed to identify compounds with unanticipated activity in the presence of an MEK inhibitor and led to identification of inhibitors of IGF1R. Results were validated using cell-based proliferation, apoptosis, cell-cycle, and gene knockdown assays; immunoprecipitation and immunoblotting; and a noninvasive in vivo bioluminescence model of acute myeloid leukemia (AML).
Results: Mechanistically, IGF1R protein expression/activity was substantially increased in mutant RAS-expressing cells, and suppression of RAS led to decreases in IGF1R. Synergy between MEK and IGF1R inhibitors correlated with induction of apoptosis, inhibition of cell-cycle progression, and decreased phospho-S6 and phospho-4E-BP1. In vivo, NSG mice tail veins injected with OCI-AML3-luc+ cells showed significantly lower tumor burden following 1 week of daily oral administration of 50 mg/kg NVP-AEW541 (IGF1R inhibitor) combined with 25 mg/kg AZD6244 (MEK inhibitor), as compared with mice treated with either agent alone. Drug combination effects observed in cell-based assays were generalized to additional mutant RAS-positive neoplasms.
Conclusions: The finding that downstream inhibitors of RAS signaling and IGF1R inhibitors have synergistic activity warrants further clinical investigation of IGF1R and RAS signaling inhibition as a potential treatment strategy for RAS-driven malignancies. Clin Cancer Res; 20(21); 5483–95. ©2014 AACR.
High-Throughput Drug Screen Identifies Chelerythrine as a Selective Inducer of Death in a TSC2-null Setting
Authors: Medvetz Doug , Sun Yang , Li Chenggang , Khabibullin Damir , Balan Murugabaskar , Parkhitko Andrey , Priolo Carmen , Asara John M. , Pal Soumitro , Yu Jane , Henske Elizabeth P. 
Published: September 2014

Abstract
Tuberous sclerosis complex (TSC) is an autosomal dominant syndrome associated with tumors of the brain, heart, kidney, and lung. The TSC protein complex inhibits the mammalian or mechanistic target of rapamycin complex 1 (mTORC1). Inhibitors of mTORC1, including rapamycin, induce a cytostatic response in TSC tumors, resulting in temporary disease stabilization and prompt regrowth when treatment is stopped. The lack of TSC-specific cytotoxic therapies represents an important unmet clinical need. Using a high-throughput chemical screen in TSC2-deficient, patient-derived cells, we identified a series of molecules antagonized by rapamycin and therefore selective for cells with mTORC1 hyperactivity. In particular, the cell-permeable alkaloid chelerythrine induced reactive oxygen species (ROS) and depleted glutathione (GSH) selectively in TSC2-null cells based on metabolic profiling. N-acetylcysteine or GSH cotreatment protected TSC2-null cells from chelerythrine's effects, indicating that chelerythrine-induced cell death is ROS dependent. Induction of heme-oxygenase-1 (HMOX1/HO-1) with hemin also blocked chelerythrine-induced cell death. In vivo, chelerythrine inhibited the growth of TSC2-null xenograft tumors with no evidence of systemic toxicity with daily treatment over an extended period of time. This study reports the results of a bioactive compound screen and the identification of a potential lead candidate that acts via a novel oxidative stress–dependent mechanism to selectively induce necroptosis in TSC2-deficient tumors.
Implications: This study demonstrates that TSC2-deficient tumor cells are hypersensitive to oxidative stress–dependent cell death, and provide critical proof of concept that TSC2-deficient cells can be therapeutically targeted without the use of a rapalog to induce a cell death response. Mol Cancer Res; 13(1); 50–62. ©2014 AACR.
Serine Catabolism Regulates Mitochondrial Redox Control during Hypoxia
Authors: Ye Jiangbin , Fan Jing , Venneti Sriram , Wan Ying-Wooi , Pawel Bruce R. , Zhang Ji , Finley Lydia W.S. , Lu Chao , Lindsten Tullia , Cross Justin R. , Qing Guoliang , Liu Zhandong , Simon M. Celeste , Rabinowitz Joshua D. , Thompson Craig B. 
Published: September 2014

Abstract
The de novo synthesis of the nonessential amino acid serine is often upregulated in cancer. In this study, we demonstrate that the serine catabolic enzyme, mitochondrial serine hydroxymethyltransferase (SHMT2), is induced when MYC-transformed cells are subjected to hypoxia. In mitochondria, SHMT2 can initiate the degradation of serine to CO2 and NH4+, resulting in net production of NADPH from NADP+. Knockdown of SHMT2 in MYC-dependent cells reduced cellular NADPH:NADP+ ratio, increased cellular reactive oxygen species, and triggered hypoxia-induced cell death. In vivo, SHMT2 suppression led to impaired tumor growth. In MYC-amplified neuroblastoma patient samples, there was a significant correlation between SHMT2 and hypoxia-inducible factor-1 α (HIF1α), and SHMT2 expression correlated with unfavorable patient prognosis. Together, these data demonstrate that mitochondrial serine catabolism supports tumor growth by maintaining mitochondrial redox balance and cell survival.
Significance: In this study, we demonstrate that the mitochondrial enzyme SHMT2 is induced upon hypoxic stress and is critical for maintaining NADPH production and redox balance to support tumor cell survival and growth. Cancer Discov; 4(12); 1406–17. ©2014 AACR.
See related commentary by Martínez-Reyes and Chandel, p. 1371
This article is highlighted in the In This Issue feature, p. 1355
In vivo activation and functions of the protease factor XII
Authors: Björkqvist Jenny , Nickel Katrin , Stavrou Evi , Renné Thomas 
Published: September 2014

SummaryCombinations of proinflammatory and procoagulant reactions are the unifying principle for a variety of disorders affecting the cardiovascular system. Factor XII (FXII, Hageman factor) is a plasma protease that initiates the contact system. The biochemistry of the contact system in vitro is well understood; however, its in vivo functions are just beginning to emerge. The current review concentrates on activators and functions of the FXII-driven contact system in vivo. Elucidating its physiologic activities offers the exciting opportunity to develop strategies for the safe interference with both thrombotic and inflammatory diseases.
The influence of type 2 diabetes on fibrin clot properties in patients with coronary artery disease
Authors: Neergaard-Petersen Søs , Hvas Anne-Mette , Kristensen Steen , Grove Erik , Larsen Sanne , Phoenix Fladia , Kurdee Zeyad , Grant Peter , Ajjan Ramzi 
Published: September 2014

SummaryType 2 diabetes mellitus (T2DM) increases the risk of coronary thrombosis and both conditions are associated with altered fibrin clot properties. However, the influence of T2DM on fibrin clot properties in patients with coronary artery disease (CAD) remains unclear. We aimed to investigate the influence of T2DM on fibrin clot properties in patients with CAD. Fibrin clot structure and fibrinolysis were investigated in 581 CAD patients (148 with T2DM) using turbidimetric assays, confocal and scanning electron microscopy. Clots made from plasma and plasma-purified fibrinogen were studied, and plasma levels of inflammatory markers were analysed. T2DM patients had increased clot maximum absorbance compared with non-diabetic patients (0.36 ± 0.1 vs 0.33 ± 0.1 au; p=0.01), displayed longer lysis time (804 [618;1002] vs 750 [624;906] seconds; p=0.03) and showed more compact fibrin structure assessed by confocal and electron microscopy. Fibrinogen levels were elevated in T2DM (p< 0.001), but clots made from purified fibrinogen showed no differences in fibrin properties in the two populations. Adjusting for fibrinogen levels, T2DM was associated with C-reactive protein and complement C3 plasma levels, with the former correlating with clot maximum absorbance (r=0.24, p< 0.0001) and the latter with lysis time (r=0.30, p< 0.0001). Independent of fibrinogen levels, females had more compact clots with prolonged lysis time compared with males (all p-values< 0.001). In conclusion, T2DM is associated with prothrombotic changes in fibrin clot properties in patients with CAD. This is related to quantitative rather than qualitative changes in fibrinogen with a possible role for inflammatory proteins.
Platelets in neonates: Central mediators in haemostasis, antimicrobial defence and inflammation
Authors: Schulze Harald , Andres Oliver , Speer Christian P. 
Published: September 2014

SummaryPlatelets are not only centrally involved in haemostasis, but also in antimicrobial defence and inflammation. Since evaluation of platelet physiology in the particular patient group of preterm and term neonatal infants is highly restricted for ethical reasons, there are hardly any data available in healthy and much less in extremely immature or ill neonates. By summarising current knowledge and addressing both platelet researchers and neonatologists, we describe neonatal platelet count and morphology, report on previous analyses of neonatal platelet function in primary haemostasis and provide insights into recent advances in platelet immunology that considerably impacts our clinical view on the critically ill neonatal infant. We conclude that neonatal platelets, originating from liver megakaryocytes, substantially differ from adult platelets and may play a pivotal role in the pathophysiology of neonatal sepsis or intraventricular haemorrhage, both complications which seriously augment perinatal morbidity and mortality.
Factor Va alternative conformation reconstruction using atomic force microscopy
Authors: Chaves Rui , Dahmane Selma , Odorico Michael , Nicolaes Gerry , Pellequer Jean-Luc 
Published: September 2014

SummaryProtein conformational variability (or dynamics) for large macromolecules and its implication for their biological function attracts more and more attention. Collective motions of domains increase the ability of a protein to bind to partner molecules. Using atomic force microscopy (AFM) topographic images, it is possible to take snapshots of large multi-component macromolecules at the single molecule level and to reconstruct complete molecular conformations. Here, we report the application of a reconstruction protocol, named AFM-assembly, to characterise the conformational variability of the two C domains of human coagulation factor Va (FVa). Using AFM topographic surfaces obtained in liquid environment, it is shown that the angle between C1 and C2 domains of FVa can vary between 40° and 166°. Such dynamical variation in C1 and C2 domain arrangement may have important implications regarding the binding of FVa to phospholipid membranes.
Direct Conversion of Adult Skin Fibroblasts to Endothelial Cells by Defined Factors
Authors: Han Jung-Kyu , Chang Sung-Hwan , Cho Hyun-Ju , Choi Saet-Byeol , Ahn Hyo-Suk , Lee Jaewon , Jeong Heewon , Youn Seock-Won , Lee Ho-Jae , Kwon Yoo-Wook , Cho Hyun-Jai , Oh Byung-Hee , Oettgen Peter , Park Young-Bae , Kim Hyo-Soo 
Published: September 2014

Background—
Cell-based therapies to augment endothelial cells (ECs) hold great therapeutic promise. Here, we report a novel approach to generate functional ECs directly from adult fibroblasts.

Methods and Results—

Eleven candidate genes that are key regulators of endothelial development were selected. Green fluorescent protein (GFP)–negative skin fibroblasts were prepared from Tie2-GFP mice and infected with lentiviruses allowing simultaneous overexpression of all 11 factors. Tie2-GFP
+
cells (0.9%), representing Tie2 gene activation, were detected by flow cytometry. Serial stepwise screening revealed 5 key factors (Foxo1, Er71, Klf2, Tal1, and Lmo2) that were required for efficient reprogramming of skin fibroblasts into Tie2-GFP
+
cells (4%). This reprogramming strategy did not involve pluripotency induction because neither Oct4 nor Nanog was expressed after 5 key factor transduction. Tie2-GFP
+
cells were isolated using fluorescence-activated cell sorting and designated as induced ECs (iECs). iECs exhibited endothelium-like cobblestone morphology and expressed EC molecular markers. iECs possessed endothelial functions such as
Bandeiraea simplicifolia
-1 lectin binding, acetylated low-density lipoprotein uptake, capillary formation on Matrigel, and nitric oxide production. The epigenetic profile of iECs was similar to that of authentic ECs because the promoters of VE-cadherin and Tie2 genes were demethylated. mRNA profiling showed clustering of iECs with authentic ECs and highly enriched endothelial genes in iECs. In a murine model of hind-limb ischemia, iEC implantation increased capillary density and enhanced limb perfusion, demonstrating the in vivo viability and functionality of iECs.

Conclusions—
We demonstrated the first direct conversion of adult fibroblasts to functional ECs. These results suggest a novel therapeutic modality for cell therapy in ischemic vascular disease.
A revised generic arrangement for the eagle ray family Myliobatidae, with definitions for the valid genera
Authors: WHITE WILLIAM T. 
Published: September 2014

The generic arrangement of the eagle rays (Family Myliobatidae) is revised and the genus Pteromylaeus Garman, 1913 is placed into the synonymy of Aetomylaeus Garman, 1908. Definitions are provided for the three valid genera, Aetobatus, Aetomylaeus and Myliobatis, and nomenclatural issues are discussed. Aetobatus differs from the latter two genera in having: a deeply notched nasal curtain, both jaws with a single row of chevron-shaped teeth, broadly rounded pectoral-fin free rear tips, pectoral fins separate from rostral lobe and joining head at level of eye. Aetomylaeus differs from the other two genera in having: pectoral fins separate from rostral lobe and joining head below level of eye, and stinging spine absent or present (usually not well developed when present). Myliobatis differs from the other two genera in having the pectoral fins joined to the rostral lobe by a subocular ridge. A list of valid species is provided, including a list of junior synonyms. Myliobatis australis Macleay, 1881 from southern Australia is placed into the synonymy of the previously considered endemic New Zealand species, M. tenuicaudatus Hector, 1877.
Teleconnections between Tropical Pacific SST Anomalies and Extratropical Southern Hemisphere Climate
Authors: Ciasto Laura M. , Simpkins Graham R. , England Matthew H. 
Published: September 2014

Abstract
Teleconnections from tropical Pacific sea surface temperature (SST) anomalies to the high-latitude Southern Hemisphere (SH) are examined using observations and reanalysis. Analysis of tropical Pacific SST anomalies is conducted separately for the central Pacific (CP) and eastern Pacific (EP) regions. During the austral cold season, extratropical SH atmospheric Rossby wave train patterns are observed in association with both EP and CP SST variability. The primary difference between the patterns is the westward displacement of the CP-related atmospheric anomalies, consistent with the westward elongation of CP-related convective SST required for upper-level divergence and Rossby wave generation. Consequently, CP-related patterns of SH SST, Antarctic sea ice, and temperature anomalies also exhibit a westward displacement, but otherwise, the cold season extratropical SH teleconnections are largely similar. During the warm season, however, extratropical SH teleconnections associated with tropical CP and EP SST anomalies differ substantially. EP SST variability is linked to largely zonally symmetric structures in the extratropical atmospheric circulation, which projects onto the southern annular mode (SAM), and is strongly related to the SH temperature and sea ice fields. In contrast, CP SST variability is only weakly related to the SH atmospheric circulation, temperature, or sea ice fields and no longer exhibits any clear association with the SAM. One hypothesized mechanism suggests that the relatively weak CP-related SST anomalies are not able to substantially impact the background flow of the subtropical jet and its subsequent interaction with equatorward-propagating waves associated with variability in the SAM. However, there is currently no widely established mechanism that links tropical Pacific SST anomalies to the SAM.
Evaluating LSM-Based Water Budgets over a West African Basin Assisted with a River Routing Scheme
Authors: Getirana Augusto C. V. , Boone Aaron , Peugeot Christophe 
Published: September 2014

AbstractWithin the framework of the African Monsoon Multidisciplinary Analysis (AMMA) Land Surface Model Intercomparison Project phase 2 (ALMIP-2), this study evaluates the water balance simulated by the Interactions between Soil, Biosphere, and Atmosphere (ISBA) over the upper Ouémé River basin, in Benin, using a mesoscale river routing scheme (RRS). The RRS is based on the nonlinear Muskingum–Cunge method coupled with two linear reservoirs that simulate the time delay of both surface runoff and base flow that are produced by land surface models. On the basis of the evidence of a deep water-table recharge in that region, a reservoir representing the deep-water infiltration (DWI) is introduced. The hydrological processes of the basin are simulated for the 2005–08 AMMA field campaign period during which rainfall and streamflow data were intensively collected over the study area. Optimal RRS parameter sets were determined for three optimization experiments that were performed using daily streamflow at five gauges within the basin. Results demonstrate that the RRS simulates streamflow at all gauges with relative errors varying from −20% to 3% and Nash–Sutcliffe coefficients varying from 0.62 to 0.90. DWI varies from 24% to 67% of the base flow as a function of the subbasin. The relatively simple reservoir DWI approach is quite robust, and further improvements would likely necessitate more complex solutions (e.g., considering seasonality and soil type in ISBA); thus, such modifications are recommended for future studies. Although the evaluation shows that the simulated streamflows are generally satisfactory, further field investigations are necessary to confirm some of the model assumptions.