bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Tyrosine Kinase Inhibitor E-3810 Combined with Paclitaxel Inhibits the Growth of Advanced-Stage Triple-Negative Breast Cancer Xenografts
Authors: Bello Ezia , Taraboletti Giulia , Colella Gennaro , Zucchetti Massimo , Forestieri Daniele , Licandro Simonetta A. , Berndt Alexander , Richter Petra , D'Incalci Maurizio , Cavalletti Ennio , Giavazzi Raffaella , Camboni Gabriella , Damia Giovanna 
Published: December 2012

AbstractE-3810 is a novel small molecule that inhibits VEGF receptor-1, -2, and -3 and fibroblast growth factor receptor-1 tyrosine kinases at nmol/L concentrations currently in phase clinical II. In preclinical studies, it had a broad spectrum of antitumor activity when used as monotherapy in a variety of human xenografts. We here investigated the activity of E-3810 combined with different cytotoxic agents in a MDA-MB-231 triple-negative breast cancer xenograft model. The molecule could be safely administered with 5-fluorouracil, cisplatin, and paclitaxel. The E-3810–paclitaxel combination showed a striking activity with complete, lasting tumor regressions; the antitumor activity of the combination was also confirmed in another triple-negative breast xenograft, MX-1. The activity was superior to that of the combinations paclitaxel+brivanib and paclitaxel+sunitinib. Pharmacokinetics studies suggest that the extra antitumor activity of the combination is not due to higher paclitaxel tumor levels, which in fact were lower in mice pretreated with all three kinase inhibitors, and the paclitaxel plasma levels excluded reduced drug availability. Pharmacodynamic studies showed that E-3810, brivanib, and sunitinib given as single agents or in combination with paclitaxel reduced the number of vessels, but did not modify vessel maturation. Reduced tumor collagen IV and increased plasma collagen IV, associated with increased matrix metalloproteinases (MMP), particularly host MMP-9, indicate a proteolytic remodeling of the extracellular matrix caused by E-3810 that in conjunction with the cytotoxic effect of paclitaxel on the tumor cells (caspase-3/7 activity) may contribute to the striking activity of their combination. These data support the therapeutic potential of combining E-3810 with conventional chemotherapy. Mol Cancer Ther; 12(2); 131–40. ©2012 AACR.
Morbidity and Mortality in Heart Transplant Candidates Supported With Mechanical Circulatory Support
Authors: Wever-Pinzon Omar , Drakos Stavros G. , Kfoury Abdallah G. , Nativi Jose N. , Gilbert Edward M. , Everitt Melanie , Alharethi Rami , Brunisholz Kim , Bader Feras M. , Li Dean Y. , Selzman Craig H. , Stehlik Josef 
Published: December 2012

Background—
Survival of patients on left ventricular assist devices (LVADs) has improved. We examined the differences in risk of adverse outcomes between LVAD-supported and medically managed candidates on the heart transplant waiting list.

Methods and Results—

We analyzed mortality and morbidity in 33 073 heart transplant candidates registered on the United Network for Organ Sharing (UNOS) waiting list between 1999 and 2011. Five groups were selected: patients without LVADs in urgency status 1A, 1B, and 2; patients with pulsatile-flow LVADs; and patients with continuous-flow LVADs. Outcomes in patients requiring biventricular assist devices, total artificial heart, and temporary VADs were also analyzed. Two eras were defined on the basis of the approval date of the first continuous-flow LVAD for bridge to transplantation in the United States (2008). Mortality was lower in the current compared with the first era (2.1%/mo versus 2.9%/mo;
P
<0.0001). In the first era, mortality of pulsatile-flow LVAD patients was higher than in status 2 (hazard ratio [HR], 2.15;
P
<0.0001) and similar to that in status 1B patients (HR, 1.04;
P
=0.61). In the current era, patients with continuous-flow LVADs had mortality similar to that of status 2 (HR, 0.80;
P
=0.12) and lower mortality compared with status 1A and 1B patients (HR, 0.24 and 0.47;
P
<0.0001 for both comparisons). However, status upgrade for LVAD-related complications occurred frequently (28%) and increased the mortality risk (HR, 1.75;
P
=0.001). Mortality was highest in patients with biventricular assist devices (HR, 5.00;
P
<0.0001) and temporary VADs (HR, 7.72;
P
<0.0001).

Conclusions—
Mortality and morbidity on the heart transplant waiting list have decreased. Candidates supported with contemporary continuous-flow LVADs have favorable waiting list outcomes; however, they worsen significantly once a serious LVAD-related complication occurs. Transplant candidates requiring temporary and biventricular support have the highest risk of adverse outcomes. These results may help to guide optimal allocation of donor hearts.
Late Sodium Current Inhibition Reverses Electromechanical Dysfunction in Human Hypertrophic Cardiomyopathy
Authors: Coppini Raffaele , Ferrantini Cecilia , Yao Lina , Fan Peidong , Del Lungo Martina , Stillitano Francesca , Sartiani Laura , Tosi Benedetta , Suffredini Silvia , Tesi Chiara , Yacoub Magdi , Olivotto Iacopo , Belardinelli Luiz , Poggesi Corrado , Cerbai Elisabetta , Mugelli Alessandro 
Published: December 2012

Background—
Hypertrophic cardiomyopathy (HCM), the most common mendelian heart disorder, remains an orphan of disease-specific pharmacological treatment because of the limited understanding of cellular mechanisms underlying arrhythmogenicity and diastolic dysfunction.

Methods and Results—

We assessed the electromechanical profile of cardiomyocytes from 26 HCM patients undergoing myectomy compared with those from nonfailing nonhypertrophic surgical patients by performing patch-clamp and intracellular Ca
2+
(Ca
2+
i
) studies. Compared with controls, HCM cardiomyocytes showed prolonged action potential related to increased late Na
+
(
I
NaL
) and Ca
2+
(
I
CaL
) currents and decreased repolarizing K
+
currents, increased occurrence of cellular arrhythmias, prolonged Ca
2+
i
transients, and higher diastolic Ca
2+
i
. Such changes were related to enhanced Ca
2+
/calmodulin kinase II (CaMKII) activity and increased phosphorylation of its targets. Ranolazine at therapeutic concentrations partially reversed the HCM-related cellular abnormalities via
I
NaL
inhibition, with negligible effects in controls. By shortening the action potential duration in HCM cardiomyocytes, ranolazine reduced the occurrence of early and delayed afterdepolarizations. Finally, as a result of the faster kinetics of Ca
2+
i
transients and the lower diastolic Ca
2+
i
, ranolazine accelerated the contraction-relaxation cycle of HCM trabeculae, ameliorating diastolic function.

Conclusions—

We highlighted a specific set of functional changes in human HCM myocardium that stem from a complex remodeling process involving alterations of CaMKII-dependent signaling, rather than being a direct consequence of the causal sarcomeric mutations. Among the several ion channel and Ca
2+
i
handling proteins changes identified, an enhanced
I
NaL
seems to be a major contributor to the electrophysiological and Ca
2+
i
dynamic abnormalities of ventricular myocytes and trabeculae from patients with HCM, suggesting potential therapeutic implications of
I
NaL
inhibition.
Understanding Hadley Cell Expansion versus Contraction: Insights from Simplified Models and Implications for Recent Observations
Authors: Tandon Neil F. , Gerber Edwin P. , Sobel Adam H. , Polvani Lorenzo M. 
Published: December 2012

Abstract
This study seeks a deeper understanding of the causes of Hadley Cell (HC) expansion, as projected under global warming, and HC contraction, as observed under El Niño. Using an idealized general circulation model, the authors show that a thermal forcing applied to a narrow region around the equator produces “El Niño–like” HC contraction, while a forcing with wider meridional extent produces “global warming–like” HC expansion. These circulation responses are sensitive primarily to the thermal forcing’s meridional structure and are less sensitive to its vertical structure. If the thermal forcing is confined to the midlatitudes, the amount of HC expansion is more than three times that of a forcing of comparable amplitude that is spread over the tropics. This finding may be relevant to recently observed trends of rapid tropical widening.
The shift of the HC edge is explained using a very simple model in which the transformed Eulerian mean (TEM) circulation acts to diffuse heat meridionally. In this context, the HC edge is defined as the downward maximum of residual vertical velocity in the upper troposphere ; this corresponds well with the conventional Eulerian definition of the HC edge. In response to a positive thermal forcing, there is anomalous diabatic cooling, and hence anomalous TEM descent, on the poleward flank of the thermal forcing. This causes the HC edge () to shift toward the descending anomaly, so that a narrow forcing causes HC contraction and a wide forcing causes HC expansion.
Mesoscale Eddy Buoyancy Flux and Eddy-Induced Circulation in Eastern Boundary Currents
Authors: Colas François , Capet Xavier , McWilliams James C. , Li Zhijin 
Published: December 2012

Abstract
A dynamical interpretation is made of the mesoscale eddy buoyancy fluxes in the Eastern Boundary Currents off California and Peru–Chile, based on regional equilibrium simulations. The eddy fluxes are primarily shoreward and upward across a swath several hundred kilometers wide in the upper ocean; as such they serve to balance mean offshore air–sea heating and coastal upwelling. In the stratified interior the eddy fluxes are consistent with the adiabatic hypothesis associated with a mean eddy-induced velocity advecting mean buoyancy and tracers. Furthermore, with a suitable gauge choice, the horizontal fluxes are almost entirely aligned with the mean horizontal buoyancy gradient, consistent with the advective parameterization scheme of Gent and McWilliams. The associated diffusivity κ is surface intensified, matching the vertical stratification profile. The fluxes span the across-shore band of high eddy energy, but their alongshore structure is unresolved because of sampling limitations. In the surface layer the eddy flux is significantly diabatic with a shallow eddy-induced circulation cell and downgradient lateral diapycnal flux. The dominant eddy generation process is baroclinic instability, but there are significant regional differences between the upwelling systems in the flux and κ that are not consistent with simple instability theory.
Evaluation and Recommendations for Improving the Accuracy of an Inexpensive Water Temperature Logger
Authors: Lentz S. J. , Churchill J. H. , Marquette C. , Smith J. 
Published: December 2012

Abstract
Onset's HOBO U22 Water Temp Pros are small, reliable, relatively inexpensive, self-contained temperature loggers that are widely used in studies of oceans, lakes, and streams. An in-house temperature bath calibration of 158 Temp Pros indicated root-mean-square (RMS) errors ranging from 0.01° to 0.14°C, with one value of 0.23°C, consistent with the factory specifications. Application of a quadratic calibration correction substantially reduced the RMS error to less than 0.009°C in all cases. The primary correction was a bias error typically between −0.1° and 0.15°C. Comparison of water temperature measurements from Temp Pros and more accurate temperature loggers during two oceanographic studies indicates that calibrated Temp Pros have an RMS error of ~0.02°C throughout the water column at night and beneath the surface layer influenced by penetrating solar radiation during the day. Larger RMS errors (up to 0.08°C) are observed near the surface during the day due to solar heating of the black Temp Pro housing. Errors due to solar heating are significantly reduced by wrapping the housing with white electrical tape.
The Biomechanical Stability of Distal Clavicle Excision Versus Symmetric Acromioclavicular Joint Resection
Authors: Pandhi Nikhil G. , Esquivel Amanda O. , Hanna Jason D. , Lemos David W. , Staron Jeffrey S. , Lemos Stephen E. 
Published: December 2012

Background: Treatment for acromioclavicular (AC) joint pain may include distal clavicle excision (DCE). It is possible that DCE can disrupt the surrounding ligaments, leading to increased AC joint laxity. Purpose: To determine the load to failure and stiffness of the AC joint after DCE and symmetric acromioclavicular joint resection (ACJR). Study Design: Controlled laboratory study. Methods: Specimens were randomly assigned to 1 of 2 groups: 1-cm DCE (n = 10) or symmetric (5-mm excision of acromion and distal clavicle) ACJR (n = 10). The specimens were loaded intact in the anterior-posterior plane to determine anteroposterior translation. This was repeated after surgery and compared. The specimens were loaded at 2 mm/s until clinical failure. Force and displacement were recorded, and stiffness was calculated. Results: The peak load to failure for the DCE group was 387.8 N (standard error of the mean [SEM], 31.4 N) and for the ACJR group was 468.5 N (SEM, 30.9 N) ( P = .035). The average stiffness for the DCE group was 35.2 N/mm (SEM, 2.5 N/mm) and for the ACJR group was 37.4 N/mm (SEM, 2.3 N/mm) ( P = .11). There was no significant difference in the anteroposterior translation before and after resection for either group ( P > .05). Conclusion: This cadaveric study demonstrates that the anterior-posterior load to clinical failure of the AC joint after 5 mm of resection from the distal clavicle and medial acromion is significantly greater than 1 cm of the resected distal clavicle alone. Clinical Relevance: Performing ACJR may improve joint stability, leading to fewer complications when compared with DCE.
Diffusion Tensor Imaging Reveals White Matter Changes Associated With Cognitive Status in Patients With Parkinson’s Disease
Authors: Deng Bingmei , Zhang Yuhu , Wang Lijuan , Peng Kairun , Han Lixin , Nie Kun , Yang Hongjun , Zhang Li , Wang Jun 
Published: December 2012

Objective : Cognitive deficit and white matter alteration relationships in Parkinson’s disease (PD) were investigated. Methods : Comparison of 64 patients with PD (M:F, 34:30; 64.4 ± 10.4 years) classified as cognitively normal (PD-CogNL, n = 24), mild cognitive impairment (PD-MCI, n = 30), and dementia (PD-D, n = 10) with 21 healthy participants (M:F, 10:11; 60.1 ± 13.6 years) was conducted using white matter fractional anisotropy (FA), region-of-interest analysis, and diffusion tensor imaging. Results : The PD-D and PD-MCI exhibited higher Unified Parkinson’s Disease Rating Scale motor scores ( P < .001; P < .01) and Hoehn-Yahr stages ( P < .001; P < .05) and FA reductions in left frontal/right temporal white matter and bilateral anterior cingulated bundles. Largest FA reductions occurred in PD-D left anterior cingulated bundle and corpus callosum splenium. Disease durations of PD-D = 6.8 ± 6.86, PD-MCI = 5.1 ± 2.9, and PD-CogNL = 4.7 ± 3.4 years, suggesting progressive deterioration. Conclusions : Cerebral white matter deterioration may underlie progressive cognitive impairment in PD.
The effect of hydrochemical conditions and pH of the environment on phyllosilicate transformations in the weathering zone of pyrite-bearing schists in Wieściszowice (SW Poland)
Authors: Uzarowicz Ł. , Šegvic B. , Michalik M. , Bylina P. 
Published: December 2012

AbstractThe influence of hydrological conditions and the pH of the environment on chlorite and mica transformations in the acidic weathering zone of pyrite-bearing schists was studied. Phyllosilicate transformations were investigated in the area of the abandoned pyrite open-pit mine in Wieściszowice (Lower Silesia, SW Poland) using X-ray diffractometry (XRD), Fourier transform infrared (FTIR) spectroscopy and chemical methods. (Mg, Fe)-chlorite, micas (muscovite and paragonite), quartz, feldspars and pyrite were reported to be the most abundant minerals occurring in pyrite-bearing schists. Phyllosilicate transformations were significantly stronger in dry conditions than in wet ones. This conclusion was supported by the fact that the inherited phyllosilicates predominated in the clay mineral fraction of waterlogged saprolites, whereas the secondary swelling minerals were minor components. In dry and extremely acidic saprolites (pH < 3), trioctahedral chlorite was dissolved and transformed into clay minerals (e.g. smectite and kaolinite), whereas swelling clays (smectite mainly) were formed at the expense of dioctahedral micas. The pH of water is an important factor influencing phyllosilicate transformations in waterlogged conditions. The phyllosilicate alterations under the influence of extremely acidic waters (pH < 3) were more advanced than in moderately acidic ones (pH of 4.6), as the secondary clay minerals seemed to be represented exclusively by smectite in the former, whereas HIMs and mixed-layer minerals such as R0 I-S-Ch, R0 I-S, as well as R1 Ch-V and/or R1 Ch-S occurred in the latter.
Clay mineralogy and rock strength of a mid-German diabase: implications for improved quality control
Authors: Kaufhold S. , Dill H. G. , Dohrmann R. 
Published: December 2012

AbstractBasalts and related magmatic rocks such as diabase are frequently used as raw materials in the building and construction industry as dimension stones or as aggregates, where they may form the sub-bases of roads or railway embankments. A major characteristic controlling the quality of the raw materials is the rock strength, which can be affected by the presence of swellable clay minerals (smectites). Increasing smectite content is generally considered to increasingly affect rock integrity. Industrial practice, in which the smectite content is monitored via cation exchange capacity (CEC) methods, on the other hand, showed that both mechanically stable smectite-rich and unstable smectite-poor materials exist. We therefore studied the CEC–strength relation based on twelve samples from a German diabase quarry.As could be expected, the sample with the highest CEC was the least stable. However, the comparison of the rock strength with the CEC of the other samples was less clear. Comparing the CEC of powders and of the 1–2 mm fraction of the same sample provided additional information. In the case of samples which are relatively stable (in spite of high CEC values), the CEC values of the powders were significantly higher than those of the 1–2 mm fraction. Samples with less rock strength, on the other hand, showed equal CEC values of the powder and the 1–2 mm fraction. This difference may be explained by different accessibilities of the smectites for CEC exchange solutions during typical experiments.In conclusion, the application of the CEC method for quality control considering both powdered and 1–2 mm samples allows a more precise estimation of the rock strength to be made, particularly for the comparison of different materials. Although measurement of two CEC values (after both sieving and grinding) would complicate quality control, the present study indicates that valuable additional information, i.e. semi-quantitative information on the accessibility of smectites, is gained.
Certification and quality criteria of peloids used for therapeutic purposes
Authors: Quintela A. , Terroso D. , Ferreira da Silva E. , Rocha F. 
Published: December 2012

AbstractThe empirical application of muds for therapeutic purposes is widely known. This is called pelotherapy and consists of the local or generalized application of a mixture of a solid phase and a liquid phase (peloid) for the recovery of arthro-rheumatic issues, bone-muscle traumatic damage and dermatological pathologies. During the time of mixing (maturation process) the mud is progressively colonized by thermophilic microorganisms that contribute to improvements in the peloid quality and endow the mud with organic substances. Several studies report diatoms as the main agent of thermal muds capable of producing anti-inflammatory sulphoglycolipid which renders the mud suitable for this use. The effect of the temperature is also considered important for therapeutic purposes.Recent studies assessed physical, chemical and technological properties of some peloids in use at spa centres. Some maturation surveys have also been performed in recent years. The need for quality criteria establishment and certification of clayey products intended to be used currently is evident, especially for peloids which have therapeutic action. Consequently, this study aims at the compilation and analysis of some characteristics of peloids from the literature in order to contribute to a major database that allows the establishment of regulations and quality criteria for suitable applications of peloids.
Micromilieu-controlled glauconitization in fecal pellets at Oker (Central Germany)
Authors: Baldermann A. , Grathoff G. H. , Nickel C. 
Published: December 2012

AbstractAlthough numerous models for the formation of glauconite have been presented, the precise process and micro-environment of glauconitization are still poorly constrained. We characterize the special micromilieu of glauconitization developed during early diagenesis and present a model for glauconite formation in fecal pellets.Glauconitization at Oker (Central Germany) occurred predominantly in fecal pellets deposited in a shallow marine-lagoonal environment during the Kimmeridgian. Within the fecal pellets, rapid oxidation of organic matter provides the post-depositional, physicochemical conditions favourable for glauconitization. Replacements of matrix calcite, dissolution of detrital quartz, K-feldspar, and clay minerals, and Fe redox reactions were observed within the early micro-environment, followed by the precipitation of euhedral pyrite, matrix-replacive dolomite, and megaquartz accompanied by I-S formation as thin section analyses and SEM observations show. Carbonate geochemical compositions based on ICP-OES and stable oxygen and carbon isotope signatures demonstrate that glauconite formation started in a suboxic environment at a pH of 7–8 and a temperature of 22±3°C to 37±2°C at maximum.TEM-EDX-SAED and XRD analyses on separated glauconite fecal pellets and on the <2 μm clay mineral fraction reveal the predominance of authigenic 1Md-glauconite, 1Md-glauconite-smectite, and 1Mdcis-vacant I-S, besides accessory detrital 2M1-illite and montmorillonite. Kinetic modelling of the glauconite (93–94% Fe-illite layers and 6–7% Fe-smectite layers, R3) and of I-S (66–68% Al-illite layers and 32–34% Al-smectite layers, R1) leads us to conclude that the I-S formed solely by slow burial diagenesis, whereas the glauconite formed close to the seafloor, suggesting significantly faster kinetics of the glauconitization reaction compared with smectite-illitization related to burial diagenesis. Thermodynamically, the substitution of octahedral Al3+ for Fe3+ and Mg2+ during the Fe-Mg-smectite to glauconite reaction via the formation of glauconite-smectite mixed-layered clay minerals may have resulted in a higher reaction rate for this low-temperature glauconitization process.