bluuebunny/crossref_metadata_2025 huggingface dataset:
Latent heating characteristics of the MJO computed from TRMM Observations
Authors: Barnes Hannah C. , Zuluaga Manuel D. , Houze Robert A.
Published: January 2015

The Tropical Rainfall Measurement Mission's (TRMM) Spectral Latent Heating algorithm shows the contributions of different forms of convection to the latent heating profiles of the Madden‐Julian Oscillation over the central Indian and West Pacific Oceans. In both oceanic regions, storms containing broad stratiform regions produce increased upper level heating during active Madden‐Julian Oscillation (MJO) phases. The largest differences between the central Indian and West Pacific Ocean heating are associated with heating produced by convective elements. Examination of the most extreme forms of convection shows that mesoscale organized convection often produces at least as much latent heat as young vigorous deep convection. Heating from nonextreme (often midlevel‐topped) convection is an important component of the MJO heating in both regions in all stages of the MJO. Over the central Indian Ocean the heating profile changes from having a maximum at 2 km due to nonextreme convection to a profile during the active stage that has two maxima: one at 3 km due to nonextreme convection and 6 km owing to numerous mature mesoscale storms with broad stratiform precipitation components. Over the West Pacific, the maxima at 3 and 6 km are present in all MJO stages, but the magnitude of the 6 km maximum sharply increases in the active MJO stage due to an increase in the number of storms with broad stratiform precipitation areas.
Evaluating uncertainty in convective cloud microphysics using statistical emulation
Authors: Johnson J. S. , Cui Z. , Lee L. A. , Gosling J. P. , Blyth A. M. , Carslaw K. S.
Published: January 2015

The microphysical properties of convective clouds determine their radiative effects on climate, the amount and intensity of precipitation as well as dynamical features. Realistic simulation of these cloud properties presents a major challenge. In particular, because models are complex and slow to run, we have little understanding of how the considerable uncertainties in parameterized processes feed through to uncertainty in the cloud responses. Here we use statistical emulation to enable a Monte Carlo sampling of a convective cloud model to quantify the sensitivity of 12 cloud properties to aerosol concentrations and nine model parameters representing the main microphysical processes. We examine the response of liquid and ice‐phase hydrometeor concentrations, precipitation, and cloud dynamics for a deep convective cloud in a continental environment. Across all cloud responses, the concentration of the Aitken and accumulation aerosol modes and the collection efficiency of droplets by graupel particles have the most influence on the uncertainty. However, except at very high aerosol concentrations, uncertainties in precipitation intensity and amount are affected more by interactions between drops and graupel than by large variations in aerosol. The uncertainties in ice crystal mass and number are controlled primarily by the shape of the crystals, ice nucleation rates, and aerosol concentrations. Overall, although aerosol particle concentrations are an important factor in deep convective clouds, uncertainties in several processes significantly affect the reliability of complex microphysical models. The results suggest that our understanding of aerosol‐cloud interaction could be greatly advanced by extending the emulator approach to models of cloud systems.
Superparamagnetic Liposomes for MRI Monitoring and External Magnetic Field‐Induced Selective Targeting of Malignant Brain Tumors
Authors: Marie Hélène , Lemaire Laurent , Franconi Florence , Lajnef Sonia , Frapart Yves‐Michel , Nicolas Valérie , Frébourg Ghislaine , Trichet Michael , Ménager Christine , Lesieur Sylviane
Published: January 2015

Magnetic‐fluid‐loadedliposomes (MFLs) of optimized magnetic responsiveness are newly worked out from the entrapment of superparamagnetic maghemite nanocrystals in submicronic PEG‐ylated rhodamine‐labelled phospholipid vesicles. This nanoplatform provides an efficient tool for the selective magnetic targeting of malignant tumors localized in brain and non‐invasive traceability by MRI through intravascular administration. As assessed by in vivo 7‐T MRI and ex vivo electron spin resonance, 4‐h exposure to 190‐T m–1 magnetic field gradient efficiently concentrates MFLs into human U87 glioblastoma implanted in the striatum of mice. The magnetoliposomes are then longer retained therein as checked by MRI monitoring over a 24‐h period. Histological analysis by confocal fluorescence microscopy confirms the significantly boosted accumulation of MFLs in the malignant tissue up to the intracellular level. Electron transmission microscopy reveals effective internalization by endothelial and glioblastoma cells of the magnetically conveyed MFLs as preserved vesicle structures. The magnetic field gradient emphasizes MFL distribution solely in the tumors according to the enhanced permeability and retention (EPR) effect while comparatively very low amounts are recovered in the other cerebral areas. Such a selective targeting precisely traceable by MRI is promising for therapeutic applications since the healthy brain tissue can be expected to be spared during treatments by deleterious anticancer drugs carried by magnetically guided MFLs.
Human sickness behavior: Ultimate and proximate explanations
Authors: Shattuck Eric C. , Muehlenbein Michael P.
Published: January 2015

Sickness behavior, a coordinated set of behavioral changes in response to infection, lies at the intersection of immunology, endocrinology, and evolutionary biology. Sickness behavior is elicited by pro‐inflammatory cytokines, is thought to be an adaptive means of redirecting energy away from disadvantageous behaviors and toward mounting an effective immune response, and may be modulated by hormones, including testosterone and oxytocin. Research on sickness behavior in humans has lagged behind non‐human animal research due to methodological complexities. Here we review what is known about sickness behavior in humans, the effects of various hormones on sickness behavior, the possible role of cytokine gene variation in influencing sickness behavior responses, and the ways in which culture and gender norms could similarly influence these behavioral changes. We also propose methodologies for advancing further studies of sickness behavior in humans. Am J Phys Anthropol 157:1–18, 2015. © 2015 Wiley Periodicals, Inc.
Physiological consequences of abnormal connectivity in a developmental epilepsy
Authors: Shafi Mouhsin M. , Vernet Marine , Klooster Debby , Chu Catherine J. , Boric Katica , Barnard Mollie E. , Romatoski Kelsey , Westover M. Brandon , Christodoulou Joanna A. , Gabrieli John D. E. , Whitfield‐Gabrieli Susan , Pascual‐Leone Alvaro , Chang Bernard S.
Published: January 2015

Objective

Many forms of epilepsy are associated with aberrant neuronal connections, but the relationship between such pathological connectivity and the underlying physiological predisposition to seizures is unclear. We sought to characterize the cortical excitability profile of a developmental form of epilepsy known to have structural and functional connectivity abnormalities.

Methods

We employed transcranial magnetic stimulation (TMS) with simultaneous electroencephalographic (EEG) recording in 8 patients with epilepsy from periventricular nodular heterotopia and matched healthy controls. We used connectivity imaging findings to guide TMS targeting and compared the evoked responses to single‐pulse stimulation from different cortical regions.

Results

Heterotopia patients with active epilepsy demonstrated a relatively augmented late cortical response that was greater than that of matched controls. This abnormality was specific to cortical regions with connectivity to subcortical heterotopic gray matter. Topographic mapping of the late response differences showed distributed cortical networks that were not limited to the stimulation site, and source analysis in 1 subject revealed that the generator of abnormal TMS‐evoked activity overlapped with the spike and seizure onset zone.

Interpretation

Our findings indicate that patients with epilepsy from gray matter heterotopia have altered cortical physiology consistent with hyperexcitability, and that this abnormality is specifically linked to the presence of aberrant connectivity. These results support the idea that TMS‐EEG could be a useful biomarker in epilepsy in gray matter heterotopia, expand our understanding of circuit mechanisms of epileptogenesis, and have potential implications for therapeutic neuromodulation in similar epileptic conditions associated with deep lesions. Ann Neurol 2015;77:487–503
Influence of the β‐Sheet Content on the Mechanical Properties of Aggregates during Amyloid Fibrillization
Authors: Ruggeri Francesco Simone , Adamcik Jozef , Jeong Jae Sun , Lashuel Hilal A. , Mezzenga Raffaele , Dietler Giovanni
Published: January 2015

Amyloid fibrils associated with neurodegenerative diseases, such as Parkinson’s and Alzheimer’s, consist of insoluble aggregates of α‐synuclein and Aβ‐42 proteins with a high β‐sheet content. The aggregation of both proteins occurs by misfolding of the monomers and proceeds through the formation of intermediate oligomeric and protofibrillar species to give the final fibrillar cross‐β‐sheet structure. The morphological and mechanical properties of oligomers, protofibrils, and fibrils formed during the fibrillization process were investigated by thioflavin T fluorescence and circular dichroism in combination with AFM peak force quantitative nanomechanical technique. The results reveal an increase in the Young’s modulus during the transformation from oligomers to mature fibrils, thus inferring that the difference in their mechanical properties is due to an internal structural change from a random coil to a structure with increased β‐sheet content.
Reversible Control of Nanoparticle Functionalization and Physicochemical Properties by Dynamic Covalent Exchange
Authors: della Sala Flavio , Kay Euan R.
Published: January 2015

Existing methods for the covalent functionalization of nanoparticles rely on kinetically controlled reactions, and largely lack the sophistication of the preeminent oligonucleotide‐based noncovalent strategies. Here we report the application of dynamic covalent chemistry for the reversible modification of nanoparticle (NP) surface functionality, combining the benefits of non‐biomolecular covalent chemistry with the favorable features of equilibrium processes. A homogeneous monolayer of nanoparticle‐bound hydrazones can undergo quantitative dynamic covalent exchange. The pseudomolecular nature of the NP system allows for the in situ characterization of surface‐bound species, and real‐time tracking of the exchange reactions. Furthermore, dynamic covalent exchange offers a simple approach for reversibly switching—and subtly tuning—NP properties such as solvophilicity.
Thermoset composites functionalized with carbon nanofiber sheets for EMI shielding
Authors: Zhao Zhongfu , Zhou Yongsen , Zhang Chunqing , Wang Zhanyue
Published: January 2015

Carbon nanofiber sheets were developed through filtering well‐dispersed carbon nanofiber (CNF) through filtering well‐dispersed aqueous solution of CNF particles with 0.4 μm hydrophilic polycarbonate membrane by the aid of high‐pressure air. They were used to functionalize composites by the resin transfer molding method. Their functionalized composites were characterized with scanning electron microscopy (SEM), four‐point probes and a vector network analyzer to measure their morphologies, electrical conductivity, and electromagnetic interference (EMI) shielding performance over the frequency range of 8–12 GHz (X band), respectively. Their morphologies show that CNF particles are overlapped and tightly connected with each other in their interconnected networks. The CNF sheets are exposed on the surface, although their networks are partially penetrated by polyester resins. Their electrical conductivity can be 3.0 ± 0.2 Scm−1 or so, much higher by ten orders of magnitude than the reported electrical conductivity of CNF‐filled composites. Their EMI shielding effectiveness slightly varies in a range of −30 dB to −35 dB as a function of frequency, much higher than that of most CNF or carbon nanotube–filled composites. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41873.
Shape‐memory bioresorbable terpolymer composite with antirestenotic drug
Authors: Jaworska Joanna , Jelonek Katarzyna , Sobota Michal , Kasperczyk Janusz , Dobrzynski Piotr , Musial‐Kulik Monika , Smola‐Dmochowska Anna , Janeczek Henryk , Jarzabek Bozena
Published: January 2015

Shape‐memory polymers (SMPs) that combine shape‐memory, biodegradability, and controlled drug release properties are very promising for medical and pharmaceutical application. Moreover, incorporation of antirestenotic drug into SMP biodegradable stent seems to be an interesting solution because of possibility to combine the mechanical support that provides stent and also drug elution. The aim of our study was to analyze the effect of incorporation of sirolimus into poly(l‐lactide‐co‐glycolide‐co‐trimethylene carbonate) on physicochemical and mechanical properties, degradation, and shape‐memory effect of the terpolymer. For this purpose, sirolimus was incorporated into the terpolymer by injection molding method. It has been demonstrated that drug‐free terpolymer after injection molding characterized insignificant changes in terpolymer composition. Degradation of materials during processing was not observed. Incorporation of drug molecules did not change shape‐memory properties of terpolymer. 1H‐ and 13C‐NMR spectra of poly(lactide‐co‐glycolide‐co‐trimethylene carbonate) confirmed that changes during degradation were similar for terpolymer and terpolymer with sirolimus. Sustained and regular release of sirolimus was observed. The developed material presents potential for biomedical and pharmaceutical applications. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41902.
Effect of adding nano‐titanium dioxide on the microstructure, mechanical properties and in vitro bioactivity of a freeze cast merwinite scaffold
Authors: Nezafati Nader , Hafezi Masoud , Zamanian Ali , Naserirad Mandana
Published: January 2015

In the present research, merwinite (M) scaffolds with and without nano‐titanium dioxide (titania) were synthesized by water‐based freeze casting method. Two different amounts (7.5 and 10 wt%) of n‐TiO2 were added to M scaffolds. They were sintered at temperature of 1573.15°K and at cooling rate of 4°K/min. The changes in physical and mechanical properties were investigated. The results showed that although M and M containing 7.5 wt% n‐TiO2 (MT7.5) scaffolds had approximately the same microstructures in terms of pore size and wall thickness, these factors were different for sample MT10. In overall, the porosity, volume and linear shrinkage were decreased by adding different weight ratios of n‐TiO2 into the M structure. According to the obtained mechanical results, the optimum mechanical performance was related to the sample MT7.5 (E = 51 MPa and σ = 2 MPa) with respect to the other samples, i.e.: M (E = 47 MPa and σ = 1.8 MPa) and MT10 (E = 32 MPa and σ = 1.4 MPa). The acellular in vitro bioactivity experiment confirmed apatite formation on the surfaces of all samples for various periods of soaking time. Based on cell study, the sample which possessed favorable mechanical behavior (MT7.5) supported attachment and proliferation of osteoblastic cells. These results revealed that the MT7.5 scaffold with improved mechanical and biological properties could have a potential to be used in bone substitute. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:550–556, 2015
Surgical cutdown versus percutaneous access in transfemoral transcatheter aortic valve implantation: Insights from the Brazilian TAVI registry
Authors: Bernardi Fernando L.M. , Gomes Wilton F. , de Brito Fabio S. , Mangione Jose A. , Sarmento‐Leite Rogério , Siqueira Dimitry , Carvalho Luiz A. , Tumelero Rogério , Guerios Enio E. , Lemos Pedro A.
Published: January 2015

Objective

To compare the 1‐year outcomes of complete percutaneous approach versus surgical vascular approach for transfemoral transcatheter aortic valve implantation (TAVI), among “real‐world” patients from the multi‐center Brazilian TAVI registry.

Background

Vascular access still remains a major challenge for TAVI via transfemoral approach. Vascular access through complete percutaneous approaches or through open surgical vascular techniques seems to be acutely similar. However, the long‐term outcomes of both techniques remain poorly described.

Methods

The study population comprised all patients treated via transfemoral route in the Brazilian TAVI registry, a “real‐world”, nation‐based, multi‐center study. Patients were divided according to the initial vascular access approach (percutaneous vs. surgical) and clinically followed‐up for 1 year. The primary endpoint was the incidence of combined adverse events all‐cause mortality, life‐threatening bleeding, and/or major vascular complication at 1 year.

Results

A total of 402 patients from 18 centers comprised the study population (percutaneous approach in 182 patients; surgical cutdown approach 220 patients). The incidence of combined adverse events was not different in the percutaneous and the surgical groups at 30 days (17.6% vs. 16.3%; P = 0.8) and at 1 year (primary endpoint) (30.9% vs. 28.8%; P = 0.8). Also, the study groups overall were comparable regarding the incidence of each individual safety adverse events at 30 days and at 1 year.

Conclusion

Total percutaneous techniques or surgical cutdown and closure may provide similar safety and effectiveness during the first year of follow‐up in patients undergoing transfemoral TAVI. © 2015 Wiley Periodicals, Inc.
Structural Investigation of the High Spin→Low Spin Relaxation Dynamics of the Porous Coordination Network [Fe(pz)Pt(CN)4]⋅2.6 H2O
Authors: Delgado Teresa , Tissot Antoine , Besnard Céline , Guénée Laure , Pattison Philip , Hauser Andreas
Published: January 2015

The Hoffman‐type coordination compound [Fe(pz)Pt(CN)4]⋅2.6 H2O (pz=pyrazine) shows a cooperative thermal spin transition at around 270 K. Synchrotron powder X‐Ray diffraction studies reveal that a quantitative photoinduced conversion from the low‐spin (LS) state into the high‐spin (HS) state, based on the light‐induced excited spin‐state trapping effect, can be achieved at 10 K in a microcrystalline powder. Time‐resolved measurements evidence that the HS→LS relaxation proceeds by a two‐step mechanism: a random HS→LS conversion at the beginning of the relaxation is followed by a nucleation and growth process, which proceeds until a quantitative HS→LS transformation has been reached.
The Fate of NHC‐Stabilized Dicarbon
Authors: Georgiou Dayne C. , Stringer Bradley D. , Hogan Conor F. , Barnard Peter J. , Wilson David J. D. , Holzmann Nicole , Frenking Gernot , Dutton Jason L.
Published: January 2015

The attempted synthesis of NHC‐stabilized dicarbon (NHCCCNHC) through deprotonation of a doubly protonated precursor ([NHCCHCHNHC]2+) is reported. Rather than deprotonation, a clean reduction to NHCCHCHNHC is observed with a variety of bases. The apparent resistance towards deprotonation to the target compound led to a reinvestigation of the electronic structure of NHC→CC←NHC, which showed that the highest occupied molecular orbital/lowest unoccupied molecular orbital (HOMO/LUMO) gap is likely too small to allow for isolation of this species. This is in contrast to the recent isolation of the cyclic alkylaminocarbene analogue (cAACCCcAAC), which has a large HOMO–LUMO gap. A detailed theoretical study illuminates the differences in electronic structures between these molecules, highlighting another case of the potential advantages of using cAAC rather than NHC as a ligand. The bonding analysis suggests that the dicarbon compounds are well represented in terms of donor–acceptor interactions L→C2←L (L=NHC, cAAC).
Mesoporous Alumina from Colloidal Biotemplating of Al Clusters
Authors: Sachse Alexander , Cardoso Laura , Kostov Krassimir L. , Gérardin Corine , Belamie Emmanuel , Alonso Bruno
Published: January 2015

A simple and green synthesis route was disclosed for the achievement of mesoporous alumina microparticles employing polysaccharide nanoparticles (α‐chitin nanorods) as templates. Pore textures can be tuned by the cationic alumina precursor. Compared to small cations, the use of Al13 and Al30 oxo‐hydroxo clusters leads to better defined and elongated mesopores. Electron microscopy and spectroscopic (13C, 27Al NMR, XPS) measurements demonstrated that this is related to the effective coating of α‐chitin nanorods by these pre‐condensed colloids.
DFT Study of the Molybdenum‐Catalyzed Deoxydehydration of Vicinal Diols
Authors: Lupp Daniel , Christensen Niels Johan , Dethlefsen Johannes R. , Fristrup Peter
Published: January 2015

The mechanism of the molybdenum‐catalyzed deoxydehydration (DODH) of vicinal diols has been investigated using density functional theory. The proposed catalytic cycle involves condensation of the diol with an MoVI oxo complex, oxidative cleavage of the diol resulting in an MoIV complex, and extrusion of the alkene. We have compared the proposed pathway with several alternatives, and the results have been corroborated by comparison with the molybdenum‐catalyzed sulfoxide reduction recently published by Sanz et al. and with experimental observations for the DODH itself. Improved understanding of the mechanism should expedite future optimization of molybdenum‐catalyzed biomass transformations.
Robustness Screen in Enantioselective Catalysis Enabled Generation of Enantioenriched Heterocyclic Scaffolds in One Pot
Authors: Bagle Pradip N. , Shinde Valmik S. , Patil Nitin T.
Published: January 2015

Enantioselective catalysis has emerged as a powerful synthetic paradigm and has accelerated the development of new methods to make diverse chiral molecules. Generally, these reactions are very sensitive to the steric and electronic environment present in the catalyst as well as the substrates. With this scenario, the presence of an additional component in the reaction mixture is expected to add complexity in achieving the enantioselective variants. Herein, we report that various enantioenriched molecules could be obtained from multiple starting materials in one pot. The reaction of aminoaromatics A with alkynols B1, B2, B3…︁Bn with a AuI/chiral Brønsted acid catalyst afforded AB1*, AB2*, AB3*…ABn*; while, the reaction of alkynols B with aminoaromatics A1, A2, A3…An under the same reaction conditions gave A1B*, A2B*, A3B*…AnB*.
RhII‐Catalyzed [3+2] Cycloaddition of 2 H‐Azirines with N‐Sulfonyl‐1,2,3‐Triazoles
Authors: Zhao Yun‐Zhou , Yang Hai‐Bin , Tang Xiang‐Ying , Shi Min
Published: January 2015

RhII‐catalyzed intermolecular [3+2] cycloaddition of 2 H‐azirines with N‐sulfonyl‐1,2,3‐triazoles is disclosed, in which a series of fully functionalized pyrroles is produced via rhodium azavinyl carbene intermediates. A distinct feature of this reaction is that the azavinyl carbene serves as a [2 C] equivalent, instead of as [1 C] or aza‐[3 C] synthons, which have been reported previously in cyclopropanations and [3+n] cycloadditions. Moreover, this methodology has also been successfully applied in the total synthesis of URB447 as well as the formal synthesis of Atorvastatin (Lipitor).
Synthesis of Coumarin‐Pillar[5]arene as a Selective Fluorescent Probe for Methyl‐Parathion
Authors: Zhang Fan , Cao Xianliang , Tian Demei , Li Haibing
Published: January 2015

A novel coumarin‐pillar[5]arene derivative (P5C10) was prepared. Fluorescence spectroscopy indicates that P5C10 shows good selectivity towards methyl‐parathion. A combination of NMR spectra, MALDI‐TOF spectra and computational calculations reveals the formation of a host‐guest complex driven by π‐π stacking interactions.
Influence of Metallic Modification on Ethylbenzene Dealkylation over ZSM‐5 Zeolites
Authors: Hu Chao , Li Junhui , Jia Wenzhi , Liu Min , Hao Zhixian , Zhu Zhirong
Published: January 2015

A series of metal‐modified HZSM‐5 catalysts were prepared by impregnation and were used for ethylbenzene dealkylation of the mixed C8 aromatics (ethylbenzene, m‐xylene and o‐xylene). The effects of different supported metals (Pt, Pd, Ni, Mo) on catalytic performance, including reaction conditions, were investigated. The physicochemical properties of catalysts were characterized by means of XRD, BET, TEM and NH3‐TPD. Experimental results showed that metallic modification obviously increased the ethylbenzene conversion and reduced the coke deposition, greatly improving the catalyst stability. The distinction of ethylbenzene conversion depended on the interaction between hydrogenation reactivity and acidic cracking of bifunctional metal‐modified zeolites. Compared with Pt and Ni, Pd and Mo were easier to disperse into HZSM‐5 micropores during loading metals. The acidic density of different metal‐modified HZSM‐5 declined in the following order: HZSM‐5>Pt/HZSM‐5>Pd/HZSM‐5>Ni/HZSM‐5>Mo/HZSM‐5. The activity of ethylene hydrogenation decreased with Pt/HZSM‐5>Pd/HZSM‐5>Ni/HZSM‐5>Mo/HZSM‐5. In comparison, Pd/HZSM‐5 showed the best catalytic performance with both high activity and high selectivity, with less cracking loss of m‐xylene and o‐xylene. Moreover, the following reaction conditions were found to be preferable for ethylbenzene dealkylation over Pd/HZSM‐5: 340°C, 1.5 MPa H2, WHSV 4 h−1, H2/C8 4 mol/mol.
Four Pillar[5]arene Constitutional Isomers: Synthesis, Crystal Structures, and Host‐Guest Complexation of Their Derivatives with Paraquat in Water
Authors: Zhou Yujuan , Yao Yong , Huang Feihe
Published: January 2015

A pillar[5]arene prepared from monomer 1 has four constitutional isomers. Although these constitutional isomers have the same molecular formula, their other properties that we have investigated are more or less different. They have different melting points, different NMR spectra and different crystal structures. Furthermore, the corresponding four anionic constitutional pillar[5]arene isomers derived from these four constitutional isomers showed different binding abilities with paraquat G in water. The association constants of 3a⊃G, 3b⊃G, 3c⊃G and 3d⊃G were determined to be (3.33±0.46)×104 L·mol−1, (5.00±0.63)×104 L·mol−1, (3.33±0.28)×104 L·mol−1, and (1.43±0.09)×104 L·mol−1, respectively.
Characterizing Major Bleeding in Patients With Nonvalvular Atrial Fibrillation: A Pharmacovigilance Study of 27 467 Patients Taking Rivaroxaban
Authors: Tamayo Sally , Frank Peacock W. , Patel Manesh , Sicignano Nicholas , Hopf Kathleen P. , Fields Larry E. , Sarich Troy , Wu Shujian , Yannicelli Daniel , Yuan Zhong
Published: January 2015

Background

In nonvalvular atrial fibrillation (NVAF), rivaroxaban is used to prevent stroke and systemic embolism.

Objective

To evaluate major bleeding (MB) in NVAF patients treated with rivaroxaban in a real‐world clinical setting.

Methods

From January 1, 2013, to March 31, 2014, US Department of Defense electronic health care records were queried to describe MB rates and demographics. Major bleeding was identified using a validated algorithm.

Results

Of 27 467 patients receiving rivaroxaban, 496 MB events occurred in 478 patients, an incidence of 2.86 per 100 person‐years (95% confidence interval: 2.61‐3.13). The MB patients were older, mean (SD) age of 78.4 (7.7) vs 75.7 (9.7) years, compared with non‐MB patients. Patients with MB had higher rates of hypertension (95.6% vs 75.8%), coronary artery disease (64.2% vs 36.7%), heart failure (48.5% vs 23.7%), and renal disease (38.7% vs 16.7%). Of MB patients, 63.2% were taking 20 mg, 32.2% 15 mg, and 4.6% 10 mg of rivaroxaban. Four percent of MB patients took warfarin within the prior 30 days. Major bleeding was most commonly gastrointestinal (88.5%) or intracranial (7.5%). Although 46.7% of MB patients received a transfusion, none had sufficient evidence of receiving any type of clotting factor. Fourteen died during their MB hospitalization, yielding a fatal bleeding incidence rate of 0.08 per 100 person‐years (95% confidence interval: 0.05‐0.14). Mean age at death was 82.4 years.

Conclusions

In this large observational study, the MB rate was generally consistent with the registration trial results, and fatal bleeds were rare.
Relationship of light scatter change and Cdc42‐regulated actin status
Authors: Hong Lin , Chavez Stephanie , Smagley Yelena , Chigaev Alexandre , Sklar Larry A.
Published: January 2015

Background

Cdc42 GTPase has important roles in regulating intracellular actin reorganization. The current methods to monitor actin changes are typically complex and point by point.

Methods

The effects of Cdc42 inhibitors on the side scatter changes were tested in a newly developed continuous assay using the flow cytometer. Staining with fluorescently labeled phalloidin was used for comparison.

Results

Cdc42‐specific inhibitors caused dose‐dependent changes of both the right‐angle side scatter and the phalloidin‐stained actin.

Conclusions

The right‐angle light scatter change can be used as a method to circumvent phalloidin staining and be an early convenient step in screening Cdc42 inhibitors. © 2015 International Clinical Cytometry Society
The molecular regulation of arteriovenous specification and maintenance
Authors: Fish Jason E. , Wythe Joshua D.
Published: January 2015

The formation of a hierarchical vascular network, composed of arteries, veins, and capillaries, is essential for embryogenesis and is required for the production of new functional vasculature in the adult. Elucidating the molecular mechanisms that orchestrate the differentiation of vascular endothelial cells into arterial and venous cell fates is requisite for regenerative medicine, as the directed formation of perfused vessels is desirable in a myriad of pathological settings, such as in diabetes and following myocardial infarction. Additionally, this knowledge will enhance our understanding and treatment of vascular anomalies, such as arteriovenous malformations (AVMs). From studies in vertebrate model organisms, such as mouse, zebrafish, and chick, a number of key signaling pathways have been elucidated that are required for the establishment and maintenance of arterial and venous fates. These include the Hedgehog, Vascular Endothelial Growth Factor (VEGF), Transforming Growth Factor‐β (TGF‐β), Wnt, and Notch signaling pathways. In addition, a variety of transcription factor families acting downstream of, or in concert with, these signaling networks play vital roles in arteriovenous (AV) specification. These include Notch and Notch‐regulated transcription factors (e.g., HEY and HES), SOX factors, Forkhead factors, β‐Catenin, ETS factors, and COUP‐TFII. It is becoming apparent that AV specification is a highly coordinated process that involves the intersection and carefully orchestrated activity of multiple signaling cascades and transcriptional networks. This review will summarize the molecular mechanisms that are involved in the acquisition and maintenance of AV fate, and will highlight some of the limitations in our current knowledge of the molecular machinery that directs AV morphogenesis. Developmental Dynamics 244:391–409, 2015. © 2015 Wiley Periodicals, Inc.
Assessing the phylogeographic history of the montane caddisfly Thremma gallicum using mitochondrial and restriction‐site‐associated DNA (RAD) markers
Authors: Macher Jan‐Niklas , Rozenberg Andrey , Pauls Steffen U. , Tollrian Ralph , Wagner Rüdiger , Leese Florian
Published: January 2015

Repeated Quaternary glaciations have significantly shaped the present distribution and diversity of several European species in aquatic and terrestrial habitats. To study the phylogeography of freshwater invertebrates, patterns of intraspecific variation have been examined primarily using mitochondrial DNA markers that may yield results unrepresentative of the true species history. Here, population genetic parameters were inferred for a montane aquatic caddisfly, Thremma gallicum, by sequencing a 658‐bp fragment of the mitochondrial CO1 gene, and 12,514 nuclear RAD loci. T. gallicum has a highly disjunct distribution in southern and central Europe, with known populations in the Cantabrian Mountains, Pyrenees, Massif Central, and Black Forest. Both datasets represented rangewide sampling of T. gallicum. For the CO1 dataset, this included 352 specimens from 26 populations, and for the RAD dataset, 17 specimens from eight populations. We tested 20 competing phylogeographic scenarios using approximate Bayesian computation (ABC) and estimated genetic diversity patterns. Support for phylogeographic scenarios and diversity estimates differed between datasets with the RAD data favouring a southern origin of extant populations and indicating the Cantabrian Mountains and Massif Central populations to represent highly diverse populations as compared with the Pyrenees and Black Forest populations. The CO1 data supported a vicariance scenario (north–south) and yielded inconsistent diversity estimates. Permutation tests suggest that a few hundred polymorphic RAD SNPs are necessary for reliable parameter estimates. Our results highlight the potential of RAD and ABC‐based hypothesis testing to complement phylogeographic studies on non‐model species.
Metabolic variation in natural populations of wild yeast
Authors: Samani Pedram , Low‐Decarie Etienne , McKelvey Kyra , Bell Thomas , Burt Austin , Koufopanou Vassiliki , Landry Christian R. , Bell Graham
Published: January 2015

Ecological diversification depends on the extent of genetic variation and on the pattern of covariation with respect to ecological opportunities. We investigated the pattern of utilization of carbon substrates in wild populations of budding yeast Saccharomyces paradoxus. All isolates grew well on a core diet of about 10 substrates, and most were also able to grow on a much larger ancillary diet comprising most of the 190 substrates we tested. There was substantial genetic variation within each population for some substrates. We found geographical variation of substrate use at continental, regional, and local scales. Isolates from Europe and North America could be distinguished on the basis of the pattern of yield across substrates. Two geographical races at the North American sites also differed in the pattern of substrate utilization. Substrate utilization patterns were also geographically correlated at local spatial scales. Pairwise genetic correlations between substrates were predominantly positive, reflecting overall variation in metabolic performance, but there was a consistent negative correlation between categories of substrates in two cases: between the core diet and the ancillary diet, and between pentose and hexose sugars. Such negative correlations in the utilization of substrate from different categories may indicate either intrinsic physiological trade‐offs for the uptake and utilization of substrates from different categories, or the accumulation of conditionally neutral mutations. Divergence in substrate use accompanies genetic divergence at all spatial scales in S. paradoxus and may contribute to race formation and speciation.
Hierarchical analysis of genetic structure in the habitat‐specialist Eastern Sand Darter (Ammocrypta pellucida)
Authors: Ginson Robert , Walter Ryan P. , Mandrak Nicholas E. , Beneteau Courtney L. , Heath Daniel D.
Published: January 2015

Quantifying spatial genetic structure can reveal the relative influences of contemporary and historic factors underlying localized and regional patterns of genetic diversity and gene flow – important considerations for the development of effective conservation efforts. Using 10 polymorphic microsatellite loci, we characterize genetic variation among populations across the range of the Eastern Sand Darter (Ammocrypta pellucida), a small riverine percid that is highly dependent on sandy substrate microhabitats. We tested for fine scale, regional, and historic patterns of genetic structure. As expected, significant differentiation was detected among rivers within drainages and among drainages. At finer scales, an unexpected lack of within‐river genetic structure among fragmented sandy microhabitats suggests that stratified dispersal resulting from unstable sand bar habitat degradation (natural and anthropogenic) may preclude substantial genetic differentiation within rivers. Among‐drainage genetic structure indicates that postglacial (14 kya) drainage connectivity continues to influence contemporary genetic structure among Eastern Sand Darter populations in southern Ontario. These results provide an unexpected contrast to other benthic riverine fish in the Great Lakes drainage and suggest that habitat‐specific fishes, such as the Eastern Sand Darter, can evolve dispersal strategies that overcome fragmented and temporally unstable habitats.
5′‐Ectonucleotidase/CD73 expression on lymph‐circulating lymphocytes and lymphatic endothelial cells offers new paths to explore barrier function
Authors: Sidibé Adama , Imhof Beat A
Published: January 2015

5′‐Nucleotidase/CD73 is a key enzyme in the regulation of purinergic signaling, hydrolyzing extracellular AMP to produce adenosine, which is critical in the blood vascular system and in immunosuppression. CD73 is expressed by both blood endothelial cells and lymphatic endothelial cells. Although the role of CD73 on blood endothelial cells in controlling vascular permeability and leukocyte trafficking has been studied, the role of lymphatic CD73 has thus far remained unknown. In this issue of European Journal of Immunology, Yegutkin et al. [Eur. J. Immunol. 2015. 45: 562–573] compare CD73 activity in the endothelia of lymphatics and blood vessels and investigate the CD73+ lymphocyte subpopulations possibly involved in immunoregulation. This Commentary will discuss how the authors′ work sheds light on the differential use of CD73 by these two cell populations to control endothelial permeability and sprouting.
Rapid determination of branched chain amino acids in human blood plasma by pressure‐assisted capillary electrophoresis with contactless conductivity detection
Authors: Tůma Petr , Gojda Jan
Published: January 2015

A CE method with contactless conductivity detection has been developed for the clinical determination of the branched chain amino acids (BCAAs) valine, isoleucine and leucine in human blood plasma. The CE separation was performed in an optimised BGE with composition of 3.2 M acetic acid in 20% v/v methanol, pH 2.0. The achieved separation time was 125 s when using a capillary with an effective length of 14.7 cm, electric field intensity of 0.96 kV/cm and simultaneous application of a hydrodynamic pressure of 50 mbar. The separation efficiency in blood plasma equalled 461 000 theoretical plates/m for valine and isoleucine, and 455 000 theoretical plates/m for leucine; the detection limits are equal to 0.4 μM for all three amino acids. The RSD values for repeatability of the migration time equalled 0.1% for measurements during a single day and 0.3% for measurements on different days; the RSD values for repeatability of the peak areas equalled 2.3–2.6% for measurements during a single day and 2.7–4.6% for measurements on different days. It followed from the performed tests that the plasmatic levels of BCAAs attain a maximum 60 min after intravenous application of an infusion of BCAAs.
Role of copper and iron in methane oxidation and bacterial biopolymer accumulation
Authors: Chidambarampadmavathy Karthigeyan , Obulisamy P. Karthikeyan , Heimann Kirsten
Published: January 2015

The aim of this review was to elucidate the role of copper and iron in regulating methane (CH4) oxidation and subsequent biopolymer (i.e. polyhydroxyalkanoate [PHA]) accumulation in methanotrophic bacteria. Specifically, the review emphasizes the “copper switch mechanism” that alters CH4 oxidizing enzyme activities, that is soluble‐ and particulate methane monooxygenases, in type II methanotrophic bacteria. Both copper and iron are essential nutrients and reports demonstrate that addition of either can improve PHA accumulation. However, based on analyses of available data, a major knowledge gap regarding a clear understanding of the interactive effects in regulating methane monooxygenase enzyme activities/gene expressions was identified in this review.
Cultural evolution over the last 40 years in China: Using the Google Ngram Viewer to study implications of social and political change for cultural values
Authors: Zeng Rong , Greenfield Patricia M.
Published: January 2015

Chinese people have held collectivistic values such as obligation, giving to other people, obedience and sacrifice of personal interests for thousands of years. In recent decades, China has undergone rapid economic development and urbanisation. This study investigates changing cultural values in China from 1970 to 2008 and the relationship of changing values to ecological shifts. The conceptual framework for the study was Greenfield's (2009) theory of social change and human development. Changing frequencies of contrasting Chinese words indexing individualistic or collectivistic values show that values shift along with ecological changes (urbanisation, economic development and enrollment in higher education), thereby adapting to current sociodemographic contexts. Words indexing adaptive individualistic values increased in frequency between 1970 and 2008. In contrast, words indexing less adaptive collectivistic values either decreased in frequency in this same period of time or else rose more slowly than words indexing contrasting individualistic values.
Laser‐induced shockwave paired with FRET: A method to study cell signaling
Authors: Gomez‐Godinez Veronica , Preece Daryl , Shi Linda , Khatibzadeh Nima , Rosales Derrick , Pan Yijia , Lei Lie , Wang Yingxiao , Berns Michael W.
Published: January 2015

Cells within the body are subject to various forces; however, the details concerning the way in which cells respond to mechanical stimuli are not well understood. We demonstrate that laser‐induced shockwaves (LIS) combined with biosensors based on fluorescence resonance energy transfer (FRET) is a promising new approach to study biological processes in single live cells. As “proof‐of‐concept,” using a FRET biosensor, we show that in response to LIS, cells release intracellular calcium. With the parameters used, cells retain their morphology and remain viable. LIS combined with FRET permits observation of the cells immediate response to a sudden shear force. Microsc. Res. Tech. 78:195–199, 2015. © 2015 Wiley Periodicals, Inc.
Evaluation of the dosimetric impact of applying flattening filter‐free beams in intensity‐modulated radiotherapy for early‐stage upper thoracic carcinoma of oesophagus
Authors: Zhang Wuzhe , Lin Zhixiong , Yang Zhining , Fang Weisheng , Lai Peibo , Lu Jiayang , Wu Vincent WC
Published: January 2015

Introduction

Flattening filter‐free (FFF) radiation beams have recently become clinically available on modern linear accelerators in radiation therapy. This study aimed to evaluate the dosimetric impact of using FFF beams in intensity‐modulated radiotherapy (IMRT) for early‐stage upper thoracic oesophageal cancer.

Methods

Eleven patients with primary stage upper thoracic oesophageal cancer were recruited. For each patient, two IMRT plans were computed using conventional beams (Con‐P) and FFF beams (FFF‐P), respectively. Both plans employed a five‐beam arrangement and were prescribed with 64 Gy to (planning target volume) PTV1 and 54 Gy to PTV2 in 32 fractions using 6 MV photons. The dose parameters of the target volumes and organs at risks (OARs), and treatment parameters including the monitor units (MU) and treatment time (TT) for Con‐P and FFF‐P were recorded and compared.

Results

The mean D5 of PTV1 and PTV2 were higher in FFF‐P than Con‐P by 0.4 Gy and 0.3 Gy, respectively. For the OARs, all the dose parameters did not show significant difference between the two plans except the mean V5 and V10 of the lung in which the FFF‐P was lower (46.7% vs. 47.3% and 39.1% vs. 39.6%, respectively). FFF‐P required 54% more MU but 18.4% less irradiation time when compared to Con‐P.

Conclusion

The target volume and OARs dose distributions between the two plans were comparable. However, FFF‐P was more effective in sparing the lung from low dose and reduced the mean TT compared with Con‐P. Long‐term clinical studies are suggested to evaluate the radiobiological effects of FFF beams.
Impact of nuclear factor‐κB on restoration of neuron growth and differentiation in hippocampus of degenerative brain
Authors: Aloor Rohit , Zhang Christine , Bandyopadhyay Mausumi , Dasgupta Subhajit
Published: January 2015

The mode of action of nuclear factor‐κB (NF‐κB) has been extensively observed in different aspects of cell growth and proliferation. The transcription factor regulates various genes controlling inflammation and anti‐inflammatory responses in different tissues. Thus, NF‐κB signal gains a therapeutic prospect. The activation of NF‐κB requires nuclear localization of its p65 subunit. Research also indicates an impact of phosphorylated p65 on the transcription of genes during cell growth and the immune response. Following the trends in investigations over decades, different observations suggest that NF‐κB activation and phosphorylation of p65 regulate neuronal plasticity. Also, inhibition of NF‐κB activation is a well‐demonstrated way to attenuate inflammation. In addition to anti‐inflammatory drugs, recent researches unwind a way to regulate regeneration and repair tissue damage. Thus, keeping a critical view on NF‐κB signals, we propose the importance of natural or synthetic NF‐κB activators for neurogenesis. © 2015 Wiley Periodicals, Inc.
The Moderating Role of Personal Need for Structure on the Evaluation of Incrementally New Products versus Really New Products
Authors: Kim Jun San , Hahn Minhi , Yoon Yeosun
Published: January 2015

Previous literature about the impacts of product newness on consumers’ acceptance of new products pointed out that consumers are more prone to purchase incrementally new products (INPs) than really new products (RNPs). This study investigated the moderating role of individual difference in personal need for structure (PNS) on consumers’ evaluation of INP versus RNP. The inverted‐U evaluation pattern of the schema congruity effect was predicted to be left‐skewed for high‐PNS consumers and right‐skewed for low‐PNS consumers as regards their evaluations of INP versus RNP. The results of Study 1 showed that low‐PNS consumers evaluated RNPs higher than INPs. High‐PNS consumers evaluated INPs higher than RNPs consistent with the prediction; however, the result was not significant. Relative to this issue, the moderating role of PNS on consumers’ evaluation of INP versus RNP may have been affected by consumers’ product category knowledge. The results of Study 2 verified the left‐ and right‐skewed inverted‐U hypotheses and showed that the moderating effect of PNS was evident only for novice consumers. Theoretical contributions and managerial implications from the results of the studies are discussed.
Catch and Shoot: The Influence of Advergame Mechanics on Preference Formation
Authors: Kuo Andrew , Rice Dan Hamilton
Published: January 2015

The use of advergames for the purpose of brand and product promotion is growing in popularity as the mobile gaming industry expands. The extant research on advergames, however, has focused primarily on factors influencing the effectiveness of in‐game advertising (e.g., banner and pop‐up ads appearing beside gameplay). Therefore, this research seeks to examine the impact of branded content integrated directly into the mechanics of a game. Across two studies, the influence of common game mechanics (e.g., shooting, collecting, avoiding) on affective and attentional processes are investigated by manipulating the design elements of a custom advergame. The results suggest that advergame mechanics can influence subsequent choices through perceptual fluency and affective transfer. Additionally, perceived difficulty was found to moderate the relationship between affective response and choice.