bluuebunny/crossref_metadata_2025 huggingface dataset:
Mantle flow through a tear in the Nazca slab inferred from shear wave splitting
Authors: Lynner Colton , Anderson Megan L. , Portner Daniel E. , Beck Susan L. , Gilbert Hersh
Published: July 2017

A tear in the subducting Nazca slab is located between the end of the Pampean flat slab and normally subducting oceanic lithosphere. Tomographic studies suggest mantle material flows through this opening. The best way to probe this hypothesis is through observations of seismic anisotropy, such as shear wave splitting. We examine patterns of shear wave splitting using data from two seismic deployments in Argentina that lay updip of the slab tear. We observe a simple pattern of plate‐motion‐parallel fast splitting directions, indicative of plate‐motion‐parallel mantle flow, beneath the majority of the stations. Our observed splitting contrasts previous observations to the north and south of the flat slab region. Since plate‐motion‐parallel splitting occurs only coincidentally with the slab tear, we propose mantle material flows through the opening resulting in Nazca plate‐motion‐parallel flow in both the subslab mantle and mantle wedge.
Time lag between deformation and seismicity along monogenetic volcanic unrest periods: The case of El Hierro Island (Canary Islands)
Authors: Lamolda Héctor , Felpeto Alicia , Bethencourt Abelardo
Published: July 2017

Between 2011 and 2014 there were at least seven episodes of magmatic intrusion in El Hierro Island, but only the first one led to a submarine eruption in 2011–2012. In order to study the relationship between GPS deformation and seismicity during these episodes, we compare the temporal evolution of the deformation with the cumulative seismic energy released. In some of the episodes both deformation and seismicity evolve in a very similar way, but in others a time lag appears between them, in which the deformation precedes the seismicity. Furthermore, a linear correlation between decimal logarithm of intruded magma volume and decimal logarithm of total seismic energy released along the different episodes has been observed. Therefore, if a future magmatic intrusion in El Hierro Island follows this behavior with a proper time lag, we could have an a priori estimate on the order of magnitude the seismic energy released would reach.
Estimating water retention curves and strength properties of unsaturated sandy soils from basic soil gradation parameters
Authors: Wang Ji‐Peng , Hu Nian , François Bertrand , Lambert Pierre
Published: July 2017

This study proposed two pedotransfer functions (PTFs) to estimate sandy soil water retention curves. It is based on the van Genuchten's water retention model and from a semiphysical and semistatistical approach. Basic gradation parameters of
as particle size at 60% passing and the coefficient of uniformity
are employed in the PTFs with two idealized conditions, the monosized scenario and the extremely polydisperse condition, satisfied. Water retention tests are carried out on eight granular materials with narrow particle size distributions as supplementary data of the UNSODA database. The air entry value is expressed as inversely proportional to
and the parameter
, which is related to slope of water retention curve, is a function of
. The proposed PTFs, although have fewer parameters, have better fitness than previous PTFs for sandy soils. Furthermore, by incorporating with the suction stress definition, the proposed pedotransfer functions are imbedded in shear strength equations which provide a way to estimate capillary induced tensile strength or cohesion at a certain suction or degree of saturation from basic soil gradation parameters. The estimation shows quantitative agreement with experimental data in literature, and it also explains that the capillary‐induced cohesion is generally higher for materials with finer mean particle size or higher polydispersity.
Comparative Phenomenological Study of Fracture Behavior of Ceramic and Glass Foams under Compressive Stress Using In Situ X‐Ray Microtomography
Authors: Hubálková Jana , Voigt Claudia , Schmidt Anne , Moritz Kirsten , Aneziris Christos G.
Published: July 2017

This contribution is dealing with the phenomenological characterization of the cracking and damage of two different brittle foam materials (ceramic foams and glass foams) under compressive load. The compression tests were performed in situ in X‐ray microtomograph in order to visualize the formation of single crack and crack patterns in 3D. Successive microtomographic scans at different levels of compression strain provide an insight into the stressed microstructure of the ceramic and glass foams. The linked evaluation of the microtomographic scans and registered load‐displacement curves clarify the different mechanical response of ceramic and glass foams. Both, ceramic and glass foams show in the early stages of load nearly elastic response. The compressive loading above the elastic region induces different behavior. Ceramic foams response with local failure of single struts and edges to increasing loading. In case of glass foams, the response is depending on whether the cells are predominantly open or close. Predominantly open cell glass foams features very brittle behavior whereas close cell glass foams show pseudo‐ductile behavior with a formation of a crushing band transversal to the loading direction.
MUC1 Aptamer Targeted SERS Nanoprobes
Authors: Pal Suchetan , Harmsen Stefan , Oseledchyk Anton , Hsu Hsiao‐Ting , Kircher Moritz F.
Published: July 2017

Recently, surface‐enhanced Raman scattering (SERS) nanoprobes (NPs) have shown promise in the field of cancer imaging due to their unparalleled signal specificity and high sensitivity. This study reports the development of a DNA aptamer targeted SERS NP. Recently, aptamers are being investigated as a viable alternative to more traditional antibody targeting due to their low immunogenicity and low cost of production. A strategy is developed to functionalize SERS NPs with DNA aptamers, which target Mucin1 (MUC1) in human breast cancer (BC). Thorough in vitro characterization studies demonstrate excellent serum stability and specific binding of the targeted NPs to MUC1. In order to test their in vivo targeting capability, MUC1‐targeted SERS NPs are coinjected with nontargeted or blocked MUC1‐targeted SERS NPs in BC xenograft mouse models. A two‐tumor mouse model with differential expression of MUC1 (MDA‐MB‐468 and MDA‐MB‐453) is used to control for active versus passive targeting in the same animals. The results show that the targeted SERS NPs home to the tumors via active targeting of MUC1, with low levels of passive targeting. This strategy is expected to be an advantageous alternative to antibody‐based targeting and useful for targeted imaging of tumor extent, progression, and therapeutic response.
Unraveling the Orientation of MoS2 on TiO2 for Photocatalytic Water Splitting
Authors: Tang Chao , Xu Weiwei , Chen Chongyang , Li Youyong , Xu Lai
Published: July 2017

The heterostructure of 2D material with different orientations and TiO2 has been proven to be a good candidate for photocatalytic water splitting. However, the detailed mechanism of the orientation of 2D materials with TiO2 has not been explored. Herein, different combinations of edge‐on MoS2 or basal‐on MoS2 with TiO2 are investigated systematically. The adsorption energy, the activation energy barrier, as well as the charge distribution reveal that edge‐on heterostructures have better efficiency in the separation of photoelectron–hole pairs and can enhance the efficiency of hydrogen evolution reaction. This work studies the differences in mechanisms of edge‐on and basal‐on heterostructures in hydrogen evolution reactions. The simulated results provide significant theoretical foundation for the design of new materials.
Long‐Term Live‐Cell STED Nanoscopy of Primary and Cultured Cells with the Plasma Membrane HIDE Probe DiI‐SiR
Authors: Thompson Alexander D. , Omar Mitchell H. , Rivera‐Molina Felix , Xi Zhiqun , Koleske Anthony J. , Toomre Derek K. , Schepartz Alanna
Published: July 2017

Super‐resolution imaging of live cells over extended time periods with high temporal resolution requires high‐density labeling and extraordinary fluorophore photostability. Herein, we achieve this goal by combining the attributes of the high‐density plasma membrane probe DiI‐TCO and the photostable STED dye SiR‐Tz. These components undergo rapid tetrazine ligation within the plasma membrane to generate the HIDE probe DiI‐SiR. Using DiI‐SiR, we visualized filopodia dynamics in HeLa cells over 25 min at 0.5 s temporal resolution, and visualized dynamic contact‐mediated repulsion events in primary mouse hippocampal neurons over 9 min at 2 s temporal resolution. HIDE probes such as DiI‐SiR are non‐toxic and do not require transfection, and their apparent photostability significantly improves the ability to monitor dynamic processes in live cells at super‐resolution over biologically relevant timescales.
From a Molecular 2Fe‐2Se Precursor to a Highly Efficient Iron Diselenide Electrocatalyst for Overall Water Splitting
Authors: Panda Chakadola , Menezes Prashanth W. , Walter Carsten , Yao Shenglai , Miehlich Matthias E. , Gutkin Vitaly , Meyer Karsten , Driess Matthias
Published: July 2017

A highly active FeSe2 electrocatalyst for durable overall water splitting was prepared from a molecular 2Fe‐2Se precursor. The as‐synthesized FeSe2 was electrophoretically deposited on nickel foam and applied to the oxygen and hydrogen evolution reactions (OER and HER, respectively) in alkaline media. When used as an oxygen‐evolution electrode, a low 245 mV overpotential was achieved at a current density of 10 mA cm−2, representing outstanding catalytic activity and stability because of Fe(OH)2/FeOOH active sites formed at the surface of FeSe2. Remarkably, the system is also favorable for the HER. Moreover, an overall water‐splitting setup was fabricated using a two‐electrode cell, which displayed a low cell voltage and high stability. In summary, the first iron selenide material is reported that can be used as a bifunctional electrocatalyst for the OER and HER, as well as overall water splitting.
Adding Azathioprine to Remission‐Induction Glucocorticoids for Eosinophilic Granulomatosis With Polyangiitis (Churg‐Strauss), Microscopic Polyangiitis, or Polyarteritis Nodosa Without Poor Prognosis Factors
Authors: Puéchal Xavier , Pagnoux Christian , Baron Gabriel , Quémeneur Thomas , Néel Antoine , Agard Christian , Lifermann François , Liozon Eric , Ruivard Marc , Godmer Pascal , Limal Nicolas , Mékinian Arsène , Papo Thomas , Ruppert Anne‐Marie , Bourgarit Anne , Bienvenu Boris , Geffray Loïck , Saraux Jean‐Luc , Diot Elisabeth , Crestani Bruno , Delbrel Xavier , Sailler Laurent , Cohen Pascal , Le Guern Véronique , Terrier Benjamin , Groh Matthieu , Le Jeunne Claire , Mouthon Luc , Ravaud Philippe , Guillevin Loïc ,   the French Vasculitis Study Group
Published: July 2017

Objective

In most patients with nonsevere systemic necrotizing vasculitides (SNVs), remission is achieved with glucocorticoids alone, but one‐third experience a relapse within 2 years. This study was undertaken to determine whether the addition of azathioprine (AZA) to glucocorticoids could achieve a higher sustained remission rate of newly diagnosed nonsevere eosinophilic granulomatosis with polyangiitis (Churg‐Strauss) (EGPA), microscopic polyangiitis (MPA), or polyarteritis nodosa (PAN).

Methods

All patients included in this double‐blind trial received glucocorticoids, gradually tapered over 12 months, and were randomized to receive AZA or placebo for 12 months, with stratification according to SNV (EGPA or MPA/PAN). The primary end point was the combined rate of remission induction failures and minor or major relapses at month 24.

Results

Ninety‐five patients (51 with EGPA, 25 with MPA, and 19 with PAN) met the inclusion criteria, were randomized, and received at least 1 dose of AZA (n = 46) or placebo (n = 49). At month 24, 47.8% of the patients receiving AZA versus 49% of the patients receiving placebo had remission induction failures or relapses (P = 0.86). Secondary end points were comparable between the AZA and placebo arms. These included initial remission rate (95.7% versus 87.8%), total relapse rate (44.2% versus 40.5%), and glucocorticoid use. Two patients in the placebo arm died; 22 patients in the AZA arm (47.8%) and 23 patients in the placebo arm (46.9%) experienced ≥1 severe adverse event. For EGPA patients, the primary end point (48% in the AZA arm versus 46.2% in the placebo arm) and the percent of patients who experienced asthma/rhinosinusitis exacerbations (24% in the AZA arm versus 19.2% in the placebo arm) were comparable between treatment arms.

Conclusion

Addition of AZA to glucocorticoids for the induction of remission of nonsevere SNVs does not improve remission rates, lower relapse risk, spare steroids, or diminish the EGPA asthma/rhinosinusitis exacerbation rate.
Systematic review of management of chronic pain after surgery
Authors: Wylde V , Dennis J , Beswick A D , Bruce J , Eccleston C , Howells N , Peters T J , Gooberman-Hill R
Published: July 2017

Background

Pain present for at least 3 months after a surgical procedure is considered chronic postsurgical pain (CPSP) and affects 10–50 per cent of patients. Interventions for CPSP may focus on the underlying condition that indicated surgery, the aetiology of new-onset pain or be multifactorial in recognition of the diverse causes of this pain. The aim of this systematic review was to identify RCTs of interventions for the management of CPSP, and synthesize data across treatment type to estimate their effectiveness and safety.

Methods

MEDLINE, Embase, PsycINFO, CINAHL and the Cochrane Library were searched from inception to March 2016. Trials of pain interventions received by patients at 3 months or more after surgery were included. Risk of bias was assessed using the Cochrane risk-of-bias tool.

Results

Some 66 trials with data from 3149 participants were included. Most trials included patients with chronic pain after spinal surgery (25 trials) or phantom limb pain (21 trials). Interventions were predominantly pharmacological, including antiepileptics, capsaicin, epidural steroid injections, local anaesthetic, neurotoxins, N-methyl-d-aspartate receptor antagonists and opioids. Other interventions included acupuncture, exercise, postamputation limb liner, spinal cord stimulation, further surgery, laser therapy, magnetic stimulation, mindfulness-based stress reduction, mirror therapy and sensory discrimination training. Opportunities for meta-analysis were limited by heterogeneity. For all interventions, there was insufficient evidence to draw conclusions on effectiveness.

Conclusion

There is a need for more evidence about interventions for CPSP. High-quality trials of multimodal interventions matched to pain characteristics are needed to provide robust evidence to guide management of CPSP.
Characterization and discrimination of raw and vinegar‐baked Bupleuri radix based on UHPLC‐Q‐TOF‐MS coupled with multivariate statistical analysis
Authors: Lei Tianli , Chen Shifeng , Wang Kai , Zhang Dandan , Dong Lin , Lv Chongning , Wang Jing , Lu Jincai
Published: July 2017

Bupleuri Radix is a commonly used herb in clinic, and raw and vinegar‐baked Bupleuri Radix are both documented in the Pharmacopoeia of People's Republic of China. According to the theories of traditional Chinese medicine, Bupleuri Radix possesses different therapeutic effects before and after processing. However, the chemical mechanism of this processing is still unknown. In this study, ultra‐high‐performance liquid chromatography with quadruple time‐of‐flight mass spectrometry coupled with multivariate statistical analysis including principal component analysis and orthogonal partial least square‐discriminant analysis was developed to holistically compare the difference between raw and vinegar‐baked Bupleuri Radix for the first time. As a result, 50 peaks in raw and processed Bupleuri Radix were detected, respectively, and a total of 49 peak chemical compounds were identified. Saikosaponin a, saikosaponin d, saikosaponin b3, saikosaponin e, saikosaponin c, saikosaponin b2, saikosaponin b1, 4′′‐O‐acetyl‐saikosaponin d, hyperoside and 3′,4′‐dimethoxy quercetin were explored as potential markers of raw and vinegar‐baked Bupleuri Radix. This study has been successfully applied for global analysis of raw and vinegar‐processed samples. Furthermore, the underlying hepatoprotective mechanism of Bupleuri Radix was predicted, which was related to the changes of chemical profiling.
Determination of tigecycline in human plasma by LC–MS/MS and its application to population pharmacokinetics study in Chinese patients with hospital‐acquired pneumonia
Authors: Shao Rong , Li Xingang , Hu Yangmin , Chen Jinliang , Lou Honggang , Dai Haibin
Published: July 2017

A selective, sensitive and rapid liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed and validated for the determination of tigecycline (TGC) in human plasma, using tigecycline‐d9 as an internal standard (IS). Analytical samples were prepared using a protein precipitation method coupled with a concentration process. The analyte and IS were separated on a reversed‐phase Waters Acquity UPLC® BEH‐C18 column (2.1 × 50 mm i.d., 1.7 μm) with a flow rate of 0.25 mL/min. The mobile phase consisted of water, containing 0.2% formic acid (v/v) with 10 mm ammonium formate (A) and acetonitrile (B). The mass spectrometer was operated in selected reaction monitoring mode through electrospray ionization ion mode using the transitions of m/z 586.2 → 513.1 and m/z 595.1 → 514.0 for TGC and IS, respectively. The linearity of the method was in the range of 10–5000 ng/mL. Intra‐ and inter‐batch precision (CV) for TGC was <9.27%, and the accuracy ranged from 90.06 to 107.13%. This method was successfully applied to the analysis of samples from hospital‐acquired pneumonia patients treated with TGC, and a validated population pharmacokinetic model was established. This developed method could be useful to predict pharmacokinetics parameters and valuable for further pharmacokinetics/pharmacodynamics studies.
Small Molecules Inspired by the Natural Product Withanolides as Potent Inhibitors of Wnt Signaling
Authors: Sheremet Michael , Kapoor Shobhna , Schröder Peter , Kumar Kamal , Ziegler Slava , Waldmann Herbert
Published: July 2017

Wnt signaling is a fundamental pathway that drives embryonic development and is essential for stem cell maintenance and tissue homeostasis. Dysregulation of Wnt signaling is linked to various diseases, and a constitutively active Wnt pathway drives tumorigenesis. Thus, disruption of the Wnt response is deemed a promising strategy for cancer drug discovery. However, only few clinical drug candidates that target Wnt signaling are available so far, and new small‐molecule modulators of Wnt‐related processes are in high demand. Here we describe the synthesis of small molecules inspired by withanolide natural products by using a pregnenolone‐derived β‐lactone as the key intermediate that was transformed into a δ‐lactone appended to the D‐ring of the steroidal scaffold. This natural‐product‐inspired compound library contained potent inhibitors of Wnt signaling that act upstream of the destruction complex to stabilize Axin in a tankyrase‐independent manner.
MDA‐MB‐231 and 8701BC breast cancer lines promote the migration and invasiveness of ECV304 cells on 2D and 3D type‐I collagen matrix
Authors: Saladino Silvia , Salamone Monica , Ghersi Giulio
Published: July 2017

Tumor angiogenesis is a multiphasic process, having the extracellular matrix remodeling as critical step. Different classes of proteolytic enzymes in matrix digestion/remodeling are involved. The role of lytic enzymes and their activation mode have not been completely elucidated. Herein, the crosstalk between endothelia and tumor cells, by realization of bi‐ and three‐dimensional endothelial and breast cancer cells co‐cultures, were studied in vitro. Particularly, the effects of two tumor conditioned media (TCM) were assessed about endothelial proliferation, migration, and invasiveness. An increase in expression of pro‐MMP9 was detected when endothelial cells were cultured in the presence of both TCM; such as an up‐regulation of MMP1 and MMP14 and a down‐regulation of MMP7. Moreover the increased MMP2 gene expression from one of them and the stimulation MMP3 synthesis from the other one were observed; an increases of β3‐integrin, VEGFA, and DPP4 molecules were detected when endothelia cells are cultured with both TCM. The selection/characterization of elements present in conditioned media from breast cancer cells differently affect endothelial cells, make them potential effectors useful in breast cancer treatment.
Evaluating the impact of the London Pathway Project
Authors: Jolliffe Darrick , Cattell Jack , Raza Annabelle , Minoudis Philip
Published: July 2017

Background

The London Pathway Project (LPP) is an innovative whole‐systems approach to addressing the needs of offenders who have severe personality disorder, with the goal of reducing their risk of harm. Previous research has evaluated the initial implementation of the LPP.

Aims

This paper focused on evaluating the impact of the LPP on a number of criminogenic needs over time and its impact on the risk of reoffending and harm compared with a similar group who did not experience the pathway.

Method

Data for men who had been identified for the LPP were used to explore changes in key criminogenic needs an average of 11 months after commencing on the pathway. In addition, Offender Assessment System data was used to match men who had experienced the LPP for at least 12 months to a comparison group on key demographic and criminal history variables. Changes in validated risk assessment devices and changes in practitioners' perception of risk were examined.

Results

The LPP was associated with desirable within‐individual change for most of the criminogenic needs explored. However, strong non‐desirable changes in lifestyle and associates were also identified, but this was particularly the case for those sentenced to prison. When compared with a matched group, those identified for the pathway showed a significant reduction on an objective measure of risk of reoffending but were rated as having significantly increased risk of harm on the basis of practitioner's perceptions. There was no evidence that greater progression along the pathway was associated with greater benefits.

Conclusions

This is the first impact evaluation of the LPP, and the results were generally positive in terms of its relation to criminogenic needs and risks. Much more research that clearly links project inputs to actual behavioural outcomes, such as later reoffending, is needed.

Implications

This initial evaluation of the impact of the LPP could be used as baseline data to examine the impact of the pathway over time, and with greater precision (e.g. matching on personality features). Copyright © 2017 John Wiley & Sons, Ltd.
S, N Dual‐Doped Graphene Fibers: A High‐Performance Electrode Material for Supercapacitors
Authors: Kan Yanfang , Ma Xinlong , Ning Guoqing , Li Yongfeng , Zhou Yasong
Published: July 2017

Sulfur and nitrogen dual‐doped graphene fibers (SNGFs) were prepared through an optimized chemical vapor deposition. The SNGFs exhibit a stable 3D fibrous structure, high surface area, abundant mesopores, uniform distribution of S and N atoms and more defects. As electrodes for supercapacitors, the specific capacitance of SNGFs reaches 311 F g−1. The SNGF//SNGF symmetric supercapacitor delivers maximum energy and power densities of 37.7 W h kg−1 and 14 kW kg−1, with excellent cycling stability (92.2 % capacitance remained after 5000 cycles). The result indicates that the SNGFs are a promising candidate as a high‐quality electrode material for supercapacitors.
Measurement of Drug‐Stabilized Topoisomerase II Cleavage Complexes by Flow Cytometry
Authors: de Campos Nebel Marcelo , Palmitelli Micaela , González‐Cid Marcela
Published: July 2017

The poisoning of Topoisomerase II (Top2) has been found to be useful as a therapeutic strategy for the treatment of several tumors. The mechanism of Top2 poisons involves a drug‐mediated stabilization of a Top2‐DNA complex, termed Top2 cleavage complex (Top2cc), which maintains a 5′ end of DNA covalently bound to a tyrosine from Top2 through a phosphodiester group. Drug‐stabilized Top2cc leads to Top2‐linked‐DNA breaks, which are believed to mediate their cytotoxicity. Several time‐consuming or cell type‐limiting assays have been used in the past to study drug‐stabilized Top2cc. Here, we describe a flow cytometry‐based method that allows a rapid assessment of drug‐induced Top2cc, which is suitable for high throughput analysis in almost any kind of human cell. The analyses of the drug‐induced Top2cc in the cell cycle context and the possibility to track its removal are additional benefits from this methodology. © 2017 by John Wiley & Sons, Inc.
CyTOF Mass Cytometry for Click Proliferation Assays
Authors: Tosevski Vinko , Ulashchik Egor , Trovato Andrea , Cappella Paolo
Published: July 2017

Novel cell analyzers, including polychromatic flow cytometers and isotopical cytometry by time of flight (CyTOF) mass cytometers, enable simultaneous measurement of virtually bondless characteristics at the single‐cell level. BrdU assays for quantifying cellular proliferation are common but have several limitations, including the need for a DNA denaturation step and inability to simultaneously resolve multiple parameters and phenotypic complexity. Click chemistry reactions have become popular in the past decade, as they can resolve these issues. This protocol introduces a novel assay able to bridge flow cytometry and CyTOF analysis for active S‐phase determination in cell cycle applications, combining well‐established click chemistry with a novel iodo‐deoxyuridine (IdU) azide derivative and a cross‐reactive anti‐IdU antibody for detecting incorporated EdU during DNA synthesis. This method is preferred over traditional BrdU‐based assays for complex and multiparametric experiments. It provides a feasible cost‐effective approach for detecting ethynyl‐labeled nucleotides, with the advantage of combining flow and mass cytometry analyses. © 2017 by John Wiley & Sons, Inc.
Animal Model of Chronic Migraine‐Associated Pain
Authors: Moye Laura S. , Pradhan Amynah A. A.
Published: July 2017

Migraine is a debilitating condition that affects hundreds of millions of people worldwide. A subset of these patients experience chronic migraine, resulting in long‐term disability and a severely lowered quality of life. The development of novel migraine therapies has been slow, partially due to the small number of predictive animal models. We have recently developed a novel model of chronic migraine‐associated pain, using the known human migraine trigger, nitroglycerin. Injection of nitroglycerin evokes an acute mechanical hyperalgesia, which is sensitive to the acute migraine therapy sumatriptan. In addition, chronic administration of nitroglycerin produces a progressive and sustained decrease in basal mechanical responses, and this hypersensitivity is blocked by migraine preventatives such as topiramate. This mouse model of chronic migraine can be used to study the mechanisms underlying progression of migraine from an episodic to a chronic disorder, and for identifying and screening novel acute and preventive migraine therapies. © 2017 by John Wiley & Sons, Inc.
Incorporating thresholds into understanding salinity tolerance: A study using salt‐tolerant plants in salt marshes
Authors: He Qiang , Silliman Brian R. , Cui Baoshan
Published: July 2017

Although salinity in many ecosystems such as salt marshes can be extremely high, an asymmetry in salinity range between experimental studies (relatively narrow) and field conditions (potentially broad) has strongly affected current understanding of plant salinity tolerance. To improve understanding, it is thus important to examine plant tolerances over a broad range of salinities and identify potential tolerance thresholds. We examine tolerances of two widely distributed marsh plants, Suaeda salsa and Salicornia europaea, to salinities ranging from 0 to 100 g/kg, and determine survival, above‐ and belowground biomass after 8 weeks of salinity treatment. Both species, Sa. europaea in particular, have much broader salinity tolerances than other plants previously examined, (2) plant survival, above‐ and belowground biomass have remarkably different responses to salinity, and (3) there is a nonlinear, threshold response of S. salsa to salinity, above which S. salsa survivorship drastically decreases. These results provide multiple important insights. Our study suggests that the potential for using these halophytes to revegetate and restore salt‐affected land may be greater than previously thought, and highlights the importance of studying multiple plant responses. Importantly, our study calls for a better integration of thresholds into understanding plant salinity tolerances and their applications.
Contrast‐enhanced computed tomography with myocardial three‐dimensional printing can guide treatment in symptomatic hypertrophic obstructive cardiomyopathy
Authors: Hamatani Yasuhiro , Amaki Makoto , Kanzaki Hideaki , Yamashita Kizuku , Nakashima Yasuteru , Shibata Atsushi , Okada Atsushi , Takahama Hiroyuki , Hasegawa Takuya , Shimahara Yusuke , Sugano Yasuo , Fujita Tomoyuki , Shiraishi Isao , Yasuda Satoshi , Kobayashi Junjiro , Anzai Toshihisa
Published: July 2017

Both surgical myectomy and percutaneous transluminal septal myocardial ablation are effective treatments for drug‐refractory symptomatic hypertrophic obstructive cardiomyopathy (HOCM). However, in some cases, it is not easy to elucidate the abnormal structure of left ventricular outflow obstruction to adopt these treatments. Here, we presented a young female patient with drug‐refractory symptomatic HOCM. In this case, contrast‐enhanced computed tomography enabled us to assess the suitability of percutaneous transluminal septal myocardial ablation. By creating three‐dimensional printed models using computed tomography data, we could also visualize intracardiac structure and simulate the surgical procedure. A multimodality assessment strategy is useful for evaluating patients complicated with drug‐refractory symptomatic HOCM.
A Phase 2a dose‐escalation study of the safety, tolerability, pharmacokinetics and haemodynamic effects of BMS‐986231 in hospitalized patients with heart failure with reduced ejection fraction
Authors: Tita Cristina , Gilbert Edward M. , Van Bakel Adrian B. , Grzybowski Jacek , Haas Garrie J. , Jarrah Mohammad , Dunlap Stephanie H. , Gottlieb Stephen S. , Klapholz Marc , Patel Parag C. , Pfister Roman , Seidler Tim , Shah Keyur B. , Zieliński Tomasz , Venuti Robert P. , Cowart Douglas , Foo Shi Yin , Vishnevsky Alexander , Mitrovic Veselin
Published: July 2017

Aims

This study was designed to evaluate the safety, tolerability and haemodynamic effects of BMS‐986231, a novel second‐generation nitroxyl donor with potential inotropic, lusitropic and vasodilatory effects in patients hospitalized with decompensated heart failure and reduced ejection fraction (HFrEF).

Methods and results

Forty‐six patients hospitalized with decompensated HFrEF were enrolled into four sequential dose‐escalation cohorts in this double‐blind, randomized, placebo‐controlled Phase 2a study. Patients with baseline pulmonary capillary wedge pressure (PCWP) of ≥20 mmHg and a cardiac index of ≤2.5 L/min/m2 received one 6‐h i.v. infusion of BMS‐986231 (at 3, 5, 7 or 12 µg/kg/min) or placebo. BMS‐986231 produced rapid and sustained reductions in PCWP, as well as consistent reductions in time‐averaged pulmonary arterial systolic pressure, pulmonary arterial diastolic pressure and right atrial pressure. BMS‐986231 increased non‐invasively measured time‐averaged stroke volume index, cardiac index and cardiac power index values, and decreased total peripheral vascular resistance. There was no evidence of increased heart rate, drug‐related arrhythmia or symptomatic hypotension with BMS‐986231. Analyses of adverse events throughout the 30‐day follow‐up did not identify any toxicities specific to BMS‐986231, with the potential exception of infrequent mild‐to‐moderate headaches during infusion. There were no treatment‐related serious adverse events.

Conclusions

BMS‐986231 demonstrated a favourable safety and haemodynamic profile in patients hospitalized with advanced heart failure. Based on preclinical data and these study's findings, it is possible that the haemodynamic benefits may be mediated by inotropic and/or lusitropic as well as vasodilatory effects. The therapeutic potential of BMS‐986231 should be further assessed in patients with heart failure.
Physicochemical characteristics of pristine and functionalized graphene
Authors: Bourdo Shawn E. , Al Faouri Radwan , Sleezer Robert , Nima Zeid A. , Lafont Andersen , Chhetri Bijay P. , Benamara Mourad , Martin Betty , Salamo Gregory J. , Biris Alexandru S.
Published: July 2017

Graphene‐based nanomaterials have received significant attention in the last decade due to their interesting properties. Its electrical and thermal conductivity and strength make graphene well suited for a variety of applications, particularly for use as a composite material in plastics. Furthermore, much work is taking place to utilize graphene as a biomaterial for uses such as drug delivery and tissue regeneration scaffolds. Owing to the rapid progress of graphene and its potential in many marketplaces, the potential toxicity of these materials has garnered attention. Graphene, while simple in its purest form, can have many different chemical and physical properties. In this paper, we describe our toxicity evaluation of pristine graphene and a functionalized graphene sample that has been oxidized for enhanced hydrophilicity, which was synthesized from the pristine sample. The samples were characterized by X‐ray photoelectron spectroscopy, Raman spectroscopy, infrared spectroscopy, thermogravimetric analysis, zeta‐potential, atomic force microscopy and electron microscopy. We discuss the disagreement between the size of imaged samples analyzed by atomic force microscopy and by transmission electron microscopy. Furthermore, the samples each exhibit quite different surface chemistry and structure, which directly affects their interaction with aqueous environments and is important to consider when evaluating the toxicity of materials both in vitro and in vivo. Copyright © 2017 John Wiley & Sons, Ltd.
Notable Drug–Drug Interaction Between Etizolam and Itraconazole in Poor Metabolizers of Cytochrome P450 2C19
Authors: Yamamoto Takehito , Furihata Kenichi , Hisaka Akihiro , Moritoyo Takashi , Ogoe Kazuaki , Kusayama Shizuko , Motohashi Keiju , Mori Akiko , Iwatsubo Takeshi , Suzuki Hiroshi
Published: July 2017

In this study, impact of a polymorphism of CYP2C19 on drug–drug interaction (DDI) was examined for etizolam. The effect of itraconazole (a strong CYP3A inhibitor) on the pharmacokinetics of etizolam (a substrate of CYP2C19 and CYP3A) was assessed in both extensive metabolizers (EMs) and poor metabolizers (PMs) of CYP2C19. Sixteen participants (8 EMs and 8 PMs) received a single oral dose of etizolam (0.25 mg) on day 1. The participants ingested itraconazole (200 mg twice a day) on days 2–5. On day 5, participants received an oral dose of etizolam (0.25 mg) again. Before coadministration of itraconazole (day 1), the area under the time–plasma concentration curve from time zero to infinity (AUC∞) of etizolam was higher in PMs than in EMs (2.65‐fold, P < .01). Coadministration of itraconazole increased the AUC∞ of etizolam 1.66‐fold and 2.34‐fold in EMs and PMs, respectively (day 5). Consequently, AUC∞ was 6.18‐fold higher in PMs with itraconazole than that in EMs without itraconazole. The increase by itraconazole was larger in PMs (P < .01). In heterozygous EMs (hEMs), AUC∞ was simulated to be 2.56‐fold higher with itraconazole than that in EMs without itraconazole. We found that in vitro measurements of fraction metabolized (fm) using the liver microsome prepared from PM donors would be helpful to predict polymorphism‐dependent DDIs. These results suggest that the PMs and hEMs of a polymorphic CYP would be at higher risk of DDIs relative to EMs for drugs metabolized by both polymorphic and nonpolymorphic CYPs such as etizolam.
Temporal and spatial variability of surface‐based inversions over Europe based on ERA‐Interim reanalysis
Authors: Palarz Angelika , Celiński‐Mysław Daniel , Ustrnul Zbigniew
Published: July 2017

Tropospheric temperature inversions seem to be an important feature of climate, as well as a significant factor affecting air quality and fog formation. The aim of this article is to investigate the temporal and spatial variability of surface‐based inversions (SBIs) over Europe. It is based on data derived from the ERA‐Interim reanalysis for the period 1981–2015. The study examines diurnal, seasonal and multiannual variability of temperature inversions based on their frequency, depth and strength. These three parameters are characterized by strong temporal variability – diurnal and seasonal, as well as strong spatial differentiation. It has been confirmed that the energy budget is the key factor responsible for diurnal, and partly seasonal variability of SBI occurrence. Its negative values lead to an intense cooling of active surface and initiate the formation of the radiative inversions, which are the most common type of inversion occurring over the mainland of Europe. Temperature inversions usually form shortly after dusk, increasing gradually their depth and strength until sunrise. At 0000 Universal Time Coordinated (UTC), SBI frequency attains higher values in the summer than in the winter over the predominant part of Europe. However, the inversion layers occurring then are noticeably shallower and weaker. Surface type strongly affects SBI properties. This is mostly marked in terms of the distinct differentiation between marine and land areas as well as the impact of vast glaciers located across Greenland and western part of Iceland. Moreover, the distribution of SBI depth and strength is shaped by atmospheric circulation. For instance, their higher values occur over Eastern Europe in the winter, which is associated with the influence of a seasonal high pressure system found over Russia. Taking into account multiannual variability, SBI parameters, primarily depth and strength, exhibit the most significant negative changes in the winter.
An air mass‐derived cool season climatology of synoptically forced Appalachian cold‐air damming
Authors: Ellis Andrew W. , Marston Michael L. , Nelson Daniel A.
Published: July 2017

An air mass approach was used to identify episodes of cool season cold‐air damming (CAD) within the central Appalachian Mountains region of the eastern United States. Daily air mass type data were used to identify days on which moist polar (MP) air was regionally evident east of the mountains, while non‐MP air was in place at nearby stations west of the mountains. Over a 35‐year study period, 219 CAD days were identified (>6 per year) with the annual frequency exhibiting no trend but suggesting that El Niño (La Niña) coincides with a greater (lesser) frequency of CAD days in winter (December–February). Synoptic atmospheric composites reveal west‐to‐east migration of a parent anticyclone to a classic position along the border of the northeastern United States and southeastern Canada. This coincides with a pattern of amplifying and slowly eastward‐moving 500 hPa height anomalies characterized by positive (negative) values over eastern (western) North America that are signalled a few days in advance by the index representing the Pacific‐North American teleconnection pattern. Confinement of the CAD below the 850 hPa level is evident in the synoptic wind field, while the composite vertical profile of the atmosphere within the CAD environment further depicts the shallow nature of the surface‐based cool, moist air. Northeasterly winds at the surface veer to southeasterly within a few hundred metres above the surface, and then southwesterly at less than one km above the surface, at the 850 hPa level. The air mass approach to CAD identification appears to successfully identify regional occurrences of synoptically forced CAD, although it likely does not detect local and/or diabatically forced CAD.
The tissue residues of sodium dehydroacetate used as feed preservative in swine
Authors: Liu Hao , Han Lingling , Xie Jiayu , Wu Yingchao , Xie Yang , Zhang Yumei
Published: July 2017

BACKGROUND

Sodium dehydroacetate (Na‐DHA) is a food and feed additive with antimicrobial effects. There is little information on Na‐DHA residue levels in foods derived from animals. In this study, Na‐DHA residue levels in swine tissues were determined by HLPC, and the pharmacokinetics of Na‐DHA in tissues were determined.

RESULTS

The Na‐DHA residue levels in swine tissues were <1.2 mg kg−1 at different withdrawal time after thirty‐two Duroc × Landrace × Yorkshire pigs were administered 200 mg Na‐DHA kg−1 through the feed for 30 days. In decreasing order of Na‐DHA residue levels, the tissues were kidney > liver > muscle > fat. The pharmacokinetics of Na‐DHA followed a binomial regression model, and the half‐time of Na‐DHA in swine tissues was 9.07 days for kidney, 7.19 days for liver, 6.66 days for muscle, and 5.39 days for fat tissue. The accuracy of the HPLC method for Na‐DHA determination ranged from 80.18% to 91.33% recovery, with coefficients of variation <6.4%, limit of detection of 0.08 mg kg−1, and limit of quantification of 0.2 mg kg−1.

CONCLUSION

Na‐DHA included at 200 mg kg−1 in a swine diet is a safe feed additive based on residue elimination and ADI values reported. © 2017 Society of Chemical Industry
Rheology and microstructure of myofibrillar protein–olive oil composite gels: effect of different non‐meat protein as emulsifier
Authors: Wu Mangang , Fei Litian , Zhuang Tao , Lei Shumin , Ge Qingfeng , Yu Hai , Wang Jiahao , Wang Yaosong
Published: July 2017

BACKGROUND

Heat‐induced composite gels were prepared with 20 g kg−1 (2%) myofibrillar protein (MP) sol and 100 g kg−1 (10%) olive oil pre‐emulsified by MP or non‐meat protein in 0.6 mol L−1 NaCl, at pH 6.2. The effect of different non‐meat protein (soy protein isolate, egg‐white protein isolate and sodium caseinate) pre‐emulsions on the rheological properties and microstructure of MP gel was evaluated.

RESULTS

Adding emulsion enhanced the gel strength of MP gel except for the soy protein isolate (SPI) as emulsifier group, but all emulsion group markedly improved (P < 0.05) the water‐holding capacity and the storage modulus (G′) of MP gels. SDS‐PAGE show that some non‐meat protein bands partially participated in the formation of MP composite gels with different kinds of emulsion added. Micrographs revealed that these emulsions made the gels become denser and more compact with subtle diverse effects.

CONCLUSION

Different meat or non‐meat proteins as emulsifier have varied impacts on the rheology and microstructure of MP gels, indicating the potential and feasibility of these non‐meat proteins as emulsifiers to modify the textural properties in comminuted meat products. © 2017 Society of Chemical Industry
Identification of suitable reference genes during the formation of chlamydospores in Clonostachys rosea 67‐1
Authors: Zhang Jun , Sun Zhanbin , Li Shidong , Sun Manhong
Published: July 2017

Clonostachys rosea is a potential biocontrol fungus that can produce highly resistant chlamydospores under specific conditions. To investigate the genes related to chlamydospore formation, we identified reliable reference genes for quantification of gene expression in C. rosea 67‐1 during sporulation. In this study, nine reference genes, actin (ACT), elongation factor 1 (EF1), glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH), histone (HIS), RNA polymerase II CTD phosphatase Fcp1 (RPP), succinate‐semialdehyde dehydrogenase (SSD), TATA‐binding protein (TBP), ubiquitin (UBQ), and ubiquitin‐conjugating enzyme (UCE), were selected and cloned from 67‐1, and their expression stability during chlamydospore formation was determined using reverse transcription quantitative PCR and assessed using the software geNorm, NormFinder and BestKeeper. The Ct values of the candidates ranged from 19.9 to 29.7, among which HIS, ACT and SSD exhibited high expression levels. The statistical analysis showed that ACT and SSD were most stably expressed, while UBQ and GAPDH showed relatively large variations under different culture conditions. Calculation of pairwise variation value indicated that two reference genes were required for precise quantification. Finally, ACT and SSD were selected to normalize gene expression during chlamydospore production in C. rosea 67‐1. To the best of our knowledge, this is the first report of SSD as a reference gene. This study will facilitate the accurate quantification of differentially expressed genes during the generation of chlamydospores and contribute to the investigation of the molecular mechanism underlying chlamydospore formation in C. rosea.
Global brain metabolic quantification with whole‐head proton MRS at 3 T
Authors: Kirov Ivan I. , Wu William E. , Soher Brian J. , Davitz Matthew S. , Huang Jeffrey H. , Babb James S. , Lazar Mariana , Fatterpekar Girish , Gonen Oded
Published: July 2017

Total N‐acetyl‐aspartate + N‐acetyl‐aspartate–glutamate (NAA), total creatine (Cr) and total choline (Cho) proton MRS (1H–MRS) signals are often used as surrogate markers in diffuse neurological pathologies, but spatial coverage of this methodology is limited to 1%–65% of the brain. Here we wish to demonstrate that non‐localized, whole‐head (WH) 1H–MRS captures just the brain's contribution to the Cho and Cr signals, ignoring all other compartments. Towards this end, 27 young healthy adults (18 men, 9 women), 29.9 ± 8.5 years old, were recruited and underwent T1‐weighted MRI for tissue segmentation, non‐localizing, approximately 3 min WH 1H–MRS (TE/TR/TI = 5/10/940 ms) and 30 min 1H–MR spectroscopic imaging (MRSI) (TE/TR = 35/2100 ms) in a 360 cm3 volume of interest (VOI) at the brain's center. The VOI absolute NAA, Cr and Cho concentrations, 7.7 ± 0.5, 5.5 ± 0.4 and 1.3 ± 0.2 mM, were all within 10% of the WH: 8.6 ± 1.1, 6.0 ± 1.0 and 1.3 ± 0.2 mM. The mean NAA/Cr and NAA/Cho ratios in the WH were only slightly higher than the “brain‐only” VOI: 1.5 versus 1.4 (7%) and 6.6 versus 5.9 (11%); Cho/Cr were not different. The brain/WH volume ratio was 0.31 ± 0.03 (brain ≈ 30% of WH volume). Air‐tissue susceptibility‐driven local magnetic field changes going from the brain outwards showed sharp gradients of more than 100 Hz/cm (1 ppm/cm), explaining the skull's Cr and Cho signal losses through resonance shifts, line broadening and destructive interference. The similarity of non‐localized WH and localized VOI NAA, Cr and Cho concentrations and their ratios suggests that their signals originate predominantly from the brain. Therefore, the fast, comprehensive WH‐1H‐MRS method may facilitate quantification of these metabolites, which are common surrogate markers in neurological disorders.