bluuebunny/crossref_metadata_2025 huggingface dataset:
The age of iron and iron source attribution in the ocean
Authors: Holzer Mark , Frants Marina , Pasquier Benoît
Published: September 2016

We use tracers to partition dissolved iron (dFe) into the contributions from each source within a numerical model of the iron cycle without perturbing the system. These contributions are further partitioned according to the time since injection into the ocean, which defines their iron‐age spectrum and mean iron age. The utility of these diagnostics is illustrated for a family of inverse model estimates of the iron cycle, constrained by a data‐assimilated circulation and available dFe measurements. The source contributions are compared with source anomalies defined as the differences between solutions with and without the source in question. We find that in the Southern Ocean euphotic zone, the hydrothermal and sediment contributions range from 15% to 30% of the total each, which the anomalies underestimate by a factor of ∼2 because of the nonlinearity of scavenging. The iron age is only reset by scavenging and attains a mean of several hundred years in the Southern Ocean euphotic zone, revealing that aeolian iron there is supplied primarily from depth as regenerated dFe. Tagging iron according to source region and pathways shows that 70–80% of the aeolian dFe in the euphotic zone near Antarctica is supplied from north of 46°S via paths that reach below 1 km depth. Hydrothermal iron has the oldest surface mean ages on the order of middepth ventilation times. A measure of uncertainty is provided by the systematic variations of our diagnostics across the family of iron cycle estimates, each member of which has a different aeolian source strength.
High atmospheric horizontal resolution eliminates the wind‐driven coastal warm bias in the southeastern tropical Atlantic
Authors: Milinski Sebastian , Bader Jürgen , Haak Helmuth , Siongco Angela Cheska , Jungclaus Johann H.
Published: September 2016

We investigate the strong warm bias in sea surface temperatures (SST) of the southeastern tropical Atlantic that occurs in most of the current global climate models. We analyze this bias in the Max Planck Institute Earth System Model at different horizontal resolutions ranging from 0.1° to 0.4° in the ocean and 0.5° to 1.8° in the atmosphere. High atmospheric horizontal resolution eliminates the SST bias close to the African coast, due to an improved representation of surface wind stress near the coast. This improvement affects coastal upwelling and horizontal ocean circulation, as confirmed with dedicated sensitivity experiments. The wind stress improvements are partly caused by the better represented orography at higher horizontal resolution in the spectral atmospheric model. The reductions of the coastal SST bias obtained through higher horizontal resolution do not, however, translate to a reduction of the large‐scale bias extending westward from the African coast into the southeastern tropical Atlantic.
Frictional evolution, acoustic emissions activity, and off‐fault damage in simulated faults sheared at seismic slip rates
Authors: Passelègue François. X. , Spagnuolo Elena , Violay Marie , Nielsen Stefan , Di Toro Giulio , Schubnel Alexandre
Published: September 2016

We present a series of high‐velocity friction tests conducted on Westerly granite, using the Slow to HIgh Velocity Apparatus (SHIVA) installed at Istituto Nazionale di Geofisica e Vulcanologia Roma with acoustic emissions (AEs) monitored at high frequency (4 MHz). Both atmospheric humidity and pore fluid (water) pressure conditions were tested, under effective normal stress
in the range 5–20 MPa and at target sliding velocities Vs in the range 0.003–3 m/s. Under atmospheric humidity two consecutive friction drops were observed. The first one is related to flash weakening, and the second one to the formation and growth of a continuous layer of melt in the slip zone. In the presence of fluid, a single drop in friction was observed. Average values of fracture energy are independent of effective normal stress and sliding velocity. However, measurements of elastic wave velocities on the sheared samples suggested that larger damage was induced for 0.1 < Vs<0.3 m/s. This observation is supported by AEs recorded during the test, most of which were detected after the initiation of the second friction drop, once the fault surface temperature was high. Some AEs were detected up to a few seconds after the end of the experiments, indicating thermal rather than mechanical cracking. In addition, the presence of pore water delayed the onset of AEs by cooling effects and by reducing of the heat produced, supporting the link between AEs and the production and diffusion of heat during sliding. Using a thermoelastic crack model developed by Fredrich and Wong (1986), we confirm that damage may be induced by heat diffusion. Indeed, our theoretical results predict accurately the amount of shortening and shortening rate, supporting the idea that gouge production and gouge comminution are in fact largely controlled by thermal cracking. Finally, we discuss the contribution of thermal cracking in the seismic energy balance. In fact, while a dichotomy exists in the literature regarding the partitioning between fracture and heat energy, the experimental evidence reported here suggests that both contribute to fault weakening and off‐fault damage.
3‐D multiobservable probabilistic inversion for the compositional and thermal structure of the lithosphere and upper mantle: III. Thermochemical tomography in the Western‐Central U.S.
Authors: Afonso Juan Carlos , Rawlinson Nicholas , Yang Yingjie , Schutt Derek L. , Jones Alan G. , Fullea Javier , Griffin William L.
Published: September 2016

We apply a novel 3‐D multiobservable probabilistic tomography method that we have recently developed and benchmarked, to directly image the thermochemical structure of the Colorado Plateau and surrounding areas by jointly inverting P wave and S wave teleseismic arrival times, Rayleigh wave dispersion data, Bouguer anomalies, satellite‐derived gravity gradients, geoid height, absolute (local and dynamic) elevation, and surface heat flow data. The temperature and compositional structures recovered by our inversion reveal a high level of correlation between recent basaltic magmatism and zones of high temperature and low Mg# (i.e., refertilized mantle) in the lithosphere, consistent with independent geochemical data. However, the lithospheric mantle is overall characterized by a highly heterogeneous thermochemical structure, with only some features correlating well with either Proterozoic and/or Cenozoic crustal structures. This suggests that most of the present‐day deep lithospheric architecture reflects the superposition of numerous geodynamic events of different scale and nature to those that created major crustal structures. This is consistent with the complex lithosphere‐asthenosphere system that we image, which exhibits a variety of multiscale feedback mechanisms (e.g., small‐scale convection, magmatic intrusion, delamination, etc.) driving surface processes. Our results also suggest that most of the present‐day elevation in the Colorado Plateau and surrounding regions is the result of thermochemical buoyancy sources within the lithosphere, with dynamic effects (from sublithospheric mantle flow) contributing only locally up to ∼15–35%.
Wind relaxation and a coastal buoyant plume north of Pt. Conception, CA: Observations, simulations, and scalings
Authors: Suanda Sutara H. , Kumar Nirnimesh , Miller Arthur J. , Di Lorenzo Emanuele , Haas Kevin , Cai Donghua , Edwards Christopher A. , Washburn Libe , Fewings Melanie R. , Torres Rachel , Feddersen Falk
Published: September 2016

In upwelling regions, wind relaxations lead to poleward propagating warm water plumes that are important to coastal ecosystems. The coastal ocean response to wind relaxation around Pt. Conception, CA is simulated with a Regional Ocean Model (ROMS) forced by realistic surface and lateral boundary conditions including tidal processes. The model reproduces well the statistics of observed subtidal water column temperature and velocity at both outer and inner‐shelf mooring locations throughout the study. A poleward‐propagating plume of Southern California Bight water that increases shelf water temperatures by
5°C is also reproduced. Modeled plume propagation speed, spatial scales, and flow structure are consistent with a theoretical scaling for coastal buoyant plumes with both surface‐trapped and slope‐controlled dynamics. Plume momentum balances are distinct between the offshore (>30 m depth) region where the plume is surface‐trapped, and onshore of the 30 m isobath (within 5 km from shore) where the plume water mass extends to the bottom and is slope controlled. In the onshore region, bottom stress is important in the alongshore momentum equation and generates vertical vorticity that is an order of magnitude larger than the vorticity in the plume core. Numerical experiments without tidal forcing show that modeled surface temperatures are biased 0.5°C high, potentially affecting plume propagation distance and persistence.
Effective Polysulfide Rejection by Dipole‐Aligned BaTiO3 Coated Separator in Lithium–Sulfur Batteries
Authors: Yim Taeeun , Han Seung Ho , Park Nam Hwan , Park Min‐Sik , Lee Ji Hoon , Shin Jaeho , Choi Jang Wook , Jung Yongju , Jo Yong Nam , Yu Ji‐Sang , Kim Ki Jae
Published: September 2016

Although the exceptional theoretical specific capacity (1672 mAh g−1) of elemental sulfur makes lithium–sulfur (Li–S) batteries attractive for upcoming rechargeable battery applications (e.g., electrical vehicles, drones, unmanned aerial vehicles, etc.), insufficient cycle lives of Li–S cells leave a substantial gap before their wide penetration into commercial markets. Among the key features that affect the cyclability, the shuttling process involving polysulfides (PS) dissolution is most fatal. In an effort to suppress this chronic PS shuttling, herein, a separator coated with poled BaTiO3 or BTO particles is introduced. Permanent dipoles that are formed in the BTO particles upon the application of an electric field can effectively reject PS from passing through the separator via electrostatic repulsion, resulting in significantly improved cyclability, even when a simple mixture of elemental sulfur and conductive carbon is used as a sulfur cathode. The coating of BTO particles also considerably suppresses thermal shrinkage of the poly(ethylene) separator at high temperatures and thus enhances the safety of the cell adopting the given separator. The incorporation of poled particles can be universally applied to a wide range of rechargeable batteries (i.e., metal‐air batteries) that suffer from cross‐contamination of charged species between both electrodes.
Thermally Activated Delayed Fluorescence Material as Host with Novel Spiro‐Based Skeleton for High Power Efficiency and Low Roll‐Off Blue and White Phosphorescent Devices
Authors: Wang Ya‐Kun , Sun Qi , Wu Sheng‐Fan , Yuan Yi , Li Qian , Jiang Zuo‐Quan , Fung Man‐Keung , Liao Liang‐Sheng
Published: September 2016

Efficiency roll‐off in blue organic light‐emitting diodes especially at high brightness still remains a vital issue for which the excitons density‐dependent mechanism of host materials takes most responsibility. Additionally, the efficiency roll‐off leads to high power consumption and reduces the operating lifetime because higher driving voltage and current are required. Here, by subtly modifying the triphenylamine to oxygen‐bridged quasi‐planar structure, a novel thermally activated delayed fluorescence type blue host Tri‐o‐2PO is successfully developed. Efficiency roll‐off based on Tri‐o‐2PO is ultralow with external quantum efficiency (EQE) just dropping by around 2% in the high luminance range from 1000 cd m−2 to 10 000 cd m−2. As expected, low turn‐on voltage (≈2.9 V) of device is also achieved, which is close to the theory limit value (≈2.62 V). Super‐high power efficiency (≈60 lm W−1) and EQE (>22%) are also achieved when utilizing Tri‐o‐2PO as host. Furthermore, two‐color warm‐white light with CIE of (0.45, 0.43) and correlated color temperature of 2921 K is also fabricated and a champion EQE of 21% is delivered. These excellent performances prove the strategy of bridging the triphenylamine to reduce ΔEst is validated and suggest the great potential of this novel skeleton.
Controllable Synthesis of 2D and 1D MoS2 Nanostructures on Au Surface
Authors: Xu Hai , Ding Zijing , Nai Chang Tai , Bao Yang , Cheng Fang , Tan Sherman J. R. , Loh Kian Ping
Published: September 2016

A bottom‐up growth approach based on the assembly of binary atomic constituents delivers precise control over the edge termination and dimensions of nanostructures. Here, the dimensional crossover of MoS2 from 1D nanoribbons to 2D islands synthesized by the assembly of Mo and S atoms on Au(100) surface is studied. Low‐temperature scanning tunneling microscopy and in situ Q‐plus non‐contact atomic force microscopy are employed to elucidate the edge structure of MoS2 nanoribbons at the atomic scale, where three types of zigzag Mo‐edges with different sulfur terminations are observed. It is found that the thermodynamic instability of the armchair edges causes the 1D system to develop faceted zigzag edges which manifests in the morphological evolution from 1D ribbons to 2D triangles as the system size increases.
Improvement of Lithium Storage Performance of Molybdenum Trioxide by a Synergistic Effect of Surface Coating and Oxygen Vacancies
Authors: Yang Chenglong , Liu Xiaowu , Yang Zhenzhong , Gu Lin , Yu Yan
Published: September 2016

3D hierarchical flower‐like carbon coated MoO3−x nanosheets (denoted as MoO3−x NS@C) have been successfully fabricated by a simple hydrothermal method. When used as anode for Li‐ion batteries, the MoO3−x NS@C electrode exhibits excellent cycle performance and outstanding rate capabilities. The charge capacity can reach 1025 mAh g−1 over 150 cycles, and 62% of the charge capacity is retained when the current density increases to 2000 mA g−1. The improved lithium storage performance of MoO3−x NS@C is attributed to the synergistic effect of oxygen vacancies and the carbon coating, which not only enhance the electric conductivity and Li‐ion diffusion coefficient but also lead to superior structural stability and cyclability of the MoO3−x NS@C electrode during repeated lithiation/delithiation process.
Synthesis of Chiral Dihydrobenzofurans and Phthalides by Asymmetric Transfer Hydrogenation via Dynamic Kinetic Resolution: A Strategy for Total Synthesis of Daldinins A, B, and C and Concentricolide
Authors: Fang Lizhen , Lyu Qinghua , Lu Chenjuan , Li Huanhuan , Liu Saisai , Han Lili
Published: September 2016

A versatile and efficient strategy for the total synthesis of the anti‐HIV‐1 agent concentricolide and its analogues daldinins A, B, and C has been established. This strategy offers a mild and facile access to these benzo annulated compounds, bearing multiple stereocenters in good yield with 99% enantiomeric excess (ee) and 93% diastereomeric excess (de) values. Construction of the corresponding syn dihydrobenzofuran and phthalide groups can be achieved in one step by Noyori's asymmetric transfer hydrogenation, via dynamic kinetic resolution.

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Influence of Date Syrup as a Carbon Source on Bacterial Cellulose Production by Acetobacter xylinum 0416
Authors: Lotfiman Samaneh , Awang Biak Dayang Radiah , Ti Tey Beng , Kamarudin Suryani , Nikbin Saeid
Published: September 2016

To improve bacterial cellulose (BC) applications, researchers have expanded their efforts with BC productivity and its properties. The objectives of this study are to evaluate the possibility and efficacy of using extracted date syrup as a carbon source for Acetobacter xylinum 0416 in BC production in a static culture. The sugar content of extracted date syrup was identified by HPLC. Different concentrations of dates and different culturing times were tested. The produced BCs were characterized and their respective properties were compared with a BC produced from Hestrin and Schramm (HS) medium. The most effective BC amount was attained with 3% (w/v) date in the medium on day 8. The modified HS medium (DHS) increased production by 68% (P < 0.05). Morphological analysis by scanning electron microscopy revealed more disorganized arrangements in BC fiber obtained from DHS medium (BC‐DHS) than that from HS medium (BC‐HS). Thermogravimetric analysis revealed no significant changes in BC‐DHS thermostability compared to BC‐HS. However, the crystallinity of BC‐DHS improved (P < 0.05). The results of Fourier transform infrared spectroscopy demonstrated that the carbonyl group in BC‐DHS is more active than that of BC‐HS. Furthermore, the properties of BC‐DHS showed excellent potential for use in many applications.
Biochemical surrogate markers of hemolysis do not correlate with directly measured erythrocyte survival in sickle cell anemia
Authors: Quinn Charles T. , Smith Eric P. , Arbabi Shahriar , Khera Paramjit K. , Lindsell Christopher J. , Niss Omar , Joiner Clinton H. , Franco Robert S. , Cohen Robert M.
Published: September 2016

Hemolysis is a key feature of sickle cell anemia (HbSS). Direct quantitation of hemolysis could be used as an objective outcome in clinical trials of new therapeutics for HbSS and would also enable better human studies of the pathogenesis of complications of HbSS that are ostensibly hemolysis‐related, such as pulmonary hypertension. However, contemporary human studies in HbSS have used only surrogate markers of hemolysis rather than direct measurements of RBC survival. We directly quantified hemolysis in HbSS by measuring survival of an age cohort of RBCs labeled with a stable isotope, administered orally as 15N‐glycine, a metabolic precursor of heme. The atomic excess of 15N in heme extracted from blood was monitored by mass spectrometry over time. We performed 13 labeling experiments in 11 individuals with HbSS. Mean RBC survival was 31.9 days (range 14.1–53.6). Both HbF level, a known determinant of hemolysis, and absolute reticulocyte count (ARC), an index of the marrow's response to hemolysis, correlated with directly measured RBC survival (r = 0.61, P < 0.002; r = −0.84, P < 0.001). However, commonly used biochemical surrogates of hemolysis (LDH, AST, bilirubin, and plasma free hemoglobin) did not correlate with directly measured RBC survival. These biochemical surrogates should be interpreted cautiously, at best, in clinical trials and human physiologic studies in HbSS. ARC was the best correlate of total hemolysis, but only 70% of the variation in RBC survival was reflected in this marker. If greater accuracy is required in human studies, 15N‐glycine RBC labeling can directly and accurately quantify hemolysis. Am. J. Hematol. 91:1195–1201, 2016. © 2016 Wiley Periodicals, Inc.
A Quantitative Fluorescence‐Based Assay for Assessing LIM Domain–Peptide Interactions
Authors: Robertson Neil O. , Shah Manan , Matthews Jacqueline M.
Published: September 2016

We have developed Förster resonance energy transfer (FRET)‐based experiments for measuring the binding affinity, off‐rates, and inferred on‐rates for interactions between a family of transcriptional regulators and their intrinsically disordered binding partners. It was difficult to evaluate these interactions previously, as the transcriptional regulators are obligate binding proteins that aggregate in the absence of a binding partner. The assays rely on fusion constructs where binding domains are linked by a flexible tether containing a specific protease site, with fluorescent proteins at either end that display FRET when the complex is formed. Loss of FRET is monitored after cutting the tether followed by dilution or competition with a non‐fluorescent peptide. These methods allowed a wide range of binding affinities (10−9–10−5 m) to be determined. Our data indicate that interactions of closely related proteins can have surprisingly different binding properties.
Polarity‐Reversed Allylations of Aldehydes, Ketones, and Imines Enabled by Hantzsch Ester in Photoredox Catalysis
Authors: Qi Li , Chen Yiyun
Published: September 2016

The polarity reversal (umpolung) reaction is an invaluable tool for reversing the chemical reactivity of carbonyl and iminyl groups, which subsequent cross‐coupling reactions to form C−C bonds offers a unique perspective in synthetic planning and implementation. Reported herein is the first visible‐light‐induced polarity‐reversed allylation and intermolecular Michael addition reaction of aldehydes, ketones, and imines. This chemoselective reaction has broad substrate scope and the engagement of alkyl imines is reported for the first time. The mechanistic investigations indicate the formation of ketyl (or α‐aminoalkyl) radicals from single‐electron reduction, where the Hantzsch ester is crucial as the electron/proton donor and the activator.
Gene expression of glycyrrhizin acid and accumulation of endogenous signaling molecule in Glycyrrhiza uralensis Fisch adventitious roots after Saccharomyces cerevisiae and Meyerozyma guilliermondii applications
Authors: Li Jianli , Liu Shujie , Wang Juan , Li Jing , Li Jinxin , Gao Wenyuan
Published: September 2016

This study reports the best culture conditions for roots growth and accumulation of active components by optimizing the parameters. Glycyrrhiza uralensis adventitious roots metabolites were significantly increased after adding Saccharomyces cerevisiae and Meyerozyma guilliermondii. The highest contents of polysaccharide, glycyrrhizic acid, glycyrrhetinic acid, and total flavonoids were obtained in M. guilliermondii group; the content of glycyrrhizic acid was 5.3‐fold higher than the control. In control and treatment groups, 12 compounds were identified by high‐performance liquid chromatography–electrospray ionization–tandem mass spectrometry (HPLC–ESI–MS/MS), among which some new compounds have been detected in elicitor groups including 5,7‐dihydroxyflavanone, glycyrrhisoflavanone, licorice saponin J2, uralsaponin B, (3R)‐vestitol, and uralenol. Meyerozyma guilliermondii significantly upregulated the expression of the genes such as 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase, farnesyl diphosphate synthase, geranyl diphosphate synthase, squalene synthase, squalene epoxidase, β‐amyrin synthase, and CYP88D6 and CYP72A154. Meanwhile, it increased the biosynthesis of signaling molecules (nitric oxide, salicylic acid, and jasmonic acid) in defense mechanism.
Stimuli‐responsive delivery of therapeutics for diabetes treatment
Authors: Yu Jicheng , Zhang Yuqi , Bomba Hunter , Gu Zhen
Published: September 2016

Diabetic therapeutics, including insulin and glucagon‐like peptide 1 (GLP‐1), are essential for diabetic patients to regulate blood glucose levels. However, conventional treatments that are based on subcutaneous injections are often associated with poor glucose control and a lack of patient compliance. In this review, we focus on the different stimuli‐responsive systems to deliver therapeutics for diabetes treatment to improve patient comfort and prevent complications. Specifically, the pH‐responsive systems for oral drug delivery are introduced first. Then, the closed‐loop glucose‐responsive systems are summarized based on different glucose‐responsive moieties, including glucose oxidase, glucose binding protein, and phenylboronic acid. Finally, the on‐demand delivery systems activated by external remote triggers are also discussed. We conclude by discussing advantages and limitations of current strategies, as well as future opportunities and challenges in this area.
Light‐Activated Triazabutadienes for the Modification of a Viral Surface
Authors: Jensen Stephanie M. , Kimani Flora W. , Jewett John C.
Published: September 2016

Chemical crosslinking is a versatile tool for the examination of biochemical interactions, in particular host–pathogen interactions. We report the critical first step toward the goal of probing these interactions by the synthesis and use of a new heterobifunctional crosslinker containing a triazabutadiene scaffold. The triazabutadiene is stable to protein conjugation and liberates a reactive aryl diazonium species upon irradiation with 350 nm light. We highlight the use of this technology by modifying the surface of several proteins, including the dengue virus envelope protein.
Catalytic Aerial Oxidation of Biomass‐Derived Furans to Furan Carboxylic Acids in Water over Bimetallic Nickel–Palladium Alloy Nanoparticles
Authors: Gupta Kavita , Rai Rohit K. , Dwivedi Ambikesh D. , Singh Sanjay K.
Published: September 2016

Bimetallic Ni1−xPdx (0.10≤x≤0.75) alloy nanoparticle catalysts were synthesised and successfully employed for the catalytic aerial oxidation of biomass‐derived furans, such as 2‐furfuraldehyde (furfural), 2‐furfuryl alcohol (furfuryl alcohol), 5‐hydroxymethyl‐2‐furfural (5‐HMF), 5‐methyl‐2‐furfural (MF) and 5‐methyl‐2‐furfuryl alcohol (MFA), to selectively afford the corresponding furan carboxylic acids (2‐furoic acid, furan‐2,5‐dicarboxylic acid (FDCA) and 5‐methyl‐2‐furoic acid (MFCA)) in water at 80 °C. Among the studied Ni1−xPdx nanoparticle catalysts, Ni0.90Pd0.10 nanoparticle catalyst outperformed the others, achieving high yields of the corresponding furan carboxylic acid products. The presence of Ni in the Ni1−xPdx nanoparticle catalysts was advantageous, because it not only enhanced the catalytic activity for the facile oxidation of biomass‐derived furans using aerial oxygen to achieve high catalytic turnover, but also provided excellent stability to the Ni0.90Pd0.10 nanoparticle catalyst towards air and water and thus significantly enhanced its recyclability (up to 10 catalytic runs). The experiments revealed that the catalytic oxidation of 5‐HMF proceeded by the initial oxidation of the formyl group to carboxylic acid, and, subsequently, the conversion of alcohol to carboxylic acid via the formyl group to form FDCA. Moreover, the one‐pot direct transformation of fructose to furan carboxylic acid products (such as FDCA) was also achieved by using the Ni0.90Pd0.10 nanoparticle catalyst.
Coupling the Charging Current and the Electron‐Transfer Process: The Effect on Impedance Spectra
Authors: Du Guoqing , Mantia Fabio La
Published: September 2016

By using a 1D simulation of the charge‐transfer process, taking into account the nature of the electron‐tunnelling and the effect of the electric field in the double layer, we analysed the coupling between double layer charging and faradaic reaction and assessed how this influences the shape of impedance spectra simulated under equilibrium conditions for a redox couple. We carried out the simulations with different concentrations of redox couple and supporting electrolyte at different equilibrium potential. We observed that, independent of the conditions of the simulation, all the data sets could be fitted by a simple Randles circuit. Our results show that the coupling process of faradaic and charging currents is manifested as a deviation of the behaviour of the charge transfer and interface differential capacitance from the expected values; in particular, we show that the electric field affects very strongly the charge transfer resistance, and also that the charge accumulated on the double layer is affected by the electron‐transfer.
Calorimetric Studies and Structural Aspects of Ionic Liquids in Designing Sorption Materials for Thermal Energy Storage
Authors: Brünig Thorge , Krekić Kristijan , Bruhn Clemens , Pietschnig Rudolf
Published: September 2016

The thermal properties of a series of twenty‐four ionic liquids (ILs) have been determined by isothermal titration calorimetry (ITC) with the aim of simulating processes involving water sorption. For eleven water‐free ILs, the molecular structures have been determined by X‐ray crystallography in the solid state, which have been used to derive the molecular volumes of the ionic components of the ILs. Moreover, the structures reveal a high prevalence of hydrogen bonding in these compounds. A relationship between the molecular volumes and the experimentally determined energies of dilution could be established. The highest energies of dilution observed in this series were obtained for the acetate‐based ILs, which underlines their potential as working fluids in sorption‐based thermal energy storage systems.
Enzalutamide in castration‐resistant prostate cancer patients with visceral disease in the liver and/or lung: Outcomes from the randomized controlled phase 3 AFFIRM trial
Authors: Loriot Yohann , Fizazi Karim , de Bono Johann S. , Forer David , Hirmand Mohammad , Scher Howard I.
Published: September 2016

BACKGROUND

Patients with metastatic castration‐resistant prostate cancer (mCRPC) and visceral metastases have a worse prognosis than those with nonvisceral metastases. Treatment with the androgen receptor inhibitor enzalutamide in the phase 3 AFFIRM trial led to significant improvements in outcomes for patients with mCRPC. For the current report, the authors analyzed the efficacy of enzalutamide among patients from the AFFIRM trial who had visceral disease.

METHODS

Patients who had liver and/or lung metastases at baseline were selected for prespecified overall survival (OS) and exploratory post hoc analyses, including prostate‐specific antigen (PSA) response and the time to PSA and radiographic progression.

RESULTS

In patients who had liver metastases (n = 92), enzalutamide was associated with a lower risk of radiographic progression (hazard ratio [HR], 0.645; 95% confidence interval [CI], 0.413‐1.008), improved 12‐month OS (37.7% vs 20.6%) and radiographic progression‐free survival (rPFS) (11.6% vs 3.0%) rates, and higher PSA response rates (35.1% vs 4.8%) compared with placebo. Enzalutamide‐treated patients who had lung metastases (n = 104) had improved median OS (HR, 0.848; 95% CI, 0.510‐1.410), a substantially reduced risk of radiographic progression (HR, 0.386; 95% CI, 0.259‐0.577), improved 12‐month OS (65.1% vs 55.3%) and rPFS (30.9% vs 8.2%) rates, increased time to PSA progression (HR, 0.358; 95% CI, 0.204‐0.627), and a better PSA response rate (52.1% vs 4.9%) compared with those who received placebo. No increase in treatment‐related adverse events was observed for the visceral metastases cohort compared with the nonvisceral metastases cohort.

CONCLUSIONS

Across multiple endpoints, patients who have visceral metastases have better outcomes with enzalutamide than with placebo. Cancer 2017;123:253–262. © 2016 American Cancer Society.
Antiangiogenic agents in head and neck squamous cell carcinoma: Tired of going solo
Authors: Chau Nicole G. , Haddad Robert I.
Published: September 2016

Antiangiogenic therapies as single agents have failed to demonstrate significant antitumor activity in heavily pretreated, unselected populations with recurrent/metastatic head and neck squamous cell carcinoma. Much work is needed to evaluate rational strategies for combining antiangiogenic agents with other systemic therapies or with radiotherapy for head and neck squamous cell carcinoma to move the field forward. See also pages 3641‐9.
Computational Study of the Interactions between Benzene and Crystalline Ice Ih: Ground and Excited States
Authors: Sharma Divya , Sameera W. M. C. , Andersson Stefan , Nyman Gunnar , Paterson Martin J.
Published: September 2016

Ground‐state geometries of benzene on crystalline ice cluster model surfaces (Ih) are investigated. It is found that the binding energies of benzene‐bound ice complexes are sensitive to the dangling features of the binding sites. We used time‐dependent DFT to study the UV spectroscopy of benzene, ice clusters, and benzene–ice complexes, by employing the M06‐2X functional. It is observed that the size of the ice cluster and the dangling features have minor effects on the UV spectral characteristics. Benzene‐mediated electronic excitations of water towards longer wavelengths (above 170 nm) are noted in benzene‐bound ice clusters, where the cross‐section of photon absorption by water is negligible, in good agreement with recent experimental results (Thrower et al., J. Vac. Sci. Technol. A, 2008, 26, 919–924). The intensities of peaks associated with water excitations in benzene–ice complexes are found to be higher than in isolated ice clusters. The π→π* electronic transition of benzene in benzene–ice complexes undergoes a small redshift compared with the isolated benzene molecule, and this holds for all benzene‐bound ice complexes.
Compression and the origins of Zipf's law for word frequencies
Authors: Ferrer‐i‐Cancho Ramon
Published: September 2016

Here we sketch a new derivation of Zipf's law for word frequencies based on optimal coding. The structure of the derivation is reminiscent of Mandelbrot's random typing model but it has multiple advantages over random typing: (1) it starts from realistic cognitive pressures, (2) it does not require fine tuning of parameters, and (3) it sheds light on the origins of other statistical laws of language and thus can lead to a compact theory of linguistic laws. Our findings suggest that the recurrence of Zipf's law in human languages could originate from pressure for easy and fast communication. © 2016 Wiley Periodicals, Inc. Complexity 21: 409–411, 2016
Transporter‐Mediated Hepatic Uptake Plays an Important Role in the Pharmacokinetics and Drug–Drug Interactions of Montelukast
Authors: Varma MV , Kimoto E , Scialis R , Bi Y , Lin J , Eng H , Kalgutkar AS , El‐Kattan AF , Rodrigues AD , Tremaine LM
Published: September 2016

Montelukast, a leukotriene receptor antagonist commonly prescribed for treatment of asthma, is primarily metabolized by cytochrome P450 (CYP)2C8, and has been suggested as a probe substrate for investigating CYP2C8 activity in vivo. We evaluated the quantitative role of hepatic uptake transport in its pharmacokinetics and drug–drug interactions (DDIs). Montelukast was characterized with significant active uptake in human hepatocytes, and showed affinity towards organic anion transporting polypeptides (OATPs) in transfected cell systems. Single‐dose rifampicin, an OATP inhibitor, decreased montelukast clearance in rats and monkeys. Clinical DDIs of montelukast were evaluated using physiologically based pharmacokinetic modeling; and simulation of the interactions with gemfibrozil–CYP2C8 and OATP1B1/1B3 inhibitor, clarithromycin–CYP3A and OATP1B1/1B3 inhibitor, and itraconazole–CYP3A inhibitor, implicated OATPs‐CYP2C8‐CYP2C8 interplay as the primary determinant of montelukast pharmacokinetics. In conclusion, hepatic uptake plays a key role in the pharmacokinetics of montelukast, which should be taken into account when interpreting clinical interactions.
Essential competencies in prescribing: A first european cross‐sectional study among 895 final‐year medical students
Authors: Brinkman DJ , Tichelaar J , Schutte T , Benemei S , Böttiger Y , Chamontin B , Christiaens T , Likic R , Maˇiulaitis R , Marandi T , Monteiro EC , Papaioannidou P , Pers YM , Pontes C , Raskovic A , Regenthal R , Sanz EJ , Tamba BI , Wilson K , Vries TP de , Richir MC , Agtmael MA van ,   on behalf of the Working Group Research on CPT Education of the European Association for Clinical Pharmacology and Therapeutics (EACPT)
Published: September 2016

European medical students should have acquired adequate prescribing competencies before graduation, but it is not known whether this is the case. In this international multicenter study, we evaluated the essential knowledge, skills, and attitudes in clinical pharmacology and therapeutics (CPT) of final‐year medical students across Europe. In a cross‐sectional design, 26 medical schools from 17 European countries were asked to administer a standardized assessment and questionnaire to 50 final‐year students. Although there were differences between schools, our results show an overall lack of essential prescribing competencies among final‐year students in Europe. Students had a poor knowledge of drug interactions and contraindications, and chose inappropriate therapies for common diseases or made prescribing errors. Our results suggest that undergraduate teaching in CPT is inadequate in many European schools, leading to incompetent prescribers and potentially unsafe patient care. A European core curriculum with clear learning outcomes and assessments should be urgently developed.
Cannabinoid disposition in oral fluid after controlled smoked, vaporized, and oral cannabis administration
Authors: Swortwood Madeleine J. , Newmeyer Matthew N. , Andersson Maria , Abulseoud Osama A. , Scheidweiler Karl B. , Huestis Marilyn A.
Published: September 2016

Oral fluid (OF) is an important matrix for monitoring drugs. Smoking cannabis is common, but vaporization and edible consumption also are popular. OF pharmacokinetics are available for controlled smoked cannabis, but few data exist for vaporized and oral routes. Frequent and occasional cannabis smokers were recruited as participants for four dosing sessions including one active (6.9% Δ9‐tetrahydrocannabinol, THC) or placebo cannabis‐containing brownie, followed by one active or placebo cigarette, or one active or placebo vaporized cannabis dose. Only one active dose was administered per session. OF was collected before and up to 54 (occasional) or 72 (frequent) h after dosing from cannabis smokers. THC, 11‐hydroxy‐THC (11‐OH‐THC), 11‐nor‐9‐carboxy‐THC (THCCOOH), tetrahydrocannabivarin (THCV), cannabidiol (CBD), and cannabigerol (CBG) were quantified by liquid chromatography‐tandem mass spectrometry. OF cannabinoid Cmax occurred during or immediately after cannabis consumption due to oral mucosa contamination. Significantly greater THC Cmax and significantly later THCV, CBD, and CBG tlast were observed after smoked and vaporized cannabis compared to oral cannabis in frequent smokers only. No significant differences in THC, 11‐OH‐THC, THCV, CBD, or CBG tmax between routes were observed for either group. For occasional smokers, more 11‐OH‐THC and THCCOOH‐positive specimens were observed after oral dosing than after inhaled routes, increasing % positive cannabinoid results and widening metabolite detection windows after oral cannabis consumption. Utilizing 0.3 µg/L THCV and CBG cut‐offs resulted in detection windows indicative of recent cannabis intake. OF pharmacokinetics after high potency CBD cannabis are not yet available precluding its use currently as a marker of recent use. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.
Genotype‐dependent metabolism of exogenous testosterone – new biomarkers result in prolonged detectability
Authors: Piper Thomas , Schänzer Wilhelm , Thevis Mario
Published: September 2016

Testosterone (T) misuse still represents a major problem in sports drug testing. Many strategies have been developed and applied to routine doping controls in recent years to enable both to identify suspicious samples in initial testing procedures and to confirm the exogenous origin of urinary T by means of carbon isotope ratio (CIR) determinations. Depending on the tested individual's genotype of UGT2B17, significantly different amounts of T are glucuronidated and excreted, which results in unaffected T/epitestosterone ratios after T misuse in those subjects with the deletion/deletion polymorphism (del/del). The aim of this study was to investigate differences in metabolic pathways of orally administered T between persons of del/del and insertion/insertion (ins/ins) genetic polymorphism. Therefore, a recently established method using hydrogen isotope ratios together with high‐resolution and high‐accuracy mass spectrometry was applied after administration of deuterated T to n = 4 subjects including both genotypes. Participants collected urine specimens directly before and for up to 8 days after the application. Urine aliquots were prepared to yield unconjugated, glucuronidated, and sulphoconjugated fractions of urinary steroids. Besides the significant difference in the excretion of T‐glucuronide, all measured metabolites varied rather on an individual basis than due to a genotype difference. New T metabolites (both methylated and de‐methylated) were detected and investigated regarding their potential to enhance the screening for T misuse. Sulphoconjugated epiandrosterone was further identified as the biomarker allowing for a prolonged retrospective detection of T misuse by means of CIR determinations for up to 5 days compared to 1 day if currently applied sports drug testing procedures were used. Copyright © 2016 John Wiley & Sons, Ltd.
Head regeneration in hemichordates is not a strict recapitulation of development
Authors: Luttrell Shawn M. , Gotting Kirsten , Ross Eric , Alvarado Alejandro Sánchez , Swalla Billie J.
Published: September 2016

Background: Head or anterior body part regeneration is commonly associated with protostome, but not deuterostome invertebrates. However, it has been shown that the solitary hemichordate Ptychodera flava possesses the remarkable capacity to regenerate their entire nervous system, including their dorsal neural tube and their anterior head‐like structure, or proboscis. Hemichordates, also known as acorn worms, are marine invertebrate deuterostomes that have retained chordate traits that were likely present in the deuterostome ancestor, placing these animals in a vital position to study regeneration and chordate evolution. All acorn worms have a tripartite body plan, with an anterior proboscis, middle collar region, and a posterior trunk. The collar houses a hollow, dorsal neural tube in ptychoderid hemichordates and numerous chordate genes involved in brain and spinal cord development are expressed in a similar anterior–posterior spatial arrangement along the body axis. Results: We have examined anterior regeneration in the hemichordate Ptychodera flava and report the spatial and temporal morphological changes that occur. Additionally, we have sequenced, assembled, and analyzed the transcriptome for eight stages of regenerating P. flava, revealing significant differential gene expression between regenerating and control animals. Conclusions: Importantly, we have uncovered developmental steps that are regeneration‐specific and do not strictly follow the embryonic program. Developmental Dynamics 245:1159–1175, 2016. © 2016 The Authors. Developmental Dynamics published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists
Myocardial iron content and mitochondrial function in human heart failure: a direct tissue analysis
Authors: Melenovsky Vojtech , Petrak Jiri , Mracek Tomas , Benes Jan , Borlaug Barry A. , Nuskova Hana , Pluhacek Tomas , Spatenka Jaroslav , Kovalcikova Jana , Drahota Zdenek , Kautzner Josef , Pirk Jan , Houstek Josef
Published: September 2016

Aims

Iron replacement improves clinical status in iron‐deficient patients with heart failure (HF), but the pathophysiology is poorly understood. Iron is essential not only for erythropoiesis, but also for cellular bioenergetics. The impact of myocardial iron deficiency (MID) on mitochondrial function, measured directly in the failing human heart, is unknown.

Methods and results

Left ventricular samples were obtained from 91 consecutive HF patients undergoing transplantation and 38 HF‐free organ donors (controls). Total myocardial iron content, mitochondrial respiration, citric acid cycle and respiratory chain enzyme activities, respiratory chain components (complex I–V), and protein content of reactive oxygen species (ROS)‐protective enzymes were measured in tissue homogenates to quantify mitochondrial function. Myocardial iron content was lower in HF compared with controls (156 ± 41 vs. 200 ± 38 µg·g−1 dry weight, P < 0.001), independently of anaemia. MID (the lowest iron tercile in HF) was associated with more extensive coronary disease and less beta‐blocker usage compared with non‐MID HF patients. Compared with controls, HF patients displayed reduced myocardial oxygen2 respiration and reduced activity of all examined mitochondrial enzymes (all P < 0.001). MID in HF was associated with preserved activity of respiratory chain enzymes but reduced activity of aconitase and citrate synthase (by –26% and –15%, P < 0.05) and reduced expression of catalase, glutathione peroxidase, and superoxide dismutase 2.

Conclusion

Myocardial iron content is decreased and mitochondrial functions are impaired in advanced HF. MID in HF is associated with diminished citric acid cycle enzyme activities and decreased ROS‐protecting enzymes. MID may contribute to altered myocardial substrate use and to worsening of mitochondrial dysfunction that exists in HF.
Pulmonary artery pressure‐guided heart failure management: US cost‐effectiveness analyses using the results of the CHAMPION clinical trial
Authors: Martinson Melissa , Bharmi Rupinder , Dalal Nirav , Abraham William T. , Adamson Philip B.
Published: September 2016

Aims

Haemodynamic‐guided heart failure (HF) management effectively reduces decompensation events and need for hospitalizations. The economic benefit of clinical improvement requires further study.

Methods and results

An estimate of the cost‐effectiveness of haemodynamic‐guided HF management was made based on observations published in the randomized, prospective single‐blinded CHAMPION trial. A comprehensive analysis was performed including healthcare utilization event rates, survival, and quality of life demonstrated in the randomized portion of the trial (18 months). Markov modelling with Monte Carlo simulation was used to approximate comprehensive costs and quality‐adjusted life years (QALYs) from a payer perspective. Unit costs were estimated using the Truven Health MarketScan database from April 2008 to March 2013. Over a 5‐year horizon, patients in the Treatment group had average QALYs of 2.56 with a total cost of US$56 974; patients in the Control group had QALYs of 2.16 with a total cost of US$52 149. The incremental cost‐effectiveness ratio (ICER) was US$12 262 per QALY. Using comprehensive cost modelling, including all anticipated costs of HF and non‐HF hospitalizations, physician visits, prescription drugs, long‐term care, and outpatient hospital visits over 5 years, the Treatment group had a total cost of US$212 004 and the Control group had a total cost of US$200 360. The ICER was US$29 593 per QALY.

Conclusions

Standard economic modelling suggests that pulmonary artery pressure‐guided management of HF using the CardioMEMS™ HF System is cost‐effective from the US‐payer perspective. This analysis provides the background for further modelling in specific country healthcare systems and cost structures.
Lymph node biopsy analysis reveals an altered immunoregulatory balance already during the at‐risk phase of autoantibody positive rheumatoid arthritis
Authors: Ramwadhdoebe Tamara H. , Hähnlein Janine , Maijer Karen I. , van Boven Leonard J. , Gerlag Danielle M. , Tak Paul P. , van Baarsen Lisa G. M.
Published: September 2016

The balance between proinflammatory and regulatory CD4+ T cells is tightly controlled in lymphoid organs. In autoimmune diseases this balance is altered in the periphery and target tissue of patients. However, not much is known about the balance initiated in lymphoid organs during the development of disease. Since systemic autoimmunity is present years before the clinical manifestations of rheumatoid arthritis (RA), it is possible to study the immunoregulatory balance during the earliest (preclinical) phases of disease. Here, we report for the first time the frequency and phenotype of proinflammatory and regulatory CD4+ T cells in lymph node biopsies obtained from autoantibody positive individuals at risk for developing RA, patients with established disease and healthy controls. The frequency of proinflammatory LN Th1 cells was increased in RA patients compared with HCs, while the frequency of regulatory T cells was lower in LN biopsies of RA‐risk individuals. Upon in vitro stimulation LN CD4+ T cells produced lower levels of proinflammatory cytokines, IFN‐γ and IL‐17A, in both RA‐risk individuals and early RA patients. This study shows that already during the earliest phases of systemic autoimmunity the immunoregulatory balance between proinflammatory and regulatory CD4+ T cells is altered in LN tissue.