bluuebunny/crossref_metadata_2025 huggingface dataset:
Interstellar hydrogen ionization in the heliosheath
Authors: Gruntman Mike
Published: July 2015

The expanding solar wind plasma undergoes a shock transition at the interstellar boundary of the solar system and fills the inner heliosheath, the region between the termination shock and the heliopause. The nonequilibrium heliosheath plasma is a main source of energetic neutral atoms that allow remote probing of the heliospheric interface region. Global models of the heliosphere interaction with the interstellar medium often disregard solar photoionization and electron impact ionization of interstellar gas in the heliosheath. When ionization is included, it is commonly treated in a simplified manner and complexity of heliospheric interactions obscures its effect on the properties of the plasma. This work concentrates on physical estimates of ionization and shows that it may lead to significant mass loading of plasma flows in the heliosheath. In turn, mass loading would slow down plasma flows and deplete populations of nonthermal energetic protons. The magnitude of the effect depends on poorly understood and largely unknown energy transfer to electrons at the termination shock and beyond. The presented estimates show that inclusion of ionization is indispensable for global heliospheric modeling and for interpretation of heliosphere imaging in fluxes of energetic neutral atoms.
Recent Progress on Stability Enhancement for Cathode in Rechargeable Non‐Aqueous Lithium‐Oxygen Battery
Authors: Chang Zhi‐wen , Xu Ji‐jing , Liu Qing‐chao , Li Lin , Zhang Xin‐bo
Published: July 2015

The pressing demand on the electronic vehicles with long driving range on a single charge has necessitated the development of next‐generation high‐energy‐density batteries. Non‐aqueous Li‐O2 batteries have received rapidly growing attention due to their higher theoretical energy densities compared to those of state‐of‐the‐art Li‐ion batteries.To make them practical for commercial applications, many critical issues must be overcome, including low round‐trip efficiency and poor cycling stability, which are intimately connected to the problems resulting from cathode degradation during cycling. Encouragingly, during the past years, much effort has been devoted to enhancing the stability of the cathode using a variety of strategies and these have effectively surmounted the challenges derived from cathode deteriorations,thus endowing Li‐O2 batteries with significantly improved electrochemical performances. Here, a brief overview of the general development of Li‐O2 battery is presented. Then, critical issues relevant to the cathode instability are discussed and remarkable achievements in enhancing the cathode stability are highlighted. Finally, perspectives towards the development of next generation highly stable cathode are also discussed.
The Role of the NDQ Motif in Sodium‐Pumping Rhodopsins
Authors: Inoue Keiichi , Konno Masae , Abe‐Yoshizumi Rei , Kandori Hideki
Published: July 2015

Sodium‐pumping rhodopsins (NaRs) are light‐driven outward Na+ pumps. NaRs have a conserved Asn, Asp, and Gln motif (NDQ) in the third transmembrane helix (helix C). The NDQ motif is thus expected to play a crucial role in the operation of the Na+ pump. Herein, we studied the photocycles of the NDQ‐motif mutants of Krokinobacter rhodopsin 2 (KR2), the first discovered NaR, by flash photolysis, to obtain insight into the mechanism of Na+ transport. For example, the KR2 N112A mutant did not accumulate the transient red‐shifted Na+‐bound state, suggesting that Asn112 is vital for the binding of Na+ ions. Additionally, Q123A and Q123V mutants showed significantly slower Na+ uptake and recovery of the initial state. Overall, the Gln123 residue was found to contribute to the optimization of the kinetics of sodium‐ion uptake and release. These results demonstrate that the cooperative operation of the three residues of the NDQ motif are important in the operation of the Na+ pump.
Silicates as Latent Alkyl Radical Precursors: Visible‐Light Photocatalytic Oxidation of Hypervalent Bis‐Catecholato Silicon Compounds
Authors: Corcé Vincent , Chamoreau Lise‐Marie , Derat Etienne , Goddard Jean‐Philippe , Ollivier Cyril , Fensterbank Louis
Published: July 2015

This works introduces hypervalent bis‐catecholato silicon compounds as versatile sources of alkyl radicals upon visible‐light photocatalysis. Using Ir[(dF(CF3)ppy)2(bpy)](PF6) (dF(CF3)ppy=2‐(2,4‐difluorophenyl)‐5‐trifluoromethylpyridine, bpy=bipyridine) as catalytic photooxidant, a series of alkyl radicals, including highly reactive primary ones can be generated and engaged in various intermolecular homolytic reactions. Based on cyclic voltammetry, Stern–Volmer studies, and supported by calculations, a mechanism involving a single‐electron transfer from the silicate to the photoactivated iridium complex has been proposed. This oxidative photocatalyzed process can be efficiently merged with nickel‐catalyzed CC cross‐coupling reactions.
Performance on the Adult Rheumatology In‐Training Examination and Relationship to Outcomes on the Rheumatology Certification Examination
Authors: Lohr Kristine M. , Clauser Amanda , Hess Brian J. , Gelber Allan C. , Valeriano‐Marcet Joanne , Lipner Rebecca S. , Haist Steven A. , Hawley Janine L. , Zirkle Sarah , Bolster Marcy B. ,   for the American College of Rheumatology Committee on Rheumatology Training and Workforce Issues
Published: July 2015

Objective

The American College of Rheumatology (ACR) Adult Rheumatology In‐Training Examination (ITE) is a feedback tool designed to identify strengths and weaknesses in the content knowledge of individual fellows‐in‐training and the training program curricula. We determined whether scores on the ACR ITE, as well as scores on other major standardized medical examinations and competency‐based ratings, could be used to predict performance on the American Board of Internal Medicine (ABIM) Rheumatology Certification Examination.

Methods

Between 2008 and 2012, 629 second‐year fellows took the ACR ITE. Bivariate correlation analyses of assessment scores and multiple linear regression analyses were used to determine whether ABIM Rheumatology Certification Examination scores could be predicted on the basis of ACR ITE scores, United States Medical Licensing Examination scores, ABIM Internal Medicine Certification Examination scores, fellowship directors’ ratings of overall clinical competency, and demographic variables. Logistic regression was used to evaluate whether these assessments were predictive of a passing outcome on the Rheumatology Certification Examination.

Results

In the initial linear model, the strongest predictors of the Rheumatology Certification Examination score were the second‐year fellows’ ACR ITE scores (β = 0.438) and ABIM Internal Medicine Certification Examination scores (β = 0.273). Using a stepwise model, the strongest predictors of higher scores on the Rheumatology Certification Examination were second‐year fellows’ ACR ITE scores (β = 0.449) and ABIM Internal Medicine Certification Examination scores (β = 0.276). Based on the findings of logistic regression analysis, ACR ITE performance was predictive of a pass/fail outcome on the Rheumatology Certification Examination (odds ratio 1.016 [95% confidence interval 1.011–1.021]).

Conclusion

The predictive value of the ACR ITE score with regard to predicting performance on the Rheumatology Certification Examination supports use of the Adult Rheumatology ITE as a valid feedback tool during fellowship training.
Evaluating topic representations for exploring document collections
Authors: Aletras Nikolaos , Baldwin Timothy , Lau Jey Han , Stevenson Mark
Published: July 2015

Topic models have been shown to be a useful way of representing the content of large document collections, for example, via visualization interfaces (topic browsers). These systems enable users to explore collections by way of latent topics. A standard way to represent a topic is using a term list; that is the top‐n words with highest conditional probability within the topic. Other topic representations such as textual and image labels also have been proposed. However, there has been no comparison of these alternative representations. In this article, we compare 3 different topic representations in a document retrieval task. Participants were asked to retrieve relevant documents based on predefined queries within a fixed time limit, presenting topics in one of the following modalities: (a) lists of terms, (b) textual phrase labels, and (c) image labels. Results show that textual labels are easier for users to interpret than are term lists and image labels. Moreover, the precision of retrieved documents for textual and image labels is comparable to the precision achieved by representing topics using term lists, demonstrating that labeling methods are an effective alternative topic representation.
Analyzing Web behavior in indoor retail spaces
Authors: Ren Yongli , Tomko Martin , Salim Flora Dilys , Ong Kevin , Sanderson Mark
Published: July 2015

We analyze 18‐ million rows of Wi‐Fi access logs collected over a 1‐year period from over 120,000 anonymized users at an inner city shopping mall. The anonymized data set gathered from an opt‐in system provides users' approximate physical location as well as web browsing and some search history. Such data provide a unique opportunity to analyze the interaction between people's behavior in physical retail spaces and their web behavior, serving as a proxy to their information needs. We found that (a) there is a weekly periodicity in users' visits to the mall; (b) people tend to visit similar mall locations and web content during their repeated visits to the mall; (c) around 60% of registered Wi‐Fi users actively browse the web, and around 10% of them use Wi‐Fi for accessing web search engines; (d) people are likely to spend a relatively constant amount of time browsing the web while the duration of their visit may vary; (e) the physical spatial context has a small, but significant, influence on the web content that indoor users browse; and (f) accompanying users tend to access resources from the same web domains.
Selective C−H and C−C Bond Activation: Electronic Regimes as a Tool for Designing d10 MLn Catalysts
Authors: Wolters Lando P. , Bickelhaupt F. Matthias
Published: July 2015

We wish to understand how a transition‐metal catalyst can be rationally designed so as to selectively activate one particular bond in a substrate, herein, C−H and C−C bonds in ethane. To this end, we quantum chemically analyzed the activity and selectivity of a large series of model catalysts towards ethane and, for comparison, methane, by using the activation strain model and quantitative molecular orbital theory. The model catalysts comprise d10 MLn complexes with coordination numbers n=0, 1, and 2; metal centers M=Co−, Rh−, Ir−, Ni, Pd, Pt, Cu+, Ag+, and Au+; and ligands L=NH3, PH3, and CO. Our analyses reveal that rather subtle electronic differences between bonds can be exploited to induce a lower barrier for activating one or the other, depending, among other factors, on the catalyst's electronic regime (i.e., s‐regime versus d‐regime catalysts). Interestingly, the concepts and design principles emerging from this work can also be applied to the more challenging problem of differentiating between activation of the C−H bonds in ethane versus those in methane.
Short Synthesis of [5]‐ and [7]Phenacenes with Silyl Groups at the Axis Positions
Authors: Roy David , Maekawa Hiroyuki , Murai Masahito , Takai Kazuhiko
Published: July 2015

[5]Phenacene with trimethylsilyl groups at the axis positions was synthesized by the ruthenium‐catalyzed direct C−H arylation of a 1‐formyl‐7‐phenanthrene‐derived aldimine, followed by sequential Wittig olefination and bismuth‐catalyzed cyclization of the resulting vinyl ethers. By using the same synthetic building blocks and sequential Wittig olefination and photocyclization, the number of fused benzene rings was readily increased to seven to afford 3,12‐disilyl[7]phenacene. The introduction of silyl groups endowed the [n]phenacene frameworks with good solubility, as well as enabling further functionalization. The electronic structure of these new [n]phenacenes was determined by photophysical measurements and by density functional theory calculations, which clearly implied effective conjugation throughout the entire π framework.
Enhanced Charge Separation Efficiency in Pyridine‐Anchored Phthalocyanine‐Sensitized Solar Cells by Linker Elongation
Authors: Ikeuchi Takuro , Agrawal Saurabh , Ezoe Masayuki , Mori Shogo , Kimura Mutsumi
Published: July 2015

A series of zinc phthalocyanine sensitizers (PcS22–24) having a pyridine anchoring group are designed and synthesized to investigate the structural dependence on performance in dye‐sensitized solar cells. The pyridine‐anchor zinc phthalocyanine sensitizer PcS23 shows 79 % incident‐photon to current‐conversion efficiency (IPCE) and 6.1 % energy conversion efficiency, which are comparable with similar phthalocyanine dyes having a carboxylic acid anchoring group. Based on DFT calculations, the high IPCE is attributed with the mixture of an excited‐state molecular orbital of the sensitizer and the orbitals of TiO2. Between pyridine and carboxylic acid anchor dyes, opposite trends are observed in the linker‐length dependence of the IPCE. The red‐absorbing PcS23 is applied for co‐sensitization with a carboxyl‐anchor organic dye D131 that has a complementary spectral response. The site‐selective adsorption of PcS23 and D131 on the TiO2 surface results in a panchromatic photocurrent response for the whole visible‐light region of sun light.
The changing influence of El Niño on the Great Plains low‐level jet
Authors: Liang Yu‐Chiao , Yu Jin‐Yi , Lo Min‐Hui , Wang Chunzai
Published: July 2015

This study finds that the El Niño influences on the summer Great Plains low‐level jet (GPLLJ) are different for the Central Pacific (CP) and Eastern Pacific (EP) types during their decaying phases. While the CP El Niño induces negative sea level pressure anomalies over the Gulf of Mexico to drive anomalous northerly winds weakening the GPLLJ, the EP El Niño intensifies the GPLLJ by inducing anomalous surface air temperature gradient between the northeastern and southwestern United States. The recent emerging CP El Niño can weaken the GPLLJ to lead to a drier environment in the central United States.
Interest‐driven avatar neighbor‐organizing for P2P transmission in distributed virtual worlds
Authors: Wang Mingfei , Jia Jinyuan , Xie Ning , Zhang Chenxi
Published: July 2015

The neighbor table/distributed hash table (DHT) is used to choose the data supplier for data‐dispatching services in distributed virtual environments based on peer‐to‐peer networks. It is essential that a stable and efficient neighbor table/DHT be maintained. Because the avatar has much freedom to roam, the spatial distribution of nodes is not uniform, and the logical topology may change dramatically. Therefore, traditional construction mechanisms, such as the neighbor‐discovery mechanism based on spatial distance or DHT, may involve fierce churn in the neighbor table and frequent message exchanges. In this paper, we proposed a dynamic node‐organizing mechanism that aims to solve these challenging problems by applying the avatar's behavioral characteristics to the neighbor maintenance mechanism and scene data transmission. First, we have summarized the common social behaviors of avatars and extracted their characteristics. We then propose an interest‐similarity measuring algorithm to divide the node into diverse clusters. Next, we measure the cluster stability in terms of interest entropy while constructing a stable neighbor mesh for each node in a cluster. We have conducted extensive simulation experiments that simulate avatar behaviors in a popular massively multiplayer online game. The results show that our proposed mechanism achieved a substantial alleviation of neighbor churn and reduced information exchange, which improves the transmission efficiency in distributed virtual environments. Copyright © 2015 John Wiley & Sons, Ltd.
CFD Analysis of Heat Transfer across the Laminar Wavy Film on a Centrifugal Molecular Distillator
Authors: Yu Jiang , Zeng Aiwu , Yuan Xigang , Zhang Xinyu , Ju Ji
Published: July 2015

Laminar wave dynamics and the associated heat transfer across the spinning film is a highly important process in chemical engineering, but there is still a lack of sufficient investigation of the transfer flux based on the fundamental hydrodynamics parameters. A two‐dimensional computational fluid dynamics simulation of the spinning film on a centrifugal molecular distillator is performed in order to explore the effect of the interfacial wave behavior on the heat transfer. Numerical results reveal that the heat transfer is enhanced by the convective motions in the waves. Resulting from these findings, the relationship between the operation parameters and heat transfer is also discussed.
Effects of Alkyl Chain Length and Hydrogen Bonds on the Cooperative Self‐Assembly of 2‐Thienyl‐Type Diarylethenes at a Liquid/Highly Oriented Pyrolytic Graphite (HOPG) Interface
Authors: Yokoyama Soichi , Hirose Takashi , Matsuda Kenji
Published: July 2015

An appropriate understanding of the process of self‐assembly is of critical importance to tailor nanostructured order on 2D surfaces with functional molecules. Photochromic compounds are promising candidates for building blocks of advanced photoresponsive surfaces. To investigate the relationship between molecular structure and the mechanism of ordering formation, 2‐thienyl‐type diarylethenes with various lengths of alkyl side chains linked through an amide or ester group were synthesized. Their self‐assemblies at a liquid/solid interface were investigated by scanning tunneling microscopy (STM). The concentration dependence of the surface coverage was analyzed by using a cooperative model for a 2D surface based on two characteristic parameters: the nucleation equilibrium constant (Kn) and the elongation equilibrium constant (Ke). The following conclusions can be drawn. 1) The concentration at which a stable 2D molecular ordering is observed by STM exponentially decreases with increasing length of the alkyl chain. 2) Compounds bearing amide groups have higher degrees of cooperativity in self‐assembly on 2D surfaces (i.e., σ, which is defined as Kn/Ke) than compounds with ester groups. 3) The self‐assembly process of the open‐ring isomer of an ester derivative is close to isodesmic, whereas that of the closed‐ring isomer is cooperative because of the difference in equilibrium constants for the nucleation step (i.e., Kn) between the two isomers.
Photoinduced Carbon Monoxide Release from Half‐Sandwich Iron(II) Carbonyl Complexes by Visible Irradiation: Kinetic Analysis and Mechanistic Investigation
Authors: Jiang Xiujuan , Chen Limei , Wang Xiu , Long Li , Xiao Zhiyin , Liu Xiaoming
Published: July 2015

Three half‐sandwich iron(II) complexes, [Fe(η5‐Cp)(cis‐CO)2X] (X−=Cl−, Br−, I−), were synthesized and characterized. The kinetics of the CO‐releasing behaviour of these complexes upon illumination by visible irradiation in various media was investigated. Our results indicated that the CO release was significantly affected by the auxiliary ligands. Of the three light sources used (blue, green, and red), blue light exhibited the highest efficiency. In the photoinduced CO release, the solvents and exogenous nucleophiles in the media were involved, which allowed their CO‐releasing reaction to comply with pseudo first‐order model rather than the characteristic zero‐order model for a photochemical reaction. In aqueous media (D2O), an intermediate bearing the core of {FeII(cis‐CO)2} involving cleavage of cyclopentadiene was detected. Despite the non‐absorption of the red light, its illumination combined with nucleophilic substitution did cause considerable CO release. Assessment of the cytotoxicity of the three complexes indicated that they showed good biocompatibility.
Phosphorescent Platinum(II) Complexes with C^C* Cyclometalated NHC Dibenzofuranyl Ligands: Impact of Different Binding Modes on the Decay Time of the Excited State
Authors: Tronnier Alexander , Wagenblast Gerhard , Münster Ingo , Strassner Thomas
Published: July 2015

Two C^C* cyclometalated platinum(II) N‐heterocyclic carbene (NHC) complexes with the general formula [(C^C*)Pt(O^O)] (C^C*=1‐dibenzofuranyl‐3‐methylbenzimidazolylidene; O^O=dimesitoylmethane) have been synthesized and extensively characterized, including solid‐state structure determination, 195Pt NMR spectroscopy, and 2D NMR (COSY, HSQC, HMBC, NOESY) spectroscopy to elucidate the impact of their structural differences. The two regioisomers differ in the way the dibenzofuranyl (DBF) moiety of the NHC ligand is bound to the metal center, which induces significant changes in their physicochemical properties, especially on the decay time of the excited state. Quantum yields of over 80 % and blue emission colors were measured.
A “good death” with irreversible liver disease: Talking with patients and families about deteriorating health and dying
Authors: Boyd Kirsty , Kimbell Barbara , Murray Scott , Iredale John
Published: July 2015

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Overall health‐related quality of life in patients with end‐stage liver disease
Authors: Younossi Zobair , Henry Linda
Published: July 2015

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Histologic and noninvasive estimates of liver fibrosis
Authors: Bedossa Pierre , Patel Keyur , Castera Laurent
Published: July 2015

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Is palliative care appropriate in the liver transplant candidate?
Authors: Pai Rohit , Karvellas Constantine J.
Published: July 2015

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Application of MS Transport Assays to the Four Human γ‐Aminobutyric Acid Transporters
Authors: Schmitt Sebastian , Höfner Georg , Wanner Klaus T.
Published: July 2015

γ‐Aminobutyric acid (GABA) transporters (GATs) are promising drug targets for various diseases associated with imbalances in GABAergic neurotransmission. For the development of new drugs or pharmacological tools addressing GATs, screening techniques to identify new inhibitors and to characterize their potency at each GAT subtype are indispensable. By now, the technique by far dominating is based on radiolabeled GABA. We recently described “MS Transport Assays” for hGAT‐1 by employing (2H6)GABA as the substrate. In the present study, we applied this approach to all four human GAT subtypes and determined the KM values for GAT‐mediated transport of (2H6)GABA at each subtype. Furthermore, a comprehensive set of GAT inhibitors reflecting the whole range of potency and subtype selectivity known so far was evaluated for their potency. The comparison of pIC50 values obtained in conventional [3H]GABA uptake assays with those obtained in MS Transport Assays indicated the reliability of the latter. The MS Transport Assays enable a throughput similar to that of conventional radiometric transport assays performed in a 96‐well format but avoid the use of radiolabeled substrates.
Impact of care at comprehensive cancer centers on outcome: Results from a population‐based study
Authors: Wolfson Julie A. , Sun Can‐Lan , Wyatt Laura P. , Hurria Arti , Bhatia Smita
Published: July 2015

BACKGROUND

Rigorous processes ensure quality of research and clinical care at National Cancer Institute‐designated comprehensive cancer centers (NCICCCs). Unmeasurable elements of structure and process of cancer care delivery warrant evaluation. To the authors' knowledge, the impact of NCICCC care on survival and access to NCICCCs for vulnerable subpopulations remain unstudied.

METHODS

The current study's population‐based cohort of 69,579 patients had newly diagnosed adult‐onset (aged 22‐65 years) cancers reported to the Los Angeles County cancer registry between 1998 and 2008. Geographic information systems were used for geospatial analysis.

RESULTS

With regard to overall survival across multiple diagnoses, patients not receiving their first planned treatment at NCICCCs experienced poorer outcomes compared with those treated at NCICCCs; differences persisted on multivariable analyses after adjusting for clinical and sociodemographic factors (hepatobiliary: hazard ratio [HR], 1.5; 95% confidence interval [95% CI], 1.4‐1.7 [P<.001]; lung: HR, 1.4; 95% CI, 1.3‐1.6 [P<.001]; pancreatic: HR, 1.5; 95% CI, 1.3‐1.7 [P<.001]; gastric: HR, 1.3; 95% CI, 1.1‐1.7 [P = .01]; breast: HR, 1.3; 95% CI, 1.1‐1.5 [P<.001]; and colorectal: HR, 1.2; 95% CI, 1.0‐1.4 [P = .05]). With regard to barriers to care, multivariable analyses revealed that a lower likelihood of treatment at NCICCCs was associated with race/ethnicity (African‐American: OR range across diagnoses: 0.4‐0.7 [P<.03]; Hispanic: OR range, 0.5‐0.7 [P<.04]); lack of private insurance (public: OR range, 0.6‐0.8 [P<.004]; uninsured: OR range, 0.1‐0.5 [P<.04]); less than high socioeconomic status (high‐middle: OR range, 0.4‐0.7 [P<.02]; middle: OR range, 0.3‐0.5 [P<.001]; and low: OR range, 0.2‐0.6 [P<.01]), and residing >9 miles from the nearest NCICCC (OR range, 0.5‐0.7 [P<.02]).

CONCLUSIONS

Among individuals aged 22 to 65 years residing in Los Angeles County with newly diagnosed adult‐onset cancer, those who were treated at NCICCCs experienced superior survival compared with those treated at non‐NCICCC facilities. Barriers to care at NCICCCs included race/ethnicity, insurance, socioeconomic status, and distance to an NCICCC. Cancer 2015;121:3885–3893. © 2015 American Cancer Society.
Clinicopathologic features associated with efficacy and long‐term survival in metastatic melanoma patients treated with BRAF or combined BRAF and MEK inhibitors
Authors: Menzies Alexander M. , Wilmott James S. , Drummond Martin , Lo Serigne , Lyle Megan , Chan Matthew M. K. , Thompson John F. , Guminski Alex , Carlino Matteo S. , Scolyer Richard A. , Kefford Richard F. , Long Georgina V.
Published: July 2015

BACKGROUND

The degree of response and the duration of survival of patients treated with mitogen‐activated protein kinase (MAPK) inhibitors are highly variable. Whether baseline clinicopathologic factors can predict the clinical course with treatment is largely unknown.

METHODS

For 142 consecutive immunotherapy‐ and MAPK inhibitor–naive patients with BRAF‐mutant metastatic melanoma who were treated during clinical trials with BRAF inhibitors (n = 111) or a combination of dabrafenib and trametinib (n = 31), clinicopathologic factors were correlated with the response to MAPK inhibitors and survival.

RESULTS

The median follow‐up was 15.7 months (range, 0.6‐60.5 months). The 2‐, 3‐, and 4‐year overall survival (OS) rates were 43%, 24%, and 24%, respectively. A multivariate analysis demonstrated that the only clinicopathologic factors associated with longer progression‐free survival (PFS) and OS were female sex and a normal pretreatment serum lactate dehydrogenase (LDH) level. The BRAF V600E genotype and an absence of primary melanoma ulceration were also independently associated with longer PFS but not OS. The median OS was 23.5 months for patients with normal LDH levels and 7.3 months for those with elevated LDH levels (hazard ratio, 0.31; P < .001). Complete responders had the best survival, but disease progression still occurred in 2 of 7 patients.

CONCLUSIONS

Long‐term survival occurs for a minority of patients receiving MAPK inhibitor treatment alone. Sex, serum LDH, BRAF genotype, and primary melanoma ulceration status are independent factors associated with treatment outcomes. Patients with a complete response to treatment have the best survival, but relapses still occur. Cancer 2015;121:3826–3835. © 2015 American Cancer Society.
Estimated glomerular filtration rate changes in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors
Authors: Yilmaz Musa , Lahoti Amit , O'Brien Susan , Nogueras‐González Graciela M. , Burger Jan , Ferrajoli Alessandra , Borthakur Gautam , Ravandi Farhad , Pierce Sherry , Jabbour Elias , Kantarjian Hagop , Cortes Jorge E.
Published: July 2015

BACKGROUND

Chronic use of tyrosine kinase inhibitors (TKIs) may lead to previously unrecognized adverse events. This study evaluated the incidence of acute kidney injury (AKI) and chronic kidney disease (CKD) in chronic‐phase (CP) chronic myeloid leukemia (CML) patients treated with imatinib, dasatinib, and nilotinib.

METHODS

Four hundred sixty‐eight newly diagnosed CP CML patients treated with TKIs were analyzed. The molecular and cytogenetic response data, creatinine, and glomerular filtration rate (GFR) were followed from the start of therapy to the last follow‐up (median, 52 months). GFR was estimated with the Modification of Diet in Renal Disease equation.

RESULTS

Nineteen patients (4%) had TKI‐associated AKI. Imatinib was associated with a higher incidence of AKI in comparison with dasatinib and nilotinib (P = .014). Fifty‐eight patients (14%) developed CKD while they were receiving a TKI; 49 of these patients (84%) did so while they were being treated with imatinib (P < .001). Besides imatinib, age, a history of hypertension, and diabetes mellitus were also associated with the development of CKD. In patients with no CKD at the baseline, imatinib was shown to reduce GFR over time. Interestingly, imatinib did not cause a significant decline in the GFRs of patients with a history of CKD. Imatinib, dasatinib, and nilotinib increased the mean GFR after 3 months of treatment, and nilotinib led with the most significant increase (P < .001). AKI or CKD had no significant impact on overall cytogenetic and molecular response rates or survival.

CONCLUSIONS

The administration of TKIs may be safe in the setting of CKD in CP CML patients, but close monitoring is still warranted. Cancer 2015;121:3894–3904. © 2015 American Cancer Society.
Reflections from a chair: Leadership of a clinical department at an academic medical center
Authors: Willett Christopher G.
Published: July 2015

The leadership position of an academic departmental chair can be a positive and rewarding opportunity. These rewards principally stem from the success of the faculty, residents, other trainees, nurses, and everyone supporting the department. With health care reform and the constraints of the federal budget, increasing attention and time has become directed toward administrative management. There are multiple and often competing constituencies and agendas requiring thoughtful strategies to achieve departmental goals. The objectives of a chair are advancing patient care, education, and research. True excellence of a department is achieved by the innovation of its faculty. Cancer 2015;121:3795–3798. © 2015 American Cancer Society.
Symptom profiles in children with advanced cancer: Patient, family caregiver, and oncologist ratings
Authors: Zhukovsky Donna S. , Rozmus Cathy L. , Robert Rhonda S. , Bruera Eduardo , Wells Robert J. , Chisholm Gary B. , Allo Julio A. , Cohen Marlene Z.
Published: July 2015

BACKGROUND

Systematic symptom assessment is not routinely performed in pediatric oncology. The objectives of the current study were to characterize the symptoms of pediatric oncology outpatients and evaluate agreement between patient and proxy reports and the association between children's ratings and oncologists' treatment recommendations.

METHODS

Two versions of the pediatric Memorial Symptom Assessment Scale (pMSAS) were translated into Spanish. An age‐appropriate and language‐appropriate pMSAS was administered independently before visits to the oncologist to patients and family caregivers (caregivers) and after visits to consenting oncologists. Statistical analysis included Spearman correlation coefficients and weighted kappa values.

RESULTS

English and Spanish results were similar and were combined. A total of 60 children and their caregivers completed the pMSAS. The children had a median age of 10 years (range, 7‐18 years); approximately 62% were male and 33% were Spanish‐speaking. Fourteen oncologists completed the pMSAS for 25 patients. Nine patients (15%) had no symptoms and 38 patients (63%) reported ≥2 symptoms. The most common symptoms were fatigue (12 patients; 40%) and itch (9 patients; 30%) for the younger children and pain (15 patients; 50%) and lack of energy (13 patients; 45%) among the older children. Total and subscale score agreement varied by proxy type and subscale, ranging from fair to good for most comparisons. Agreement for individual symptoms between the patient and proxy ranged from a kappa of −0.30 (95% confidence interval, −0.43 to −0.01) to 0.91 (95% confidence interval, 0.75 to 1.00). Three of 51 symptomatic patients (6%) had treatment recommendations documented in the electronic health record.

CONCLUSIONS

Symptoms are common and cross several functional domains. Proxy and child reports are often not congruent, possibly explaining apparent undertreatment among this group of patients. Cancer 2015;121:4080–4087. © 2015 American Cancer Society.
Fludarabine, cyclophosphamide, and multiple‐dose rituximab as frontline therapy for chronic lymphocytic leukemia
Authors: Short Nicholas J. , Keating Michael J. , Wierda William G. , Faderl Stefan , Ferrajoli Alessandra , Estrov Zeev , Smith Susan C. , O'Brien Susan M.
Published: July 2015

BACKGROUND

Fludarabine, cyclophosphamide, and rituximab (FCR) result in durable responses in patients with previously untreated chronic lymphocytic leukemia (CLL). Previous reports have suggested that in patients with relapsed CLL, a dose‐intensified rituximab regimen increases response rates in comparison with standard‐dose rituximab. It is unknown whether rituximab intensification of the FCR regimen will result in improved response rates and patient outcomes in patients with previously untreated CLL.

METHODS

A single‐arm study was conducted to evaluate the safety and efficacy of a modified FCR regimen with multiple‐dose rituximab (FCR3) in 65 patients with previously untreated CLL. The results were compared with those for a historical cohort treated with FCR.

RESULTS

The overall response rate to FCR3 was 97%, with 75% of the patients achieving a complete remission. Minimal residual disease negativity was achieved for 62% of the patients according to flow cytometry. The median time to progression (TTP) was 81 months, and the median overall survival (OS) was not reached, with 58% of the patients still alive at a median survivor follow‐up of 9.7 years. Grade 3 or 4 neutropenia, grade 3 or 4 thrombocytopenia, and major infections were observed with 45%, 5%, and 1.9% of the FCR3 courses, respectively. Therapy‐related myelodysplastic syndrome (t‐MDS) or therapy‐related acute myelogenous leukemia (t‐AML) developed in 7 patients (11%; P < .01 vs the historical FCR cohort).

CONCLUSIONS

In patients with previously untreated CLL, FCR3 resulted in response rates, TTP, and OS similar to those of a historical cohort of patients treated with FCR. FCR3 was associated with an increased incidence of t‐MDS/t‐AML. Cancer 2015;121:3869–3876. © 2015 American Cancer Society.
A Topological Approach to Cheeger‐Gromov Universal Bounds for von Neumann ρ‐Invariants
Authors: Cha Jae Choon
Published: July 2015

Using deep analytic methods, Cheeger and Gromov showed that for any smooth (4k‐1)‐manifold there is a universal bound for the von Neumann L2 ρ‐invariants associated to arbitrary regular covers. We present a proof of the existence of a universal bound for topological (4k‐1)‐manifolds, using L2‐signatures of bounding 4k‐manifolds. We give explicit linear universal bounds for 3‐manifolds in terms of triangulations, Heegaard splittings, and surgery descriptions. We show that our explicit bounds are asymptotically optimal. As an application, we give new lower bounds of the complexity of 3‐manifolds that can be arbitrarily larger than previously known lower bounds. As ingredients of the proofs that seem interesting on their own, we develop a geometric construction of efficient 4‐dimensional bordisms of 3‐manifolds over a group and develop an algebraic topological notion of uniformly controlled chain homotopies.© 2016 Wiley Periodicals, Inc.
Scalable multi‐dimensional RNN query processing
Authors: Ji Changqing , Qu Wenyu , Li Zhiyang , Xu Yujie , Li Yuanyuan , Wu Junfeng
Published: July 2015

Reverse nearest neighbor (RNN) queries are the complimentary problem and particular interest in the past few years, such as location‐based services, profile‐based marketing, resource allocation, and traffic monitoring system. The one major drawback for the existing RNN is that it has inherent sequential nature and uses in‐memory algorithm, which limits its applicability to large‐scale spatial data queries. This paper proposes scalable algorithms for RNN queries in a distributed environment. Firstly, we investigate the Basic‐scalable reverse nearest neighbor (SRNN) initialization query method based on the inverted grid index. Secondly, two optimization methods Lazy‐SRNN and Eager‐SRNN are proposed to effectively process scalable multi‐dimensional RNN queries. Among them, Lazy‐SRNN prunes the search space when all RNN objects are discovered in one pass; Eager‐SRNN attempts to prune spatial objects incrementally as soon as they are visited. In addition, the SRNN algorithm is proved to be the first attempt for the exact scalable RNN algorithms in a distributed environment on multi‐dimensional data sets. We show in an extensive experimental evaluation on real‐world and synthetic data the scalability and the performance of our novel approach. Copyright © 2015 John Wiley & Sons, Ltd.
Secure routing and resource allocation based on game theory in cooperative cognitive radio networks
Authors: Fang He , Xu Li , Xiao Liang
Published: July 2015

The era of big data is here now, and spectrum resources are increasingly scarce in heterogeneous network environment. The spectrum efficiency and secure transmission of big data are important issues. Cognitive radio has been proposed to address the issue of spectrum efficiency, and is a hot topic in the literatures. In multi‐hop cooperative cognitive radio networks (CCRNs), secondary users need the primary users' authorization to be relays. Most existing centralized route selection schemes ignore the energy allocation, and thus are inefficient. Moreover, the incomplete of information in multi‐hop network leads to many difficulties in cooperation. Inspired by the game theory, a novel strategy is proposed in this paper to defend against insider attacks based on trust. This strategy is denoted as secure routing and resource allocation based on game theory in CCRNs (SRGC). With a reputation updating process and distributed learning algorithm, the proposed strategy can find a ‘best’ route, which is relatively safe for each primary transmitter, and at the same time fully utilizes the spectrum and energy. Using NS2, simulations indicate that SRGC can well fit into CCRNs, improve the network performance and defend against the routing disruption attacks. Compared with other schemes, the SRGC results in a performance with better adaptability to the distributed environment. Moreover, SRGC can maximize the average throughput and minimize the data drop ratios. Copyright © 2015 John Wiley & Sons, Ltd.
Trust‐based security‐level evaluation method for dynamic service‐oriented environments
Authors: Kołaczek Grzegorz , Juszczyszyn Krzysztof , Świątek Paweł , Grzech Adam , Schauer Patryk , Stelmach Paweł , Falas Łukasz
Published: July 2015

A method of decision‐making in security‐level estimation process of service‐based applications in future Internet architecture is proposed. We demonstrate how distributed services can be composed to form an application run within the next‐generation network infrastructure and their security level may be assessed. Our approach is illustrated by the experiments carried on exemplary application (virtual laboratory online lab, using future Internet IPv6 QoS architecture), in which our method was evaluated against two types of attacks observed with the use of traffic anomaly detection methods. Copyright © 2015 John Wiley & Sons, Ltd.
An energy‐aware performance analysis of SWIMM: Smith–Waterman implementation on Intel's Multicore and Manycore architectures
Authors: Rucci Enzo , García Carlos , Botella Guillermo , De Giusti Armando , Naiouf Marcelo , Prieto‐Matías Manuel
Published: July 2015

Alignment is essential in many areas such as biological, chemical and criminal forensics. The well‐known Smith–Waterman (SW) algorithm is able to retrieve the optimal local alignment with quadratic time and space complexity. There are several implementations that take advantage of computing parallelization, such as manycores, FPGAs or GPUs, in order to reduce the alignment effort. In this research, we adapt, develop and tune the SW algorithm named SWIMM on a heterogeneous platform based on Intel's Xeon and Xeon Phi coprocessor. SWIMM is a free tool available in a public git repository https://github.com/enzorucci/SWIMM. We efficiently exploit data and thread‐level parallelism, reaching up to 380 GCUPS on heterogeneous architecture, 350 GCUPS for the isolated Xeon and 50 GCUPS on Xeon Phi. Despite the heterogeneous implementation obtaining the best performance, it is also the most energy‐demanding. In fact, we also present a trade‐off analysis between performance and power consumption. The greenest configuration is based on an isolated multicore system that exploits AVX2 instruction set architecture reaching 1.5 GCUPS/Watts. Copyright © 2015 John Wiley & Sons, Ltd.
Estimation of Lattice Enthalpies of Ionic Liquids Supported by Hirshfeld Analysis
Authors: Preiss Ulrich P. , Zaitsau Dzmitry H. , Beichel Witali , Himmel Daniel , Higelin Alexander , Merz Klaus , Caesar Niklas , Verevkin Sergey P.
Published: July 2015

New measurements of vaporization enthalpies for 15 1:1 ionic liquids are performed by using a quartz‐crystal microbalance. Collection and analysis of 33 available crystal structures of organic salts, which comprise 13 different cations and 12 anions, is performed. Their dissociation lattice enthalpies are calculated by a combination of experimental and quantum chemical quantities and are divided into the relaxation and Coulomb components to give an insight into elusive short‐range interaction enthalpies. An empirical equation is developed, based on interaction‐specific Hirshfeld surfaces and solvation enthalpies, which enables the estimation of the lattice enthalpy by using only the crystal‐structure data.
Rational Design of a Hierarchical Tin Dendrite Electrode for Efficient Electrochemical Reduction of CO2
Authors: Won Da Hye , Choi Chang Hyuck , Chung Jaehoon , Chung Min Wook , Kim Eun‐Hee , Woo Seong Ihl
Published: July 2015

Catalysis is a key technology for the synthesis of renewable fuels through electrochemical reduction of CO2. However, successful CO2 reduction still suffers from the lack of affordable catalyst design and understanding the factors governing catalysis. Herein, we demonstrate that the CO2 conversion selectivity on Sn (or SnOx/Sn) electrodes is correlated to the native oxygen content at the subsurface. Electrochemical analyses show that the reduced Sn electrode with abundant oxygen species effectively stabilizes a CO2.− intermediate rather than the clean Sn surface, and consequently results in enhanced formate production in the CO2 reduction. Based on this design strategy, a hierarchical Sn dendrite electrode with high oxygen content, consisting of a multi‐branched conifer‐like structure with an enlarged surface area, was synthesized. The electrode exhibits a superior formate production rate (228.6 μmol h−1 cm−2) at −1.36 VRHE without any considerable catalytic degradation over 18 h of operation.
Novel full‐spectral flow cytometry with multiple spectrally‐adjacent fluorescent proteins and fluorochromes and visualization of in vivo cellular movement
Authors: Futamura Koji , Sekino Masashi , Hata Akihiro , Ikebuchi Ryoyo , Nakanishi Yasutaka , Egawa Gyohei , Kabashima Kenji , Watanabe Takeshi , Furuki Motohiro , Tomura Michio
Published: July 2015

Flow cytometric analysis with multicolor fluoroprobes is an essential method for detecting biological signatures of cells. Here, we present a new full‐spectral flow cytometer (spectral‐FCM). Unlike conventional flow cytometer, this spectral‐FCM acquires the emitted fluorescence for all probes across the full‐spectrum from each cell with 32 channels sequential PMT unit after dispersion with prism, and extracts the signals of each fluoroprobe based on the spectral shape of each fluoroprobe using unique algorithm in high speed, high sensitive, accurate, automatic and real‐time. The spectral‐FCM detects the continuous changes in emission spectra from green to red of the photoconvertible protein, KikGR with high‐spectral resolution and separates spectrally‐adjacent fluoroprobes, such as FITC (Emission peak (Em) 519 nm) and EGFP (Em 507 nm). Moreover, the spectral‐FCM can measure and subtract autofluorescence of each cell providing increased signal‐to‐noise ratios and improved resolution of dim samples, which leads to a transformative technology for investigation of single cell state and function. These advances make it possible to perform 11‐color fluorescence analysis to visualize movement of multilinage immune cells by using KikGR‐expressing mice. Thus, the novel spectral flow cytometry improves the combinational use of spectrally‐adjacent various FPs and multicolor fluorochromes in metabolically active cell for the investigation of not only the immune system but also other research and clinical fields of use. © 2015 The Authors. Cytometry Part A Published by Wiley Periodicals, Inc. on behalf of ISAC
Efficacy of mineralocorticoid receptor antagonism in the acute myocardial infarction phase: eplerenone versus spironolactone
Authors: Fraccarollo Daniela , Galuppo Paolo , Sieweke Jan‐Thorben , Napp L. Christian , Grobbecker Paul , Bauersachs Johann
Published: July 2015

Aims

The selective mineralocorticoid receptor (MR) antagonist eplerenone given early in patients with acute myocardial infarction (MI) improves clinical outcome, whereas little is known about the effectiveness of early spironolactone therapy. We aimed to compare the ability of eplerenone and spironolactone to promote cardiac repair after experimental MI.

Methods and results

Starting immediately after coronary artery ligation, C57BL/6J mice were treated with placebo, eplerenone, or spironolactone. At 7 days, treatment with eplerenone or spironolactone reduced thinning and expansion of healing infarct and improved early left ventricular chamber enlargement. Remarkably, eplerenone therapy resulted in significantly greater improvement than spironolactone of left ventricular contractile function and relaxation, associated with a more considerable leftward and downward shift of the pressure volume curve. Seven‐day survival rate was significantly increased only in eplerenone treated mice. Moreover, eplerenone was superior to spironolactone in ameliorating neovessel formation in the injured myocardium. Optimized flow cytometry analysis of the monocyte differentiation marker Ly6C revealed predominant accumulation of Ly6Chigh monocytes/macrophages at the site of ischemic injury during the early inflammatory phase in placebo‐treated mice. In contrast, MR antagonism, especially by eplerenone, led to a skewing of the monocyte/macrophage population toward a higher frequency of healing promoting Ly6Clow cells.

Conclusion

The MR antagonist eplerenone versus spironolactone showed superior efficacy during the acute MI phase with more beneficial effects on survival, early cardiac dilation, and functional decline. Modulation of monocyte maturation and enhanced infarct neovessel formation appears to play a pivotal role.