bluuebunny/crossref_metadata_2025 huggingface dataset:
Spacer Effects on in vivo Properties of DOTA‐Conjugated Dimeric [Tyr3]Octreotate Peptides Synthesized by a “CuI‐Click” and “Sulfo‐Click” Ligation Method
Authors: Yim Cheng‐Bin , van der Wildt Berend , Dijkgraaf Ingrid , Joosten Lieke , Eek Annemarie , Versluis Cees , Rijkers Dirk T. S. , Boerman Otto C. , Liskamp Rob M. J.
Published: February 2011

We report on the SSTR2‐binding properties of a series of four dimeric [Tyr3]octreotate analogues with different spacer lengths (nine, 19, 41, and 57 atoms) between the peptides. Two analogues (9 and 57 atoms) were selected as precursors for the design, synthesis, and biological evaluation of DOTA‐conjugated dimeric [Tyr3]octreotate analogues for tumor targeting. These compounds were synthesized by using a two‐stage click ligation procedure: a CuI‐catalyzed 1,3‐dipolar cycloaddition (“copper‐click” reaction) and a thio acid/sulfonyl azide amidation (“sulfo‐click” reaction). The IC50 values of these DOTA‐conjugated [Tyr3]octreotate analogues were comparable, and internalization studies showed that the nine‐atom 111In‐DOTA‐labeled [Tyr3]octreotate dimer had rapid and high receptor binding. Biodistribution studies with BALB/c nude mice bearing subcutaneous AR42J tumors showed that the 111In‐labeled [Tyr3]octreotate dimer (nine atoms) had a high tumor uptake at 1 h p.i. (38.8±8.3 % ID g−1), and excellent tumor retention at 4 h p.i. (40.9±2.5 % ID g−1). However, the introduction of the extended hydrophilic 57 atoms spacer led to rapid clearance from the circulation; this limited tumor accumulation of the radiotracer (21.4±4.9 % ID g−1 at 1 h p.i.). These findings provide important insight on dimerization and spacer effects on the in vivo properties of DOTA‐conjugated [Tyr3]octreotate dimers.
Catalytic Co‐Homologation of Alkanes and Dimethyl Ether and Promotion by Adamantane as a Hydride Transfer Co‐Catalyst
Authors: Simonetti Dante A. , Ahn John H. , Iglesia Enrique
Published: February 2011

We provide kinetic and isotopic evidence for the co‐homologation of linear and branched alkanes with dimethyl ether (DME) to form larger branched alkanes and isobutane on H‐BEA zeolites, and for the role of adamantane as a hydride transfer co‐catalyst that allows the activation of CH bonds in alkanes at low temperatures (<500 K) on Brønsted acid sites. Branched alkanes (isobutane, isopentane, and 2,3‐dimethylbutane) present in equimolar mixtures with DME form the corresponding alkenes via hydride transfer to bound alkoxides (formed in DME homologation steps) and subsequent deprotonation; these alkenes, derived from the added alkanes, are then methylated to lengthen their chain by using DME‐derived C1 species, as shown by the isotopologues formed in reactions of 13C‐DME with 12C‐alkanes. Linear alkanes are much less reactive than branched alkanes, because of their stronger CH bonds and larger carbenium ion formation energies, which determines hydride‐transfer rates to a given acceptor molecule. Adamantane increased the hydride‐transfer rates to bound alkoxides from branched alkanes, and even from unreactive linear alkanes, while also increasing their extent of incorporation into DME homologation pathways; adamantane acts as a reversible hydrogen donor that mediates dehydrogenation of alkanes at low temperatures on acid sites. The co‐homologation of alkanes with DME avoids the need for carbon rejection in the form of arenes to satisfy the hydrogen balance in the DME conversion to alkanes, provides a robust strategy for increasing the chain length and extent of branching in light alkanes through the selective addition of C1 species, and mitigates the formation of unsaturated by‐products ubiquitous in the homologation of DME or methanol on Brønsted acids.
How Does Aromaticity Rule the Thermodynamic Stability of Hydroporphyrins?
Authors: Otero Nicolás , Fias Stijn , Radenković Slavko , Bultinck Patrick , Graña Ana M. , Mandado Marcos
Published: February 2011

Several measures of aromaticity including energetic, magnetic, and electron density criteria are employed to show how aromatic stabilization can explain the stability sequence of hydroporphyrins, ranging from porphin to octahydroporphin, and their preferred hydrogenation paths. The methods employed involve topological resonance energies and their circuit energy effects, bond resonance energies, multicenter delocalization indices, ring current maps, magnetic susceptibilities, and nuclear‐independent chemical shifts. To compare the information obtained by the different methods, the results have been put in the same scale by using recently proposed approaches. It is found that all of them provide essentially the same information and lead to similar conclusions. Also, hydrogenation energies along different hydrogenation paths connecting porphin with octahydroporphin have been calculated with density functional theory. It is shown by using the methods mentioned above that the relative stability of different hydroporphyrin isomers and the observed inaccessibility of octahydroporphin both synthetically and in nature can be perfectly rationalized in terms of aromaticity.
Prospective study of growth and development in older girls and risk of benign breast disease in young women
Authors: Berkey Catherine S. , Willett Walter C. , Frazier A. Lindsay , Rosner Bernard , Tamimi Rulla M. , Colditz Graham A.
Published: February 2011

BACKGROUND:

In adult women with retrospective data, childhood adiposity, pubertal growth and development were associated with benign breast disease (BBD) and/or breast cancer. The authors prospectively evaluated these childhood/adolescent characteristics and BBD risk.

METHODS:

The Growing Up Today Study (GUTS) included females, aged 9‐15 years in 1996, who completed annual questionnaires through 2001, then 2003, 2005, and 2007. Participants annually/biennially provided information on menarche, height, and weight, from which the authors derived body mass index (BMI in kg/m2). Peak height growth velocity (PHV in cm/year) was estimated from longitudinal data. On 2005‐2007 surveys, 6899 females (18‐27 years of age) reported whether a healthcare provider ever diagnosed BBD (n = 147), and whether it was confirmed by biopsy (n = 67). Logistic models investigated risk factors adjusted for age, alcohol, pregnancy, and maternal history.

RESULTS:

More childhood adiposity (odds ratio [OR], 0.91/[kg/m2]; P = .04) and shorter adult height (OR, 0.93/inch shorter; P = .07) were associated with lower risk of biopsy‐confirmed BBD. Girls with most rapid height growth were at increased risk (OR, 2.12; P = .09) relative to those with the slowest growth. Age at menarche was not associated (OR, 1.11/year; P = .32) nor was adult BMI (adjusted for childhood BMI: OR, 1.01/[kg/m2]; P = .98); larger BMI increases (childhood to adulthood) were not protective (OR + 1.04/[kg/m2]; P = .37). Among girls with maternal breast cancer, those with more rapid growth had higher risk (OR, 1.47/[cm/year]; P = .02). All estimates were age‐adjusted.

CONCLUSIONS:

Increased BBD risk (likely evolving to elevated breast cancer risk) was observed in thinner girls, girls with the most rapid growth, and taller women. Contrary to expectations, later menarche age was not protective against BBD, consistent with studies that found BBD patients are not protected against breast cancer by later menarche. Cancer 2011. © 2011 American Cancer Society.
Using GI‐G‐1 queuing model for rtPS performance evaluation in 802.16 networks
Authors: Kao Shang‐Juh , Chuang Chia‐Chuan
Published: February 2011

Among the scheduling services, rtPS (real‐time polling service) is designated for real‐time applications. Among three packet delay intervals, performance effect on polling interval has been widely studied, but less on the intervals of scheduling and delivery. To evaluate the performance of delay‐sensitive rtPS applications, instead of using continuous queueing model, a discrete‐time GI‐G‐1 model, which considers intervals of polling, scheduling, and delivery, is proposed. By taking VoIP as a typical rtPS application, the transmission latency under different QoS settings, polling probability, and traffic load are presented. The latency is also compared among various codec schemes. The results indicate that when the codec rate is either fulfilled or dissatisfied by the promised bandwidth of service levels, the performance is highly dependent upon the polling probability, no matter what the traffic condition is. However, if the codec rate is in between the promised bandwidth of various service levels, the polling probability is a dominant factor in light traffic environment, while the settings on QoS parameters will strongly determine the performance in heavy traffic situation. In addition to the verification using simulation, the bandwidth utilization derived from the GI‐G‐1 model can be applied to improve the serving capacity of base stations. Copyright © 2011 John Wiley & Sons, Ltd.
Skype‐Hunter: A real‐time system for the detection and classification of Skype traffic
Authors: Adami Davide , Callegari Christian , Giordano Stefano , Pagano Michele , Pepe Teresa
Published: February 2011

In the previous years, Skype has gained more and more popularity, since it is seen as the best VoIP software with good quality of sound, ease of use and one that works everywhere and with every OS. Because of its great diffusion, both the operators and the users are, for different reasons, interested in detecting Skype traffic.

In this paper we propose a real‐time algorithm (named Skype‐Hunter) to detect and classify Skype traffic. In more detail, this novel method, by means of both signature‐based and statistical procedures, is able to correctly reveal and classify the signaling traffic as well as the data traffic (calls and file transfers). To assess the effectiveness of the algorithm, experimental tests have been performed with several traffic data sets, collected in different network scenarios. Our system outperforms the ‘classical’ statistical traffic classifiers as well as the state‐of‐the‐art ad hoc Skype classifier. Copyright © 2011 John Wiley & Sons, Ltd.
Acute hypercapnic respiratory failure associated with hemodialysis
Authors: Palacios Carlos R. Franco , Altayeh Abdullah , Qian Qi
Published: February 2011

Patients undergoing hemodialysis are subject to recurrent acid‐base perturbations. Prior to each dialysis treatment, they are relatively acidemic, which is corrected rapidly during dialysis. We report a patient with obesity, obstructive lung disease, and pneumonia who developed acute respiratory failure triggered by an inﬂux of high bicarbonate during dialysis. This case emphasizes that in patients with severely compromised respiratory reserve, a large amount of bicarbonate inﬂux during hemodialysis may cause acute CO2 accumulation and ventilatory distress. An individualized approach with judicious adjustment of the dialysate bicarbonate concentration may be necessary. Dial. Transplant. © 2011 Wiley Periodicals, Inc.
Taste bud cells of adult mice are responsive to Wnt/β‐catenin signaling: Implications for the renewal of mature taste cells
Authors: Gaillard Dany , Barlow Linda A.
Published: February 2011

Wnt/β‐catenin signaling initiates taste papilla development in mouse embryos, however, its involvement in taste cell turnover in adult mice has not been explored. Here we used the BATGAL reporter mouse model, which carries an engineered allele in which the LacZ gene is expressed in the presence of activated β‐catenin, to determine the responsiveness of adult taste bud cells to canonical Wnt signaling. Double immunostaining with markers of differentiated taste cells revealed that a subset of Type I, II, and III taste cells express β‐galactosidase. Using in situ hybridization, we showed that β‐catenin activates the transcription of the LacZ gene mainly in intragemmal basal cells that are immature taste cells, identified by their expression of Sonic Hedgehog (Shh). Finally, we showed that β‐catenin activity is significantly reduced in taste buds of 25‐week‐old mice compared with 10‐week‐old animals. Our data suggest that Wnt/β‐catenin signaling may influence taste cell turnover by regulating cell differentiation. Reduced canonical Wnt signaling in older mice could explain in part the loss of taste sensitivity with aging, implicating a possible deficiency in the rate of taste cell renewal. More investigations are now necessary to understand if and how Wnt signaling regulates adult taste cell turnover. genesis 49:295–306, 2011. © 2011 Wiley‐Liss, Inc.
Podosomal proteins as causes of human syndromes: A role in craniofacial development?
Authors: Cejudo‐Martin Pilar , Courtneidge Sara A.
Published: February 2011

Podosomes and invadopodia are actin‐rich protrusions of the plasma membrane important for matrix degradation and cell migration. Most of the information in this field has been obtained in cancer cells, where the presence of invadopodia has been related to increased invasiveness and metastatic potential. The importance of the related podosome structure in other pathological or physiological processes that require cell invasion is relatively unexplored. Recent evidence indicates that essential components of podosomes are responsible for several human syndromes, some of which are characterized by serious developmental defects involving the craniofacial area, skeleton and heart, and very poor prognosis. Here we will review them and discuss the possible role of podosomes as a player in correct embryo development. genesis 49:209–221, 2011. © 2011 Wiley‐Liss, Inc.
Automatic Train Operation Using Autonomic Prediction of Train Runs
Authors: Asuka Masashi , Kataoka Kenji , Komaya Kiyotoshi , Nishida Syogo
Published: February 2011

In this paper, we present an automatic train control method adaptable to disturbed train traffic conditions. The proposed method presumes transmission of detected time of a home track clearance to trains approaching the station by employing equipment of Digital ATC (Automatic Train Control). Using the information, each train controls its acceleration by a method that consists of two approaches. First, by setting a designated restricted speed, the train controls its running time to arrive at the next station in accordance with predicted delay. Second, the train predicts the time at which it will reach the current braking profile generated by Digital ATC, along with the time when the braking profile transits ahead. By comparing them, the train correctly chooses the coasting drive mode in advance to avoid deceleration due to the current braking profile. We evaluated the effectiveness of the proposed method regarding driving conditions, energy consumption, and reduction of delays by simulation. © 2011 Wiley Periodicals, Inc. Electr Eng Jpn, 175(3): 65–73, 2011; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.10020/eej.21080
Ammonia and Dinitrogen Activation by Surface Organometallic Chemistry on Silica‐Grafted Tantalum Hydrides
Authors: Chow Catherine , Taoufik Mostafa , Quadrelli Elsje Alessandra
Published: February 2011

Ammonia N–H bond activation and dinitrogen N≡N cleavage with dihydrogen on an isolated metal atom have been achieved with the silica‐grafted TaIII and TaV hydrides [(≡SiO)2TaH] (2a) and [(≡SiO)2TaH3] (2b), accessed through surface organometallic chemistry (SOMC). The synthesis of the starting tantalum hydrides 2a and 2b by grafting tris(neopentyl)neopentylidenetantalum(V), Ta(=CH–tBu)Np3, on silica yields well‐defined, isolated tantalum atoms. Silsesquioxane molecular modelling shows that the mechanism of the grafting reaction implies a tetraalkyl intermediate [(≡SiO)TaNp4]. The starting hydrides 2a and 2b react stoichiometrically and catalytically with alkanes in reactions such as alkane metathesis, cross‐metathesis between ethane and toluene, and methane coupling to form ethane. Mechanistic studies show the relevance of tantalum carbenes and Chauvin‐like metallacyclobutane intermediates in most of these reactions. Finally, the stoichiometric N2 cleavage and NH3 activation to the final imido amido tantalum(V) complex [(≡SiO)2Ta(NH)(NH2)] (3) are reviewed and discussed mechanistically. In the N≡N cleavage reaction, dihydrogen adducts on silica‐grafted isolated tantalum atoms appear to play a central role. The ammonia reaction occurs by bifunctional activation through the Lewis acid/Lewis base couple formed by a metal centre and a coordinated nitrogen atom, the so‐called “NH effect”. Such bifunctional activation is also observed for the heterolytic cleavage of H2 by [(≡SiO)2Ta(NH)(NH2)] (3).
Vertically Well‐Aligned In2O3 Cone‐Like Nanowire Arrays Grown on Indium Substrates
Authors: Yin Wenyan , Doty Matt , Ni Chaoying , Hu Changwen , Cao Minhua , Wei Bingqing
Published: February 2011

Single‐crystalline, cone‐like In2O3 nanowire (NW) arrays were directly synthesized on the surface of indium grains without any catalyst by using a simple chemical vapor deposition (CVD) method. The indium grains served both as the indium source, which reacted with different oxygen sources, and the substrate for the growth of the cone‐like In2O3 NW arrays. The controllable synthesis of the cone‐like In2O3 NW arrays with variable densities, sizes, and morphologies were achieved by adjusting the oxygen sources. A possible mechanism was proposed for the formation of the cone‐like In2O3 NW arrays. The photoluminescence spectrum of the low‐density, cone‐like In2O3 NW arrays shows emission in a wide range, from the visible (yellow light) into the near infrared region.
Ring‐Shaped J‐Type and Star‐Shaped H‐Type Nanostructures of an Unsymmetrical (Phthalocyaninato)zinc Complex
Authors: Tian Naichang , Ma Pan , Wang Quanbo , Zhang Xianyao , Jiang Jianzhuang , Bai Ming
Published: February 2011

Unsymmetrical (phthalocyaninato)zinc complex 1 was synthesized by transesterification and self‐assembled into ring‐shaped nanostructures with J‐type aggregation at the chloroform/water interface and into star‐shaped nanostructures with H‐type aggregation in the chloroform/methanol system, respectively. Its self‐assembly properties have been studied by spectroscopic, transmission electron microscopy (TEM), scanning electron microscopy (SEM), and X‐ray diffraction (XRD) techniques. The star‐shaped nanostructures were found to have better semiconducting properties than the ring‐shaped nanostructures due to the more effective intermolecular π‐electron delocalization. The results appear to represent the first example of nanostructures with J‐ and H‐type molecular conformations self‐assembled from the same phthalocyanine compound in different solvent systems with novel ring‐ and star‐shaped morphologies, respectively.
Influence of N‐Substitution on the Oxidation of 2‐Pyridylmethylamines with Bis(trimethylsilyl)amides of Iron(III) – Synthesis of Heteroleptic Iron(II) 2‐Pyridylmethylamides
Authors: Malassa Astrid , Schulze Benjamin , Stein‐Schaller Brigitte , Görls Helmar , Weber Birgit , Westerhausen Matthias
Published: February 2011

The reaction of (thf)Fe[N(SiMe3)2]2Cl with (2‐pyridylmethyl)(diphenylphosphanyl)amine (1) in hot tetrahydrofuran (THF) yields dinuclear [(ClFe)2{μ‐N(SiMe3)2}{Ph2P(NCH2Py)2}] (2) and [ClFe{Ph2P(O)‐NCH2Py}]2 (3) with the oxygen atom stemming from THF degradation. The formation of 2 requires a P–N bond cleavage and reformation leading to the tetradendate diphenyl‐bis(2‐pyridylmethylamido)phosphonium ion. If this reaction of (thf)Fe[N(SiMe3)2]2Cl with 1 is performed at room temperature, no P–N bond cleavage is observed. Instead of that, ether degradation occurs yielding [Fe4(μ4‐O)(μ2‐Cl)2(Ph2P‐NCH2Py)4] (4) with a central oxygen‐centered iron tetrahedron as well as complex 3. Recrystallization of 3 from dichloromethane leads to addition of HCl and to the formation of [FeCl2·{Ph2P(O)‐N(H)‐CH2Py}] (5). The phosphonium ion of 2 is isoelectronic to the corresponding diphenyl‐bis(2‐pyridylmethylamino)silane (6). Lithiation of 6 followed by a metathetical reaction with (thf)2FeCl2 yields the trinuclear complex [Fe3Cl2{Ph2Si(NCH2Py)2}2] (7) with antiferromagnetic interactions.
Discrete Molecular Squares {[(en)M(CN)]4}4+ Derived from [(en)M(CN)2] (M = PtII, PdII)
Authors: Galstyan Anzhela , Sanz Miguel Pablo J. , Wolf Jacqueline , Freisinger Eva , Lippert Bernhard
Published: February 2011

C2h‐symmetrical tetranuclear metallacycles {[M(en)(CN)]4}(NO3)4 with M = PdII (4) and PtII (5) have been prepared upon reacting M(en)(CN)2 [M = PdII (1), PtII (2)] with [M(en)(H2O)2](NO3)2. Replacement of the nitrate anions of 5 by terephthalate anions yields the corresponding salt 5a. The X‐ray crystal structures of 1, 4, 5, and 5a have been determined. In the metallacycles 4, 5, and 5a the four metals form almost ideal squares with average M···M distances of ca. 5.05 Å (5, 5a) and 5.08 Å (4) along the sides. As shown by 1H NMR spectroscopy, the Pt square 5 is stable in aqueous solution, whereas the Pd square 4 undergoes rearrangement reactions upon aging or the presence of other Pd species such as (bpy)PdII. Preliminary studies on the possibility of non‐covalent interactions of 4 and 5 with model nucleobases in water reveal that only 5 is useful in this respect. According to the concentration‐dependence 1H NMR study, there is an interaction with the purine base 9‐ethyladenine, molecular details of which are unclear at this stage, however. Compound 4 is substitutionally labile and is transformed into the coordination compound 8 with 1‐methylcytosine. Two more side products, produced during the various reactions carried out, were characterized by X‐ray crystallography: [Pt(en)2][Pt(CN)4] (3) and [Pd(bpy)(en)](SO4)·3H2O (7).
Synthesis and Reactivity of a New Oxidation‐Labile Heterobimetallic Mn6Zn2 Carbamate Cluster and Precursor to Nanosized Magnetic Oxide Particles
Authors: Domide Dan , Hübner Olaf , Behrens Silke , Walter Olaf , Wadepohl Hubert , Kaifer Elisabeth , Himmel Hans‐Jörg
Published: February 2011

The synthesis and characterization of the new octanuclear mixed carbamate complex [Zn2Mn6(μ4‐O)2(O2CN(iPr)2)12] is reported. This complex is readily oxidized by O2 to give [Zn2Mn6(μ4‐O)2(μ3‐O)(O2CN(iPr)2)12] featuring a central O atom statistically distributed over two sites within the void of the inner Mn6 cage of the carbamate complex. In relation to the situation before oxidation, the metal cage is expanded by a change of the carbamate bonding mode. The two carbamate complexes were used as precursors to magnetic oxide nanoparticles under mild conditions (210–270 °C depending on the heating rate). A mixture of crystalline ZnMn2O4 and MnO nanoparticles resulted. The experimental data are complemented by some quantum chemical (DF) calculations.
Synthesis of Chiral Furopyrrolizidinones through a Key Tandem Cope Elimination/1,3‐Dipolar Cycloaddition Reaction of Tricyclic Lactones
Authors: Li Yu‐Jang , Chuang Hsiang‐Yu , Yeh Shang‐Ming , Huang Weng‐Sang
Published: February 2011

Highly functionalized chiral furo‐pyrrolizidinones containing contiguous quaternary centers were synthesized in moderate to good yields by treatment of various hexahydro‐3,4‐dioxa‐8a‐aza‐as‐indacen‐2‐ones with m‐CPBA under basic conditions through a tandem Cope elimination/1,3‐dipolar cycloaddition reaction sequence, followed by N–O cleavage and lactam ring cyclization.
Economic and technical management of an aggregation agent for electric vehicles: a literature survey
Authors: Bessa Ricardo J. , Matos Manuel A.
Published: February 2011

The foreseeable increase in the use of electric vehicles (EV) led to the discussion on intermediate entities that could help manage a great number of EV. An aggregation agent for electric vehicles is a commercial middleman between a system operator (SO) and plug‐in EV. From the SO perspective, the aggregator is seen as a large source of generation or load, which could provide ancillary services such as spinning and regulating reserve. Generally, these services will be provided in the day‐ahead and intraday electricity markets. In addition, the aggregator also participates in the electricity market with supply and demand energy bids. This paper provides a comprehensive bibliographic survey on the aggregator role in the power system operation and electricity market. The scope of the survey covers 59 references divided in journal, conference proceedings, thesis, research papers, and technical reports published after 1994. These papers are put into several technical categories: electricity market and EV technical and economic issues; aggregation agent concept, role and business model; algorithms for EV management as a load/resource. Copyright © 2011 John Wiley & Sons, Ltd.
A new time‐domain based power system frequency estimation algorithm
Authors: Seyedi Heresh , Sanaye‐Pasand Majid
Published: February 2011

Frequency stability is one of the most important features of power systems. It is closely dependent on the value of system frequency. In the present day modern power systems, fast and accurate frequency estimation has become quite vital. Any mistake in accurate estimation of frequency may threaten the frequency stability or at least lead to system operation problems. In this paper, a new time‐domain based power system frequency estimation algorithm is proposed. Different abnormal events such as frequency decline due to load‐generation mismatch are modeled and ability of the new frequency measurement technique to track the frequency is tested. Performance of the new method is evaluated and compared with an existing frequency estimation algorithm. Simulation results confirm advantages of the new approach over the existing method. Copyright © 2011 John Wiley & Sons, Ltd.
Variational data assimilation using targetted random walks
Authors: Cotter S. L. , Dashti M. , Stuart A. M.
Published: February 2011

The variational approach to data assimilation is a widely used methodology for both online prediction and for reanalysis. In either of these scenarios, it can be important to assess uncertainties in the assimilated state. Ideally, it is desirable to have complete information concerning the Bayesian posterior distribution for unknown state given data. We show that complete computational probing of this posterior distribution is now within the reach in the offline situation. We introduce a Markov chain–Monte Carlo (MCMC) method which enables us to directly sample from the Bayesian posterior distribution on the unknown functions of interest given observations. Since we are aware that these methods are currently too computationally expensive to consider using in an online filtering scenario, we frame this in the context of offline reanalysis. Using a simple random walk‐type MCMC method, we are able to characterize the posterior distribution using only evaluations of the forward model of the problem, and of the model and data mismatch. No adjoint model is required for the method we use; however, more sophisticated MCMC methods are available which exploit derivative information. For simplicity of exposition, we consider the problem of assimilating data, either Eulerian or Lagrangian, into a low Reynolds number flow in a two‐dimensional periodic geometry. We will show that in many cases it is possible to recover the initial condition and model error (which we describe as unknown forcing to the model) from data, and that with increasing amounts of informative data, the uncertainty in our estimations reduces. Copyright © 2011 John Wiley & Sons, Ltd.
Implicit finite element schemes for the stationary compressible Euler equations
Authors: Gurris Marcel , Kuzmin Dmitri , Turek Stefan
Published: February 2011

A semi‐implicit finite element scheme and a Newton‐like solver are developed for the stationary compressible Euler equations. Since the Galerkin discretization of the inviscid fluxes is potentially oscillatory and unstable, the troublesome antidiffusive part is constrained within the framework of algebraic flux correction. A generalization of total variation diminishing (TVD) schemes is employed to blend the original Galerkin scheme with its nonoscillatory low‐order counterpart. Unlike standard TVD limiters, the proposed limiting strategy is fully multidimensional and readily applicable to unstructured meshes. However, the nonlinearity and nondifferentiability of the limiter function makes efficient computation of stationary solutions a highly challenging task, especially in situations when the Mach number is large in some subdomains and small in other subdomains. In this paper, a semi‐implicit scheme is derived via a time‐lagged linearization of the Jacobian operator, and a Newton‐like method is obtained in the limit of infinite CFL numbers. Special emphasis is laid on the numerical treatment of weakly imposed characteristic boundary conditions. A boundary Riemann solver is used to avoid unphysical boundary states. It is shown that the proposed approach offers unconditional stability, as well as higher accuracy and better convergence behavior than algorithms in which the boundary conditions are implemented in a strong sense. The overall spatial accuracy of the constrained scheme and the benefits of the new boundary treatment are illustrated by grid convergence studies for 2D benchmark problems. Copyright © 2011 John Wiley & Sons, Ltd.
Comparing costs and outcomes across programmes of health care
Authors: Martin Stephen , Rice Nigel , Smith Peter C.
Published: February 2011

This paper examines the expenditure choices of local health authorities operating under fixed budget constraints. It applies a theoretical model of budgeting to a data set from 303 English Primary Care Trusts (PCTs) across ten broad programmes of health care to derive estimates of the elasticity of expenditure in each programme with respect to the total income of the PCT. The results suggest quite similar income elasticities across most programmes, in the range 0.644–1.128. The only outlier is the musculoskeletal programme with an elasticity of about 0.46. The modelling also derives estimates of spending elasticities with respect to medical needs and thereby permits calculation of the implicit cost of saving a life year in five programmes of care. The results are important as they indicate to policy makers how specific programme areas might be affected by general budgetary reductions. Copyright © 2011 John Wiley & Sons, Ltd.
Randomized comparison of reduced fat and reduced carbohydrate hypocaloric diets on intrahepatic fat in overweight and obese human subjects
Authors: Haufe Sven , Engeli Stefan , Kast Petra , Böhnke Jana , Utz Wolfgang , Haas Verena , Hermsdorf Mario , Mähler Anja , Wiesner Susanne , Birkenfeld Andreas L. , Sell Henrike , Otto Christoph , Mehling Heidrun , Luft Friedrich C. , Eckel Juergen , Schulz-Menger Jeanette , Boschmann Michael , Jordan Jens
Published: February 2011

Obesity-related hepatic steatosis is a major risk factor for metabolic and cardiovascular disease. Fat reduced hypocaloric diets are able to relieve the liver from ectopically stored lipids. We hypothesized that the widely used low carbohydrate hypocaloric diets are similarly effective in this regard. A total of 170 overweight and obese, otherwise healthy subjects were randomized to either reduced carbohydrate (n = 84) or reduced fat (n = 86), total energy restricted diet (−30% of energy intake before diet) for 6 months. Body composition was estimated by bioimpedance analyses and abdominal fat distribution by magnetic resonance tomography. Subjects were also submitted to fat spectroscopy of liver and oral glucose tolerance testing. In all, 102 subjects completed the diet intervention with measurements of intrahepatic lipid content. Both hypocaloric diets decreased body weight, total body fat, visceral fat, and intrahepatic lipid content. Subjects with high baseline intrahepatic lipids (>5.56%) lost ≈7-fold more intrahepatic lipids compared with those with low baseline values (<5.56%) irrespective of diet composition. In contrast, changes in visceral fat mass and insulin sensitivity were similar between subgroups, with low and high baseline intrahepatic lipids.

Conclusion:

A prolonged hypocaloric diet low in carbohydrates and high in fat has the same beneficial effects on intrahepatic lipid accumulation as the traditional low-fat hypocaloric diet. The decrease in intrahepatic lipids appears to be independent of visceral fat loss and is not tightly coupled with changes in whole body insulin sensitivity during 6 months of an energy restricted diet. (HEPATOLOGY 2011)
Osteoblast‐secreted factors enhance the expression of dysadherin and CCL2‐dependent migration of renal carcinoma cells
Authors: Schüler Yvonne , Lee‐Thedieck Cornelia , Geiger Konstanze , Kaiser Tatjana , Ino Yoshinori , Aicher Wilhelm K. , Klein Gerd
Published: February 2011

Renal cell carcinoma (RCC) frequently metastasizes to the bone marrow. These metastases are characterized by extensive osteolytic lesions. The mechanism, however, by which RCC cells metastasize to bone marrow remains poorly understood. To unravel the role of bone marrow cells in this context, we performed cell adhesion and migration assays using human RCC cell lines to analyze the influence of resident bone marrow cells on renal tumor cells. The strongest adhesion of RCC cells was observed to osteoblasts. Moreover, conditioned medium of osteoblasts (OB‐CM) significantly increased RCC cell migration. By gene expression analysis dysadherin was identified as a transcript whose expression could be elevated more than twofold in RCC cells when exposed to OB‐CM. Suppression of dysadherin expression in RCC cells by siRNA reduced their ability to migrate in the presence of OB‐CM. Furthermore, the RCC cells secreted high amounts of the chemokine CCL2 when tumor cells migrated under the influence of osteoblast‐secreted factors. CCL2 neutralization strongly reduced the migratory ability of the RCC cells. Silencing the expression of dysadherin in RCC cells resulted in a twofold reduction of CCL2 protein expression indicating a dysadherin‐dependent expression of the chemokine. Taken together, our data show that osteoblasts are the major cell type of the bone marrow that affect RCC cells by secreting factors that increase the expression of dysadherin and CCL2 in the tumor cells leading to enhanced cell migration. These data suggest an osteoblast‐induced autocrine mechanism for a facilitated homing of RCC cells to the bone marrow.
Spectrin αII and βII tetramers contribute to platinum anticancer drug resistance in ovarian serous adenocarcinoma
Authors: Maeda Osamu , Shibata Kiyosumi , Hosono Satoyo , Fujiwara Sawako , Kajiyama Hiroaki , Ino Kazuhiko , Nawa Akihiro , Tamakoshi Koji , Kikkawa Fumitaka
Published: February 2011

To overcome drug resistance in ovarian carcinoma, novel resistance mechanisms must be elucidated for clinical application. We purified 2 proteins in the 300 kDa range from cisplatin‐resistant cells (NOS2CR2) by affinity chromatography with cisplatin‐exposed Glutathione Sepharose 4B. The purified proteins were identified as spectrin αII and βII by peptide mass mapping analysis. Western blot analysis detected greater expression of spectrin αII and βII in NOS2CR2 than in wild‐type cells (NOS2). The same result was obtained for spectrin βII expression by immunohistochemical staining. To determine whether spectrin αII and βII contribute to resistance, a drug sensitivity test was performed on SKOV3 ovarian cancer cells transfected with small interfering RNA. Sensitivity to platinum drugs was increased in the expression reduced cells. In a clinical study of five ovarian serous adenocarcinoma cases, tumor specimens taken after treatment with carboplatin stained more strongly for spectrin βII expression than untreated specimens. Fifty‐two tumor specimens from 46 patients with ovarian serous adenocarcinoma were immunohistochemically stained for spectrin βII and scored. Tumors previously treated by chemotherapy scored higher than those not treated. Of 27 cases with detectable residual tumors at the time of surgery, cases scoring 4–6 had shorter progression‐free survival periods after platinum‐based chemotherapy than cases scoring 0–3 (p = 0.012). The cytoskeleton proteins Spectrin αII and βII contributed to drug resistance by anchoring the GS‐Pt complex to the cell membrane, arresting cisplatin activity. Thus spectrin βII may be a useful predictor of platinum sensitivity in ovarian serous adenocarcinoma.
Lower sensitivity of screening mammography after previous benign breast surgery
Authors: van Breest Smallenburg Vivian , Duijm Lucien E.M. , Voogd Adri C. , Groenewoud Johanna H. , Jansen Frits H. , van Beek Mike , Louwman Marieke W.J.
Published: February 2011

Few data are available on the effect of previous benign breast surgery on screening mammography accuracy. We determined whether sensitivity of screening mammography and tumor characteristics are different for women with and without previous benign breast surgery. We included a consecutive series of 317,398 screening mammograms of women screened between 1997 and 2008. During 2‐year follow‐up, clinical data, breast imaging, biopsy and surgery reports were collected from women with screen‐detected or interval breast cancers. Screening sensitivity, tumor biology and tumor stages were compared between 168 women with breast cancer and prior ipsilateral benign breast surgery and 2,039 women with breast cancer but without previous ipsilateral, benign breast surgery. The sensitivity of screening mammography was significantly lower for women with prior surgery [64.3% (108/168) versus 73.4% (1,496/2,039), p = 0.01]. The concomitant increased interval cancer risk remained significant after logistic regression adjustment for age and breast density (OR = 1.5, 95% CI: 1.1–2.1). Comparing screen‐detected cancers in women with and without prior breast surgery, no significant differences in estrogen receptor status (p = 0.56), mitotic activity (p = 0.17), proportions of large (T2+) tumors (p = 0.6) or lymph node positive tumors (p = 0.4) were found. Also for interval cancers, no differences were found in estrogen receptor status (p = 0.41), mitotic activity (p = 0.39), proportions of large tumors (p = 0.9) and lymph node positive tumors (p = 0.5) between women with and without prior breast surgery. We conclude that sensitivity of screening mammography is significantly lower in women with previous benign breast surgery than without, but tumor characteristics are comparable both for screen detected cancers and interval cancers.
TMZ‐induced PrPc/par‐4 interaction promotes the survival of human glioma cells
Authors: Zhuang Dongxiao , Liu Yingchao , Mao Ying , Gao Liang , Zhang Haishi , Luan Shihai , Huang Fengping , Li Qingquan
Published: February 2011

Malignant gliomas recur even after extensive surgery and chemo‐radiotherapy. Although a relatively novel chemotherapeutic agent, temozolomide (TMZ), has demonstrated promising activity against gliomas, the effects last only a few months and drug resistance develops thereafter in many cases. It has been acknowledged that glioma cells respond to TMZ treatment by undergoing G2/M arrest, but not apoptosis. Here we demonstrate a phase‐specific chemotherapy resistance due to cellular prion protein (PrPc) in human glioma cells upon TMZ treatment. TMZ‐induced G2/M‐arrested cultures show an upregulation of PrPc expression and are more resistant, whereas G1/S‐phase cells that show decreased levels of PrPc are more sensitive to apoptosis. Furthermore, an investigation into the biological significance of PrPc association with par‐4 provided the first evidence of a relationship between the endogenous levels of PrPc and the resistance of glioma cells to the apoptotic effects of TMZ. Upon TMZ treatment, PrPc exerts its antiapoptotic activity by inhibiting PKA‐mediated par‐4 phosphorylation that are important for par‐4 activation, nuclear entry and initiation of apoptosis. In context with cell cycle‐dependent responses to chemotherapy, the data from this study suggest the possibility of exploiting the PrPc‐dependent pathway to improve the efficacy of TMZ‐based regimen for patients with gliomas.
Cross‐Linking Organic and Polyoxometalate Chemistries
Authors: Thorimbert Serge , Hasenknopf Bernold , Lacôte Emmanuel
Published: February 2011

This paper is a choral personal account on a longstanding and fruitful collaboration of organic and inorganic chemists to develop new hybrid polyoxometallic systems. .We explain our motivation and the context of our work that led to polyoxometalates with highly functional and reactive organic groups. Our approach yielded catalytically, biologically, and photochemically active systems.
Testing the ONIOM G2R3 model against donor–acceptor dissociation energies of group 13–15 complexes: Accuracy comparable to CCSD(T)/aug‐CC‐pVTZ at a fraction of the resource cost
Authors: Gilbert Thomas M.
Published: February 2011

The ability of the composite three‐layer ONIOM G2R3 (OG2R3) method to match experimental dissociation energies for group 13–15 donor–acceptor complexes was examined for a database of 34 complexes. The composite approach provides energies that agree reasonably with experiment, performing nearly as well as both the CCSD(T)/aug‐CC‐pVTZ and CCSD(T)/6‐311+G(2df, 2p) models for small molecules and nearly as well as the latter for slightly larger ones. Broadly, all three models exhibit average absolute errors of ∼3 kcal mol−1, and root mean square errors of ∼4 kcal mol−1. The average signed error suggest that the OG2R3 approach systematically underbinds by ∼2.3 kcal mol−1; if this is used as a general correction, the approach performs as well or better than the pure CCSD(T) models. However, the OG2R3 model can be applied to molecules too large to be studied by the other CCSD(T) methods, as it requires only a fraction of the time and computer resources. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Pharmacophore alignment search tool: Influence of the third dimension on text‐based similarity searching
Authors: Hähnke Volker , Klenner Alexander , Rippmann Friedrich , Schneider Gisbert
Published: February 2011

Previously (Hähnke et al., J Comput Chem 2010, 31, 2810) we introduced the concept of nonlinear dimensionality reduction for canonization of two‐dimensional layouts of molecular graphs as foundation for text‐based similarity searching using our Pharmacophore Alignment Search Tool (PhAST), a ligand‐based virtual screening method. Here we apply these methods to three‐dimensional molecular conformations and investigate the impact of these additional degrees of freedom on virtual screening performance and assess differences in ranking behavior. Best‐performing variants of PhAST are compared with 16 state‐of‐the‐art screening methods with respect to significance estimates for differences in screening performance. We show that PhAST sorts new chemotypes on early ranks without sacrificing overall screening performance. We succeeded in combining PhAST with other virtual screening techniques by rank‐based data fusion, significantly improving screening capabilities. We also present a parameterization of double dynamic programming for the problem of small molecule comparison, which allows for the calculation of structural similarity between compounds based on one‐dimensional representations, opening the door to a holistic approach to molecule comparison based on textual representations. © 2011 Wiley Periodicals, Inc. J Comput Chem , 2011.
Paths to which the nudged elastic band converges
Authors: Sheppard Daniel , Henkelman Graeme
Published: February 2011

A recent letter to the editor (Quapp and Bofill, J Comput Chem 2010, 31, 2526) claims that the nudged elastic band (NEB) method can converge toward gradient extremal paths and not to steepest descent paths, as has been assumed. Here, we show that the NEB does in fact converge to steepest descent paths and that the observed tendency for the NEB to approach gradient extremal paths was a consequence of implementation errors. We also note that while the NEB finds steepest descent paths, these are not necessarily minimum energy paths in the sense of being a set of points which are minima in the potential energy surface perpendicular to the path. An example is given where segments of steepest descent paths follow potential energy ridges. © 2011 Wiley Periodicals, Inc. J Comput Chem , 2011.
Modeling the electron density kernels
Authors: Szarek Paweł , Komorowski Ludwik
Published: February 2011

Existing approximation to the softness kernel, successfully explored in earlier work, has been extended; the normal Gauss distribution function has been used instead of the Dirac delta. The softness kernel becomes continuous functions in space and may be used to calculate the linear response function of the electron density. Three‐dimensional visualization of the softness kernel and the linear response function are presented for a nitrogen atom as a working example. By using a single parameter of the spatial Gauss distribution, the novel softness kernel has been adjusted to be consistent with the standard form of the hardness kernel, representing the leading fraction of the electronic interactions in the system. © 2011 by Wiley Periodicals, Inc.
Extraction properties of phthalic acid and aromatic polycarboxylic acids using various solvents
Authors: Zhou Zhiyong , Qin Wei
Published: February 2011

BACKGROUND: To explore the extraction properties of aromatic acids produced in the oxidation of coal, the extraction equilibrium of phthalic acid (as a typical product) was studied using three solvents, 1‐octanol, 50% tributylphosphate (TBP)/kerosene, and 10% trialkylphosphine oxide (TRPO)/kerosene, and the feasibility of separating phthalic, [1,1′‐biphenyl]‐2,2′‐dicarboxylic and trimellitic acids is discussed.

RESULTS: Phthalic acid extraction followed the sequence: 10% TRPO > 50% TBP > 1‐octanol, with recoveries from the TRPO and TBP systems being much larger than that for 1‐octanol. The stoichiometry of formation of the complexes of TBP and TRPO with phthalic acid was 1:1. The apparent extraction equilibrium constant for TRPO is much larger than that for TBP. The distribution coefficient of [1,1′‐biphenyl]‐2,2′‐dicarboxylic acid is much larger than that of the other two acids using 1‐octanol as the extractant and this acid could be removed by 1‐octanol from a mixture of the three acids. The extraction equilibrium correlations obtained for the individual acid component systems can be used to predict that of the acid mixture.

CONCLUSION: The extent of phthalic acid extraction by the three solvents investigated is as follows: 10% TRPO > 50% TBP > 1‐octanol. The stoichiometry of the complex formation of TBP or TRPO and phthalic acid is 1:1, and the apparent extraction equilibrium constant for TRPO is much larger than that for TBP. 1‐octanol shows a good extractive selectivity for [1,1′‐biphenyl]‐2,2′‐dicarboxylic acid as compared with phthalic and trimellitic acids. Copyright © 2011 Society of Chemical Industry
Ethanol—the primary renewable liquid fuel
Authors: Datta Rathin , Maher Mark A. , Jones Coleman , Brinker Richard W.
Published: February 2011

This perspective paper establishes that ethanol has a long history of very good performance as a renewable liquid fuel blended with gasoline and can be used in over 80% of the automobile and other light duty transportation vehicles. It fits very well into the future of the combination of electricity and renewable liquid fuel for such transportation. It has also been established that renewable biomass feedstock is highly oxygenated and ethanol can be produced with high yields and efficiency with some conversion technologies—particularly the ‘Hybrid’ of gasification with bioconversion—that have been developed to the commercial implementation stage. Recent major studies conducted by the USDA, DOE and major National Laboratories have projected that large and sustainable biomass feedstock supplies are available and are going to be available to efficiently produce this ethanol in very large quantities of around 340 billion liters per year in the USA. The experience gained over the past 70 years in the south‐eastern USA has been summarized to further support the fact that efficient and sustainable biomass supply can be developed and maintained to support much increased usage. Copyright © 2011 Society of Chemical Industry