bluuebunny/crossref_metadata_2025 huggingface dataset:
Ratio of Right to Left Ventricular Ejection: A Pilot Study Using Doppler to Detect Interventricular Dyssynchrony
Authors: López‐Candales Angel , Edelman Kathy
Published: April 2011

Background:

Chronic pulmonary hypertension (cPH) is known to delay maximal right ventricular (RV) deformation, causing mechanical dyssynchrony, which previously has been identified only through the use of myocardial tissue Doppler imaging. However, alterations between RV and left ventricular (LV) ejection should be easily identified during routine echocardiographic examinations.

Hypothesis:

We hypothesized that assessment of differences in ejection fraction between left and right ventricles would be detected using pulsed Doppler.

Methods:

Standard echo and Doppler data were collected from 30 patients without PH (mean age, 53 ± 7 y; mean pulmonary artery systolic pressure [PASP], 31 ± 5 mm Hg) and from 40 patients with cPH (mean age, 53 ± 13 y, P not significant; mean PASP, 82 ± 24 mm Hg, P<0.00001). Temporal differences in the ejection of both ventricles were measured as the ratio of total duration of RV to LV outflow tract (RVOT and LVOT) pulsed Doppler signals.

Results:

A ratio (<0.99) of RVOT to LVOT total duration of ejection was found not only to be the best Doppler parameter to identify an abnormal pulmonary artery systolic pressure, with a 90% sensitivity and 100% specificity (area under the curve 0.958, P = 0.0001), but also identified differences in the temporal ejection between the 2 ventricles, or dyssynchrony, as a result of cPH.

Conclusions:

The ratio of pulsed Doppler RV to LV total duration of ejection is easily obtainable and appears useful in identifying the presence of interventricular dyssynchrony in cPH patients. A prospective study is now required to determine if this Doppler ratio can identify minute changes in the ejection of both ventricles as a result of changes in disease status or response to PH therapy. © 2011 Wiley Periodicals, Inc.

The authors have no funding, financial relationships, or conflicts of interest to disclose.
Seasonal Variation in Heart Failure Hospitalization
Authors: Gallerani Massimo , Boari Benedetta , Manfredini Fabio , Manfredini Roberto
Published: April 2011

Background:

A seasonal variation has been reported for occurrence of acute cardiovascular events, such as myocardial infarction, sudden death, and rupture/dissection of aortic aneurysms.

Hypothesis:

The aim of this study was to determine whether a seasonal variation exists for heart failure (HF) hospitalization.

Methods:

The study included all cases of HF admissions to Ferrara Hospital between January 2002 and December 2009. The sample was divided into subgroups by gender, age, cardiovascular risk factors, patients' outcome, and order of ICD‐9 codes (first diagnosis, accessory diagnosis). On the basis of date of admission, cases have been analyzed for seasonal variation and annual frequency. For seasonal analysis, monthly cases were categorized into four 3‐month intervals by seasons. Moreover, monthly admissions have been also adjusted for number of days, and the average number of admissions per month has been used.

Results:

The database included 15 954 patients with the ICD‐9‐CM codes of HF (420–429). Hospital admissions for HF were most frequent in winter (28.4%) and least in summer (20.4%). Chronobiological analysis yielded a significant peak in January for total cases and all subgroups considered. No differences were found for subgroups by gender, age, fatal cases, presence of hypertension and diabetes mellitus, patients' outcome, and order of ICD‐9 codes (first diagnosis, accessory diagnosis).

Conclusions:

A seasonal periodicity for HF hospitalization was demonstrated, with a peak in winter months, independent of gender, age, major cardiovascular risk factor, and patients' outcome. These data could be useful for practitioners to improve causative prevention measures, therapeutic management, and educational strategies. © 2011 Wiley Periodicals, Inc.

The authors have no funding, financial relationships, or conflicts of interest to disclose.
Ranolazine for the Treatment of Heart Failure With Preserved Ejection Fraction: Background, Aims, and Design of the RALI‐DHF Study
Authors: Jacobshagen Claudius , Belardinelli Luiz , Hasenfuss Gerd , Maier Lars S.
Published: April 2011

Background:

Heart failure with preserved ejection fraction (HFpEF), formerly referred to as diastolic heart failure (DHF), accounts for >50% of all HF patients. So far, there has been no specific treatment for impaired left ventricular (LV) relaxation. Data from in vitro and animal studies indicate that ranolazine improves diastolic function by inhibiting the late sodium current.

Hypothesis:

RAnoLazIne for the Treatment of Diastolic Heart Failure (RALI‐DHF) is a prospective, single‐center, randomized, double‐blind, placebo‐controlled proof‐of‐concept study to determine if ranolazine compared with placebo will be more effective in improving diastolic function in patients with HFpEF.

Methods:

Twenty patients with HFpEF (EF ≥ 50% and ratio of transmitral Doppler early filling velocity to tissue Doppler early diastolic mitral annular velocity [E/E′] >15 or N‐terminal pro‐type brain natriuretic peptide >220 pg/mL) will be randomized to receive ranolazine or placebo in a 1.5:1 ratio during their catheterization if the LV end‐diastolic pressure is ≥18 mm Hg and the time constant of relaxation (τ) is ≥50 ms. Treatment will consist of intravenous infusion of study drug (or placebo) for 24 hours, followed by oral treatment for a total of 14 days.

Endpoints:

The study will include the following exploratory endpoints: (1) change from baseline to 30 minutes from initiation of intravenous study drug administration during cardiac catheterization hemodynamic parameters at both resting and paced (120 beats per minute) conditions: τ, LV end‐diastolic pressure, and dP/dtmin.; and (2) change from baseline to day 14 in E/E′, maximal oxygen consumption, and N‐terminal pro‐type brain natriuretic peptide.

Conclusions:

The RALI‐DHF study is designed as a translational study to bridge the gap between basic science and therapeutics and to determine if ranolazine, compared with placebo, will be more effective in improving diastolic function in patients with HFpEF. © 2011 Wiley Periodicals, Inc.

Dr. Maier is funded by the German Research Foundation (DFG) through a Heisenberg grant (MA1982/4‐1) and a Klinische Forschergruppe grant (MA1982/2‐2). The RALI‐DHF trial is funded by a grant from Gilead Sciences, Inc. (Palo Alto, CA). Dr. Belardinelli is employed by Gilead. Dr. Maier has a collaborative/research grant with Gilead. Drs. Maier and Jacobshagen received honoraria from Berlin‐Chemie. The authors have no other funding, financial relationships, or conflicts of interest to disclose.
Drug‐Eluting Stents vs Intracoronary Brachytherapy for In‐Stent Restenosis: A Meta‐Analysis
Authors: Lu Yong‐Guang , Chen Yan‐Mei , Li Lang , Zhao Rong‐Zhen , Fu Chun‐Hui , Yan Hua
Published: April 2011

Background:

It has been reported that drug‐eluting stents (DES) were superior to intracoronary brachytherapy (ICBT) in patients with in‐stent restenosis (ISR). However, it is unknown whether there might be differences between DES and ICBT in terms of efficacy and safety in large sample size and long‐term follow‐up.

Hypothesis:

The aim of this study was to determine whether DES implantation remains favorable in large sample size and long‐term follow‐up when compared with ICBT among patients with ISR.

Methods:

We conducted a search in MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials without language restrictions. A meta‐analysis of 1942 cases from 12 controlled trials of DES vs ICBT for ISR was performed.

Results:

Drug‐eluting stents were significantly more effective in reducing target‐vessel revascularization (TVR) (odds ratio [OR]: 0.44, 95% confidence interval [CI]: 0.23–0.81, P = 0.009) and binary restenosis (OR: 0.34, 95% CI: 0.26–0.46, P<0.00001) compared with ICBT at midterm follow‐up. There were no significant differences between DES and ICBT in cardiac death, myocardial infarction (MI), and late stent thrombosis at midterm follow‐up. A statistical significance has been found between the 2 groups in TVR (OR: 0.61, 95% CI: 0.43–0.86, P = 0.005) at long‐term follow‐up. There were no significant differences in cardiac death and MI between the 2 groups at long‐term follow‐up.

Conclusions:

These findings provide evidence that DES is superior to ICBT for the treatment of ISR in TVR and binary restenosis reduction, but not in cardiac death, MI, and late stent thrombosis reduction. © 2011 Wiley Periodicals, Inc.

Yong‐Guang Lu, MD, and Yan‐Mei Chen, MD, contributed equally to this work. The authors have no funding, financial relationships, or conflicts of interest to disclose.
Phase 1/2 study of everolimus in advanced hepatocellular carcinoma
Authors: Zhu Andrew X. , Abrams Thomas A. , Miksad Rebecca , Blaszkowsky Lawrence S. , Meyerhardt Jeffrey A. , Zheng Hui , Muzikansky Alona , Clark Jeffrey W. , Kwak Eunice L. , Schrag Deborah , Jors Kathryn R. , Fuchs Charles S. , Iafrate A. John , Borger Darrell R. , Ryan David P.
Published: April 2011

BACKGROUND:

The phosphoinositide 3‐kinase/Akt/mammalian target of rapamycin pathway plays a critical role in the pathogenesis of hepatocellular carcinoma (HCC). We performed a single‐arm, phase 1/2 study of everolimus in patients with advanced HCC.

METHODS:

Patients with histologically confirmed measurable advanced HCC, 0‐2 prior regimens, and adequate hematologic, hepatic, and renal functions received everolimus at 5 mg/day or 10 mg/day orally (6 weeks/cycle). The primary end points were determination of a safe dosage of everolimus (phase 1) and progression‐free survival (PFS) at 24 weeks (phase 2).

RESULTS:

Twenty‐eight patients were enrolled and evaluable for efficacy and toxicity. No dose‐limiting toxicities were observed at the 5 mg/day (n = 3) or 10 mg/day (n = 6) dosage level in phase 1. Twenty‐five patients received everolimus at 10 mg/day. Grade 3‐4 adverse events included lymphopenia (n = 3), aspartate transaminase (n = 3), hyponatremia (n = 2), and 1 patient each with anemia, alanine transaminase, hyperglycemia, proteinuria, rash, and hypoxia. One patient (4%) had partial response (95% confidence interval [CI], 0.9%‐19.6%). The median PFS and overall survival were 3.8 months (95% CI, 2.1‐4.6) and 8.4 months (95% CI, 3.9‐21.1), respectively. The estimated PFS rate at 24 weeks was 28.6% (95% CI, 7.9%‐49.3%).

CONCLUSION:

Everolimus was well tolerated in patients with advanced HCC, and 10 mg/day was defined as the phase 2 dosage. Although the study did not proceed to the second stage of phase 2, preliminary antitumor activity was observed with everolimus in patients with advanced HCC, most of whom had prior systemic treatment. Cancer 2011. © 2011 American Cancer Society.
A new model for chromotherapy application
Authors: Aktekın Denız Başbinar , Şımşek Yusuf
Published: April 2011

Although the effects of colors on the emotion have been studied, there have been differing results. Influences like age, culture, and personal stimulation are important factors in this phenomenon. Different chakra systems are well matched with different colors, and one of the chromotherapeutic methods is constructed to this chakra system as complementary and alternative medicine. However, as a consequence of the new findings and developments arising in color‐related research, we propose new model supported with afterimage and complementarity for this chakra system. © 2011 Wiley Periodicals, Inc. Col Res Appl, 2011
Semiclassical limit of quantum dynamics with rough potentials and well‐posedness of transport equations with measure initial data
Authors: Ambrosio Luigi , Figalli Alessio , Friesecke Gero , Giannoulis Johannes , Paul Thierry
Published: April 2011

In this paper we study the semiclassical limit of the Schrodinger equation. Under mild regularity assumptions on the potential U, which include Born‐Oppenheimer potential energy surfaces in molecular dynamics, we establish asymptotic validity of classical dynamics globally in space and time for “almost all” initial data, with respect to an appropriate reference measure on the space of initial data. In order to achieve this goal we prove existence, uniqueness, and stability results for the flow in the space of measures induced by the continuity equation. © 2011 Wiley Periodicals, Inc.
Recognition and Ordering at Surfaces: The Importance of Handedness and Footedness
Authors: Mark Andrew G. , Forster Matthew , Raval Rasmita
Published: April 2011

The expression of chirality at surfaces, arising from the adsorption of chiral molecules, is usually discussed in terms of the molecular handedness. However, the adsorption process often leads to a new manifestation of chirality in the form of the adsorption footprint. Therefore, in order to fully define the chirality of the interface we propose that both the handedness and the footedness of the system must be considered. To illustrate this point, we describe the ordering behavior of the molecules tartaric acid, succinic acid, proline, and 3‐pyrroline‐2‐carboxylic (PCA) on a Cu(110) surface using deconvolution maps separating the arrangement of enantiomers, conformers, adsorption footprints and rotamers within an organized assembly. Tartaric and succinic acid mimic the behavior of a conventional 3D conglomerate and racemic compound in terms of both the handedness and footedness, respectively. However, racemic PCA and proline, while expressing a random solid solution of enantiomers and conformers, both display unexpected degrees of order when adsorbate footprint and orientation are considered.
Regioselective Synthesis of 3‐Carbo‐5‐phosphonylpyrazoles through a One‐Pot Claisen–Schmidt/1,3‐Dipolar Cycloaddition/Oxidation Sequence
Authors: Martin Anthony R. , Mohanan Kishor , Toupet Loic , Vasseur Jean‐Jacques , Smietana Michael
Published: April 2011

A one‐pot reaction involving an aldehyde, a methyl ketone, and the Bestmann–Ohira reagent has been developed for the synthesis of variously substituted 3‐carbo‐5‐phosphonylpyrazoles. Our synthetic methodology features a domino Claisen–Schmidt/1,3‐dipolar cycloaddition/oxidation sequence, which leads to the target compounds in excellent yields. We further demonstrated that this unprecedented sequence could also be combined with a copper‐catalyzed azide–alkyne cycloaddition in a one‐pot, four‐step cascade process generating five new bonds and two heterocyclic rings.
Integration of 3‐D cell cultures in fluidic microsystems for biological screenings
Authors: Witte Hartmut , Stubenrauch Mike , Fröber Ulrike , Fischer Robert , Voges Danja , Hoffmann Martin
Published: April 2011

A life support system for the cultivation of adherent 2‐D and scaffold‐based 3‐D cell cultures in a microfluidic device, a Bio‐Micro‐Electro‐Mechanical System (BioMEMS) is presented. The miniaturization level and system set‐up allow incubator‐independent operation modes and long‐term experiments with real‐time microscope observation. A dedicated seeding procedure for adherent cells into the microstructures is one key issue of the BioMEMS developed. Several seeding methods for the cells were evaluated. Biocompatibility of all materials, surfaces and methods could be demonstrated. First experiments with several cell types show the feasibility of the approach employing standard laboratory protocols. At present, the modular design and set‐up offer a broad application spectrum as well as its future extension to e.g. cultivation of other cell types, coupled cultivation chambers and the implementation of other manipulation or analysis components.
Microfluidic devices and true‐color sensor as platform for glucose oxidase and laccase assays
Authors: Demirkol Dilek Odaci , Dornbusch Kay , Feller Karl‐Heinz , Timur Suna
Published: April 2011

The commonly used assay for measuring glucose oxidase (GOx) and laccase (Lac) activity, based on spectrophotometric test using 2,2′‐azinobis‐(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS), has been adapted to measure these enzyme activities via microfluidic devices. The effects of flow rate and concentration of substrates were examined. The developed assays allowed analyzing GOx and Lac activities in the range of 0.8–8.0 Unit (0.1–1.0 mg/mL) and 0.9–17.7 Unit (0.1–2.0 mg/mL), respectively. Moreover, repeatability tests were obtained for both enzyme assays.
Encapsulation of Langerhans' islets: Microtechnological developments for transplantation
Authors: Wiedemeier Stefan , Ehrhart Friederike , Mettler Esther , Gastrock Gunter , Forst Thomas , Weber Matthias M. , Zimmermann Heiko , Metze Josef
Published: April 2011

There is an increasing trend to apply microsystems and microfluidics to solve medical and biomedical tasks. Microfluidic modules are used to modify and manipulate cells and cell clusters for therapeutic applications. Specifically, a method and technical system for encapsulation of Langerhans' islets as an option for the future treatment of diabetes mellitus is described. Type‐1 diabetes patients suffer from an absolute lack of the hormone insulin caused by an autoimmune process destroying the Langerhans' islets. One way to restore glucose‐dependent insulin secretion is the transplantation of human pancreatic islet cells (85% beta cells) from cadaveric donors. However, to prevent the rejection of the transplanted cells by the immune system of the host, a life long immunosuppressive medication is necessary. One possible way to prevent this rejection would be the transplantation of immunoseparated Langerhans' islets, which are encapsulated in a 3D‐alginate matrix polymerized with ions like Ba2+. As has been successfully shown in animal experiments, this technique would furthermore allow the transplantation of xenograft islets and thus help to solve the problem of shortage in donor organs. We present a microfluidics‐based system for encapsulation of cells in alginate.
Effects of potential dietary inhibitors of endogenous DNA damage on mutagenesis and lipid peroxidation in lacZ mice
Authors: Kosinska Wieslawa , Khmelnitsky Michael , Kim Jung Hyun , Zhao Zhong‐Lin , Guttenplan Joseph B.
Published: April 2011

The effects of a nine month administration of dietary: (1) 3H‐1,2‐dithiole‐3‐thione (D3T), (2) N‐acetylcysteine (NAC), (3) antioxidant vitamin mix, (vitamin C+E), (4) free radical scavenger, amifostine, and (5) calorie restriction, (CR), on mutagenesis and lipid peroxidation in lung, kidney, spleen and liver of lacZ transgenic mice were examined. These agents/diets were chosen because they might inhibit certain proposed mechanisms of endogenous damage to DNA. The agents were added to a high fat, reduced antioxidant AIN‐76 diet, to better approximate a Western style diet than the conventional AIN‐76 diet. As the lacZ gene is not expressed, mutations in that gene are neutral, and simply accumulate over time. The mutant fractions in control mice increased about 50–100%. Most of the agents inhibited to various extents the age‐related increase in mutagenesis in lung, kidney, and/or spleen, but no inhibition was observed in liver. There was no significant effect of age on lipid peroxidation levels in controls, possibly reflecting steady state turnover of lipid peroxidation products. Almost all of the treatments except D3T inhibited lipid peroxidation in most organs to different degrees. The vitamin C+E mix was the most effective at inhibiting lipid peroxidation, but a single most effective inhibitor of mutagenesis could not be discerned. Some associations were observed between the reduction in lipid peroxidation and the inhibition of mutagenesis. The results are consistent with a partial role for oxidative stress in the age‐related increase in mutagenesis. These observations may have implications for chemoprevention of carcinogenesis. Environ. Mol. Mutagen., 2011. © 2011 Wiley‐Liss, Inc.
Fenthion and terbufos induce DNA damage, the expression of tumor‐related genes, and apoptosis in HEPG2 cells
Authors: Wu Jong‐C. , Hseu You‐Cheng , Tsai Jui‐Shan , Chen Lei‐Chin , Chye Soi M. , Chen Chin‐H. , Ching Chen Ssu
Published: April 2011

This study investigates the effects of fenthion and terbufos, two organophosphorous pesticides, on DNA damage, tumor‐related gene expression, and apoptosis in HepG2 cells. We found that exposure to concentrations ranging from 50 to 200 μM of fenthion and terbufos for 2 hr caused significant death in HepG2 cells. Both compounds induced DNA damage in a concentration‐dependent manner as measured using the alkaline comet assay. Tumor‐related genes (jun, myc, andfos) and apoptosis‐related genes (socs3, tnfaip3, ppp1r15a, andnr4a1) were up‐regulated by both compounds. Finally, both compounds induced apoptosis. The results demonstrate that both terbufos and fenthion induce DNA damage and should be considered potentially hazardous to humans. Environ. Mol. Mutagen., 2011. © 2011 Wiley‐Liss, Inc.
Characterization of environmental chemicals with potential for DNA damage using isogenic DNA repair‐deficient chicken DT40 cell lines
Authors: Yamamoto Kimiyo N. , Hirota Kouji , Kono Koichi , Takeda Shunichi , Sakamuru Srilatha , Xia Menghang , Huang Ruili , Austin Christopher P. , Witt Kristine L. , Tice Raymond R.
Published: April 2011

Included among the quantitative high throughput screens (qHTS) conducted in support of the US Tox21 program are those being evaluated for the detection of genotoxic compounds. One such screen is based on the induction of increased cytotoxicity in seven isogenic chicken DT40 cell lines deficient in DNA repair pathways compared to the parental DNA repair‐proficient cell line. To characterize the utility of this approach for detecting genotoxic compounds and identifying the type(s) of DNA damage induced, we evaluated nine of 42 compounds identified as positive for differential cytotoxicity in qHTS (actinomycin D, adriamycin, alachlor, benzotrichloride, diglycidyl resorcinol ether, lovastatin, melphalan, trans‐1,4‐dichloro‐2‐butene, tris(2,3‐epoxypropyl)isocyanurate) and one non‐cytotoxic genotoxic compound (2‐aminothiamine) for (1) clastogenicity in mutant and wild‐type cells; (2) the comparative induction of γH2AX positive foci by melphalan; (3) the extent to which a 72‐hr exposure duration increased assay sensitivity or specificity; (4) the use of 10 additional DT40 DNA repair‐deficient cell lines to better analyze the type(s) of DNA damage induced; and (5) the involvement of reactive oxygen species in the induction of DNA damage. All compounds but lovastatin and 2‐aminothiamine were more clastogenic in at least one DNA repair‐deficient cell line than the wild‐type cells. The differential responses across the various DNA repair‐deficient cell lines provided information on the type(s) of DNA damage induced. The results demonstrate the utility of this DT40 screen for detecting genotoxic compounds, for characterizing the nature of the DNA damage, and potentially for analyzing mechanisms of mutagenesis. Environ. Mol. Mutagen., 2011. © 2011 Wiley‐Liss, Inc.y
Semiactive fuzzy control of the seismic response of building frames with MR dampers
Authors: Das Diptesh , Datta T. K. , Madan Alok
Published: April 2011

A fuzzy‐logic control algorithm, based on the fuzzification of the MR damper characteristics, is presented for the semiactive control of building frames under seismic excitation. The MR damper characteristics are represented by force–velocity and force–displacement curves obtained from the sinusoidal actuation test. The method does not require any analytical model of MR damper characteristics, such as the Bouc‐Wen model, to be incorporated into the control algorithm. The control algorithm has a feedback structure and is implemented by using the fuzzy‐logic and Simulink toolboxes of MATLAB. The performance of the algorithm is studied by using it to control the responses of two example buildings taken from the literature—a three‐storey building frame, in which controlled responses are obtained by clipped‐optimal control and a ten‐storey building frame. The results indicate that the proposed scheme provides nearly the same percentage reduction of responses as that obtained by the clipped‐optimal control with much less control force and much less command voltage. Position of the damper is found to significantly affect the controlled responses of the structure. It is observed that any increase in the damper capacity beyond a saturation level does not improve the performance of the controller. Copyright © 2011 John Wiley & Sons, Ltd.
Nonstationary seismic responses of structure with nonlinear stiffness subject to modulated Kanai–Tajimi excitation
Authors: Jin X. L. , Huang Z. L. , Leung A. Y. T.
Published: April 2011

A simple structure under earthquake excitation is modeled as a single‐degree‐of‐freedom system with nonlinear stiffness subject to modulated Kanai–Tajimi excitation. The nonstationary responses including the nonstationary probability densities of the system responses and the statistical moments are obtained in semi‐analytical form. By applying the stochastic averaging method based on the generalized harmonic functions, the averaged Fokker–Planck–Kolmogorov(FPK) equation governing the nonstationary probability density of the amplitude is derived. Then, the solution of the FPK equation is approximately expressed by a series expansion in terms of a set of properly selected basis functions with time‐dependent coefficients. According to the Galerkin method, the time‐dependent coefficients are solved from a set of linear first‐order differential equations. Thus, the nonstationary probability densities of the amplitude and the state responses as well as the statistic moments of the amplitude are obtained. Finally, two types of the modulating functions, i.e. constant function and exponential function, are considered to give some semi‐analytical formulae. The proposed procedures are checked against the Monte Carlo simulation. The effects of the structure natural frequency and the intensity of the excitation as well as the ground stiffness on the system responses are discussed. It should be pointed out that the proposed method is good for broadband excitation and light damping. Copyright © 2011 John Wiley & Sons, Ltd.
Is the pig a good umami sensing model for humans? A comparative taste receptor study
Authors: Roura Eugeni , Humphrey Brooke , Klasing Kirk , Swart Marcel
Published: April 2011

The diversity of taste perception across species reflects a dietary adaptation to different ecological niches. Laboratory rodents have been widely used as models for human nutritional studies including the understanding of peripheral chemosensing. Nevertheless the diet type as well as the anatomical and functional features of bigger mammals such as the pig may merit further consideration as models for humans. Recently, the porcine umami taste receptor pTas1r1/pTas1r3 and porcine mGluR4 gene sequences have become available. The aim of this study was to compare the umami sensing biology with emphasis in T1R1 sequences, Venus flytrap (VFT) ligand binding domains and l‐amino acid agonists of several mammalian species including human, pig and laboratory rodents. Compared to their corresponding human gene orthologues, receptor homologies where highest for the dog (T1r1 and T1r3) and the pig (mGluR4) and lowest for the mouse (T1r1, T1r3 and mGluR4). Th human T1R1 VFT domain contains 10 different amino acid residues critically involved in ligand binding. All 10 amino acid residues are conserved, both in terms of type and location, within the pig VFT domain. In turn, the arginine and histidine (both charged polar) residues at key positions 307 and 308 appear as threonine and tyrosine (both neutral polar) residues in mouse and rat sequences. Comparison of derived molecular models seems to offer a good explanation regarding the differences of in vivo preference data for l‐amino acids in rats, pigs and humans. Overall, the umami sensing in pigs show higher similarity to that in humans than the umami sensing in laboratory rodents. Copyright © 2011 John Wiley & Sons, Ltd.
Lost and found in sweeteners: forgotten molecules and unsolved problems in the chemistry of sweet compounds
Authors: Bassoli Angela , Borgonovo Gigliola , Morini Gabriella
Published: April 2011

The chemistry of sweet compounds has been an ideal training ground for researchers in the field of taste for a very long time. Sweeteners have a huge importance in the food and pharmaceutical industries, but they have also attracted much interest in connection with their biological function and the general mechanism of action of sweet compounds. Several factors contributed to a large and varied production of scientific data in this field: among these the existence of several active compounds in the plant kingdom, the diversity of structural, stereochemical and conformational hallmarks, the intriguing aspects related to their modulation, inhibition and synergy. Among all molecules that have been isolated and synthesized, only a few have successfully reached the final goal of commercial development while some have been used to derive models and structure–activity relationships. Nevertheless, there is a number of very interesting compounds of natural or synthetic origin that – after a short period of popularity – were apparently lost or forgotten, without any further development. The article will give an overview on some of these compounds and discuss, in the light of current knowledge, the contribution that chemistry still could give in the sweeteners area. Copyright © 2011 John Wiley & Sons, Ltd.
Combining a level‐set method and a mixed stabilized P1/P1 formulation for coupling Stokes–Darcy flows
Authors: Pacquaut G. , Bruchon J. , Moulin N. , Drapier S.
Published: April 2011

The aim of this work is to focus on the Stokes–Darcy coupled problem in order to simulate numerically, with the finite element method, composite manufacturing processes based on liquid resin infusion. In this study, a macroscopic description is used. The computational domain can be divided into two non‐miscible sub‐domains: a purely fluid domain and a porous medium. In the purely fluid domain, the fluid flows according to the Stokes equations, while in the porous medium, the fluid flows into the preforms according to the Darcy equations. Specific conditions have to be considered on the fluid/porous medium interface. The corresponding weak formulation is obtained by summing up the variational forms of the Stokes and Darcy equations over the whole domain. It is solved by a mixed velocity/pressure finite element method. In the purely fluid domain, a first‐order mixed P1+/ P1 finite element is used. However, in the porous medium, the Ladysenskaya–Brezzi–Babuska stability condition is not satisfied, and a P1/P1 finite element is preferred. It is stabilized with the Hughes Variational Multiscale formulation. The originality of our approach is two fold. First, one single unstructured mesh is considered for the whole domain. Second, the interface between the purely fluid domain and the porous medium is represented by a level‐set function. The level‐set framework is also used to capture the resin flow front. At the end of this paper, numerical simulations of such manufacturing processes by resin infusion/injection are presented. Copyright © 2011 John Wiley & Sons, Ltd.
A parallel finite element sliding mesh technique for the simulation of viscous flows in agitated tanks
Authors: Rivera Christian A. , Heniche Mourad , Bertrand François , Glowinski Roland , Tanguy Philippe A.
Published: April 2011

A parallel sliding mesh algorithm for the finite element simulation of viscous fluid flows in agitated tanks is presented. Lagrange multipliers are used at the sliding interfaces to enforce the continuity between the fixed and moving subdomains. The novelty of the method consists of the coupled solution of the resulting velocity–pressure‐Lagrange multipliers system of equations by an ILU(0)‐QMR solver. A penalty parameter is introduced for both the interface and the incompressibility constraints to avoid pivoting problems in the ILU(0) algorithm. To handle the convective term, both the Newton–Raphson scheme and the semi‐implicit linearization are tested. A penalty parameter is introduced for both the interface and the incompressibility constraints to avoid the failure of the ILU(0) algorithm due to the lack of pivoting. Furthermore, this approach is versatile enough so that it allows partitioning of sliding and fixed subdomains if parallelization is required. Although the sliding mesh technique is fairly common in CFD, the main advantage of the proposed approach is its low computational cost due to the inexpensive and parallelizable calculations that involve preconditioned sparse iterative solvers. The method is validated for Couette and coaxial stirred tanks. Copyright © 2011 John Wiley & Sons, Ltd.
A random walk down the options market
Authors: Jiang George J. , Tian Yisong S.
Published: April 2011

Under the efficient market hypothesis, option‐implied forward variance forms a martingale and changes in forward variance follow a random walk. In this study, we extract forward variance from option prices following a model‐free approach and empirically test the random walk hypothesis. Although results from standard orthogonality tests support the martingale restriction, further results from autoregressive regressions seem to reject the martingale restriction as daily changes in forward variance are found to exhibit negative autocorrelation. However, this anomalous pattern of negative correlation is fully explained by illiquidity effects. Overall, the findings support the random walk hypothesis and informational efficiency of the options market. © 2011 Wiley Periodicals, Inc. Jrl Fut Mark 32:505–535, 2012
Ageing in people with autistic spectrum disorder
Authors: Mukaetova‐Ladinska E. B. , Perry E. , Baron M. , Povey C. ,   on behalf of the Autism Ageing Writing Group
Published: April 2011

Background

Although autism in children and in adults attracts attention with respect to clinical and research needs, autism in the older individuals has not been considered to any degree. We review the evidence for urgently addressing the question of ageing in people with autistic spectrum disorder (ASD), focusing on those with disability.

Methods

Perspectives are reviewed in relation to demographics, experiences of relatives or carers, anticipated residential care needs, requirement for specifically designed cognitive assessment tools and importance of initiating new brain ageing research initiatives in this area.

Results

With escalating numbers of ASD individuals with disability reaching old age, provision of care is the paramount issue that is only beginning to be addressed in a few European communities and in the USA. How ageing affects cognition in such individuals as they reach an age no longer consistent with parental care is unknown, lacking any published evidence, and there is a clear need to design cognitive and behavioural assessment tools appropriate to ageing in ASD individuals with disability, as was the case with respect to dementia as a whole. Although there is a growing body of evidence on pathological, imaging, neuropharmacological and other key brain abnormalities in ASD, these are, to date, confined to children and young (only rarely to middle aged) adults.

Conclusions

The need for new initiatives in research into ageing in ASD is urgent. Apart from a growing care crisis, the prospect of understanding brain ageing in this population may bring potential rewards beyond immediate clinical need given the precedent of Down syndrome. Copyright © 2011 John Wiley & Sons, Ltd.
Deoxygenation of isocyanates via transient electrophilic terminal phosphinidene complexes: Are strained P‐heterocycles involved?
Authors: Schulten Christian , von Frantzius Gerd , Schnakenburg Gregor , Streubel Rainer
Published: April 2011

Synthesis of 1,3,2,4σ3λ3−dioxadiphosphetane complexes 3a,b and 4a,b was achieved via thermal decomposition of 2H‐azaphosphirene complexes of chromium (1a) and tungsten (1b) in the presence of tert‐butyl isocyanate; as reactive intermediates 3‐imino‐oxaphosphirane complexes 8a,b are proposed, which decompose to give phosphinidene oxide complexes 9a,b. The intermediacy of the latter is inferred from a cross‐dimerization experiment (decomposition of a 1:1 mixture of 2H‐azaphosphirene complexes 1a,b with tert‐butyl isocyanate), which furnished the mixed metal dinuclear cis and trans complexes 5a/b and 6a/b. 31P NMR spectroscopy revealed the formation of [bis(trimethylsilyl)methyl]cyanophosphane complexes 11a,b as by‐products. Thermal reaction of complex 1b with the less bulky ethyl isocyanate furnished the novel 1,3,4σ3λ3‐diazaphospholidin‐5‐imin‐2‐one complex 7 together with complexes 3b and 4b. For the latter case, 3‐imino‐oxaphosphirane (12) and azaphosphiridin‐3‐one (13) complexes are proposed as reactive intermediates. All final products were characterized by multinuclear NMR spectroscopy, IR, MS, and single‐crystal X‐ray crystallography in the cases of complexes 3b and 4a,b. DFT calculations strongly support the transient formation and decomposition of 3‐imino‐oxaphosphirane complex 12 to form 9b and isonitrile. Azaphosphiridin‐3‐one complex 13 was characterized computationally as the methyl model. In accordance with the calculations, final products 1,3,2,4σ3λ3‐dioxadiphosphetane complexes 3a,b and 4a,b form by dimerization of transient terminal phosphinidene oxide complexes 9a,b. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 22:275–286, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.20677
Electrochemically switchable supramolecular complex between bisporphyrin cleft and electron‐deficient aromatic guest
Authors: Ikeda Toshiaki , Watanabe Akihide , Oshita Tomoko , Haino Takeharu
Published: April 2011

The host–guest complexation between bisporphyrin cleft 1 and flat aromatic guest 2 was controlled by an electrochemical reaction. The first oxidation potentials of 1 showed the anodic shift upon the addition of 2. On the basis of the square scheme, the association constant of 1 with 2 was estimated to be at least 50 times larger than that of cation radical 12·+ with 2. This demonstrated that the electrochemical oxidation obviously reduced the binding ability of 1. The reversible nature of the switchable complexation between 1 and 2 was confirmed by cyclic voltammetry. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 22:590–593, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.20702
Synthesis and reactivities of dihydrosilanes tethered with two thioether moieties
Authors: Takeda Nobuhiro , Nakamura Tetsu , Imamura Ayako , Unno Masafumi
Published: April 2011

Dihydrosilanes tethered with two thioether moieties, [2‐(RSCH2)C6H4]2SiH2(1a: R = t‐Bu; 1b: R = i‐Pr; 1c: R = Ph), were synthesized. Dihydrosilane 1b did not react with methanol, benzaldehyde, and carboxylic acids; this result may suggest very weak activation of the SiH bonds in 1b. The corresponding dibromosilanes 4 and diiodosilanes 5 were synthesized by dihalogenation of 1 using N‐bromosuccinimide and I2, respectively, whereas the dichlorosilanes 3 were synthesized by reaction of 2‐(RSCH2)C6H4 Li with SiCl4. Reaction of 1b with [PtCl2 (cod)] in the presence of Et3N gave the corresponding bissilylplatinum complex, [Pt{SiH[2‐(RSCH2)‐ C6H4]2}2], the structure of which was determined by NMR and IR spectrometry and X‐ray crystallography. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 22:438–445, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.20706
Effects of heterole spacers on the structural, optical, and electrochemical properties of 2,5‐bis(1,5‐diphenylphosphol‐2‐yl)heteroles
Authors: Matano Yoshihiro , Saito Arihiro , Fujita Masato , Imahori Hiroshi
Published: April 2011

2,5‐Bis(1,5‐diphenylphosphol‐2‐yl)he‐terole derivatives were prepared via Pd‐catalyzed Stille‐type cross‐coupling reactions of α‐(tributylstannyl) phosphole or α‐iodophosphole with the corresponding 2,5‐difunctionalized heteroles (pyrrole, furan, and thiophene). X‐ray crystallographic analyses of three σ4‐P derivatives have elucidated that the coplanar phosphole‐heterole‐phosphole π‐networks are constructed in both anti–anti and syn–anti conformations. In the case of the pyrrole‐linked σ4‐P derivatives, there is a weak hydrogen‐bonding interaction between NH and P=X (X = O, S) groups. The optical and electrochemical properties of the σ3‐P and σ4‐P=O derivatives were revealed experimentally by means of UV–vis absorption/emission spectroscopy and cyclic/differential pulse voltammetry. In all the heterole‐linked derivatives, the P‐oxidation lowers LUMO levels more efficiently than HOMO levels and, as a result, narrows HOMO–LUMO gaps. In each series (σ3‐P or σ4‐P=O), the lowest π–π* transition energies of the phosphole–heterole–phosphole π‐systems were found to decrease in the following order: thiophene > furan > pyrrole, and their electrochemical oxidation and reduction potentials shift to the negative side in the same order. These results basically reflect the differences in ionization potential and electron affinity of the central heterole spacers. Density functional theory calculations on the model compounds supported the experimentally observed results. The HOMO of the molecule resides on the conjugated polyene network of the π‐system, whereas the LUMO is strongly located on the phosphole subunits. The present comparative study demonstrates, for the first time, that the intriguing electronic structures and the fundamental properties of the 2,5‐bis(1,5‐diphenylphosphol‐2‐yl)heteroles can be finely tuned by simple selection of the appropriate heterole spacer. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 22:457–470, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.20708
Reaction ofo‐(HSiR2)(BMes2)C6H4with a fluoride ion: Fluoride attack at silicon and hydride transfer from silicon to boron to form FSi⋅⋅⋅HB interaction
Authors: Kawachi Atsushi , Morisaki Hiroshi , Tani Atsushi , Zaima Masatoshi , Yamamoto Yohsuke
Published: April 2011

Reactions ofo‐(HSiR2)(BMes2)C6H4(R = Me (3a), Ph (3b)) with a fluoride ion afford [o‐(FSiR2)(HBMes2)C6H4]−(R = Me (5a), Ph (5b)), which involve the FSi⋅⋅⋅HB interaction to render the silicon atom pentacoordinate. The FSi⋅⋅⋅HB interaction in5awas confirmed by X‐ray crystallographic analysis and “atoms‐in‐molecules” (AIM) analysis. © 2011 Wiley Periodicals, Inc. Heteroatom Chem 22:471–475, 2011; View this article online atwileyonlinelibrary.com. DOI 10.1002/hc.20709
A study of hippocampal structure‐function relations along the septo‐temporal axis
Authors: Jarrard Leonard E. , Luu Lisa P. , Davidson Terry L.
Published: April 2011

This study examined structural–functional differences along the septo‐temporal axis of hippocampus using radial‐maze tasks that involved two different memory processes [reference memory (RM) and working memory (WM)], and the use of two kinds of information (spatial vs. nonspatial cue learning). In addition, retention of the nonspatial cue task was tested nine weeks following completion of acquisition, and the rats then underwent discrimination reversal training. Ibotenic acid lesions limited to either the dorsal pole, intermediate area, or ventral pole had minimal effects on acquisition of the complex place and cue discrimination tasks. The one exception was that rats with lesions confined to the dorsal third of hippocampus made more WM errors on the spatial task (but not the cue task) early in training. Selective lesions of the three hippocampal regions had no effects on either long‐term retention or reversal of the nonspatial cue discrimination task. In contrast, rats that had all of the hippocampus removed were severely impaired in learning the spatial task, making many RM and WM errors, whereas on the nonspatial cue task, the impairment was limited to WM errors. Further analysis of the WM errors made in acquisition showed that rats with complete lesions were significantly more likely on both the spatial and nonspatial cue tasks to reenter arms that had been baited and visited on that trial compared to arms that had not been baited. A similar pattern of errors emerged for complete hippocampal lesioned rats during reversal discrimination. This pattern of errors suggests that in addition to an impairment in handling spatial information, complete removal of hippocampus also interferes with the ability to inhibit responding to cues that signal reward under some conditions but not under others. The finding that selective lesions limited to the intermediate zone of the hippocampus produce no impairment in either WM (“rapid place learning”) or RM in our radial maze tasks serve to limit the generality of the conclusion of Bast et al. (Bast et al. (2009) PLos Biol 7:730‐746) that the intermediate area is needed for behavioral performance based on rapid learning about spatial cues. © 2011 Wiley Periodicals, Inc.
Greater running speeds result in altered hippocampal phase sequence dynamics
Authors: Maurer Andrew P. , Burke Sara N. , Lipa Peter , Skaggs William E. , Barnes Carol A.
Published: April 2011

Hebb (1949) described a “phase sequence” to be the sequential activation of sets of cell assemblies. Within the hippocampus, cell assemblies have been described as groups of coactive neurons whose place fields overlap. Membership of assemblies in a phase sequence changes systematically as a rat travels through an environment, serving to accelerate the temporal order that place fields are encountered during a single theta cycle. This sweeping forward of network activity (“look ahead”), results in locations in front of the animal being transiently represented. In this experiment, a population vector‐based reconstruction method was used to capture the look ahead and reveals that the composition of the phase sequence changes with velocity, such that more cell assemblies are active within a theta cycle at higher running speeds. These results are consistent with hypotheses suggesting that hippocampal networks generate short time scale predictions of future events to optimize behavior. © 2011 Wiley Periodicals, Inc.
5‐HT1A and 5‐HT7 receptors differently modulate AMPA receptor‐mediated hippocampal synaptic transmission
Authors: Costa L. , Trovato C. , Musumeci S.A. , Catania M.V. , Ciranna L.
Published: April 2011

We have studied the effects of 5‐HT1A and 5‐HT7 serotonin receptor activation in hippocampal CA3‐CA1 synaptic transmission using patch clamp on mouse brain slices. Application of either 5‐HT or 8‐OH DPAT, a mixed 5‐HT1A/5‐HT7 receptor agonist, inhibited AMPA receptor‐mediated excitatory post synaptic currents (EPSCs); this effect was mimicked by the 5‐HT1A receptor agonist 8‐OH PIPAT and blocked by the 5‐HT1A antagonist NAN‐190. 8‐OH DPAT increased paired‐pulse facilitation and reduced the frequency of mEPSCs, indicating a presynaptic reduction of glutamate release probability. In another group of neurons, 8‐OH DPAT enhanced EPSC amplitude but did not alter paired‐pulse facilitation, suggesting a postsynaptic action; this effect persisted in the presence of NAN‐190 and was blocked by the 5‐HT7 receptor antagonist SB‐269970. To confirm that EPSC enhancement was mediated by 5‐HT7 receptors, we used the compound LP‐44, which is considered a selective 5‐HT7 agonist. However, LP‐44 reduced EPSC amplitude in most cells and instead increased EPSC amplitude in a subset of neurons, similarly to 8‐OH DPAT. These effects were respectively antagonized by NAN‐190 and by SB‐269970, indicating that under our experimental condition LP‐44 behaved as a mixed agonist. 8‐OH DPAT also modulated the current evoked by exogenously applied AMPA, inducing either a reduction or an increase of amplitude in distinct neurons; these effects were respectively blocked by 5‐HT1A and 5‐HT7 receptor antagonists, indicating that both receptors exert a postsynaptic action. Our results show that 5‐HT1A receptors inhibit CA3‐CA1 synaptic transmission acting both pre‐ and postsynaptically, whereas 5‐HT7 receptors enhance CA3‐CA1 synaptic transmission acting exclusively at a postsynaptic site. We suggest that a selective pharmacological targeting of either subtype may be envisaged in pathological loss of hippocampal‐dependent cognitive functions. In this respect, we underline the need for new selective agonists of 5‐HT7 receptors. © 2011 Wiley Periodicals, Inc.