bluuebunny/crossref_metadata_2025 huggingface dataset:
YPSP01-12 - Lipid Metabolism Changes After Switching To Ziprasidone
Authors: Dragasek J. , Palova E. , Lukacsova I. , Drimalova M. , Breznoscakova D. , Mirossay P.
Published: June 2010

Introduction

Increasing numbers of reports concerning lipid dysregulation, diabetes and hyperglycaemia in patients treated with atypical antipsychotics have raised concerns about a possible association between these metabolic effects and treatment with these medications.

Objectives

The available literature notes that ziprasidone is a weight-neutral antipsychotic and that lipids anomalies improve when patient are switched from other atypical antipsychotics to ziprasidone.

Aims

The purpose of this study was to examine the association of treatment with ziprasidone and changes in serum levels of cholesterol, triglycerides, serum levels of glucose and BMI changes.

Methods

Prospective, cohort, multicenter, open design in 373 in- and outpatients treated with ziprasidone for broad spectrum of psychotic disorders in flexible dose manner. The analysis was done in group of patients with no previous antipsychotic treatment or discontinuation of antipsychotic treatment longer than 3 months compared to group of patients directly switched from another antipsychotic treatment to ziprasidone.

Results

Changes in fasting serum levels of total cholesterol were significant from baseline at week 24 in subgroup of patients directly switched from another antipsychotic treatment to ziprasidone (5,12 vs 4,94 mmol/l, p< 0,05, ANOVA).

Conclusions

We have observed statistical significant difference in fasting serum levels of total cholesterol in patients directly switched from another antipsychotic treatment to ziprasidone.
YPSP01-13 - The Effects Of A Literary Workshop For Increase Assertivity In Patients With Eating Disorders: A Randomized Controlled Trial
Authors: Pingani L. , Arnone F. , Chierici M.L. , De Bernardis E. , Donelli S. , Ferrari S. , Zucchi G. , Turrini G. , Rigatelli M.
Published: June 2010

Introduction

The Social Skill Training is structured as a cognitive-behavioral therapy for rehabilitation plans whereby the patient can develop and recover social skills.

Aim

To verify the effects of a literary workshop for increase assertiveness in patients with eating disorders.

Methods

Thirty-two patients consequently admitted to the Ward for Eating Disorders at the Private Clinic “Villa Maria Luigia” in the North of Italy were recruited in the study, and all of them agreed to take part in it. Of the 32 patients, 8 were randomly assigned to treatment and 24 to care as usual, being the difference between treatment and care as usual only represented by the literary workshop. The Rathus Assertiveness Schedule and Verbal Fluency Test (phonemic and semantic) was administered to all patients in the first and last week of hospitalization. The literary workshop consists in 16 weekly 45-minute group sessions. Issues of expressiveness through the use of writing are addressed during the sessions.

Results

A significant improvement of semantic skills (t=-5.60; p< 0.01 vs. t=1.43; p=0.17), phonetic skills (t=-3.66; p< 0.01 vs. t=1.35; p=0.19) and assertiveness (t=4.47; p< 0.01 vs. t=0.94; p=0.93) was registered in the literary workshop group.

Conclusions

Effectiveness of the literary workshop in a rehabilitation program for patients suffering from eating disorders is suggested: improved communication and language skills might have a positive and significant impact on patients’ levels of assertiveness.
P01-412 - Disulfiram And Cognitive Behavioral Therapy In Advance Treatment Of Alcoholism
Authors: Stankovic M. , Alcaz S. , Vucetic Arsic S. , Nikic M. , Pejic S. , Popovic R. , Jovanovic D.
Published: June 2010

Objectives

Disulfiram is an aversive medication that works by making the drinking of alcohol an unpleasant experience (FDA approved since 1951) and most study of understanding alcohol abuse and dependence are based on it. Also, the combined Cognitive Behavioral Therapy (CBT) and disulfiram assurance treatment was substantially effective in patients with alcohol disorders.

Methods

We conducted 150 male patients range of age 20-60 and treated in Special Hospital on Addictions for 3 months period of time (inpatient setting).The recommended dose of disulfiram was 250 mg. All patients were diagnosis of alcohol dependence according the ICD-X, excluded psychosis and no one was unable to take disulfiram for medical reason. We used medical history of illness, psychiatric interview and semi structured CBT protocol for alcohol disorder and CBT sessions (2 sessions per week). Control group were 80 patients on disulfiram assurance therapy (alone).

Results

CBT plus disulfiram assurance (N=150): 93(62%) maintaining sobriety and absence of drinking for 3 months; 44 (29,33%) maintaining sobriety for 2 months and 13 (8,66%) absence of drinking only 1 - 1,5 month.Disulfiram assurance therapy alone (control group) (N=80): 41 (51,25%) maintaining sobriety of drinking for 3 months; 22 (27,5%) less than 3 months; 10 (12,5%) for 1,5 - 2 months and 7 patients (8,75%) drop-out after a week without no relevant or medical reasons.

Conclusions

In this paper was shown the high level of effectiveness for the CBT combined with disulfiram assurance therapy according the maintaining sobriety and absence of drinking.
L'invariant de Suslin en caractéristique positive
Authors: Wouters Tim
Published: June 2010

Pour unek-algèbre simple centraleAd'indice inversible dansk, Suslin a défini un invariant cohomologique deSK1(A) ‘Sus2’. Dans ce texte, nous généralisons cet invariant à toutek-algèbre simple centrale par un relèvement de la caractéristique positive à la caractéristique 0. Pour pouvoir définir cet invariant, on a besoin des groupes de cohomologie des différentielles logarithmiques de Kato [Kat1].
Idiosyncratic Risk, Long-Term Reversal, and Momentum
Authors: McLean R. David
Published: June 2010

This paper tests whether the persistence of the momentum and reversal effects is the result of idiosyncratic risk limiting arbitrage. Idiosyncratic risk deters arbitrage, regardless of the arbitrageur’s diversification. Reversal is prevalent only in high idiosyncratic risk stocks, suggesting that idiosyncratic risk limits arbitrage in reversal mispricing. This finding is robust to controls for transaction costs, informed trading, and systematic relations between idiosyncratic risk and subsequent returns. Momentum is not related to idiosyncratic risk. Momentum generates a smaller aggregate return than reversal, so the findings along with those in related studies suggest that transaction costs are sufficient to prevent arbitrageurs from eliminating momentum mispricing.
Estimating the Equity Premium
Authors: Donaldson R. Glen , Kamstra Mark J. , Kramer Lisa A.
Published: June 2010

Existing empirical research investigating the size of the equity premium has largely consisted of a series of innovations around a common theme: producing a better estimate of the equity premium by using better data or a better estimation technique. The equity premium estimate that emerges from most of this work matches one moment of the data alone: the mean difference between an estimate of the return to holding equity and a risk-free rate. We instead match multiple moments of U.S. market data, exploiting the joint distribution of the dividend yield, return volatility, and realized excess returns, and find that the equity premium lies within 50 basis points of 3.5%, a range much narrower than was achieved in previous studies. Additionally, statistical tests based on the joint distribution of these moments reveal that only those models of the conditional equity premium that embed time variation, breaks, and/or trends are supported by the data. In order to develop the joint distribution of the dividend yield, return volatility, and excess returns, we need a model of price and return fundamentals. We document that even recently developed analytically tractable models that permit autocorrelated dividend growth rates and discount rates impose restrictions that are rejected by the data. We therefore turn to a wider range of models, requiring numerical solution methods and parameter estimation by the simulated method of moments.
Effect of an improved local ingredient-based complementary food fortified or not with iron and selected multiple micronutrients on Hb concentration
Authors: Ouédraogo Hermann Z , Traoré Tahirou , Zèba Augustin N , Dramaix-Wilmet Michèle , Hennart Philippe , Donnen Philippe
Published: June 2010

Objective

To assess the effect of an improved local ingredient-based gruel fortified or not with selected multiple micronutrients (MM) on Hb concentration of young children.

Design

In a nutrition centre that we opened in their villages, children received either MM supplement (containing iron, zinc, vitamin A, vitamin C and iodine) with the improved gruel (MMGG) or the improved gruel only (GG), twice daily, 6 d/week, for 6 months. We assessed baseline and endpoint Hb concentration and anthropometric indices.

Setting

Kongoussi, a rural and poor district of Burkina Faso.

Subjects

In a community-based trial, we randomly assigned 131 children aged 6–23 months with Hb concentrations in the range of 80–109 g/l into two groups.

Results

The groups did not differ significantly at baseline. Mean baseline Hb concentration was 89·2 (sd 6·5) g/l and 90·3 (sd 8·4) g/l in the GG and the MMGG, respectively (P = 0·42). It increased to 104·1 (sd 11·4) g/l in the GG (P < 0·001) and 107·6 (sd 14·7) g/l in the MMGG (P < 0·001). The between-group difference of 3·5 (95 % CI −1·0, 8·1) g/l in mean (sd) endpoint Hb concentration was not significant (P = 0·13). The endpoint anthropometric indices were not different between the groups.

Conclusions

This MM supplement had no additional effect on Hb concentration. Thorough studies are needed to evaluate the actual efficacy of the gruel before its introduction into household routine.
Frequent use of staff canteens is associated with unhealthy dietary habits and obesity in a Norwegian adult population
Authors: Kjøllesdal Marte Råberg , Holmboe-Ottesen Gerd , Wandel Margareta
Published: June 2010

Objective

To explore socio-economic differences in use of staff canteens and whether frequent use of staff canteens is associated with different food patterns and obesity.

Design

Cross-sectional study using three self-administered questionnaires, two of them including food frequency questions. Factor analysis was used to explore food patterns.

Setting

Oslo, Norway, 2000–2001.

Subjects

In total 8943 adult, working Oslo citizens.

Results

Frequent (≥3 times/week) use of staff canteens was most likely among men, younger workers and those in the highest education and income groups. However, after adjustment for demographic, socio-economic and lifestyle factors, those with highest education were least likely to use staff canteens frequently. Frequent eating in staff canteens was positively associated with a Western food pattern (based on fat-rich food, fast food and red meat) and inversely associated with a traditional food pattern (based on boiled potatoes and gravy, and less rice, pasta and oil) in multivariate analyses. Unadjusted, frequent eating in staff canteens was also inversely associated with a prudent food pattern (based on fruit, vegetables, fish, legumes and oil). The likelihood of being obese (BMI ≥ 30 kg/m2) increased significantly with frequent eating in staff canteens, also when adjusted for demographic and socio-economic variables. Adjustment for the food patterns attenuated this relationship, but it was still significant.

Conclusions

Frequent eating in staff canteens was negatively related to socio-economic position and positively associated with unhealthy dietary habits. This partly explained higher odds for obesity among frequent users of staff canteens. Future research should assess the availability and food options of staff canteens.
ON A NONABELIAN BALOG–SZEMERÉDI-TYPE LEMMA
Authors: SANDERS TOM
Published: June 2010

We show that if G is a group and A⊂G is a finite set with ∣A2∣≤K∣A∣, then there is a symmetric neighbourhood of the identity S such that Sk⊂A2A−2 and ∣S∣≥exp (−KO(k))∣A∣.
Antioxidant Role of Plasma Carotenoids in Bronchopulmonary Dysplasia in Preterm Infants
Authors: Vogelsang Annelies , van Lingen Richard A. , Slootstra Janine , Dikkeschei Bert D. , Kollen Boudewijn J. , Schaafsma Anne , van Zoeren-Grobben Diny
Published: June 2010

Objectives: Oxidative stress is implicated in the pathogenesis of bronchopulmonary dysplasia (BPD) and consequently, it might be theorized that sufficient antioxidant defenses are needed to prevent BPD. We hypothesized that, except for vitamins E and A, carotenoids may be important in this defense. Carotenoids are present in human milk; however, they are not added to parenteral nutrition, the main food source of preterm infants in the first week of life. Aim: To evaluate prospectively the role of carotenoids in BPD in a cohort of preterm infants. Methods: The plasma concentrations of F2α-isoprostane, α- and β-carotene, lycopene, lutein, vitamin A, and the vitamin E/cholesterol ratio were studied at days 1, 3, and 7 in a cohort of 109 preterm infants, of whom 19 had BPD. Results: When comparing the BPD and control group, infants in the BPD group were younger (p<0.001) and β-carotene (day 7, p<0.01) and vitamin A concentrations were lower (days 3 and 7, p<0.001). Lycopene, lutein, α-carotene, vitamin E, and F2α-isoprostane concentrations did not differ between groups. Conclusions: Plasma β-carotene and vitamin A concentrations are lower in BPD infants which may result in a reduction of their antioxidant protection.
Wie Schülerinnen und Schüler ihre Lernumwelt wahrnehmen
Authors: Gärtner Holger
Published: June 2010

Eine hinreichende Übereinstimmung von Schülerwahrnehmungen ihrer Lernumwelt ist in vielen Studien mit Mehrebenenstruktur Voraussetzung für die Aggregation von Individualdaten, wenn die gemessenen Konstrukte auf Aggregatebene die geteilte Wahrnehmung der Klasse darstellen sollen. Wie weit Schülerwahrnehmungen ihrer Lernumwelt innerhalb einer Klasse übereinstimmen, lässt sich anhand verschiedener Indizes quantifizieren. Die vorliegende Studie geht der Frage nach, wie weit vier gängige Indizes der Beurteilerübereinstimmung zu vergleichbaren Ergebnissen kommen. Zur Bestimmung der Übereinstimmungsindizes wurde auf Daten des Selbstevaluationsportals des Instituts für Schulqualität der Länder Berlin und Brandenburg zurückgegriffen. Aus 424 Klassen liegen von N = 7.965 Schüler/innen Daten zur Wahrnehmung des Unterrichts vor. Die verschiedenen Übereinstimmungsmaße korrelieren sehr hoch miteinander, die Anwendung verschiedener Schwellenwerte für eine akzeptable Übereinstimmung offenbart jedoch gravierende Unterschiede zwischen den Indizes. Des Weiteren scheint die Höhe der gefundenen Übereinstimmung stark vom erfragten Konstrukt abzuhängen.
Isotopic constraints on alkalinity, dissolved organic carbon, and atmospheric carbon dioxide fluxes in the Mississippi River
Authors: Dubois Kristal D. , Lee Dongho , Veizer Ján
Published: June 2010

We examined carbon cycling in the Mississippi River using stable isotopes of inorganic carbon and dissolved oxygen. Eighteen sites were sampled along the river and its tributaries over 1 year. We estimate using a conservative approach that the flux of CO2 to the atmosphere (1 × 1013 g C yr−1) approximately equaled the flux of alkalinity to the Gulf of Mexico (9.7 × 1012 g C yr−1) and greatly exceeded the flux of dissolved organic carbon (1.5 × 1012 g C yr−1). Though only a first‐order estimate, our work shows that the atmospheric flux of CO2 is significant and should not be ignored when examining the carbon budget of the Mississippi River. As expected, because of the large area covered by the Mississippi watershed, the isotopic composition of dissolved inorganic carbon, δ13CDIC, varied widely. In the Ohio and upper and lower Mississippi basins, δ13CDIC indicates that the source of inorganic carbon in the rivers is primarily from carbonate dissolution by soil CO2. Dissolved inorganic carbon in the Missouri River was enriched in 13C, and the isotopic composition of dissolved oxygen in this river suggests that this results from an excess of aquatic photosynthesis over respiration.
Chemical combinations elucidate pathway interactions and regulation relevant to Hepatitis C replication
Authors: Owens Christopher M , Mawhinney Christina , Grenier Jill M , Altmeyer Ralf , Lee Margaret S , Borisy Alexis A , Lehár Joseph , Johansen Lisa M
Published: June 2010

The search for effective Hepatitis C antiviral therapies has recently focused on host sterol metabolism and protein prenylation pathways that indirectly affect viral replication. However, inhibition of the sterol pathway with statin drugs has not yielded consistent results in patients. Here, we present a combination chemical genetic study to explore how the sterol and protein prenylation pathways work together to affect hepatitis C viral replication in a replicon assay. In addition to finding novel targets affecting viral replication, our data suggest that the viral replication is strongly affected by sterol pathway regulation. There is a marked transition from antagonistic to synergistic antiviral effects as the combination targets shift downstream along the sterol pathway. We also show how pathway regulation frustrates potential hepatitis C therapies based on the sterol pathway, and reveal novel synergies that selectively inhibit hepatitis C replication over host toxicity. In particular, combinations targeting the downstream sterol pathway enzymes produced robust and selective synergistic inhibition of hepatitis C replication. Our findings show how combination chemical genetics can reveal critical pathway connections relevant to viral replication, and can identify potential treatments with an increased therapeutic window.
Global coordination of transcriptional control and mRNA decay during cellular differentiation
Authors: Amorim Maria J , Cotobal Cristina , Duncan Caia , Mata Juan
Published: June 2010

The function of transcription in dynamic gene expression programs has been extensively studied, but little is known about how it is integrated with RNA turnover at the genome‐wide level. We investigated these questions using the meiotic gene expression program of Schizosaccharomyces pombe. We identified over 80 transcripts that co‐purify with the meiotic‐specific Meu5p RNA‐binding protein. Their levels and half‐lives were reduced in meu5 mutants, demonstrating that Meu5p stabilizes its targets. Most Meu5p‐bound RNAs were also targets of the Mei4p transcription factor, which induces the transient expression of ∼500 meiotic genes. Although many Mei4p targets showed sharp expression peaks, Meu5p targets had broad expression profiles. In the absence of meu5, all Mei4p targets were expressed with similar kinetics, indicating that Meu5p alters the global features of the gene expression program. As Mei4p activates meu5 transcription, Mei4p, Meu5p and their common targets form a feed‐forward loop, a motif common in transcriptional networks but not studied in the context of mRNA decay. Our data provide insight into the topology of regulatory networks integrating transcriptional and posttranscriptional controls.
Improved emission of ferroelectric electron emitter by surface treatments in gas atmosphere
Authors: Sugiyama Tomohiko , Ohwada Iwao , Nanataki Tsutomu , Eryu Osamu , Ichimura Masaya , Gomi Manabu
Published: June 2010

The effects of surface treatments in H2, N2, and O2 on electron emission have been investigated for a ferroelectric electron emitter with a unique porous electrode. The electron emission was markedly enhanced after surface treatment in H2 at 90 kPa. The electron emission density was about 500 nC/cm2, 1.6 times higher than that of a nontreated emitter. On the other hand, electron emission after surface treatment in O2 at 90 kPa was decreased to about two-third of that of the nontreated emitter. These results indicate that electron emission can be significantly influenced by modification of the ferroelectric surface state.
Influence of the substrate stiffness on the crystallization process of sputtered TbFe2 thin films
Authors: Ranchal R. , Prieto J. L. , Sánchez P. , Aroca C.
Published: June 2010

Despite the giant magnetostriction of TbFe2, this material has a very limited popularity in real applications, due to the difficulties for obtaining the Laves phase on thin films. Here we report on the properties of annealed TbFe2 films deposited by sputtering on different substrates and with different buffer materials. We find that the presence of the highly magnetostrictive Laves phase is not necessarily related to crystallinity of the substrate. Strikingly we find a correlation between the degree of TbFe2 crystallization and the rigidity of the substrate or the buffer layer underneath the TbFe2. This opens the possibility of easy manufacturing of devices based on TbFe2 layers.
Linear and nonlinear refractive index of As–Se–Ge and Bi doped As–Se–Ge thin films
Authors: Sharma Pankaj , Katyal S. C.
Published: June 2010

The present work reports the linear and nonlinear refractive index for (As2Se3)90Ge10 and [(As2Se3)90Ge10]95Bi5 thin films. The formulation proposed by Fournier and Snitzer has been used to predict the nonlinear behavior of refractive index. The linear refractive index and Wemple–DiDomenico parameters were used for the determination of nonlinear refractive index in the wavelength region 0.4 to 1.5 μm. Linear refractive index has been determined using the well known Swanepoel method. This is observed that nonlinear refractive index increases linearly with increasing linear refractive index. With Bi addition this has been found that nonlinear refractive index increases by 2.4 times, while on comparing with pure and doped silica glasses results are 2–3 orders higher. Density and molar volume has also been calculated. The obtained results may lead to yield more sensitive optical limiting devices and these glasses may be used as an optical material for high speed communication fibers.
Reactor for in situ measurements of spatially resolved kinetic data in heterogeneous catalysis
Authors: Horn R. , Korup O. , Geske M. , Zavyalova U. , Oprea I. , Schlögl R.
Published: June 2010

The present work describes a reactor that allows in situ measurements of spatially resolved kinetic data in heterogeneous catalysis. The reactor design allows measurements up to temperatures of 1300 °C and 45 bar pressure, i.e., conditions of industrial relevance. The reactor involves reactants flowing through a solid catalyst bed containing a sampling capillary with a side sampling orifice through which a small fraction of the reacting fluid (gas or liquid) is transferred into an analytical device (e.g., mass spectrometer, gas chromatograph, high pressure liquid chromatograph) for quantitative analysis. The sampling capillary can be moved with μm resolution in or against flow direction to measure species profiles through the catalyst bed. Rotation of the sampling capillary allows averaging over several scan lines. The position of the sampling orifice is such that the capillary channel through the catalyst bed remains always occupied by the capillary preventing flow disturbance and fluid bypassing. The second function of the sampling capillary is to provide a well which can accommodate temperature probes such as a thermocouple or a pyrometer fiber. If a thermocouple is inserted in the sampling capillary and aligned with the sampling orifice fluid temperature profiles can be measured. A pyrometer fiber can be used to measure the temperature profile of the solid catalyst bed. Spatial profile measurements are demonstrated for methane oxidation on Pt and methane oxidative coupling on Li/MgO, both catalysts supported on reticulated α−Al2O3 foam supports.
Entropic resonant activation
Authors: Mondal Debasish , Das Moupriya , Ray Deb Shankar
Published: June 2010

Varying cross section of confinement of a Brownian particle in two or higher dimensions results in an effective entropic barrier in reduced dimension. When the boundaries are subjected to periodic modulation, it is possible to observe a resonance of the mean first passage time between the lobes of a bilobal confined system as a function of the modulating frequency of the walls of the enclosure. The entropic resonant activation and the associated features, which are characteristic of the shape and size of the confinement, are amenable to a theoretical analysis in terms of a two-state model.
The ν5 antisymmetric stretching mode of linear C7 revisited in high resolution
Authors: Krieg J. , Lutter V. , Hardy F.-X. , Schlemmer S. , Giesen T. F.
Published: June 2010

The ν5 antisymmetric stretching mode of the linear carbon cluster C7 has been revisited using a sensitive high-resolution spectrometer, including an external-cavity quantum cascade laser covering the range of interest of 1894–1901 cm−1. 50 transitions of the ν5-band have been recorded and analyzed together with 45 transitions of the ν4-band measured by Neubauer-Guenther et al. [J. Chem. Phys. 127, 014313 (2007)]. We determined the band centers, rotational and centrifugal constants very precisely. In addition, 29 hot band transitions have been measured and tentatively assigned to the ν5+ν11−ν11 hot band. A global fit of the hot bands ν5+ν11−ν11 and ν4+ν11−ν11 is presented. Derived l-type doubling constants allow for an experimental estimation of the ν11-band center.
Instantaneous normal modes, resonances, and decay channels in the vibrational relaxation of the amide I mode of N-methylacetamide-D in liquid deuterated water
Authors: Bastida Adolfo , Soler Miguel Angel , Zúñiga José , Requena Alberto , Kalstein Adrián , Fernández-Alberti Sebastián
Published: June 2010

A nonequilibrium molecular dynamics (MD) study of the vibrational relaxation of the amide I mode of deuterated N-methylacetamide (NMAD) in aqueous (D2O) solution is carried out using instantaneous normal modes (INMs). The identification of the INMs as they evolve over time, which is necessary to analyze the energy fluxes, is made by using a novel algorithm which allows us to assign unequivocally each INM to an individual equilibrium normal mode (ENM) or to a group of ENMs during the MD simulations. The time evolution of the energy stored in each INM is monitored and the occurrence of resonances during the relaxation process is then investigated. The decay of the amide I mode, initially excited with one vibrational quantum, is confirmed to fit well to a biexponential function, implying that the relaxation process involves at least two mechanisms with different rate constants. By freezing the internal motions of the solvent, it is shown that the intermolecular vibration-vibration channel to the bending modes of the solvent is closed. The INM analysis reveals then the existence of a major and faster decay channel, which corresponds to an intramolecular vibrational redistribution process and a minor, and slower, decay channel which involves the participation of the librational motions of the solvent. The faster relaxation pathway can be rationalized in turn using a sequential kinetic mechanism of the type P→M+L→L, where P (parent) is the initially excited amide I mode, and M (medium) and L (low) are specific midrange and lower-frequency NMAD vibrational modes, respectively.
Planar semipolar (101¯1) GaN on (112¯3) sapphire
Authors: Schwaiger Stephan , Argut Ilona , Wunderer Thomas , Rösch Rudolf , Lipski Frank , Biskupek Johannes , Kaiser Ute , Scholz Ferdinand
Published: June 2010

We report on the growth of planar semipolar (101¯1) GaN on (112¯3) prepatterned sapphire. This is a method that allows the growth of semipolar oriented (101¯1) GaN on large scale. Using x-ray diffraction only the peaks of the desired (101¯1) plane could be observed. Scanning electron, transmission electron, and atomic force microscopy measurements show an atomically flat surface. Further investigations using photoluminescence spectroscopy show spectra that are dominated by the near band edge emission. The high crystal quality is furthermore confirmed by the small full width at half maximum values of x-ray rocking curve measurements of less than 400 arcsec.
First principles prediction of the metastability of the Ge2Mn phase and its synthesis pathways
Authors: Arras E. , Slipukhina I. , Torrent M. , Caliste D. , Deutsch T. , Pochet P.
Published: June 2010

In this letter, we performed first principles calculations to investigate the stability of a [100]-compatible Ge2Mn compound. Based on a thermodynamical approach, we propose and assess the C16 structure (Al2Cu prototype) to be only slightly metastable as compared to the other Ge–Mn compounds. The reported structural and magnetic properties of this Ge2Mn compound make it a potentially interesting compound for spintronic applications, all the more since a simple way to stabilize it as a bulk film is proposed.
Activity of any class IA PI3K isoform can sustain cell proliferation and survival
Authors: Foukas Lazaros C. , Berenjeno Inma M. , Gray Alexander , Khwaja Asim , Vanhaesebroeck Bart
Published: June 2010

Small molecule inhibitors of PI3K for oncology mainly target the class I PI3Ks, comprising the p110α, β, γ, and δ isoforms, of which only p110α is mutated in cancer. To assess the roles of class I PI3K isoforms in cell proliferation and survival, we generated immortalized mouse leukocyte and fibroblast models in which class I PI3Ks were inactivated by genetic and pharmacological approaches. In IL3-dependent hemopoietic progenitor cells (which express all four class I PI3K isoforms), genetic inactivation of either p110α or p110δ did not affect cell proliferation or survival or sensitize to p110β or p110γ inactivation. Upon compound inactivation of p110α and p110δ, which removed >90% of p85-associated PI3K activity, remarkably, cells continued to proliferate effectively, with p110β assuming an essential role in signaling and cell survival. Furthermore, under these conditions of diminished class I PI3K activity, input from the ERK pathway became important for cell survival. Similar observations were made in mouse embryonic fibroblasts (which mainly express p110α and p110β) in which p110α or p110β could sustain cell proliferation as a single isoform. Taken together, these data demonstrate that a small fraction of total class I PI3K activity is sufficient to sustain cell survival and proliferation. Persistent inhibition of selected PI3K isoforms can allow the remaining isoform(s) to couple to upstream signaling pathways in which they are not normally engaged. Such functional redundancy of class IA PI3K isoforms upon sustained PI3K inhibition has implications for the development and use of PI3K inhibitors in cancer.
Predicting global atmospheric ice nuclei distributions and their impacts on climate
Authors: DeMott P. J. , Prenni A. J. , Liu X. , Kreidenweis S. M. , Petters M. D. , Twohy C. H. , Richardson M. S. , Eidhammer T. , Rogers D. C.
Published: June 2010

Knowledge of cloud and precipitation formation processes remains incomplete, yet global precipitation is predominantly produced by clouds containing the ice phase. Ice first forms in clouds warmer than -36 °C on particles termed ice nuclei. We combine observations from field studies over a 14-year period, from a variety of locations around the globe, to show that the concentrations of ice nuclei active in mixed-phase cloud conditions can be related to temperature and the number concentrations of particles larger than 0.5 μm in diameter. This new relationship reduces unexplained variability in ice nuclei concentrations at a given temperature from ∼10
3
to less than a factor of 10, with the remaining variability apparently due to variations in aerosol chemical composition or other factors. When implemented in a global climate model, the new parameterization strongly alters cloud liquid and ice water distributions compared to the simple, temperature-only parameterizations currently widely used. The revised treatment indicates a global net cloud radiative forcing increase of ∼1 W m
-2
for each order of magnitude increase in ice nuclei concentrations, demonstrating the strong sensitivity of climate simulations to assumptions regarding the initiation of cloud glaciation.
Regulation of PTEN/Akt and MAP kinase signaling pathways by the ubiquitin ligase activators Ndfip1 and Ndfip2
Authors: Mund Thomas , Pelham Hugh R. B.
Published: June 2010

Ndfip1 and Ndfip2 are related endosomal membrane proteins that bind to and activate members of the Nedd4 family of E3 ubiquitin ligases. These ligases in turn affect receptor tyrosine kinase signaling by ubiquitinating several key components of the signaling pathways. Here we investigate the role of the Ndfip proteins in EGF signaling. We show that they associate with the EGF receptor and PTEN, and control the ubiquitination and abundance of PTEN, c-Cbl, and Src family kinases. Ndfip2, but not Ndfip1, also binds to and is phosphorylated by Src and Lyn, and can act as a scaffold for Src phosphorylation of Ndfip1 and potentially other substrates. Depletion of Ndfip1 inhibits Akt activation in EGF-stimulated HeLa cells, stimulates activation of Jnk, and enhances cell multiplication. Thus Ndfip1 and Ndfip2 are physically and functionally associated with multiple components of the EGF signaling cascade, and their levels modulate the relative output of different signaling pathways.
Inhibitor of growth-4 promotes IκB promoter activation to suppress NF-κB signaling and innate immunity
Authors: Coles Andrew H. , Gannon Hugh , Cerny Anna , Kurt-Jones Evelyn , Jones Stephen N.
Published: June 2010

Ing4 is a member of the inhibitor of growth (ING) family of chromatin-modifying proteins. Biochemical experiments indicate that Ing4 is a subunit of the HB01-JADE-hEAF6 histone acetyltransferase complex responsible for most nucleosomal histone H4 acetylation in eukaryotes, and transfection studies suggest that Ing4 may regulate a wide variety of cellular processes, including DNA repair, apoptosis, cell-cycle regulation, metastasis, angiogenesis, and tumor suppression. However, in vivo evidence for a physiological role for Ing4 in cell-growth regulation is lacking. We have generated Ing4-deficient mice to explore the role of Ing4 in development, tumorigenesis, and in NF-κB signaling. Ing4-null mice develop normally and are viable. Although mice deficient for Ing4 fail to form spontaneous tumors, they are hypersensitive to LPS treatment and display elevated cytokine responses. Macrophages isolated from Ing4-null mice have increased levels of nuclear p65/RelA protein, resulting in increased RelA binding to NF-κB target promoters and up-regulation of cytokine gene expression. However, increased promoter occupancy by RelA in LPS-stimulated, Ing4-null cells does not always correlate with increased NF-κB target-gene expression, as RelA activation of a subset of cytokine promoters also requires Ing4 for proper histone H4 acetylation. Furthermore, activation of the IκBα promoter by RelA is also Ing4-dependent, and LPS-stimulated, Ing4-null cells have reduced levels of IκBα promoter H4 acetylation and IκB gene expression. Thus, Ing4 negatively regulates the cytokine-mediated inflammatory response in mice by facilitating NF-κB activation of IκB promoters, thereby suppressing nuclear RelA levels and the activation of select NF-κB target cytokines.
Population robustness arising from cellular heterogeneity
Authors: Paszek Pawel , Ryan Sheila , Ashall Louise , Sillitoe Kate , Harper Claire V. , Spiller David G. , Rand David A. , White Michael R. H.
Published: June 2010

Heterogeneity between individual cells is a common feature of dynamic cellular processes, including signaling, transcription, and cell fate; yet the overall tissue level physiological phenotype needs to be carefully controlled to avoid fluctuations. Here we show that in the NF-κB signaling system, the precise timing of a dual-delayed negative feedback motif [involving stochastic transcription of inhibitor κB (IκB)-α and -ε] is optimized to induce heterogeneous timing of NF-κB oscillations between individual cells. We suggest that this dual-delayed negative feedback motif enables NF-κB signaling to generate robust single cell oscillations by reducing sensitivity to key parameter perturbations. Simultaneously, enhanced cell heterogeneity may represent a mechanism that controls the overall coordination and stability of cell population responses by decreasing temporal fluctuations of paracrine signaling. It has often been thought that dynamic biological systems may have evolved to maximize robustness through cell-to-cell coordination and homogeneity. Our analyses suggest in contrast, that this cellular variation might be advantageous and subject to evolutionary selection. Alternative types of therapy could perhaps be designed to modulate this cellular heterogeneity.
Robust control of the seasonal expression of the
Arabidopsis FLC
gene in a fluctuating environment
Authors: Aikawa Shinichiro , Kobayashi Masaki J. , Satake Akiko , Shimizu Kentaro K. , Kudoh Hiroshi
Published: June 2010

Plants flower in particular seasons even in natural, fluctuating environments. The molecular basis of temperature-dependent flowering-time regulation has been extensively studied, but little is known about how gene expression is controlled in natural environments. Without a memory of past temperatures, it would be difficult for plants to detect seasons in natural, noisy environments because temperature changes occurring within a few weeks are often inconsistent with seasonal trends. Our 2-y census of the expression of a temperature-dependent flowering-time gene,
AhgFLC
, in a natural population of perennial
Arabidopsis halleri
revealed that the regulatory system of this flowering-time gene extracts seasonal cues as if it memorizes temperatures over the past 6 wk. Time-series analysis revealed that as much as 83% of the variation in the
AhgFLC
expression is explained solely by the temperature for the previous 6 wk, but not by the temperatures over shorter or longer periods. The accuracy of our model in predicting the gene expression pattern under contrasting temperature regimes in the transplant experiments indicates that such modeling incorporating the molecular bases of flowering-time regulation will contribute to predicting plant responses to future climate changes.
Synergistic allelochemicals from a freshwater cyanobacterium
Authors: Leão Pedro N. , Pereira Alban R. , Liu Wei-Ting , Ng Julio , Pevzner Pavel A. , Dorrestein Pieter C. , König Gabriele M. , Vasconcelos Vitor M. , Gerwick William H.
Published: June 2010

The ability of cyanobacteria to produce complex secondary metabolites with potent biological activities has gathered considerable attention due to their potential therapeutic and agrochemical applications. However, the precise physiological or ecological roles played by a majority of these metabolites have remained elusive. Several studies have shown that cyanobacteria are able to interfere with other organisms in their communities through the release of compounds into the surrounding medium, a phenomenon usually referred to as allelopathy. Exudates from the freshwater cyanobacterium
Oscillatoria
sp. had previously been shown to inhibit the green microalga
Chlorella vulgaris
. In this study, we observed that maximal allelopathic activity is highest in early growth stages of the cyanobacterium, and this provided sufficient material for isolation and chemical characterization of active compounds that inhibited the growth of
C. vulgaris
. Using a bioassay-guided approach, we isolated and structurally characterized these metabolites as cyclic peptides containing several unusually modified amino acids that are found both in the cells and in the spent media of
Oscillatoria
sp. cultures. Strikingly, only the mixture of the two most abundant metabolites in the cells was active toward
C. vulgaris
. Synergism was also observed in a lung cancer cell cytotoxicity assay. The binary mixture inhibited other phytoplanktonic organisms, supporting a natural function of this synergistic mixture of metabolites as allelochemicals.
Analysis of in vivo dynamics of influenza virus infection in mice using a GFP reporter virus
Authors: Manicassamy Balaji , Manicassamy Santhakumar , Belicha-Villanueva Alan , Pisanelli Giuseppe , Pulendran Bali , García-Sastre Adolfo
Published: June 2010

Influenza A virus is being extensively studied because of its major impact on human and animal health. However, the dynamics of influenza virus infection and the cell types infected in vivo are poorly understood. These characteristics are challenging to determine, partly because there is no efficient replication-competent virus expressing an easily traceable reporter gene. Here, we report the generation of a recombinant influenza virus carrying a GFP reporter gene in the NS segment (NS1-GFP virus). Although attenuated when compared with wild-type virus, the NS1-GFP virus replicates efficiently in murine lungs and shows pathogenicity in mice. Using whole-organ imaging and flow cytometry, we have tracked the dynamics of influenza virus infection progression in mice. Imaging of murine lungs shows that infection starts in the respiratory tract in areas close to large conducting airways and later spreads to deeper sections of the lungs. In addition to epithelial cells, we found GFP-positive antigen-presenting cells, such as CD11b+CD11c−, CD11b−CD11c+, and CD11b+CD11c+, as early as 24 h after intranasal infection. In addition, a significant proportion of NK and B cells were GFP positive, suggesting active infection of these cells. We next tested the effects of the influenza virus inhibitors oseltamivir and amantadine on the kinetics of in vivo infection progression. Treatment with oseltamivir dramatically reduced influenza infection in all cell types, whereas, surprisingly, amantadine treatment more efficiently blocked infection in B and NK cells. Our results demonstrate high levels of immune cells harboring influenza virus antigen during viral infection and cell-type–specific effects upon treatment with antiviral agents, opening additional avenues of research in the influenza virus field.
Organometallic mechanism of action and inhibition of the 4Fe-4S isoprenoid biosynthesis protein GcpE (IspG)
Authors: Wang Weixue , Li Jikun , Wang Ke , Huang Cancan , Zhang Yong , Oldfield Eric
Published: June 2010

We report the results of a series of chemical, EPR, ENDOR, and HYSCORE spectroscopic investigations of the mechanism of action (and inhibition) of GcpE,E-1-hydroxy-2-methyl-but-2-enyl-4-diphosphate (HMBPP) synthase, also known as IspG, an Fe4S4cluster-containing protein. We find that the epoxide of HMBPP when reduced by GcpE generates the same transient EPR species as observed on addition of the substrate, 2-C-methyl-D-erythritol-2, 4-cyclo-diphosphate. ENDOR and HYSCORE spectra of these transient species (using2H,13C and17O labeled samples) indicate formation of an Fe-C-H containing organometallic intermediate, most likely a ferraoxetane. This is then rapidly reduced to a ferracyclopropane in which the HMBPP product forms anη2-alkenylπ- (orπ/σ) complex with the 4th Fe in the Fe4S4cluster, and a similar “metallacycle” also forms between isopentenyl diphosphate (IPP) and GcpE. Based on this metallacycle concept, we show that an alkyne (propargyl) diphosphate is a good (Ki ∼ 300 nM) GcpE inhibitor, and supported again by EPR and ENDOR results (a13C hyperfine coupling of ∼7 MHz), as well as literature precedent, we propose that the alkyne forms anotherπ/σmetallacycle, anη2-alkynyl, or ferracyclopropene. Overall, the results are of broad general interest because they provide new mechanistic insights into GcpE catalysis and inhibition, with organometallic bond formation playing, in both cases, a key role.
Escherichia coli
induces DNA damage in vivo and triggers genomic instability in mammalian cells
Authors: Cuevas-Ramos Gabriel , Petit Claude R. , Marcq Ingrid , Boury Michèle , Oswald Eric , Nougayrède Jean-Philippe
Published: June 2010

Escherichia coli
is a normal inhabitant of the human gut. However,
E. coli
strains of phylogenetic group B2 harbor a genomic island called “
pks
” that codes for the production of a polyketide-peptide genotoxin, Colibactin. Here we report that in vivo infection with
E. coli
harboring the
pks
island, but not with a
pks
isogenic mutant, induced the formation of phosphorylated H2AX foci in mouse enterocytes. We show that a single, short exposure of cultured mammalian epithelial cells to live

pks
+
E. coli

at low infectious doses induced a transient DNA damage response followed by cell division with signs of incomplete DNA repair, leading to anaphase bridges and chromosome aberrations. Micronuclei, aneuploidy, ring chromosomes, and anaphase bridges persisted in dividing cells up to 21 d after infection, indicating occurrence of breakage–fusion–bridge cycles and chromosomal instability. Exposed cells exhibited a significant increase in gene mutation frequency and anchorage-independent colony formation, demonstrating the infection mutagenic and transforming potential. Therefore, colon colonization with these
E. coli
strains harboring the
pks
island could contribute to the development of sporadic colorectal cancer.
Engineered bacterial communication prevents
Vibrio cholerae
virulence in an infant mouse model
Authors: Duan Faping , March John C.
Published: June 2010

To investigate the possibility of using commensal bacteria as signal mediators for inhibiting the disease cholera, we stably transformed
Escherichia coli
Nissle 1917 (Nissle) to express the autoinducer molecule cholera autoinducer 1 (CAI-1) (shown previously to prevent virulence when present with another signaling molecule, autoinducer 2, at high concentrations) and determined the effect on
Vibrio cholerae
virulence gene expression and colonization in an infant mouse model. We found that pretreatment of mice for 8 h with Nissle engineered to express CAI-1 (Nissle-cqsA) greatly increased the mice’s survival (92%) from ingestion of
V. cholerae
. Pretreatment with Nissle-cqsA for only 4 h increased survival by 77%, whereas ingesting Nissle-cqsA at the same time as
V. cholerae
increased survival rates by 27%. Immunostaining revealed an 80% reduction in cholera toxin binding to the intestines of mice pretreated for 8 h with Nissle-cqsA. Further, the numbers of
V. cholerae
in treated mouse intestines was reduced by 69% after 40 h. This finding points to an easily administered and inexpensive approach where commensal bacteria are engineered to communicate with invasive species and potentially prevent human disease.
In vivo assembly of nanoparticle components to improve targeted cancer imaging
Authors: Perrault Steven D. , Chan Warren C. W.
Published: June 2010

Many small molecular anticancer agents are often ineffective at detecting or treating cancer due to their poor pharmacokinetics. Using nanoparticles as carriers can improve this because their large size reduces clearance and improves retention within tumors, but it also slows their rate of transfer from circulation into the tumor interstitium. Here, we demonstrate an alternative strategy whereby a molecular contrast agent and engineered nanoparticle undergo in vivo molecular assembly within tumors, combining the rapid influx of the smaller and high retention of the larger component. This strategy provided rapid tumor accumulation of a fluorescent contrast agent, 16- and 8-fold faster than fluorescently labeled macromolecule or nanoparticle controls achieved. Diagnostic sensitivity was 3.0 times that of a passively targeting nanoparticle, and this improvement was achieved 3 h after injection. The advantage of the in vivo assembly approach for targeting is rapid accumulation of small molecular agents in tumors, shorter circulation time requirements, possible systemic clearance while maintaining imaging sensitivity in the tumor, and nanoparticle anchors in tumors can be utilized to alter the pharmacokinetics of contrast agents, therapeutics, and other nanoparticles. This study demonstrates molecular assembly of nanoparticles within tumors, and provides a new basis for the future design of nanomaterials for medical applications.