bluuebunny/crossref_metadata_2025 huggingface dataset:
Sequence-Verified Two-Allele Transposon Mutant Library for Pseudomonas aeruginosa PAO1
Authors: Held Kiara , Ramage Elizabeth , Jacobs Michael , Gallagher Larry , Manoil Colin
Published: September 2012

Mutant hunts using comprehensive sequence-defined libraries make it possible to identify virtually all of the nonessential functions required for different bacterial processes. However, the success of such screening depends on the accuracy of mutant identification in the mutant library used. To provide a high-quality library for
Pseudomonas aeruginosa
PAO1, we created a sequence-verified collection of 9,437 transposon mutants that provides genome coverage and includes two mutants for most genes. Mutants were cherry-picked from a larger library, colony-purified, and resequenced both individually using Sanger sequencing and in a pool using Tn-seq. About 8% of the insertion assignments were corrected, and in the final library nearly 93% of the transposon locations were confirmed by at least one of the resequencing procedures. The extensive sequence verification and inclusion of more than one mutant for most genes should help minimize missed or erroneous genotype-phenotype assignments in studies using the new library.
Chronic urticaria following acute hepatitis A: Figure 1
Authors: Griffin Paul M , Kevat Dev A S , McCarthy James S , Woods Marion L
Published: September 2012

Urticaria has a documented association with the prodromal phases of hepatitis A, B and, although still contentious, likely hepatitis C. Despite the documented association there are few actual reported cases of urticaria occurring with hepatitis A infection and in all of the cases reported so far the urticaria preceded the diagnosis of hepatitis A and was acute rather than chronic. We describe a case of urticaria occurring following acute infection with hepatitis A, which persisted beyond 6 weeks and therefore was by definition chronic. Although chronic urticaria has been reported to be associated with other forms of viral hepatitis, to the best of our knowledge this has not been reported previously with hepatitis A.
A trans European Union difference in the decline intransfatty acids in popular foods: a market basket investigation
Authors: Stender Steen , Astrup Arne , Dyerberg Jørn
Published: September 2012

Objectives

To minimise the intake of industrialtransfatty acids (I-TFA) some countries have introduced labelling, while others have introduced legislative limits on the content of I-TFA in food. However, most countries still rely on food producers to voluntarily reduce the I-TFA content in food. The objective of the present study was to investigate the efficiency of these strategies in the EU.

Design

The potential consumption of I-TFA was assessed in a market basket investigation by analysing the I-TFA content in popular foods.

Setting

A standardised purchase methodology was used in 16 EU countries in 2005 and again in 2009.

Samples

Seventy servings of French fries and chicken nuggets, 90 packages of microwave popcorn, and 442 samples of biscuits/cakes/wafers with ‘partially hydrogenated vegetable fat’ listed high on the list of ingredients were analysed. A high-transmenu was defined as a large serving of French fries and nuggets, 100 g of microwave popcorn and 100 g of biscuits/wafers/cakes.

Results

In 2005, a high-transmenu provided above 30 g of I-TFA in five EU countries in Eastern Europe and 20–30 g in eight EU countries in Western Europe. In 2009 the values in Hungary, Poland and the Czech Republic remained high between 10 and 20 g, whereas they were less than 2 g in Germany, France and the UK.

Conclusions

In 2009 contents of I-TFA in popular foods in Western Europe appear low but, in spite of some reduction, still high in Eastern European EU countries. These findings suggest that millions of people in the EU still consume I-TFA in amounts that substantially increase their risk of coronary heart disease.
Risk of repeat visits, hospitalisation and death after uncompleted and completed visits to the emergency department: a prospective observation study
Authors: Geirsson Oli Pall , Gunnarsdottir Oddny Sigurborg , Baldursson Jon , Hrafnkelsson Birgir , Rafnsson Vilhjalmur
Published: September 2012

Objectives

The needs of patients with uncompleted visits to the emergency department (ED) are uncertain. The aim was to evaluate ED patients who leave against medical advice (AMA) and who leave without being seen (WBS) regarding repeat ED visits, hospitalisation and mortality within 30 days.

Methods

The National University Hospital operates the only ED for adults in the capital area of Reykjavik. The source of data was the electronic records for patients 18 years or older, who left AMA, who left WBS, who had the ICD-10 code Z53.2, or who completed their visits. ED visits, hospital admissions and the death registry are filed with the personal identification number, which enabled recognition of the index visit, and the outcomes, rates of return visits, hospitalisation and death.

Results

Of 107 119 patients, 77 left AMA, 4471 left WBS and 423 had code Z53.2. The HR for returning to the ED within 30 days was 4.79 for AMA patients, 4.84 for WBS patients and 3.67 for Z53.2 patients. The HR for hospitalisation within 30 days was 6.90 for AMA patients, 1.09 for WBS patients and 1.07 for Z53.2 patients. The HR for death within 30 days was 10.97 for AMA patients, 0.84 for WBS and no deaths occurred among Z53.2 patients.

Discussion

During 30 days follow-up, AMA and WBS patients had an increased rate of repeat ED visits compared with those patients who completed their ED visits. AMA patients also had an increased rate of hospitalisations.
ON LOCAL DILATATION INVARIANCE
Authors: CLARK T. E. , LOVE S. T.
Published: September 2012

The relationship between local Weyl scaling invariant models and local dilatation invariant actions is critically scrutinized. While actions invariant under local Weyl scalings can be constructed in a straightforward manner, actions invariant under local dilatation transformations can only be achieved in a very restrictive case. The invariant couplings of matter fields to an Abelian vector field carrying a nontrivial scaling weight can be easily built, but an invariant Abelian vector kinetic term can only be realized when the local scale symmetry is spontaneously broken.
SINGULARITIES OF STATIONARY SOLUTIONS TO THE VLASOV–POISSON SYSTEM IN A POLYGON
Authors: KARAMI FAHD , LABRUNIE SIMON , PINÇON BRUNO
Published: September 2012

We present an existence result for the stationary Vlasov–Poisson system in a bounded domain of ℝN, with more general hypotheses than considered so far in the literature. In particular, we prove the equivalence of the kinetic approach (which consists in looking for the equilibrium distribution function) and the potential approach (where the unknown is the electrostatic potential at equilibrium). We study the dependence of the solution on parameters such as the total mass of the distribution, or those entering in the boundary conditions of the potential. Focusing on the case of a plane polygon, we study the singular behavior of the solution near the re-entrant corners, and examine the dependence of the singularity coefficients on the parameters of the problem. Numerical experiments illustrate and confirm the analysis.
BDDC PRECONDITIONERS FOR ISOGEOMETRIC ANALYSIS
Authors: BEIRÃO DA VEIGA L. , CHO D. , PAVARINO L. F. , SCACCHI S.
Published: September 2012

A Balancing Domain Decomposition by Constraints (BDDC) preconditioner for Isogeometric Analysis of scalar elliptic problems is constructed and analyzed by introducing appropriate discrete norms. A main result of this work is the proof that the proposed isogeometric BDDC preconditioner is scalable in the number of subdomains and quasi-optimal in the ratio of subdomain and element sizes. Another main result is the numerical validation of the theoretical convergence rate estimates by carrying out several two- and three-dimensional tests on serial and parallel computers. These numerical experiments also illustrate the preconditioner performance with respect to the polynomial degree and the regularity of the NURBS basis functions, as well as its robustness with respect to discontinuities of the coefficient of the elliptic problem across subdomain boundaries.
MOMENT PRESERVING FINITE VOLUME SCHEMES FOR SOLVING POPULATION BALANCE EQUATIONS INCORPORATING AGGREGATION, BREAKAGE, GROWTH AND SOURCE TERMS
Authors: KUMAR RAJESH , KUMAR JITENDRA , WARNECKE GERALD
Published: September 2012

In this work we present some moment preserving finite volume schemes (FVS) for solving population balance equations. We are considering unified numerical methods to simultaneous aggregation, breakage, growth and source terms, e.g. for nucleation. The criteria for the preservation of different moments are given. The property of conservation is a special case of preservation. First we present a FVS which shows the preservation with respect to one-moment depending upon the processes under consideration. In case of the aggregation and breakage it satisfies first-moment preservation whereas for the growth and nucleation we observe zeroth-moment preservation. This is due to the well-known property of conservativity of FVS. However, coupling of all the processes shows no preservation for any moments. To overcome this issue, we reformulate the cell average technique into a conservative formulation which is coupled together with a modified upwind scheme to give moment preservation with respect to the first two-moments for all four processes under consideration. This allows for easy coupling of these processes. The preservation is proven mathematically and verified numerically. The numerical results for the first two-moments are verified for various coupled processes where analytical solutions are available.
Maximal k-ideals and r-ideals in semirings
Authors: Han Song-Chol
Published: September 2012

Some properties of (left) k-ideals and r-ideals of a semiring are considered by the help of the congruence class semiring. It is proved that a proper k-ideal of a semiring with an identity is prime if it is a maximal left k-ideal. An equivalent condition for a proper r-ideal of a semiring being a maximal (left) r-ideal is established. It is shown that (left) r-ideals and (left) k-ideals coincide for an additively idempotent semiring, though the former is a special kind of the latter in general. It is proved that a proper k-ideal of an incline with an identity is a maximal k-ideal if and only if the corresponding congruence class semiring is the Boolean semiring.
GORENSTEIN INJECTIVE MODULES AND A GENERALIZATION OF ISCHEBECK FORMULA
Authors: SAZEEDEH REZA
Published: September 2012

Let (R,[Formula: see text]) be a commutative Noetherian local ring and let M and N be nonzero finitely generated R-modules of finite injective dimension and finite Gorenstein injective dimension, respectively. In this paper, we prove a generalization of Ischebeck formula, that is [Formula: see text].
REGULARITY AND STRONG REGULARITY IN THE CONTEXT OF CERTAIN CLASSES OF RINGS
Authors: ZIEMBOWSKI MICHAŁ
Published: September 2012

We consider the ring R[x]/(xn+1), where R is a ring, R[x] is the ring of polynomials in an indeterminant x, (xn+1) is the ideal of R[x] generated by xn+1 and n is a positive integer. The aim of this paper is to show that regularity or strong regularity of a ring R is necessary and sufficient condition under which the ring R[x]/(xn+1) is an example of a ring which belongs to some important classes of rings. In this context, we discuss distributive rings, Bézout rings, Gaussian rings, quasi-morphic rings, semihereditary rings, and rings which have weak dimension less than or equal to one.
BIDIAGONAL PAIRS, THE LIE ALGEBRA 𝔰𝔩2, AND THE QUANTUM GROUP Uq(𝔰𝔩2)
Authors: FUNK-NEUBAUER DARREN
Published: September 2012

We introduce a linear algebraic object called a bidiagonal pair. Roughly speaking, a bidiagonal pair is a pair of diagonalizable linear transformations on a finite-dimensional vector space, each of which acts in a bidiagonal fashion on the eigenspaces of the other. We associate to each bidiagonal pair a sequence of scalars called a parameter array. Using this concept of a parameter array we present a classification of bidiagonal pairs up to isomorphism. The statement of this classification does not explicitly mention the Lie algebra 𝔰𝔩2or the quantum group Uq(𝔰𝔩2). However, its proof makes use of the finite-dimensional representation theory of 𝔰𝔩2and Uq(𝔰𝔩2). In addition to the classification we make explicit the relationship between bidiagonal pairs and modules for 𝔰𝔩2and Uq(𝔰𝔩2).
COMPUTABILITY OF SPIKING NEURAL P SYSTEMS WITH ANTI-SPIKES
Authors: METTA VENKATA PADMAVATI , KRITHIVASAN KAMALA , GARG DEEPAK
Published: September 2012

Spiking neural P systems with anti-spikes (for short, SN PA systems) can encode the binary digits in a natural way using two types of objects called anti-spikes and spikes. In this paper, we use SN PA systems to perform the arithmetic operation like 2's complement, addition and subtraction of binary numbers. They are also used to simulate NAND and NOR gates.
Observations and Analysis of Relationship between Water Vapor and Aerosols by Using Raman Lidar
Authors: Wang Yufeng , Hua Dengxin , Wang Li , Tang Jie , Mao Jietai , Kobayashi Takao
Published: September 2012

A UV vibrational Raman lidar has been built and used to make quantitative measurements of water vapor and aerosol optical properties over Xi'an, China. Vertical profiles of the water vapor mixing ratio and aerosol extinction coefficient are retrieved. The water vapor mixing ratio is calibrated with radiosonde data. The diurnal variations of the water vapor mixing ratio, aerosol extinction coefficient, and aerosol optical depth are obtained. The results obtained in the form of a time-height indicator (THI) display clearly showed the relationship between water vapor and aerosols, in which the gradual enhancement of water vapor density results in aerosol accumulation in the early morning, in particular in the lower troposphere. The seasonal variations of the water vapor mixing ratio and aerosol optical depth over Xi'an were observed and analyzed using the average monthly distribution obtained by lidar for the first time, which will provide useful scientific data and real-time monitoring methods for studying local climate change.
Wavelength Switching of Erbium-Doped Fiber Laser by Optical Injection into Overlapped Laser Cavities
Authors: Tang Jeng-Bin , Hsieh Kai-Jein , Wang Likarn
Published: September 2012

We present a wavelength switching scheme with three overlapped erbium-doped fiber laser (EDFL) cavities. The design issue on obtaining switching among different wavelengths has not been fully discussed yet. In this study, we give a discussion on the effect of external optical injection power on the wavelength switching among three wavelengths. We also show that the side-mode-suppression ratio achievable is dependent on the light power injected into the fiber laser cavity and the wavelength of the injection light. The EDFL designed here lases at the wavelengths 1545.3, 1550.2, and 1555.2 nm with achievable side-mode-suppression ratios of 27.5, 34.4, and 34.8 dB, respectively.
Generalized X-code
Authors: Luo Xianghong , Shu Jiwu
Published: September 2012

Many RAID-6 codes have been proposed in the literature, but each has its limitations. Horizontal code has the ability to adapt to the arbitrary size of a disk array but its high computational complexity is a major shortcoming. In contrast, the computational complexity of vertical code (e.g. X-code) often achieves the theoretical optimality, but vertical code is limited to using a prime number as the size of the disk array In this article, we propose a novel efficient RAID-6 code for arbitrary size of disk array: generalized X-code. We move the redundant elements along their calculation diagonals in X-code onto two specific disks and change two data elements into redundant elements in order to realize our new code. The generalized X-code achieves optimal encoding and updating complexity and low decoding complexity; in addition, it has the ability to adapt to arbitrary size of disk array. Furthermore, we also provide a method for generalizing horizontal code to achieve optimal encoding and updating complexity while keeping the code's original ability to adapt to arbitrary size of disk array.
A robust high-capacity affine-transformation-invariant scheme for watermarking 3D geometric models
Authors: Gao Xifeng , Zhang Caiming , Huang Yan , Deng Zhigang
Published: September 2012

In this article we propose a novel, robust, and high-capacity watermarking method for 3D meshes with arbitrary connectivities in the spatial domain based on affine invariants. Given a 3D mesh model, a watermark is embedded as affine-invariant length ratios of one diagonal segment to the residing diagonal intersected by the other one in a coplanar convex quadrilateral. In the extraction process, a watermark is recovered by combining all the watermark pieces embedded in length ratios through majority voting. Extensive experimental results demonstrate the robustness, high computational efficiency, high capacity, and affine-transformation-invariant characteristics of the proposed approach.
Exposing MP3 audio forgeries using frame offsets
Authors: Yang Rui , Qu Zhenhua , Huang Jiwu
Published: September 2012

Audio recordings should be authenticated before they are used as evidence. Although audio watermarking and signature are widely applied for authentication, these two techniques require accessing the original audio before it is published. Passive authentication is necessary for digital audio, especially for the most popular audio format: MP3. In this article, we propose a passive approach to detect forgeries of MP3 audio. During the process of MP3 encoding the audio samples are divided into frames, and thus each frame has its own frame offset after encoding. Forgeries lead to the breaking of framing grids. So the frame offset is a good indication for locating forgeries, and it can be retrieved by the identification of the quantization characteristic. In this way, the doctored positions can be automatically located. Experimental results demonstrate that the proposed approach is effective in detecting some common forgeries, such as deletion, insertion, substitution, and splicing. Even when the bit rate is as low as 32 kbps, the detection rate is above 99%.
Disruption of Nox2 and TNFRp55/p75 eliminates cardioprotection induced by anisomycin
Authors: Zhao Ting C. , Zhang Ling , Liu Jun T. , Guo Tai L.
Published: September 2012

Transient activation of p38 through anisomycin is demonstrated to precondition the heart against myocardial injury. However, it remains unknown whether specific TNF-α receptor (TNFR) p55/p75 and Nox2, a subunit of NADPH oxidase, are involved in this event. We sought to investigate whether the genetic disruption of TNFRp55/p75 and Nox2 eliminated cardioprotection elicited by anisomycin and whether p38-dependent activation of Nox2 stimulated TNFR to ultimately achieve protective effects. Adult wild-type and TNFR p55/p75−/−and Nox2−/−mice received intraperitoneal injections of anisomycin (0.1 mg/kg), a potent activator of p38. The hearts were subjected to 30 min myocardial ischemia/30 min reperfusion in the Langendorff perfused heart after 24 h. Left ventricular function was measured, and infarct size was determined. Myocardial TNF-α protein, Nox2, and superoxides releases were detected. Gel kinase assay was employed to detect the effect of p38 on Nox2 phosphorylation. Activation of p38 through anisomycin produces marked improvements in left ventricular functional recovery, and the reduction of myocardial infarction, which were abrogated by disruption of Nox2 and TNFR p55/p75. Disruption of Nox2 and TNFR p55/p75 abolished the effect of anisomycin-induced reduction of infarct size. Anisomycin induced the production of TNF-α, which was abrogated in Nox2−/−mice and by treatment with SB203580, but not by disruption of p55/p75. Anisomycin treatment resulted in an increase in Nox2 protein and the phosphorylation of Nox2, which was blocked by inhibition of p38. Taken together, these results indicate that stimulation of the Nox2 and TNFR p55/p75 pathway is a novel approach to anisomycin-induced cardioprotection.
Shear elastic modulus can be used to estimate an index of individual muscle force during a submaximal isometric fatiguing contraction
Authors: Bouillard Killian , Hug François , Guével Arnaud , Nordez Antoine
Published: September 2012

The present study was designed to determine whether fatigue alters the ability to estimate an index of individual muscle force from shear elastic modulus measurements ( experiment I), and to test the ability of this technique to highlight changes in load sharing within a redundant muscle group during an isometric fatiguing task ( experiment II). Twelve subjects participated in experiment I, which consisted of smooth linear torque ramps from 0 to 80% of maximal voluntary contraction (MVC) performed before and after an isometric fatigue protocol, beginning at 40% of MVC and stopped when the force production dropped below 30% of MVC. Although the relationships between modulus and torque were very similar for pre- and postfatigue [root mean square deviation (RMSdeviation) = 3.7 ± 2.6% of MVC], the relationships between electromyography activity level and torque were greatly altered by fatigue (RMSdeviation = 10.3 ± 2.6% of MVC). During the fatiguing contraction, shear elastic modulus provided a significantly lower RMSdeviation between measured torque and estimated torque than electromyography activity level (5.7 ± 0.9 vs. 15.3 ± 3.8% of MVC). Experiment II performed with eight participants consisted of an isometric knee extension at 25% of MVC sustained until exhaustion. Opposite changes in shear elastic modulus were observed between synergists (vastus medialis, vastus lateralis, and rectus femoris) of some participants, reflecting changes in load sharing. In conclusion, despite the fact that we did not directly estimate muscle force (in Newtons), this is the first demonstration of an experimental technique to accurately quantify relative changes in force in an individual human muscle during a fatiguing contraction.
County Differences in Mortality among Foreign-Born Compared to Native Swedes 1970–1999
Authors: Albin Björn , Hjelm Katarina , Ekberg Jan , Elmståhl Sölve
Published: September 2012

Background. Regional variations in mortality and morbidity have been shown in Europe and USA. Longitudinal studies have found increased mortality, dissimilarities in mortality pattern, and differences in utilization of healthcare between foreign- and native-born Swedes. No study has been found comparing mortality among foreign-born and native-born Swedes in relation to catchment areas/counties.Methods. The aim was to describe and compare mortality among foreign-born persons and native Swedes during 1970–1999 in 24 counties in Sweden. Data from the Statistics Sweden and the National Board of Health and Welfare was used, and the database consisted of 723,948 persons, 361,974 foreign-born living in Sweden in 1970 and aged 16 years and above and 361,974 matched Swedish controls.Results. Latest county of residence independently explained higher mortality among foreign-born persons in all but four counties; OR varied from 1.01 to 1.29. Counties with a more rural structure showed the highest differences between foreign-born persons and native controls. Foreign-born persons had a lower mean age (1.0–4.3 years) at time of death.Conclusion. County of residence influences mortality; higher mortality is indicated among migrants than native Swedes in counties with a more rural structure. Further studies are needed to explore possible explanations.
Persistent Amplification of DNA Damage Signal Involved in Replicative Senescence of Normal Human Diploid Fibroblasts
Authors: Suzuki Masatoshi , Suzuki Keiji , Kodama Seiji , Yamashita Shunichi , Watanabe Masami
Published: September 2012

Foci of phosphorylated histone H2AX and ATM are the surrogate markers of DNA double strand breaks. We previously reported that the residual foci increased their size after irradiation, which amplifies DNA damage signals. Here, we addressed whether amplification of DNA damage signal is involved in replicative senescence of normal human diploid fibroblasts. Large phosphorylated H2AX foci (>1.5 μm diameter) were specifically detected in presenescent cells. The frequency of cells with large foci was well correlated with that of cells positive for senescence-associatedβ-galactosidase staining. Hypoxic cell culture condition extended replicative life span of normal human fibroblast, and we found that the formation of large foci delayed in those cells. Our immuno-FISH analysis revealed that large foci partially localized at telomeres in senescent cells. Importantly, large foci of phosphorylated H2AX were always colocalized with phosphorylated ATM foci. Furthermore, Ser15-phosphorylated p53 showed colocalization with the large foci. Since the treatment of senescent cells with phosphoinositide 3-kinase inhibitor, wortmannin, suppressed p53 phosphorylation, it is suggested that amplification of DNA damage signaling sustains persistent activation of ATM-p53 pathway, which is essential for replicative senescence.
The Initial Learning Curve for Robot-Assisted Sleeve Gastrectomy: A Surgeon’s Experience While Introducing the Robotic Technology in a Bariatric Surgery Department
Authors: Vilallonga Ramon , Fort José Manuel , Gonzalez Oscar , Caubet Enric , Boleko Angeles , Neff Karl John , Armengol Manel
Published: September 2012

Objective. Robot-assisted sleeve gastrectomy has the potential to treat patients with obesity and its comorbidities. To evaluate the learning curve for this procedure before undergoing Roux en-Y gastric bypass is the objective of this paper.Materials and Methods. Robot-assisted sleeve gastrectomy was attempted in 32 consecutive patients. A survey was performed in order to identify performance variables during completion of the learning curve. Total operative time (OT), docking time (DT), complications, and length of hospital stay were compared among patients divided into two cohorts according to the surgical experience. Scattergrams and continuous curves were plotted to develop a robotic sleeve gastrectomy learning curve.Results. Overall OT time decreased from 89.8 minutes in cohort 1 to 70.1 minutes in cohort 2, with less than 5% change in OT after case 19. Time from incision to docking decreased from 9.5 minutes in cohort 1 to 7.6 minutes in cohort 2. The time required to dock the robotic system also decreased. The complication rate was the same in the two cohorts.Conclusion. Our survey indicates that technique and outcomes for robot-assisted sleeve gastrectomy gradually improve with experience. We found that the learning curve for performing a sleeve gastrectomy using the da Vinci system is completed after about 20 cases.
Mutated KRAS Is an Independent Negative Prognostic Factor for Survival in NSCLC Stage III Disease Treated with High-Dose Radiotherapy
Authors: Hallqvist A. , Enlund F. , Andersson C. , Sjögren H. , Hussein A. , Holmberg E. , Nyman J.
Published: September 2012

Background. The main attention regarding prognostic and predictive markers in NSCLC directs towards the EGFR-targeted pathway, where the most studied genetic alterations include EGFR mutations, EGFR copy number, and KRAS mutations. We wanted to explore the prognostic impact of mutated KRAS in the stage III setting treated with high-dose radiochemotherapy. Methods. Samples were obtained from patients participating in two prospective studies of locally advanced NSCLC receiving combined radiochemotherapy: the RAKET study, a randomized phase II study where patients were treated with induction chemotherapy (carboplatin/paclitaxel) followed by concurrent radiochemotherapy, and the Satellite trial, a phase II study with induction chemotherapy (cisplatin/docetaxel) followed by radiotherapy concurrent cetuximab. The samples were analysed regarding KRAS mutations, EGFR mutations, and EGFR FISH positivity. Results. Patients with mutated KRAS had a significantly inferior survival, which maintained its significance in a multivariate analysis when other possible prognostic factors were taken into account. The prevalence of KRAS mutations, EGFR mutations, and EGFR FISH positivity were 28.8%, 7.5%, and 19.7%, respectively. Conclusion. Mutated KRAS is an independent negative prognostic factor for survival in NSCLC stage III disease treated with combined radiochemotherapy. The prevalence of KRAS mutations and EGFR mutations are as expected in this Scandinavian population.
On the One‐Leg Methods for Solving Nonlinear Neutral Differential Equations with Variable Delay
Authors: Wang Wansheng , Li Shoufu
Published: September 2012

Based on A‐stable one‐leg methods and linear interpolations, we introduce four algorithms for solving neutral differential equations with variable delay. A natural question is which algorithm is better. To answer this question, we analyse the error behavior of the four algorithms and obtain their error bounds under a one‐sided Lipschitz condition and some classical Lipschitz conditions. After extensively numerically experimenting, we give a positive conclusion.
Neuropilin-1–Dependent Regulation of EGF-Receptor Signaling
Authors: Rizzolio Sabrina , Rabinowicz Noa , Rainero Elena , Lanzetti Letizia , Serini Guido , Norman Jim , Neufeld Gera , Tamagnone Luca
Published: September 2012

Neuropilin-1 (NRP1) is a coreceptor for multiple extracellular ligands. NRP1 is widely expressed in cancer cells and in advanced human tumors; however, its functional relevance and signaling mechanisms are unclear. Here, we show that NRP1 expression controls viability and proliferation of different cancer cells, independent of its short intracellular tail. We found that the extracellular domain of NRP1 interacts with the EGF receptor (EGFR) and promotes its signaling cascade elicited upon EGF or TGF-α stimulation. Upon NRP1 silencing, the ability of ligand-bound EGFR to cluster on the cell surface, internalize, and activate the downstream AKT pathway is severely impaired. EGFR is frequently activated in human tumors due to overexpression, mutation, or sustained autocrine/paracrine stimulation. Here we show that NRP1-blocking antibodies and NRP1 silencing can counteract ligand-induced EGFR activation in cancer cells. Thus our findings unveil a novel molecular mechanism by which NRP1 can control EGFR signaling and tumor growth. Cancer Res; 72(22); 5801–11. ©2012 AACR.
The FGFR4-G388R Single-Nucleotide Polymorphism Alters Pancreatic Neuroendocrine Tumor Progression and Response to mTOR Inhibition Therapy
Authors: Serra Stefano , Zheng Lei , Hassan Manal , Phan Alexandria T. , Woodhouse Linda J. , Yao James C. , Ezzat Shereen , Asa Sylvia L.
Published: September 2012

Pancreatic neuroendocrine tumors (pNET), also known as islet cell tumors, exhibit a wide range of biologic behaviors ranging from long dormancy to rapid progression. Currently, there are few molecular biomarkers that can be used to predict recurrence/metastasis or response to therapy. This study examined the predictive and prognostic value of a single nucleotide polymorphism substituting an arginine (R) for glycine (G) in codon 388 of the FGFR4 transmembrane domain. We established the FGFR4 genotype of 71 patients with pNETs and correlated genotype with biologic behavior. We created an in vivo model of pNET with BON1 cells and transfected them with either FGFR4-G388 or FGFR4-R388 to determine the mechanism of action and to examine response to the mTOR inhibitor everolimus. We then validated the predictive results of experimental studies in a group of patients treated with everolimus. FGFR4-R388 is associated with more aggressive clinical behavior in patients with pNETs with a statistically significant higher risk of advanced tumor stage and liver metastasis. Using an orthotopic mouse xenograft model, we show that FGFR4-R388 promotes tumor progression by increasing intraperitoneal spread and metastatic growth within the liver. Unlike FGFR4-G388, FGFR4-R388 BON1 tumors exhibited diminished responsiveness to everolimus. Concordantly, there was a statistically significant reduction in response to everolimus in patients with FGFR4-R388. Our findings highlight the importance of the FGFR4 allele in pNET progression and identify a predictive marker of potential therapeutic importance in this disease. Cancer Res; 72(22); 5683–91. ©2012 AACR.
Gliomagenesis Arising from Pten- and Ink4a/Arf-Deficient Neural Progenitor Cells Is Mediated by the p53-Fbxw7/Cdc4 Pathway, Which Controls c-Myc
Authors: Kim Hong Sug , Woolard Kevin , Lai Chen , Bauer Peter O. , Maric Dragan , Song Hua , Li Aiguo , Kotliarova Svetlana , Zhang Wei , Fine Howard A.
Published: September 2012

Glioblastoma multiforme is the most common type of primary malignant brain tumor and may arise from a cell with neural stem-like properties. Deregulation of the retinoblastoma, phosphoinositide-3 kinase (PI3K), and p53 pathways are molecular hallmarks of this disease. Recent work has shown that p53−/−Pten−/− mice form gliomas in a c-Myc–dependent manner. To explore the role of the INK4A/ARF locus and Pten deletions in gliomagenesis, we generated Pten−/−Ink4a/Arf−/− mouse neural stem cells (mNSC) and such cells were highly proliferative, self-renewing, relatively refractory to differentiation, and induced both low- and high-grade glioma formation in vivo. In contrast to p53−/−Pten−/− mNSCs, however, Pten−/−Ink4a/Arf−/− mNSCs do not express appreciable levels of c-Myc in vitro, although glioma stem cells derived from thesecells did. Sequencing of Pten−/−Ink4a/Arf−/− mNSC–derived tumors revealed spontaneous mutations in Tp53 in vivo with subsequent downregulation of Fbxw7. Expression of p53 mutants in Pten−/−Ink4a/Arf−/− mNSC or knockdown of Fbxw7 resulted in reexpression of c-Myc with enhanced Pten−/−Ink4a/Arf−/− mNSC tumorigenecity. We propose that p53 mutations contribute to gliomagenesis by both allowing the overexpression of c-Myc through downregulation of Fbxw7 and by protecting against c-Myc–induced apoptosis. Cancer Res; 72(22); 6065–75. ©2012 AACR.
Family-Based and Case-Control Study of Glutamate Receptor GRIK3 Ser310Ala Polymorphism in Alcohol Dependence
Authors: Grzywacz A. , Małecka I. , Suchanecka A. , Bieńkowski P. , Samochowiec J.
Published: September 2012

Aim: The aim of this study was to evaluate the role of the glutamate receptor subunit-7 (GluR7, GRIK 3) rs6691840 (Ser310Ala, T928G) in the pathogenesis of alcohol dependence (AD). Methods: DNA was provided from AD patients (n = 209) and healthy control subjects (n = 308) all of Polish descent. The history of alcoholism was obtained using the Polish version of the SSAGA (Semi-Structured Assessment for the Genetics of Alcoholism). We conducted case-control association study and transmission disequilibrium test (TDT). GRIK3 functional polymorphism was genotyped by the PCR-RFLP method. Results: Analyses revealed that polymorphism Ser310Ala of GRIK3 gene is not associated with AD or any of its subgroups. TDT reveled an adequate transmission of both alleles in the group of alcohol families. Conclusions: These findings replicate and extend our previous research results that do not support the hypothesis of the role of rs6691840 in the pathogenesis of AD.
Low Cholesterol, Statins and Outcomes in Patients with First-Ever Acute Ischemic Stroke
Authors: Koton Silvia , Molshatzki Noa , Bornstein Natan M. , Tanne David ,   on behalf of the NASIS Investigators
Published: September 2012

Background: High cholesterol has been associated with better stroke outcomes. Conversely, a protective effect of prestroke statin use in the acute phase of stroke has been reported. The effect of low cholesterol on outcome in patients with and without prestroke statin treatment has not been studied. We assessed the association between low cholesterol and ischemic stroke short- and long-term outcomes and studied potential interactions with statin treatment in patients with a first-ever ischemic stroke in a prospective national registry. Methods: Ischemic stroke patients in the National Acute Stroke Israeli (NASIS) registry with a first-ever stroke and no previous disability, dementia or cancer admitted in all hospitals nationwide during 2-month periods in 2004, 2007 and 2010 were included (n = 1,895). Cholesterol levels ≤155 mg/dl (1st quintile) were defined as low cholesterol and patients treated with statins for at least 7 days before stroke onset were categorized as prestroke statin treated. Severe stroke (NIHSS ≥11), total anterior circulation infarction, poor functional outcome (defined as discharged to a nursing facility or modified Rankin Scale >3 or death), and mortality at discharge and at 3 years were the study outcomes. Associations between low cholesterol and outcomes at discharge were assessed separately in patients with and without prestroke statin treatment using multiple logistic regression analyses. Mortality at 3 years was assessed in a subset of 681 patients with Cox proportional hazard models. Results: Patients were 67.4 ± 13.5 years old on average; 43.1% were women. Low cholesterol was associated with higher rates of stroke risk factors. Controlling for age, sex, hypertension, diabetes, current smoking, ischemic heart disease, congestive heart failure and atrial fibrillation, low cholesterol was significantly associated with severe stroke, total anterior circulation infarction and poor functional outcome in patients with and without statin treatment. There were no interactions between low cholesterol and prestroke statin therapy in association with outcomes. Short- and long-term mortality rates were increased for patients with low cholesterol (5.2% at discharge and 35% at 3-years) compared with higher levels (2.5% at discharge and 20.5% at 3 years). Adjusted mortality risks were increased for patients with low cholesterol; however, this finding was statistically significant only for patients not on statins before the stroke. Conclusions: Low cholesterol is associated with increased stroke severity and poorer functional outcome in patients with and without prestroke statin use. Low-cholesterol statin-naive patients show increased risks of mortality. ‘Reverse epidemiology’ in the association between cholesterol and outcome is possible in patients with ischemic stroke.
Tolvaptan Improves Left Ventricular Dysfunction after Myocardial Infarction in Rats
Authors: Yamazaki Takanori , Izumi Yasukatsu , Nakamura Yasuhiro , Yamashita Naoto , Fujiki Hiroyuki , Osada-Oka Mayuko , Shiota Masayuki , Hanatani Akihisa , Shimada Kenei , Iwao Hiroshi , Yoshiyama Minoru
Published: September 2012

Background—

Arginine vasopressin, which promotes the reabsorption of renal water is increased in chronic heart failure. Here, we compared the effects of tolvaptan, a newly developed nonpeptide V
2
receptor antagonist, with those of furosemide, a loop diuretic, and a combination of these 2 agents in rats with left ventricular dysfunction after myocardial infarction (MI).

Methods and Results—

After 10 weeks of MI induction, the rats were separated them into the following 6 groups adjusted to the infarct size: a vehicle group, a group treated with 15 mg·kg
-1
·day
-1
of furosemide, 2 groups treated with 3 or 10 mg·kg
−1
·day
−1
of tolvaptan; and 2 groups treated with 15 mg·kg
−1
·day
−1
of furosemide plus 3 or 10 mg·kg
−1
·day
−1
tolvaptan. Each treatment agent was administered for 4 weeks, and all groups had similar blood pressure levels and infarct size. The tolvaptan-treated groups were found to have lower levels of left ventricular end-diastolic and systolic cardiac volumes than the vehicle group did. Furthermore, the improvement in the ejection fraction in the tolvaptan-treated groups was significantly greater than those in the vehicle group. ED-1 immunostaining and Sirius red staining revealed that tolvaptan significantly repressed MI-induced macrophage infiltration and interstitial fibrosis in the left ventricle, respectively. Tolvaptan attenuated the MI-induced mRNA expressions of atrial and brain natriuretic peptides, monocyte chemotactic protein-1, transforming growth factor-β1, arginine vasopressin V
1a
receptor, and endothelin-1 in the marginal infarct region.

Conclusions—

Tolvaptan may improve cardiac dysfunction after MI, which is partially mediated by the suppression of V
1a
receptor, neurohumoral activation and inflammation.
Comparison of Velocity Vector Imaging Echocardiography With Magnetic Resonance Imaging in Mouse Models of Cardiomyopathy
Authors: Azam Salman , Desjardins Candida L. , Schluchter Mark , Liner Anna , Stelzer Julian E. , Yu Xin , Hoit Brian D.
Published: September 2012

Background—

Myocardial strain imaging using echocardiography can be a cost-effective method to quantify ventricular wall motion objectively, but few studies have compared strain measured with echocardiography against magnetic resonance imaging (MRI) in small animals.

Methods and Results—

We compared circumferential strain (CS) and radial strain (RS) measured with echocardiography (velocity vector imaging [VVI]) to displacement encoding with stimulated-echo MRI in 2 mouse models of cardiomyopathy. In 3-month-old mice with gene targeted deficiency of cardiac myosin-binding protein-C (cMyBP-C
−/−
, n=6) or muscle LIM protein (MLP
−/−
, n=6), and wild-type mice (n=8), myocardial strains were measured at 3 cross-sectional levels and averaged to obtain global strains. There was modest correlation between VVI and MRI measured strains, with global CS yielding stronger correlation compared with global RS (CS R
2
=0.4452 versus RS R
2
=0.2794, both
P
<0.05). Overall, strain measured by VVI was more variable than MRI (
P
<0.05) and the limits of agreement were slightly, but not significantly (
P
=0.14), closer for global CS than RS. Both VVI and MRI strain measurements showed significantly lower global CS strain in the knockout groups compared with the wild type. The VVI (but not MRI) CS strain measurements were different between the 2 knockout groups (−14.5±3.8% versus −6.6±4.0%, cMyBP-C
−/−
versus MLP
−/−
respectively,
P
<0.05).

Conclusions—

Measurements of left ventricular CS and RS are feasible in small animals using 2-dimensional echocardiography. VVI and MRI strain measurements correlated modestly and the agreement between the modalities tended to be greater for CS than RS. Although VVI and MRI strains were able to differentiate between wild-type and knockout mice, only global CS VVI differentiated between the 2 models of cardiomyopathy.
Monash Transient Ischemic Attack Triaging Treatment
Authors: Sanders Lauren M. , Srikanth Velandai K. , Jolley Damien J. , Sundararajan Vijaya , Psihogios Helen , Wong Kitty , Ramsay David , Phan Thanh G.
Published: September 2012

Background and Purpose—

Controversy surrounds the need for routine hospital admission for transient ischemic attack. The Monash Transient Ischemic Attack Triaging Treatment (M3T) model adopts rapid management in the emergency department followed by outpatient management prioritized by stroke mechanism. We compared safety and processes of care between M3T and the previous model of routine admission.

Methods—

Study cohorts consisted of patients managed with M3T (2004–2007) and the previous model (2003–2004). We determined 90-day stroke outcome using clinical and medical record review and data linkage to the population level state-wide hospital discharge morbidity database. We compared models of care using risk difference analysis, followed by logistic regression to adjust for previous indicators of risk. Secondary outcomes were proportions admitted, proportions undergoing carotid ultrasound, times to ultrasound and revascularization, and medication prescription.

Results—

In M3T (mean age, 64.7±14.7) 85/488 (17.4%) patients were admitted compared with 117/169 (62.9%) in the previous model (mean age, 72.5±13.9). With near-complete follow-up, 90-day stroke outcome was 1.50% (95% confidence interval, 0.73%–3.05%) in M3T and 4.67% (95% confidence interval, 2.28%–9.32%) in the previous model (
P
=0.03). Compared with the previous model, the adjusted odds ratio of stroke for M3T was 0.46 (95% confidence interval, 0.12–1.68;
P
=0.24). M3T was associated with greater proportions undergoing carotid ultrasound (
P
<0.001) and receiving antiplatelet therapy (
P
=0.005).

Conclusions—

The M3T system was associated with low 90-day stroke outcome in transient ischemic attack patients, providing proof of concept that these patients may be managed safely without routine hospital admission using a closely supervised protocol in the emergency department.
CT Interpretation in a Telestroke Network
Authors: Demaerschalk Bart M. , Bobrow Bentley J. , Raman Rema , Ernstrom Karin , Hoxworth Joseph M. , Patel Ameet C. , Kiernan Terri-Ellen J. , Aguilar Maria I. , Ingall Timothy J. , Dodick David W. , Meyer Brett C. ,   for the Stroke Team Remote Evaluation Using a Digital Observation Camera (STRokE DOC) in Arizona—The Initial Mayo Clinic Experience (AZ TIME) Investigators
Published: September 2012

Background and Purpose—

The American Stroke Association guidelines emphasized the need for further high-quality studies that assess agreement by radiologists and nonradiologists engaged in emergency telestroke assessments and decision-making. Therefore, the objective of this study was to determine the level of agreement of baseline brain CT scan interpretations of patients with acute stroke presenting to telestroke spoke hospitals between central reading committee neuroradiologists and each of 2 groups, spoke hospital radiologists and hub hospital vascular neurologists (telestrokologists).

Methods—

The Stroke Team Remote Evaluation Using a Digital Observation Camera Arizona trial was a prospective, urban single-hub, rural 2-spoke, randomized, blinded, controlled trial of a 2-way, site-independent, audiovisual telemedicine and teleradiology system designed for remote evaluation of adult patients with acute stroke versus telephone consultation to assess eligibility for treatment with intravenous thrombolysis. In the telemedicine arm, the subjects’ CT scans were interpreted by the hub telestrokologist and in the telephone arm by the spoke radiologist. All subjects’ CT scans were subsequently interpreted centrally, independently, and blindly by 2 hub neuroradiologists. The primary CT outcome was determination of a CT-based contraindication to thrombolytic treatment. Kappa statistics and exact agreement rates were used to analyze interobserver agreement.

Results—

Fifty-four subjects underwent random assignment. The overall agreement for the presence of radiological contraindications to thrombolysis was excellent (0.91) and did not differ substantially between the hub telestrokologist to neuroradiologist and spoke radiologist to neuroradiologist (0.92 and 0.89, respectively).

Conclusions—

In the context of a telestroke network designed to assess patients with acute stroke syndromes, agreement over the presence or absence of radiological contraindications to thrombolysis was excellent whether the comparisons were between a telestrokologist and neuroradiologist or between spoke radiologist and neuroradiologist.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00623350.
Learning about Climate Change: Finance Ministries in International Climate Change Politics
Authors: Skovgaard Jakob
Published: September 2012

In the course of the last four years, finance ministries have increasingly become involved in the international climate change negotiations. Their involvement has to a large degree been an outcome of the framing of climate change as a market failure. This framing calls for an active climate change policy and is at odds with the framing of climate change policy that was previously predominant in finance ministries: that it constitutes expenditure to be avoided. The persistence of both framings has led to clashes within and between finance ministries with respect to climate change. The article calls for further research focusing on the role of the two frames and of finance ministries as actors in climate change politics.