bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of choline kinase in human endothelial cells
Authors: Mori Noriko , Gadiya Mayur , Wildes Flonné , Krishnamachary Balaji , Glunde Kristine , Bhujwalla Zaver M.
Published: June 2013

High choline kinase‐α (Chk‐α) expression is frequently observed in cancer cells, making it a novel target for pharmacological and molecular inhibition. As inhibiting agents are delivered systemically, it is important to determine Chk‐α expression levels in endothelial cells that line both normal and tumor vasculature, and the effect of Chk‐α downregulation on these cells. Here, we characterized Chk‐α expression and the effect of its downregulation in human umbilical vein endothelial cells (HUVECs) relative to MDA‐MB‐231 human breast cancer cells. We used small interfering RNA (siRNA) to downregulate Chk‐α expression. Basal mRNA levels of Chk‐α were approximately three‐fold lower in HUVECs relative to MDA‐MB‐231 breast cancer cells. Consistent with the differences in Chk‐α protein levels, phosphocholine levels were approximately 10‐fold lower in HUVECs relative to MDA‐MB‐231 cells. Transient transfection with siRNA‐Chk resulted in comparable levels of mRNA and protein in MDA‐MB‐231 breast cancer cells and HUVECs. However, there was a significant reduction in proliferation in MDA‐MB‐231 cells, but not in HUVECs. No significant difference in CD31 immunostaining was observed in tumor sections obtained from mice injected with control luciferase‐short hairpin (sh)RNA or Chk‐shRNA lentivirus. These data suggest that systemically delivered agents that downregulate Chk‐α in tumors will not affect endothelial cell proliferation during delivery, and further support the development of Chk‐α downregulation as a cancer‐specific treatment. Copyright © 2013 John Wiley & Sons, Ltd.
Resonant inductive decoupling (RID) for transceiver arrays to compensate for both reactive and resistive components of the mutual impedance
Authors: Avdievich Nikolai I. , Pan Jullie W. , Hetherington Hoby P.
Published: June 2013

Transceiver surface coil arrays improve transmit performance (B1/√kW) and B1 homogeneity for head imaging up to 9.4 T. To further improve reception performance and parallel imaging, the number of array elements must be increased with a corresponding decrease in their size. With a large number of small interacting antennas, decoupling is one of the most challenging aspects in the design and construction of transceiver arrays. Previously described decoupling techniques using geometric overlap, inductive or capacitive decoupling have focused on the elimination of the reactance of the mutual impedance only, which can limit the obtainable decoupling to –10 dB as a result of residual mutual resistance. A novel resonant inductive decoupling (RID) method, which allows compensation for both reactive and resistive components of the mutual impedance between the adjacent surface coils, has been developed and verified experimentally. This method provides an easy way to adjust the decoupling remotely by changing the resonance frequency of the RID circuit through the adjustment of a variable capacitor. As an example, a single‐row (1 × 16) 7‐T transceiver head array of n = 16 small overlapped surface coils using RID decoupling between adjacent coils was built. In combination with overlapped coils, the RID technique achieved better than –24 dB of decoupling for all adjacent coils. Copyright © 2013 John Wiley & Sons, Ltd.
Characterization and anticorrosive properties of poly(2,3‐dimethylaniline)/nano‐Al2O3 composite synthesized by emulsion polymerization
Authors: Li Zhitao , Ma Li , Li Wanglin , Gan Mengyu , Qiu Wei , Yan Jun
Published: June 2013

Poly(2,3‐dimethylaniline)/nano‐Al2O3 composite (PAC) was synthesized by emulsion polymerization using dodecyl benzene sulfonic acid as emulsifier and dopant. The structure of PAC was characterized by Fourier fransformation infrared spectroscopy, UV–visible adsorption spectroscopy, and field emission scanning electron microscopy. The thermal stability was studied by thermogravimetric analysis, and the electrochemical performances were studied by cyclic voltammetry measurements. Epoxy coatings containing PAC and poly(2,3‐dimethylaniline) (P(2,3‐DMA)), respectively, were painted on steel, and accelerated immersion tests were performed to evaluate the anticorrosion property of the coatings in 3.5% NaCl solution. The results showed that the addition of PAC and P(2,3‐DMA) could improve the anticorrosion performance of epoxy coating significantly and the PAC coating had higher corrosion resistance than that of P(2,3‐DMA). Copyright © 2013 John Wiley & Sons, Ltd.
Combined noninvasive ventilation and mechanical in‐exsufflator in the treatment of pediatric acute neuromuscular respiratory failure
Authors: Chen Tai‐Heng , Hsu Jong‐Hau , Wu Jiunn‐Ren , Dai Zen‐Kong , Chen I‐Chen , Liang Wen‐Chen , Yang San‐Nan , Jong Yuh‐Jyh
Published: June 2013

Objectives

The present study aims to evaluate the efficacy and complications of combined noninvasive ventilation (NIV) and assisted coughing by mechanical in‐exsufflator (MIE) for acute respiratory failure (ARF) in children with neuromuscular disease (NMD).

Methods

A prospective study was conducted in the pediatric intensive care unit. Children with NMD and ARF treated by combined NIV and MIE were included. Treatment success was defined as freedom from tracheal intubation during the hospital stay. Physiologic indices including PaO2, PaCO2, pH, and PaO2/FiO2 were recorded before and 12, 24 hr after the use of NIV/MIE.

Results

Combined NIV/MIE was used in 15 NMD children (mean: 8.1 years, range: 3 months to 18 years) with 16 cases of ARF. There was no mortality in this cohort. Treatment success was achieved in 12 cases (75%), including six cases (38%) demanding “Do Not Intubate.” ARF was due to pneumonia, with a mean baseline PaCO2 of 73.2 ± 19.0 mmHg. In the success group, hypercarbia and acidosis improved after use of NIV/MIE for 24 hr (PaCO2: 71.7 ± 18.6 mmHg vs. 55.8 ± 11.6 mmHg, P < 0.01; pH: 7.29 ± 0.07 vs. 7.38 ± 0.05, P < 0.01). All patients tolerated NIV/MIE well despite transient skin pressure sores in five cases.

Conclusions

Combined NIV/MIE is a safe and effective approach to rapidly improve physiologic indices and decrease the need for intubation in NMD children with ARF. NIV/MIE provides a good alternative for those refusing intubation. Pediatr Pulmonol. 2014; 49:589–596. © 2013 Wiley Periodicals, Inc.
Diabetes requiring insulin – recent developments in management
Authors: Bennett Katie , Joseph Frank
Published: June 2013

Choice of insulin in the treatment of diabetes should be based on patient preference, lifestyle, blood glucose profile and risk of hypoglycaemia. Our Drug review focusses on key points and recent advances in the management of diabetes requiring insulin, followed by sources of further information and a review of the prescription data.
Medicines and prescribing support online from NICE
Authors: Chrisp Paul
Published: June 2013

In order to keep up to date prescribers need quick and easy access to the latest evidence‐based information. The MPC at NICE has been developing online medicines and prescribing information services to meet this need.
Using continuous data on tumour measurements to improve inference in phase II cancer studies
Authors: Wason James M.S. , Seaman Shaun R.
Published: June 2013

In phase II cancer trials, tumour response is either the primary or an important secondary endpoint. Tumour response is a binary composite endpoint determined, according to the Response Evaluation Criteria in Solid Tumors, by (1) whether the percentage change in tumour size is greater than a prescribed threshold and (2) (binary) criteria such as whether a patient develops new lesions. Further binary criteria, such as death or serious toxicity, may be added to these criteria. The probability of tumour response (i.e. ‘success’ on the composite endpoint) would usually be estimated simply as the proportion of successes among patients. This approach uses the tumour size variable only through a discretised form, namely whether or not it is above the threshold. In this article, we propose a method that also estimates the probability of success but that gains precision by using the information on the undiscretised (i.e. continuous) tumour size variable. This approach can also be used to increase the power to detect a difference between the probabilities of success under two different treatments in a comparative trial. We demonstrate these increases in precision and power using simulated data. We also apply the method to real data from a phase II cancer trial and show that it results in a considerably narrower confidence interval for the probability of tumour response. © 2013 The authors. Statistics in Medicine published by John Wiley & Sons, Ltd.
The Evolution of Robotic Bariatric Surgery
Authors: Wilson Erik B. , Sudan Ranjan
Published: June 2013

Introduction

The growth of bariatric surgery has resulted in varying types of procedures with increasing complexity. Robotic digital platforms are employed in bariatric surgery to address this increasing complexity in the high‐risk obese patient population with difficult anatomy.

Materials and Methods

This review explores the literature and examines the reported outcomes and complications in using robotics for bariatric surgery. Robotic approaches to adjustable gastric banding, sleeve gastrectomy, gastric bypass, and biliopancreatic diversion with duodenal switch are examined. Revisional cases, learning curves, and cost effectiveness are reviewed, with an eye toward the future of bariatric surgery as the use of robotics is adopted.

Conclusion

Digital platforms are showing great promise as enabling technology which advance bariatric outcomes. With increasingly complex bariatric cases being performed and revised, the insertion of digital information between the surgeon and the patient leads to better operations for the patient and the surgeon.
Worst Case and Probabilistic Analysis of the 2-Opt Algorithm for the TSP
Authors: Englert Matthias , Röglin Heiko , Vöcking Berthold
Published: June 2013

2-Opt is probably the most basic local search heuristic for the TSP. This heuristic achieves amazingly good results on “real world” Euclidean instances both with respect to running time and approximation ratio. There are numerous experimental studies on the performance of 2-Opt. However, the theoretical knowledge about this heuristic is still very limited. Not even its worst case running time on 2-dimensional Euclidean instances was known so far. We clarify this issue by presenting, for every$p\in\mathbb{N}$, a family ofLpinstances on which 2-Opt can take an exponential number of steps.

Previous probabilistic analyses were restricted to instances in whichnpoints are placed uniformly at random in the unit square [0,1]2, where it was shown that the expected number of steps is bounded by$\tilde{O}(n^{10})$for Euclidean instances. We consider a more advanced model of probabilistic instances in which the points can be placed independently according to general distributions on [0,1]d, for an arbitraryd≥2. In particular, we allow different distributions for different points. We study the expected number of local improvements in terms of the numbernof points and the maximal densityϕof the probability distributions. We show an upper bound on the expected length of any 2-Opt improvement path of$\tilde{O}(n^{4+1/3}\cdot\phi^{8/3})$. When starting with an initial tour computed by an insertion heuristic, the upper bound on the expected number of steps improves even to$\tilde{O}(n^{4+1/3-1/d}\cdot\phi^{8/3})$. If the distances are measured according to the Manhattan metric, then the expected number of steps is bounded by$\tilde{O}(n^{4-1/d}\cdot\phi)$. In addition, we prove an upper bound of$O(\sqrt[d]{\phi})$on the expected approximation factor with respect to allLpmetrics.

Let us remark that our probabilistic analysis covers as special cases the uniform input model withϕ=1 and a smoothed analysis with Gaussian perturbations of standard deviationσwithϕ∼1/σd.
In silico aided metabolic engineering of Klebsiella oxytoca and fermentation optimization for enhanced 2,3-butanediol production
Authors: Park Jong Myoung , Song Hyohak , Lee Hee Jong , Seung Doyoung
Published: June 2013

Klebsiella oxytoca naturally produces a large amount of 2,3-butanediol (2,3-BD), a promising bulk chemical with wide industrial applications, along with various byproducts. In this study, the in silico gene knockout simulation of K. oxytoca was carried out for 2,3-BD overproduction by inhibiting the formation of byproducts. The knockouts of ldhA and pflB genes were targeted with the criteria of maximization of 2,3-BD production and minimization of byproducts formation. The constructed K. oxytoca ΔldhA ΔpflB strain showed higher 2,3-BD yields and higher final concentrations than those obtained from the wild-type and ΔldhA strains. However, the simultaneous deletion of both genes caused about a 50 % reduction in 2,3-BD productivity compared with K. oxytoca ΔldhA strain. Based on previous studies and in silico investigation that the agitation speed during 2,3-BD fermentation strongly affected cell growth and 2,3-BD synthesis, the effect of agitation speed on 2,3-BD production was investigated from 150 to 450 rpm in 5-L bioreactors containing 3-L culture media. The highest 2,3-BD productivity (2.7 g/L/h) was obtained at 450 rpm in batch fermentation. Considering the inhibition of acetoin for 2,3-BD production, fed-batch fermentations were performed using K. oxytoca ΔldhA ΔpflB strain to enhance 2,3-BD production. Altering the agitation speed from 450 to 350 rpm at nearly 10 g/L of acetoin during the fed-batch fermentation allowed for the production of 113 g/L 2,3-BD, with a yield of 0.45 g/g, and for the production of 2.1 g/L/h of 2,3-BD.
THE PRICING OF MORTALITY-LINKED CONTINGENT CLAIMS: AN EQUILIBRIUM APPROACH
Authors: Tsai Jeffrey T. , Tzeng Larry Y.
Published: June 2013

This study introduces an equilibrium approach to price mortality-linked securities in a discrete time economy, assuming that the mortality rate has a transformed normal distribution. This pricing method complements current studies on the valuation of mortality-linked securities, which only have discrete trading opportunities and insufficient market trading data. Like the Wang transform, the valuation relationship is still risk-neutral (preference-free) and the mortality-linked security is priced as the expected value of its terminal payoff, discounted by the risk-free rate. This study provides an example of pricing the Swiss Re mortality bond issued in 2003 and obtains an approximated closed-form solution.
STATISTICAL INFERENCE FOR COPULAS IN HIGH DIMENSIONS: A SIMULATION STUDY
Authors: Embrechts Paul , Hofert Marius
Published: June 2013

Statistical inference for copulas has been addressed in various research papers. Due to the complicated theoretical results, studies have been carried out mainly in the bivariate case, be it properties of estimators or goodness-of-fit tests. However, from a practical point of view, higher dimensions are of interest. This work presents the results of large-scale simulation studies with particular focus on the question to what extent dimensionality influences point and interval estimators.
SOME DISTRIBUTIONAL PROPERTIES OF A CLASS OF COUNTING DISTRIBUTIONS WITH CLAIMS ANALYSIS APPLICATIONS
Authors: Willmot Gordon E. , Woo Jae-Kyung
Published: June 2013

We discuss a class of counting distributions motivated by a problem in discrete surplus analysis, and special cases of which have applications in stop-loss, discrete Tail value at risk (TVaR) and claim count modelling. Explicit formulas are developed, and the mixed Poisson case is considered in some detail. Simplifications occur for some underlying negative binomial and related models, where in some cases compound geometric distributions arise naturally. Applications to claim count and aggregate claims models are then given.
The Animal Kingdom
Authors: Cuvier Georges
Published: June 2013

Georges Cuvier (1769–1832), made a peer of France in 1819 in recognition of his work, was perhaps the most important European scientist of his day. His most famous work, Le Règne Animal, was published in French in 1817; Edward Griffith (1790–1858), a solicitor and amateur naturalist, embarked on in 1824, with a team of colleagues, an English version which resulted in this illustrated sixteen-volume edition with additional material, published between 1827 and 1835. Cuvier was the first biologist to compare the anatomy of fossil animals with living species, and he named the now familiar 'mastodon' and 'megatherium'. However, his studies convinced him that the evolutionary theories of Lamarck and St Hilaire were wrong, and his influence on the scientific world was such that the possibility of evolution was widely discounted by many scholars both before and after Darwin. Volume 2 is the second of four books on mammals.
Large-time evolution of statistical moments of wind–wave fields
Authors: Annenkov Sergei Y. , Shrira Victor I.
Published: June 2013

We study the long-term evolution of weakly nonlinear random gravity water wave fields developing with and without wind forcing. The focus of the work is on deriving, from first principles, the evolution of the departure of the field statistics from Gaussianity. Higher-order statistical moments of elevation (skewness and kurtosis) are used as a measure of this departure. Non-Gaussianity of a weakly nonlinear random wave field has two components. The first is due to nonlinear wave–wave interactions. We refer to this component as ‘dynamic’, since it is linked to wave field evolution. The other component is due to bound harmonics. It is non-zero for every wave field with finite amplitude, contributes both to skewness and kurtosis of gravity water waves and can be determined entirely from the instantaneous spectrum of surface elevation. The key result of the work, supported both by direct numerical simulation (DNS) and by the analysis of simulated and experimental (JONSWAP) spectra, is that in generic situations of a broadband random wave field the dynamic contribution to kurtosis is small in absolute value, and negligibly small compared with the bound harmonics component. Therefore, the latter dominates, and both skewness and kurtosis can be obtained directly from the instantaneous wave spectra. Thus, the departure of evolving wave fields from Gaussianity can be obtained from evolving wave spectra, complementing the capability of forecasting spectra and capitalizing on the existing methodology. We find that both skewness and kurtosis are significant for typical oceanic waves; the non-zero positive kurtosis implies a tangible increase of freak wave probability. For random wave fields generated by steady or slowly varying wind and for swell the derived large-time asymptotics of skewness and kurtosis predict power law decay of the moments. The exponents of these laws are determined by the degree of homogeneity of the interaction coefficients. For all self-similar regimes the kurtosis decays twice as fast as the skewness. These formulae complement the known large-time asymptotics for spectral evolution prescribed by the Hasselmann equation. The results are verified by the DNS of random wave fields based on the Zakharov equation. The predicted asymptotic behaviour is shown to be very robust: it holds both for steady and gusty winds.
Bifurcation in a thin liquid film flowing over a locally heated surface
Authors: Katkar Harshwardhan H. , Davis Jeffrey M.
Published: June 2013

We investigate the nonlinear dynamics of a two-dimensional film flowing down a finite heater, for a non-volatile and a volatile liquid. An oscillatory instability is predicted beyond a critical value of the Marangoni number using linear stability theory. Continuation along the Marangoni number using a nonlinear evolution equation is employed to trace the bifurcation diagram associated with the oscillatory instability. Hysteresis, a characteristic attribute of a subcritical Hopf bifurcation, is observed in a critical parametric region. The bifurcation is universally observed for both a non-volatile film and a volatile film.
New exact relations for easy recovery of steady wave profiles from bottom pressure measurements
Authors: Clamond Didier
Published: June 2013

This paper is about the determination of a free surface wave profile from a given pressure distribution at the bottom. For a two-dimensional irrotational steady surface water wave propagating over a flat horizontal bed, this problem is solved analytically in an implicit form. Explicit solutions can be easily obtained numerically via fixed point iterations, whose convergence is outlined mathematically and numerically. This new surface reconstruction procedure does not involve the resolution of a differential or an integral equation, i.e. the surface is given by algebraic local relations. Thus, this formulation permits the free surface recovery in a simpler and more efficient way than previous methods.
Supplementation of diets with bovine colostrum influences immune function in dogs
Authors: Satyaraj Ebenezer , Reynolds Arleigh , Pelker Robyn , Labuda Jeff , Zhang Peifang , Sun Peichuan
Published: June 2013

While the need for colostrum in neonates is well established, the systemic effect of feeding bovine colostrum (BC) to adult humans is gaining increasing attention. However, no systematic studies evaluating the immunomodulatory effect of BC in dogs have been reported. The aim of the present study was to evaluate the immunomodulatory effect of dietary supplementation of BC in dogs. The study was conducted in two phases: pre-test (8 weeks) and test (40 weeks), with twenty-four dogs (mean age 2·5 years) randomised into two groups. In the ‘pre-test’ phase, both groups were fed a nutritionally complete diet. At the end of the ‘pre-test’ phase, all dogs received a canine distemper virus (CDV) vaccine, and dogs in the ‘test group’ were switched to a diet supplemented with 0·1 % spray-dried BC. Response to the CDV vaccine was evaluated by measuring vaccine-specific plasma IgG levels. Gut-associated lymphoid tissue response was assessed by measuring faecal IgA levels. Gut microbiota were evaluated by the temporal temperature gel electrophoresis methodology. Dogs fed the BC-supplemented diet demonstrated a significantly higher vaccine response and higher levels of faecal IgA when compared with the control group. Supplementing diets with BC also resulted in significantly increased gut microbiota diversity and stability in the test group. In conclusion, diets supplemented with BC significantly influence immune response in dogs.
Effects of nitric oxide synthase inhibition on glutamine action in a bacterial translocation model
Authors: Santos Rosana G. C. , Quirino Iara E. P. , Viana Mirelle L. , Generoso Simone V. , Nicoli Jacques R. , Martins Flaviano S. , Nogueira-Machado José A. , Arantes Rosa M. E. , Correia Maria I. T. D. , Cardoso Valbert N.
Published: June 2013

Glutamine may be a precursor for NO synthesis, which may play a crucial role in bacterial translocation (BT). The goal of the present study was to investigate the potential effects of glutamine on BT and the immunological response in an experimental model of NO synthase inhibition by NG-nitro-L-arginine methyl ester (l-NAME). Mice were randomly assigned to four groups: sham; intestinal obstruction (IO); IO+500 mg/kg per d glutamine (GLN); IO+GLN plus 10 mg/kg per d l-NAME (GLN/LN). The groups were pretreated for 7 d. BT was induced by ileal ligation and was assessed 18 h later by measuring the radioactivity of 99mTc-Escherichiacoli in the blood and organs. Mucosal damage was determined using a histological analysis. Intestinal permeability (IP) was assessed by measuring the levels of 99mTc-diethylenetriaminepentaacetic acid in the blood at 4, 8 and 18 h after surgery. IgA and cytokine concentrations were determined by ELISA in the intestinal fluid and plasma, respectively. BT was increased in the GLN/LN and IO groups than in the GLN and sham groups. IP and intestinal mucosa structure of the sham, GLN and GLN/LN groups were similar. The GLN group had the highest levels of interferon-γ, while IL-10 and secretory IgA levels were higher than those of the IO group but similar to those of the GLN/LN group. The present results suggest that effects of the glutamine pathway on BT were mediated by NO. The latter also interferes with the pro-inflammatory systemic immunological response. On the other hand, IP integrity preserved by the use of glutamine is independent of NO.
Understanding Currency Policy and Central Banking in China
Authors: Chin Gregory T.
Published: June 2013

China's trade and financial surpluses, exchange rate, and currency reserves make headlines, daily, around the world. As such, it is more imperative than ever to understand the inner workings of currency policy in China. Yet the exercise of power and decision making in these areas has received surprisingly little attention in Chinese politics, political economy, and, arguably, economics.
Observation of repetitive bursts in emission of fast ions and neutrons in sub-nanosecond laser-solid experiments
Authors: Krása J. , Klír D. , Velyhan A. , Margarone D. , Krouský E. , Jungwirth K. , Skála J. , Pfeifer M. , Kravárik J. , Kubeš P. , Řezáč K. , Ullschmied J.
Published: June 2013

A massive deuterated polyethylene target was exposed to laser intensities of about 3 × 1016 W/cm2 employing the 3-TW Prague Asterix Laser System (PALS). We achieved a yield of 2 × 108 neutrons per laser shot. Average time-of-flight signals of scintillation detectors operated in current mode reveal broad energy spectra of fusion neutrons with dominating energy of about 2.45 MeV. The energy dependence of the neutron yield shows a consistency in results of nanosecond, picosecond and sub-picosecond experiments. Here we also show that ions emitted in the backward direction from the front target surface have a multi-peak energy spectrum, which is caused by burst emission mechanisms.
FREEDOM AS A POLITICAL IDEAL
Authors: Wall Steven
Published: June 2013

I shall assume that a well-ordered state is one that promotes the
freedom of its subjects. My question is what is the kind of freedom that
the state ought to promote? This question is different from the question
of what freedom is. It might be thought, for example, that freedom
consists in the autonomous pursuit of valuable goals and projects, but
that the state cannot directly promote this freedom. On this view, the
state would not be able to make its citizens free. However, it might be
able to do things that make it easier or more likely for them to be free.
The freedom that the state promotes might be merely an aspect of or a
condition for the freedom that really matters.
Monitoring, firms’ compliance and imposition of fines: evidence from the Federal Industrial Inspection Program in Mexico City
Authors: Escobar Ninel , Chávez Carlos
Published: June 2013

We analyze the performance of the Federal Industrial Inspection Program operated by the Federal Attorney for Environmental Protection (PROFEPA) in Mexico City. We seek to answer three questions: What drives the inspections? What determines non-compliance? And what drives imposition of fines? We use firm-level data that identify certain characteristics of the firms, PROFEPA's inspections, compliance results and fines for all air polluting firms under the Program during the period January 2000–October 2008. We obtain three main results. First, PROFEPA's inspections have focused on larger firms devoted to industrial activities located in poor and dense municipalities. Second, past inspections were significant and have a high marginal effect on compliance. Third, the severity of the infraction was not relevant to the decision to impose a fine but rather to its amount.
Life insurance underwriting in the United States – yesterday, today and tomorrow
Authors: Klein Allen M.
Published: June 2013

Underwriting in the United States (US) life insurance marketplace has evolved tremendously over the last several decades. This paper will take a brief look at that history, from the older underwriting techniques still in use today to the introduction of smoker/nonsmoker distinctions in about 1980 to the evolution of preferred underwriting in the late 1980s, and finally to a movement toward simplified issue underwriting and a new approach to older age underwriting today.
Is there a place in the UK Defined Contribution pensions market for a guaranteed savings product?
Authors: Eason S. , Barker P. , Foroughi G. , Harsant J. , Hunter D. , Jarvis S. , Jones G. , Knava V. , Murphy P. , Murray K. , Muthulingam J. , Odozi N. , Page T. , Washoma K. , Webb A.
Published: June 2013

The UK has seen a significant transition from Defined Benefit (“DB”) to Defined Contribution (“DC”) for occupational pension saving. The planned automatic enrolment program starting in 2012 is expected to increase the use of DC. The main features of DC are that investment risk falls onto the individual during the pre-retirement phase and that there are no guarantees as to investment returns or the level of pension. In July 2012, Steve Webb, the Pensions Minister, challenged industry to think hard about meeting the need for more certainty about pension savings in DC plans and to consider providing an affordable ‘Money Safe’ guarantee where the member would get back at least the nominal value of their contributions (individual, employer and tax relief). This paper explores whether this is viable for the mass market.
ON THE EVOLUTIONARY STABILITY OF RATIONAL EXPECTATIONS
Authors: Parke William R. , Waters George A.
Published: June 2013

Evolutionary game theory provides a fresh perspective on the prospect that agents with heterogeneous expectations might eventually come to agree on a single expectation corresponding to the efficient markets hypothesis. We establish conditions under which agreement on a unique forecast is stable, but also show that persistent heterogeneous expectations can arise if those conditions do not hold. The critical element is the degree of curvature in the payoff weighting functions agents use to value forecasting performance. We illustrate our results in the context of an asset pricing model where a martingale solution competes with the fundamental solution for agents' attention.
Texture Indicators for Segmentation of Polyomavirus Particles in Transmission Electron Microscopy Images
Authors: Proença Maria C. , Nunes José F.M. , de Matos António P.A.
Published: June 2013

A fully automatic approach to locate polyomavirus particles in transmission electron microscopy images is presented that can localize intact particles, many damaged capsids, and an acceptable percentage of superposed ones. Performance of the approach is quantified in 25 electron micrographs containing nearly 390 particles and compared with the interpretation of the micrographs by two independent electron microscopy experts. All parameterization is based on the particle expected dimensions. This approach uses indicators calculated from the local co-occurrence matrix of gray levels to assess the textured pattern typical of polyomavirus and prune the initial set of candidates. In more complicated backgrounds, about 2–10% of the elements survive. A restricted set of the accepted points is used to evaluate the typical average and variance and to reduce the set of survivors accordingly. These intermediate points are evaluated using (i) a statistical index concerning the radiometric distribution of a circular neighborhood around the centroid of each candidate and (ii) a structural index resuming the expected morphological characteristics of eight radial intensity profiles encompassing the area of the possible particle. This hierarchical approach attains 90% efficiency in the detection of entire virus particles, tolerating a certain lack of differentiation in the borders and a certain amount of shape alterations.
Understanding the needs of family caregivers of older adults dying with dementia
Authors: Thompson Genevieve N. , Roger Kerstin
Published: June 2013

Objectives:

A challenge in understanding the needs of dementia family caregivers (DFC) within the purview of dementia as a terminal illness rests on the fact that literature in this area is dispersed across disciplines and not specifically grounded within the realm of palliative care. The objective of this paper is to describe the domains of DFC needs and their impact on the delivery of palliative care services.

Methods:

A literature search pertaining to dementia family caregivers and palliative/end-of-life care was conducted using the databases Medline, CINHAL, Ageline, PsychInfo, and Scopus for articles published in the English language between 1997 and 2011.

Results:

Supporting family caregivers of individuals with dementia throughout the disease trajectory requires consideration of caregivers : (1) physical, emotional, and psychological needs; (2) information and decisional support needs; and (3) instrumental support needs. The unique nature and prolonged duration of these needs directly influences the palliative care services and supports required by these family caregivers.

Significance of results:

Understanding the scope of DFC needs help further our understanding of how these needs may impact the delivery of palliative care services, and assists in developing a model of care for those dying from dementia and for their family caregivers.
Graphical design method for unequal power dividers based on phase-balanced SIW tee-junctions
Authors: Contreras Soraya , Peden Alain
Published: June 2013

This paper presents a detailed procedure to design substrate integrated waveguide (SIW) Tee-junctions with wide-range split-power ratio (from 1:1 to 1:8) and phase-balanced outputs. A set of curves was generated using an electromagnetic (EM) simulator to graphically determine the required parameters for the desired junction. Since such curves are provided, no further electromagnetic simulation is required when applying the proposed method. Input return loss at central frequency is guaranteed to be better than 18 dB. If an optimization procedure is required, the parameters obtained from this methodology may be used as initial values for such a process. Moreover, design rules are given for implementing 1 → 2Nunequal power dividers with phase-balanced outputs. To demonstrate the accuracy of the proposed graphical method, three implementation examples are provided: two Tee-junctions and a 1 → 4 power divider.
Physiotherapeuten in Deutschland
Authors: Scherer Carolin , Steinmann Natascha , Roes Martina
Published: June 2013

„Direct Access“ – die eigenständige und selbstständige Behandlung von Patienten durch Physiotherapeuten ohne vorherige Ausstellung ärztlicher Verordnungen – findet in Deutschland wenig Anklang. Gründe hierfür sind u. a. veraltete Berufsgesetze und einer immer größer werdenden Diskrepanz zwischen Ausbildung und Realität.
Was bietet die Pflegedidaktik?
Authors: Dütthorn Nadin , Walter Anja , Arens Frank
Published: June 2013

Die Mitglieder der Sektion Bildung der Deutschen Gesellschaft für Pflegewissenschaft analysierten den aktuellen Stand der Pflegedidaktik als Disziplin. Aus dieser Arbeit ist ein pflegedidaktisches Analyseinstrument zur inhaltlichen Auseinandersetzung mit Ergebnissen der Pflegedidaktik entstanden, welches in diesem Beitrag vorgestellt wird.
Eine Zeit der Veränderung: Der Berufseinstieg in der Gesundheits- und Krankenpflege
Authors: Sorber Michaela
Published: June 2013

Der Berufseinstieg ist ein markanter Abschnitt in der Erwerbsbiographie Pflegender, welcher von einem intensiven Erleben geprägt ist. In dieser sensiblen Zeit werden für die weitere berufliche Tätigkeit die Weichen gestellt, gerade in Hinsicht auf die Fähigkeit zur Verantwortungsübernahme und der Herausbildung eines beruflichen Selbstkonzeptes, wie Tewes (2002) bereits argumentiert hat.
Integrative genomics of gene and metabolic regulation by estrogen receptors α and β, and their coregulators
Authors: Madak‐Erdogan Zeynep , Charn Tze‐Howe , Jiang Yan , Liu Edison T , Katzenellenbogen John A , Katzenellenbogen Benita S
Published: June 2013

The closely related transcription factors (TFs), estrogen receptors ERα and ERβ, regulate divergent gene expression programs and proliferative outcomes in breast cancer. Utilizing breast cancer cells with ERα, ERβ, or both receptors as a model system to define the basis for differing response specification by related TFs, we show that these TFs and their key coregulators, SRC3 and RIP140, generate overlapping as well as unique chromatin‐binding and transcription‐regulating modules. Cistrome and transcriptome analyses and the use of clustering algorithms delineated 11 clusters representing different chromatin‐bound receptor and coregulator assemblies that could be functionally associated through enrichment analysis with distinct patterns of gene regulation and preferential coregulator usage, RIP140 with ERβ and SRC3 with ERα. The receptors modified each other's transcriptional effect, and ERβ countered the proliferative drive of ERα through several novel mechanisms associated with specific binding‐site clusters. Our findings delineate distinct TF‐coregulator assemblies that function as control nodes, specifying precise patterns of gene regulation, proliferation, and metabolism, as exemplified by two of the most important nuclear hormone receptors in human breast cancer.
BDNF–TrkB signaling in striatopallidal neurons controls inhibition of locomotor behavior
Authors: Besusso Dario , Geibel Mirjam , Kramer Dana , Schneider Tomasz , Pendolino Valentina , Picconi Barbara , Calabresi Paolo , Bannerman David M. , Minichiello Liliana
Published: June 2013

The physiology of brain-derived neurotrophic factor signaling in enkephalinergic striatopallidal neurons is poorly understood. Changes in cortical Bdnf expression levels, and/or impairment in brain-derived neurotrophic factor anterograde transport induced by mutant huntingtin (mHdh) are believed to cause striatopallidal neuron vulnerability in early-stage Huntington’s disease. Although several studies have confirmed a link between altered cortical brain-derived neurotrophic factor signaling and striatal vulnerability, it is not known whether the effects are mediated via the brain-derived neurotrophic factor receptor TrkB, and whether they are direct or indirect. Using a novel genetic mouse model, here, we show that selective removal of brain-derived neurotrophic factor–TrkB signaling from enkephalinergic striatal targets unexpectedly leads to spontaneous and drug-induced hyperlocomotion. This is associated with dopamine D2 receptor-dependent increased striatal protein kinase C and MAP kinase activation, resulting in altered intrinsic activation of striatal enkephalinergic neurons. Therefore, brain-derived neurotrophic factor/TrkB signaling in striatopallidal neurons controls inhibition of locomotor behavior by modulating neuronal activity in response to excitatory input through the protein kinase C/MAP kinase pathway.
Introduction: Biomarkers in Translational and Personalized Medicine
Authors: Kumar Chanchal , van Gool Alain J.
Published: June 2013

Biomarkers have become a buzzword in the biomedical field and are expected to enable much innovation in the years to come. Their predominant promise resides in two application areas: translational medicine and personalized medicine, whose activities are strongly aimed to improve the management of disease. However, to many the ultimate potential of biomarkers is to change disease management (reactive mode) into health management (preventive mode), in other words keeping healthy people healthy rather than curing diseased patients. Key drivers for such change are molecular biomarkers that allow earlier and more sensitive detection of onset of disease, better molecular classification of disease, improved personalized treatment, and improved monitoring of treatment effects. Many lessons can be learned from pharmaceutical industry where for considerable time biomarkers have been key drivers in drug development projects. This experience in biomarker discovery, validation, development and implementation can potentially be applied to other areas of human medicine including nutriceuticals. We here review the role of biomarkers in pharmaceutical drug development, focussing on translational and personalized medicine, and discuss trends, challenges and opportunities in this field.
Discovery and Validation Case Studies, Recommendations: Bottlenecks in Biomarker Discovery and Validation by Using Proteomic Technologies
Authors: Pavlou Maria P. , Blasutig Ivan M. , Diamandis Eleftherios P.
Published: June 2013

Discovery and validation of disease biomarkers is a long and arduous procedure that requires the collaboration of major stakeholders (academia, industry and government) and is accompanied with a high risk of failure. The challenges faced during protein‐biomarker development are multidimensional and present at every phase. Researchers need to be aware of the potential limitations in order to plan an efficient study that produces results that can be critically interpreted. The present chapter provides an insight into the barriers that a potential biomarker must overcome to move from the bench towards the clinic.
TLR‐7 Agonists for the Treatment of Viral Hepatitis
Authors: Halcomb Randall L.
Published: June 2013

This chapter summarizes selected small‐molecule Toll‐like receptor 7 (TLR‐7) agonists that have been developed for viral hepatitis infections. An introduction to the rationale for TLR‐7 as a target for HCV and HBV is presented. The initial discovery of interferon inducers that were later found to be TLR‐7 agonists, and how they led to the initiation of drug discovery programs, are also described. The primary focus is a summary of the characteristics and structure–activity relationships in each of the major classes of agonists that have advanced into development and also findings in clinical trials for hepatitis C infection where available. Finally, an outlook for this class of compounds for the treatment of hepatitis B and C is presented.
Classical Linear Regression by the Least Squares Method
Authors: Manuel Andrade‐Garda José , Carlosena‐Zubieta Alatzne , María Soto‐Ferreiro Rosa , Teran‐Baamonde Javier , Thompson Michael
Published: June 2013

The objective of this chapter is to present some fundamental issues that every atomic spectrometry practitioner should keep in mind when developing a calibration. However familiar this may sound it is definitely a critical step, as important as the development of proper experimental measurement conditions.

The fundamentals of the least squares fit are presented and discussed, with special emphasis on the practical limitations we currently experience in laboratories. Many discussions will be devoted to validation of the model and to clarification of some misconceptions that appear sometimes in the literature. The widely applied standard additions method is reviewed and discussed to show that extrapolation is a risky practice that can be avoided very easily.

Polynomials of order two (quadratic) provide the analyst with a readily available means of matching points from a curved calibration to a function suitable for interpolation. However, extra caution is necessary to avoid lack of fit, and even small extrapolations beyond the calibrated range are unwise.

Finally, two appendixes are included to discuss in some detail the correct use of the Mandel’s test for linearity and how to compare two regression lines (typically, the aqueous calibration fit and the standard additions one).
A general anaesthetic propofol inhibits aquaporin-4 in the presence of Zn2+
Authors: Kato Jungo , Hayashi Mariko Kato , Aizu Shinnosuke , Yukutake Yoshinori , Takeda Junzo , Yasui Masato
Published: June 2013

AQP4 (aquaporin-4), a water channel protein that is predominantly expressed in astrocyte end-feet, plays an important role in the brain oedema formation, and is thereby considered to be a potential therapeutic target. Using a stopped-flow analysis, we showed that propofol (2,6-diisopropylphenol), a general anaesthetic drug, profoundly inhibited the osmotic water permeability of AQP4 proteoliposomes in the presence of Zn2+. This propofol inhibition was not observed in AQP1, suggesting the specificity for AQP4. In addition, the inhibitory effects of propofol could be reversed by the removal of Zn2+. Other lipid membrane fluidizers also similarly inhibited AQP4, suggesting that the modulation of protein–lipid interactions plays an essential role in the propofol-induced inhibition of AQP4. Accordingly, we used Blue native PAGE and showed that the profound inhibition caused by propofol in the presence of Zn2+ is coupled with the reversible clustering of AQP4 tetramers. Site-directed mutagenesis identified that Cys253, located at the membrane interface connecting to the C-terminal tail, is responsible for Zn2+-mediated propofol inhibition. Overall, we discovered that propofol specifically and reversibly inhibits AQP4 through the interaction between Zn2+ and Cys253. The findings provide new insight into the functional regulation of AQP4 and may facilitate the identification of novel AQP4-specific inhibitors.
Diacylglycerol kinase θ couples farnesoid X receptor-dependent bile acid signalling to Akt activation and glucose homoeostasis in hepatocytes
Authors: Cai Kai , Sewer Marion B.
Published: June 2013

DGKs (diacylglycerol kinases) catalyse the conversion of diacylglycerol into PA (phosphatidic acid), a positive modulator of mTOR (mammalian target of rapamycin). We have found that chenodeoxycholic acid and the synthetic FXR (farnesoid X receptor) ligand GW4064 induce the mRNA and protein expression of DGKθ in the HepG2 cell line and in primary human hepatocytes. Reporter gene studies using 1.5 kB of the DGKθ promoter fused to the luciferase gene revealed that bile acids increase DGKθ transcriptional activity. Mutation of putative FXR-binding sites attenuated the ability of GW4046 to increase DGKθ luciferase activity. Consistent with this finding, ChIP (chromatin immunoprecipitation) assays demonstrated that bile acid signalling increased the recruitment of FXR to the DGKθ promoter. Furthermore, GW4064 evoked a time-dependent increase in the cellular concentration of PA. We also found that GW4064 and PA promote the phosphorylation of mTOR, Akt and FoxO1 (forkhead box O1), and that silencing DGKθ expression significantly abrogated the ability of GW4046 to promote the phosphorylation of these PA-regulated targets. DGKθ was also required for bile-acid-dependent decreased glucose production. Taken together, our results establish DGKθ as a key mediator of bile-acid-stimulated modulation of mTORC2 (mTOR complex 2), the Akt pathway and glucose homoeostasis.
Coordinated target assignment via a finite‐time gain measurement approach
Authors: He Fenghua , Ji Denggao , Yao Yu , Zhang Peng , Chen Weishan
Published: June 2013

In this study, the authors consider a coordinated target assignment problem where a group of unmanned flight vehicles cooperate with each other to combat with a set of target vehicles which may perform various manoeuvres. Each flight vehicle is expected to be optimally assigned to a manoeuvring target vehicle such that the maximal possibility of successful interception can be guaranteed. Considering the course of the engagement, the target assignment should be achieved in terms of the performance over a limited time interval. The authors establish a linear time‐varying system in a finite‐time horizon to study the target assignment problem. A cost function is proposed based on the finite‐time generalised H2 gain measurement and the finite‐time final value performance measurement which can be viewed as the metric of the maximal required acceleration and the zero miss distance. For computation, the properties and performance criterion of the finite‐time generalised H2 gain are proved. The computation of the finite‐time final value performance measurement is also treated. The targets are assigned by minimising the value of the overall assignment evaluation function. Finally, the authors give some simulation results to illustrate the effectiveness of the proposed target assignment method.