bluuebunny/crossref_metadata_2025 huggingface dataset:
Why does ‘good ecological status’ matter?
Authors: Everard Mark
Published: June 2011

Achievement of ‘good ecological status’ under the EU Water Framework Directive (WFD), and various ‘environmental outcomes’ under other legislation and strategies, are accepted as important by environmental interests. However, support from the wider public may be largely altruistic. ‘Ecosystem services’ can better relate ecosystem health to societal benefits, helping communicate the advantages of achieving good status and securing support for environmental priorities. A series of ecosystem services case studies provides lessons about promoting public understanding of the benefits of achieving environmental targets. Framing desired WFD goals in terms of ecosystem service outcomes can optimise societal benefits proved by ‘programmes of measures’ and avert unintended consequences, compared with traditional, discipline‐specific management approaches. It can also highlight potential contributions from ecosystem‐based technologies to achieving multiple benefits across ecosystem service categories. ‘Siloed’ institutions and budgets are likely to perpetuate fragmented approaches unless explicit measures are taken to achieve more systemic outcomes.
Diversity of neuropsin (KLK8)‐dependent synaptic associativity in the hippocampal pyramidal neuron
Authors: Ishikawa Yasuyuki , Tamura Hideki , Shiosaka Sadao
Published: June 2011

Non‐technical summary  Activity‐dependent synaptic plasticity is widely accepted to provide a cellular basis for learning and memory. Synaptic associativity could be involved in activity‐dependent synaptic plasticity, because it distinguishes between local mechanisms of synaptic tags and cell‐wide mechanisms that are responsible for the synthesis of plasticity‐related proteins. We report that a plasticity‐related serine protease, neuropsin, is involved in the tag‐setting process during long‐term potentiation (LTP) at basal and apical dendritic inputs. Neuropsin is involved in synaptic associativity during LTP at apical dendritic inputs via integrin β1 and CaMKII signalling. Thus, neuropsin is a candidate molecule for LTP‐specific tag‐setting and could regulate the transformation of early to late LTP during synaptic associativity. These findings may provide the understanding of the regulation of synaptic associativity as complex information‐processing systems.
Maternal dexamethasone and EEG hyperactivity in preterm fetal sheep
Authors: Davidson Joanne O. , Quaedackers Josine S. L. T. , George Sherly A. , Gunn Alistair Jan , Bennet Laura
Published: June 2011

Non‐technical summary Long‐acting glucocorticoids such as dexamethasone are commonly given to women at risk of preterm labour. While they significantly improve survival of the prematurely born infant, their effects on preterm brain activity is surprisingly unclear. We found that, in sheep, a conventional clinical course of maternal dexamethasone treatment was associated with dramatic, evolving low‐frequency hyperactivity of the fetal EEG. This activity reflected a striking shift to less‐frequent but higher amplitude EEG waveforms, and unexpectedly, EEG waveforms whose duration and pattern were highly consistent with seizure activity. After resolution of hyperactivity, the EEG showed changes consistent with maturation of sleep architecture, and reassuringly there was no histological evidence of brain injury 5 days after first exposure. The long‐term implications are uncertain, but these effects may contribute to improved neonatal outcomes.
Synthesis of Double Wall Carbon Nanotubes Using Sulfur as Catalyst
Authors: Al-Hartomy O. A. , SHAH M. A.
Published: June 2011

The requirements of simple and reliable protocols for the synthesis of nanostructures with controlled morphology continue to be a major challenge in nanoscale. We demonstrate a novel and simplified synthesis technique for double wall carbon nanotubes using flotation chemical vapour deposition by adding a small amount of sulfur into the catalyst. Double wall nanotubes (DWNTs) provide ideal geometries for numerous fundamental structural, electronic, thermal, and vibrational studies. The diameter distribution of DWNTs is 25 ± 10 nm except one which is ∼148.6 nm.
Characteristics of Turbulent Three-Dimensional Offset Jets
Authors: Agelin-Chaab M. , Tachie M. F.
Published: June 2011

Three-dimensional turbulent offset jets were investigated using a particle image velocimetry technique. Three jet exit Reynolds numbers, Rej = 5000, 10,000, and 20,000, and four offset heights, h/d = 0.5, 1.0, 2.0, and 4.0, were studied. The mean flow and turbulence statistics were studied over larger downstream distances than in previous studies. The decay and spread rates were found to be nearly independent of Reynolds number and offset height at certain exit diameters (x = 73d) downstream and h/d ≤ 2. The decay rates of 1.18 ± 0.03 and spread rates of 0.055 ± 0.001 and 0.250 ± 0.005 in the wall-normal and lateral directions were obtained, respectively. The reattachment lengths are also independent of Rej but increase with offset height. The locations of the maximum mean velocities increased linearly with streamwise distance in the self-similar region. It was observed that profiles of the mean velocities, turbulence intensities, and Reynolds shears stresses are nearly independent of Rej and h/d far downstream. The triple products in the symmetry plane indicated turbulence transport from the outer region of the jet towards the wall region.
TWIK-1 Two-Pore Domain Potassium Channels Change Ion Selectivity and Conduct Inward Leak Sodium Currents in Hypokalemia
Authors: Ma Liqun , Zhang Xuexin , Chen Haijun
Published: June 2011

Very low extracellular K
+
concentrations, which can trigger cardiac arrhythmias, cause TWIK-1 potassium channels to become permeable to Na
+
.
Sitamaquine Overcomes ABC-Mediated Resistance to Miltefosine and Antimony inLeishmania
Authors: Pérez-Victoria José M. , Bavchvarov Boris I. , Torrecillas Iván R. , Martínez-García Marta , López-Martín Carmen , Campillo Mercedes , Castanys Santiago , Gamarro Francisco
Published: June 2011

Although oral miltefosine represented an important therapeutic advance in the treatment of leishmaniasis, the appearance of resistance remains a serious threat. LMDR1/LABCB4, a P-glycoprotein-like transporter included in theLeishmaniaABC (ATP-binding cassette) family, was the first molecule shown to be involved in experimental miltefosine resistance. LMDR1 pumps drugs out of the parasite, thereby decreasing their intracellular accumulation. Sitamaquine, another promising oral drug for leishmaniasis, is currently in phase 2b clinical trials. The physicochemical features of this drug suggested to us that it could be considered for use as an LMDR1 inhibitor. Indeed, we report herein that nonleishmanicidal concentrations of sitamaquine reverse miltefosine resistance in a multidrug resistanceLeishmania tropicaline that overexpresses LMDR1. This reversal effect is due to modulation of the LMDR1-mediated efflux of miltefosine. In addition, sitamaquine is not a substrate of LMDR1, as this transporter does not affect sitamaquine accumulation or sensitivity in the parasite. Likewise, we show that ketoconazole, another oral leishmanicidal drug known to interact with ABC transporters, is also able to reverse LMDR1-mediated miltefosine resistance, although with a lower efficiency than sitamaquine. Molecular docking on a three-dimensional homology model of LMDR1 showed different preferential binding sites for each substrate-inhibitor pair, thus explaining this different behavior. Finally, we show that sitamaquine is also able to modulate the antimony resistance mediated by MRPA/LABCC3, another ABC transporter involved in experimental and clinical antimony resistance in this parasite. Taken together, these data suggest that the combination of sitamaquine with miltefosine or antimony could avoid the appearance of resistance mediated by these membrane transporters inLeishmania.
Susceptibility of Vertilmicin to Modifications by Three Types of Recombinant Aminoglycoside-Modifying Enzymes
Authors: Yuan Min , Han Hui , Li Cong-Ran , Yang Xin-Yi , Li Guo-Qing , Cen Shan , Kang Xi-Xiong , Si Shu-Yi , Jiang Jian-Dong , You Xue-Fu
Published: June 2011

The susceptibilities of vertilmicin and seven reference aminoglycosides to modifications by six recombinant aminoglycoside-modifying enzymes, AAC(6′)-Ie, APH(2′′)-Ia, AAC(6′)-Ie-APH(2′′)-Ia, ANT(2′′)-Ia, AAC(6′)-Ib, and AAC(6′)-Ib-cr, were studied by coupled spectrophotometric assays in microtiter plates. In comparison to other aminoglycosides, the susceptibility of vertilmicin was 45.8- to 250.0-fold lower for AAC(6′)-Ie acetylation, 39.2- to 116.7-fold lower for AAC(6′)-Ie-APH(2′′)-Ia acetylation, and 1.8- to 7.5-fold lower for ANT(2′′)-Ia adenylation (except that shown by amikacin) while relatively comparable for AAC(6′)-Ib acetylation, AAC(6′)-Ib-cr acetylation, APH(2′′)-Ia phosphorylation, and AAC(6′)-Ie-APH(2′′)-Ia phosphorylation.
Is ischaemia-modified albumin a test for venous thromboembolism?
Authors: Hogg Kerstin , Hinchliffe Edward , Halsam Shonagh , Valkov Alex , Lecky Fiona
Published: June 2011

Objective

Patients with symptoms of deep vein thrombosis (DVT) and pulmonary embolism (PE) commonly present to the emergency department (ED). The aim of this study was to assess the role of ischaemia-modified albumin (IMA) testing in the diagnosis of venous thromboembolism (VTE).

Methods

This was a prospective diagnostic cohort study. Inpatients and ED patients >16 years of age investigated for PE or DVT at a single hospital were eligible for study consent. Blinded IMA analysis was performed on the first blood sample taken from each patient. Patients underwent reference standard investigation for PE or DVT, including 3-month follow-up. Receiver operating characteristic (ROC) curves were constructed for IMA and the IMA:albumin ratio in the diagnosis of all VTE, PE and DVT. A sensitivity analysis was performed.

Results

452 patients were consented and investigated for DVT, and 354 patients were consented and investigated for PE (806 in total). 348 patients investigated for PE had IMA testing as did 195 of the first 199 DVT patients. VTE prevalence was 19.7%. The IMA:albumin ratio performed better than IMA alone. The area under the ROC curve (AUC) for IMA:albumin in all VTE was 0.60 (95% CI 0.54 to 0.66), in DVT 0.56 (95% CI 0.46 to 0.65) and in PE 0.63 (95% CI 0.56 to 0.71). In ED patients with symptoms of PE, the AUC for IMA:albumin was 0.69 (95% CI 0.60 to 0.78).

Conclusions

IMA testing cannot be used alone to diagnose DVT or PE, although there is a moderate association with PE in ED patients.
MODEL CHECKING FOR VERIFICATION OF MANDATORY ACCESS CONTROL MODELS AND PROPERTIES
Authors: HU VINCENT C. , KUHN D. RICHARD , XIE TAO , HWANG JEEHYUN
Published: June 2011

Mandatory access control (MAC) mechanisms control which users or processes have access to which resources in a system. MAC policies are increasingly specified to facilitate managing and maintaining access control. However, the correct specification of the policies is a very challenging problem. To formally and precisely capture the security properties that MAC should adhere to, MAC models are usually written to bridge the rather wide gap in abstraction between policies and mechanisms. In this paper, we propose a general approach for property verification for MAC models. The approach defines a standardized structure for MAC models, providing for both property verification and automated generation of test cases. The approach expresses MAC models in the specification language of a model checker and expresses generic access control properties in the property language. Then the approach uses the model checker to verify the integrity, coverage, and confinement of these properties for the MAC models and finally generates test cases via combinatorial covering array for the system implementations of the models.
AUTOMATIC VERIFICATION OF OPTIMIZATION ALGORITHMS: A CASE STUDY OF A QUADRATIC ASSIGNMENT PROBLEM SOLVER
Authors: MERKEL ROBERT , WANG DAOMING , LIN HUIMIN , CHEN TSONG YUEH
Published: June 2011

Metamorphic testing is a technique for the verification of software output without a complete testing oracle. Mathematical optimization, implemented in software, is a problem for which verification can often be challenging. In this paper, we apply metamorphic testing to one such optimization problem, the quadratic assignment problem (QAP). From simple observations of the properties of the QAP, we describe how to derive a number of metamorphic relations useful for verifying the correctness of a QAP solver. We then compare the effectiveness of these metamorphic relations, in "killing" mutant versions of an exact QAP solver, to a simulated oracle. We show that metamorphic testing can be as effective as the simulated oracle for killing mutants. We examine the relative effectiveness of different metamorphic relations, both singly and in combination, and conclude that combining metamorphic relations can be significantly more effective than using a single relation.
THE EFFECT OF HUMAN CAPITAL ON SOCIAL CAPITAL AMONG ENTREPRENEURS
Authors: OTTÓSSON HANNES , KLYVER KIM
Published: June 2011

Using data collected from 714 entrepreneurs in a random sample of 10,000 Danes, this study provides an investigation of the effect of human capital on social capital among entrepreneurs. Previous entrepreneurship research has extensively investigated the separated effect of human capital and social capital on different entrepreneurial outputs. The study takes a step back and investigates how these two capital concepts are related — specifically how human capital influences social capital. In general, human capital and social capital were found to be co-productive, and increased human capital seems to increase the level of social capital concurrently. The dependence between human capital and social capital has tremendous implications for policy making and entrepreneurs.
DEFINING LISTED FAMILY CONTROLLED CORPORATIONS — AN AGENCY THEORY PERSPECTIVE
Authors: LAU JAMES
Published: June 2011

Recent research shows that a significant proportion of listed corporations in a number of major financial markets across the world are classified as family firms. That classification is based on a number of different definitions of a family firm, using criteria such as an ownership threshold and/or the presence of a family member on the board of directors and/or in the top managerial positions. The lack of a universal definition of listed family controlled corporations may undermine the comparability or even the validity of any empirical results reported. This paper aims to resolve the diversity of definitions in use by developing an operational definition of listed family controlled corporations that is consistent with agency theory — the most commonly adopted theoretical framework in existing empirical studies. Based on agency theory, I argue that the key difference between family and non-family firms lies in the control of the decision making processes of the corporation. I further argue that a family needs to dominate the management control structure in order to control decision making processes.
Realization of New Electronically Controllable Grounded and Floating Simulated Inductance Circuits Using Voltage Differencing Differential Input Buffered Amplifiers
Authors: Prasad Dinesh , Bhaskar D. R. , Pushkar K. L.
Published: June 2011

A new active circuit is proposed for the realisation of lossless grounded and floating inductance employing Voltage Differencing Differential Input Buffered Amplifiers (VD-DIBAs). The proposed grounded simulated inductance circuit employs two VD-DIBAs and a single-grounded capacitor whereas the floating simulated inductance circuit employs three VD-DIBAs and a grounded capacitor. The circuit for grounded inductance does not require any realization conditions whereas in case of floating inductance, only equality of two transconductances is needed. Some sample results demonstrating the applications of the new simulated inductors using VD-DIBAs have been given to confirm the workability of the new circuits.
Gaucher Disease and Cancer: Concept and Controversy
Authors: Choy Francis Y. M. , Campbell Tessa N.
Published: June 2011

Gaucher disease is an inherited disorder caused by a deficiency in the lysosomal hydrolase glucocerebrosidase. There is a wide spectrum of clinical presentations, with the most common features being hepatosplenomegaly, skeletal disease, and cytopenia. Gaucher disease has been classified into three broad phenotypes based upon the presence or absence of neurological involvement: Type 1 (nonneuronopathic), Type 2 (acute neuronopathic), and Type 3 (subacute neuronopathic). The two main treatment options include enzyme replacement therapy and substrate reduction therapy. Recently, discussion has escalated around the association of Gaucher disease and cancer, with conflicting reports as to whether Gaucher patients have an increased risk of malignancy. In this review, we present both the concept and controversy surrounding the association of Gaucher disease with cancer.
Quantitatively Controlled Fabrication of Uniaxially Aligned Nanofibrous Scaffold for Cell Adhesion
Authors: Park Suk Hee , Hong Jung Woo , Shin Jennifer Hyunjong , Yang Dong-Yol
Published: June 2011

In light of tissue engineering, development of a functional and controllable scaffold which can promote cell proliferation and differentiation is crucial. In this study, we introduce a controllable collection method of the electrospinning process for regularly-distributed and uniaxially oriented nanofiber scaffold and evaluate the effects of aligned nanofiber density on adhesion of dermal fibroblasts. The suggested spinning collector features an inclined void gap, which allows easy transfer of uniformly aligned fibers onto other surfaces. By undergoing multiple transfers, the density of the nanofibers can be quantitatively controlled. The resultant polycaprolactone (PCL) nanofibers had well-defined nanotopography in a 400–600 nm range. Human dermal fibroblasts were seeded on aligned nanofiber scaffolds of different densities achieved by varying the number of transfers. Cell morphology and actin stress fiber formation was accessed after seven days. The experimental results indicate that the contact guidance of the cells along the fiber alignment can be more activated with more than one guidance feature on a cell; that is, the high density of fiber is attained in so much that fiber spacing gets below the cell size.
Pore Structure Control of Ordered Mesoporous Silica Film Using Mixed Surfactants
Authors: Ha Tae-Jung , Im Hyeon-Gyoon , Yoon Seok-Jin , Jang Ho Won , Park Hyung-Ho
Published: June 2011

Materials with nanosized and well-arranged pores have been researched actively in order to be applied to new technology fields. Especially, mesoporous material containing various pore structures is expected to have different pore structure. To form a mixed pore structure, ordered mesoporous silica films were prepared with a mixture of surfactant; Brij-76 and P-123 block copolymer. In mixed surfactant system, mixed pore structure was observed in the region of P-123/(Brij-76 + P-123) with about 50.0 wt.% while a single pore structure was observed in regions which have large difference in ratio between Brij-76 and P-123 through the X-ray diffraction analysis. Regardless of surfactant ratio, porosity was retained almost the same. It is expected that ordered mesoporous silica film with mixed pore structure can be one of the new materials which has distinctive properties.
Tenofovir Nephrotoxicity: 2011 Update
Authors: Fernandez-Fernandez Beatriz , Montoya-Ferrer Ana , Sanz Ana B. , Sanchez-Niño Maria D. , Izquierdo Maria C. , Poveda Jonay , Sainz-Prestel Valeria , Ortiz-Martin Natalia , Parra-Rodriguez Alejandro , Selgas Rafael , Ruiz-Ortega Marta , Egido Jesus , Ortiz Alberto
Published: June 2011

Tenofovir is an acyclic nucleotide analogue reverse-transcriptase inhibitor structurally similar to the nephrotoxic drugs adefovir and cidofovir. Tenofovir is widely used to treat HIV infection and approved for treatment of hepatitis B virus. Despite initial cell culture and clinical trials results supporting the renal safety of tenofovir, its clinical use is associated with a low, albeit significant, risk of kidney injury. Proximal tubular cell secretion of tenofovir explains the accumulation of the drug in these mitochondria-rich cells. Tenofovir nephrotoxicity is characterized by proximal tubular cell dysfunction that may be associated with acute kidney injury or chronic kidney disease. Withdrawal of the drug leads to improvement of analytical parameters that may be partial. Understanding the risk factors for nephrotoxicity and regular monitoring of proximal tubular dysfunction and serum creatinine in high-risk patients is required to minimize nephrotoxicity. Newer, structurally similar molecular derivatives that do not accumulate in proximal tubules are under study.
Genes Encoding Callose Synthase and Phytochrome A Are Adjacent to a MAP3Kα-Like Gene in Beta vulgaris US H20
Authors: Kuykendall L. David , Shao Jonathan Y.
Published: June 2011

MAP3Kα, a gene that encodes a key conserved protein kinase,
is responsible for initiating a rapid cascade of cellular events
leading to localized cell death. Hypersensitive response, as it is
termed, enables genetically resistant plants to limit microbial
invasion under the right environmental conditions. Since knowledge
of close physically linked genes is important for genome analysis
and possibly for improving disease resistance, systematic DNA
sequence analysis, gene annotation, and protein BLASTs were
performed to identify and characterize genes in close physical
proximity to a MAP3Kα-like gene in Beta vulgaris L. US H20. On the same 125 Kb BAC, callose synthase (BvCS) and phytochrome A (PhyA) genes were within 50 Kb of MAP3Kα. The close physical linkage of these genes may result from selection for coordinated responses to disease pressure. Bert, a new chromodomain-carrying gypsy-like LTR retrotransposon, resides within an intron of the BvCS gene, where it is transcribed from the opposing strand.
Peroxidation of n-3 Polyunsaturated Fatty Acids Inhibits the Induction of iNOS Gene Expression in Proinflammatory Cytokine-Stimulated Hepatocytes
Authors: Araki Yoshiro , Matsumiya Miho , Matsuura Takashi , Oishi Masaharu , Kaibori Masaki , Okumura Tadayoshi , Nishizawa Mikio , Takada Hideho , Kwon A-Hon
Published: June 2011

Eicosapentaenoic acid and docosahexaenoic acid (EPA/DHA), n-3 polyunsaturated fatty acids (PUFAs), have a variety of biological activities including anti-inflammatory and anticancer effects. We hypothesized that their peroxidized products contributed in part to anti-inflammatory effects. In the liver, the production of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) has been implicated as one of the factors in hepatic inflammation and injury. We examined whether the peroxidation of EPA/DHA influences the induction of iNOS and NO production in proinflammatory cytokine-stimulated cultured hepatocytes, which isin vitroliver inflammation model. Peroxidized EPA/DHA inhibited the induction of iNOS and NO production in parallel with the increased levels of their peroxidation, whereas unoxidized EPA/DHA had no effects at all. Peroxidized EPA/DHA reduced the activation of transcription factor, NF-κB, and the expression of the iNOS antisense transcript, which are involved in iNOS promoter transactivation (mRNA synthesis) and its mRNA stabilization, respectively. These findings demonstrated that peroxidized products of EPA/DHA suppressed the induction of iNOS gene expression through both of the transcriptional and posttranscriptional steps, leading to the prevention of hepatic inflammation.
Modeling the Release Kinetics of Poorly Water-Soluble Drug Molecules from Liposomal Nanocarriers
Authors: Loew Stephan , Fahr Alfred , May Sylvio
Published: June 2011

Liposomes are frequently used as pharmaceutical nanocarriers to deliver poorly water-soluble drugs such as temoporfin, cyclosporine A, amphotericin B, and paclitaxel to their target site. Optimal drug delivery depends on understanding the release kinetics of the drug molecules from the host liposomes during the journey to the target site and at the target site. Transfer of drugs in model systems consisting of donor liposomes and acceptor liposomes is known from experimental work to typically exhibit a first-order kinetics with a simple exponential behavior. In some cases, a fast component in the initial transfer is present, in other cases the transfer is sigmoidal. We present and analyze a theoretical model for the transfer that accounts for two physical mechanisms, collisions between liposomes and diffusion of the drug molecules through the aqueous phase. Starting with the detailed distribution of drug molecules among the individual liposomes, we specify the conditions that lead to an apparent first-order kinetic behavior. We also discuss possible implications on the transfer kinetics of (1) high drug loading of donor liposomes, (2) attractive interactions between drug molecules within the liposomes, and (3) slow transfer of drugs between the inner and outer leaflets of the liposomes.
Poly(amidoamine)-Cholesterol Conjugate Nanoparticles Obtained by Electrospraying as Novel Tamoxifen Delivery System
Authors: Cavalli R. , Bisazza A. , Bussano R. , Trotta M. , Civra A. , Lembo D. , Ranucci E. , Ferruti P.
Published: June 2011

A new poly(amidoamine)-cholesterol (PAA-cholesterol) conjugate was synthesized, characterized and used to produce nanoparticles by the electrospraying technique. The electrospraying is a method of liquid atomization that consists in the dispersion of a solution into small charged droplets by an electric field. Tuning the electrospraying process parameters spherical PAA-chol nanoparticles formed. The PAA-cholesterol nanoparticles showed sizes lower than 500 nm and spherical shape. The drug incorporation capacity was investigated using tamoxifen, a lipophilic anticancer drug, as model drug. The incorporation of the tamoxifen did not affect the shape and sizes of nanoparticles showing a drug loading of 40%. Tamoxifen-loaded nanoparticles exhibited a higher dose-dependent cytotoxicity than free tamoxifen, while blank nanoparticles did not show any cytotoxic effect at the same concentrations. The electrospray technique might be proposed to produce tamoxifen-loaded PAA-chol nanoparticle in powder form without any excipient in a single step.
Preparation of DNA/Gold Nanoparticle Encapsulated in Calcium Phosphate
Authors: Ito Tomoko , Ibe Koyuki , Uchino Tomohiro , Ohshima Hiroyuki , Otsuka Makoto
Published: June 2011

Biocompatible DNA/gold nanoparticle complex with a protective calcium phosphate (CaP) coating was prepared by incubating DNA/gold nanoparticle complex coated by hyaluronic acid in SBF (simulated body fluid) with a Ca concentration above 2 mM. The CaP-coated DNA complex was revealed to have high compatibility with cells and resistance against enzymatic degradation. By immersion in acetate buffer (pH 4.5), the CaP capsule released the contained DNA complex. This CaP capsule including a DNA complex is promising as a sustained-release system of DNA complexes for gene therapy.
The Pharmacopsychometric Triangle to Illustrate the Effectiveness of T-PEMF Concomitant with Antidepressants in Treatment Resistant Patients: A Double-Blind, Randomised, Sham-Controlled Trial Revisited with Focus on the Patient-Reported Outcomes
Authors: Bech P. , Gefke M. , Lunde M. , Lauritzen L. , Martiny K.
Published: June 2011

Background. Our T-PEMF trial has been revisited with focus on the pharmacopsychometric triangle in which effect size is used when comparing wanted versus unwanted clinical effects and quality of life as outcomes. In this analysis, we have especially focused on the self-reported HAM-D6.Methods. The antidepressive medication which the patients were resistant to was kept unchanged during the five weeks of active versus sham T-PEMF.Results. In total 21, patients received active T-PEMF, and 19 patients received sham T-PEMF. The effect size was 1.02 and 0.90, respectively, on HAM-D6and HAM-D6-S. Concerning side effects, the active T-PEMF reduced the baseline score on concentration problems with an effect size of 0.44 while inducing more autonomic symptoms than sham T-PEMF with an effect size of −0.41. The advantage of active over sham T-PEMF obtained an effect size of 0.48.Conclusion. Active T-PEMF was found superior to sham T-PEMF within the pharmacopsychometric triangle with a clinically significant effect size level above 0.40.
Effects of Postinjection Application with Late Partially Premixed Combustion on Power Production and Diesel Exhaust Gas Conditioning
Authors: Jeftić Marko , Yu Shui , Han Xiaoye , Reader Graham T. , Wang Meiping , Zheng Ming
Published: June 2011

The effects of postinjection with late partially premixed charge compression ignition (PCCI) were investigated with respect to diesel exhaust gas conditioning and potential power production. Initial tests comparing postinjection application with PCCI to that with conventional diesel high temperature combustion (HTC) indicated the existence of similar trends in terms of carbon monoxide (CO), total unburned hydrocarbon (THC), oxides of nitrogen (NOx), and smoke emissions. However, postinjection in PCCI cycles exhibited lower NOx and smoke but higher CO and THC emissions. With PCCI operation, the use of postinjection showed much weaker ability for raising the exhaust gas temperature compared to HTC. Additional PCCI investigations generally showed increasing CO and THC, relatively constant NOx, and decreasing smoke emissions, as the postinjection was shifted further from top dead center (TDC). Decreasing the overall air‐to‐fuel ratio resulted in increased hydrogen content levels but at the cost of increased smoke, THC and CO emissions. The power production capabilities of early postinjection, combined with PCCI, were investigated and the results showed potential for early postinjection power production.
Scattered Radiation Emission Imaging: Principles and Applications
Authors: Nguyen M. K. , Truong T. T. , Morvidone M. , Zaidi H.
Published: June 2011

Imaging processes built on the Compton scattering effect have been under continuing investigation since it was first suggested in the 50s. However, despite many innovative contributions, there are still formidable theoretical and technical challenges to overcome. In this paper, we review the state-of-the-art principles of the so-called scattered radiation emission imaging. Basically, it consists of using the cleverly collected scattered radiation from a radiating object to reconstruct its inner structure. Image formation is based on the mathematical concept of compounded conical projection. It entails a Radon transform defined on circular cone surfaces in order to express the scattered radiation flux density on a detecting pixel. We discuss in particular invertible cases of such conical Radon transforms which form a mathematical basis for image reconstruction methods. Numerical simulations performed in two and three space dimensions speak in favor of the viability of this imaging principle and its potential applications in various fields.
Innovative Analyses Support a Role for DNA Damage and an Aberrant Cell Cycle in Myelodysplastic Syndrome Pathogenesis
Authors: Head David R. , Jacobberger James W. , Mosse Claudio , Jagasia Madan , Dupont William , Goodman Stacey , Flye Leanne , Shinar Andrew , McClintock-Treep Sara , Stelzer Greg , Briggs Robert , Shults Keith
Published: June 2011

We used flow cytometry to analyze the cell cycle, DNA damage, and apoptosis in hematopoietic subsets in MDS marrow. Subsets were assigned using CD45, side scatter, CD34, and CD71. Cell cycle fractions were analyzed using DRAQ 5 (DNA content) and MPM-2 (mitoses). DNA damage was assessed using p-H2A.X, and apoptosis using Annexin V. Compared to controls, MDS patients demonstrated no increased mitoses in erythroid, myeloid, or CD34+ cells. Myeloid progenitors demonstrated increased G2 cells, which with no increased mitoses suggested delayed passage through G2. Myeloid progenitors demonstrated increased p-H2A.X, consistent with DNA damage causing this delay. Annexin V reactivity was equivalent in MDS and controls. Results for each parameter varied among hematopoietic compartments, demonstrating the need to analyze compartments separately. Our results suggest that peripheral cytopenias in MDS are due to delayed cell cycle passage of marrow progenitors and that this delayed passage and leukemic progression derive from excessive DNA damage.
A Randomized, Controlled Trial of Meditation for Work Stress, Anxiety and Depressed Mood in Full‐Time Workers
Authors: Manocha R. , Black D. , Sarris J. , Stough C.
Published: June 2011

Objective. To assess the effect of meditation on work stress, anxiety and mood in full‐time workers. Methods. 178 adult workers participated in an 8‐week, 3‐arm randomized controlled trial comparing a “mental silence” approach to meditation (n = 59) to a “relaxation” active control (n = 56) and a wait‐list control (n = 63). Participants were assessed before and after using Psychological Strain Questionnaire (PSQ), a subscale of the larger Occupational Stress Inventory (OSI), the State component of the State/Trait Anxiety Inventory for Adults (STAI), and the depression‐dejection (DD) subscale of the Profile of Mood States (POMS).
Results. There was a significant improvement for the meditation group compared to both the relaxation control and the wait‐list groups the PSQ (P = .026), and DD (P = .019). Conclusions. Mental silence‐orientated meditation, in this case Sahaja Yoga meditation, is a safe and effective strategy for dealing with work stress and depressive feelings. The findings suggest that “thought reduction” or “mental silence” may have specific effects relevant to work stress and hence occupational health.
Effect of ON 01910.Na, an Anticancer Mitotic Inhibitor, on Cell-Cycle Progression Correlates with RanGAP1 Hyperphosphorylation
Authors: Oussenko Irina A. , Holland James F. , Reddy E. Premkumar , Ohnuma Takao
Published: June 2011

The benzyl styryl sulfone, ON 01910.Na, is a novel anticancer agent that inhibits mitotic progression and induces apoptosis in most cancer cell lines. We examined the effect of ON 01910.Na on DNA damage–signaling molecules upstream of Cdc25C (Chk1, Chk2, and H2AX), as well as on Ran GTPase-activating protein 1 conjugated to small ubiquitin-related modifier 1 (RanGAP1·SUMO1), a mitosis coordinator. Prostate cancer, lymphoma, and leukemic cells were incubated with the drug for 4, 16, or 24 hours. Cell lysates were resolved on SDS-PAGE and analyzed by Western blot. Camptothecin and doxorubicin treatment caused activation/phosphorylation of DNA damage-responsive molecules by 4 hours, whereas ON 01910.Na did not do so. ON 01910.Na caused hyperphosphorylation of RanGAP1·SUMO1 within 4 hours that was sustained for more than 24 hours. Mild phosphorylation of Chk2 was observed only after 24-hour exposure, indicating that DNA damage response was not an initial effect of ON 01910.Na. MOLT-3 cells, synchronized by double-thymidine block, when released into a medium containing ON 01910.Na, accumulated mitotic cell number with a peak from 10 to 14 hours and remained near plateau for 20 hours, which corresponded with the time of RanGAP phosphorylation. ON 01910.Na had minimal effects on tubulin polymerization. These findings imply that ON 01910.Na neither induces DNA damage directly nor acts as a tubulin toxin. Its biological activity appears to rely on prolonged phosphorylation/hyperphosphorylation of RanGAP1·SUMO1. M-phase arrest and the consequent induction of apoptosis that follows could possibly be attributed to it. ON 01910.Na may act as an inhibitor of a RanGAP1·SUMO1 phosphatase or a stimulant of a new kinase. RanGAP1·SUMO1 appears to be a new target pathway for cancer chemotherapy. Cancer Res; 71(14); 4968–76. ©2011 AACR.
Notch Signaling in CD66+ Cells Drives the Progression of Human Cervical Cancers
Authors: Bajaj Jeevisha , Maliekal Tessy Thomas , Vivien Eric , Pattabiraman Chitra , Srivastava Sweta , Krishnamurthy H. , Giri V. , Subramanyam Deepa , Krishna Sudhir
Published: June 2011

Human epithelial tumor progression and metastasis involve cellular invasion, dissemination in the vasculature, and regrowth at metastatic sites. Notch signaling has been implicated in metastatic progression but its roles have yet to be fully understood. Here we report the important role of Notch signaling in maintaining cells expressing the carcinoembryonic antigen cell adhesion molecule CEACAM (CD66), a known mediator of metastasis. CD66 and Notch1 were studied in clinical specimens and explants of human cervical cancer, including specimens grown in a pathophysiologically relevant murine model. Gene expression profiling of CD66+ cells from primary tumors showed enhanced features of Notch signaling, metastasis, and stemness. Significant differences were also seen in invasion, colony formation, and tumor forming efficiency between CD66+ and CD66− cancer cells. Notably, CD66+ cells showed a marked sensitivity to a Notch small molecule inhibitor. In support of studies in established cell lines, we documented the emergence of a tumorigenic CD66+ cell subset within a metastatic lesion-derived cervical-cancer cell line. Similar to primary cancers, CD66 expression in the cell line was blocked by chemical and genetic inhibitors of ligand-dependent nuclear Notch signaling. Collectively, our work on the oncogenic properties of CD66+ cells in epithelial cancers provides insights into the nature of tumor progression and offers a mechanistic rationale to inhibit the Notch signaling pathway as a generalized therapeutic strategy to treat metastatic cancers. Cancer Res; 71(14); 4888–97. ©2011 AACR.
Metabolites of a Tobacco-Specific Lung Carcinogen in Children Exposed to Secondhand or Thirdhand Tobacco Smoke in Their Homes
Authors: Thomas Janet L. , Guo Hongfei , Carmella Steven G. , Balbo Silvia , Han Shaomei , Davis Andrew , Yoder Andrea , Murphy Sharon E. , An Larry C. , Ahluwalia Jasjit S. , Hecht Stephen S.
Published: June 2011

Background: People exposed to secondhand tobacco smoke (SHS) inhale the lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) which is metabolized to NNAL and its glucuroniders. These urinary metabolites, termed total NNAL, can be quantified. A related compound, iso-NNAL, has been proposed as a biomarker for exposure to smoke constituent residues on surfaces (thirdhand tobacco smoke). There is limited information in the literature on levels of total NNAL in children exposed to SHS.

Methods: We recruited 79 parent–child dyads from homes where the enrolled parent was a cigarette smoker and visited their homes. Parents were asked questions, home ambient air quality was evaluated, and children provided urine samples. Urine was analyzed for total NNAL, total cotinine, total nicotine, and iso-NNAL.

Results: Ninety percent of the children had detectable total NNAL in urine; total nicotine and total cotinine were also detected in most samples. There were significant positive relationships between biomarker levels and exposure of children in the home. Levels were highest in homes with no smoking restrictions. African American children had significantly higher levels than other children. iso-NNAL was not detected in any urine sample.

Conclusions: There was nearly universal exposure of children to the lung carcinogen NNK, due mainly to exposure to SHS from adult smokers in their homes.

Impact: Homes with adult smokers should adopt restrictions to protect their children from exposure to a potent lung carcinogen. Cancer Epidemiol Biomarkers Prev; 20(6); 1213–21. ©2011 AACR.
Crohn's Disease and Small Bowel Adenocarcinoma: A Population-Based Case–Control Study
Authors: Shaukat Aasma , Virnig Daniel J. , Howard David , Sitaraman Shanthi V. , Liff Jonathan M. , Lederle Frank A.
Published: June 2011

Background: Although Crohn's disease (CD) is thought to predispose to adenocarcinomas of the small bowel, the association has not been well studied in an older population.

Aims: The objective of our study was to evaluate the association of CD with small bowel cancer in a population-based case–control study.

Methods: All cases of small bowel cancer in persons 67 and older in the Surveillance, Epidemiology and End Results catchment area and in the Medicare claims data base were compared with cancer-free controls residing in the same geographic area. We used multivariable logistic regression models adjusted for demographic and other factors.

Results: We identified 923 cases of small bowel cancer and 142,273 controls. Although we found a strong association between CD and small bowel cancer (OR = 12.07; 95% CI: 6.07–20.80; P < 0.001), the prevalence of CD in patients with small bowel cancer was low (1.6%).

Conclusions: Although CD is a significant risk factor for small bowel cancers among individuals older than 67, the absolute risk is small.

Impact: Older individuals with CD can be reassured that although there is an association between CD and small bowel cancer, the absolute risk remains small. Cancer Epidemiol Biomarkers Prev; 20(6); 1120–3. ©2011 AACR.
Lymphoid Malignancies in U.S. Asians: Incidence Rate Differences by Birthplace and Acculturation
Authors: Clarke Christina A. , Glaser Sally L. , Gomez Scarlett L. , Wang Sophia S. , Keegan Theresa H. , Yang Juan , Chang Ellen T.
Published: June 2011

Background: Malignancies of the lymphoid cells, including non-Hodgkin lymphomas (NHL), HL, and multiple myeloma, occur at much lower rates in Asians than other racial/ethnic groups in the United States. It remains unclear whether these deficits are explained by genetic or environmental factors. To better understand environmental contributions, we examined incidence patterns of lymphoid malignancies among populations characterized by ethnicity, birthplace, and residential neighborhood socioeconomic status (SES) and ethnic enclave status.

Methods: We obtained data about all Asian patients diagnosed with lymphoid malignancies between 1988 and 2004 from the California Cancer Registry and neighborhood characteristics from U.S. Census data.

Results: Although incidence rates of most lymphoid malignancies were lower among Asian than white populations, only follicular lymphoma (FL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and nodular sclerosis (NS) HL rates were statistically significantly lower among foreign-born than U.S.-born Asians with incidence rate ratios ranging from 0.34 to 0.87. Rates of CLL/SLL and NS HL were also lower among Asian women living in ethnic enclaves or lower SES neighborhoods than those living elsewhere.

Conclusions: These observations support strong roles of environmental factors in the causation of FL, CLL/SLL, and NS HL.

Impact: Studying specific lymphoid malignancies in U.S. Asians may provide valuable insight toward understanding their environmental causes. Cancer Epidemiol Biomarkers Prev; 20(6); 1064–77. ©2011 AACR.
CYP2D6 Gene Variants and Their Association with Breast Cancer Susceptibility
Authors: Abraham Jean E. , Maranian Mel J. , Driver Kristy E. , Platte Radka , Kalmyrzaev Bolot , Baynes Caroline , Luccarini Craig , Earl Helena M. , Dunning Alison M. , Pharoah Paul D.P. , Caldas Carlos
Published: June 2011

Background: The gene encoding the phase I enzyme cytochrome P4502D6 (CYP2D6) has been previously investigated for its potential predictive role in the efficacy of breast cancer treatments such as tamoxifen, but its role in breast cancer susceptibility is unclear. This study aims to evaluate the association between germ line variations in CYP2D6 and breast cancer susceptibility.

Methods: DNA samples from 13,472 cases and controls were genotyped for seven known functional variants [minor allele frequency (MAF) ≥ 0.01] and five single nucleotide polymorphisms (SNP) that tag common genetic variation (MAF > 0.05) in CYP2D6.

Results: One relatively rare functional variant, CYP2D6*6, (MAF = 0.01) showed a modest increased association with breast cancer susceptibility (Ptrend = 0.02; OR = 1.32; 95% CI = 1.04–1.68). All other functional and tagSNPs showed no association with breast cancer susceptibility.

Conclusions: Common variants of CYP2D6 do not play a significant role in breast cancer susceptibility. However, this study raises questions regarding the role of rare variants, such as CYP2D6*6, in breast cancer susceptibility which merit further investigation.

Impact: This large case–control study, involving 13,472 women, found no evidence of any association between common CYP2D6 gene variants and breast cancer susceptibility. However, one relatively rare functional variant CYP2D6*6 showed a modest association with breast cancer susceptibility, indicating that the role of rare CYP2D6 variants in breast cancer risk is unclear and requires further investigation in an adequately powered study. Cancer Epidemiol Biomarkers Prev; 20(6); 1255–8. ©2011 AACR.
Late Outcomes of a Single-Center Experience of 400 Consecutive Thoracic Endovascular Aortic Repairs
Authors: Lee W. Anthony , Daniels Michael J. , Beaver Thomas M. , Klodell Charles T. , Raghinaru Dan E. , Hess Philip J.
Published: June 2011

Background—

In this study, we report the late outcomes of a large, decade-long single-center thoracic endovascular aortic repair experience.

Methods and Results—

A prospectively maintained registry and the electronic medical records of 400 consecutive thoracic endovascular aortic repair performed at a tertiary care center were reviewed. The distribution of pathologies treated included aneurysms (198, 49%), dissections (100, 25%), penetrating ulcers (54, 14%), traumatic transections (25, 6%), and other pathologies (23, 6%). Spinal drains were placed prophylactically in 127 cases (32%) of planned extended aortic coverage. There were no acute surgical conversions. Adjunctive surgical procedures were performed on 94 patients (24%). Subclavian revascularizations were performed selectively in only 15% of zone 0 to 2 deployments. The median length of stay was 5 days (limits, 1 and 79 days). Overall 30-day mortality was 6.5% (elective, 2.6%; urgent, 9.5%; and emergent, 20%). Permanent spinal cord ischemia occurred in 4.5% and stroke in 3%. Kaplan-Meier estimates of survival were 82%, 76%, 68%, and 60% and freedom from secondary intervention was 90%, 86%, 81%, and 78% at 6, 12, 24, and 36 months, respectively. Risk factors for mortality included stroke, urgent/emergent repair, age ≥80 years, general anesthesia, and dissection pathology.

Conclusions—

Thoracic endovascular aortic repair may be used to treat a variety of thoracic aortic pathologies with a very low risk of intraoperative conversion. Overall rates of mortality and neurological complications were relatively low but significantly increased in emergent repairs. There appeared to be a substantial number of late deaths, which may represent a combination of poor patient selection and treatment failures.