bluuebunny/crossref_metadata_2025 huggingface dataset:
The net effect of smoking on healthcare and welfare costs. A cohort study
Authors: Tiihonen Jari , Ronkainen Kimmo , Kangasharju Aki , Kauhanen Jussi
Published: December 2012

Objective

To study the net economic effect of smoking on society.

Design

Prospective cohort study.

Setting

Eastern Finland.

Patients

We studied mortality, paid income and tobacco taxes, and the cumulative costs due to pensions and medical care among tobacco smoking and non-smoking individuals in a 27-year prospective cohort study of 1976 men from Eastern Finland. These individuals were 54–60 years old at the beginning of the follow-up.

Main outcome measures

The net contribution of smoking versus non-smoking individuals to public finance balance (euros).

Results

Smoking was associated with a greater mean annual healthcare cost of €1600 per living individual during follow-up. However, due to a shorter lifespan of 8.6 years, smokers’ mean total healthcare costs during the entire study period were actually €4700 lower than for non-smokers. For the same reason, each smoker missed 7.3 years (€126 850) of pension. Overall, smokers’ average net contribution to the public finance balance was €133 800 greater per individual compared with non-smokers. However, if each lost quality adjusted life year is considered to be worth €22 200, the net effect is reversed to be €70 200 (€71.600 when adjusted with propensity score) per individual in favour of non-smoking.

Conclusions

Smoking was associated with a moderate decrease in healthcare costs, and a marked decrease in pension costs due to increased mortality. However, when a monetary value for life years lost was taken into account, the beneficial net effect of non-smoking to society was about €70 000 per individual.
A randomised controlled trial comparing surgical intervention rates between two protocols for the management of asymptomatic adnexal tumours in postmenopausal women
Authors: Nunes Natalie , Foo Xulin , Widschwendter Martin , Jurkovic Davor
Published: December 2012

Introduction

Detection of asymptomatic adnexal tumours in postmenopausal women has increased due to wider use of diagnostic ultrasound and imaging quality improvements. Reliable methods to differentiate between benign and malignant tumours are required to avoid delays in treating ovarian cancer and to prevent unnecessary interventions for benign lesions. In the UK, the Royal College of Obstetricians and Gynaecologists has issued guidance for the management of adnexal cysts in postmenopausal women, which is considered standard in routine clinical practice. The protocol utilises the Risk of Malignancy Index to assess the risk of adnexal lesion being malignant. This protocol has a relatively high intervention rate in order to avoid a delay in a cancer diagnosis. The Simple Rules Protocol designed by International Ovarian Tumour Analysis Group reports a low false-positive rate in the diagnosis of ovarian cancer without a loss of sensitivity and therefore has the potential to reduce unnecessary interventions in asymptomatic postmenopausal women with benign cysts.

Methods and analysis

140 postmenopausal women aged 40–80, with incidentally detected adnexal tumours on ultrasound scan will be recruited to this study. They will be randomly allocated, to be assessed and managed according to either of the two protocols under investigation. In both arms of the study the tumours will be classified into three groups: high, intermediate or low risk of malignancy. Women with high risk of malignancy will be referred for management in a tertiary cancer centre, women with low-risk tumours will be managed expectantly, while those with intermediate risk findings have surgery in their local hospital units. Analysis will be on an intention-to-treat basis.

Ethics and dissemination

Research ethical approval was granted by the North London Research Ethical Committee 2 (10/H0724/48). Trial results will be published according to the CONSORT statement.

Trial registration number

Registration athttp://www.controlled-trials.com/ISRCTN89034131/. ISRCTN89034131
Canada’s international and national commitments to sustain marine biodiversity1This manuscript is a companion paper to Hutchings et al. (doi:10.1139/a2012-011) and Hutchings et al. (doi:10.1139/er-2012-0049) also appearing in this issue. These three papers comprise an edited version of a February 2012 Royal Society of Canada Expert Panel Report.
Authors: VanderZwaag David L. , Hutchings Jeffrey A. , Jennings S. , Peterman Randall M.
Published: December 2012

Canada has made numerous international and national commitments to sustain marine biodiversity. International commitments include the implementation of ecosystem-based management, the establishment a network of marine protected areas, and the restoration of commercially exploited fish stocks. However, the international commitments tend to be quite general in nature with the precise governance implications of key principles, such as precaution and the ecosystem approach, being open to interpretation, thus leaving considerable room for discretion in implementation. Consequently, a plethora of soft law documents has emerged to provide more specific guidance to decision-makers and progressively develop international law and policy. Nationally, Canada has embraced a long list of commitments that are supportive of sustaining marine biodiversity through legislation and numerous policy-related documents. Nonetheless, Canada has left many of these commitments unfulfilled or inadequately fulfilled, such as (i) the development of integrated management plans for coastal and marine waters, (ii) the implementation of the precautionary approach for Canada’s fisheries, and (iii) the establishment of recovery strategies and identification of critical habitat for species at risk. Although the goal of effective protection of marine biodiversity in Canada appears to be guided by international and national commitments, there remains a clear need to fully implement, operationalize, and strengthen these commitments as articulated in the Oceans Act, fisheries management-related policies, the Species at Risk Act, and others.
A "NEAR-THE-BEST" SYSTEM-LEVEL DESIGN METHODOLOGY OF MULTI-CORE H.264 VIDEO DECODER BASED ON THE PARALLELIZED MULTI-CORE SIMULATOR
Authors: XIA BINGBING , QIAO FEI , DU ZIDONG , ZHU DI , YANG HUAZHONG
Published: December 2012

H.264 video decoder is a good choice for embedded video processing applications because of its higher compression ratio than MPEG2, although it has higher requirements of run-time computational resource. Multi-core system is the future of the embedded processor design for its power efficiency and multi-thread parallelization capability, and can be used to fit well with the requirements for such video processing algorithms. To simulate and evaluate the performance of these multi-core systems effectively, a design flow at the system level is developed, at the higher level, the combination of TLM language (SystemC) and shared-memory parallel programming model (OpenMP) is used for such transaction-level simulation, and at the lower level, a multi-core simulator based on the extension of the SimpleScalar 3.0 ToolSet is developed for the cycle-accurate level simulation. Compared with other high-level simulation methods, ours has the ability to realize the true-parallelization simulation. What is more, experiments show that such simulation methodology can effectively simulate these complex multi-core applications in a short time to get the appropriate core number and the task allocation strategy (much less than RTL-level simulation) and the results can get at less than 15% deviated from the ideal ones calculated based on Amadal's Law, so the parallelization strategy obtained from such simulation is the best one that can be further applied for the RTL-level design of the final multi-core system.
TORSION, AN ALTERNATIVE TO THE COSMOLOGICAL CONSTANT?
Authors: SCHÜCKER THOMAS , TILQUIN ANDRÉ
Published: December 2012

We confront Einstein–Cartan's theory with the Hubble diagram and obtain a negative answer to the question in the title. Contrary findings in the literature seem to stem from an error in the field equations.
LOCAL SPIN FOAMS
Authors: MAGLIARO ELENA , PERINI CLAUDIO
Published: December 2012

The central object of this paper is a holonomy formulation for spin foams. Within this new representation, we analyze three general requirements: locality, composition law and cylindrical consistency. In particular, cylindrical consistency is shown to fix the arbitrary normalization of the vertex amplitude in the case of Euclidean signature.
A TIMOSHENKO BEAM ELEMENT FOR LARGE DISPLACEMENT ANALYSIS OF PLANAR BEAMS AND FRAMES
Authors: KIEN NGUYEN DINH
Published: December 2012

A Timoshenko beam element for large displacement analysis of planar beam and frame structures is formulated in the context of the co-rotational method. The shallow arch expression is adopted for the local strain, and cubic and quadratic polynomials obtained from the field consistence approach are respectively employed to interpolate the transversal displacement and rotation. The numerical examples show that the proposed element is capable of furnishing accurate results with a smaller number of elements as compared to the elements previously used in the examples. It has also shown that the nonlinear term in the expression of the local strain plays an important role in the accuracy of the element in the large displacement analysis of beam and frame structures.
NOX2 deficiency attenuates markers of adiposopathy and brain injury induced by high-fat diet
Authors: Pepping Jennifer K. , Freeman Linnea R. , Gupta Sunita , Keller Jeffrey N. , Bruce-Keller Annadora J.
Published: December 2012

The consumption of high-fat/calorie diets in modern societies is likely a major contributor to the obesity epidemic, which can increase the prevalence of cancer, cardiovascular disease, and neurological impairment. Obesity may precipitate decline via inflammatory and oxidative signaling, and one factor linking inflammation to oxidative stress is the proinflammatory, pro-oxidant enzyme NADPH oxidase. To reveal the role of NADPH oxidase in the metabolic and neurological consequences of obesity, the effects of high-fat diet were compared in wild-type C57Bl/6 (WT) mice and in mice deficient in the NAPDH oxidase subunit NOX2 (NOX2KO). While diet-induced weight gains in WT and NOX2KO mice were similar, NOX2KO mice had smaller visceral adipose deposits, attenuated visceral adipocyte hypertrophy, and diminished visceral adipose macrophage infiltration. Moreover, the detrimental effects of HFD on markers of adipocyte function and injury were attenuated in NOX2KO mice; NOX2KO mice had improved glucose regulation, and evaluation of NOX2 expression identified macrophages as the primary population of NOX2-positive cells in visceral adipose. Finally, brain injury was assessed using markers of cerebrovascular integrity, synaptic density, and reactive gliosis, and data show that high-fat diet disrupted marker expression in WT but not NOX2KO mice. Collectively, these data indicate that NOX2 is a significant contributor to the pathogenic effects of high-fat diet and reinforce a key role for visceral adipose inflammation in metabolic and neurological decline. Development of NOX-based therapies could accordingly preserve metabolic and neurological function in the context of metabolic syndrome.
Slowly inactivating component of Na+ current in peri-somatic region of hippocampal CA1 pyramidal neurons
Authors: Park Yul Young , Johnston Daniel , Gray Richard
Published: December 2012

The properties of voltage-gated ion channels on the neuronal membrane shape electrical activity such as generation and backpropagation of action potentials, initiation of dendritic spikes, and integration of synaptic inputs. Subthreshold currents mediated by sodium channels are of interest because of their activation near rest, slow inactivation kinetics, and consequent effects on excitability. Modulation of these currents can also perturb physiological responses of a neuron that might underlie pathological states such as epilepsy. Using nucleated patches from the peri-somatic region of hippocampal CA1 neurons, we recorded a slowly inactivating component of the macroscopic Na+ current (which we have called INaS) that shared many biophysical properties with the persistent Na+ current, INaP, but showed distinctively faster inactivating kinetics. Ramp voltage commands with a velocity of 400 mV/s were found to elicit this component of Na+ current reliably. INaS also showed a more hyperpolarized I-V relationship and slower inactivation than those of the fast transient Na+ current ( INaT) recorded in the same patches. The peak amplitude of INaS was proportional to the peak amplitude of INaT but was much smaller in amplitude. Hexanol, riluzole, and ranolazine, known Na+ channel blockers, were tested to compare their effects on both INaS and INaT. The peak conductance of INaS was preferentially blocked by hexanol and riluzole, but the shift of half-inactivation voltage ( V1/2) was only observed in the presence of riluzole. Current-clamp measurements with hexanol suggested that INaS was involved in generation of an action potential and in upregulation of neuronal excitability.
Growth restriction in the rat alters expression of metabolic genes during postnatal cardiac development in a sex-specific manner
Authors: Wadley Glenn D. , McConell Glenn K. , Goodman Craig A. , Siebel Andrew L. , Westcott Kerryn T. , Wlodek Mary E.
Published: December 2012

This study investigated the impact of uteroplacental insufficiency and growth restriction on the expression of genes related to mitochondrial biogenesis, glucose transport, and antioxidant defenses in cardiac tissue at embryonic day 20 (E20) and postnatal days 1, 7, and 35 in male and female Wistar rats (8–10 per group). Bilateral uterine vessel ligation to induce growth restriction (Restricted) or sham surgery was performed at pregnancy day 18. In male and female Controls, expression of most cardiac genes decreased during postnatal life, including genes involved in mitochondrial biogenesis regulation such as PGC-1α, NRF-2, and mtTFA and the glucose transporter GLUT-1 ( P < 0.05). However, the pattern of gene expression during cardiac development differed in male and female Restricted rats compared with their respective Controls. These effects of restriction were observed at postnatal day 1, with female Restricted rats having delayed reductions in PGC-1α and GLUT-1, whereas males had exacerbated reductions in PGC-1α and mtTFA ( P < 0.05). By day 35, cardiac gene expression in Restricted hearts was similar to Controls, except for expression of the antioxidant enzyme MnSOD, which was significantly lower in both sexes. In summary, during postnatal life male and female Control rats have similar patterns of expression for genes involved in mitochondrial biogenesis and glucose transport. However, following uteroplacental insufficiency these gene expression patterns diverge in males and females during early postnatal life, with MnSOD gene expression reduced in later postnatal life.
Prenatal Diagnosis of Penoscrotal Hypospadia in Third Trimester by Two- and Three-Dimensional Ultrasonography: A Case Report
Authors: Rios Lívia Teresa Moreira , Araujo Júnior Edward , Nardozza Luciano Marcondes Machado , Rolo Liliam Cristine , Hatanaka Alan Roberto , Moron Antonio Fernandes , Martins Marília da Glória
Published: December 2012

Hypospadia is an abnormal development of the corpus spongiosum, that involves cavernosa urethra, as a result of an inadequate fusion of the urethral folds. The incidence ranges from 0.2 to 4.1 per 1,000 live births. Among the markers of hypospadia, isolated ventral or lateral curvature of the penis associated with shortening are the most important markers and, in severe cases, can result in the classic “tulip sign.” The diagnosis of hypospadia is uncommon unless there is a routine of detailed analysis of fetal genitalia morphology. The prenatal diagnosis is of great importance for genetic counseling and allows better planning of postnatal treatment. The three-dimensional ultrasonography (3DUS) in rendering mode enables better comprehension of the pathology by parents, facilitating postnatal planning. We report a case of penoscrotal hypospadia diagnosed at 33 weeks of gestation, suspected due to the absence of testicles in the scrotum and difficulty of penis visualization. We emphasize the findings of 3DUS and its importance in the pathology compression by parents.
Moving Earth and Building Monuments at the Carson Mounds Site, Coahoma County, Mississippi
Authors: Mehta Jayur Madhusudan , Lowe Kelsey M. , Stout-Evans Rachel , Connaway John
Published: December 2012

The application of combined techniques such as aerial imagery, sediment coring, down-hole magnetic susceptibility, and mechanized trench excavation can provide critical information on landscape formation and mound stratigraphy, specifically if they can be used to understand mound sequences and development. This paper reviews preliminary findings from recent coring and test excavations at the Carson mounds site (22CO505) in Coahoma County, Mississippi. Aerial imagery assisted in the characterization of a crevasse ridge flood deposit underlying the site and detailed field descriptions of the pedology corroborated its existence. Subsequent sediment coring and trench excavation revealed the nature of flooding in prehistory, indicating that high-intensity floods were responsible for the formation of the crevasse ridge and that lower intensity floods were potentially responsible for interruptions in mound building at the site. This suggests that the Carson settlement was initiated on an actively flooding landform. Down-hole magnetic susceptibility correlated effectively with the pedology; however, it also helped discern anthropogenic surfaces (i.e., occupational layers) that are difficult to identify visually, such as those we found in Mound C. Findings from this pilot study demonstrate the utility of sediment coring and magnetic susceptibility as effective and feasible methods for developing hypothesis-driven research.
Roles of Weight Functions to a Nonlocal Porous Medium Equation with Inner Absorption and Nonlocal Boundary Condition
Authors: Fang Zhong Bo , Zhang Jianyun , Yi Su-Cheol
Published: December 2012

This work is concerned with an initial boundary value problem for a nonlocal porous medium equation with inner absorption and weighted nonlocal boundary condition. We obtain the roles of weight function on whether determining the blowup of nonnegative solutions or not and establish the precise blow‐up rate estimates under some suitable condition.
The Interrelationship of Adenomatoid Odontogenic Tumour and Dentigerous Cyst: A Report of a Rare Case and Review of the Literature
Authors: Agarwal Anshita , Giri K. Y. , Alam Sarwar
Published: December 2012

The adenomatoid odontogenic tumor (AOT) is a relatively uncommon lesion which mainly affects females in their second decade of life, exhibiting predilection for the anterior region of the maxilla. The lesion is usually associated with the crown of an enclosed tooth, most commonly the maxillary canine. In this paper we present a case of adenomatoid odontogenic tumor associated with a dentigerous cyst affecting the left maxilla in a 15-year-old female. We also discuss clinical, radiographic, histopathologic, and therapeutic features of the case.
New 1,2,3-Triazole Iminosugars Derivatives Using Click Chemistry
Authors: Benhaoua Chahrazed
Published: December 2012

The click concept refers ease, efficient, and the selective chemicals transformations. In this study, a novel regiospecific copper (I)-catalyzed 1, 3-dipolar of terminal alkynes to azide provided a practicable synthetic pathway of triazole iminosugars derivatives. A series of new triazole-pyrrolidinols are reported in good yield.
Prevalence of Occult Hepatitis C Virus in Egyptian Patients with Chronic Lymphoproliferative Disorders
Authors: Youssef Samar Samir , Nasr Aml S. , El Zanaty Taher , El Rawi Rasha Sayed , Mattar Mervat M.
Published: December 2012

Background. Occult hepatitis C virus infection (OCI) was identified as a new form of Hepatitis C virus (HCV), characterized by undetectable HCV antibodies and HCV RNA in serum, while HCV RNA is detectable in liver and peripheral blood cells only. Aim. The aim of this study was to investigate the occurrence of OCI in Egyptian patients with lymphoproliferative disorders (LPDs) and to compare its prevalence with that of HCV in those patients. Subjects and Methods. The current study included 100 subjects, 50 of them were newly diagnosed cases having different lymphoproliferative disorders (patients group), and 50 were apparently healthy volunteers (controls group). HCV antibodies were detected by ELISA, HCV RNA was detected in serum and peripheral blood mononuclear cells (PBMCs) by reverse transcription polymerase chain reaction(RT-PCR), and HCV genotype was detected by INNO-LiPA. Results. OCI was detected in 20% of patients group, compared to only 4% OCI in controls group. HCV was detected in 26% of patients group with a slightly higher prevalence. There was a male predominance in both HCV and OCI. All HCV positive patients were genotype 4. Conclusion. Our data revealed occurrence of occult HCV infection in Egyptian LPD patients at a prevalence of 20% compared to 26% of HCV.
Small Bowel Ischemia due to Jejunum Volvulus in Pregnancy: A Case Report
Authors: Vassiliou Ioannis , Tympa Aliki , Derpapas Michalis , Kottis Georgios , Vlahos Nikolaos
Published: December 2012

The diagnosis of intestinal obstruction in pregnancy is difficult, as the symptoms may mimic pregnancy-associated complaints. The surgical management is challenging, as the mortality rate of midgut volvulus in pregnancy is high. We report the case of a 35-year-old woman at 21 weeks and 5 days of gestation with small bowel obstruction who presented to our institution with a 24 h history of colicky abdominal pain and nausea and who finally had a successful open repair.
Acute Generalized Exanthematous Pustulosis due to Tocilizumab in a Rheumatoid Arthritis Patient
Authors: Izquierdo J. H. , Bonilla-Abadía F. , Ochoa C. D. , Agualimpia A. , Tobón G. J. , Cañas C. A.
Published: December 2012

We report a female patient with rheumatoid arthritis which was refractory to methotrexate, leflunomide, and anti-TNF therapy. She was treated with anti-IL-6 tocilizumab (TCZ), with an early appearance of sterile pustules on erythematous swollen skin of trunk, back, and abdominal area. The lesions were consistent with the diagnosis of acute drug-related generalized exanthematous pustulosis (AGEP). This adverse event was controlled with medical treatment without requiring removal of TCZ.
Single‐Molecule Sandwich Immunoassay for Quantification of Alpha‐Fetoprotein Based on Evanescent Field‐Enhanced Fluorescence Imaging
Authors: Lee Seungah , Kang Seong Ho
Published: December 2012

A highly sensitive immunosensor based on a gold nanopatterned chip was developed for accurate determination of alpha‐fetoprotein (AFP) via total internal refection fluorescence microscopy (TIRFM). The surface of the gold nanopatterned chips was modified with dithiobis(succinimidyl propionate) and protein A/G for immobilization of the AFP antibody. The immunoassay created a sandwich of antigen between the AFP antibody on the chip that was modified with protein A/G, and the secondary antibody, a monoclonal anti‐human‐AFP labeled with biotin (biotin‐labeled anti‐AFP). AFP concentration was determined based on evanescent field fluorescence signal, which was generated by interaction between biotin‐labeled anti‐AFP and a streptavidin‐labeled fluorescence dye. AFP concentration could be measured in a wide dynamic linear range of 720 zM–10 nM with a detection limit of 720 zM. A significant enhanced sensitivity (~40,000‐fold) was achieved with the AFP‐nanoarray chip compared to conventional chemiluminescence immunosensors. The immunoassay exhibited a wide detection range and high sensitivity and accuracy, qualities valuable for clinical assay of AFP.
Mechanisms of Physical Activity Limitation in Chronic Lung Diseases
Authors: Vogiatzis Ioannis , Zakynthinos George , Andrianopoulos Vasileios
Published: December 2012

In chronic lung diseases physical activity limitation is multifactorial involving respiratory, hemodynamic, and peripheral muscle abnormalities. The mechanisms of limitation discussed in this paper relate to (i) the imbalance between ventilatory capacity and demand, (ii) the imbalance between energy demand and supply to working respiratory and peripheral muscles, and (iii) the factors that induce peripheral muscle dysfunction. In practice, intolerable exertional symptoms (i.e., dyspnea) and/or leg discomfort are the main symptoms that limit physical performance in patients with chronic lung diseases. Furthermore, the reduced capacity for physical work and the adoption of a sedentary lifestyle, in an attempt to avoid breathlessness upon physical exertion, cause profound muscle deconditioning which in turn leads to disability and loss of functional independence. Accordingly, physical inactivity is an important component of worsening the patients’ quality of life and contributes importantly to poor prognosis. Identifying the factors which prevent a patient with lung disease to easily carry out activities of daily living provides a unique as well as important perspective for the choice of the appropriate therapeutic strategy.
ZnO Nanoparticles-Chitosan Composite as Antibacterial Finish for Textiles
Authors: Farouk Asmaa , Moussa Shaaban , Ulbricht Mathias , Textor Torsten
Published: December 2012

The antibacterial performance of sol-gel-derived inorganic-organic hybrid polymers filled with ZnO nanoparticles-chitosan against a gram-negative bacteriumEscherichia coliand a gram-positiveMicrococcus luteushas been investigated. Three different molecular weights (MW) of chitosan (CTS) 1.36 · 105, 2.2 · 105, and 3.0 · 105 Da with equal degree of deacetylation (DD, 85%) (coded as S 85-60, He 85-250, and He 85-500) with equal degree of deacetylation (DD, 85%) were examined. ZnO was prepared by the base hydrolysis of zinc acetate in isopropanol using lithium hydroxide (LiOH · H2O) to hydrolyze the precursor. Sol-gel-based inorganic-organic hybrid polymers were modified with these oxides and were applied to cellulosic cotton (100%) and cotton/polyester (65/35%) fabrics. Inorganic-organic hybrids polymers were based on 3-glycidyloxypropyltrimethoxysilane (GPTMS). Bacteriological tests were performed in nutrient agar media on solid agar plates and in liquid broth systems using ZnO nanoparticles with average particle size of (40 nm). Our study showed the enhanced antibacterial activity of ZnO nanoparticles chitosan (different MW) of against a gram-negative bacteriumEscherichia coliDSMZ 498 and a gram-positiveMicrococcus luteusATCC 9341 in repeated experiments. The antibacterial activity of textile treated with ZnO nanoparticles chitosan increases with decreasing the molecular weight of chitosan.
Dermatoglyphic Studies among the Dumagat-Remontado Tribal Population of the Philippines
Authors: Gutierez Sally B. , Lucenario John Lou S. , Yebes Mark Jason T.
Published: December 2012

Dermatoglyphics is the study of dermal ridges. Since dermatoglyphic characters are recognized as a unique individual trait and follow a multifactorial or polygenic pattern of inheritance, it is necessary to understand the variations leading to this pattern. The present paper, through appropriate descriptive approach, has revealed the variation in the pattern of inheritance in the TFRCs of the Dumagat-Remontados from Puray, Rodriguez, Rizal, Philippines. The study also reported a large discrepancy on the total fingerprint ridge count among the Dumagat-Remontados compared to established researches. Also, the increased heterozygosity due to genetic admixture led to the dominant occurrence of the loop pattern (ulnar) in the fingerprints of this group of indigenous people as compared to few established data stating that the frequency of whorl patterns dominates the universal population and other Asian racial groups. In this study, a special feature on the fingerprint patterns of the pure Dumagat-Remontados was reported. Aside from the high frequency of loops and whorls, a distinct club dent, concluded to be a unique feature found among this tribal population, was noted from at least one of the fingers of the majority of the pure sample.
Influence of Energy and Temperature in Cluster Coalescence Induced by Deposition
Authors: Jiménez-Sáez J. C. , Pérez-Martín A. M. C. , Jiménez-Rodríguez J. J.
Published: December 2012

Coalescence induced by deposition of different Cu clusters on an epitaxial Co cluster supported on a Cu(001) substrate is studied by constant-temperature molecular dynamics simulations. The degree of epitaxy of the final system increases with increasing separation between the centres of mass of the projectile and target clusters during the collision. Structure, roughness, and epitaxial order of the supported cluster also influence the degree of epitaxy. The effect of energy and temperature is determinant on the epitaxial condition of the coalesced cluster, especially both factors modify the generation, growth and interaction among grains. A higher temperature favours the epitaxial growth for low impact parameters. A higher energy contributes to the epitaxial coalescence for any initial separation between the projectile and target clusters. The influence of projectile energy is notably greater than the influence of temperature since higher energies allow greater and instantaneous atomic reorganizations, so that the number of arisen grains just after the collision becomes smaller. The appearance of grain boundary dislocations is, therefore, a decisive factor in the epitaxial growth of the coalesced cluster.
Improved Quantum‐Inspired Evolutionary Algorithm for Engineering Design Optimization
Authors: Tsai Jinn-Tsong , Chou Jyh-Horng , Ho Wen-Hsien
Published: December 2012

An improved quantum‐inspired evolutionary algorithm is proposed for solving mixed discrete‐continuous nonlinear problems in engineering design. The proposed Latin square quantum‐inspired evolutionary algorithm (LSQEA) combines Latin squares and quantum‐inspired genetic algorithm (QGA). The novel contribution of the proposed LSQEA is the use of a QGA to explore the optimal feasible region in macrospace and the use of a systematic reasoning mechanism of the Latin square to exploit the better solution in microspace. By combining the advantages of exploration and exploitation, the LSQEA provides higher computational efficiency and robustness compared to QGA and real‐coded GA when solving global numerical optimization problems with continuous variables. Additionally, the proposed LSQEA approach effectively solves mixed discrete‐continuous nonlinear design optimization problems in which the design variables are integers, discrete values, and continuous values. The computational experiments show that the proposed LSQEA approach obtains better results compared to existing methods reported in the literature.
Mie Scattering by a Conducting Sphere Coated Uniaxial Single-Negative Medium
Authors: Geng You-Lin
Published: December 2012

We propose an accurate analytical method to compute the electromagnetic scattering from three-dimensional (3D) conducting sphere coated uniaxial anisotropic single-negative (SNG) medium. Based on the spherical vector wave functions (SVWFs) in uniaxial anisotropic medium, the electromagnetic field in homogeneous uniaxial SNG medium and free space can be expressed by the SVWFs in uniaxial SNG medium and free space. The continued boundary conditions of electromagnetic fields between the uniaxial SNG medium and free space are applied, and the tangential electrical field is vanished in the surface of conducting sphere, the coefficients of scattering fields in free space can be derived, and then the character of scattering of conducting sphere coated homogeneous uniaxial SNG medium can be obtained. Some numericals are given in the end.
Robust Tracking Control for Switched Fuzzy Systems with Fast Switching Controller
Authors: Yang Hong , Zhang Le , Liu Xiaodong
Published: December 2012

This paper addresses the problem of designing robust tracking controls for a class of switched fuzzy (SF) systems with time delay. A switched fuzzy system, which differs from existing ones, is firstly employed to describe a nonlinear system. Next, a fast switching controller consisting of a number of simple subcontrollers is proposed. The smooth transition is governed by using the fast switching controller. Tracking hybrid control schemes which are based upon a combination of the H∞ tracking theory, fast switching control algorithm, and switching law design are developed such that the H∞ model referent tracking performance is guaranteed. Since convex combination techniques are used to derive the delay independent criteria, some subsystems are allowed to be unstable. Finally, various comparisons of the elaborated examples are conducted to demonstrate the effectiveness of the proposed control design approach. All results illustrate good control performances as desired.
CLEAN Technique to Classify and Detect Objects in Subsurface Imaging
Authors: Karpat E.
Published: December 2012

An image domain CLEAN technique, for nondestructive and noncontacting subsurface imaging, is discussed. Recently introduced finite-difference time-domain- (FDTD-) based virtual tool, GrGPR, is used to create imaging scenarios and to generate synthetic scattering data through synthetic aperture (SAR) type scanning. Matlab-based imaging algorithms are used to process recorded FDTD data. The location and the geometry of the targets are obtained by image domain CLEAN technique which is extracting scattering centers from the SAR image. The effectiveness of the algorithm is tested in simulated data.
Murine Models of Nonalcoholic Fatty Liver Disease and Steatohepatitis
Authors: Ninomiya Masashi , Kondo Yasuteru , Shimosegawa Tooru
Published: December 2012

In 1980, Ludwig et al. first reported patients of steatohepatitis who lacked a history of excessive alcohol consumption but showed liver histology resembling alcoholic hepatitis and progression to cirrhosis of the liver accompanied by inflammation and fibrosis. The development of nonalcoholic steatohepatitis (NASH) is associated with obesity, diabetes mellitus, insulin resistance, and hyperlipidemia. However, the pathogenesis of NASH remains incomplete. A “multiple-hit” hypothesis for the pathogenesis of NASH based on an animal model has been proposed and remains a foundation for research in this field. We review the important dietary and genetic animal models and discuss the pathogenesis of NASH.
Solubility Data of Comonomer Pairs Relevant to Aqueous‐Phase Study in the Emulsion Copolymerization
Authors: Daswani Pooja , van Herk Alex
Published: December 2012

In emulsion copolymerizations, the two monomers might not be equally incorporated in the copolymers. Besides copolymerization in the particles, also copolymerization in the aqueous phase can take place which affects the formation of oligomeric radicals responsible for the entry of radicals into the particles. In describing copolymerization in emulsion polymerization, one can use the normal reactivity ratios in combination with the monomer feed ratios in the phase at hand (either water phase or particle phase). Most of the research works done were focused on the feed ratio of the monomers in the particle phase. This is because of the interest in the final product. But in case of water‐soluble monomers, where significant amount of polymerization already occurs in the water phase, feed ratios of monomers in the water phase have to be known. Even for less water‐soluble monomers, the feed ratios in the aqueous phase are important to know, related to entry of radicals. Therefore, to calculate feed ratios in water phase, solubilities of mixtures of monomers in this phase have been measured by using a UV‐Vis technique. It is shown that the solubility of one monomer is influenced by the presence of another monomer.
New Insights into the Chemistry of Oxovanadium(IV) Complexes with N4 Coordinating Ligands
Authors: Yadava Ashok Kumar , Yadav Hardeo Singh , Yadav Uma Shanker , Rao Devendra Pratap
Published: December 2012

The syntheses of new oxovanadium(IV) complexes having general formula [VO(mac)]SO4 have been carried out by using in situ method of preparation where vanadyl ion acts as kinetic template for the ligands derived by condensation of 2,2′-pyridil with 1,2-diaminopropane and 1,3-diaminopropane. The complexes were characterized by elemental analyses, molar conductance, magnetic moments, and spectral (infrared, electronic, and electron spin resonance) data. All the oxovanadium(IV) complexes are five coordinate wherein derived ligands act as tetradentate chelating agents.
Translational Research in Stem Cell Treatment of Neuromuscular Diseases
Authors: Orbay Hakan , Mizuno Hiroshi
Published: December 2012

Neuromuscular diseases are a heterogeneous group of diseases that lead to significant disability in effected individuals. Pharmacological treatments failed to provide any significant improvement to date. Recently, the introduction of stem cells into the field of health sciences raised the hopes for a new treatment for neuromuscular diseases. In theory, stem cells, owing to their multilineage differentiation capacity, could differentiate into myofibers and neurons and replace the degenerated cells leading to recovery of the patients. Results obtained from the preclinical studies supported this theory. However, clinical trials with stem cells could not meet the expectations mainly because of early mortality, limited migration, and differentiation of the implanted cells. Modification of the stem cells before implantation, such as introduction of deficient genes or commitment to a precursor cell line provided little improvement. The biggest barrier to overcome for a successful of stem cell treatment, which also should be the focus of the future studies, is to increase the functional integration of the donor cells with the recipient tissues. Understanding the underlying pathogenic mechanisms of the neuromuscular diseases is essential to achieve this goal.
Epigenetic Repression of miR-31 Disrupts Androgen Receptor Homeostasis and Contributes to Prostate Cancer Progression
Authors: Lin Pei-Chun , Chiu Ya-Lin , Banerjee Samprit , Park Kyung , Mosquera Juan Miguel , Giannopoulou Eugenia , Alves Pedro , Tewari Ashutosh K. , Gerstein Mark B. , Beltran Himisha , Melnick Ari M. , Elemento Olivier , Demichelis Francesca , Rubin Mark A.
Published: December 2012

Androgen receptor signaling plays a critical role in prostate cancer pathogenesis. Yet, the regulation of androgen receptor signaling remains elusive. Even with stringent androgen deprivation therapy, androgen receptor signaling persists. Here, our data suggest that there is a complex interaction between the expression of the tumor suppressor miRNA, miR-31, and androgen receptor signaling. We examined primary and metastatic prostate cancer and found that miR-31 expression was reduced as a result of promoter hypermethylation, and importantly, the levels of miR-31 expression were inversely correlated with the aggressiveness of the disease. As the expression of androgen receptor and miR-31 was inversely correlated in the cell lines, our study further suggested that miR-31 and androgen receptor could mutually repress each other. Upregulation of miR-31 effectively suppressed androgen receptor expression through multiple mechanisms and inhibited prostate cancer growth in vivo. Notably, we found that miR-31 targeted androgen receptor directly at a site located in the coding region, which was commonly mutated in prostate cancer. In addition, miR-31 suppressed cell-cycle regulators including E2F1, E2F2, EXO1, FOXM1, and MCM2. Together, our findings suggest a novel androgen receptor regulatory mechanism mediated through miR-31 expression. The downregulation of miR-31 may disrupt cellular homeostasis and contribute to the evolution and progression of prostate cancer. We provide implications for epigenetic treatment and support clinical development of detecting miR-31 promoter methylation as a novel biomarker. Cancer Res; 73(3); 1232–44. ©2012 AACR.
A Potent Combination of the Novel PI3K Inhibitor, GDC-0941, with Imatinib in Gastrointestinal Stromal Tumor Xenografts: Long-Lasting Responses after Treatment Withdrawal
Authors: Floris Giuseppe , Wozniak Agnieszka , Sciot Raf , Li Haifu , Friedman Lori , Van Looy Thomas , Wellens Jasmien , Vermaelen Peter , Deroose Christophe M. , Fletcher Jonathan A. , Debiec-Rychter Maria , Schöffski Patrick
Published: December 2012

Purpose: Oncogenic signaling in gastrointestinal stromal tumors (GIST) is sustained via PI3K/AKT pathway. We used a panel of six GIST xenograft models to assess efficacy of GDC-0941 as single agent or in combination with imatinib (IMA).

Experimental Design: Nude mice (n = 136) were grafted bilaterally with human GIST carrying diverse KIT mutations. Mice were orally dosed over four weeks, grouped as follows: (A) control; (B) GDC-0941; (C) imatinib, and (D) GDC+IMA treatments. Xenografts regrowth after treatment discontinuation was assessed in groups C and D for an additional four weeks. Tumor response was assessed by volume measurements, micro-PET imaging, histopathology, and immunoblotting. Moreover, genomic alterations in PTEN/PI3K/AKT pathway were evaluated.

Results: In all models, GDC-0941 caused tumor growth stabilization, inhibiting tumor cell proliferation, but did not induce apoptosis. Under GDC+IMA, profound tumor regression, superior to either treatment alone, was observed. This effect was associated with the best histologic response, a nearly complete proliferation arrest and increased apoptosis. Tumor regrowth assays confirmed superior activity of GDC+IMA over imatinib; in three of six models, tumor volume remained reduced and stable even after treatment discontinuation. A positive correlation between response to GDC+IMA and PTEN loss, both on gene and protein levels, was found.

Conclusion: GDC+IMA has significant antitumor efficacy in GIST xenografts, inducing more substantial tumor regression, apoptosis, and durable effects than imatinib. Notably, after treatment withdrawal, tumor regression was sustained in tumors exposed to GDC+IMA, which was not observed under imatinib. Assessment of PTEN status may represent a useful predictive biomarker for patient selection. Clin Cancer Res; 19(3); 620–30. ©2012 AACR.
Knockdown of PAK4 or PAK1 Inhibits the Proliferation of Mutant KRAS Colon Cancer Cells Independently of RAF/MEK/ERK and PI3K/AKT Signaling
Authors: Tabusa Hana , Brooks Teresa , Massey Andrew J.
Published: December 2012

The p21-activated kinase (PAK) serine/threonine kinases are important effectors of the small GTPases Rac and Cdc42, and play significant roles in controlling cell growth, motility, and transformation. Knockdown of PAK4 or PAK1 inhibited the proliferation of mutant KRAS or BRAF colon cancer cells in vitro. Dependence on PAK4 or PAK1 protein for colon cancer cell proliferation was independent of PAK4 or PAK1 protein expression levels. Mutant KRAS HCT116 colorectal cells were the most sensitive to PAK4 or PAK1 knockdown resulting in the potent inhibition of anchorage-dependent and -independent proliferation as well as the formation and proliferation of HCT116 colon cancer spheroids. This inhibition of proliferation did not correlate with inhibition of RAF/MEK/ERK or PI3K/AKT signaling. In HCT116 cells, knockdown of PAK4 or PAK1 caused changes to the actin cytoskeleton resulting in reduced basal spread and cell elongation and increased cell rounding. These cytoskeletal rearrangements seemed to be independent of LIMK/cofilin/paxillin phosphorylation. PAK4 or PAK1 knockdown initially induced growth arrest in HCT116 cells followed by cell death at later time points. Inhibition of the antiapoptotic proteins Bcl-2 and Bcl-XL with the pharmacologic inhibitor ABT-737 increased effector caspase activation and apoptosis, and reduced cell survival with PAK4 or PAK1 knockdown. These results support a role for the PAKs in the proliferation of mutant KRAS-driven colorectal carcinoma cells via pathways not involving RAF/MEK/ERK and PI3K/AKT signaling. Mol Cancer Res; 11(2); 109–21. ©2012 AACR.
miRNA-145 Targets v-ets Erythroblastosis Virus E26 Oncogene Homolog 1 to Suppress the Invasion, Metastasis, and Angiogenesis of Gastric Cancer Cells
Authors: Zheng Liduan , Pu Jiarui , Qi Teng , Qi Meng , Li Dan , Xiang Xuan , Huang Kai , Tong Qiangsong
Published: December 2012

Recent evidence shows that v-ets erythroblastosis virus E26 oncogene homolog 1 (Ets1) is implicated in tumor development and progression. However, the clinical potentials and underlying mechanisms of Ets1 in gastric cancer progression and metastasis remain largely unknown. In this study, Ets1 immunostaining was identified in 56 of 84 (66.7%) gastric cancer tissues, which was correlated with tumor invasion and metastasis. In gastric cancer specimens and cell lines, miRNA-145 (miR-145) was downregulated and inversely correlated with Ets1 expression. Bioinformatics analysis and luciferase reporter assay revealed that miR-145 directly targeted the 3′-untranslated region (3′-UTR) of Ets1 mRNA. Overexpression or knockdown of miR-145 responsively altered both the mRNA and protein levels of Ets1 and its downstream genes, matrix metalloproteinase (MMP-1)-1 and -9, in gastric cancer cell lines SGC-7901 and MKN-45. Ectopic expression of miR-145 suppressed the invasion, metastasis, and angiogenesis of SGC-7901 and MKN-45 cells in vitro and in vivo. In addition, the effects of miR-145 on Ets1 expression, migration, invasion, and angiogenesis were rescued by restoration of Ets1 expression in these cells. Furthermore, anti-miR-145 inhibitor promoted the migration, invasion, and angiogenesis, whereas siRNA-mediated Ets1 knockdown phenocopied the effects of miR-145 overexpression in gastric cancer cells. These results show that miR-145 suppresses Ets1 expression via the binding site in the 3′-UTR, thus inhibiting the invasion, metastasis, and angiogenesis of gastric cancer cells. Mol Cancer Res; 11(2); 182–93. ©2012 AACR.
Noncovalent Wild-type–Sparing Inhibitors of EGFR T790M
Authors: Lee Ho-June , Schaefer Gabriele , Heffron Timothy P. , Shao Lily , Ye Xiaofen , Sideris Steve , Malek Shiva , Chan Emily , Merchant Mark , La Hank , Ubhayakar Savita , Yauch Robert L. , Pirazzoli Valentina , Politi Katerina , Settleman Jeff
Published: December 2012

Approximately half of EGFR-mutant non–small cell lung cancer (NSCLC) patients treated with small-molecule EGFR kinase inhibitors develop drug resistance associated with the EGF receptor (EGFR) T790M “gatekeeper” substitution, prompting efforts to develop covalent EGFR inhibitors, which can effectively suppress EGFR T790M in preclinical models. However, these inhibitors have yet to prove clinically efficacious, and their toxicity in skin, reflecting activity against wild-type EGFR, may limit dosing required to effectively suppress EGFR T790M in vivo. While profiling sensitivity to various kinase inhibitors across a large cancer cell line panel, we identified indolocarbazole compounds, including a clinically well-tolerated FLT3 inhibitor, as potent and reversible inhibitors of EGFR T790M that spare wild-type EGFR. These findings show the use of broad cancer cell profiling of kinase inhibitor efficacy to identify unanticipated novel applications, and they identify indolocarbazole compounds as potentially effective EGFR inhibitors in the context of T790M-mediated drug resistance in NSCLC.

Significance: EGFR-mutant lung cancer patients who respond to currently used EGFR kinase inhibitors invariably develop drug resistance, which is associated with the EGFR T790M resistance mutation in about half these cases. We unexpectedly identified a class of reversible potent inhibitors of EGFR T790M that do not inhibit wild-type EGFR, revealing a promising therapeutic strategy to overcome T790M-associated drug-resistant lung cancers. Cancer Discov; 3(2); 168–81. ©2012 AACR.

See related commentary by Brewer and Pao, p. 138

This article is highlighted in the In This Issue feature, p. 125