bluuebunny/crossref_metadata_2025 huggingface dataset:
Ice-Sheet Dynamics
Authors: Schoof Christian , Hewitt Ian
Published: September 2012

We describe the development of mathematical models of ice sheets, focusing on underlying physics and the minimal components that successful models must contain. Our review describes the basic fluid dynamical ice-flow models currently in use; points out numerous poorly understood thermomechanical feedbacks in ice flow; and describes the current, often poorly constrained, state of models for ice-sheet sliding and subglacial drainage, as well as their role in ice-stream dynamics. We conclude with a survey of marine ice-sheet models, outlining recent developments of self-consistent free-boundary models and ongoing research into three-dimensional marine ice sheets.
Deglacial Origin of Barrier Reefs Along Low-Latitude Mixed Siliciclastic and Carbonate Continental Shelf Edges
Authors: Droxler André W. , Jorry Stéphan J.
Published: September 2012

Because the initial phase of barrier reef evolution is often buried under more recent phases of coralgal growth, the origins of modern barrier reefs have remained elusive. Direct observations on the nature of the substrate on top of which barrier reefs have developed are lacking, and simple questions about whether the substrate contributes to their overall linear morphology have remained unanswered. We present here a review dedicated to late-Quaternary shelf-edge deposition in tropical mixed siliciclastic-carbonate systems. These modern analogs are used to develop a quantitative understanding of shelf-edge barrier reef formation during different segments of relatively well-established sea-level cycles. The onset of rapid sea-level rise during early deglaciations, when siliciclastics were deposited along newly formed coasts at up-dip positions, provided opportune time windows for coralgal communities to establish themselves on top of maximum lowstand siliciclastic coastal deposits, such as beach ridges and lowstand shelf-edge deltas.
Molecular Mechanisms in Progressive Idiopathic Pulmonary Fibrosis
Authors: Steele Mark P. , Schwartz David A.
Published: September 2012

There is clear evidence that environmental exposures and genetic predisposition contribute to the pathogenesis of idiopathic pulmonary fibrosis (IPF). Cigarette smoking increases the risk of developing IPF several-fold, as do other exposures such as metal-fume and wood-dust exposure. Occupations that increase the risk of IPF are agricultural work, hairdressing, and stone polishing, supporting the role of environmental exposure in disease pathogenesis. Genetic predisposition to IPF is evident from its familial aggregation and the fact that pulmonary fibrosis develops in several rare genetic disorders. Mutations in surfactant proteins lead to pulmonary fibrosis and are associated with endoplasmic reticulum stress in alveolar type II epithelial cells. Mutations in telomerase have been found in several families with IPF, and shortened telomeres are found in sporadic cases of IPF. A common variant in mucin 5B predisposes to both familial and sporadic IPF and is present in the majority of cases, indicating sporadic IPF occurs in those with genetic predisposition.
Host Genetics of HIV Acquisition and Viral Control
Authors: Shea Patrick R. , Shianna Kevin V. , Carrington Mary , Goldstein David B.
Published: September 2012

Since the discovery of HIV as the cause of AIDS, numerous insights have been gained from studies of its natural history and epidemiology. It has become clear that there are substantial interindividual differences in the risk of HIV acquisition and course of disease. Meanwhile, the field of human genetics has undergone a series of rapid transitions that have fundamentally altered the approach to studying HIV host genetics. We aim to describe the field as it has transitioned from the era of candidate-gene studies and the era of genome-wide association studies (GWAS) to its current state in the infancy of comprehensive sequencing. In some ways the field has come full circle, having evolved from being driven almost exclusively by our knowledge of immunology, to a bias-free GWAS approach, to a point where our ability to catalogue human variation far outstrips our ability to biologically interpret it.
The Role of Anti-Inflammatory Drugs in Colorectal Cancer
Authors: Wang Dingzhi , DuBois Raymond N.
Published: September 2012

A large body of evidence indicates that genetic mutations, epigenetic changes, chronic inflammation, diet, and lifestyle are key risk factors for colorectal cancer (CRC). Prevention of CRC has long been considered a plausible approach for the population and individuals at high risk for developing this disease. A significant effort has been made in the development of novel drugs for both prevention and treatment over the past two decades. This review highlights recent advances in our understanding of the role of nonsteroidal anti-inflammatory drugs in CRC prevention and adjuvant treatment. Moreover, we focus on the molecular mechanisms underlying the antitumor effects of these drugs in CRC. The knowledge of how anti-inflammatory agents inhibit cancer formation and progression may provide a rationale for the development of more effective chemopreventive and chemotherapeutic agents with less toxicity.
Coping with Endoplasmic Reticulum Stress in the Cardiovascular System
Authors: Groenendyk Jody , Agellon Luis B. , Michalak Marek
Published: September 2012

The endoplasmic reticulum (ER) is a multifunctional intracellular organelle, a component of the cellular reticular network that allows cells to adjust to a wide variety of conditions. The cardiomyocyte reticular network is the ideal location of sensors for both intrinsic and extrinsic factors that disrupt energy and/or nutrient homeostasis and lead to ER stress, a disturbance in ER function. ER stress has been linked to both physiological and pathological states in the cardiovascular system; such states include myocardial infarction, oxygen starvation (hypoxia) and fuel starvation, ischemia, pressure overload, dilated cardiomyopathy, hypertrophy, and heart failure. The ER stress coping response (e.g., the unfolded protein response) is composed of discrete pathways that are controlled by a collection of common regulatory components that may function as a single entity involved in reacting to ER stress. These corrective strategies allow the cardiomyocyte reticular network to restore energy and/or nutrient homeostasis and to avoid cell death. Therefore, the identities of the ER stress corrective strategies are important targets for the development of therapeutic approaches for cardiovascular and other acquired disorders.
TRPA1: A Gatekeeper for Inflammation
Authors: Bautista Diana M. , Pellegrino Maurizio , Tsunozaki Makoto
Published: September 2012

Tissue damage evokes an inflammatory response that promotes the removal of harmful stimuli, tissue repair, and protective behaviors to prevent further damage and encourage healing. However, inflammation may outlive its usefulness and become chronic. Chronic inflammation can lead to a host of diseases, including asthma, itch, rheumatoid arthritis, and colitis. Primary afferent sensory neurons that innervate target organs release inflammatory neuropeptides in the local area of tissue damage to promote vascular leakage, the recruitment of immune cells, and hypersensitivity to mechanical and thermal stimuli. TRPA1 channels are required for neuronal excitation, the release of inflammatory neuropeptides, and subsequent pain hypersensitivity. TRPA1 is also activated by the release of inflammatory agents from nonneuronal cells in the area of tissue injury or disease. This dual function of TRPA1 as a detector and instigator of inflammatory agents makes TRPA1 a gatekeeper of chronic inflammatory disorders of the skin, airways, and gastrointestinal tract.
Self-Regulated Learning: Beliefs, Techniques, and Illusions
Authors: Bjork Robert A. , Dunlosky John , Kornell Nate
Published: September 2012

Knowing how to manage one's own learning has become increasingly important in recent years, as both the need and the opportunities for individuals to learn on their own outside of formal classroom settings have grown. During that same period, however, research on learning, memory, and metacognitive processes has provided evidence that people often have a faulty mental model of how they learn and remember, making them prone to both misassessing and mismanaging their own learning. After a discussion of what learners need to understand in order to become effective stewards of their own learning, we first review research on what people believe about how they learn and then review research on how people's ongoing assessments of their own learning are influenced by current performance and the subjective sense of fluency. We conclude with a discussion of societal assumptions and attitudes that can be counterproductive in terms of individuals becoming maximally effective learners.
Detection of Bacillus anthracis Spores Using Peptide Functionalized SERS-Active Substrates
Authors: Sengupta Atanu , Shende Chetan , Farquharson Stuart , Inscore Frank
Published: October 2012

The need for portable technologies that can rapidly identify biological warfare agents (BWAs) in the field remains an international priority as expressed at the 2011 Biological Weapons Convention. In recent years, the ability of surface-enhanced Raman spectroscopy (SERS) to rapidly detect various BWAs at very low concentrations has been demonstrated. However, in the specific case of Bacillus anthracis, differentiation at the species level is required since other bacilli are common in the environment, representing potential false-positive responses. To overcome this limitation, we describe the use of a peptide attached to the SERS-active metal that selectively binds Bacillus anthracis-Sterne as the target analyte. Using this approach, 109  B. anthracis-Sterne spores/mL produced an intense dipicolinic acid spectrum upon the addition of acetic acid, while the same concentration and treatment of B. cereus and B. subtilis did not.
Similarity Solutions of MHD Mixed Convection Flow with Variable Reactive Index, Magnetic Field, and Velocity Slip Near a Moving Horizontal Plate: A Group Theory Approach
Authors: Khan W. A. , Uddin Md. Jashim , Ismail A. I. Md.
Published: October 2012

The mixed convection of Newtonian fluid flow along a moving horizontal plate with higher‐order chemical reaction, variable concentration reactant, and variable wall temperature and concentration is considered. Velocity slip and the thermal convective boundary conditions are applied at the plate surface. The governing partial differential equations are transformed into similarity equations via dimensionless similarity transformations developed by one‐parameter continuous group method. The numerical solutions of the transformed ordinary differential equations are constructed for velocity, temperature and concentration functions, the skin friction factor, the rate of heat, and the rate of mass transfer using an implicit finite difference numerical technique. The investigated parameters are buoyancy parameters λ1, λ2, chemical reaction parameter K, suction/injection parameter fw, velocity slip parameter a convective heat transfer parameter γ, magnetic parameter M, Prandtl number Pr and Schmidt number, Sc. Comparison with results from the open literature shows a very good agreement.
Henstock-Kurzweil Integral Transforms
Authors: Sánchez-Perales Salvador , Mendoza Torres Francisco J. , Escamilla Reyna Juan A.
Published: October 2012

We show conditions for the existence, continuity, and differentiability of functions defined by , where is a function of bounded variation on with .
The Dabie Extensional Tectonic System: Structural Framework
Authors: Hou Quanlin , Zhang Hongyuan , Liu Qing , Li Jun , Wu Yudong
Published: September 2012

A previous study of the Dabie area has been supposed that a strong extensional event happened between the Yangtze and North China blocks. The entire extensional system is divided into the Northern Dabie metamorphic complex belt and the south extensional tectonic System according to geological and geochemical characteristics in our study. The Xiaotian-Mozitan shear zone in the north boundary of the north system is a thrust detachment, showing upper block sliding to the NNE, with a displacement of more than 56 km. However, in the south system, the shearing direction along the Shuihou-Wuhe and Taihu-Mamiao shear zones is tending towards SSE, whereas that along the Susong-Qingshuihe shear zone tending towards SW, with a displacement of about 12 km. Flinn index results of both the north and south extensional systems indicate that there is a shear mechanism transition from pure to simple, implying that the extensional event in the south tectonic system could be related to a magma intrusion in the Northern Dabie metamorphic complex belt. Two 40Ar-39Ar ages of mylonite rocks in the above mentioned shear zones yielded, separately, ~190 Ma and ~124 Ma, referring to a cooling age of ultrahigh-pressure rocks and an extensional era later.
Five-Phase Modular External Rotor PM Machines with Different Rotor Poles: A Comparative Simulation Study
Authors: Abdel-Khalik A. S.
Published: September 2012

The performance of fault-tolerant modular permanent magnet machines depends on the proper selection of the pole and slot numbers which result in negligible coupling between phases. The preferred slot and pole number combinations eliminate the effect of low-order harmonics in the stator magnetomotive force and thereby the vibration and stray loss are reduced. In this paper, three external rotor machines with identical machine dimensions are designed with different slots per phase per pole ratios. A simulation study is carried out using finite element analysis to compare the performance of the three machines in terms of machine torque density, ripple torque, core loss, and machine efficiency. A mathematical model based on the conventional-phase-model approach is also used for the comparative study. The simulation study is extended to depict machine performance under fault conditions.
Modelling Lake Ice Phenology with an Examination of Satellite-Detected Subgrid Cell Variability
Authors: Brown Laura C. , Duguay Claude R.
Published: September 2012

Lake ice was simulated for the province of Quebec, Canada, for both contemporary and future climate conditions using a one-dimensional thermodynamic ice model. The model was forced with NARR data (32 km) and both the daily IMS product (4 km) and the MODIS snow product (500 m) were assessed for their utility at determining lake ice phenology at the subgrid cell level (based on the 32 km NARR grid). Both products were useful for detecting ice-off; however, the MODIS product was advantageous for detecting ice-on, mainly due to the finer resolution and resulting spatial detail. The subgrid cell variability in ice-on/off dates was typically less than 2% of the mean, although it ranged up to 10% for some grid cells. The simulations were found to be within the satellite-detected subgrid cell variability: 62% of the time for ice-off and 80% of the time for ice-on. Forcing the model with future climate scenarios from the Canadian Regional Climate Model predicts the regional ice cover durations will decrease by up to 50 days from the current 1981–2010 means to the 2041–2070 means and decrease from 15 to nearly 100 days shorter from the current means to the 2071–2100 means.
Marked Regression of Left Ventricular Hypertrophy after Outflow Desobliteration in HOCM
Authors: Dimitriadis Zisis , van Buuren Frank , Bogunovic Nikola , Horstkotte Dieter , Faber Lothar
Published: October 2012

We present an HOCM patient in whom marked regression of left ventricular hypertrophy occurred within two years following outflow desobliteration by percutaneous septal ablation. Maximum wall thickness (initially documented by both echo and MRI) decreased from 34 mm to 22 mm (followup by echo only due to presence of the ICD), crossing the threshold value of 30 mm which was one of the risk markers that had triggered the primary prophylactic ICD implantation in this case prior to septal ablation.
Tribological Studies on AISI 1040 with Raw and Modified Versions of Pongam and Jatropha Vegetable Oils as Lubricants
Authors: Shashidhara Y. M. , Jayaram S. R.
Published: September 2012

The friction and wear tests on AISI 1040 are carried out under raw, modified versions of two nonedible vegetable oils Pongam (Pongamia pinnata) and Jatropha (Jatropha curcas) and also commercially available mineral oil using a pin-on-disc tribometer for various sliding distances and loads. A significant drop in friction and wear for AISI 1040 is observed under Pongam and Jatropha raw oil compared to mineral oil, for the complete tested sliding distance and load, increasing the potential of vegetable oil for tribological applications. Stribeck curves are also drawn to understand the regimes of lubrication. Both the vegetable oils showed a clear reduction in the boundary lubrication regimes, leading to an early start of full film lubrication.
Takotsubo or Stress Cardiomyopathy
Authors: Bounhoure J. P.
Published: September 2012

Many case reports have been published of reversible left ventricular dysfunction precipitated by sudden emotional stress. We have evaluated 10 women hospitalized for acute chest pain and dyspnea, mimicking an acute coronary syndrome, after a severe emotional trigger. Those patients, postmenopausal women, presented ST segment alterations on the EKG, minor elevations of cardiac enzymes, and biomarkers levels. At the coronarography there was not coronary thrombosis or severe stenosis, but the ventriculography showed wall motion abnormalities involving the left ventricular apex and midventricle, in the absence of significant obstructive coronary disease. The course was benign without complication, with a full recovery of left ventricular function in some weeks. These observations, like other reports, demonstrate the impact of emotional stress on left ventricular function and the risk of cardiovascular disease. The cause of this cardiomyopathy is still unknown, and several mechanisms have been proposed: catecholamine myocardial damage, microvascular spasm, or neural mediated myocardial stunning.
Normative Data for Bone Mass in Healthy Term Infants from Birth to 1 Year of Age
Authors: Gallo Sina , Vanstone Catherine A. , Weiler Hope A.
Published: October 2012

For over 2 decades, dual-energy X-ray absorptiometry (DXA) has been the gold standard for estimating bone mineral density (BMD) and facture risk in adults. More recently DXA has been used to evaluate BMD in pediatrics. However, BMD is usually assessed against reference data for which none currently exists in infancy. A prospective study was conducted to assess bone mass of term infants (37 to 42 weeks of gestation), weight appropriate for gestational age, and born to healthy mothers. The group consisted of 33 boys and 26 girls recruited from the Winnipeg Health Sciences Center (Manitoba, Canada). Whole body (WB) as well as regional sites of the lumbar spine (LS 1–4) and femur was measured using DXA (QDR 4500A, Hologic Inc.) providing bone mineral content (BMC) for all sites and BMD for spine. During the year, WB BMC increased by 200% (76.0±14.2versus227.0±29.7 g), spine BMC by 130% (2.35±0.42versus5.37±1.02 g), and femur BMC by 190% (2.94±0.54versus8.50±1.84 g). Spine BMD increased by 14% (0.266±0.044versus0.304±0.044 g/cm2) during the year. This data, representing the accretion of bone mass during the first year of life, is based on a representative sample of infants and will aid in the interpretation of diagnostic DXA scans by researchers and health professionals.
Morphostructural Damage in Food-Spoiling Bacteria due to the Lemon Grass Oil and Its Vapour: SEM, TEM, and AFM Investigations
Authors: Tyagi Amit Kumar , Malik Anushree
Published: October 2012

In this study, antimicrobial activity and morphostructural damages due to lemon grass oil (LGO) and its vapour (LGOV) againstEscherichia colistrains were investigated. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of LGO were determined by broth-dilution method to be 0.288 mg/mL and 0.567 mg/mL, respectively. Furthermore, the zone of inhibition (45 mm) due to the vapour phase antimicrobial efficacy evaluated using disc volatilization assay was compared with that using disc diffusion assay (i.e., 13.5 mm for the same dose of oil). The morphological and ultrastructural alterations in LGO- and LGOV-treatedE. colicells were studied using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and atomic-force microscopy (AFM). In SEM observation, LGO-treated cells appeared to be aggregated and partially deformed, while LGOV-treated cells lost their turgidity, and the cytoplasmic material completely leaked from the cells. In TEM observation, extensive intracytoplasmic changes and various abnormalities were observed in LGOV-treated cells more than LGO-treated cells. Significant variations in the height and root mean square values of untreated, LGO-, and LGOV-treatedE. colicells were noticed by AFM. Present results indicate that LGO is highly effective againstE. coliin vapour phase.
Complete Moment Convergence of Weighted Sums for Arrays of Rowwiseφ-Mixing Random Variables
Authors: Guo Ming Le
Published: September 2012

The complete moment convergence of weighted sums for arrays of rowwiseφ-mixing random variables is investigated. By using moment inequality and truncation method, the sufficient conditions for complete moment convergence of weighted sums for arrays of rowwiseφ-mixing random variables are obtained. The results of Ahmed et al. (2002) are complemented. As an application, the complete moment convergence of moving average processes based on aφ-mixing random sequence is obtained, which improves the result of Kim et al. (2008).
Experimental Investigation into the Control and Load Alleviation Capabilities of Articulated Winglets
Authors: Gatto A. , Bourdin P. , Friswell M. I.
Published: September 2012

An experimental investigation into the real-time flow and control characteristics of a flying wing with articulated winglets is described in this paper. The philosophy of the concept centres around the use of active, in-flight adjustment of each wing's winglet dihedral angle, both as a primary means of aircraft roll control (single winglet actuation) and though smaller equal and simultaneous winglet deflections, tailor and alleviate main wing load. Results presented in this paper do provide good evidence of the concept's ability to adequately perform both tasks, although for the current chosen wing/winglet configuration, roll control authority was unable to achieve, per unit of control surface deflection, the same level of performance set by modern aileron-based roll control methodologies.
Compact MIMO Microstrip Antennas for USB Dongle Operating in 2.5–2.7 GHz Frequency Band
Authors: Ssorin Vladimir , Artemenko Alexey , Maltsev Alexander , Sevastyanov Alexey , Maslennikov Roman
Published: September 2012

This paper considers design of microstrip MIMO antennas for an LTE/WiMAX USB dongle operating in the 2.5–2.7 GHz frequency band. The MIMO system includes two antenna elements with an additional requirement of high isolation between them that is especially difficult to realize due to size limitations of a USB dongle. Three approaches to achieve the needed system characteristics using microstrip PCB antennas are proposed. For the first design, high port-to-port isolation is achieved by using a decoupling techniques based on a direct connection of the antenna elements. For the second approach, high port-to-port isolation of the MIMO antenna system is realized by a lumped decorrelation capacitance between antenna elements feeding points. The third proposed antenna system does not use any special techniques, and high port-to-port isolation is achieved by using only the properties of a developed printed inverted-F antenna element. The designed MIMO antenna systems have the return loss S11and the insertion loss S21bandwidths of more than 200 MHz at the −8 dB level with the correlation coefficient lower than 0.1 and exhibit pattern diversity when different antenna elements are excited. Experimental measurements of the fabricated antenna systems proved the characteristics obtained from electromagnetic simulation.
Convexity Invariance of Fuzzy Sets under the Extension Principles
Authors: Qiu Dong , Zhang Weiquan
Published: October 2012

We discuss the convexity invariance of fuzzy sets under the extension principles. Particularly, we give a necessary and sufficient condition for a mapping to be an inverse *-convex transformation, and also obtain some sufficient conditions for a mapping to be an *-convex transformation. Two applications are given to illustrate the obtained results. Finally, we give some applications of the main results to the hyperstructure convexity invariance of type 2 fuzzy sets under hyperalgebra operations, and to the convexity invariance of fuzzy numbers under basic arithmetic operations.
Is the Macronutrient Intake of Formula-Fed Infants Greater Than Breast-Fed Infants in Early Infancy?
Authors: Hester Shelly N. , Hustead Deborah S. , Mackey Amy D. , Singhal Atul , Marriage Barbara J.
Published: September 2012

Faster weight gain early in infancy may contribute to a greater risk of later obesity in formula-fed compared to breast-fed infants. One potential explanation for the difference in weight gain is higher macronutrient intake in formula-fed infants during the first weeks of life. A systematic review was conducted using Medline to assess the macronutrient and energy content plus volume of intake in breast-fed and formula-fed infants in early infancy. All studies from healthy, term, singleton infants reporting values for the composition of breast milk during the first month of life were included. The energy content of colostrum (mean, SEM:53.6±2.5 kcal/100 mL), transitional milk (57.7±4.2 kcal/100 mL), and mature milk (65.2±1.1 kcal/100 mL) was lower than conventional infant formula (67 kcal/100 mL) on all days analyzed. The protein concentration of colostrum (2.5±0.2 g/100 mL) and transitional milk (1.7±0.1 g/100 mL) was higher than formula (1.4 g/100 mL), while the protein content of mature milk (1.3±0.1 g/100 mL) was slightly lower. Formula-fed infants consume a higher volume and more energy dense milk in early life leading to faster growth which could potentially program a greater risk of long-term obesity.
Preservation of Stability and Synchronization of a Class of Fractional‐Order Systems
Authors: Lugo-Peñaloza Armando Fabián , Flores-Godoy José Job , Fernández-Anaya Guillermo
Published: October 2012

We present sufficient conditions for the preservation of stability of fractional‐order systems, and then we use this result to preserve the synchronization, in a master‐slave scheme, of fractional‐order systems. The systems treated herein are autonomous fractional differential linear and nonlinear systems with commensurate orders lying between 0 and 2, where the nonlinear ones can be described as a linear part plus a nonlinear part. These results are based on stability properties for equilibria of fractional‐order autonomous systems and some similar properties for the preservation of stability in integer order systems. Some simulation examples are presented only to show the effectiveness of the analytic result.
Hypoglycemic Activity of Aqueous Extracts fromCatharanthus roseus
Authors: Vega-Ávila Elisa , Cano-Velasco José Luis , Alarcón-Aguilar Francisco J. , Fajardo Ortíz María del Carmen , Almanza-Pérez Julio César , Román-Ramos Rubén
Published: September 2012

Introduction.Catharanthus roseus(L.) is used in some countries to treat diabetes. The aim of this study was to evaluate the hypoglycemic activity of extracts from the flower, leaf, stem, and root in normal and alloxan-induced diabetic mice.Methods. Roots, leaves, flowers, and stems were separated to obtain organic and aqueous extracts. The blood glucose lowering activity of these extracts was determinate in healthy and alloxan-induced (75 mg/Kg) diabetic mice, after intraperitoneal administration (250 mg/Kg body weight). Blood samples were obtained and blood glucose levels were analyzed employing a glucometer. The data were statistically compared by ANOVA. The most active extract was fractioned. Phytochemical screen and chromatographic studies were also done.Results. The aqueous extracts fromC. roseusreduced the blood glucose of both healthy and diabetic mice. The aqueous stem extract (250 mg/Kg) and its alkaloid-free fraction (300 mg/Kg) significantly () reduced blood glucose in diabetic mice by 52.90 and 51.21%. Their hypoglycemic activity was comparable to tolbutamide (58.1%, ).Conclusions. The best hypoglycemic activity was presented for the aqueous extracts and by alkaloid-free stem aqueous fraction. This fraction is formed by three polyphenols compounds.
Pathogenic Role of Store-Operated and Receptor-Operated Ca2+ Channels in Pulmonary Arterial Hypertension
Authors: Fernandez Ruby A. , Sundivakkam Premanand , Smith Kimberly A. , Zeifman Amy S. , Drennan Abigail R. , Yuan Jason X.-J.
Published: September 2012

Pulmonary circulation is an important circulatory system in which the body brings in oxygen. Pulmonary arterial hypertension (PAH) is a progressive and fatal disease that predominantly affects women. Sustained pulmonary vasoconstriction, excessive pulmonary vascular remodeling, in situ thrombosis, and increased pulmonary vascular stiffness are the major causes for the elevated pulmonary vascular resistance (PVR) in patients with PAH. The elevated PVR causes an increase in afterload in the right ventricle, leading to right ventricular hypertrophy, right heart failure, and eventually death. Understanding the pathogenic mechanisms of PAH is important for developing more effective therapeutic approach for the disease. An increase in cytosolic free Ca2+ concentration ([Ca2+]cyt) in pulmonary arterial smooth muscle cells (PASMC) is a major trigger for pulmonary vasoconstriction and an important stimulus for PASMC migration and proliferation which lead to pulmonary vascular wall thickening and remodeling. It is thus pertinent to define the pathogenic role of Ca2+ signaling in pulmonary vasoconstriction and PASMC proliferation to develop new therapies for PAH. [Ca2+]cyt in PASMC is increased by Ca2+ influx through Ca2+ channels in the plasma membrane and by Ca2+ release or mobilization from the intracellular stores, such as sarcoplasmic reticulum (SR) or endoplasmic reticulum (ER). There are two Ca2+ entry pathways, voltage-dependent Ca2+ influx through voltage-dependent Ca2+ channels (VDCC) and voltage-independent Ca2+ influx through store-operated Ca2+ channels (SOC) and receptor-operated Ca2+ channels (ROC). This paper will focus on the potential role of VDCC, SOC, and ROC in the development and progression of sustained pulmonary vasoconstriction and excessive pulmonary vascular remodeling in PAH.
NaHSO4‐SiO2‐Promoted Solvent‐Free Synthesis of Benzoxazoles, Benzimidazoles, and Benzothiazole Derivatives
Authors: Kumar K. Ravi , Satyanarayana P. V. V. , Srinivasa Reddy B.
Published: September 2012

An efficient protocol has been developed for the preparation of a library of benzoxazole, benzimidazole, and benzothiazole derivatives from reactions of acyl chlorides with o‐substituted aminoaromatics in the presence of catalytic amount of silica‐supported sodium hydrogen sulphate under solvent‐free conditions. Simple workup procedure, high yield, easy availability, reusability, and use of ecofriendly catalyst are some of the striking features of the present protocol.
Hydrogen-Bonding Recognition-Induced Colorimetric Determination of Hydrazine Based on the Tryptophan Capped Gold Nanoparticles
Authors: Gao Wenhua , Xi Jing , Chen Yunsheng , Xiao Song , Wang Xingqing , Li Jun , Xiao Jincheng , Chen Yaowen
Published: October 2012

A simple, cost-effective, and rapid colorimetric method for hydrazine detection using tryptophan-caped gold nanoparticles (Trp-AuNPs) has been developed. Tryptophan (Trp) is a protein with reducibility and amino group which can reduce chloroauric acid (HAuCl4) to AuNPs and modify the surface of AuNPs simultaneously. The Trp-AuNPs could be used to quantitatively detect hydrazine and showed different responses to vary concentration of hydrazine in an aqueous solution based on the aggregation-induced color change of Trp-AuNPs. The real water sample analysis verified the conclusion. The sensitivity of the detection system was influenced by the size of AuNPs which is determined by the pH of the detection system, the concentration of Trp, and the react time. We found that higher temperature contributed to more rapidly results. The detection system can detect as low as 1 μM hydrazine. We expect our approach to have wide-ranging applications in the developing region for monitoring water quality in some areas.
An Ecofriendly and Stability‐Indicating HPLC Method for Determination of Permethrin Isomers: Application to Pharmaceutical Analysis
Authors: Afshar Minoo , Salkhordeh Niloufar , Rajabi Mehdi
Published: September 2012

A green, simple, and stability‐indicating RP‐HPLC method was developed for simultaneous determination of permethrin isomers in pharmaceutical preparations. The separation was based on a C18 analytical column (150 × 4.6 mm, i.d., 5 μm). The mobile phase consisted of ethanol: phosphoric acid solution (pH = 3) (67 : 33, v/v). The elution was carried out at 30°C temperature with a flow rate of 1.0 mL/min. Quantitation was achieved with UV detection at 215 nm. In forced degradation studies, the drug was subjected to oxidation, hydrolysis, photolysis, and heat. The method was validated for specificity, linearity, precision, accuracy, and robustness. The applied procedure was found to be linear in permethrin concentration range of 0.5–50 μg/mL with correlation coefficients of 0.9996 for each isomer. Precision was evaluated by replicate analysis in which % relative standard deviation (RSD) values for areas were found below 2.0. The recoveries obtained (99.24%–100.72%) ensured the accuracy of the developed method. The peaks of permethrin isomers well resolved from various degradation products as well as the pharmaceutical excipients. Accordingly, the proposed validated and sustainable procedure was proved to be proper for routine analyzing and stability studies of permethrin in pharmaceutical preparations.
Substituent Effects on Solvent‐Free Synthesis (MWAOS) of Dihydroquinazolinones by the Addition of Isatoic Anhydride to a Series of Phenyl‐Substituted N‐(Phenylmethylidene) Anilines
Authors: Mullasseril Abhilash
Published: September 2012

The present study concentrates on the synthesis of a series of dihydroquinazolinones by applying the green concept Microwave Assisted Organic Synthesis (MWAOS) with high atom economy. A series of phenyl‐substituted N‐(phenylmethylidene) anilines are coupled with isatoic anhydride using a microwave oven.
Contributions of Recent and Past Sexual Partnerships on Incident Human Papillomavirus Detection: Acquisition and Reactivation in Older Women
Authors: Rositch Anne F. , Burke Anne E. , Viscidi Raphael P. , Silver Michelle I. , Chang Kathryn , Gravitt Patti E.
Published: September 2012

Understanding the fraction of newly detected human papillomavirus (HPV) infections due to acquisition and reactivation has important implications on screening strategies and prevention of HPV-associated neoplasia. Information on sexual activity and cervical samples for HPV DNA detection using Roche Linear Array were collected semiannually for two years from 700 women ages 35 to 60 years. Incidence and potential fraction of HPV associated with new and lifetime sexual partnerships were estimated using Poisson regression. Cox frailty models were used to estimate hazard ratios (HR) for potential risk factors of incident HPV detection. Recent and lifetime numbers of sexual partners were both strongly associated with incident HPV detection. However, only 13% of incident detections were attributed to new sexual partners, whereas 72% were attributed to 5 or more lifetime sexual partners. Furthermore, 155 of 183 (85%) incident HPV detections occurred during periods of sexual abstinence or monogamy, and were strongly associated with cumulative lifetime sexual exposure [HR: 4.1, 95% confidence interval (CI): 2.0–8.4). This association increased with increasing age. These data challenge the paradigm that incident HPV detection is driven by current sexual behavior and new viral acquisition in older women. Our observation that most incident HPV infection was attributable to past, not current, sexual behavior at older ages supports a natural history model of viral latency and reactivation. As the more highly exposed baby-boomer generation of women with sexual debut after the sexual revolution transition to menopause, the implications of HPV reactivation at older ages on cervical cancer risk and screening recommendations should be carefully evaluated. Cancer Res; 72(23); 6183–90. ©2012 AACR.
Molecular Pathways: The Metabolic Regulator Estrogen-Related Receptor α as a Therapeutic Target in Cancer
Authors: Chang Ching-yi , McDonnell Donald P.
Published: September 2012

The estrogen-related receptor α (ERRα) is an orphan member of the nuclear receptor superfamily of transcription factors whose activity is regulated by the expression level and/or activity of its obligate coregulators, peroxisome proliferator-activated receptor γ coactivator-1 α and β (PGC-1α or PGC-1β). Under normal physiologic conditions, and in responding to different environmental stimuli, the ERRα/PGC-1 complex is involved in regulating metabolic homeostasis under conditions of high energy demand in brown adipocytes, proliferating T cells, and muscle. Interestingly, increased expression and activity of the ERRα/PGC-1 axis has also been shown to correlate with unfavorable clinical outcomes in both breast and ovarian tumors. The observation that ERRα activity is manifest in all breast tumor subtypes with particularly high activity being evident in ERα-negative, HER2-positive, and triple-negative breast cancers has raised significant interest in targeting this receptor for the treatment of those breast cancers for which therapeutic options are limited. Clin Cancer Res; 18(22); 6089–95. ©2012 AACR.
Outcomes of Phase II Clinical Trials with Single-Agent Therapies in Advanced/Metastatic Non–Small Cell Lung Cancer Published between 2000 and 2009
Authors: Janku Filip , Berry Donald A. , Gong Jing , Parsons Henrique A. , Stewart David J. , Kurzrock Razelle
Published: September 2012

Purpose: We analyzed the outcomes of single-agent phase II clinical trials in non–small cell lung cancer (NSCLC) to determine trial parameters that predicted clinical activity.

Exoerimental Design: Data on response rate (RR), progression-free survival (PFS), and overall survival (OS) from all English language, single-agent phase II trials in advanced/metastatic NSCLC indexed by PubMed (January 2000 through December 2009) were abstracted.

Results: A total of 143 single-agent phase II trials (7,701 patients) were identified. The median RR was 10%, PFS 2.8 months, and OS 7.6 months. RR and PFS correlated with OS (r = 0.46, P < 0.001, r = 0.52, P < 0.001, respectively) and RR correlated with PFS (r = 0.61, P < 0.001). Treatment arms enriched for patients with molecular targets had a higher median RR (48.8% vs. 9.7%, P = 0.005), longer median PFS (6 vs. 2.8 months, P = 0.005), and OS (11.3 vs. 7.5 months, P = 0.05) as compared with those of unselected patients. In multivariate analysis, only studies enriched for patients with molecular targets or including drugs that eventually gained FDA/EMA approval were associated with a higher RR, and longer PFS/OS.

Conclusions: In phase II trials in NSCLC, RR and PFS correlated with OS. Studies enriched for patients with putative molecular drug targets were associated with higher therapeutic benefit as compared with those of unselected populations. Clin Cancer Res; 18(22); 6356–63. ©2012 AACR.
Measurement of Tumor VEGF-A Levels with 89Zr-Bevacizumab PET as an Early Biomarker for the Antiangiogenic Effect of Everolimus Treatment in an Ovarian Cancer Xenograft Model
Authors: van der Bilt Arne R.M. , van Scheltinga Anton G.T. Terwisscha , Timmer-Bosscha Hetty , Schröder Carolien P. , Pot Linda , Kosterink Jos G.W. , van der Zee Ate G.J. , Lub-de Hooge Marjolijn N. , de Jong Steven , de Vries Elisabeth G.E. , Reyners Anna K.L.
Published: September 2012

Purpose: The mTOR pathway is frequently activated in ovarian cancers. mTOR inhibitors, such as everolimus, can reduce VEGF-A production by cancer cells. We investigated whether early everolimus treatment effects could be monitored by positron emission tomography (PET) with 89Zr-bevacizumab.

Experimental Design: The effect of everolimus on VEGF-A secretion was determined in a panel of human ovarian cancer cell lines and in A2780luc+ ovarian cancer cells xenografted subcutaneously in BALB/c mice. Mice received daily 10 mg/kg everolimus intraperitoneally (i.p.) for 14 days. PET scans with the tracer 89Zr-labeled bevacizumab were conducted before and after treatment. Ex vivo89Zr-bevacizumab biodistribution and correlative tissue analyses were conducted. Tumor VEGF-A levels were measured with ELISA and mean vascular density (MVD) was determined with immunohistochemistry.

Results: Everolimus treatment reduced VEGF-A levels in the supernatant of all cell lines. Everolimus lowered 89Zr-bevacizumab tumor uptake by 21.7% ± 4.0% [mean standardized uptake value (SUVmean) 2.3 ± 0.2 vs. 2.9 ± 0.2, P < 0.01]. Ex vivo biodistribution also showed lower tracer uptake in the tumors of treated as compared with control animals (7.8 ± 0.8%ID/g vs. 14.0 ± 1.7%ID/g, P < 0.01), whereas no differences were observed for other tissues. This coincided with lower VEGF-A protein levels in tumor lysates in treated versus untreated tumors (P = 0.04) and reduced MVD (P < 0.01).

Conclusion: Tumor VEGF-A levels are decreased by everolimus. 89Zr-bevacizumab PET could be used to monitor tumor VEGF-A levels as an early biomarker of the antiangiogenic effect of mTOR inhibitor therapy. Clin Cancer Res; 18(22); 6306–14. ©2012 AACR.
Probiotic Mechanisms of Action
Authors: Bermudez-Brito Miriam , Plaza-Díaz Julio , Muñoz-Quezada Sergio , Gómez-Llorente Carolina , Gil Angel
Published: October 2012

Probiotics are live microorganisms that provide health benefits to the host when ingested in adequate amounts. The strains most frequently used as probiotics include lactic acid bacteria and bifidobacteria. Probiotics have demonstrated significant potential as therapeutic options for a variety of diseases, but the mechanisms responsible for these effects have not been fully elucidated yet. Several important mechanisms underlying the antagonistic effects of probiotics on various microorganisms include the following: modification of the gut microbiota, competitive adherence to the mucosa and epithelium, strengthening of the gut epithelial barrier and modulation of the immune system to convey an advantage to the host. Accumulating evidence demonstrates that probiotics communicate with the host by pattern recognition receptors, such as toll-like receptors and nucleotide-binding oligomerization domain-containing protein-like receptors, which modulate key signaling pathways, such as nuclear factor-ĸB and mitogen-activated protein kinase, to enhance or suppress activation and influence downstream pathways. This recognition is crucial for eliciting measured antimicrobial responses with minimal inflammatory tissue damage. A clear understanding of these mechanisms will allow for appropriate probiotic strain selection for specific applications and may uncover novel probiotic functions. The goal of this systematic review was to explore probiotic modes of action focusing on how gut microbes influence the host.
Readthrough Strategies for Therapeutic Suppression of Nonsense Mutations in Inherited Metabolic Disease
Authors: Pérez B. , Rodríguez-Pombo P. , Ugarte M. , Desviat L.R.
Published: October 2012

Inherited metabolic diseases (IMDs) belong to the group of rare diseases due to their low individual prevalence. Most of them are inherited in autosomal recessive fashion and represent good candidates for novel therapeutical strategies aimed at recovering partial enzyme function as they lack an effective treatment, and small levels of enzymatic activity have been shown to be associated with improved outcome and milder phenotypes. Recently, a novel therapeutic approach for genetic diseases has emerged, based on the ability of aminoglycosides and other compounds in allowing translation to proceed through a premature termination codon introduced by a nonsense mutation, which frequently constitute a significant fraction of the mutant alleles in a population. In this review we summarize the essentials of what is known as suppression therapy, the different compounds that have been identified by high-throughput screens or developed using a medicinal chemistry approach and the preclinical and clinical trials that are being conducted in general and in the field of IMDs in particular. Several IMDs have shown to be good models for evaluating readthrough compounds using patients’ cells carrying nonsense mutations, monitoring for an increase in functional recovery and/or enzyme activity. Overall, the positive results obtained indicate the feasibility of the approach for different diseases and although the levels of protein function reached are low, they may be enough to alleviate the consequences of the pathology. Nonsense suppression thus represents a potential therapy or supplementary treatment for a number of IMD patients encouraging further clinical trials with readthrough drugs with improved functionality and low toxicity.
Public Opinion at the Macro Level
Authors: Erikson Robert S.
Published: October 2012

My book “The Macro Polity,” coauthored with Michael B. MacKuen and James A. Stimson and published in 2002, depicts the dynamics of public opinion and electoral politics in the United States at the macro level; the analysis is based on micro-level foundations of micro-level political behavior. This essay presents the book's main arguments, in some instances extending the analysis beyond its original 1956–1996 time frame to incorporate data from the George W. Bush administration. The central thesis is that there is more rationality and predictability to American politics when viewed in the aggregate than one might infer from considering only the limited political awareness of the average citizen.
Latino Public Opinion & Realigning the American Electorate
Authors: Segura Gary M.
Published: October 2012

The growth and significance of the Latino electorate raises important questions about its preferences, identity, and impact. In this essay, I explore three facets of Latino public opinion and offer thoughts regarding their political impact. First, I demonstrate that Latino core beliefs about the role of government are progressive. Second, I explore the ways in which national origin, nativity, and generational status reveal important differences in how Latinos think about and participate in politics; I caution against over-interpreting the importance of these differences. Finally, I offer evidence that Latino panethnic identity is sufficiently developed to constitute a political “group.” Given that this segment in the American electorate is increasingly unified and demonstrably left of center, I suggest that the growth of the Latino population and electorate could have substantial electoral and social impact.