bluuebunny/crossref_metadata_2025 huggingface dataset:
Estrategias de aprendizaje en estudiantes de odontología de una universidad pública en Cartagena, Colombia / Learning Strategies among Dental Students from a Public University in Cartagena, Colombia
Authors: Hernández Álvarez Arlteh Sandry , Torres Ortega Fernán , Fang Mercado Luis Carlos , Díaz-Caballero Antonio José
Published: December 2017

ABSTRACT. Background: Predoctoral education requires student dedication to meet academic demands and learning goals with quality. University professors often complain that students do not regulate their learning strategies and are unable to act autonomously in their professional training. Purpose: To analyze the use of self-regulated learning in dental students at a Colombian public university. Methods: A descriptive study was carried out using Lindner et al.’s Self-Regulatory Learning Inventory, 4.01 version. The inventory includes four training areas (executive, cognitive, motivation, and environment control) among fourth semester dental students (sophomores) of University of Cartagena in Colombia. Results: The average use of self-regulated learning by the dental students was low. Furthermore, the analysis shows that the score in the scale (60-119) leads to a deficient level of learning (p<0,05). Conclusions: Marked weaknesses in the group of students intervened were identified who, in some cases, did not meet adequate self-regulated learning levels for their current year of study.

 
Evaluación del efecto del plasma rico en plaquetas en diferentes tiempos y concentraciones sobre la viabilidad de fibroblastos de ligamento periodontal y osteoblastos / Evaluation of Platelet-Rich Plasma Effect at different times and concentrations ...
Authors: Acosta Gómez Adriana Paola , Gutiérrez Prieto Sandra Janeth , Bedoya Mejía María Alexandra , García Robayo Dabeiba Adriana , Moreno Serrano Ximena Edilia
Published: December 2017

ABSTRACT. Background: Growth factors used in health treatments can be obtained from a first-generation source called platelet-rich plasma. The variety of protocols to prepare PRP produces variable results regarding PRP activation time and its effects on cell proliferation and viability. Purpose: To evaluate proliferation and cell viability of periodontal ligament fibroblasts and osteoblasts stimulated with PRP in several concentrations and times after PRP activation. Methods: An in vitro study was carried out using periodontal ligament fibroblast and osteoblast cell cultures. PRP from venous blood of a healthy adult was prepared through centrifugation and activated with 10 % CaCl2. The effect on cell proliferation after application of 1 %, 3 %, and 5% PRP and platelet-poor plasma was evaluated at 0, 12, 24, 48, and 72 hours after activation through MTS. The control group consisted of culture that did not receive any treatment. Data were analyzed using Chi square, Fisher, and McNemar tests. Results: The cell viability assay showed statistically significant differences between the experimental and the control groups. Cell viability increased in cells treated with 5 % PRP 24 hours after activation (p=0.05). Conclusions: Fibroblast and osteoblast cell lines tended to be more viable 24 hours after activation with 5% PRP.
Estudio in vitro de la erosión dental asociada al chimó / In Vitro Study of Dental Erosion associated to Chimo
Authors: Febres Giordano Néstor , Gilioli Medina Paola , Olávez Cepeda Daniela , Omaña Cepeda Carlos , Solórzano Navarro Eduvigis
Published: December 2017

ABSTRACT. Background: In Venezuela, chimó is a blackish goo derived from tobacco leaf. Its consumption has been associated with systemic and oral diseases. Purpose: To identify in vitro dental erosion associated to chimó exposure. Methods: The sample consisted of 30 teeth that were assigned 10 to the negative control group, another 10 to the positive control group, and 10 to the experimental group, which were exposed respectively to artificial saliva, Coca-Cola® light, and chimó for 20 weeks. Tooth surfaces were analyzed clinically and structurally, the latter through scanning electron microscope. Results: Clinical observations showed surface color change in the negative control group; color change and surface gloss loss in the positive control group; color and surface changes in the experimental group (p=0.000). Ultrastructural analysis showed no enamel surface alterations in the negative control group. Acid etching scale values were 4 for the positive control group and 3-4 for the experimental group. The latter had signs of enamel erosion. In terms of severity of damage, the experimental group was type 1, that is, enamel loss without involving dentin. Conclusion: Under these experimental conditions, chimó caused clinical and ultrastructural enamel surface loss with type 3-4 erosion patterns, and type 1 severity.
Phytoseiid mites (Acari: Mesostigmata: Phytoseiidae) associated with Cerrado biome plants in Brazil, with description of a new species
Authors: Demite Peterson Rodrigo , Dias Monique Andrade , Cavalcante Ana Cristina Cerqueira , Ramos Marcus Vinícius Vieitas , Lofego Antonio Carlos
Published: December 2017

A survey of plants in 24 areas of the Cerrado biome in the states of Goiás and Minas Gerais (Brazil) revealed a total of 34 species of phytoseiid mites belonging to 16 genera and three subfamilies of the Phytoseiidae. A new species, Neoseiulus goiano n. sp., is described and illustrated. Morphological information is provided for the species collected in this study.
Dicarboxylic acids analyzed by time-of-flight secondary ions mass spectrometry. Part III: Pentanedioic acid
Authors: Trindade Gustavo F. , Ferreira Jose M. , Abel Marie-Laure , Baker Mark A. , Watts John F.
Published: December 2017

Time-of-flight secondary ion mass spectrometry was carried out to analyze a commercially available butanedioic acid (succinic acid) powder. Positive and negative polarity ion spectra were obtained using a 25 keV Bi3+ ion beam rastered over areas of 50 × 50 μm2. The main observed fragments were the protonated molecule [M+H]+ at 119 Da and the deprotonated molecule [M-H]− at 117 Da with their respective oligomers.
Analytical model for predicting edge diffraction in the time domain
Authors: Menounou Penelope , Nikolaou Petros
Published: December 2017

A time domain model for predicting diffraction around half planes is presented. The model renders the directive line source model [Menounou, Busch-Vishniac, and Blackstock, J. Acoust. Soc. Am. 107, 2973–2986 (2000)] valid for times long after the diffracted signal arrival and for receivers close to the shadow boundaries, where it was not valid before. The presented model unifies diffraction by plane, cylindrically and spherically spreading incident signals (being exact for plane and approximate for cylindrical/spherical) and models diffraction as radiation from a directional line source. The terms describing the directivity and the line-source radiation are appropriately modified to handle diffraction by wedges and finite-length edges, respectively. The investigation of the derived formulation leads to (i) definition of universal parameters and quantities for the study of time diffraction, (ii) derivation of a generator curve that embodies the diffracted signals at any source–receiver configuration, and (iii) derivation of similarity conditions that determine how fast/slow diffraction evolves depending on the receiver location and that provide considerable computational benefit compared to direct computations. Furthermore, three time stages in every diffracted signal are identified, which allows a priori estimation of the diffracted signal characteristics based on the incident signal duration. Finally, the model is successfully applied to sonic boom diffraction on buildings.
Satellites trace Afghanistan's lost empires
Authors: Lawler Andrew
Published: December 2017

U.S.-Afghan partnership spots ancient sites by the thousands, a first step to protection.
Ice-shrouded life sees daylight
Authors: Reese April
Published: December 2017

Antarctic expedition will probe ecosystem exposed by calving of massive iceberg.
Breaking the deadlock on ivory
Authors: Biggs Duan , Holden Matthew H. , Braczkowski Alex , Cook Carly N. , Milner-Gulland E. J. , Phelps Jacob , Scholes Robert J. , Smith Robert J. , Underwood Fiona M. , Adams Vanessa M. , Allan James , Brink Henry , Cooney Rosie , Gao Yufang , Hutton Jon , Macdonald-Madden Eve , Maron Martine , Redford Kent H. , Sutherland William J. , Possingham Hugh P.
Published: December 2017

An iterative process that recognizes different value systems may help to protect elephants
Structural basis of membrane disruption and cellular toxicity by α-synuclein oligomers
Authors: Fusco Giuliana , Chen Serene W. , Williamson Philip T. F. , Cascella Roberta , Perni Michele , Jarvis James A. , Cecchi Cristina , Vendruscolo Michele , Chiti Fabrizio , Cremades Nunilo , Ying Liming , Dobson Christopher M. , De Simone Alfonso
Published: December 2017

A structural look at α-synuclein oligomers

Fibrillar aggregates of the protein α-synuclein (αS) are the major constituents of Lewy bodies in Parkinson's disease. However, small oligomers that accumulate during the process of fibril formation are thought to cause the neuronal toxicity associated with the onset and progression of Parkinson's disease. Little is known about the detailed structural properties of αS oligomers and the molecular mechanisms that lead to their toxicity. Fusco
et al.
report the structural characterization of two forms of αS oligomers, which elucidates the fundamental structural elements giving rise to neuronal toxicity.

Science
, this issue p.
1440
Purcell effect for active tuning of light scattering from semiconductor optical antennas
Authors: Holsteen Aaron L. , Raza Søren , Fan Pengyu , Kik Pieter G. , Brongersma Mark L.
Published: December 2017

Tuning the scattering of light

The development of nanophotonic technology relies on the ability to control and manipulate light at the nanometer scale. Most devices developed to date have been passive structures or have shown only modest changes in optical properties under an external stimulus. Holsteen
et al.
tuned the resonant scattering wavelength of silicon nanowires across the entire visible spectrum simply by adjusting the height of the nanowire above a metallic mirror. This nano-electromechanical system illustrates the potential for developing active optical platforms.

Science
, this issue p.
1407
Improving regulation of microbiota transplants
Authors: Hoffmann Diane , Palumbo Francis , Ravel Jacques , Roghmann Mary-Claire , Rowthorn Virginia , von Rosenvinge Erik
Published: December 2017

Policy should balance safety, efficacy, access, and research
Arthur C. Clarke at 100
The Exploration of Space
Arthur C. Clarke
Harper & Brothers Publishers, 1951.
Childhood's End
Arthur C. Clarke
Ballantine Books, 1953.
Authors: Kilgore De Witt Douglas
Published: December 2017

Good news for the age of anxiety
Speeding up crystallization
Authors: Akola J. , Jones R. O.
Published: December 2017

Chemical insights from simulations help to design a phase-change material that can crystallize in less than a nanosecond
Fotis Kafatos (1940–2017)
Authors: Nowotny Helga
Published: December 2017

Prominent biologist and founding president of the European Research Council
Streptococcus sanguinis Noncoding
cia
-Dependent Small RNAs Negatively Regulate Expression of Type IV Pilus Retraction ATPase PilT and Biofilm Formation
Authors: Ota Chiaki , Morisaki Hirobumi , Nakata Masanobu , Arimoto Takafumi , Fukamachi Haruka , Kataoka Hideo , Masuda Yoshiko , Suzuki Noriyuki , Miyazaki Takashi , Okahashi Nobuo , Kuwata Hirotaka
Published: December 2017

Small noncoding RNAs (sRNAs) have been identified as important regulators of gene expression in various cellular processes.
cia
-dependent small RNAs (csRNAs), a group of sRNAs that are controlled by the two-component regulatory system CiaRH, are widely conserved in streptococci, but their targets have been identified only in
Streptococcus pneumoniae
.
Streptococcus sanguinis
, a pioneer colonizer of teeth and one of the most predominant bacteria in the early oral biofilm, has been shown to have six csRNAs. Using computational target prediction and the luciferase reporter assay, we identified
pilT
, a constituent of the type IV pilus operon, as a negative regulatory target for one of the csRNAs, namely, csRNA1-1, in
S. sanguinis
. RNA-RNA electrophoretic mobility shift assay using a nucleotide exchange mutant of csRNA1-1 revealed that csRNA1-1 binds directly to
pilT
mRNA. In addition, csRNA1-1 and csRNA1-2, a putative gene duplication product of csRNA1-1 that is tandemly located in the
S. sanguinis
genome, negatively regulated
S. sanguinis
biofilm formation. These results suggest the involvement of csRNAs in the colonization step of
S. sanguinis
.
Indoor air pollution and cognitive function among older Mexican adults
Authors: Saenz Joseph L , Wong Rebeca , Ailshire Jennifer A
Published: December 2017

Background

A growing body of research suggests exposure to high levels of outdoor air pollution may negatively affect cognitive functioning in older adults, but less is known about the link between indoor sources of air pollution and cognitive functioning. We examine the association between exposure to indoor air pollution and cognitive function among older adults in Mexico, a developing country where combustion of biomass for domestic energy remains common.

Method

Data come from the 2012 Wave of the Mexican Health and Aging Study. The analytic sample consists of 13 023 Mexican adults over age 50. Indoor air pollution is assessed by the reported use of wood or coal as the household’s primary cooking fuel. Cognitive function is measured with assessments of verbal learning, verbal recall, attention, orientation and verbal fluency. Ordinary least squares regression is used to examine cross-sectional differences in cognitive function according to indoor air pollution exposure while accounting for demographic, household, health and economic characteristics.

Results

Approximately 16% of the sample reported using wood or coal as their primary cooking fuel, but this was far more common among those residing in the most rural areas (53%). Exposure to indoor air pollution was associated with poorer cognitive performance across all assessments, with the exception of verbal recall, even in fully adjusted models.

Conclusions

Indoor air pollution may be an important factor for the cognitive health of older Mexican adults. Public health efforts should continue to develop interventions to reduce exposure to indoor air pollution in rural Mexico.
Level of moderate-intensity leisure-time physical activity and reduced mortality in middle-aged and elderly Chinese
Authors: Liu Ying , Wen Wanqing , Gao Yu-Tang , Li Hong-Lan , Yang Gong , Xiang Yong-Bing , Shu Xiao-Ou , Zheng Wei
Published: December 2017

Background

Few studies have prospectively evaluated the association of leisure-time physical activity (LTPA) with mortality in Asians, who are more susceptible to insulin resistance than their Caucasian counterparts.

Methods

Data from two large prospective cohort studies conducted in Shanghai were evaluated. After excluding participants who had a history of cancer, coronary heart disease or stroke at baseline, or who died within the first 3 years after study enrolment, 53 839 men and 66 888 women, followed for an average of 9.2 and 14.7 years, respectively, remained for the study.

Results

Compared with those who reported no exercise, a reduction in mortality with an HR of 0.86 (95% CI 0.80 to 0.93) was observed in those who regularly engage in moderate-intensity LTPA, even those who reported an LTPA level lower than the minimum amount recommended by the current physical activity guidelines (150 min or 7.5 metabolic equivalent hours per week). The association between moderate-intensity exercise and mortality followed a dose–response pattern until the amount of LTPA reached 3–5 times the recommended minimum level. A similar pattern of association was observed for cause-specific mortality due to cardiovascular disease (CVD), cancer or other causes.

Conclusion

Regular participation in moderate-intensity LTPA was associated with reduced mortality, particularly CVD mortality, even when the LTPA was below the minimum level recommended by current guidelines. Increasing the amount of moderate-intensity LTPA was associated with further risk reduction up to a potential threshold of 3–5 times the recommended minimum.
Submicron probes for scanning electrochemical microscopy
Authors: Li Michelle S.M. , Filice Fraser P. , Ding Zhifeng
Published: December 2017

To improve the spatial resolutions of scanning electrochemical microscopy (SECM) imaging, the laser-pulled submicron electrode fabrication method was explored in this work. Manual polishing of a laser-pulled Pt nanoelectrode exposed a Pt tip diameter of 250 nm with a ratio of the tip glass to exposed Pt disc (RG) of 30. This fabricated submicron probe was then utilized to study the electrochemical functionality of an independently addressable microband electrodes (IAME) sample using SECM. In the constant imaging mode of SECM, where the probe is scanned linearly across the sample at a fixed z position, SECM demonstrated higher resolution than that of the conventional micrometer electrodes when the feedback currents from the Pt and glass microbands were characterized. In addition, the depth scan imaging mode of SECM was also used to extract experimental horizontal line scans and probe approach curves for analysis. Three-dimensional (3D) simulations of the IAME–SECM probe experiments were explored for the first time to quantify the tip-to-sample distances, tilt angle of the sample (or electrode), and height of the Pt microbands. The experimentally characterized height was found to be similar to manufacturer specification (125 nm vs 110 nm). Furthermore, the more computationally demanding 3D simulation of the true IAME sample geometry (110 nm height of the Pt microbands) revealed minimal difference in feedback behaviours in comparison with the idealized flat geometry. The removal of this simulation complexity was proved to be sufficient for SECM analysis of the IAME sample by a 250 nm Pt probe, which greatly saves computation resources.
Motivation and implementation of traffic management strategies to reduce motor vehicle emissions in Canadian cities
Authors: Bigazzi Alexander Y. , Mohamed Amr
Published: December 2017

There is a pressing need to reduce pollution emissions from transportation and consequent negative effects on air quality, public health, and the global climate. Diverse traffic management strategies have been proposed and undertaken with primary or secondary goals of reducing motor vehicle emissions. The objective of this paper is to investigate the motivation and implementation of traffic management strategies to reduce motor vehicle emissions, with a focus on moderate-scale local and regional strategies that are broadly applicable. Public documents from 44 local, regional, and provincial government entities across Canada were reviewed for information regarding the implementation of 22 traffic management strategies. Results show that different levels of government are involved in the implementation of different types of strategies, and with a different mix of traffic, safety, and environmental motivations. Regional governments more frequently cite environmental motivations and appear to be most interested in the two strategies with the strongest empirical evidence of air quality benefits: area road pricing and low emission zones. Strengthening regional transportation planning and better integrating it with municipal and provincial planning could potentially increase the implementation of effective sustainable traffic management strategies in Canada. Additional opportunities exist through emphasizing the potential environmental co-benefits of strategies such as road pricing, speed management, and traffic signal and intersection control improvements.
Evolution as an ecosystem process: insights from genomics
Authors: Matthews Blake , Best Rebecca J. , Feulner Philine G.D. , Narwani Anita , Limberger Romana
Published: December 2017

Evolution is a fundamental ecosystem process. The study of genomic variation of organisms can not only improve our understanding of evolutionary processes, but also of contemporary and future ecosystem dynamics. We argue that integrative research between the fields of genomics and ecosystem ecology could generate new insights. Specifically, studies of biodiversity and ecosystem functioning, evolutionary rescue, and eco-evolutionary dynamics could all benefit from information about variation in genome structure and the genetic architecture of traits, whereas genomic studies could benefit from information about the ecological context of evolutionary dynamics. We propose new ways to help link research on functional genomic diversity with (reciprocal) interactions between phenotypic evolution and ecosystem change. Despite numerous challenges, we anticipate that the wealth of genomic data being collected on natural populations will improve our understanding of ecosystems.
A Property of upper level sets of Lelong numbers of currents on ℙ2
Authors: Heffers James J.
Published: December 2017

Let [Formula: see text] be a positive closed current of bidimension [Formula: see text] with unit mass on the complex projective space [Formula: see text]. For [Formula: see text] and [Formula: see text] we show that if [Formula: see text] has four points with Lelong number at least [Formula: see text], the upper level set [Formula: see text] of points of [Formula: see text] with Lelong number strictly larger than [Formula: see text] is contained within a conic with the exception of at most one point.
FINANCIAL MARKETS WITH NO RISKLESS (SAFE) ASSET
Authors: RACHEV SVETLOZAR T. , STOYANOV STOYAN V. , FABOZZI FRANK J.
Published: December 2017

We study markets with no riskless (safe) asset. We derive the corresponding Black–Scholes–Merton option pricing equations for markets where there are only risky assets which have the following price dynamics: (i) continuous diffusions; (ii) jump-diffusions; (iii) diffusions with stochastic volatilities, and; (iv) geometric fractional Brownian and Rosenblatt motions. No-arbitrage and market-completeness conditions are derived in all four cases.
Association between Two Resistin Gene Polymorphisms and Metabolic Syndrome in Jilin, Northeast China: A Case-Control Study
Authors: Fu Yingli , Yu Yaqin , Wu Yanhua , You Yueyue , Zhang Yangyu , Kou Changgui
Published: December 2017

Metabolic syndrome (MetS) is a significant health care problem worldwide and is characterized by increased fasting glucose and obesity. Resistin is a protein hormone produced both by adipocytes and immunocompetent cells, including those residing in adipose tissue, and is believed to modulate glucose tolerance and insulin action. This study examined the association of resistin gene polymorphisms, rs1862513 and rs3745368, and related haplotypes with the development of metabolic syndrome in a Han Chinese population. This case-control study was performed on 3792 subjects, including 1771 MetS cases and 2021 healthy controls from the Jilin province of China. Metabolic syndrome was defined according to the criteria of the International Diabetes Federation (IDF). Logistic regression analysis was used to estimate the relationship between gene polymorphism and MetS. Our results showed that there were no significant associations between MetS and the genotype distributions in four kinds of inheritance models, allele frequencies, and related haplotypes of resistin gene polymorphisms rs1862513 and rs3745368 (allpvalues > 0.05). Based on our study findings, we concluded that mutations in resistin genes are not associated with the presence of MetS in a Han Chinese population from Jilin province in China.
Quantitative Proteomic Analysis of Hepatic Tissue of T2DM Rhesus Macaque
Authors: Du Tingfu , Lu Shuaiyao , Jiang Qinfang , Li Yun , Ma Kaili
Published: December 2017

Type 2 diabetes mellitus (T2DM) is a metabolic disorder that severely affects human health, but the pathogenesis of the disease remains unknown. The high-fat/high-sucrose diets combined with streptozotocin- (STZ-) induced nonhuman primate animal model of diabetes are a valuable research source of T2DM. Here, we present a study of a STZ rhesus macaque model of T2DM that utilizes quantitative iTRAQ-based proteomic method. We compared the protein profiles in the liver of STZ-treated macaques as well as age-matched healthy controls. We identified 171 proteins differentially expressed in the STZ-treated groups, about 70 of which were documented as diabetes-related gene in previous studies. Pathway analyses indicated that the biological functions of differentially expressed proteins were related to glycolysis/gluconeogenesis, fatty acid metabolism, complements, and coagulation cascades. Expression change in tryptophan metabolism pathway was also found in this study which may be associations with diabetes. This study is the first to explore genome-wide protein expression in hepatic tissue of diabetes macaque model using HPLC-Q-TOF/MS technology. In addition to providing potential T2DM biomarkers, this quantitative proteomic study may also shed insights regarding the molecular pathogenesis of T2DM.
Identification of Pyrotechnic Shock Sources for Shear Type Explosive Bolt
Authors: Li Yanhua , Xiong Shihui , Li Yuan , Li Xiaogang , Wen Yuquan , Mu Huina , Li Zhiliang
Published: December 2017

To identify the shock generated sources of shear type explosive bolt, five kinds of explosive bolts with different states, including high preload, low preload, no preload, no piston shear, and only propellant combustion, were designed. The decoupling of four kinds of shock sources, including the collision of propellant combustion, piston shear weak surface, end of piston stroke, and preload release, was realized. Their acceleration responses at 15 cm from the shock source center on 60 cm × 60 cm × 1 cm equivalent aluminum plate were measured by using the piezoresistive accelerometer. On this account, the relative contribution values along with frequency and the mean relative values without regard to frequency of various sources were calculated in high and low preload. Results show that the characteristics of different shock sources are different, and the shock induced by propellant combustion is mainly caused by high frequency, while piston shear and piston impact are concentrated in medium and low frequency. In the high preload condition, the preload release is major contributor to the overall shock response output, accounting for approximately 57.51%, while the contributions of the three shock sources of propellant combustion, piston shear, and piston impact are equivalent, but they are significant contributors in the low preload condition. This study provides design reference to reduce the pyrotechnic shock of shear type explosive bolt.
Online Monitoring of Copper Damascene Electroplating Bath by Voltammetry: Selection of Variables for Multiblock and Hierarchical Chemometric Analysis of Voltammetric Data
Authors: Jaworski Aleksander , Wikiel Hanna , Wikiel Kazimierz
Published: December 2017

The Real Time Analyzer (RTA) utilizing DC- and AC-voltammetric techniques is an in situ, online monitoring system that provides a complete chemical analysis of different electrochemical deposition solutions. The RTA employs multivariate calibration when predicting concentration parameters from a multivariate data set. Although the hierarchical and multiblock Principal Component Regression- (PCR-) and Partial Least Squares- (PLS-) based methods can handle data sets even when the number of variables significantly exceeds the number of samples, it can be advantageous to reduce the number of variables to obtain improvement of the model predictions and better interpretation. This presentation focuses on the introduction of a multistep, rigorous method of data-selection-based Least Squares Regression, Simple Modeling of Class Analogy modeling power, and, as a novel application in electroanalysis, Uninformative Variable Elimination by PLS and by PCR, Variable Importance in the Projection coupled with PLS, Interval PLS, Interval PCR, and Moving Window PLS. Selection criteria of the optimum decomposition technique for the specific data are also demonstrated. The chief goal of this paper is to introduce to the community of electroanalytical chemists numerous variable selection methods which are well established in spectroscopy and can be successfully applied to voltammetric data analysis.
Metabolic Plasticity in Dendritic Cell Responses: Implications in Allergic Asthma
Authors: Mishra Amarjit
Published: December 2017

Dendritic cells (DCs) are highly specialized in antigen presentation and play a pivotal role in the initiation, progression, and perpetuation of adaptive immune responses. Emerging immune pathways are being recognized increasingly for DCs and their subsets that differentially regulate T lymphocyte function based on the type and interactions with the antigen. However, these interactions not only alter the signaling process and DC function but also render metabolic plasticity. The current review focuses on the metabolic cues of DCs that coordinate DC activation and differentiation and discuss whether targeting these fundamental cellular processes have implications to control airway inflammation and adaptive immunity. Therefore, strategies using metabolism-based therapeutic manipulation of DC functions could be developed into novel treatments for airway inflammation and asthma.
Fundamental Transverse Mode Selection (TMS#0) of Broad Area Semiconductor Lasers with Integrated Twice-Retracted 4f Set-Up and Film-Waveguide Lens
Authors: Fouckhardt Henning , Kleinschmidt Ann-Kathrin , Strassner Johannes , Doering Christoph
Published: December 2017

Previously we focused on fundamental transverse mode selection (TMS#0) of broad area semiconductor lasers (BALs) with two-arm folded integrated resonators for Fourier-optical spatial frequency filtering. The resonator had a round-trip length of 4f, where f is the focal length of the Fourier-transform element (FTE), that is, a cylindrical mirror in-between the orthogonal resonator branches. This 4f set-up can be called “retracted once” due to the reflective filter after 2f; that is, the 2f path was used forwards and backwards. Now the branches are retracted once more resulting in a compact 1f long linear resonator (called “retracted twice”) with a round-trip length of 2f. One facet accommodates the filter, while the other houses the FTE, now incorporating a film-waveguide lens. The BAL facet with the filter represents both the Fourier-transform plane (after 2f, i.e., one round-trip) as well as the image plane (after 4f, two round-trips). Thus filtering is performed even after 4f, not just after 2f. Experimental results reveal good fundamental TMS for pump currents up to 20% above threshold and a one-dimensional beam quality parameter M1D2 = 1.47. The BALs are made from AlGaInAsSb, but the concept can equally well be employed for BALs of any material system.
Chromatic Dispersion Compensation Effect Performance Enhancements Using FBG and EDFA-Wavelength Division Multiplexing Optical Transmission System
Authors: Chakkour Mounia , Aghzout Otman , Ait Ahmed Badiaa , Chaoui Fahd , El Yakhloufi Mounir
Published: December 2017

An optical transmission system using Fiber Bragg Grating (FBG) and Erbium Doped Fiber Amplifier (EDFA) with new proposed model has been analyzed to overcome chromatic dispersion and attenuation phenomena. To evaluate the transmission system performance of the received signals, a simple model of one channel transmission has been developed in the first step. Also, optical fiber length and attenuation coefficient parameters have been investigated in detail to deal with the optimized corresponding parameter values. Results show that the performance of the optimized design parameters is very efficient in terms of output power (dBm), noise figure (dB), gain (dB), and Q-Factor. The model of one channel developed previously has been adapted to a complex model of four optical channels multiplexing with different wavelengths. FBG and EDFA have been also added to WDM technology system to enhance the chromatic dispersion and the signal attenuation. Results show that the new model is more efficient in terms of Q-Factor and eye diagrams.
On Spectral Characterization of Nonuniform Hyperbolicity
Authors: Abu Alhalawa Muna , Dragičević Davor
Published: December 2017

We give a complete functional theoretic characterization of tempered exponential dichotomies in terms of the invertibility of certain linear operators acting on a suitable Frechét space. In sharp contrast to previous results, we consider noninvertible linear cocycles acting on infinite-dimensional spaces. The principal advantage of our results is that they avoid the use of Lyapunov norms.
Fabrication, Characterization, and In Vivo Evaluation of Famotidine Loaded Solid Lipid Nanoparticles for Boosting Oral Bioavailability
Authors: Shafique Muhammad , Khan Mir Azam , Khan Waheed S. , Maqsood-ur-Rehman  , Ahmad Waqar , Khan Shahzeb
Published: December 2017

Famotidine as H2 receptor has antagonistic effects on gastric secretion. Unfortunately, its hydrophobic nature contributes to its variable and poor oral bioavailability. In the current study efforts are being made to fabricate famotidine loaded solid lipid nanoparticles with narrow size distribution. Prepared nanoformulations were pharmaceutically evaluated to confirm the desired boosted oral bioavailability. Famotidine loaded nanoformulation (FFSe-4) showed particle size 111.9±1.3 nm, polydispersity index 0.464±0.03, zeta potential −33.46±2 mV, entrapment efficiency 84±2.7%, and drug loading capacity 2.709±0.13%. Drug-excipients compatibility was confirmed by Fourier transformed infrared spectroscopy. Scanning electron microscopy confirmed spherical shaped, nanosized particles. Differential scanning calorimetry and powder X-ray diffractometry confirmed the change in crystalline nature. Prepared nanoformulation was more stable at refrigerated temperature. In vitro study showed that drug release time is proportional to drug pay load and followed zero order kinetics. Release exponent (n>0.5) confirmed non-Fickian-diffusion mechanism for drug release. In vivo pharmacokinetic studies showed 2.06-fold increase in oral bioavailability of famotidine dispersed in solid lipid nanoparticles compared to commercial product. These results authenticate solid lipid nanoparticles as drug delivery system and propose prolonged release with improved oral bioavailability for famotidine.
Colorectal Cancer Consensus Molecular Subtypes Translated to Preclinical Models Uncover Potentially Targetable Cancer Cell Dependencies
Authors: Sveen Anita , Bruun Jarle , Eide Peter W. , Eilertsen Ina A. , Ramirez Lorena , Murumägi Astrid , Arjama Mariliina , Danielsen Stine A. , Kryeziu Kushtrim , Elez Elena , Tabernero Josep , Guinney Justin , Palmer Hector G. , Nesbakken Arild , Kallioniemi Olli , Dienstmann Rodrigo , Lothe Ragnhild A.
Published: December 2017

Purpose: Response to standard oncologic treatment is limited in colorectal cancer. The gene expression–based consensus molecular subtypes (CMS) provide a new paradigm for stratified treatment and drug repurposing; however, drug discovery is currently limited by the lack of translation of CMS to preclinical models.

Experimental Design: We analyzed CMS in primary colorectal cancers, cell lines, and patient-derived xenografts (PDX). For classification of preclinical models, we developed an optimized classifier enriched for cancer cell–intrinsic gene expression signals, and performed high-throughput in vitro drug screening (n = 459 drugs) to analyze subtype-specific drug sensitivities.

Results: The distinct molecular and clinicopathologic characteristics of each CMS group were validated in a single-hospital series of 409 primary colorectal cancers. The new, cancer cell–adapted classifier was found to perform well in primary tumors, and applied to a panel of 148 cell lines and 32 PDXs, these colorectal cancer models were shown to recapitulate the biology of the CMS groups. Drug screening of 33 cell lines demonstrated subtype-dependent response profiles, confirming strong response to EGFR and HER2 inhibitors in the CMS2 epithelial/canonical group, and revealing strong sensitivity to HSP90 inhibitors in cells with the CMS1 microsatellite instability/immune and CMS4 mesenchymal phenotypes. This association was validated in vitro in additional CMS-predicted cell lines. Combination treatment with 5-fluorouracil and luminespib showed potential to alleviate chemoresistance in a CMS4 PDX model, an effect not seen in a chemosensitive CMS2 PDX model.

Conclusions: We provide translation of CMS classification to preclinical models and uncover a potential for targeted treatment repurposing in the chemoresistant CMS4 group. Clin Cancer Res; 24(4); 794–806. ©2017 AACR.
Inhibiting Nuclear Phospho-Progesterone Receptor Enhances Antitumor Activity of Onapristone in Uterine Cancer
Authors: Huang Yan , Hu Wei , Huang Jie , Shen Fangrong , Sun Yunjie , Ivan Cristina , Pradeep Sunila , Dood Robert , Haemmerle Monika , Jiang Dahai , Mangala Lingegowda S. , Noh Kyunghee , Hansen Jean M. , Dalton Heather J. , Previs Rebecca A. , Nagaraja Archana S. , McGuire Michael , Jennings Nicholas B. , Broaddus Russell , Coleman Robert L. , Sood Anil K.
Published: December 2017

Although progesterone receptor (PR)–targeted therapies are modestly active in patients with uterine cancer, their underlying molecular mechanisms are not well understood. The clinical use of such therapies is limited because of the lack of biomarkers that predict response to PR agonists (progestins) or PR antagonists (onapristone). Thus, understanding the underlying molecular mechanisms of action will provide an advance in developing novel combination therapies for cancer patients. Nuclear translocation of PR has been reported to be ligand-dependent or -independent. Here, we identified that onapristone, a PR antagonist, inhibited nuclear translocation of ligand-dependent or -independent (EGF) phospho-PR (S294), whereas trametinib inhibited nuclear translocation of EGF-induced phospho-PR (S294). Using orthotopic mouse models of uterine cancer, we demonstrated that the combination of onapristone and trametinib results in superior antitumor effects in uterine cancer models compared with either monotherapy. These synergistic effects are, in part, mediated through inhibiting the nuclear translocation of EGF-induced PR phosphorylation in uterine cancer cells. Targeting MAPK-dependent PR activation with onapristone and trametinib significantly inhibited tumor growth in preclinical uterine cancer models and is worthy of further clinical investigation. Mol Cancer Ther; 17(2); 464–73. ©2017 AACR.
Antitumor Activity of Entrectinib, a Pan-TRK, ROS1, and ALK Inhibitor, in ETV6-NTRK3–Positive Acute Myeloid Leukemia
Authors: Smith Kristen M. , Fagan Patrick C. , Pomari Elena , Germano Giuseppe , Frasson Chiara , Walsh Colin , Silverman Ian , Bonvini Paolo , Li Gang
Published: December 2017

Activation of tropomyosin receptor kinase (TRK) family tyrosine kinases by chromosomal rearrangement has been shown to drive a wide range of solid tumors and hematologic malignancies. TRK fusions are actionable targets as evidenced by recent clinical trial results in solid tumors. Entrectinib (RXDX-101) is an investigational, orally available, CNS-active, highly potent, and selective kinase inhibitor against TRKA/B/C, ROS1, and ALK kinase activities. Here, we demonstrate that TRK kinase inhibition by entrectinib selectively targets preclinical models of TRK fusion–driven hematologic malignancies. In acute myelogenous leukemia (AML) cell lines with endogenous expression of the ETV6–NTRK3 fusion gene, entrectinib treatment blocked cell proliferation and induced apoptotic cell death in vitro with subnanomolar IC50 values. Phosphorylation of the ETV6–TRKC fusion protein and its downstream signaling effectors was inhibited by entrectinib treatment in a dose-dependent manner. In animal models, entrectinib treatment at clinically relevant doses resulted in tumor regression that was accompanied by elimination of residual cancer cells from the bone marrow. Our preclinical data demonstrate the potential of entrectinib as an effective treatment for patients with TRK fusion–driven AML and other hematologic malignancies. Mol Cancer Ther; 17(2); 455–63. ©2017 AACR.
High Mobility Group Box1 Inhibitor Glycyrrhizic Acid Attenuates Kidney Injury in Streptozotocin-Induced Diabetic Rats
Authors: Zhang Hong , Zhang Ru , Chen Juan , Shi Min , Li Wei , Zhang Xiangcheng
Published: December 2017

Background/Aims: High mobility group box 1 (HMGB1) is an important mediator of the inflammatory response. It has been implicated in the pathogenesis of autoimmune diseases, atherosclerosis, and obesity. However, the effects of HMGB1 on diabetic nephropathy remain unclear. Here, we investigated the potential roles and mechanisms of an HMGB1 inhibitor, glycyrrhizic acid (GA), in renal injury with the streptozotocin (STZ)-induced rat model. Methods: The diabetic rat was generated by intraperitoneal injection of STZ and then treated with the HMGB1 inhibitor GA or saline for 8 weeks. Rats were randomly divided into three groups: the normal control and saline group (Control), the diabetic rats with saline group (Diabetic) and the diabetic rats plus GA group (Diabetic+GA). Peripheral blood was obtained for measurements of blood glucose, TNF-a, IL-6 and IL-1β. The mRNA levels of proinflammatory cytokines (TNF-a, IL-6 and IL-1β), chemokines (MCP-1), intercellular adhesion molecules (ICAM-1) and TGF-β1 in the kidneys were evaluated by quantitative real-time PCR. The protein levels of phosphorylated(p) and total(t) p38 MAPK, JNK, ERK, and NF-κB were measured by western blot. Results: We found that diabetic rats showed obvious renal lesions, an elevated urinary albumin/creatinine ratio (UACR) and increased expression levels of TGF-β1 and Col-IV in the kidneys, accompanied by significantly enhanced expression levels of HMGB1, receptor for advanced glycation end products (RAGE) and toll-like receptor 4 (TLR-4) in the kidney tissue. Furthermore, the GA treatment significantly reduced the UAC levels, ameliorated renal injury, and decreased the TNF-α, 1L-6, IL-1β, MCP-1, ICAM-1, TGF-β1 and Col-IV levels. Importantly, the expression levels of HMGBI, RAGE and TLR4 in the kidney tissues of the diabetic rats were also inhibited by the GA treatment. Furthermore, the GA treatment significantly reduced the phosphorylation levels of ERK and p38 MAPK and suppressed NF-κB translocation from the cytoplasm to the nucleus. Conclusion: Our findings indicate that the HMGB1 inhibitor GA may improve renal injury and inflammatory responses in diabetic rats by regulating RAGE/TLR4-related ERK and p38 MAPK/NF-κB activation.
Antibiotics-Induced Obesity: A Mitochondrial Perspective
Authors: Andrade Melisa J. , Jayaprakash Chinchu , Bhat Smitha , Evangelatos Nikolaos , Brand Angela , Satyamoorthy Kapaettu
Published: December 2017

Antibiotics are the first line of treatment against infections and have contributed immensely to reduce the morbidity and mortality rates. Recently, extensive use of antibiotics has led to alterations of the gut microbiome, predisposition to various diseases and most importantly, increase in the emergence of antibiotic-resistant bacteria, which poses a major threat to global public health. Another major issue faced worldwide due to unregulated use of antibiotics in children as well as in adults is the influence of metabolism and body weight homeostasis, leading to obesity. Apart from the involvement of biosocial causes influencing diet, physical activity, and antibiotic use, pathogenesis of obesity is linked to interconnected functional alterations in cells, tissues and organs due to biochemical, epigenetic and genetic factors. Mitochondrial dysfunction is one such factor, which is becoming the primary focus of various aspects of research on multifactorial complex diseases and is providing new perspectives on etiology, biomarker-based diagnosis, and drug sensitivity. Through this review, we have made an attempt to present the interplay between use of antibiotics, obesity, and associated mitochondrial dysfunction. This may provide insights into the molecular basis, genetic predisposition and environmental triggers, which in turn may have potential clinical applications in the management of antibiotic use.
Disease Remission in Children and Adolescents with Intermediate Uveitis: A Survival Analysis
Authors: Borrego-Sanz Lara , Abásolo Lydia , López-Abad Consuelo , Fernández-Gutiérrez Benjamín , García-Feijoo Julián , Diaz-Valle David , Pato Esperanza , Rodriguez-Rodriguez Luis
Published: December 2017

Purpose: To report the incidence rate (IR) of remission in pediatric noninfectious intermediate uveitis (IU). Methods: Longitudinal retrospective cohort study, including 19 patients (32 eyes) between 1985 and 2014, followed-up until loss or January 2016. Remission was defined following the Standardization of Uveitis Nomenclature workshop criteria, prolonged remission as a remission spanning 12 months and until the end of follow-up, and relapse as recurrence of inflammatory activity in an eye in remission. Results: Median follow-up time was 6.3 years. IRs (95% confidence interval) for remission, relapse, and prolonged remission were 18.6 (13.1–26.5), 32.3 (20.6–50.7), and 6.7 (3.8–11.9) episodes per 100 eye-years, respectively. 48% of eyes relapsed in the first year following remission. 25 and 50% of eyes achieved prolonged remission after 5 and 10 years of follow-up, respectively. Conclusions: Inflammatory relapses may be frequent in noninfectious IU affecting children and adolescents, appearing early after remission. Also, prolonged remission seems infrequent, being achieved late during follow-up.
High-Risk Human Papillomavirus in Oral Cancer: Clinical Implications
Authors: Yete Subuhi , D'Souza Wendy , Saranath Dhananjaya
Published: December 2017

Oral cancer is the eleventh most common cancer globally, with well-established major risk factors of tobacco, areca nut, alcohol, and high-risk human papillomavirus (HR-HPV) types 16 and 18. HR-HPV16/18 are the etiologic agents of cervical cancers and a proportion of oropharyngeal cancers. HPV-associated oropharyngeal and oral cancers show better prognosis and response to therapy. However, the picture of HR-HPV16/18 and the clinical implications of oral cancers are not clear with the majority of reports combining oral cancer data with head and neck cancers. The current review compiles the global prevalence of HR-HPV16/18 in oral cancers, highlighting the unique clinical and molecular pathologic features, prognosis and therapeutic strategies in the prevention and management of HPV-positive oral cancers. The potential for the use of de-intensified therapy and prophylactic prevention in HPV-positive oral cancer patients is highlighted.