bluuebunny/crossref_metadata_2025 huggingface dataset:
Study on Compaction Characteristics and Construction Control of Mixtures of Red Clay and Gravel
Authors: Zeng Biao , Wang Lin-feng , Tian Yun , Zeng Tao-rui , Li Bing
Published: November 2018

Red clay cannot be used as embankment filler directly due to its water‐sensitive property. Gravel is usually added into red clay to enhance its performance in engineering practice. In order to investigate the influence of mixtures of red clay and gravel on the road performance, gravitational compaction experiment of red clay and vibratory compaction experiment of mixtures of red clay and gravel were conducted, respectively. The results indicate that compaction curves of red clay have double peak; the second peak is the real maximum dry density, and its corresponding moisture content is the optimal moisture content. The dry density of mixtures of red clay and gravel is influenced by the content of gravel, vibration frequency, and vibration time. The optimal content of gravel is 30%, the best vibration frequency is 45 Hz, and the optimal vibration time is 5 minutes for the mixtures of red clay and gravel in this study. The effectiveness of optimal content of gravel and optimum vibration parameters was confirmed by a CBR test. According to the compaction experiment results and actual situation in the field, a suitable construction method of subgrade using the mixtures of red clay and gravel was put forward. The feasibility of this method was also confirmed by postconstruction deformation data of the field test embankment.
Experimental Study on Cumulative Plastic Deformation of Coarse‐Grained Soil High‐Grade Roadbed under Long‐Term Vehicle Load
Authors: He Zhongming , Liu Yaxin , Tang Haolong , Xing Yihang , Bian Hanbing
Published: November 2018

According to the change characteristics of the subgrade moisture content and the mechanical calculation of several typical highways, the test scheme of the permanent deformation of coarse soil was formulated. The relationship between the permanent deformation of coarse‐grained soil and the stress level, compaction degree, moisture content, and loading frequency was studied by cyclic loading triaxle testing. The results show that the permanent deformation of coarse‐grained soil increases with the increase in partial stress and moisture content and decreases with the increase in compaction degree. The experimental data were fitted by the Tseng‐Lytton model, and the correlation coefficients were 92%, which indicated that the model could be used to predict the permanent deformation of coarse soil. The relationships between the model coefficient and the moisture content and spring back modulus were obtained by the multiple regression method. Finally, the permanent deformation of the subgrade soil was calculated by using the layered summation method and a typical subgrade pavement structure.
Stability and Hopf Bifurcation of a Delayed Epidemic Model of Computer Virus with Impact of Antivirus Software
Authors: Zhang Zizhen , Upadhyay Ranjit Kumar , Bi Dianjie , Wei Ruibin
Published: November 2018

In this paper, we investigate an SLBRS computer virus model with time delay and impact of antivirus software. The proposed model considers the entering rates of all computers since every computer can enter or leave the Internet easily. It has been observed that there is a stability switch and the system becomes unstable due to the effect of the time delay. Conditions under which the system remains locally stable and Hopf bifurcation occurs are found. Sufficient conditions for global stability of endemic equilibrium are derived by constructing a Lyapunov function. Formulae for the direction, stability, and period of the bifurcating periodic solutions are conducted with the aid of the normal form theory and center manifold theorem. Numerical simulations are carried out to analyze the effect of some of the parameters in the system on the dynamic behavior of the system.
Effects of Surface Waviness on the Nonlinear Vibration of Gas Lubricated Bearing‐Rotor System
Authors: Li Jian , Yang Shaoqi , Li Xiaoming , Li Qing
Published: November 2018

This paper presents the effects of the surface waviness on the nonlinear dynamic performance of a gas bearing‐rotor system. The coupled vibration with the elastomer is taken into consideration to fit the actual engineering application. The effects of the directions, the amplitudes, and the numbers of waves to the nonlinear dynamic performance are investigated. The results show that the existence of the surface waviness in the circumferential direction can improve the stability of the system obviously. But the surface waviness in the axial direction is damage to the system. The nonlinear dynamic performance of the system is insensitive to the number of surface waviness. The increase of the amplitude of the waviness in circumferential direction can improve the stability of the system.
Factors Associated with Recurrent Ulcers in Patients with Gastric Surgery after More Than 15 Years: A Cross-Sectional Single-Center Study
Authors: Pantea Monica , Negovan Anca , Banescu Claudia , Bataga Simona , Neagoe Radu , Mocan Simona , Iancu Mihaela
Published: November 2018

Aim. We aimed to establish the independent predictive factors (from Helicobacter pylori infection, biliary reflux, histologic features of the gastric mucosa, drugs, comorbidities, and social habits) for gastric stump ulcer occurrence more than 15 years after surgery. Methods. 76 patients with previous gastric surgery were included: 21 patients with gastric ulcer (marginal ulcer or ulcer of the rest of the gastric remnant—study group) and 55 controls (nonulcer group). Results. Helicobacter pylori infection tended to be higher in the control group than in the ulcer group (14.5% vs. 4.8%, p=0.43), without statistical significance. Alcohol consumption had a significant positive association with ulcer (p=0.008), while smoking (p=0.064), low-dose aspirin (p=0.063), and biliary reflux (p=0.106) had a tendency toward statistical signification for positive association. On univariate analysis, smoking (p=0.048, OR = 3.15, 95% CI: 1.01–9.93) and low-dose aspirin consumption (p=0.067, OR = 2.63, 95% CI: 0.95–7.68) were significantly associated with ulcer. According to the multivariable regression model, alcohol consumption (OR = 6.68, 95% CI: 1.29–41.14) and biliary reflux (OR = 6.12, 95% CI: 1.36–38.26) remained significantly associated with increased odds of stump ulcer. Conclusion. Biliary reflux and alcohol consumption, but not Helicobacter pylori infection or gastrotoxic drug, seem to be the most important predictors for ulcer recurrence in patients with gastric surgery for peptic ulcer after more than 15 years.
On Random Periodic Solution to a Neutral Stochastic Functional Differential Equation
Authors: Gao Lili , Yan Litan
Published: November 2018

In this paper, we consider the random periodic solution to a neutral stochastic functional differential equation driven by Brownian motion. We obtain the existence and uniqueness of the random periodic solution by Banach fixed point theorem. Moreover, we introduce two examples to illustrate our results.
Safety and Efficacy of Low-Level Laser Therapy in Autoimmune Thyroiditis: Long-Term Follow-Up Study
Authors: Höfling Danilo Bianchini , Chavantes Maria Cristina , Buchpiguel Carlos Alberto , Cerri Giovanni Guido , Marui Suemi , Carneiro Paulo Campos , Chammas Maria Cristina
Published: November 2018

Introduction. A randomized clinical trial (RCT) was performed to evaluate the efficacy of low-level laser therapy (LLLT) for hypothyroidism induced by chronic autoimmune thyroiditis (CAT). Objective. The objective was to assess the safety and actions of LLLT 6 years after completion of the RCT. Materials and Methods. Forty-three participants were invited to participate in this study 6 years after completion of the RCT. Twenty-five were subjected to LLLT (group L), and 18 were subjected to placebo (group P). Primary outcome measure: frequency of thyroid nodules, which were subjected to fine-needle aspiration biopsy. Secondary outcome measures: dose of levothyroxine required to treat hypothyroidism, thyroid peroxidase antibodies (anti-TPO), and anti-thyroglobulin antibodies (anti-Tg). Results. In group L, a nodule was observed in three patients, who all had a Bethesda II classification. In group P, a nodule was also observed in three patients, with two classified as Bethesda II and one as Bethesda III. The levothyroxine dose required by group L was significantly lower than that required by group P (P=0.002). The anti-TPO and anti-Tg levels did not differ between the groups. Conclusion. LLLT, by the methods described, has been shown to be safe for the treatment of hypothyroidism resulting from CAT. This trial is registered with ClinicalTrials.gov Identifier: NCT02240563.
Comparative Analysis of the Safety and Functional Outcomes of Anterior versus Retropupillary Iris-Claw IOL Fixation
Authors: Mora Paolo , Calzetti Giacomo , Favilla Stefania , Forlini Matteo , Tedesco Salvatore , Date Purva , Tagliavini Viola , Carta Arturo , Frisina Rino , Pedrotti Emilio , Gandolfi Stefano
Published: November 2018

Purpose. To compare the functional and clinical outcomes of the iris-claw intraocular lens (IOL) placed on the anterior versus posterior surface of the iris.Patients and Methods. A multicenter, retrospective study. Data on eyes that underwent anterior or retropupillary iris-claw IOL implantation because of inadequate capsular support secondary to complicated cataract surgery, trauma, and dislocated/opacified IOLs since January 2015 were analyzed. For study inclusion, evaluation results had to be available in the medical records both preoperatively and at 1 and 12 months after implantation. The following parameters were compared between the groups: best-corrected distance visual acuity (BCDVA), spherical and cylindrical refractive error, endothelial cell density (ECD), central macular thickness (CMT), and percentage and type of postoperative complications.Results. In total, 60 eyes of 60 patients aged 73 ± 13 years were included: 28 eyes (47%) involved anterior, and 32 eyes (53%) retropupillary, iris-claw IOL fixations. Preoperatively, the groups were similar in all parameters except for a significantly higher proportion of retropupillary fixations in patients who had previously experienced a closed-globe trauma (p=0.03). The groups showed comparable improvements in BCDVA after surgery (final BCDVA: 0.34 ± 0.45 vs. 0.37 ± 0.50 logMAR in the anterior and retropupillary placement groups, respectively). During follow-up, no group difference was observed in refractive error or CMT. Both groups experienced similarly marked ECD loss and showed similar incidence of postoperative complications, with cystoid macular edema being the most common complication. Multivariable linear regression showed that BCDVA at 1 month was the best predictor of the final BCDVA.Conclusions. Anterior chamber and posterior chamber iris-claw IOL fixations proved equally effective and safe for aphakic correction in eyes with inadequate capsular support.
Comparison of Factors Affecting Crash Severities in Hit-and-Run and Non-Hit-and-Run Crashes
Authors: Zhou Bei , Li Zongzhi , Zhang Shengrui
Published: November 2018

A hit-and-run (HR) crash occurs when the driver of the offending vehicle flees the crash scene without reporting it or aiding the victims. The current study aimed at contributing to existing literatures by comparing factors which might affect the crash severity in HR and non-hit-and-run (NHR) crashes. The data was extracted from the police-reported crash data from September 2017 to August 2018 within the City of Chicago. Two multinomial logistic regression models were established for the HR and NHR crash data, respectively. The odds ratio (OR) of each variable was used to quantify the impact of this variable on the crash severity. In both models, the property damage only (PDO) crash was selected as the reference group, and the injury and fatal crash were chosen as the comparison group. When the injury crash was taken as the comparison group, it was found that 12 variables contributed to the crash severities in both HR and NHR model. The average percentage deviation of OR for these 12 variables was 34%, indicating that compared with property damage, HR crashes were 34% more likely to result in injuries than NHR crashes on average. When fatal crashes were chosen as the comparison group, 2 variables were found to be statistically significant in both the HR and the NHR model. The average percentage deviation of OR for these 2 variables was 127%, indicating that compared with property damage, HR crashes were 127% more likely to result in fatalities than NHR crashes on average.
Research on a Novel Kind of Dual Polarized Stacked Printed Antenna
Authors: Zhiwei Gao , qingyuan Fang , shugang Jiang
Published: November 2018

This paper presents a dual polarized antenna with high isolation for a wide-angle scanning phased array radar. For the proposed antenna, the electronic and magnetic resources are realized through a printed monopole antenna and a slot ring antenna, respectively. A metal reflector ground was introduced to achieve the unidirectional pattern, and the ratio of front to back of the pattern was improved. The printed monopole and slot ring antenna are fed by the coaxial and electromagnetic couplings, respectively. The radiation fields emitted by the electronic current resource and magnetic current resource are approximately orthogonal to each other among large space ranges. The measured port isolation of the designed antenna is above 20 dB, and the wide beam performance can be observed. The feasibility of the proposed antenna scheme is verified.
Phosphoprotein Contributes to the Thermostability of Newcastle Disease Virus
Authors: Zhao Yang , Liu Huairan , Cong Feng , Wu Wei , Zhao Ran , Kong Xiangang
Published: November 2018

Newcastle disease (ND), caused by Newcastle disease virus (NDV), is highly contagious and represents a major threat to the poultry industry. The thermostable vaccines are not insensitive to heat and ease of storage and transportation, but the mechanism of NDV thermostability remains unknown. The phosphoprotein (P), fusion protein (F), hemagglutinin-neuraminidase protein (HN), and large polymerase protein (L) are associated with NDV virulence. The association between F, HN, or L and viral thermostability has been, respectively, studied in different reports. However, the effects of P on NDV thermostability have not been demonstrated. Here, we utilized an existing reverse genetics system in our laboratory, to generate chimeric viruses by exchanging the P protein between the thermostable NDV4-C strain and the thermolabile LaSota strain. Chimeric viruses were found to possess similar growth properties, passage stability, and virulence, as compared to those of these parental strains. Interestingly, the thermostability of the chimera with P derived from the thermolabile LaSota strain was reduced compared to that of the parental virus, and P of the thermostable NDV4-C strain enhanced chimeric virus thermostability. Our data demonstrate that P is an important factor for the thermostability of NDV and provides information regarding the molecular mechanism of NDV thermostability; moreover, these results suggest a theoretical basis for using the NDV4-C strain as a thermostable vaccine.
On the Regular Integral Solutions of a Generalized Bessel Differential Equation
Authors: Campos L. M. B. C. , Moleiro F. , Silva M. J. S. , Paquim J.
Published: November 2018

The original Bessel differential equation that describes, among many others, cylindrical acoustic or vortical waves, is a particular case of zero degree of the generalized Bessel differential equation that describes coupled acoustic-vortical waves. The solutions of the generalized Bessel differential equation are obtained for all possible combinations of the two complex parameters, order and degree, and finite complex variable, as Frobenius-Fuchs series around the regular singularity at the origin; the series converge in the whole complex plane of the variable, except for the point-at-infinity, that is, the only other singularity of the differential equation. The regular integral solutions of the first and second kinds lead, respectively, to the generalized Bessel and Neumann functions; these reduce to the original Bessel and Neumann functions for zero degree and have alternative expressions for nonzero degree.
Anticipating Cryptocurrency Prices Using Machine Learning
Authors: Alessandretti Laura , ElBahrawy Abeer , Aiello Luca Maria , Baronchelli Andrea
Published: November 2018

Machine learning and AI‐assisted trading have attracted growing interest for the past few years. Here, we use this approach to test the hypothesis that the inefficiency of the cryptocurrency market can be exploited to generate abnormal profits. We analyse daily data for 1,681 cryptocurrencies for the period between Nov. 2015 and Apr. 2018. We show that simple trading strategies assisted by state‐of‐the‐art machine learning algorithms outperform standard benchmarks. Our results show that nontrivial, but ultimately simple, algorithmic mechanisms can help anticipate the short‐term evolution of the cryptocurrency market.
Efficacy of Alveolar Ridge Preservation after Maxillary Molar Extraction in Reducing Crestal Bone Resorption and Sinus Pneumatization: A Multicenter Prospective Case-Control Study
Authors: Lombardi Teresa , Bernardello Fabio , Berton Federico , Porrelli Davide , Rapani Antonio , Camurri Piloni Alvise , Fiorillo Luca , Di Lenarda Roberto , Stacchi Claudio
Published: November 2018

Aim. To evaluate, with three-dimensional analysis, the effectiveness of alveolar ridge preservation (ARP) after maxillary molar extraction in reducing alveolar bone resorption and maxillary sinus pneumatization when compared to unassisted socket healing. Methods. Patients were included in the study following inclusion criteria and underwent minimally traumatic maxillary molar extraction followed by ARP using synthetic nanohydroxyapatite (Fisiograft Bone, Ghimas, Italy) (test group) or unassisted socket healing (control group). Cone-beam computerized tomographies (CBCT) were performed immediately after tooth extraction (T0) and 6 months postoperatively (T1). CBCTs were superimposed by using a specific software (Amira, Thermo Fisher Scientific, USA) and the following items were analyzed in both groups: (i) postextractive maxillary sinus floor expansion in coronal direction and (ii) postextractive alveolar bone dimensional changes (both vertical and horizontal). All data were tested for normality and equality of variance and subsequently analyzed by independent samples T-test and Mann–Whitney test. Results. Thirty patients were treated by three centers and twenty-six (test n=13; control n=13) were included in the final analysis. Mean sinus pneumatization at T1 was 0.69±0.48 mm in the test group and 1.04±0.67 mm in the control group (p=0.15). Mean vertical reduction of the alveolar bone at T1 was 1.62±0.49 mm in the test group and 2.01±0.84 mm in the control group (p=0.08). Mean horizontal resorption of crestal bone at T1 was 2.73±1.68 mm in test group and 3.63±2.24 mm in control group (p=0.24). Conclusions. It could be suggested that ARP performed after maxillary molar extraction may reduce the entity of sinus pneumatization and alveolar bone resorption, compared to unassisted socket healing. This technique could decrease the necessity of advanced regenerative procedures prior to dental implant placement in posterior maxilla.
Communication in Online Social Networks Fosters Cultural Isolation
Authors: Keijzer Marijn A. , Mäs Michael , Flache Andreas
Published: November 2018

Online social networks play an increasingly important role in communication between friends, colleagues, business partners, and family members. This development sparked public and scholarly debate about how these new platforms affect dynamics of cultural diversity. Formal models of cultural dissemination are powerful tools to study dynamics of cultural diversity but they are based on assumptions that represent traditional dyadic, face‐to‐face communication, rather than communication in online social networks. Unlike in models of face‐to‐face communication, where actors update their cultural traits after being influenced by one of their network contacts, communication in online social networks is often characterized by a one‐to‐many structure, in that users emit messages directly to a large number of network contacts. Using analytical tools and agent‐based simulation, we show that this seemingly subtle difference can have profound implications for emergent dynamics of cultural dissemination. In particular, we show that within the framework of our model online communication fosters cultural diversity to a larger degree than offline communication and it increases chances that individuals and subgroups become culturally isolated from their network contacts.
Experimental and Theoretical Study of Gear Dynamical Transmission Characteristic Considering Measured Manufacturing Errors
Authors: Guo Fang , Fang Zongde
Published: November 2018

In the research of gear transmission, the vibration and noise problem has received many concerns all the times. Scholars use tooth modification technique to improve the meshing state of gearings in order to reduce the vibration and noise. However, few of researchers consider the influence of measured manufacturing errors when they do the study of tooth modification. In order to investigate the efficiency of the tooth modification in the actual project, this paper proposes a dynamic model of a helical gear pair including tooth modification and measured manufacturing errors to do a deterministic analysis on the dynamical transmission performance. In this analysis, based on the measured tooth deviation, a real tooth surface (including modification and measured tooth profile error) is fitted by a bicubic B‐spline. With the tooth contact analysis (TCA) and loaded tooth contact analysis (LTCA) on the real tooth surface, the loaded transmission error, tooth surface elastic deformation, and load distribution can be determined. Based on the results, the time‐varying mesh stiffness and gear mesh impact are computed. Taking the loaded transmission error, measured cumulative pitch error, eccentricity error, time‐varying mesh stiffness, and gear mesh impact as the internal excitations, this paper establishes a 12‐degree‐of‐freedom (DOF) dynamic model of a helical gear pair and uses the Fourier series method to solve it. In two situations of low speed and high speed, the gear system dynamic response is analyzed in the time and frequency domains. In addition, an experiment is performed to validate the simulation results. The study shows that the proposed technique is useful and reliable for predicting the dynamic response of a gear system.
CX-3543 Promotes Cell Apoptosis through Downregulation of CCAT1 in Colon Cancer Cells
Authors: Yao Yu-xia , Xu Bao-hong , Zhang Yan
Published: November 2018

Aim. Colon cancer-associated transcript-1 (CCAT1), located in the vicinity of transcription factor c-Myc, was first identified in colon cancer. A small-molecule compound CX3543 (Quarfloxin) selectively targeting Myc G-quadruplexes has entered phase II clinical trials for neuroendocrine carcinomas. The aim of the study was to explore the relationship between CX3543, CCAT1, and cell apoptosis in colon cancer cells. Methods. Semiquantitative PCR was used to detect the relative expression of CCAT1 in colon cancer (CC) tissues and HT29 cell lines. Real-time PCR (RT-PCR) was also used to investigate the expression of CCAT1 and c-Myc after HT29 cells being treated by CX3543 for 24 h. Cell apoptosis assay and cell proliferation assay were conducted in HT29 cells after being treated by CX3543. Results. The results showed that the expression of CCAT1 was remarkably increased in CC tissues and HT29 cells compared to controls. CX3543 treatment reduced the expression of c-Myc and CCAT1 and promoted cell apoptosis and inhibited cell proliferation. After the expression of CCAT1 was inhibited by sh-CCAT1 transfection, the cell apoptosis rate was higher than that of control group. After the cells were treated by CCAT1 overexpression plasmid transfection and CX3543, the cell apoptosis rate was lower than that of control group. In vivo results showed that CX3543 inhibited the xenograft tumor growth of rats through downregulation of CCAT1. Conclusion. Our study demonstrated that CX3543 could inhibit the progression of colon cancer by downregulating CCAT1 expression and might be a potential drug for the treatment of colon cancer.
Prevalence and Antimicrobial Susceptibility Profile ofSalmonellaSerovars Isolated from Slaughtered Cattle in Addis Ababa, Ethiopia
Authors: Ketema Lidya , Ketema Zerihun , Kiflu Bitsu , Alemayehu Haile , Terefe Yitagele , Ibrahim Mohammed , Eguale Tadesse
Published: November 2018

Salmonellais one of the top causes of foodborne bacterial illnesses in humans. The primary sources of humanSalmonellainfection are food producing animals such as cattle, poultry, and swine. A cross-sectional study was undertaken to estimate the prevalence and to determine the serovar distribution and antimicrobial susceptibility profiles ofSalmonellaspp. isolated from fecal (n=567) and carcass swab (n=159) samples of slaughtered cattle at Addis Ababa Abattoir Enterprise and Kara’alo PLC, Abattoirs, in Addis Ababa, Ethiopia between January 2014 and April 2015.Salmonellaisolation was conducted according to Global Foodborne Infections Network Laboratory Protocol and isolates were confirmed by genus specific PCR and serotyped by slide agglutination test. Susceptibility of the isolates to 17 antimicrobials was testedusing the Kirby-Bauer disk diffusion method according to the guidelines of the Clinical and Laboratory Standards Institute. Out of the total 726 samples examined, 27 (3.7%) were positive forSalmonella. Salmonellawas detected in 4.1% (23/567) fecal and 2.5% (4/159) carcass swab samples. Twelve different serovars were identified and the most predominant serovars wereS. Dublin (n=10, 35.7%) andS. Virchow (n=5, 17.9%), followed byS. Braendrerup,S. Haifa, andS. Saintpaul which were isolated from 2 samples each (7.1%). All of theSalmonellaisolates investigated were resistant or intermediately resistant to four or more of the 17 drugs tested. High resistance rate was recorded to streptomycin 25 (89.3%), cephalothin 20 (71.4%), ampicillin 19 (67.9%), and amoxicillin+clavulanic acid 19 (67.9%). Resistance to five or more antimicrobials was detected in 20 (71.5%) of the isolates. Multidrug resistance to more than 7 antimicrobials was detected in 5 (17.9%) of the isolates. Isolation of such multidrug resistant strains ofSalmonellafrom slaughtered cattle poses a major public health concern. These findings imply the need for a strict biosecurity and regulation of antimicrobial use across the country.
Perspectives of Older Adults on Aging Well: A Focus Group Study
Authors: Halaweh Hadeel , Dahlin-Ivanoff Synneve , Svantesson Ulla , Willén Carin
Published: November 2018

Background. With increasing number of older adults worldwide, promoting health and well-being becomes a priority for aging well. Well-being and physical and mental health are closely related, and this relation may become more vital at older ages as it may contribute to aging well. The state of well-being is a multifaceted phenomenon that refers to an individual’s subjective feelings, and exploring perspectives of older adults on aging well is developing to be an important area of research. Therefore, the aim of this study was to explore perceptions on aging well among older adult Palestinians ≥60 years.Methods. A qualitative research design in the context of focus group discussions was used; seven focus groups were conducted including fifty-six participants (aged 63–81 years). Data were analyzed using a qualitative interpretative thematic approach described by Braun and Clarke.Results. Three major themes were identified,“sense of well-being,”“having good physical health,”and “preserving good mental health.”The participants perceived that aging well is influenced by positive feelings such as being joyous, staying independent, having a life purpose, self-possessed contentment, and financially secured, in addition to be socially engaged and enjoying good physical and mental health.Conclusion. This study contributes to get a better insight concerning older adults’ perspectives on aging well. Enhancing physically active lifestyle, participation in social and leisure activities, healthy eating habits, having a purpose in life, and being intellectually engaged are all contributing factors to aging well. Vital factors are to be considered in developing strategic health and rehabilitative plans for promoting aging well among older adults.
Antifibrotic Therapy Disrupts Stromal Barriers and Modulates the Immune Landscape in Pancreatic Ductal Adenocarcinoma
Authors: Elahi-Gedwillo Kianna Y. , Carlson Marjorie , Zettervall Jon , Provenzano Paolo P.
Published: November 2018

Pancreatic ductal adenocarcinoma (PDA) remains one of the deadliest forms of cancer, in part, because it is largely refractory to current therapies. The failure of most standard therapies in PDA, as well as promising immune therapies, may be largely ascribed to highly unique and protective stromal microenvironments that present significant biophysical barriers to effective drug delivery, that are immunosuppressive, and that can limit the distribution and function of antitumor immune cells. Here, we utilized stromal reengineering to disrupt these barriers and move the stroma toward normalization using a potent antifibrotic agent, halofuginone. In an autochthonous genetically engineered mouse model of PDA, halofuginone disrupted physical barriers to effective drug distribution by decreasing fibroblast activation and reducing key extracellular matrix elements that drive stromal resistance. Concomitantly, halofuginone treatment altered the immune landscape in PDA, with greater immune infiltrate into regions of low hylauronan, which resulted in increased number and distribution of both classically activated inflammatory macrophages and cytotoxic T cells. In concert with a direct effect on carcinoma cells, this led to widespread intratumoral necrosis and reduced tumor volume. These data point to the multifunctional and critical role of the stroma in tumor protection and survival and demonstrate how compromising tumor integrity to move toward a more normal physiologic state through stroma-targeting therapy will likely be an instrumental component in treating PDA.

Significance:

This work demonstrates how focused stromal re-engineering approaches to move toward normalization of the stroma disrupt physical barriers to effective drug delivery and promote antitumor immunity.

See related commentary by Huang and Brekken, p. 328
Phase III Trial of Adjuvant Sunitinib in Patients with High-Risk Renal Cell Carcinoma: Exploratory Pharmacogenomic Analysis
Authors: George Daniel J. , Martini Jean-Francois , Staehler Michael , Motzer Robert J. , Magheli Ahmed , Donskov Frede , Escudier Bernard , Li Sherry , Casey Michelle , Valota Olga , Laguerre Brigitte , Pantuck Allan J. , Pandha Hardev S. , Patel Anup , Lechuga Maria , Ravaud Alain
Published: November 2018

Purpose:

In the S-TRAC trial, adjuvant sunitinib prolonged disease-free survival (DFS) versus placebo in patients with loco-regional renal cell carcinoma at high risk of recurrence after nephrectomy. An exploratory analysis evaluated associations between SNPs in several angiogenesis- or hypoxia-related genes and clinical outcomes in S-TRAC.

Patients and Methods:

Blood samples were genotyped for 10 SNPs and one insertion/deletion mutation using TaqMan assays. DFS was compared using log-rank tests for each genotype in sunitinib versus placebo groups and between genotypes within each of three (sunitinib, placebo, and combined sunitinib plus placebo) treatment groups. P values were unadjusted.

Results:

In all, 286 patients (sunitinib, n = 142; placebo, n = 144) were genotyped. Longer DFS [HR; 95% confidence interval (CI)] was observed with sunitinib versus placebo for VEGFR1 rs9554320 C/C (HR 0.44; 95% CI, 0.21–0.91; P = 0.023), VEGFR2 rs2071559 T/T (HR 0.46; 95% CI, 0.23–0.90; P = 0.020), and eNOS rs2070744 T/T (HR 0.53; 95% CI, 0.30–0.94; P = 0.028). Shorter DFS was observed for VEGFR1 rs9582036 C/A versus C/C with sunitinib, placebo, and combined therapies (P ≤ 0.05), and A/A versus C/C with sunitinib (P = 0.022). VEGFR1 rs9554320 A/C versus A/A was associated with shorter DFS in the placebo (P = 0.038) and combined (P = 0.006) groups.

Conclusions:

Correlations between VEGFR1 and VEGFR2 SNPs and longer DFS with sunitinib suggest germline SNPs are predictive of improved outcomes with adjuvant sunitinib in patients with renal cell carcinoma. Independent validation studies are needed to confirm these findings.
Intestinal Toxicity in Rats Following Administration of CDK4/6 Inhibitors Is Independent of Primary Pharmacology
Authors: Thibault Stephane , Hu Wenyue , Hirakawa Brad , Kalabat Dalia , Franks Tania , Sung Tae , Khoh-Reiter Su , Lu Shuyan , Finkelstein Martin , Jessen Bart , Sacaan Aida
Published: November 2018

Recently three different cyclin-dependent kinase 4 and 6 (CDK4/6) dual inhibitors were approved for the treatment of breast cancer (palbociclib, ribociclib, and abemaciclib), all of which offer comparable therapeutic benefits. Their safety profiles, however, are different. For example, neutropenia is observed at varying incidences in patients treated with these drugs; however, it is the most common adverse event for palbociclib and ribociclib, whereas diarrhea is the most common adverse event observed in patients treated with abemaciclib. To understand the mechanism of diarrhea observed with these drugs and in an effort to guide the development of safer drugs, we compared the effects of oral administration of palbociclib, ribociclib, and abemaciclib on the gastrointestinal tract of rats using doses intended to produce comparable CDK4/6 inhibition. Rats administered abemaciclib, but not palbociclib or ribociclib, had fecal alterations, unique histopathologic findings, and distinctive changes in intestinal gene expression. Morphologic changes in the intestine were characterized by proliferation of crypt cells, loss of goblet cells, poorly differentiated and degenerating enterocytes with loss of microvilli, and mucosal inflammation. In the jejunum of abemaciclib-treated rats, downregulation of enterocyte membrane transporters and upregulation of genes associated with cell proliferation were observed, consistent with activation of the Wnt pathway and downstream transcriptional regulation. Among these CDK4/6 inhibitors, intestinal toxicity was unique to rats treated with abemaciclib, suggesting a mechanism of toxicity not due to primary pharmacology (CDK4/6 inhibition), but to activity at secondary pharmacologic targets.
Democracia e políticas públicas de direitos humanos
Authors: Bittar Eduardo C. B.
Published: November 2018

Este artigo é uma reflexão sobre a situação atual das políticas públicas de direitos humanos no Brasil. A reflexão está baseada em relatórios e dados sobre direitos humanos, e assume uma perspectiva empírica, descritiva e crítico-analítica. O desenvolvimento das políticas públicas de direitos humanos, nos últimos anos, diante de certas temáticas específicas, é avaliado segundo o processo de efetivação dos direitos humanos, levando-se em conta o contexto atual, a realidade brasileira e os desafios históricos presentes.
The power of eco-labels: Communicating climate change using carbon footprint labels consistent with international trade regimes under the WTO
Authors: Kloeckner Jane
Published: November 2018

Information is power. At the intersection of culture, science, mass communication, and law, this paper argues that information provided by a transparent and internationally harmonized eco-label scheme serves to enhance understanding of public policy choices for mitigating climate change.Aproduct carbon footprint (PCF) label communicates climate change information to citizen consumers and can indirectly reduce GHG emissions. PCF labels are effective response measures that countries are taking to address global warming and are not obstacles to international trade. The international community should embrace domestic PCF labeling schemes, whether voluntary or mandatory. The PCF label and associated standards, which countries may use as domestic trade measures in response to the challenges of climate change, should be consistent with the rules and regimes of WTO agreements to ensure that these schemes support fair and free international trade. At some time in the future, the UNFCCC parties may reach agreement on a domestic response, including trade measures, to reduce GHG emissions, and PCF labeling schemes may be adapted as needed to assist developing countries’ participation. The WTO should support environmental trade measures that fight global warming, such as a domestic PCF label and associated standards.
Highly Proton Conductive Zn(II)-Based Metal-Organic Framework/Nafion® Composite Membrane for Fuel Cell Application
Authors: Kabir M. D. Lutful , Kim Hee Jin , Choi Sang-June
Published: November 2018

Employing the concept of coordination networks, the conductivity of Nafion® was amplified by fabricating a composite based on Nafion® and an inexpensive and highly proton-conductive three-dimensional metal-organic framework (MOF), namely, {[(Me2NH2)3(SO4)]2[Zn2(ox)3]}n
(1, Me = methyl, ox = oxalate). The proton conductivity increased by more than 18% for the MOF 1/Nafion® composite membrane, e in comparison to pristine cast Nafion® membrane. Such improvement in conductivity can be attributed to the interionic proton
hopping through the extended hydrogen bonding networks, higher concentration of proton carriers, 3D hydrogen pathways (including nanopores on the surface of the MOF 1 crystals) and higher degree of crystallinity. Along with slightly higher thermal stability, increased ion exchange capacity
(IEC) and optimum water uptake were observed, with the addition of 1 wt.% of MOF 1 to Nafion® appearing to be maximally efficient. This study offers a cost-effective and facile fabrication technique for a variety of proton exchange membranes with characteristic proton-conducting
properties for fuel cell applications.
Amphiphilic Blocks Copolymer-Stabilized Electro Catalytic Properties of Platinum Nanoparticles for Methanol Electro Oxidation in Acidic Medium
Authors: Guo Dao-Jun , Cui Shu-Kun
Published: November 2018

Pt/C nanoparticle catalysts were synthesized using amphiphilic blocks copolymer as reducing and stabilizing agent by varying the pH value of the reaction mixtures. The property and structure of Pt/C catalysts were explored by transmission electron microscopy (TEM), energy dispersive
X-ray spectroscopy (EDS) and X-ray diffraction (XRD). The electrochemical catalytic activity for methanol oxidation of the as-prepared Pt/C hybrid was observed by chronoamperometry, cyclic voltammetry. The catalytic activity of the Pt/C catalysts shows much better than the commercial Pt/C
(Johnson Matthey) catalysts for methanol oxidation.
Defining Learning in Educational Leadership: Reframing the Narrative
Authors: Myran Steve , Sutherland Ian
Published: November 2018

Purpose: The purpose of this article is to reframe our field’s narrative around the science of learning. We seek to (1) describe the patterns within educational leadership and administration that are conceptually tethered to scientific management and highlight the absence of clearly defined conceptions of learning, (2) provide a synthesis of the science of learning, and (3) offer a “progressive problem shift” that promotes such a reframing. Methods: An integration of theory building methods with problem posing/identification strategies is designed to deconstruct the field of educational leadership through a science of learning lens and build toward theory that is more adaptive to our goals of leading for learning. Findings: Our findings stem from the central observation that educational leadership and administration has to date produced no conceptual or explicit operational definition of learning. Lacking such a definition, the field has been vulnerable to outlooks about learning that default to assumptions notably shaped by scientific management. This is in contrast to our review of the learning sciences literature, which emphasizes that learning is dependent on the active and deliberate agency of the learner and a host of introspective outlooks and behaviors and that these individual learning characteristics are situated within complex and dynamic social contexts that serve to mediate and shape learning. Implications and Conclusions: We argue that the future of our field rests, in large measure, on our ability to address the incongruences between our field’s foundations in scientific management and the science of learning.
Supporting Immigrant Families and Rural Schools: The Boundary-Spanning Possibilities of an Adult ESL Program
Authors: Shiffman Catherine Dunn
Published: November 2018

Purpose: There has been a significant increase in the number of immigrant families moving to rural communities across the United States. Yet limited research exists that explores relationships between immigrant families and schools in these communities. Rural school districts are often challenged by insufficient resources, expertise, and infrastructure to respond. Adult English as a second language (ESL) programs can be valuable partners. This article explores how instructors in a regional adult ESL program supported relationships between immigrant families and schools in a rural Virginia school district. Research Methods: A case study was conducted between 2014 and 2015. Data collection included observations of adult ESL classes; semistructured interviews with adult ESL instructors, parents of school-age children, and school district leaders and teachers; open-ended questions on a parent survey; and documents. Findings: Four interrelated practices of the adult ESL instructors facilitated understanding and communication between immigrant families and K-12 educators. Adult ESL instructors disseminated information, explained cultural norms and expectations, coached family-school interactions, and created opportunities to connect families and educators. Supporting conditions included characteristics of the adult ESL classes, district leadership and sense of urgency, and multilayered relationships of professionals and actions of the adult ESL coordinator. Implications for Practice: Given the right conditions, adult ESL programs can be valuable partners for rural education leaders seeking to strengthen engagement with immigrant families. These programs can facilitate linkages between schools and adult ESL learners who are parents or caregivers and can be a professional development resource for building district capacity to engage with immigrant families.
Outcomes for Black Students in Team-Based Learning Courses
Authors: Macke Caroline , Canfield James , Tapp Karen , Hunn Vanessa
Published: November 2018

Racial inequity in postsecondary education is a significant social problem. Black students’ academic success is often hindered by feelings of isolation, particularly at predominantly White institutions (PWIs). Educators should ensure that their teaching strategies promote a sense of belonging. Team-based learning (TBL) is a small-group pedagogy that is being used at an increasing rate. The extant literature has not yet examined the impact of TBL on Black students. The current study compared the academic outcomes of White and Black students enrolled in TBL courses. In this study of 148 social work students, academic outcomes were operationalized as grade point average (GPA), course grade, and peer evaluation score. Findings indicate that although Black students had comparable GPAs and course grades, they scored significantly lower on peer evaluations. Implications are discussed.
Identifying unified kinetic model parameters for thermal decomposition of polymer matrix composites
Authors: Sihn Sangwook , Ehlert Gregory J , Roy Ajit K , Vernon Jonathan P
Published: November 2018

Predicting thermal responses of composite materials requires accurate input parameters derived from reliable thermal property characterization and kinetic models. Composite material properties and decomposition kinetics vary with temperature and heating rate. Typically, conventional kinetic models derived from thermogravimetric analysis data result in multiple sets of kinetic model parameters, which are difficult to implement into numerical simulations under widely varying temperature and heating rate conditions. Here, a methodology was developed to reliably predict decomposition processes of composite materials with a single (i.e., unified) set of kinetic model parameters. The unified kinetic model parameters for each of four different composite materials were used to accurately predict decomposition kinetics observed over the entire range of experimental temperatures and heating rates. Furthermore, this broadly applicable methodology may predict decomposition from limited data sets, and is expected to extrapolate reliably measurable data to experimentally challenging heating rates and temperatures.
Induction of M2 Macrophages Prevents Bone Loss in Murine Periodontitis Models
Authors: Zhuang Z. , Yoshizawa-Smith S. , Glowacki A. , Maltos K. , Pacheco C. , Shehabeldin M. , Mulkeen M. , Myers N. , Chong R. , Verdelis K. , Garlet G.P. , Little S. , Sfeir C.
Published: November 2018

Periodontitis is characterized by the progressive destruction of tooth-supporting alveolar bone, which is mainly caused by chronic inflammation in response to persistent bacterial insult. It has recently become clear that the pathogenesis of periodontitis is associated with a high ratio of proinflammatory M1 (classically activated) macrophages to anti-inflammatory M2 (alternatively activated). To decrease the inflammatory activity, we locally delivered the C-C motif chemokine ligand 2 (CCL2) using controlled-release microparticles (MPs). CCL2 is known to promote chemotaxis of M0 or M2 phenotype macrophages to the inflamed site and induce M2 phenotype polarization locally. Our in vitro data showed that CCL2 increased the number of M2 phenotype macrophages, decreased TNF-α secretion, and enhanced chemotaxis of RAW264.7 cells toward CCL2 MPs. Moreover, we induced periodontal disease in 2 animal models through inoculation of Porphyromonas gingivalis and ligature around the murine molar. Micro–computed tomography analysis showed significant reduction of alveolar bone loss in the CCL2 MP treatment group when compared with a blank MP group and a no-treatment periodontitis group in both models. Immunohistologic analysis showed a significant increase in the M2 phenotype subset and a decrease in the M1 phenotype subset in the CCL2 MP group of the P. gingivalis–induced model. Also, in both models, tartrate-resistant acidic phosphatase staining showed significantly fewer numbers of osteoclasts in the CCL2 MP group in alveolar bone area. Moreover, quantitative polymerase chain reaction results showed a significant increase in IL-1RA (interleukin 1 receptor antagonist) mRNA expression and a decrease in RANKL (receptor activator of nuclear factor kappa-Β ligand) mRNA expression in the CCL2 MP group in the ligature model. In summary, manipulation of endogenous M2 phenotype macrophages with CCL2 MPs decreased the M1 phenotype:M2 phenotype ratio and prevented alveolar bone loss in mouse periodontitis models. The delivery of CCL2 MPs provides a novel approach to treat periodontal disease.