bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrous Ethanol Steam Reforming and Thermochemical Recuperation to Improve Dual-Fuel Diesel Engine Emissions and Efficiency
Authors: Hwang Jeffrey T. , Kane Seamus P. , Northrop William F.
Published: January 2019

Dual-fuel strategies can enable replacement of diesel fuel with low reactivity biofuels like hydrous ethanol. Our previous work has shown that dual-fuel strategies using port injection of hydrous ethanol can replace up to 60% of diesel fuel on an energy basis. However, they yield negligible benefits in NOx emissions, soot emissions, and brake thermal efficiency (BTE) over conventional single fuel diesel operation. Pretreatment of hydrous ethanol through steam reforming before mixing with intake air offers the potential to both increase BTE and decrease soot and NOx emissions. Steam reforming can upgrade the heating value of the secondary fuel through thermochemical recuperation (TCR) and produces inert gases to act as a diluent similar to exhaust gas recirculation. This study experimentally investigated a novel thermally integrated steam reforming reactor that uses sensible and chemical energy in the exhaust to provide the necessary heat for hydrous ethanol steam reforming. An off-highway diesel engine was operated at three speed and load settings with varying hydrous ethanol flow rates reaching fumigant energy fractions of up to 70%. The engine achieved soot reductions of close to 90% and minor NOx reductions; however, carbon monoxide and unburned hydrocarbon emissions increased. A first law energy balance using the experimental data shows that efficient TCR effectively upgraded the heating value of the secondary fuel. Overall, hydrous ethanol steam reforming using TCR can lead to 23% increase in fuel heating value at 100% conversion, a limit approached in the conducted experiments.
Optimization of a nanoscale field emission cell with a planar blade-shaped multilayer graphene/SiC emitter
Authors: Jityaev Igor L. , Svetlichnyi Alexander M.
Published: January 2019

The paper reports an investigation of planar field emission cathodes with a nanoscale interelectrode gap in high electric fields. The multilayer graphene film is used as a rectangular blade-shaped cathode. The authors carry out simulations of the distribution of the electric field strength along the emitting surface. Six types of distribution of the field enhancement factor are revealed by the simulations. The localized enhancement of the electric field strength at the blade corners is observed. The influence of the anode parameters on the emission homogeneity along the emitting surface of the cathode in strong electric fields is determined. The analysis of the simulation results suggests that an increase in the rounding-off radius of the emitter corner does not contribute to the complete elimination of the field enhancement factor heterogeneity. Additional anode modification makes it possible to obtain a homogeneous field enhancement factor along the emitting surface of the cathode and to improve the stability of the emission.
Synthetic WSe
2
monolayers with high photoluminescence quantum yield
Authors: Kim Hyungjin , Ahn Geun Ho , Cho Joy , Amani Matin , Mastandrea James P. , Groschner Catherine K. , Lien Der-Hsien , Zhao Yingbo , Ager Joel W. , Scott Mary C. , Chrzan Daryl C. , Javey Ali
Published: January 2019

A simple substrate decoupling method with optimized growth conditions enables a high-quality synthetic monolayer semiconductor.
Observation of twist-induced geometric phases and inhibition of optical tunneling via Aharonov-Bohm effects
Authors: Parto Midya , Lopez-Aviles Helena , Antonio-Lopez Jose E. , Khajavikhan Mercedeh , Amezcua-Correa Rodrigo , Christodoulides Demetrios N.
Published: January 2019

A new type of geometric phase in twisted optical fibers enables optical tunneling suppression via the Aharonov-Bohm effect.
Genetic and structural insights into broad neutralization of hepatitis C virus by human V
H
1-69 antibodies
Authors: Tzarum Netanel , Giang Erick , Kong Leopold , He Linling , Prentoe Jannick , Augestad Elias , Hua Yuanzi , Castillo Shaun , Lauer Georg M. , Bukh Jens , Zhu Jiang , Wilson Ian A. , Law Mansun
Published: January 2019

We elucidate the role of human V
H
1-69 antibodies in broad neutralization of HCV to facilitate rational vaccine design.
Efficacy and Safety of Pyronaridine-Artesunate plus Single-Dose Primaquine for Treatment of Uncomplicated
Plasmodium falciparum
Malaria in Eastern Cambodia
Authors: Leang Rithea , Mairet-Khedim Melissa , Chea Huch , Huy Rekol , Khim Nimol , Mey Bouth Denis , Dorina Bustos Maria , Ringwald Pascal , Witkowski Benoit
Published: January 2019

In Cambodia, multidrug-resistant
Plasmodium falciparum
undermines the treatment of uncomplicated malaria, and new therapeutic options are needed. Pyronaridine-artesunate has not previously been evaluated in eastern Cambodia.
High Prevalence of Bedaquiline Resistance in Treatment-Naive Tuberculosis Patients and Verapamil Effectiveness
Authors: Ghajavand Hasan , Kargarpour Kamakoli Mansour , Khanipour Sharareh , Pourazar Dizaji Shahin , Masoumi Morteza , Rahimi Jamnani Fatemeh , Fateh Abolfazl , Siadat Seyed Davar , Vaziri Farzam
Published: January 2019

In the regions where bedaquiline (BDQ) is introduced into the regimen, analysis of MIC and screening for preexisting resistance mutations could be crucial. The high prevalence of isolates with high BDQ MICs without prior exposure to BDQ was worrisome.
Poly(ADP-Ribose) Polymerases in Host-Pathogen Interactions, Inflammation, and Immunity
Authors: Brady Pamlea N. , Goel Anupam , Johnson Margaret A.
Published: January 2019

The literature review presented here details recent research involving members of the poly(ADP-ribose) polymerase (PARP) family of proteins. Among the 17 recognized members of the family, the human enzyme PARP1 is the most extensively studied, resulting in a number of known biological and metabolic roles.
Conserved Role for Biofilm Matrix Polysaccharides in
Candida auris
Drug Resistance
Authors: Dominguez E. G. , Zarnowski R. , Choy H. L. , Zhao M. , Sanchez H. , Nett Jeniel E. , Andes D. R.
Published: January 2019

Candida auris
is an emerging fungal threat linked to poor patient outcomes. The factors responsible for this apparent increase in pathogenicity remain largely unknown. Biofilm formation has been suggested as an important factor for persistence of this organism in patients and the environment. Our findings reveal one mechanism utilized by
C. auris
to evade the effect of triazole antifungal therapy during biofilm growth. The conservation of the protective biofilm matrix among
Candida
spp. suggests that is a promising pan-fungal
Candida
biofilm drug target.
Audrey Iris Peniston
Authors: Ware A. M. , Murray Max , Boyd Jack , Jarrett Oswald
Published: January 2019

Dedicated to her profession, she did not spare her words when animals were mishandled.
Fetal alcohol spectrum disorder (FASD) affects the hippocampal levels of histone variant H2A.Z-2
Authors: Gretzinger Taylor L. , Tyagi Monica , Fontaine Christine J. , Cheema Manjinder S. , González-Perez María , Freeman Melissa E. , Christie Brian R. , Ausió Juan
Published: January 2019

Fetal alcohol spectrum disorder (FASD) is caused by prenatal exposure to ethanol and has been linked to neurodevelopmental impairments. Alcohol has the potential to alter some of the epigenetic components that play a critical role during development. Previous studies have provided evidence that prenatal exposure to ethanol results in abnormal epigenetic patterns (i.e., hypomethylation) of the genome. The aim of this study was to determine how prenatal exposure to ethanol in rats affects the hippocampal levels of expression of two important brain epigenetic transcriptional regulators involved in synaptic plasticity and memory consolidation: methyl CpG-binding protein 2 (MeCP2) and histone variant H2A.Z. Unexpectedly, under the conditions used in this work we were not able to detect any changes in MeCP2. Interestingly, however, we observed a significant decrease in H2A.Z, accompanied by its chromatin redistribution in both female and male FASD rat pups. Moreover, the data from reverse-transcription qPCR later confirmed that this decrease in H2A.Z is mainly due to down-regulation of its H2A.Z-2 isoform gene expression. Altogether, these data provide strong evidence that prenatal exposure to ethanol alters histone variant H2A.Z during neurogenesis of rat hippocampus.
Joule–Thomson expansion in AdS black hole with a global monopole
Authors: Ahmed Rizwan C. L. , Naveena Kumara A. , Vaid Deepak , Ajith K. M.
Published: January 2019

In this paper, we investigate the Joule–Thomson effects of AdS black holes with a global monopole. We study the effect of the global monopole parameter [Formula: see text] on the inversion temperature and isenthalpic curves. The obtained result is compared with Joule–Thomson expansion of van der Waals fluid, and the similarities were noted. Phase transition occuring in the extended phase space of this black hole is analogous to that in van der Waals gas. Our study shows that global monopole parameter [Formula: see text] plays a very important role in Joule–Thomson expansion.
Structure and mechanical properties of laser-MIG hybrid welded SAF 2507 super duplex stainless steel joints
Authors: Qi Kai , Li Ruifeng , Wang Guangjin , Sun Zhe
Published: January 2019

Joining of super duplex stainless steel (SDSS) is still a challenge, in particular, the need to control the phase balance in the weld metal. In this paper, laser-MIG hybrid welding process was used to join SAF 2507 SDSS plates. The effects of welding parameters on weld appearance, microstructure and phase distribution and mechanical properties were studied systematically. Results showed that the arc/laser hybrid effect was more significant when the arc led the laser with 2 mm distance. It was indicated that arc current mainly affected the weld width while laser power mainly affected weld penetration depth. The composition and microstructure varied a lot at different positions in the weld due to the differences in peak temperature and cooling rate. From top to root, the content of ferrite phase increased and austenite phase decreased. With optimized welding parameters, due to the increase of heat input and the introduction of welding wire, the ferrite/austenite phase balance in the weld metal was obtained. Mechanical property tests showed that the joints exhibited higher tensile strength but lower toughness compared to base metal.
A Novel Memductor‐Based Chaotic System and Its Applications in Circuit Design and Experimental Validation
Authors: Xiong Li , Lu Yanjun , Zhang Yongfang , Zhang Xinguo
Published: January 2019

This paper is expected to introduce a novel memductor‐based chaotic system. The local dynamical entities, such as the basic dynamical behavior, the divergence, the stability of equilibrium set, and the Lyapunov exponent, are all investigated analytically and numerically to reveal the dynamic characteristics of the new memductor‐based chaotic system as the system parameters and the initial state of memristor change. Subsequently, an active control method is derived to study the synchronous stability of the novel memductor‐based chaotic system through making the synchronization error system asymptotically stable at the origin. Further to these, a memductor‐based chaotic circuit is designed, realized, and applied to construct a new memductor‐based secure communication circuit by employing the basic electronic components and memristor. Furthermore, the design principle of the memductor‐based chaotic circuit is thoroughly analyzed and the concept of “the memductor‐based chaotic circuit defect quantification index” is proposed for the first time to verify whether the chaotic output is consistent with the mathematical model. A good qualitative agreement is shown between the simulations and the experimental validation results.
Ester-Producing Mechanism of Ethanol O-acyltransferaseEHT1Gene inPichia pastorisfrom Shanxi Aged Vinegar
Authors: Chen Jia , Nan Ruipeng , Wang Rufu , Zhang Lixin , Shi Junfeng
Published: January 2019

The ethanol O-acyltransferaseEHT1is an important element of key signaling pathways and is widely expressed in yeast strains. In this study, we investigated the expression ofEHT1 in the overexpression lines or knockout system ofPichia pastorisusing qRT-PCR and western blotting. The amount of total protein was determined using the Bradford method; the esterase activity was determined using p-nitrophenyl acetate as a substrate, and the production of volatile fatty acids in wild-type, knockout, and over-expression systems was detected using SPME GC-MS. The esterase activity ofEHT1-knockoutP. pastoriswas significantly lower than that in wild type (P<0.01), and the activities of esterase in threeEHT1-overexpressing strains—OE-1, OE-2, and OE-3—were significantly higher than those in wild type (P<0.01). In theEHT1-knockout strain products, the contents of nine volatile fatty acids were significantly lower than those in wild type (P<0.01), and the relative percentages of three fatty acids, methyl nonanoate, methyl decanoate, and ethyl caprate, were significantly lower than those in the other six species in the wild-type and knockout groups (P<0.05). The nine volatile fatty acids in the fermentation products of the overexpressedEHT1 gene were significantly higher than those in the wild-type group (P<0.01). The relative percentages of the three fatty acid esters, methyl nonanoate, methyl caprate, and ethyl caprate, were significantly higher than those in the other six species (P<0.05).EHT1 plays an important regulatory role in esterase activity and the production of medium-chain volatile fatty acids.
Eigen Solution of Neural Networks and Its Application in Prediction and Analysis of Controller Parameters of Grinding Robot in Complex Environments
Authors: Tang Shixi , Gu Jinan , Tang Keming , Ding Wei , Shang Zhengyang
Published: January 2019

The robot dynamic model is often rarely known due to various uncertainties such as parametric uncertainties or modeling errors existing in complex environments. It is a key problem to find the relationship between the changes of neural network structure and the changes of input and output environments and their mutual influences. Firstly, this paper defined the conceptions of neural network solution, neural network eigen solution, neural network complete solution, and neural network partial solution and the conceptions of input environments, output environments, and macrostructure of neural networks. Secondly, an eigen solution theory of general neural networks was proposed and proven including consistent approximation theorem, eigen solution existence theorem, consistency theorem of complete solution, the partial solution, and none solution theorem of neural networks. Lastly, to verify the eigen solution theory of neural networks, the proposed theory was applied to a novel prediction and analysis model of controller parameters of grinding robot in complex environments with deep neural networks and then build prediction model with deep learning neural networks for controller parameters of grinding robot. The morphological subfeature graph with multimoment was constructed to describe the block surface morphology using rugosity, standard deviation, skewness, and kurtosis. The results of theoretical analysis and experimental test show that the output traits have an optional effect with joint action. When the input features functioning in prediction increase, higher predicted accuracy can be obtained. And when the output traits involving in prediction increase, more output traits can be predicted. The proposed prediction and analysis model with deep neural networks can be used to find and predict the inherent laws of the data. Compared with the traditional prediction model, the proposed model can predict output features simultaneously and is more stable.
Skeletal Muscle Resident Progenitor Cells Coexpress Mesenchymal and Myogenic Markers and Are Not Affected by Chronic Heart Failure-Induced Dysregulations
Authors: Dmitrieva R. I. , Lelyavina T. A. , Komarova M. Y. , Galenko V. L. , Ivanova O. A. , Tikanova P. A. , Khromova N. V. , Golovkin A. S. , Bortsova M. A. , Sergushichev A. , Sitnikova M. Yu. , Kostareva A. A.
Published: January 2019

Background and Purpose. In heart failure (HF), metabolic alterations induce skeletal muscle wasting and decrease of exercise capacity and quality of life. The activation of skeletal muscle regeneration potential is a prospective strategy to reduce muscle wasting; therefore, the aim of this project was to determine if functional properties of skeletal muscle mesenchymal progenitor cells (SM-MPC) were affected by HF-induced functional and metabolic dysregulations. Methods. Gastrocnemius muscle biopsy samples were obtained from 3 healthy donors (HD) and 12 HF patients to purify mRNA for further analysis and to isolate SM-MPC. Cells were expanded in vitro and characterized by immunocytochemistry and flow cytometry for expression of mesenchymal (CD105/CD73/CD166/CD146/CD140b/CD140a/VIM) and myogenic (Myf5/CD56/MyoG) markers. Cells were induced to differentiate and were then analyzed by immunostaining and Q-PCR to verify the efficiency of differentiation. The expression of genes that control muscle metabolism and development was compared for HD/HF patients in both muscle biopsy and in vitro-differentiated myotubes. Results. The upregulation of MYH3/MYH8/Myf6 detected in HF skeletal muscle along with metabolic alterations indicates chronic pathological activation of the muscle developmental program. SM-MPC isolated from HD and HF patients represented a mixed population that coexpresses both mesenchymal and myogenic markers and differs from AD-MMSC, BM-MMSC, and IMF-MSC. The functional properties of SM-MPC did not differ between HD and HF patients. Conclusion. In the present work, we demonstrate that the metabolic and functional alterations we detected in skeletal muscle from HF patients do not dramatically affect the functional properties of purified and expanded in vitro SM-MPC. We speculate that skeletal muscle progenitor cells are protected by their niche and under beneficial circumstances could contribute to muscle restoration and prevention and treatment of muscle wasting. The potential new therapeutic strategies of HF-induced skeletal muscle wasting should be targeted on both activation of SM-MPC regeneration potential and improvement of skeletal muscle metabolic status to provide a favorable environment for SM-MPC-driven muscle restoration.
Analytical Fuzzy Predictive Control Applied to Wastewater Treatment Biological Processes
Authors: Vallejo LLamas Pedro M. , Vega Pastora
Published: January 2019

A novel control fuzzy predictive control law is proposed and successfully applied to a wastewater treatment process in this paper. The proposed control law allows us to evaluate the control signal in an analytical way, each sampling time being a nonlinear and fuzzy alternative to other classic predictive controllers. The control law is based on the formalization of the internal fuzzy predictive model of the process as linear time‐varying state space equations that are updated every discrete time instant to take into account the nonlinearity effects due to disturbance action and changes in the operating point with time. The model is then used to evaluate the predictions, and, taking them as a starting point and considering them as a paradigm of the predictive functional control strategy, a control law, it is derived in an analytical and explicit way by imposing on the outputs of the follow‐up of certain reference trajectories previously established. The work presented here addresses the application of this particular strategy of intelligent predictive control to the case of an activated sludge wastewater treatment process successfully in a simulation environment of a real plant taking into account real data for the disturbance records. Such a process is multivariable, nonlinear, time varying, and difficult to control due to its biological nature. The proposed control law can be straightforwardly used within a dual-mode MPC scheme to handle constraints, as a nonlinear and fuzzy alternative to the classic state feedback control law.
The Impact of Social Inclusion on the Social Development of Students with a General Learning Difficulty in Postprimary Education in Ireland
Authors: King Niall , Ryan Barry J.
Published: January 2019

Over the past decade, there has been a societal push for social inclusion in Ireland for students with special educational needs (SEN). As a result, the number of dedicated special needs schools has dramatically decreased across the country as students with SEN enrol, instead, in mainstream schools. Dedicated SEN schools provided an environment in which students with a general learning difficulty (GLD) could develop at a pace suited to them. However, this developmental pace is different for GLD students in a mainstream school. This research explores the social development of students with a GLD in a mainstream school in postprimary education in Ireland. Informed by educational policies, both national and international, this research aims to find whether we are, as a society, inclusive of all educational needs in postprimary education, specifically students with GLD. The research question explicitly explores if students with a GLD have enhanced social development as a result of being part of a mainstream school setting. Employing a mixed methods case-study methodology, key emergent themes were observed and, overall, it was concluded that in a suitable environment, both physical and cultural, the social skills of students with a GLD can improve, primarily through increased social interaction with their peers.
Solid Indeterminate Pulmonary Nodules Less Than or Equal to 250 mm3: Application of the Updated Fleischner Society Guidelines in Clinical Practice
Authors: Borghesi Andrea , Michelini Silvia , Nocivelli Giorgio , Silva Mario , Scrimieri Alessandra , Pezzotti Stefania , Maroldi Roberto , Farina Davide
Published: January 2019

Background. The latest version of the Fleischner Society guidelines for management of incidental pulmonary nodules was published in 2017. The main purpose of these guidelines is to reduce the number of unnecessary computed tomography (CT) examinations during the follow-up of small indeterminate nodules. Objective. The present study aimed to evaluate the performance of these guidelines for management of solid indeterminate pulmonary nodules (SIPNs) ≤ 250 mm3. Materials and Methods. During a 7-year period, we retrospectively reviewed the chest CT scans of 672 consecutive patients with SIPNs. The study sample was selected according to the following inclusion criteria: solitary SIPN; diameter ≥ 3 mm; volume ≤ 250 mm3; two or more CT scans performed with the same scanner and same acquisition/reconstruction protocol; thin-section 1-mm images in DICOM format; histologic diagnosis or follow-up ≥ 2 years; and no oncological history. Applying these criteria, a total of 27 patients with single SIPNs ≤ 250 mm3 were enrolled. For each SIPN, the volume and doubling time were calculated using semiautomatic software throughout the follow-up period. For each SIPN, we applied the Fleischner Society guidelines, and the recommended management was compared to what was actually done. Results. A significant volumetric increase was detected in 5/27 (18.5%) SIPNs; all growing nodules were observed in high-risk patients. In these SIPNs, a histologic diagnosis of malignancy was obtained. Applying the Fleischner Society recommendations, all five malignant nodules would have been identified. None of the SIPNs < 100 mm3 in low-risk patients showed significant growth during the follow-up period. The application of the new guidelines would have led to a significant reduction in follow-up CT examinations (Hodges-Lehmann median difference, -2 CT scans; p = 0.0001). Conclusion. The application of the updated Fleischner Society guidelines has been shown to be effective in the management of SIPNs ≤ 250 mm3 with a significant reduction in radiation dose.
Employability among Statistics Graduates: Graduates’ Attributes, Competence, and Quality of Education
Authors: Woya Ashenafi Abate
Published: January 2019

An aspect of quality in higher education is the quality of the outcomes achieved. Higher education adds value by developing job-related skills and competencies. It is also not known to what extent, graduates’ competence goes in line with the demands of the employers. This study was to assess the employability and competency of statistics graduates. Data were collected using a structured questionnaire and analysis the using SPSS version 23. This study employed a Kaplan–Meier estimate to compare the duration of unemployed times from two or more groups. To assess whether there is a real difference between groups, we used Log-rank test. From a total of 303 statistics graduates, 17.7% were unemployed and 82.3% were employed. Of employed graduates, 65.8% had a permanent worker and the rest 16.5% of graduates had a temporary worker. The mean duration of unemployed statistics graduate at Bahir Dar University was 12.9 month (95% CI, (9.9, 15.9)). This study revealed that there is a percentage of graduates who are not yet employed and never been employed. Therefore, the department must be a linkage with the different government organization and NGO.This may improve the employability of statistics graduates.
Riesgos asociados a los hijos de mujeres con trastornos alimentarios
Authors: Cordella-Masini María Patricia , Aedo Karina , Ramirez Verónica
Published: January 2019

Resumen Se analiza literatura sobre la influencia materna que los trastornos alimentarios y de la ingestión de alimentos (TAI) tienen sobre el desarrollo psíquico de los hijos. De 1.096 artículos encontrados en PubMed, PsycINFO, Scielo, ProQuest Health & Medical Collection, 32 aportan información relevante organizada en 6 categorías: 1-Alimentación; 2-Antropometría; 3-Percepción materna de los hijos; 4-Percepción de los hijos hacia sus madres; 5-Estilo parental; 6-Psicopatología de los hijos.La evidencia muestra influencia de TAI materno sobre el psico - desarrollo de los hijos. Se discuten mecanismos involucrados y se sugiere seguir avanzando en investigación y clínica
Salud Mental en Chile
Authors: Torres Rafael
Published: January 2019

Editorial
SIX2 Mediates Late-Stage Metastasis via Direct Regulation of SOX2 and Induction of a Cancer Stem Cell Program
Authors: Oliphant Michael U.J. , Vincent Melanie Y. , Galbraith Matthew D. , Pandey Ahwan , Zaberezhnyy Vadym , Rudra Pratyaydipta , Johnson Katherine R. , Costello James C. , Ghosh Debashis , DeGregori James , Espinosa Joaquin M. , Ford Heide L.
Published: January 2019

The capacity for tumor cells to metastasize efficiently is directly linked to their ability to colonize secondary sites. Here we identify Six2, a developmental transcription factor, as a critical regulator of a breast cancer stem cell program that enables metastatic colonization. In several triple-negative breast cancer (TNBC) models, Six2 enhanced the expression of genes associated with embryonic stem cell programs. Six2 directly bound the Sox2 Srr2 enhancer, promoting Sox2 expression and downstream expression of Nanog, which are both key pluripotency factors. Regulation of Sox2 by Six2 enhanced cancer stem cell properties and increased metastatic colonization. Six2 and Sox2 expression correlated highly in breast cancers including TNBC, where a Six2 expression signature was predictive of metastatic burden and poor clinical outcome. Our findings demonstrate that a SIX2/SOX2 axis is required for efficient metastatic colonization, underscoring a key role for stemness factors in outgrowth at secondary sites.

Significance:

These findings provide novel mechanistic insight into stemness and the metastatic outgrowth of triple-negative breast cancer cells.
Ovarian Tumor Cell Expression of Claudin-4 Reduces Apoptotic Response to Paclitaxel
Authors: Breed Christopher , Hicks Douglas A. , Webb Patricia G. , Galimanis Carly E. , Bitler Benjamin G. , Behbakht Kian , Baumgartner Heidi K.
Published: January 2019

A significant factor contributing to poor survival rates for patients with ovarian cancer is the insensitivity of tumors to standard-of-care chemotherapy. In this study, we investigated the effect of claudin-4 expression on ovarian tumor cell apoptotic response to cisplatin and paclitaxel. We manipulated claudin-4 gene expression by silencing expression [short hairpin RNA (shRNA)] in cells with endogenously expressed claudin-4 or overexpressing claudin-4 in cells that natively do not express claudin-4. In addition, we inhibited claudin-4 activity with a claudin mimic peptide (CMP). We monitored apoptotic response by caspase-3 and Annexin V binding. We examined proliferation rate by counting the cell number over time as well as measuring the number of mitotic cells. Proximity ligation assays, immunoprecipitation (IP), and immunofluorescence were performed to examine interactions of claudin-4. Western blot analysis of tubulin in cell fractions was used to determine the changes in tubulin polymerization with changes in claudin-4 expression. Results show that claudin-4 expression reduced epithelial ovarian cancer (EOC) cell apoptotic response to paclitaxel. EOCs without claudin-4 proliferated more slowly with enhanced mitotic arrest compared with the cells expressing claudin-4. Furthermore, our results indicate that claudin-4 interacts with tubulin, having a profound effect on the structure and polymerization of the microtubule network. In conclusion, we demonstrate that claudin-4 reduces the ovarian tumor cell response to microtubule-targeting paclitaxel and disrupting claudin-4 with CMP can restore apoptotic response.

Implications:

These results suggest that claudin-4 expression may provide a biomarker for paclitaxel response and can be a target for new therapeutic strategies to improve response.
Periprostatic Adipose Tissue Favors Prostate Cancer Cell Invasion in an Obesity-Dependent Manner: Role of Oxidative Stress
Authors: Laurent Victor , Toulet Aurélie , Attané Camille , Milhas Delphine , Dauvillier Stéphanie , Zaidi Falek , Clement Emily , Cinato Mathieu , Le Gonidec Sophie , Guérard Adrien , Lehuédé Camille , Garandeau David , Nieto Laurence , Renaud-Gabardos Edith , Prats Anne-Catherine , Valet Philippe , Malavaud Bernard , Muller Catherine
Published: January 2019

Prostate gland is surrounded by periprostatic adipose tissue (PPAT), which is increasingly believed to play a paracrine role in prostate cancer progression. Our previous work demonstrates that adipocytes promote homing of prostate cancer cells to PPAT and that this effect is upregulated by obesity. Here, we show that once tumor cells have invaded PPAT (mimicked by an in vitro model of coculture), they establish a bidirectional crosstalk with adipocytes, which promotes tumor cell invasion. Indeed, tumor cells induce adipocyte lipolysis and the free fatty acids (FFA) released are taken up and stored by tumor cells. Incubation with exogenous lipids also stimulates tumor cell invasion, underlining the importance of lipid transfer in prostate cancer aggressiveness. Transferred FFAs (after coculture or exogenous lipid treatment) stimulate the expression of one isoform of the pro-oxidant enzyme NADPH oxidase, NOX5. NOX5 increases intracellular reactive oxygen species (ROS) that, in turn, activate a HIF1/MMP14 pathway, which is responsible for the increased tumor cell invasion. In obesity, tumor-surrounding adipocytes are more prone to activate the depicted signaling pathway and to induce tumor invasion. Finally, the expression of NOX5 and MMP14 is upregulated at the invasive front of human tumors where cancer cells are in close proximity to adipocytes and this process is amplified in obese patients, underlining the clinical relevance of our results.

Implications:

Our work emphasizes the key role of adjacent PPAT in prostate cancer dissemination and proposes new molecular targets for the treatment of obese patients exhibiting aggressive diseases.
Changes in Health and Wellbeing in the Years Leading up to a Cancer Diagnosis: A Prospective Cohort Study
Authors: Jackson Sarah E. , Williams Kate , Beeken Rebecca J. , Steptoe Andrew
Published: January 2019

Emerging evidence suggests cancer survivors suffer impairments in health and wellbeing that predate their diagnosis. This study prospectively examined changes from 4 to 6 years prediagnosis to 0 to 2 years postdiagnosis. Data were from 477 cancer survivors and 5,451 cancer-free comparisons participating in the English Longitudinal Study of Ageing. We examined group-by-time interactions for self-rated health, quality of life (QoL), depression, life satisfaction and impairments in mobility, activities of daily living (ADL), and instrumental ADLs (IADL). All health and wellbeing markers worsened over time in both groups. A greater decline in cancer survivors’ self-rated health was evident as early as 2 to 4 years prediagnosis (P < 0.001). Around diagnosis, there were greater declines in IADL impairment (P < 0.001), QoL (P < 0.001), and depression (P < 0.001) in cancer survivors than in controls. Mobility and ADL impairments were consistently more prevalent among cancer survivors (P < 0.001), and life satisfaction was consistently lower (P = 0.004), but the rate of change over time did not differ significantly between groups. These results suggest there may be early signs of deterioration in perceived health that precede development of symptoms leading to cancer diagnosis by many years. Some of the impaired wellbeing in cancer patients may be long-standing, while other changes are more acute and may require targeted support following diagnosis.
Chemical Peeling as an Innovative Treatment Alternative to Oral Antifungals for Onychomycosis in Special Circumstances
Authors: Sonthalia Sidharth , Jakhar Deepak , Yadav Pravesh , Kaur Ishmeet
Published: January 2019

Toe nail onychomycosis (ONM) is a common problem in elderly patients. Treatment in diabetic patients with associated comorbidities such as congestive heart failure becomes a challenge. Oral antifungals are best avoided owing to most of them being contraindicated or unsafe due to comorbidities and/or risk of drug interactions stemming from polypharmacy. Topical agents alone are not effective. Unlike isolated ONM in healthy and younger patients, ONM involving multiple nails in geriatric and diabetic patients warrants treatment as it serves as a source of recurrent tinea of the feet and other sites, and even contributes to formation of diabetic foot ulcers. Long-pulsed Nd:YAG and fractional CO2 laser (in addition to antifungals) have been reported to provide gratifying results in toe nail ONM. But high treatment cost is a major limitation. Nail peeling with glycolic acid (GA) and low-concentration croton-oil free phenol (CFP) peels have been used in different nail conditions but not specifically for ONM. We report the successful use of Black peel (a superficial-to-medium depth peel used typically for anti-acne and cosmetic indications), a combination of 50% black acetic acid, 0.5% salicylic acid, 6% tetrahydrojasmonic acid, 10% bio sulphur, and 0.1% potassium iodide, in two difficult cases with ONM of multiple nails, the rationale of use being the additional anti-fungal effects of all the peel components.
KLF11 (Krüppel-Like Factor 11) Inhibits Arterial Thrombosis via Suppression of Tissue Factor in the Vascular Wall
Authors: Liang Wenying , Fan Yanbo , Lu Haocheng , Chang Ziyi , Hu Wenting , Sun Jinjian , Wang Huilun , Zhu Tianqing , Wang Jintao , Adili Reheman , Garcia-Barrio Minerva T. , Holinstat Michael , Eitzman Daniel , Zhang Jifeng , Chen Y. Eugene
Published: January 2019

Objective—

Mutations in Krüppel like factor-11 (
KLF11
), a gene also known as maturity-onset diabetes mellitus of the young type 7, contribute to the development of diabetes mellitus. KLF11 has anti-inflammatory effects in endothelial cells and beneficial effects on stroke. However, the function of KLF11 in the cardiovascular system is not fully unraveled. In this study, we investigated the role of KLF11 in vascular smooth muscle cell biology and arterial thrombosis.

Approach and Results—

Using a ferric chloride–induced thrombosis model, we found that the occlusion time was significantly reduced in conventional
Klf11
knockout mice, whereas bone marrow transplantation could not rescue this phenotype, suggesting that vascular KLF11 is critical for inhibition of arterial thrombosis. We further demonstrated that vascular smooth muscle cell–specific
Klf11
knockout mice also exhibited significantly reduced occlusion time. The expression of tissue factor (encoded by the
F3
gene), a main initiator of the coagulation cascade, was increased in the artery of
Klf11
knockout mice, as determined by real-time quantitative polymerase chain reaction and immunofluorescence. Furthermore, vascular smooth muscle cells isolated from
Klf11
knockout mouse aortas showed increased tissue factor expression, which was rescued by KLF11 overexpression. In human aortic smooth muscle cells, small interfering RNA–mediated knockdown of KLF11 increased tissue factor expression. Consistent results were observed on adenovirus-mediated overexpression of KLF11. Mechanistically, KLF11 downregulates
F3
at the transcriptional level as determined by reporter and chromatin immunoprecipitation assays.

Conclusions—

Our data demonstrate that KLF11 is a novel transcriptional suppressor of
F3
in vascular smooth muscle cells, constituting a potential molecular target for inhibition of arterial thrombosis.
Between-network Functional Connectivity Is Modified by Age and Cognitive Task Domain
Authors: Varangis Eleanna , Razlighi Qolamreza , Habeck Christian G. , Fisher Zachary , Stern Yaakov
Published: January 2019

Research on the cognitive neuroscience of aging has identified myriad neurocognitive processes that are affected by the aging process, with a focus on identifying neural correlates of cognitive function in aging. This study aimed to test whether internetwork connectivity among six cognitive networks is sensitive to age-related changes in neural efficiency and cognitive functioning. A factor analytic connectivity approach was used to model network interactions during 11 cognitive tasks grouped into four primary cognitive domains: vocabulary, perceptual speed, fluid reasoning, and episodic memory. Results showed that both age and task domain were related to internetwork connectivity and that some of the connections among the networks were associated with performance on the in-scanner tasks. These findings demonstrate that internetwork connectivity among several cognitive networks is not only affected by aging and task demands but also shows a relationship with task performance. As such, future studies examining internetwork connectivity in aging should consider multiple networks and multiple task conditions to better measure dynamic patterns of network flexibility over the course of cognitive aging.
Explicit and Ambiguous Threat Processing: Functionally Dissociable Roles of the Amygdala and Bed Nucleus of the Stria Terminalis
Authors: Naaz Farah , Knight Lindsay K. , Depue Brendan E.
Published: January 2019

Highly influential models have proposed that responses to different types of threat are mediated by partially segregated neural systems, with the amygdala underlying phasic responses to explicit threat (fear) and the bed nucleus of the stria terminalis (BNST) mediating sustained responses to ambiguous threat (anxiety). However, newer models have suggested similar recruitment of both regions across a wide spectrum of threat. Therefore, to empirically test these models and further elucidate the activation profiles and connectivity patterns of the amygdala and the BNST during threat processing, 20 participants were scanned using high-resolution fMRI (1.5 mm3). Using fearful faces and human screams as aversive stimuli, two threat conditions were created: Explicit Threat in which threats were certain and predictable (fear) and Ambiguous Threat in which threats were uncertain and unpredictable (anxiety). Results indicated that, although the amygdala and the BNST both showed heightened engagement across both threat conditions, the amygdala showed preferential engagement during Explicit Threat and displayed functional connectivity with regions involved in stimulus processing and motor response. By contrast, the BNST preferentially responded during Ambiguous Threat and exhibited functional connectivity with prefrontal regions underlying interoception and rumination. Furthermore, correlations with questionnaires measuring trait anxiety, worry, and rumination suggested that individual differences in affective style play a modulatory role in regional recruitment and network connectivity during threat processing.
Social entrepreneurship interventions in the HIV/AIDS sector: A social entrepreneurship–social work perspective
Authors: Chandra Yanto , Shang Liang
Published: January 2019

Despite the growing interest in social entrepreneurship research in the social work literature, very little research examines how social entrepreneurs tackle social work challenges in the HIV/AIDS sector. Consequently, we lack research on how social entrepreneurship might contribute to social work’s domain of healthcare. In this article, we employ grounded theory research to study how a group of social entrepreneurs ( N = 58) selected as Fellows by Ashoka, one of the world’s most influential social entrepreneurship support organizations, solve HIV/AIDS problems. This article identifies four major interventions that social entrepreneurs employed in tackling HIV/AIDS problems: relational, service, economic, and policy. We analyzed these four primary interventions and classified them into a typology based on (1) locus of change (institutional-oriented or macro social work vs agent-oriented or micro social work), (2) resources used (material/utilitarian vs symbolic/normative), and (3) client–social enterprise relations (client as recipient vs client as co-creator). This article contributes to social work research by demonstrating the possibility of integrating multilevel (e.g. micro and macro) and multidimensional (e.g. service, economic, and policy) interventions in addressing HIV/AIDS problems. It also suggests avenues for future research to lessen the gap between social work and social entrepreneurship research so as to advance social work research.
Rejecting Humanae Vitae: The Social Costs of Denying the Obvious
Authors: Klaus Hanna
Published: January 2019

Since contraceptives have been used to remove fertility from the conjugal act, the social consequences predicted in the encyclical Humanae vitae, such as the rise in cohabitation, decline of marriage, rise of divorce, and single parenthood, have exceeded expectations. The degradation of the sexual act from total mutual self-giving to momentary union has led to doubting the significance of the biological truth of the body and opened the door to gender fluidity. Promiscuity became normative, and the need for consent became eroded until women revolted with the #MeToo movement. Promiscuity, cohabitation, and divorce have resulted in 40 percent of children born to unmarried parents whose tenuous unions often leave the children in melded and dysfunctional families. Relation-free “hookups” have become the norm among young adults, leaving a flood of emotionally damaged women, an epidemic of sexually transmitted infections, and unplanned pregnancies, to which the healthcare industry has responded by doubling down on the means which caused the problem in the first place with near-coercive promotion of long-acting, reversible contraceptives (LARCs). LARCs must be inserted and removed professionally and make reproductive choice moot. Respecting the truth of the body is the precise counter measure. A woman’s cyclic fertility is easily observed with reliable biomarkers—natural family planning—which requires the whole person. Fertility awareness–based methods of family planning have no side effects, are easy to learn, and can be used to achieve as well as delay conception. The self-discovery inherent in learning fertility literacy has empowered adolescent girls and boys to understand and value their sexuality and fertility and avoid choosing harmful behaviors. Why does society continue to treat fertility as if it were a disease?

Removing the idea of pregnancy from the sexual act as the result of readily available contraception has effectively limited choices about sexual behavior to the satisfaction of momentary desires. As Humanae vitae predicted, fewer marriages were contracted, divorce increased and now 40% of children are born out of wedlock despite extensive public education campaigns to promote contraception. Side effects of the hormonal pill have reduced their use so health care professionals have doubled down, providing long acting contraceptives which do not require the user to exercise choice before each act of intercourse, or of taking a pill. There is a much better way to regulate births–to learn to read the book of nature. Fertility is not a disease to be removed from the body. All that is needed is to understand the natural signs of fertility–natural family planning, now called FABM–Fertility Awareness-Based Methods. These have no side effects, enhance couple communication and offer effective choice for child spacing and demonstrably support premarital chastity for teens.
Retrieving and Modifying Traumatic Memories: Recent Research Relevant to Three Controversies
Authors: Engelhard Iris M. , McNally Richard J. , van Schie Kevin
Published: January 2019

The purpose of this article is to review recent research that is relevant to three controversies concerning memory for trauma. First, we briefly review the debate about recovered memories of childhood sexual abuse, summarizing a third interpretation distinct from both the repression and false-memory accounts. Second, we address new findings related to claims that memories of trauma, especially in people with posttraumatic stress disorder, are especially fragmented and disorganized. Third, we discuss research designed to test whether eye movements in eye-movement desensitization and reprocessing therapy are effective.
Perturbing Anticipation: Jazz, Effective-History, Dialogue, and the Nonrepresentational Movement of Hermeneutic Understanding
Authors: Freeman Melissa
Published: January 2019

Process ontologies focus on the constitutive activity of becoming-other and describe the movement of hermeneutic understanding as it performs its mode of being anew. Inherent to this process is the work of effective-history, which denotes our condition as historical beings and the effects history has on our being, doing, and understanding. In this article, I argue that philosophical hermeneutics provides a mode of participation that supports qualitative researchers committed to entering this flux and reimagining new methodological possibilities for research. Philosophical hermeneutics conceptualized as jazz improvisation perturbs preconceived notions of tradition, dialogue, anticipation, and time to support this critical role.
Book Review: Ribas-Mateos, N. 2016: Migration, Mobilities and the Arab Spring
Authors: Wood Peter D. A.
Published: January 2019

Ribas-Mateos, N. 2016: Migration, Mobilities and the Arab Spring. Cheltenham, UK: Edward Elgar Publishing. xvi + 196 pp. £63.00 (Cloth). ISBN: 978 1 78536 194 4.
Child participation in evaluating social protection projects: Do global development actors walk the talk?
Authors: Hulshof Henk
Published: January 2019

This article assesses the compliance of key international development actors with children’s right to participation in evaluating social protection programmes they support in Africa. As children in sub-Saharan Africa assume an increasingly large share of global poverty, their right to be heard in these programmes is critical. The article elaborates on the legal requirements for the implementation of Article 12 of the UN Convention on the Rights of the Child (CRC) and demonstrates the practical relevance of children’s participation. The article concludes that as children are left out of the design and planning phase of social protection programmes, their role in monitoring and evaluation (M&E) can only be marginal.