bluuebunny/crossref_metadata_2025 huggingface dataset:
Rituximab Is Ineffective for Treatment of Fatigue in Primary Biliary Cholangitis: A Phase 2 Randomized Controlled Trial
Authors: Khanna Amardeep , Jopson Laura , Howel Denise , Bryant Andrew , Blamire Andrew , Newton Julia L. , Jones David E.
Published: May 2018

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease. Half of patients experience debilitating fatigue, which is currently untreatable. Previous studies have shown muscle bioenergetic abnormalities in PBC, including increased muscle acidosis with exercise linked to the antimitochondrial antibody (AMA) diagnostic of the disease, and reduced anaerobic threshold. In this study we addressed the hypothesis that fatigue in PBC is driven by muscle bioenergetic abnormality related to AMA, and that AMA reduction with B‐cell depletion therapy will improve fatigue. In our single‐center phase 2 randomized controlled trial, 57 participants aged 18 years or older with PBC and moderate to severe fatigue were randomized to receive two doses of either rituximab (1000 mg) or saline (placebo). The primary outcome measure was fatigue severity assessed using the PBC‐40 fatigue domain at 3 months. Secondary outcome measures included patient‐reported outcomes and immunological and bioenergetics disease parameters. Experimental outcomes included biochemical markers of disease severity. Improvement in fatigue score at 3 months was seen in both arms, with no significant difference (adjusted mean difference −0.9 [95% confidence interval −4.6 to 3.1]). Little difference was observed in other patient‐reported outcomes or physical activity. Significant anaerobic threshold improvement was seen in the rituximab group, only but this was not associated with fatigue improvement. No treatment‐emergent serious adverse events were seen. Conclusions: Rituximab was safe over the 12‐month study period but showed no evidence of effectiveness for the treatment of fatigue in PBC. Anaerobic threshold improvement was seen, potentially linking AMA with muscle bioenergetics dysfunction; however, this was not related to improvement in fatigue. Rituximab had some evidence of a beneficial effect on alkaline phosphatase levels in this largely ursodeoxycholic acid (UDCA)–responding, early‐disease stage cohort. (Hepatology 2018; 00:000‐000).
The Long Noncoding RNA Cancer Susceptibility 9 and RNA Binding Protein Heterogeneous Nuclear Ribonucleoprotein L Form a Complex and Coregulate Genes Linked to AKT Signaling
Authors: Klingenberg Marcel , Groß Matthias , Goyal Ashish , Polycarpou‐Schwarz Maria , Miersch Thilo , Ernst Anne‐Sophie , Leupold Jörg , Patil Nitin , Warnken Uwe , Allgayer Heike , Longerich Thomas , Schirmacher Peter , Boutros Michael , Diederichs Sven
Published: May 2018

The identification of viability‐associated long noncoding RNAs (lncRNAs) might be a promising rationale for new therapeutic approaches in liver cancer. Here, we applied an RNA interference screening approach in hepatocellular carcinoma (HCC) cell lines to find viability‐associated lncRNAs. Among the multiple identified lncRNAs with a significant impact on HCC cell viability, we selected cancer susceptibility 9 (CASC9) due to the strength of its phenotype, expression, and up‐regulation in HCC versus normal liver. CASC9 regulated viability across multiple HCC cell lines as shown by clustered regularly interspaced short palindromic repeats interference and single small interfering RNA (siRNA)–mediated and siRNA pool–mediated depletion of CASC9. Further, CASC9 depletion caused an increase in apoptosis and a decrease of proliferation. We identified the RNA binding protein heterogeneous nuclear ribonucleoprotein L (HNRNPL) as a CASC9 interacting protein by RNA affinity purification and validated it by native RNA immunoprecipitation. Knockdown of HNRNPL mimicked the loss‐of‐viability phenotype observed upon CASC9 depletion. Analysis of the proteome (stable isotope labeling with amino acids in cell culture) of CASC9‐depleted and HNRNPL‐depleted cells revealed a set of coregulated genes which implied a role of the CASC9:HNRNPL complex in AKT signaling and DNA damage sensing. CASC9 expression levels were elevated in patient‐derived tumor samples compared to normal control tissue and had a significant association with overall survival of HCC patients. In a xenograft chicken chorioallantoic membrane model, we measured decreased tumor size after knockdown of CASC9. Conclusion: Taken together, we provide a comprehensive list of viability‐associated lncRNAs in HCC; we identified the CASC9:HNRNPL complex as a clinically relevant viability‐associated lncRNA/protein complex which affects AKT signaling and DNA damage sensing in HCC.
Anthropomorphizing information to enhance trust in autonomous vehicles
Authors: Niu Dongfang , Terken Jacques , Eggen Berry
Published: May 2018

Trust is an essential condition for accepting and relying on autonomous vehicles. One of the well‐studied factors contributing to trust in automation systems is anthropomorphism. It is expected that anthropomorphism may also enhance trust in the field of autonomous vehicles. A study is presented that investigated the effect of anthropomorphic embodiment for information about the vehicle's maneuvers on people's trust in autonomous vehicles. In a driving simulator experiment deploying a between‐subjects design, participants (N = 39) were exposed to varying amounts of information displaying upcoming actions of an autonomous vehicle (symbolic information or symbolic + anthropomorphic information). Each group rated trust and liking for the test condition against a reference condition where no information about the upcoming actions was provided through questionnaires. Symbolic + anthropomorphic information resulted in significantly more trust than symbolic information. Through one‐sample tests, it was found that ratings for symbolic + anthropomorphic information were significantly different from no information, while symbolic information by itself was not. Ratings for perceived anthropomorphism were positively correlated with trust and liking. It is concluded that anthropomorphizing information may foster the perception of autonomous vehicles as social agents and enhance trust in those vehicles.
The importance of and need for rapid hydrologic assessments in Latin America
Authors: Riveros‐Iregui Diego A. , Covino Timothy P. , González-Pinzón Ricardo
Published: May 2018

Long‐term observations are critical in hydrology to understand the dynamics of biological and physicochemical processes involved in and affected by the flux of water. Long‐term observations have been employed to provide basic understanding of the water cycle (e.g., infiltration, evaporation, run‐off generation, and groundwater–surface water interactions), but they are lacking in hydrologically relevant regions such as the Andes Mountains, including alpine watersheds. Although the call for long‐term data acquisition in Latin America has been made, the establishment of long‐term data collection centres remains logistically challenging. This ever‐growing scientific gap hinders our understanding of differences and similarities in hydrological processes of tropical and temperate regions. Furthermore, technological advances such as in situ optical sensors for water quantity and quality remain cost‐prohibitive for both short and long deployment at most existing research sites in Latin America, restricting researchers pursuing research funding or developing meaningful, intersite comparisons and syntheses. Here, we emphasize the importance of and need for rapid assessments (i.e., field campaigns conducted over a few days) for improved hypothesis development and mechanistic understanding of hydrological dynamics in Latin America. We report on rapid assessments conducted in the high‐elevation mountains (>3,000 m) of Colombia. Our results highlight rapidly changing dynamics in nutrient retention potential and dissolved CO2 (pCO2), as well as highly variable spatial distribution of water quality parameters (N, C, P, Cl) in areas with varying land use. We present an initial examination of the effects of land‐use change on stream nutrient dynamics in one of the most biodiverse and threatened ecosystems on Earth. We conclude that rapid assessments not only are necessary but also represent a cost‐effective way to develop clear, testable hypotheses to advance a hydrologic research agenda in Latin America and work towards long‐term hydrological knowledge and information for use by other scientists.
Chitosan/biphasic calcium phosphate scaffolds functionalized with BMP‐2‐encapsulated nanoparticles and RGD for bone regeneration
Authors: Gan Donglin , Liu Min , Xu Tong , Wang Kefeng , Tan Hui , Lu Xiong
Published: May 2018

Advancements in bone tissue engineering require the improvement of tissue scaffolds, which should not only exhibit suitable mechanical properties and highly porous structures, but also effectively carry signaling molecules that can mediate bone formation and tissue regeneration. In the present study, we established chitosan/biphasic calcium phosphate (CS/BCP) scaffolds functionalized with Arg–Gly–Asp (RGD) and BMP‐2‐loaded nanoparticles. The resulting scaffolds were highly similar to natural bone extracellular matrix (ECM) in terms of composition and structural properties. First, we synthesized CS/BCP composite bionic scaffolds via the freeze‐drying method. Then, RGD peptides were covalently conjugated onto the scaffolds via the EDC/NHS method. The BMP‐2‐encapsulated BSA nanoparticles were prepared via a desolvation method and then coated with CS and oxidized alginate to achieve sustained release of BMP‐2. In vitro cell culture and in vivo implantation tests confirmed that RGD and BMP‐2 synergistically enhanced cell attachment and spreading by providing integrin binding surface and facilitating osteogenic differentiation. In summary, the bioceramic/biopolymer scaffolds functionalized with signaling biomolecules successfully provided a favorable microenvironment for bone formation and thus serve as potential candidates for use in bone tissue engineering. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2613–2624, 2018.
Decreased expression of hsa_circ_0137287 predicts aggressive clinicopathologic characteristics in papillary thyroid carcinoma
Authors: Lan Xiabin , Cao Jun , Xu Jiajie , Chen Chao , Zheng Chuanming , Wang Jiafeng , Zhu Xuhang , Zhu Xin , Ge Minghua
Published: May 2018

Background

Circular RNA (circRNA) is a new type of noncoding RNA that can serve as ideal biomarkers. Evidence has showed that circRNAs play an important role in carcinogenesis and cancer development. However, little is known about the diagnostic value of circRNAs in papillary thyroid carcinoma (PTC) as well as their associations with clinicopathologic characteristics of patients with PTC.

Methods

The expression levels of hsa_circ_0137287 were detected in 120 PTC and 60 adjacent noncancerous thyroid tissues by quantitative real‐time polymerase chain reaction. The relationships between the expression of hsa_circ_0137287 in PTC and the clinicopathologic factors were analyzed. Finally, receiver operating characteristic (ROC) curves were generated to assess the diagnostic value of hsa_circ_0137287 as a biomarker for PTC.

Results

The expression of hsa_circ_0137287 was significantly downregulated in PTC tissues compared with adjacent noncancerous tissues (P < .0001). Downregulation of hsa_circ_0137287 correlated with aggressive clinicopathologic characteristics of PTC such as extrathyroidal extension (P < .001), lymph node metastasis (P = .022), advanced T stage (P < .001) and larger tumor size (P < .001). The ROC curves revealed that hsa_circ_0137287 had a potential diagnostic value in predicting malignancy, extrathyroidal extension and lymph node metastasis. The area under curves were 0.8973 (95% CI = 0.8452‐0.9494, P < .0001), 0.6885 (95%CI = 0.5908‐0.7862, P = .0009), and 0.6691(95%CI = 0.5641‐0.7742, P = .0034), respectively.

Conclusions

Our findings suggest that hsa_circ_0137287 may serve as a novel biomarker for PTC.
Aspiration pneumonia induces muscle atrophy in the respiratory, skeletal, and swallowing systems
Authors: Komatsu Riyo , Okazaki Tatsuma , Ebihara Satoru , Kobayashi Makoto , Tsukita Yoko , Nihei Mayumi , Sugiura Hisatoshi , Niu Kaijun , Ebihara Takae , Ichinose Masakazu
Published: May 2018

Background

Repetition of the onset of aspiration pneumonia in aged patients is common and causes chronic inflammation. The inflammation induces proinflammatory cytokine production and atrophy in the muscles. The proinflammatory cytokines induce muscle proteolysis by activating calpains and caspase‐3, followed by further degradation by the ubiquitin‐proteasome system. Autophagy is another pathway of muscle atrophy. However, little is known about the relationship between aspiration pneumonia and muscle. For swallowing muscles, it is not clear whether they produce cytokines. The main objective of this study was to determine whether aspiration pneumonia induces muscle atrophy in the respiratory (the diaphragm), skeletal (the tibialis anterior, TA), and swallowing (the tongue) systems, and their possible mechanisms.

Methods

We employed a mouse aspiration pneumonia model and computed tomography (CT) scans of aged pneumonia patients. To induce aspiration pneumonia, mice were inoculated with low dose pepsin and lipopolysaccharide solution intra‐nasally 5 days a week. The diaphragm, TA, and tongue were isolated, and total RNA, proteins, and frozen sections were stored. Quantitative real‐time polymerase chain reaction determined the expression levels of proinflammatory cytokines, muscle E3 ubiquitin ligases, and autophagy related genes. Western blot analysis determined the activation of the muscle proteolysis pathway. Frozen sections determined the presence of muscle atrophy. CT scans were used to evaluate the muscle atrophy in aged aspiration pneumonia patients.

Results

The aspiration challenge enhanced the expression levels of proinflammatory cytokines in the diaphragm, TA, and tongue. Among muscle proteolysis pathways, the aspiration challenge activated caspase‐3 in all the three muscles examined, whereas calpains were activated in the diaphragm and the TA but not in the tongue. Activation of the ubiquitin‐proteasome system was detected in all the three muscles examined. The aspiration challenge activated autophagy in the TA and the tongue, whereas weak or little activation was detected in the diaphragm. The aspiration challenge resulted in a greater proportion of smaller myofibers than in controls in the diaphragm, TA, and tongue, suggesting muscle atrophy. CT scans clearly showed that aspiration pneumonia was followed by muscle atrophy in aged patients.

Conclusions

Aspiration pneumonia induced muscle atrophy in the respiratory, skeletal, and swallowing systems in a preclinical animal model and in human patients. Diaphragmatic atrophy may weaken the force of cough to expectorate sputum or mis‐swallowed contents. Skeletal muscle atrophy may cause secondary sarcopenia. The atrophy of swallowing muscles may weaken the swallowing function. Thus, muscle atrophy could become a new therapeutic target of aspiration pneumonia.
Plastic rates of development and the effect of thermal extremes on offspring fitness in a cold‐climate viviparous lizard
Authors: Cunningham George D. , Fitzpatrick Luisa J. , While Geoffrey M. , Wapstra Erik
Published: May 2018

Populations at the climatic margins of a species’ distribution can be exposed to conditions that cause developmental stress, resulting in developmental abnormalities. Even within the thermal range of normal development, phenotypes often vary with developmental temperature (i.e., thermal phenotypic plasticity). These effects can have significant consequences for organismal fitness and, thus, population persistence. Reptiles, as ectotherms, are particularly vulnerable to thermal effects on development and are, therefore, considered to be at comparatively high risk from changing climates. Understanding the extent and direction of thermal effects on phenotypes and their fitness consequences is crucial if we are to make meaningful predictions of how populations and species will respond as climates warm. Here, we experimentally manipulated the thermal conditions experienced by females from a high‐altitude, cold‐adapted population of the viviparous skink, Niveoscincus ocellatus, to examine the consequences of thermal conditions at the margins of this population's normal temperature range. We found strong effects of thermal conditions on the development of key phenotypic traits that have implications for fitness. Specifically, we found that offspring born earlier as a result of high temperatures during gestation had increased growth over the first winter of life, but there was no effect on offspring survival, nor was there an effect of developmental temperature on the incidence of developmental abnormalities. Combined, our results suggest that advancing birth dates that result from warming climates may have positive effects in this population via increased growth.
Sexual and somatic development of wood frog tadpoles along a thermal gradient
Authors: Lambert Max R. , Smylie Meredith S. , Roman Amber J. , Freidenburg L. Kealoha , Skelly David K.
Published: May 2018

All amphibian species are known to have genetic sex determination. However, a variety of environmental conditions can moderate sexual differentiation, in some cases leading to sex reversal and skewed sex ratios. While there has been a recent focus on chemically‐induced sex reversal in amphibians, temperature can also influence sexual differentiation. Building upon a classic 1929 study by Emil Witschi, we assessed temperature‐mediated sex reversal. Witschi found that the wood frog sex ratio is 100% male at a high temperature (32°C) compared to a 50:50 sex ratio at 20°C. This pattern is consistent with multiple models of environmentally mediated sexual differentiation in vertebrates. To better understand thermally mediated sex reversal, we raised wood frogs at temperature increments of ∼1°C between 19 and 34°C. Mirroring earlier findings, wood frog metamorph sex ratios are indistinguishable from 50:50 at the lowest temperature and entirely male at the highest temperatures. In between, sex ratios become increasingly male‐dominated as temperatures increase, implying a steadily increasing tendency toward female‐to‐male sex reversal in warmer environments. There was no evidence of a threshold temperature effect on reversal patterns. We also show that, compared to males, females metamorphose larger and later in cooler conditions but earlier and smaller under warmer conditions. While the ecological relevance in this species is unknown, these results conform to the Charnov–Bull model of sex determination (in which female‐to‐male sex reversal can increase fitness to genetic females at higher temperatures), suggesting the system would reward further study.
Preclinical evaluation of potential infection‐imaging probe [68Ga]Ga‐DOTA‐K‐A9 in sterile and infectious inflammation
Authors: Nielsen Karin M. , Jørgensen Nis P. , Kyneb Majbritt H. , Borghammer Per , Meyer Rikke L. , Thomsen Trine R. , Bender Dirk , Jensen Svend B. , Nielsen Ole L. , Alstrup Aage K.O.
Published: May 2018

The development of bacteria‐specific infection radiotracers is of considerable interest to improve diagnostic accuracy and enabling therapy monitoring. The aim of this study was to determine if the previously reported radiolabelled 1,4,7,10‐tetraazacyclododecane‐N,N′,N″,N‴‐tetraacetic acid (DOTA) conjugated peptide [68Ga]Ga‐DOTA‐K‐A9 could detect a staphylococcal infection in vivo and distinguish it from aseptic inflammation. An optimized [68Ga]Ga‐DOTA‐K‐A9 synthesis omitting the use of acetone was developed, yielding 93 ± 0.9% radiochemical purity. The in vivo infection binding specificity of [68Ga]Ga‐DOTA‐K‐A9 was evaluated by micro positron emission tomography/magnetic resonance imaging of 15 mice with either subcutaneous Staphylococcus aureus infection or turpentine‐induced inflammation and compared with 2‐deoxy‐2‐[18F]fluoro‐D‐glucose ([18F]FDG). The scans showed that [68Ga]Ga‐DOTA‐K‐A9 accumulated in all the infected mice at injected doses ≥3.6 MBq. However, the tracer was not found to be selective towards infection, since the [68Ga]Ga‐DOTA‐K‐A9 also accumulated in mice with inflammation. In a concurrent in vitro binding evaluation performed with a 5‐carboxytetramethylrhodamine (TAMRA) fluorescence analogue of the peptide, TAMRA‐K‐A9, the microscopy results suggested that TAMRA‐K‐A9 bound to an intracellular epitope and therefore preferentially targeted dead bacteria. Thus, the [68Ga]Ga‐DOTA‐K‐A9 uptake observed in vivo is presumably a combination of local hyperemia, vascular leakiness and/or binding to an epitope present in dead bacteria.
National‐level Indicators of Androgens are Related to the Global Distribution of Scientific Productivity and Science Nobel Prizes
Authors: van der Linden Dimitri , Dutton Edward , Madison Guy
Published: May 2018

There are national differences in scientific activity that are not well accounted for by economic and intellectual factors alone. We examine the novel hypothesis that androgen levels may also play a role. Androgens are often referred to as male hormones, but are present in both men and women, and have been linked to performance in other domains, such as sports and entrepreneurship. National‐level empirical data on scientific productivity, in terms of numbers of publications, and science Nobel laureates were compared to seven national‐level androgen indicators; namely androgenic body hair, the length of theCAGrepeat on the androgen receptor gene, prostate cancer incidence, male and female 2D:4D finger ratio, and sex frequency and number of partners. The majority of these indicators were associated in the expected direction with per capita number of scientific publications and Nobel prizes. Moreover, several indicators significantly interacted with national‐level estimates of intelligence, such that androgen levels are related to measures of the scientific achievement only when the level of intelligence is relatively high. These findings may partly explain the global distribution of scientific productivity, achievements, and Nobel prizes.
Memory T cell subsets in healthy gingiva and periodontitis tissues
Authors: Mahanonda Rangsini , Champaiboon Chantrakorn , Subbalekha Keskanya , Sa‐Ard‐Iam Noppadol , Yongyuth Arsarn , Isaraphithakkul Benjarat , Rerkyen Pimprapa , Charatkulangkun Orawan , Pichyangkul Sathit
Published: May 2018

Background

In the gingival sulcus, effective and balanced innate and adaptive immune responses against subgingival plaque microbiome are crucial to maintain immune homeostasis. In this study, we investigated the memory T cell subsets in healthy gingiva and periodontitis tissues.

Methods

Anatomical localization of T cells (CD3+, CD4+, and CD8+) in healthy gingiva and periodontitis tissues were examined immunohistochemically. Subsets of memory T cells from isolated gingival cells were analyzed by flow cytometry using a cocktail of monoclonal antibodies (anti‐CD69, anti‐CD103, anti‐CD45RA, anti‐CCR7, anti‐CD28, and anti‐CD95). Intracellular cytokine staining of interleukin (IL)‐17 and interferon (IFN)‐γ expression on memory T cells in periodontitis tissues was also investigated.

Results

We found that healthy gingiva contains two memory T cell populations; a CD69− recirculating population and a CD69+ gingiva‐resident memory T cell population. CD4+ T cells with transitional memory (TTM) phenotype (CD45RA−CCR7−CD28+CD95+) constitute the major subset within these two populations. A significant increase in the proportion of CD4+CD69+CD103− memory T cells was observed in periodontitis tissues compared with healthy gingiva. CD4+ memory T cells from periodontitis tissues produced either IL‐17 or IFN‐γ whereas CD8+ memory T cells produced only IFN‐γ.

Conclusions

Our findings suggest that recirculating and gingiva‐resident memory T cells could represent an important part of the immune surveillance network in the connective tissue, maintaining periodontal homeostasis. Imbalance of subgingival bacterial communities could damage gingival barrier allowing bacterial antigens to get access to the deeper connective tissue where they activate memory T cells leading to deleterious inflammation; a hallmark of periodontitis.
Rheology of Quaternary Ammonium Gemini Surfactant Solutions: Effects of Surfactant Concentration and Counterions
Authors: Yang Xiaojiang , Mao Jincheng , Zhang Zhaoyang , Zhang Heng , Yang Bo , Zhao Jinzhou
Published: May 2018

To prepare high‐performance clean fracturing fluids, cationic surfactants with a Gemini structure were synthesized as thickening agents. Distinct elastic characteristics at a sweep frequency of 0.1–10 Hz and shear resistance at high temperature were shown. Viscosity remained at about 150 mPa s after shearing for 60 min at 140 °C and 170 s−1. Stability investigation on cationic Gemini surfactant solution revealed that both viscosity and viscoelasticity were greatly affected by the surfactant concentration, temperature, and the amount of inorganic salt (potassium chloride). Complete formulation of a surfactant micelle structure in an aqueous solution requires a certain amount of time.
Comparison of sentinel lymph node biopsy guided by blue dye with or without indocyanine green in early breast cancer
Authors: Shen Songjie , Xu Qianqian , Zhou Yidong , Mao Feng , Guan Jinghong , Sun Qiang
Published: May 2018

Background

There were limited data available for a head‐to‐head comparison of the identification rate and survival between the combined method of indocyanine green fluorescence and blue dye versus the traditional blue dye alone method for sentinel lymph node (SLN) biopsy.

Methods

From January 2013 to December 2015, 523 eligible breast cancer patients were included in this nonrandomized prospective analysis. The identification rates, the number of SLNs identified, and the disease‐free survival (DFS) between the two mapping methods were compared.

Results

The identification rate of SLNs was significantly higher with the combined method than that with the blue dye alone method (99.2% vs 93.3%, respectively; P < 0.001). The average number of SLNs identified per patient in the combined method group was 3.7 ± 2.4, which was more than that in the blue dye alone group (3.2 ± 1.6; P = 0.004). With a median follow‐up of 29 months, 0.5% patients in the combined group, and 1.3% patients in the blue dye group had axillary recurrences. The DFS between the two groups showed no significant difference (P = 0.161).

Conclusion

The combined method achieved a higher identification rate and lower rate of axillary recurrence compared to the blue dye alone method.
A study on microstructure evolution and corrosion resistance of cutting layer metal of 7055 aluminum alloy based on extreme environment
Authors: Zhang Ping , Wang Youqiang , Li Weihui , Wang Qing , Li Yuanyuan
Published: May 2018

In order to evaluate the mechanism of microstructure evolution and corrosion resistance of 7055 aluminum alloy in extreme environment, 7055 aluminum alloy which was subjected to T6I4 heat treatment was selected as the research object. High speed machining experiments were performed at low temperature (−60 °C) and high temperature (350 °C). The experimental results show that the dislocation density at low temperature is higher than that at high temperature under the same cutting speed and feed rate, and the grain size at low temperature is higher than that at high temperature too. Under the high temperature environment, with the increasing cutting speed, the degree of fibrouse texture of the grains is weakened and the dynamic recrystallization is obviously enhanced. With the increase of the feed rate, the microstructure is elongated and deformed in the direction of deformation after low temperature cutting, also, incomplete recrystallization occurs in 7055. The larger the feed amount is, the finer and longer the fibrouse grains of the metallographic structure of cutting layer metal of 7055 aluminum alloy.The higher the cutting speed, the smaller the dislocation density. No dislocations were found in the microstructure of the 7055 aluminum alloy cutting layer in the high temperature environment but at higher cutting speed the number of precipitated phase is reduced and the GP‐zones and η'‐phases are transformed into η‐phases. In the high temperature environment, the weight percentage of Al element in Al(OH)3 decreases by 45%, the weight percentage of O element decreases by 16%, In the high temperature environment, there is a small amount of Cl elements in the corrosion products of the cutting layer metal after cutting, Cl elements are relatively low in weight percent, Cl− is mainly to destroy the oxide film When the corrosion occurs, also, Cl− and Al3+ form a water‐soluble compound.
Effect of sulphate on the corrosion behavior of bronze under a chloride‐containing thin electrolyte layer
Authors: Liao Xiaoning , Cao Fahe , Zhang Jianqing
Published: May 2018

The effect of sulphate on the corrosion behavior of bronze under a chloride‐containing thin electrolyte layer (TEL) during wet–dry cycles has been studied by means of in situ electrochemical techniques and ex situ physical characterization. In the initial stage, corrosion rates of bronze under a chloride‐containing TEL decrease in the presence of sulphate, due to the fact that pit corrosion is inhibited by the sulphate. After long‐term exposure, however, corrosion rates are accelerated by sulphate addition, implying a synergistic effect between these components. This synergistic effect is ascribed to inhibition of the formation of protective Pb‐containing products by sulphate.
Comparative study of devices for hydrogen permeation measurements
Authors: Rudomilova Darya , Petrek Tomáš , Prošek Tomáš , Šefl Václav , Duchaczek Hubert , Zwettler Florian , Muhr Andreas , Luckeneder Gerald
Published: May 2018

New devices for measurement of hydrogen permeability in steels using electric resistance sensors have been assessed. Diffusion coefficients of two types of advanced high strength steels obtained with the traditional electrochemical permeation technique using the Devanathan–Stachurski permeation setup and the novel techniques are compared. The EPT technique is found to be more appropriate for laboratory assessment of hydrogen permeability due to generally better control over the experiment and data evaluation. The novel setups can be a good choice for comparative hydrogen measurements in real environments, including atmospheric ones, because of simpler sample preparation and small size of hydrogen probes.
Influence of rare earths alloying addition on the corrosion behavior of Zn in neutral aerated sodium chloride solution
Authors: Rosalbino Francesco , Macciò Daniele , Scavino Giorgio , Saccone Adriana
Published: May 2018

The effect of rare earth metals (Gd, Dy, Er,) addition on the corrosion behavior of Zn has been investigated. The corrosion resistance of Zn99Gd1, Zn99Dy1, and Zn99Er1 (at%) alloys has been assessed by open circuit potential and electrochemical impedance spectroscopy (EIS) measurements carried out in a 0.1 M NaCl solution, at approximately neutral pH, without stirring and in contact with the air. For comparison, the electrochemical tests have also been carried out on unalloyed Zn. Moreover, the surface morphology and nature of the corrosion products have been investigated. The results indicated that rare earths addition significantly improves the corrosion behavior of unalloyed Zn. This improvement is most likely due to enhanced barrier properties of the corrosion products layer and additional active corrosion protection originated from the inhibiting action of the lanthanide ions entrapped as oxides/hydroxides in this surface layer.
Integration of Biomaterials into Sensors Based on Organic Thin‐Film Transistors
Authors: Wu Xiaohan , Zhou Jiachen , Huang Jia
Published: May 2018

Sensors based on organic thin‐film transistors (OTFTs) present various advantages, including high sensitivity and mechanical flexibility, thus possessing potential applications such as wearable devices and biomedical electronics for health monitoring, etc. However, such applications are partially limited by the biocompatibility, biodegradability, and sensitivity to target analytes of OTFT‐based sensors, which can be improved by the incorporation of diverse biomaterials. This article presents a brief review from the viewpoint of the type of the integrated biomaterials, including naturally occurring biomacromolecules such as proteins, enzymes, and deoxyribonucleic acid, as well as biocompatible polymers such as polylactide, poly(lactide‐co‐glycolide), poly(ethylene glycol), cellulose, polydimethylsiloxane, parylene, etc. It is believed that future work in this field should be devoted to the selectivity, sensitivity, and stability improvement as well as the high‐level integration and sophistication on the basis of the OTFT‐based sensors for physical, chemical, and biological sensing applications.
Development of a 3D ultrasound guidance system for permanent breast seed implantation
Authors: Michael Justin , Morton Daniel , Batchelar Deidre , Hilts Michelle , Crook Juanita , Fenster Aaron
Published: May 2018

Purpose

Permanent breast seed implantation (PBSI) is a promising radiotherapy technique for early‐stage breast cancer, completed in a single visit by permanently implanting 103Pd seeds using needles inserted through a template and guided by two‐dimensional (2D) ultrasound (US). However, operator dependence has been highlighted as a limitation of this procedure. Consequently, we propose and have developed an intraoperative guidance system using three‐dimensional (3D) US and an instrumented mechanical arm to provide intraoperative 3D imaging and needle template tracking.

Methods

A mechatronic 3D US scanner reconstructs a 3D image from 150 2D images. A tracked mechanical arm mounted to the scanner locates four fiducial points on the template, registering the template to the 3D image. 3D reconstruction was validated for linear and volumetric measurement accuracy using phantoms of known geometry. In vivo breast US image quality was evaluated in a healthy volunteer. The encoded arm was calibrated and validated using a jig with divots at known locations relative to the scanner and the scanner registered to the 3D US image using intersecting strings in a fluid‐filled test jig. Template registration accuracy was assessed using a machined test jig. Tracking accuracy was assessed in a liquid medium by comparing tracked and imaged needle tip positions. Finally, the system was used to guide a mock procedure in a patient‐specific phantom and micro‐CT imaging used to evaluate its accuracy.

Results

Geometric validation showed median distances within ±1.1% of expected values and volumetric validation showed differences of ≤4.1%. Tracking arm point measurements showed an average error of 0.43 mm and 3D US volume registration showed target registration error ≤0.9 mm. Mean template registration accuracy in each axis of translation/rotation was ≤1.3 mm/1.0°. Mean needle‐targeting error was 2.5 mm and 1.6° for needle tips and trajectories, respectively. Mean needle tip and angular errors of the phantom procedure were 2.1 mm and 2.6°. Modeled seed displacement of the phantom procedure showed mean error of 2.6 mm and a maximum of 3.8 mm.

Conclusions

A 3D US guidance system for PBSI has been developed. Benchtop performance and image quality in volunteer scans are satisfactory. A phantom PBSI procedure was successfully delivered using the system with maximum seed error within dosimetric benchmarks (<5 mm). Translation of the device into the clinic is forthcoming.
Optimal control strategy of SEIR endemic model with continuous age‐structure in the exposed and infectious classes
Authors: Khan Asaf , Zaman Gul
Published: May 2018

In this paper, we consider an endemic Susceptible‐Exposed‐Infectious‐Recovered model with continuous age‐structure for exposed and infectious classes. This work is appropriate for those infectious diseases that have exposed period such as tuberculosis and herpes virus infection. Key result is the existence of an optimal control problem. To control the spread of the disease, we use an objective functional with a suitable control and present an optimal control problem. Finally, we present some simulations that support our theoretical findings and show the effectiveness of the model.
Binding Site Transitions Across Strained Oxygenated and Hydroxylated Pt(111)
Authors: Shuttleworth Ian G.
Published: May 2018

The effects of strain σ on the binding position preference of oxygen atoms and hydroxyl groups adsorbed on Pt(111) have been investigated using density functional theory. A transition between the bridge and FCC binding occurs under compressive strain of the O/Pt(111) surface. A significant reconstruction occurs under compressive strain of the OH/Pt(111) surface, and the surface OH groups preferentially occupy on‐top (bridge) positions at highly compressive (less compressive/tensile) strains. Changes to magnetisation of the O‐ and OH‐populated surfaces are discussed and for O/Pt(111) oxygenation reduces the surface magnetism via a delocalised mechanism. The origins of the surface magnetisation for both O‐ and OH‐bearing systems are discussed in terms of the state‐resolved electronic populations and of the surface charge density.
Thermo‐ and glucose‐sensitive microgels with improved salt tolerance for controlled insulin release in a physiological environment
Authors: Gu Shiling , Yang Liu , Li Shirui , Yang Junjiao , Zhang Bo , Yang Jing
Published: May 2018

The response to temperature and glucose, high salt tolerance and self‐regulated drug delivery are simultaneously probable by applying a multifunctional microgel in a rational design by a colloid chemistry method. Such smart microgels were fabricated with thermoresponsive N‐isopropylacrylamide, glucose‐sensitive (2‐phenylboronic esters‐1,3‐dioxane‐5‐ethyl)methyl acrylate (PBDEMA) and water‐soluble crosslinker poly(ethylene glycol) diacrylate through a precipitation emulsion method. These colloidal nanoparticles exhibited PBDEMA‐composition‐dependent responsive behavior with changing temperature and ionic strength. Amongst them, the microgel with 20.7 mol% PBDEMA with a narrow size distribution is suitable for diabetes treatment because it can adapt to the surrounding medium of different glucose concentrations over a clinically relevant range (0–2.0 mg mL−1), control the release of preloaded insulin and is highly stable under normal physiological conditions. Preliminary experiments suggest these highly stable microgels have the potential to be used for self‐regulated therapy and monitoring the response to treatment. © 2018 Society of Chemical Industry
Folding with a protein's native shortcut network
Authors: Khor Susan
Published: May 2018

A complex network approach to protein folding is proposed, wherein a protein's contact map is reconceptualized as a network of shortcut edges, and folding is steered by a structural characteristic of this network. Shortcut networks are generated by a known message passing algorithm operating on protein residue networks. It is found that the shortcut networks of native structures (SCN0s) are relevant graph objects with which to study protein folding at a formal level. The logarithm form of their contact order (SCN0_lnCO) correlates significantly with folding rate of two‐state and nontwo‐state proteins. The clustering coefficient of SCN0s (CSCN0) correlates significantly with folding rate, transition‐state placement and stability of two‐state folders. Reasonable folding pathways for several model proteins are produced when CSCN0 is used to combine protein segments incrementally to form the native structure. The folding bias captured by CSCN0 is detectable in non‐native structures, as evidenced by Molecular Dynamics simulation generated configurations for the fast folding Villin‐headpiece peptide. These results support the use of shortcut networks to investigate the role protein geometry plays in the folding of both small and large globular proteins, and have implications for the design of multibody interaction schemes in folding models. One facet of this geometry is the set of native shortcut triangles, whose attributes are found to be well‐suited to identify dehydrated intraprotein areas in tight turns, or at the interface of different secondary structure elements.
Stability of structurally entangled protein dimers
Authors: Zhao Yani , Cieplak Marek
Published: May 2018

We studied stretching, folding and thermodynamic properties of structurally entangled protein dimers. The tests for entanglement involve four‐terminal pulling. We study the dynamics of such pulling and contrast it with the standard two‐terminal one. The two‐chain entanglement is qualitatively characterized by its entangled core, which is defined as the minimal structure that is entangled. The existence of the entangled cores is found to be affecting both the mechanical and folding properties of the proteins. We also show that the folding pathways of the entangled proteins are not universal but the bottleneck is always the formation of the entangled conformation. We demonstrate that entanglement enhances thermodynamic stability.
Revisiting the “parallel lives” thesis: Neighbourhood attachment and residential integration of ethnic minorities in England
Authors: Wang Senhu , Ramsden Mark
Published: May 2018

Recent debates about the failures of multiculturalism have questioned whether ethnic minorities gradually integrate into the British society or instead lead “parallel lives” in segregated communities. Using nationally representative data (2011–2012), we contribute to the debate by investigating the associations between ethnic minority neighbourhood attachment and neighbourhood ethnic composition. Our results show that although all ethnic minorities report higher neighbourhood attachment than White British as local share of coethnics increases, the associations are not significant. However, Pakistanis, Bangladeshis, and Indians do report significantly weaker neighbourhood attachment than do White British as the local share of White British increases. Importantly, we find that these patterns are particularly pronounced for second‐generation Pakistanis and Bangladeshis as compared with their first‐generation counterparts. These findings suggest that ethnic residential mixing does not automatically imply residential integration and there may be a risk of increasing ethnic segregation among the younger generations of Pakistanis and Bangladeshis.
Experiences of migration, parent–child interaction, and the life satisfaction of children in Ghana and China
Authors: Wu Qiaobing , Cebotari Victor
Published: May 2018

This study is a pioneer effort to comparatively examine how the life satisfaction of children is influenced by their experiences of migration and by their interactions with parents in two geographical contexts: Ghana and China. It also provides evidence of how these relationships differ across gender groups in the two countries. This study uses survey data collected in 2010 and 2013 from school children and youths aged 11–20 in Ghana (N = 1,622) and China (N = 2,171), respectively. Results indicate that children (a) who previously migrated but returned and currently live with both parents and (b) who currently stay behind and have no previous migration experience are generally less likely to be satisfied with life. On the other hand, greater resilience in the outcome is associated with emotional support from parents. Also, there is suggestive evidence that Chinese girls are more vulnerable to the effects of parental migration and of being, at one point of life, migrant themselves. This evidence is not replicated among Chinese boys. In Ghana, girls of migrant parents without a personal migration experience and boys in non‐migrant families who returned from abroad show some degree of vulnerability when assessing their life satisfaction. These findings add nuance to a field of research that has yet to conceptualise the complexity of children's experiences with migration and the way this complexity associates with child well‐being.
In vitro and in vivo metabolic profiles of fasiglifam using ultrahigh‐performance liquid chromatography combined with Q‐Exactive Orbitrap tandem mass spectrometry
Authors: Li Jin‐Qi , Li Jie , Wang Jia‐Feng , Zhang Shu‐han , He Dan , Yong Rong‐Sheng , She Shu‐Ya
Published: May 2018

Rationale

Fasiglifam is an orally available and selective partial agonist of hGPR40 receptor, which was unexpectedly terminated at phase III clinical trials due to its severe hepatotoxicity. To fully understand the mechanism of action of fasiglifam, it is necessary to investigate its in vitro and in vivo metabolic profiles.

Methods

For in vitro metabolism, fasiglifam was incubated with rat or human liver microsomes in the presence of β‐nicotinamide adenine dinucleotide phosphate tetrasodium salt, glutathione (GSH) and uridine diphosphate glucuronic acid trisodium salt for 60 min. For in vivo metabolism, fasiglifam was orally administered to rats at a single dose of 20 mg/kg and the bile was collected. In vitro and in vivo samples were analyzed by the developed ultrahigh‐performance liquid chromatography combined with Q‐Exactive Orbitrap tandem mass spectrometry. The structures of metabolites were proposed according to their accurate masses and fragment ions.

Results

A total of eight metabolites, including an acyl‐GSH adduct, were detected and identified. M1 (acylglucuronide) and M5 (carboxylic acid derivative) were the major metabolites of fasiglifam. Metabolic pathways of fasiglifam involved oxygenation, oxidative dealkylation, dehydrogenation, glucuronidation and GSH conjugation. Fasiglifam may undergo metabolic bioactivation via acylglucuronide.

Conclusions

Oxidative dealkylation and glucuronidation were the predominant metabolic pathways of fasiglifam in vitro and in vivo. Metabolic bioactivation via acylglucuronide may be the perpetrator of its hepatotoxicity. Our findings would be helpful in understanding the disposition of fasiglifam as well as its hepatotoxicity.
Sarcoid‐resembling granulomatous lung disease secondary to occupational magnetite iron dust exposure
Authors: Xiao Lewis , Kookana Anil , McClure Robert , Heraganahally Subash
Published: May 2018

Non‐caseating granulomatous pulmonary conditions resembling sarcoidosis secondary to industrial/occupation exposure to magnetite iron ore dusts have been rarely documented in the literature. This is a case report of a 58‐year‐old blast crew member involved in iron ore/magnetite mining who presented with a 12‐month history of chronic dry cough. High‐resolution computed tomography revealed bilateral interstitial opacities. Lung biopsy demonstrated sarcoid‐like granulomatous inflammation. Oral corticosteroid treatment improved the cough. Radiological features did not resolve despite treatment and yet remained stable following no subsequent exposure to iron mining dust.
Robotic left colectomy with complete mesocolectomy for splenic flexure and descending colon cancer, compared with a laparoscopic procedure
Authors: Kim Jin Cheon , Lee Jong Lyul , Yoon Yong Sik , Kim Chan Wook , Park In Ja , Lim Seok‐Byeong
Published: May 2018

Background

Its relatively low incidence and its surgical complexity mean that a standardized technique for left colectomy has not yet been established for splenic flexure and descending colon cancer (SF‐DCC).

Methods

Seventy‐three patients (robot‐assisted left colectomy with complete mesocolectomy [R‐LCCM], n = 20; laparoscopic left colectomy with complete mesocolectomy [L‐LCCM], n = 53) with SF‐DCC were enrolled at the Asan Medical Center (Seoul, Korea).

Results

R‐LCCM conveniently enables dexterous dissection for the multi‐directional approaches during left mesocolic mobilization. A conversion to open surgery was required in two patients of the L‐LCCM group, but not in the R‐LCCM group. A positive circumferential resection margin was exclusively identified in two patients in the L‐LCCM group. Mean lymph node harvest was 21 with no difference between the two groups.

Conclusions

Although R‐LCCM provided few remarkable advantages over L‐LCCM, it could be considered as an efficient approach in patients with SF‐DCC.