bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanical and physical properties of protein‐starch based plastics produced by extrusion and injection molding
Authors: Huang H. C. , Chang T. C. , Jane J.
Published: January 2018

Processing conditions, ingredient ratio, and moisture content were optimized for making soy protein/starch based plastics using a twin‐screw extruder and an injection molding machine. A metering pump and a high speed mixer were used for ingredient mixing. The optimal processing temperature for injection molding was 130°C, and the moisture content of extruded pellets was 10–14%. Processing effects were investigated by measuring the tensile properties and water resistance of specimens. Reduction of water and glycerol in mixtures increased the barrel pressure of the extruder. Mold release was improved by incorporating 0.25 parts tallow per 100 parts of solid material (soy protein and starch). The water absorption of the specimens was reduced by adding acids to adjust the pH to the isoelectric point of soy proteins (pH 4.5). Effects of storage at different relative humidities were studied. The processibility of pellets was stable after a 4‐wk‐storage period, despite some moisture loss. Injection‐molded specimens, after being stored for up to 6 mon at dry conditions [50 and 11% relative humidity (RH)] at room temperature and for 4 wk in a 50°C oven, showed no surface crack. However, humid (93% RH) storage at room temperature promoted fungal growth after storage for 3 mon, indicating that preservatives such as potassium sorbate and propionic acid were needed.
How We Fall Apart: Similarities of Human Aging in 10 European Countries
Authors: Abeliansky Ana Lucia , Strulik Holger
Published: January 2018

We analyze human aging—understood as health deficit accumulation—for a panel of European individuals, using four waves of the Survey of Health, Aging and Retirement in Europe (SHARE data set) and constructing a health deficit index. Results from log-linear regressions suggest that, on average, elderly European men and women develop approximately 2.5 % more health deficits from one birthday to the next. In nonlinear regressions (akin to the Gompertz-Makeham model), however, we find much greater rates of aging and large differences between men and women as well as between countries. Interestingly, these differences follow a particular regularity (akin to the compensation effect of mortality) and suggest an age at which average health deficits converge for men and women and across countries. This age, which may be associated with human life span, is estimated as 102 ± 2.6 years.
Health Insurance and the Aging: Evidence From the Seguro Popular Program in Mexico
Authors: Parker Susan W. , Saenz Joseph , Wong Rebeca
Published: January 2018

Aimed at covering the large fraction of workers in the informal sector without access to a social security program, the Mexican public health insurance program Seguro Popular began in 2002 and now reaches more than 50 million individuals. We estimate impacts of Seguro Popular for the population aged 50 and older on a set of indicators related to health care including utilization, diagnostic/preventive tests, and treatment conditional on being ill. Using the longitudinal Mexican Health and Aging Study over the period 2001–2012, we conduct before and after difference-in-difference matching impact estimators. Our results suggest large and important effects of the Program on utilization and diagnostic tests. We find overall smaller effects on the probability of being in treatment for individuals with chronic diseases, but these effects are concentrated in rural areas with relatively more health services versus rural areas with lower levels of health services. These results suggest that, to the extent that health services become more available in rural areas lacking services, effects of health insurance may increase.
The Captive's Quest for Freedom
Authors: Blackett R. J. M.
Published: January 2018

This magisterial study, ten years in the making by one of the field's most distinguished historians, will be the first to explore the impact fugitive slaves had on the politics of the critical decade leading up to the Civil War. Through the close reading of diverse sources ranging from government documents to personal accounts, Richard J. M. Blackett traces the decisions of slaves to escape, the actions of those who assisted them, the many ways black communities responded to the capture of fugitive slaves, and how local laws either buttressed or undermined enforcement of the federal law. Every effort to enforce the law in northern communities produced levels of subversion that generated national debate so much so that, on the eve of secession, many in the South, looking back on the decade, could argue that the law had been effectively subverted by those individuals and states who assisted fleeing slaves.
Numerical simulation and analysis of condensation shocks in cavitating flow
Authors: Budich Bernd , Schmidt S. J. , Adams N. A.
Published: January 2018

We analyse unsteady cavity dynamics, cavitation patterns and instability mechanisms governing partial cavitation in the flow past a sharp convergent–divergent wedge. Reproducing a recent reference experiment by numerical simulation, the investigated flow regime is characterised by large-scale cloud cavitation. In agreement with the experiments, we find that cloud shedding is dominated by the periodic occurrence of condensation shocks, propagating through the two-phase medium. The physical model is based on the homogeneous mixture approach, the assumption of thermodynamic equilibrium, and a closed-form barotropic equation of state. Compressibility of water and water vapour is taken into account. We deliberately suppress effects of molecular viscosity, in order to demonstrate that inertial effects dominate the flow evolution. We qualify the flow predictions, and validate the numerical approach by comparison with experiments. In agreement with the experiments, the vapour volume fraction within the partial cavity reaches values${>}80\,\%$for its spanwise average. Very good agreement is further obtained for the shedding Strouhal number, the cavity growth and collapse velocities, and for typical coherent flow structures. In accordance with the experiments, the simulations reproduce a condensation shock forming at the trailing part of the partial cavity. It is demonstrated that it satisfies locally Rankine–Hugoniot jump relations. Estimation of the shock propagation Mach number shows that the flow is supersonic. With a magnitude of only a few kPa, the pressure rise across the shock is much lower than for typical cavity collapse events. It is thus far too weak to cause cavitation erosion directly. However, by affecting the dynamics of the cavity, the flow aggressiveness can be significantly altered. Our results indicate that, in addition to classically observed re-entrant jets, condensation shocks feed an intrinsic instability mechanism of partial cavitation.
Paradoxes of the self: the autobiographical construction of the subject in the Italian Communist Party and in Italian neo-feminism
Authors: Baroni Walter Stefano
Published: January 2018

This article compares the autobiographical practices used by the Partito Comunista Italiano (PCI) in the aftermath of the Second World War with those developed by Italian neo-feminism from the late 1960s onwards. The former involved a repeated injunction for activists to write about and express themselves upon joining the party, in what amounted to self-criticism. The latter, meanwhile, took shape as a result of self-consciousness exercises practised by feminist groups in various cities across Italy. The terms of comparison of this article aim to describe what changed and what remained the same in the technologies used to produce the political self within the Italian Left in the twentieth century, beginning from its split in the 1960s. In this context, the paper reveals that the communist and feminist experiences were supported by the same discursive mechanism, which hinged on a paradoxical enunciation of the self. Communist activists and feminists thus faced the same difficulty in political self-expression, which was resolved in two different ways, both equally unsatisfactory. In conclusion, examining the communist autobiographical injunction allows a radical critical reappraisal of the idea that the use of the first person and the political affirmation of subjectivity are determining features exclusively bound to the feminist experience.
Dietary fat intake associated with bone mineral density among visfatin genotype in obese people
Authors: Khorrami-Nezhad Leila , Mirzaei Khadijeh , Maghbooli Zhila , Keshavarz Seyed Ali
Published: January 2018

Osteoporosis and adipose tissue are closely related with many contradictions. Visfatin is an adipokine that is related to osteoporosis and adiposity. This nutrigenomics study examined the interaction between visfatin genotypes and dietary fat intake, with regard to bone mineral density (BMD) among an obese population. In this cross-sectional study, 336 subjects were enrolled; the mean age was 38·25 (sd 11·69) years and the mean BMI was 31·79 (sd 4·77) kg/m2. Laboratory measurements were lipid profile, insulin and fasting blood sugar. Bone density measurements were assessed by dual-energy X-ray absorptiometry. Dietary data were collected through a 3-d 24-h dietary recall. Genotyping for visfatin gene SNP (rs2110385) was performed by the PCR-restriction fragment length polymorphism method. The frequency of GG, GT and TT genotypes were 33·92 48·51 and 17·54 %, respectively, and 86·6 % of participants were women. The results showed that subjects with TT genotypes had significantly higher lumbar BMD, T score and z score (P<0·0001). After categorisation by percentage of fat intake (30 % of total energy content as a cut-off point), no interaction was found, but when categorised by fat types, we found an interaction between visfatin genotypes and dietary PUFA intake in terms of the hip T score and z score (P=0·043, B= −0·08; P=0·04, B= −0·078, respectively). There was a significant relationship between high PUFA intake and lower energy and protein intake. When participants were categorised by median PUFA intake (22·8 g), it was concluded that subjects with GG genotype who had high PUFA-intake diets had lower hip z scores and T scores, unlike the other genotypes.
Beneficial effects of consumption of acerola, cashew or guava processing by-products on intestinal health and lipid metabolism in dyslipidaemic female Wistar rats
Authors: Batista Kamila Sabino , Alves Adriano Francisco , Lima Marcos dos Santos , da Silva Laiane Alves , Lins Priscilla Paulo , de Sousa Gomes Jéssyca Alencar , Silva Alexandre Sérgio , Toscano Lydiane Tavares , de Albuquerque Meireles Bruno Raniere Lins , de Magalhães Cordeiro Angela Maria Tribuzy , da Conceição Maria Lúcia , de Souza Evandro Leite , Aquino Jailane de Souza
Published: January 2018

This study assessed the effects of diet supplementation with industrial processing by-products of acerola (Malpighia emarginataD.C.), cashew (Anacardium occidentaleL.) and guava (Psidium guajavaL.) fruit on the intestinal health and lipid metabolism of female Wistar rats with diet-induced dyslipidaemia. Female rats were randomly divided into five groups: healthy control, dyslipidaemic control and dyslipidaemic experimental receiving acerola, cashew or guava processing by-products. Fruit processing by-products were administered (400 mg/kg body weight) via orogastric administration for 28 consecutive days. Acerola, cashew and guava by-products caused body weight reduction (3·42, 3·08 and 5·20 %, respectively) in dyslipidaemic female rats. Dyslipidaemic female rats receiving fruit by-products, especially from acerola, presented decreased faecal pH, visceral fat, liver fat and serum lipid levels, as well as increased faecal moisture, faecal fat excretion, faecalBifidobacteriumspp. andLactobacillusspp. counts and amounts of organic acids in faeces. Administration of the tested fruit processing by-products protected colon and liver from tissue damage (e.g. destruction of liver and colon cells and increased fat deposition in hepatocytes) induced by dyslipidaemic diet. Dietary fibres and phenolic compounds in tested fruit by-products may be associated with these positive effects. The industrial fruit processing by-products studied, mainly from acerola, exert functional properties that could enable their use to protect the harmful effects on intestinal health and lipid metabolism caused by dyslipidaemic diet.
Usual nutrient intake adequacy among young, rural Zambian children
Authors: Caswell Bess L. , Talegawkar Sameera A. , Siamusantu Ward , West Keith P. , Palmer Amanda C.
Published: January 2018

Inadequate nutrient intakes put children at risk for impaired growth and development. We described diet, usual intakes of energy and macro- and micronutrients and prevalence of nutrient intake adequacies among 4–8-year-old Zambian children. Children not yet in school and living in Mkushi District, Central Province, Zambia were enrolled into an efficacy trial of pro-vitamin A biofortified maize. Children in the non-intervened arm were included in this analysis (n 202). Dietary intake data were collected by tablet-based 24-h recall on a monthly basis over the 6-month trial. Observed nutrient intakes were derived from reported food quantities, standard recipes and food composition tables. Usual nutrient intake distributions were modelled based on observed intakes. Prevalence of inadequacy was estimated by comparing the usual nutrient intake distribution to the nutrient requirement distribution. Frequency and quantity of consumption of commonly reported foods were described and key sources of energy and nutrients were identified. Median usual energy intake was 6422 kJ/d (1535 kcal/d). Most childrens’ macronutrient intakes fell within recommended ranges (74–98 %). Estimated prevalences of inadequate intakes of Fe, folate, vitamin B12 and Ca were 25, 57, 76 and >99 %, respectively. Estimated prevalences of inadequacy for other micronutrients were low (0·1–2·2 %). Commonly consumed foods included maize, vegetable oil, tomatoes, rape leaves and small fish (>0·6 servings/d), whereas meat, eggs or dairy were rarely eaten (<0·2 servings/d). These findings suggest that the heavily plant-based diet of rural Zambian children provides inadequate Ca, folate, vitamin B12 and Fe to meet recommended nutrient intakes.
Does non-echo-planar diffusion-weighted magnetic resonance imaging have a role in assisting the clinical diagnosis of cholesteatoma in selected cases?
Authors: Nash R , Lingam R K , Chandrasekharan D , Singh A
Published: January 2018

Objective:

To determine the diagnostic performance of diffusion-weighted magnetic resonance imaging in the assessment of patients with suspected, but not clinically evident, cholesteatoma.

Methods:

A retrospective analysis of a prospectively collected database of non-echo-planar diffusion-weighted magnetic resonance imaging studies (using a half-Fourier single-shot turbo-spin echo sequence) was conducted. Clinical records were retrospectively reviewed to determine indications for imaging and operative findings. Seventy-eight investigations in 74 patients with suspected cholesteatoma aged 5.7–79.2 years (mean, 41.7 years) were identified. Operative confirmation was available in 44 ears. Diagnostic accuracy of the imaging technique was calculated using operative findings as a ‘gold standard’. Sensitivity of the investigation was examined via comparison with clinically evident cholesteatoma.

Results:

The accuracy of diffusion-weighted magnetic resonance imaging in assessment of suspected cholesteatoma was 63.6 per cent. The imaging technique was significantly less accurate in assessment of suspected cholesteatoma than clinically evident disease (p< 0.001).

Conclusion:

Computed tomography and diffusion-weighted magnetic resonance imaging may be complementary in assessment of suspected cholesteatoma, but should be used with caution, and clinical judgement is paramount.
Episodic memory and the witness trump card
Authors: Henry Jeremy , Craver Carl
Published: January 2018

We accept Mahr & Csibra's (M&C's) causal claim that episodic memory provides humans with the means for evaluating the veracity of reports about non-occurrent events. We reject their evolutionary argument that this is the proper function of episodic memory. We explore three intriguing implications of the causal claim, for cognitive neuropsychology, comparative psychology, and philosophy.
Encoding third-person epistemic states contributes to episodic reconstruction of memories
Authors: Kampis Dora , Keszei András , Király Ildikó
Published: January 2018

We propose an extension to Mahr & Csibra's (M&C's) theory. For successful episodic memory formation, potentially relevant aspects of a situation need to be identified and encodedonlineand retained for prospective interactions.To be maximally convincing, the communicator not only has to encode not justanycontextual detail, but also has to track informationin relation tosocial partners.
False memories, nonbelieved memories, and the unresolved primacy of communication
Authors: Nash Robert A.
Published: January 2018

Mahr & Csibra (M&C) make a compelling case for a communicative function of episodic remembering, but a less compelling case that this is its primary function. Questions arise on whether confirming their predictions would support their account sufficiently, on the communicative function of preserving rich, nonbelieved memories, and on the epistemic benefits of developing false memories via the acceptance of misinformation.
Enhanced action control as a prior function of episodic memory
Authors: Rau Philipp , Botterill George
Published: January 2018

Improved control of agency is likely to be a prior and more important function of episodic memory than the epistemic-communicative role pinpointed by Mahr & Csibra (M&C). Taking the memory trace upon which scenario construction is based to be a stored internal model produced in past perceptual processing promises to provide a better account of autonoetic character than metarepresentational embedding.
Constructive episodic simulation, flexible recombination, and memory errors
Authors: Schacter Daniel L. , Carpenter Alexis C. , Devitt Aleea , Roberts Reece P. , Addis Donna Rose
Published: January 2018

According to Mahr & Csibra (M&C), the view that the constructive nature of episodic memory is related to its role in simulating future events has difficulty explaining why memory is often accurate. We hold this view, but disagree with their conclusion. Here we consider ideas and evidence regarding flexible recombination processes in episodic retrieval that accommodate both accuracy and distortion.
Doing without metarepresentation: Scenario construction explains the epistemic generativity and privileged status of episodic memory
Authors: Werning Markus , Cheng Sen
Published: January 2018

Episodic memories are distinct from semantic memories in that they are epistemically generative and privileged. Whereas Mahr & Csibra (M&C) develop a metarepresentational account of epistemic vigilance, we propose an explanation that builds on our notion of scenario construction: The way an event of the past is presented in episodic memory recall explains the epistemic generativity and privilegedness of episodic memory.
Emulation of pilot control behavior across a Stewart platform simulator
Authors: Eftekhari Mojtaba , Karimpour Hossein
Published: January 2018

This paper presents a model-based controller consisting of a feedback linearization scheme and a state-dependent proportional derivative (PD) controller adapted to a parallel flight simulator Stewart mechanism. This parallel robot is considered to emulate motions of highly maneuverable aircrafts, which require well-trained pilots. The simulations are based upon a reduced-model prototype built in order to verify kinematic design aspects and control laws. Indeterminacies in the mass distribution of the system will generally affect model-based controllers, necessitating compensation or the employment of robust control methods. Through introducing the pilot's sensorial feedback of acceleration, the pilot's behavior in giving commands is emulated via an optimization process, which tunes the controller coefficients accordingly. Stability of the designed control system is guaranteed via the Lyapunov approach. To further explore the system through perilous flight scenarios, three pre-designed maneuvers are selected as test cases. It is expected that closed-loop control tasks in which a pilot tracks a target, while at the same time the controller rejects disturbances and adapts itself to the pilot's progressive skills, are ameliorated through this arrangement. Numerical results show that the proposed method is found robust in the training process in conditions of parameters indeterminacy.
Strong Tracking Sigma Point Predictive Variable Structure Filter for Attitude Synchronisation Estimation
Authors: Cao Lu , Qiao Dong , Lei Han , Wang Gongbo
Published: January 2018

In this paper, a novel Strong Tracking Sigma-Point Predictive Variable Structure Filter (ST-SP-PVSF) is presented as a further development of the Adaptive Predictive Variable Structure Filter (APVSF) for attitude synchronisation during Satellite Formation Flying (SFF). First, the sequence orthogonal principle is adopted to enhance the robustness of the APVSF for any nonlinear system with uncertain model errors. Then, sigma-point sampling strategies (such as unscented transfer, cubature rule and Stirling's polynomial interpolation) are introduced to extend the APVSF with the ability to capture the second central moment's information on the model errors to update the system model with higher precision. The new methodology has advantages in dealing with the various types of uncertainties or model errors compared with the APVSF. In addition, it does not need to choose the limit boundary layer ψlim it for system estimation, which reduces the sensitivity to the initial parameters and improves its adaptive ability over the APVSF. Simulations are performed to demonstrate that the proposed method is more suitable for attitude synchronisation estimation of the SFF system.
Is birth weight associated with blood pressure among African children and adolescents? A systematic review
Authors: Lule S. A. , Elliott A. M. , Smeeth L. , Webb E. L.
Published: January 2018

There is substantial evidence of an inverse association between birth weight and later blood pressure (BP) in populations from high-income countries, but whether this applies in low-income countries, where causes of low birth weight are different, is not certain. Objective: We conducted a review of the evidence on the relationship between birth weight and BP among African children and adolescents. Medline, EMBASE, Global Health and Web of Science databases were searched for publications to October 2016. Papers reporting the relationship between birth weight and BP among African children and adolescents were assessed. Bibliographies were searched for further relevant publications. Selected papers were summarized following the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines. In total, 16 papers from 13 studies conducted in nine African countries (Nigeria, Republic of Seychelles, Gambia, Democratic Republic of Congo, Cameroon, South Africa, Algeria, Zimbabwe and Angola) were reviewed. Eight studies were cohorts, while five were cross-sectional. The relationship between birth weight and later BP varied with age of the participants. Studies in neonates showed a consistently positive association, while predominantly inverse associations were seen among children, and studies in adolescents were inconsistent. Based on the limited number of studies identified, the relationship between birth weight and later BP may vary with age in African children and adolescents. Not all studies adequately controlled for confounding, notably gender or age. Whether the inverse relationship between birth weight and BP in later life observed in Western settings is also seen in Africa remains unclear.
The Headington Institute Resilience Inventory (HIRI): Development and Validation for Humanitarian Aid Workers
Authors: Nolty Anne A. T. , Bosch Donald S. , An Eric , Clements Crystal T. , Buckwalter J. Galen
Published: January 2018

We developed the Headington Institute Resilience Inventory as a psychometrically valid, multifactored self-report measure to identify dimensions of resilience for international aid workers. We define resilience as the capacity to adapt during traumatic incidents so that one not only just survives but survives well. By utilizing a dynamic approach to resilience to predict this adaptive capacity, we aim to identify dimensions that could lead to personalized protective training exercises, essential because of the work in areas of constant tension where there is a high risk of exposure to traumatic events. From 84 theory-driven items, through exploratory and confirmatory factor analyses with 2 samples of aid workers ( ns = 724 and 829), we identified and refined the most robust factors. Our resulting 7-factor, 33-item measure had αs greater than .69 for all factors, test–retest reliability coefficients between .79 and .94, and an estimate of composite scale reliability of .82. The findings are congruent with social–cognitive theories of resilience, which provide a plausible understanding of resilience as a multifaceted, dynamic construct. Although continued research is needed to fully validate the construct of resilience, this framework identifies dimensions of protective assets that are believed to be amenable to development, thus providing aid workers with a working definition of resilience.
The Development and Validation of a Chinese Proactive Coping Inventory Among Chinese College Students
Authors: Tian Lu , Heppner P. Paul
Published: January 2018

The current study reports the development of a dispositional Chinese Proactive Coping (CPC) Inventory to assess proactive coping activities, which intend to interfere with or prepare for potential future stressors, among Chinese college students. The results of exploratory and confirmatory factor analyses using two samples of Chinese college students ( N = 459) suggested the viability and stability of a four-factor model: Active Preparation for Potential Stressors, Utilizing Knowledge of Potential Stressors, Contextual Consideration of Proactive Actions, and Approaching Proactive Actions. The 17-item CPC provided strong evidences of psychometric properties, and the proactive coping strategies represented in the items were helpful in resolving life problems. In addition, concurrent, construct, and incremental validity estimates suggest the CPC (a) was conceptually not only quite different than the reactive coping inventories but also slightly positively related, (b) was associated with a range of indices of psychological adjustment, and (c) uniquely predicted additional variance in coping outcomes beyond social desirability. The results suggest the importance of broadening coping theories to include proactive coping reflecting the complex nature of human coping behaviors.
Therapeutic potential of targeting S100A11 in malignant pleural mesothelioma
Authors: Sato Hiroki , Sakaguchi Masakiyo , Yamamoto Hiromasa , Tomida Shuta , Aoe Keisuke , Shien Kazuhiko , Yoshioka Takahiro , Namba Kei , Torigoe Hidejiro , Soh Junichi , Tsukuda Kazunori , Tao Hiroyuki , Okabe Kazunori , Miyoshi Shinichiro , Pass Harvey I. , Toyooka Shinichi
Published: January 2018

Malignant pleural mesothelioma (MPM) is an aggressive tumor with an unfavorable prognosis. The standard therapeutic approaches are limited to surgery, chemotherapy, and radiotherapy. Because the consequent clinical outcome is often unsatisfactory, a different approach in MPM treatment is required. S100A11, a Ca2+-binding small protein with two EF-hands, is frequently upregulated in various human cancers. Interestingly, it has been found that intracellular and extracellular S100A11 have different functions in cell viability. In this study, we focused on the impact of extracellular S100A11 in MPM and explored the therapeutic potential of an S100A11-targeting strategy. We examined the secretion level of S100A11 in various kinds of cell lines by enzyme-linked immunosorbent assay. Among them, six out of seven MPM cell lines actively secreted S100A11, whereas normal mesothelial cell lines did not secrete it. To investigate the role of secreted S100A11 in MPM, we inhibited its function by neutralizing S100A11 with an anti-S100A11 antibody. Interestingly, the antibody significantly inhibited the proliferation of S100A11-secreting MPM cells in vitro and in vivo. Microarray analysis revealed that several pathways including genes involved in cell proliferation were negatively enriched in the antibody-treated cell lines. In addition, we examined the secretion level of S100A11 in various types of pleural effusions. We found that the secretion of S100A11 was significantly higher in MPM pleural effusions, compared to others, suggesting the possibility for the use of S100A11 as a biomarker. In conclusion, our results indicate that extracellular S100A11 plays important roles in MPM and may be a therapeutic target in S100A11-secreting MPM.
LRIG2 is a growth suppressor of Hec-1A and Ishikawa endometrial adenocarcinoma cells by regulating PI3K/AKT- and EGFR-mediated apoptosis and cell-cycle
Authors: Suh Dae-Shik , Park Si Eun , Jin Hanyong , Lee Kangseok , Bae Jeehyeon
Published: January 2018

Although endometrial cancer is the most common type of gynecological malignancy in developed countries, its molecular etiology is not well understood. Leucine-rich repeat and immunoglobulin-like domain 2 (LRIG2) is an evolutionarily conserved gene, but its functions in the endometrium are unknown. In this study, we found that LRIG2 is highly downregulated in endometrial adenocarcinoma patients and that it functions as a tumor suppressor. LRIG2 induced the mitochondrion-mediated apoptotic pathways by regulating stoichiometric balance among BCL-2 family proteins, whereby pro-survival members, MCL-1 and BCL-xL, were downregulated and pro-apoptotic BAK and BAX were upregulated. LRIG2 also inhibited proliferation of the Hec-1A and Ishikawa endometrial adenocarcinoma cells by upregulating p21. LRIG2 induced BAX- and BAK-dependent cell death that was efficiently prevented by MCL-1 overexpression. Furthermore, we found that LRIG2 unexpectedly phosphor-activates phosphoinositide 3-kinase (PI3K)/AKT and epidermal growth factor receptor (EGFR), which are conventionally accepted as survival signaling cues in diverse types of cancer. We observed that PI3K/AKT and EGFR serve as key kinases that have roles as growth suppressors of Hec-1A endometrial cancer cells by mediating the LRIG2-induced modulation of the BCL-2 family of proteins and p21. In vivo delivery of antisense DNAs against LRIG2 promoted the Hec-1A endometrial tumor growth in a xenograft mouse model, and immunoblotting of these tumor extracts showed consistent modulation of AKT, EGFR, the BCL-2 family members, and p21. Thus, our results demonstrated that LRIG2 is a growth suppressor of endometrial adenocarcinoma cells.
Anthelmintic niclosamide suppresses transcription of BCR-ABL fusion oncogene via disabling Sp1 and induces apoptosis in imatinib-resistant CML cells harboring T315I mutant
Authors: Jin Bei , Wang Chengyan , Shen Yingying , Pan Jingxuan
Published: January 2018

Tyrosine kinase BCR-ABL fusion protein is the driver in patients with chronic myeloid leukemia (CML). The gate-keeper mutation T315I is the most challenging mutant due to its resistance to most tyrosine kinase inhibitors (TKIs). The third generation TKI ponatinib is the only effective TKI to treat CML patients harboring T315I-BCR-ABL mutation, but with high rate of major arterial thrombotic events. Alternative strategies to specifically target T315I-BCR-ABL are needed for the treatment of CML patients harboring such a mutation. Given that Sp1 is a fundamental transcriptional factor to positively regulate WT-BCR-ABL fusion oncogene, the purpose of this investigation was aimed at evaluating the anti-tumor activity and the underlying mechanism in terms of Sp1 regulational effect on the transcription of T315I-BCR-ABL fusion oncogene. Like in WT-BCR-ABL, we identified enrichment of Sp1 on the promoter of T315I-BCR-ABL fusion gene. Treatment of WT- and T315I-BCR-ABL-expressing CML cells by niclosamide diminished such an enrichment of Sp1, and decreased WT- and T315I-BCR-ABL transcription and its downstream signaling molecules such as STAT5 and Akt. Further, niclosamide significantly inhibited the proliferation and induced apoptosis through intrinsic pathway. The in vivo efficacy validation of p-niclosamide, a water soluble derivative of niclosamide, showed that p-niclosamide significantly inhibited the tumor burden of nude mice subcutaneously bearing T315I-BCR-ABL-expressing CML cells, and prolonged the survival of allografted leukemic mice harboring BaF3-T315I-BCR-ABL. We conclude that niclosamide is active against T315I-BCR-ABL-expressing cells, and may be a promising agent for CML patients regardless of T315I mutation status.
TACC3 transcriptionally upregulates E2F1 to promote cell growth and confer sensitivity to cisplatin in bladder cancer
Authors: Lin Zhi-Rui , Wang Meng-Yao , He Shi-Yang , Cai Zhi-Ming , Huang Wei-Ren
Published: January 2018

Accumulating evidence has shown that transforming acidic coiled-coil 3 (TACC3) is deregulated in a broad spectrum of cancers. In the present study, we reported that TACC3 was markedly elevated in bladder cancer, especially in muscle-invasive bladder cancers (MIBCs). The upregulation of TACC3 was positively associated with tumor invasiveness, grade, T stage, and progression in patients with bladder cancer. Furthermore, a Kaplan–Meier survival analysis showed that patients with bladder cancer whose tumors had high TACC3 expression experienced a dismal prognosis compared with patients whose tumors had low TACC3 expression. Functional studies have found that TACC3 is a prerequisite for the development of malignant characteristics of bladder cancer cells, including cell proliferation and invasion. Moreover, TACC3 promoted G1/S transition, which was mediated via activation of the transcription of E2F1, eventually enhancing cell proliferation. Notably, the overexpression of TACC3 or E2F1 indicates a high sensitivity to cisplatin. Taken together, these findings define a tumor-supportive role for TACC3, which may also serve as a prognostic and therapeutic indicator in bladder cancers
Molecular snapshots of APE1 proofreading mismatches and removing DNA damage
Authors: Whitaker Amy M. , Flynn Tony S. , Freudenthal Bret D.
Published: January 2018

Human apurinic/apyrimidinic (AP) endonuclease 1 (APE1) is an essential DNA repair enzyme which uses a single active site to process DNA damage via two distinct activities: (1) AP-endonuclease and (2) 3′ to 5′ exonuclease. The AP-endonuclease activity cleaves at AP-sites, while the exonuclease activity excises bulkier 3′ mismatches and DNA damage to generate clean DNA ends suitable for downstream repair. Molecular details of the exonuclease reaction and how one active site can accommodate various toxic DNA repair intermediates remains elusive despite being biologically important. Here, we report multiple high-resolution APE1–DNA structural snapshots revealing how APE1 removes 3′ mismatches and DNA damage by placing the 3′ group within the intra-helical DNA cavity via a non-base flipping mechanism. This process is facilitated by a DNA nick, instability of a mismatched/damaged base, and bending of the DNA. These results illustrate how APE1 cleanses DNA dirty-ends to generate suitable substrates for downstream repair enzymes.
Dendritic core-shell nickel-iron-copper metal/metal oxide electrode for efficient electrocatalytic water oxidation
Authors: Zhang Peili , Li Lin , Nordlund Dennis , Chen Hong , Fan Lizhou , Zhang Biaobiao , Sheng Xia , Daniel Quentin , Sun Licheng
Published: January 2018

Electrochemical water splitting requires efficient water oxidation catalysts to accelerate the sluggish kinetics of water oxidation reaction. Here, we report a promisingly dendritic core-shell nickel-iron-copper metal/metal oxide electrode, prepared via dealloying with an electrodeposited nickel-iron-copper alloy as a precursor, as the catalyst for water oxidation. The as-prepared core-shell nickel-iron-copper electrode is characterized with porous oxide shells and metallic cores. This tri-metal-based core-shell nickel-iron-copper electrode exhibits a remarkable activity toward water oxidation in alkaline medium with an overpotential of only 180 mV at a current density of 10 mA cm−2. The core-shell NiFeCu electrode exhibits pH-dependent oxygen evolution reaction activity on the reversible hydrogen electrode scale, suggesting that non-concerted proton-electron transfers participate in catalyzing the oxygen evolution reaction. To the best of our knowledge, the as-fabricated core-shell nickel-iron-copper is one of the most promising oxygen evolution catalysts.
Automated NMR resonance assignments and structure determination using a minimal set of 4D spectra
Authors: Evangelidis Thomas , Nerli Santrupti , Nováček Jiří , Brereton Andrew E. , Karplus P. Andrew , Dotas Rochelle R. , Venditti Vincenzo , Sgourakis Nikolaos G. , Tripsianes Konstantinos
Published: January 2018

Automated methods for NMR structure determination of proteins are continuously becoming more robust. However, current methods addressing larger, more complex targets rely on analyzing 6–10 complementary spectra, suggesting the need for alternative approaches. Here, we describe 4D-CHAINS/autoNOE-Rosetta, a complete pipeline for NOE-driven structure determination of medium- to larger-sized proteins. The 4D-CHAINS algorithm analyzes two 4D spectra recorded using a single, fully protonated protein sample in an iterative ansatz where common NOEs between different spin systems supplement conventional through-bond connectivities to establish assignments of sidechain and backbone resonances at high levels of completeness and with a minimum error rate. The 4D-CHAINS assignments are then used to guide automated assignment of long-range NOEs and structure refinement in autoNOE-Rosetta. Our results on four targets ranging in size from 15.5 to 27.3 kDa illustrate that the structures of proteins can be determined accurately and in an unsupervised manner in a matter of days.
A dual role for the N-terminal domain of the IL-3 receptor in cell signalling
Authors: Broughton Sophie E. , Hercus Timothy R. , Nero Tracy L. , Kan Winnie L. , Barry Emma F. , Dottore Mara , Cheung Tung Shing Karen S. , Morton Craig J. , Dhagat Urmi , Hardy Matthew P. , Wilson Nicholas J. , Downton Matthew T. , Schieber Christine , Hughes Timothy P. , Lopez Angel F. , Parker Michael W.
Published: January 2018

The interleukin-3 (IL-3) receptor is a cell-surface heterodimer that links the haemopoietic, vascular and immune systems and is overexpressed in acute and chronic myeloid leukaemia progenitor cells. It belongs to the type I cytokine receptor family in which the α-subunits consist of two fibronectin III-like domains that bind cytokine, and a third, evolutionarily unrelated and topologically conserved, N-terminal domain (NTD) with unknown function. Here we show by crystallography that, while the NTD of IL3Rα is highly mobile in the presence of IL-3, it becomes surprisingly rigid in the presence of IL-3 K116W. Mutagenesis, biochemical and functional studies show that the NTD of IL3Rα regulates IL-3 binding and signalling and reveal an unexpected role in preventing spontaneous receptor dimerisation. Our work identifies a dual role for the NTD in this cytokine receptor family, protecting against inappropriate signalling and dynamically regulating cytokine receptor binding and function.
Global observations of reflectors in the mid-mantle with implications for mantle structure and dynamics
Authors: Waszek Lauren , Schmerr Nicholas C. , Ballmer Maxim D.
Published: January 2018

Seismic tomography indicates that flow is commonly deflected in the mid-mantle. However, without a candidate mineral phase change, causative mechanisms remain controversial. Deflection of flow has been linked to radial changes in viscosity and/or composition, but a lack of global observations precludes comprehensive tests by seismically detectable features. Here we perform a systematic global-scale interrogation of mid-mantle seismic reflectors with lateral size 500–2000 km and depths 800–1300 km. Reflectors are detected globally with variable depth, lateral extent and seismic polarity and identify three distinct seismic domains in the mid-mantle. Near-absence of reflectors in seismically fast regions may relate to dominantly subvertical heterogeneous slab material or small impedance contrasts. Seismically slow thermochemical piles beneath the Pacific generate numerous reflections. Large reflectors at multiple depths within neutral regions possibly signify a compositional or textural transition, potentially linked to long-term slab stagnation. This variety of reflector properties indicates widespread compositional heterogeneity at mid-mantle depths.
Mitochondrial levels determine variability in cell death by modulating apoptotic gene expression
Authors: Márquez-Jurado Silvia , Díaz-Colunga Juan , das Neves Ricardo Pires , Martinez-Lorente Antonio , Almazán Fernando , Guantes Raúl , Iborra Francisco J.
Published: January 2018

Fractional killing is the main cause of tumour resistance to chemotherapy. This phenomenon is observed even in genetically identical cancer cells in homogeneous microenvironments. To understand this variable resistance, here we investigate the individual responses to TRAIL in a clonal population of HeLa cells using live-cell microscopy and computational modelling. We show that the cellular mitochondrial content determines the apoptotic fate and modulates the time to death, cells with higher mitochondrial content are more prone to die. We find that all apoptotic protein levels are modulated by the mitochondrial content. Modelling the apoptotic network, we demonstrate that these correlations, and especially the differential control of anti- and pro-apoptotic protein pairs, confer mitochondria a powerful discriminatory capacity of apoptotic fate. We find a similar correlation between the mitochondria and apoptotic proteins in colon cancer biopsies. Our results reveal a different role of mitochondria in apoptosis as the global regulator of apoptotic protein expression.
Gamma and beta bursts during working memory readout suggest roles in its volitional control
Authors: Lundqvist Mikael , Herman Pawel , Warden Melissa R. , Brincat Scott L. , Miller Earl K.
Published: January 2018

Working memory (WM) activity is not as stationary or sustained as previously thought. There are brief bursts of gamma (~50–120 Hz) and beta (~20–35 Hz) oscillations, the former linked to stimulus information in spiking. We examined these dynamics in relation to readout and control mechanisms of WM. Monkeys held sequences of two objects in WM to match to subsequent sequences. Changes in beta and gamma bursting suggested their distinct roles. In anticipation of having to use an object for the match decision, there was an increase in gamma and spiking information about that object and reduced beta bursting. This readout signal was only seen before relevant test objects, and was related to premotor activity. When the objects were no longer needed, beta increased and gamma decreased together with object spiking information. Deviations from these dynamics predicted behavioral errors. Thus, beta could regulate gamma and the information in WM.
Female sexual behavior in mice is controlled by kisspeptin neurons
Authors: Hellier Vincent , Brock Olivier , Candlish Michael , Desroziers Elodie , Aoki Mari , Mayer Christian , Piet Richard , Herbison Allan , Colledge William Henry , Prévot Vincent , Boehm Ulrich , Bakker Julie
Published: January 2018

Abstract

Sexual behavior is essential for the survival of many species. In female rodents, mate preference and copulatory behavior depend on pheromones and are synchronized with ovulation to ensure reproductive success. The neural circuits driving this orchestration in the brain have, however, remained elusive. Here, we demonstrate that neurons controlling ovulation in the mammalian brain are at the core of a branching neural circuit governing both mate preference and copulatory behavior. We show that male odors detected in the vomeronasal organ activate kisspeptin neurons in female mice. Classical kisspeptin/Kiss1R signaling subsequently triggers olfactory-driven mate preference. In contrast, copulatory behavior is elicited by kisspeptin neurons in a parallel circuit independent of Kiss1R involving nitric oxide signaling. Consistent with this, we find that kisspeptin neurons impinge onto nitric oxide-synthesizing neurons in the ventromedial hypothalamus. Our data establish kisspeptin neurons as a central regulatory hub orchestrating sexual behavior in the female mouse brain.
Configurable topological textures in strain graded ferroelectric nanoplates
Authors: Kim Kwang-Eun , Jeong Seuri , Chu Kanghyun , Lee Jin Hong , Kim Gi-Yeop , Xue Fei , Koo Tae Yeong , Chen Long-Qing , Choi Si-Young , Ramesh Ramamoorthy , Yang Chan-Ho
Published: January 2018

Topological defects in matter behave collectively to form highly non-trivial structures called topological textures that are characterised by conserved quantities such as the winding number. Here we show that an epitaxial ferroelectric square nanoplate of bismuth ferrite subjected to a large strain gradient (as much as 105 m−1) associated with misfit strain relaxation enables five discrete levels for the ferroelectric topological invariant of the entire system because of its peculiar radial quadrant domain texture and its inherent domain wall chirality. The total winding number of the topological texture can be configured from − 1 to 3 by selective non-local electric switching of the quadrant domains. By using angle-resolved piezoresponse force microscopy in conjunction with local winding number analysis, we directly identify the existence of vortices and anti-vortices, observe pair creation and annihilation and manipulate the net number of vortices. Our findings offer a useful concept for multi-level topological defect memory.
Differential coding of reward and movement information in the dorsomedial striatal direct and indirect pathways
Authors: Shin Jung Hwan , Kim Dohoung , Jung Min Whan
Published: January 2018

The direct and indirect pathways of the basal ganglia have long been thought to mediate behavioral promotion and inhibition, respectively. However, this classic dichotomous model has been recently challenged. To better understand neural processes underlying reward-based learning and movement control, we recorded from direct (dSPNs) and indirect (iSPNs) pathway spiny projection neurons in the dorsomedial striatum of D1-Cre and D2-Cre mice performing a probabilistic Pavlovian conditioning task. dSPNs tend to increase activity while iSPNs decrease activity as a function of reward value, suggesting the striatum represents value in the relative activity levels of dSPNs versus iSPNs. Lick offset-related activity increase is largely dSPN selective, suggesting dSPN involvement in suppressing ongoing licking behavior. Rapid responses to negative outcome and previous reward-related responses are more frequent among iSPNs than dSPNs, suggesting stronger contributions of iSPNs to outcome-dependent behavioral adjustment. These findings provide new insights into striatal neural circuit operations.