bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparison of Bayesian and Monte Carlo sensitivity analysis for unmeasured confounding
Authors: McCandless Lawrence C. , Gustafson Paul
Published: April 2017

Bias from unmeasured confounding is a persistent concern in observational studies, and sensitivity analysis has been proposed as a solution. In the recent years, probabilistic sensitivity analysis using either Monte Carlo sensitivity analysis (MCSA) or Bayesian sensitivity analysis (BSA) has emerged as a practical analytic strategy when there are multiple bias parameters inputs. BSA uses Bayes theorem to formally combine evidence from the prior distribution and the data. In contrast, MCSA samples bias parameters directly from the prior distribution. Intuitively, one would think that BSA and MCSA ought to give similar results. Both methods use similar models and the same (prior) probability distributions for the bias parameters. In this paper, we illustrate the surprising finding that BSA and MCSA can give very different results. Specifically, we demonstrate that MCSA can give inaccurate uncertainty assessments (e.g. 95% intervals) that do not reflect the data's influence on uncertainty about unmeasured confounding. Using a data example from epidemiology and simulation studies, we show that certain combinations of data and prior distributions can result in dramatic prior‐to‐posterior changes in uncertainty about the bias parameters. This occurs because the application of Bayes theorem in a non‐identifiable model can sometimes rule out certain patterns of unmeasured confounding that are not compatible with the data. Consequently, the MCSA approach may give 95% intervals that are either too wide or too narrow and that do not have 95% frequentist coverage probability. Based on our findings, we recommend that analysts use BSA for probabilistic sensitivity analysis. Copyright © 2017 John Wiley & Sons, Ltd.
Facile Access to Twisted Intramolecular Charge‐Transfer Fluorogens Bearing Highly Pretwisted Donor–Acceptor Systems Together with Readily Fine‐Tuned Charge‐Transfer Characters
Authors: Luo Yanju , Wang Yan , Chen Shiqi , Wang Ning , Qi Yige , Zhang Xiaogen , Yang Minghui , Huang Yan , Li Ming , Yu Junsheng , Luo Daibing , Lu Zhiyun
Published: April 2017

Twisted intramolecular charge‐transfer (TICT) fluorogens bearing highly pretwisted geometries and readily‐fine‐tuned charge‐transfer characters are quite promising sensor and electroluminescence (EL) materials. In this study, by using 4‐aryloxy‐1,8‐naphthalimide derivatives as the molecular framework, it is demonstrated for the first time that a CO bond could serve as the central bond to construct new TICT D‐A systems. Photophysical and quantum chemical studies confirm that rotation around central CO bonds is responsible for the formation of a stable TICT state in these compounds. More importantly, owing to the structural adjustability of the aryl moiety and the strong steric interactions between the naphthalimide and the aryl ring systems, these compounds can display readily‐fine‐tuned TICT characters, hence exhibiting an adjustable solvent polarity threshold for aggregation‐induced emission (AIE) activity, and could be AIE‐active even in less‐polar toluene and nonpolar cyclohexane. Furthermore, these compounds could possess highly‐pretwisted ground‐state geometries, hence could show good EL performance. The findings reveal a facile but effective molecular constructive strategy for versatile, high‐performance optoelectronic TICT compounds.
Get ready for the genomic revolution
Authors: Kirby Roger
Published: April 2017

Prostate cancer is a recognised component of the hereditary breast and ovarian cancer (HBOC) syndrome cancer spectrum, where inherited susceptibility is accounted for by mutations in BRCA1 and BRCA2 genes. Genetic testing for BRCA1/2 mutations may provide some men with information about their risk for developing aggressive prostate cancer…
The sexual consequences of congenital pelvic anomalies
Authors: Woodhouse Christopher
Published: April 2017

Congenital pelvic anomalies are relatively rare in males. Little is known about their impact on sexual function and activity as these boys grow into men. In this article the author looks at the data available and encourages health professionals who look after such patients not to be afraid to discuss sex.
The expert medical witness: the good, the bad and the ugly
Authors: McDonald Peter
Published: April 2017

In light of the recent quashing of the conviction of surgeon David Sellu for gross negligence, Peter McDonald discusses the role of the expert medical witness and makes the case for some form of quality control or accreditation for this important role.
A surgeon's responsibility: their life in your hands
Authors: Smith Joseph
Published: April 2017

Surgeons literally take the life of their patients in their hands. In this article Joseph Smith describes the trust patients put in their surgeons and how surgeons have to respond to that trust, by only performing operations that they themselves know they are qualified and competent to perform.
Li4Ba[BN2]2 – Structure and Vibrational Spectra
Authors: Seidel Stefan , Somer Mehmet , Kiraz Kamil , Rodewald Ute Ch. , Pöttgen Rainer
Published: April 2017

The nitridoborate Li4Ba[BN2]2 was synthesized from a 4:1 molar ratio of Li3[BN]2 and Ba3[BN2]2 in an arc‐welded niobium ampoule at a maximum annealing temperature of 1173 K. The structure was refined from single‐crystal X‐ray diffractometer data: new type, P1, a = 533.9(2), b = 585.0(3), c = 860.6(4) pm, α = 80.72(3), β = 73.84(6), γ = 89.87(4)°, wR2 = 0.1196, 1429 F2 values, 50 variables. The Li4Ba[BN2]2 structure contains two crystallographically independent [BN2]3– units with 134 pm B–N distance, which are slightly bent: 178° for N2–B1–N1 and 175° for N4–B2–N3. Due to the high lithium content both [BN2]3– units have a strongly distorted coordination by 8Li+ + 3Ba2+. The four crystallographically independent lithium cations show distorted tetrahedral coordination by [BN2]3– units with Li–N distances ranging from 195 to 247 pm. IR and Raman spectra show the typical vibrations of the [BN2] unit along with a well‐resolved splitting of the ν(10Β) and ν(11B) frequencies.
Biophenols and Flavor in Extra Virgin Olive Oils from San Juan Province (Argentina)
Authors: Ceci Liliana N. , Ramírez Daniela , Mussio Daniela F. , Mattar Susana B. , Carelli Amalia A.
Published: April 2017

This work studied phenolic compounds and their relationship with flavor in extra virgin olive oils from Arbequina, Changlot Real, and Coratina cultivars from San Juan province (Argentina) in the 2012 and 2013 harvests. In 2013, the harvesting was brought forward by 15–17 days. The total and individual biophenols were analyzed by HPLC–UV. A taste panel recognized by the International Olive Council (IOC) carried out the sensory analysis. Oxidative stability was measured by accelerated oxidation assays using Rancimat equipment. The oils obtained in 2013 from the three cultivars had higher biophenol contents and particularly higher contents of secoiridoids and derivatives. The positive attributes (fruitiness, bitterness, and pungency) of the oils were more harmonious in the three cultivars in 2013 by enhancing the complexity with a wide range of green descriptors. The oxidative stability indices of the oils were also higher in the three cultivars in 2013. The multiple linear regression model suggested that the aldehyde and hydroxylic form of oleuropein aglycone (3,4‐DHPEA‐EA) was the main contributor (65.5%) to bitterness, while the dialdehyde form of decarboxymethyl ligstroside aglycone (p‐HPEA‐EDA), besides reducing bitterness, was the major contributor to pungency (52.2%). Among simple phenols, o‐coumaric acid contributed to bitterness (2.3%), and tyrosol (6.3%) and tyrosyl acetate (3.3%) were related to pungency.
First Investigation in the Biochemical Analysis of the Invasive Crab Portunus segnis from Tunisian Waters
Authors: Bejaoui Safa , Ghribi Feriel , Hatira Sameh , Chetoui Imene , Rebah Imen , Cafsi M’hamed El
Published: April 2017

The invasive Portunus segnis, an atlantic species, was recently recorded in Tunisian waters. Since its record in the Gulf of Gabes, no studies have been carried out about the biochemical analysis of this alien species. In this context, our study aims to evaluate the fatty acid profile, lipid classes (neutral and polar), and nutritional value of breast of this invasive species. Specimens sampled from the gulf of Gabes were found to be rich in protein and oil, with significant differences between sexes. The level of saturated, monounsaturated, and polyunsaturated fatty acids in neutral and polar showed a significant difference between sexes. Saturated fatty acids were significantly higher in male P. segnis compared to the female. Docosahexaenoic (DHA), eicosapentaenoic (EPA), and arachidonic (ARA) were the most predominate polyunsaturated fatty acids (PUFA) in all oil classes. Oleic (C18:1) and Palmitoleic (C16:1) were the most abundant in monounsaturated. Palmitic (C16:0) and Stearic (C18:0) were the major saturated fatty acids. Consequently, the breast of P. segnis was a valuable source of high oil quality: It is rich in essential fatty acids and has an important n‐3/n‐6 ratio in both male and female blue crab. Therefore, the atherogenicity and the thrombogenicity were also evaluated, showing that P. segnis is a shellfish of greater value for human consumption in Tunisia.
Transradial Access for Interventional Radiology: Single-Centre Procedural and Clinical Outcome Analysis
Authors: Thakor Avnesh S. , Alshammari Mohammed T. , Liu David M. , Chung John , Ho Stephen G.F. , Legiehn Gerald M. , Machan Lindsay , Fischman Aaron M. , Patel Rahul S. , Klass Darren
Published: April 2017

Purpose

The study sought to describe a single centre's technical approach to transradial intervention and report on clinical outcomes and safety.

Methods

A total of 749 transradial access (TRA) procedures were performed at a single hospital in 562 patients (174 women and 388 men). Procedures included 445 bland embolizations or chemoembolizations of the liver, 88 uterine artery embolizations, and 148 procedures for Selective Internal Radiation Therapy (Y90), which included mapping and administration. The mean age of the patients was 62 years (range 27–96 years).

Results

Four cases (0.5%) required crossover to transfemoral (tortuous anatomy, inability to secure a stable position for embolization, vessel spasm and base catheter not being of a sufficient length). A single asymptomatic, short-segment radial artery occlusion occurred (0.3%), 3 patients (0.4%) developed small hematomas postprocedurally, and 2 patients (0.7%) had transient neurological pain, which was resolved within a week without treatment. It was found that 98% of patients who had a previous femoral access procedure would choose radial access for subsequent procedures.

Conclusions

Transradial access is a safe, effective technique, with a learning curve; however, this procedure has the potential to significantly improve departmental workflow and cost savings for the department and patient experience.
Reseña del libro Conceptos clave en los estudios de género (2016), coordinado por Hortensia Moreno y Eva Alcántara
Authors: Sabido Ramos Olga
Published: April 2017

Rese˜na del libro Conceptos clave en los estudios de género (2016), coordinado por Hortensia Moreno y Eva Alcántara
travesía hacia la indeterminación: una reseña de The Argonauts de Maggie Nelson
Authors: González Saravia Peña Ana Sofía
Published: April 2017

La travesía hacia la indeterminación: una reseña de The Argonauts (2015) de Maggie Nelson
The role of interleukin‐1β and extracellular signal‐regulated kinase 1/2 in glucose‐stimulated insulin secretion
Authors: Niu Ben , Su Heng , Xia Xue‐Shan , He Qiu , Xue Yuan‐Ming , Yan Xin‐Ming
Published: April 2017

Glucose‐stimulated insulin secretion (GSIS) is one of the important physiological characteristics of islet β cells, and extracellular‐regulated protein kinase 1/2 (ERK1/2) is an important member of the mitogen‐activated protein kinase family that regulates this process. The inflammatory cytokine interleukin (IL)‐1β can inhibit the insulin secretion of pancreatic β cells, but the exact mechanism is unclear. This study was designed to investigate the inhibitory effect of IL‐1β on GSIS in βTC‐6 cells and its relation with the ERK1/2 signal transduction pathway. β‐TC6 cells were cultured and stimulated with 0mM, 1.38mM, or 5.5mM glucose. In addition, GSIS in β‐TC6 cells was blocked by IL‐1β at concentrations of 0.15 ng/mL, 1.5 ng/mL, and 15 ng/mL. After glucose stimulation and IL‐1β intervention, the insulin level in the cell supernatant was detected by radioimmunoassay, and the phosphorylation level of ERK1/2 was detected by western blotting assay. The insulin level in the 1.38mM glucose group was 108.52 ± 5.94 uIU/mL, which was significantly higher than the 0mM and 5.5mM glucose groups (p < 0.05). Compared with the 0mM glucose group, the level of ERK1/2 phosphorylation was increased in the 1.38mM and 5.5mM glucose groups. After intervention by 0.15 ng/mL, 1.5 ng/mL, and 15 ng/mL IL‐1β, the level of ERK1/2 phosphorylation induced by 1.38mM glucose stimulation decreased in a dose‐dependent manner, and the insulin level correspondingly decreased. IL‐1β can inhibit GSIS in βTC‐6 cells, which is related to its inhibition of the phosphorylation of ERK1/2.
Translating Tactical Combat Casualty Care Lessons Learned to the High-Threat Civilian Setting: Tactical Emergency Casualty Care and the Hartford Consensus
Authors: Callaway David W.
Published: April 2017

Combat operations necessitate bold thought and afford the opportunity to rapidly evolve and improve trauma care. The development and maturation of Tactical Combat Casualty Care (TCCC) is an important example of a critical process improvement strategy that reduced mortality in high-threat combat-related trauma. The Committee for Tactical Emergency Casualty Care (C-TECC) adapted the lessons of TCCC to the civilian high-threat environment and provided important all-hazards response principles for austere, dynamic, and resource-limited environments. The Hartford Consensus mobilized the resources of the American College of Surgeons to drive public policy regarding a more singular focus: hemorrhage control. The combined efforts of C-TECC and Hartford Consensus have helped redefine the practice of trauma care in high-threat scenarios across the United States.
Nature, Knowledge, and Civilisation. Connecting the Atlantic and Pacific Worlds in the Enlightenment
Authors: Irving-Stonebraker Sarah
Published: April 2017

A central feature of Scottish Enlightenment thought was the emergence of stadial or “conjectural” theories of history, in which the development of all human societies, from those in Europe, to the Seminole Indians in Florida and the Tongans of the South Pacific, could be understood and compared according to the same universal historical criteria. This paper argues that central to this tradition was an account of the relationship between “useful knowledge” and social development. This article argues that we can map the circulation of a discourse about useful knowledge, nature, and civilisation through a network of Scottish-trained physicians and naturalists that spread to the Atlantic and to the Pacific. In the Atlantic world, physicians and naturalists used the vocabulary and categories of stadial theory to classify indigenous societies: they made comparisons between the illnesses that they thought “naturally” afflicted savage cultures, as opposed to those of civilized Europeans. In the Pacific, the Edinburgh-trained surgeons and naturalists compared Tahitians, Maoris, and Australian Aborigines to black Africans and Europeans, and they commented on the presence or absence of useful knowledge as a marker of the degree of development of each civilisation.
Conceptions about teaching and learning of expressivity in music among Higher Education teachers and students
Authors: Bonastre Carolina , Muñoz Enrique , Timmers Renee
Published: April 2017

This work aimed to analyse factors related to conceptions and beliefs about expressivity in music among students and teachers. A questionnaire with 11 Likert-type items was developed covering the main factors included in the literature of teaching-learning of expressivity and emotion in music. Through exploratory factor analysis three factors were identified:expressive technique (ET), emotional expression (EE), and self-learning of expressivity (SLE). Comparisons between teachers and students showed that teachers had significant higher scores in EE with no differences in ET or SLE, although the effect size for SLE was high. The three factors are proposed as a tool for the assessment of conceptions of expressivity and its learning in both teachers and advanced students of music for teaching and research objectives.
A River Runs through It: The Yellow River and The Chinese Civil War, 1946–1947
Authors: Edgerton-Tarpley Kathryn
Published: April 2017

In June 1938 China's Nationalist government breached a major Yellow River dike in a drastic attempt to use flooding to slow the Japanese invasion. The strategic breach caused the Yellow River to abandon the northern course it had followed since 1855, and its new southeastern course led to eight years of catastrophic flooding. After World War II, the Nationalists, with extensive aid from the United Nations Relief and Rehabilitation Administration (UNRRA), aimed to close the breach and divert the river back to its pre-1938 course. However, the Chinese Communists had taken control of much of that course, and local interests there opposed the plan to bring back the river. The Yellow River diversion project thus became intensely politicized. This article examines how the diversion plan became embroiled in the Chinese Civil War of 1946–49, how the river's return to its northern course in 1947 impacted communities in its path, and how the Communists and Nationalists imagined the river and made different tactical and rhetorical uses of it during the war. I find that the campaign to reroute the river was complicated not only by the civil war but also by tension between local and national interests within the Communist Party, and that UNRRA's attempts to mediate between the Nationalists and Communists at times put the organization at odds with both parties. Moreover, in 1946 and 1947 the intense struggle to tame, make strategic use of, or cross the Yellow River became an important metaphor for the battle to control China.
The Evolution of Child Labor in Portugal, 1850–2001
Authors: Goulart Pedro , Bedi Arjun S.
Published: April 2017

Historical accounts of the evolution of child labor are limited to the United States and to the core European economies. The experience of countries outside the prosperous European core has rarely been investigated. This paper draws on data from censii, labor force, and household surveys and qualitative information such as the testimonies of various stakeholders and news articles to provide an analysis of the evolution of child labor in Portugal. The Portuguese experience is set against the backdrop of the country's economic structure and economic growth, demographic changes, educational expansion and schooling, and labor legislation. Our assessment suggests that the long-run evolution of child labor in Portugal was determined mainly by the needs of the economic structure of the country and it was the progressive adoption of skill-biased technologies that pushed children away from work. While the passage of compulsory schooling and minimum working-age laws may have provided additional impetus, they were not the main drivers as changes in these laws tended to follow declines in child labor.
The Narrowing of the Gender Wealth Gap across the Nineteenth-Century United States
Authors: McDevitt Catherine L. , Irwin James R.
Published: April 2017

Shammas (1994) documented the expansion of women's wealth holding across the nineteenth-century United States, explaining it as the result of the married women's property acts (MWPAs) passed in most of states starting circa 1840. We look at the timing of the expansion of women's wealth holding, drawing on archival and published evidence from probate records. Starting with Richmond, Virginia, and its agricultural hinterland, we consider a variety of places, urban and rural, in the South and North, to suggest a general view of the eastern United States. In rough outline, while colonial women were at most one-tenth of probated wealth holders, antebellum women were at least one-fifth. Levels of women's wealth holding increased even more. The substantial narrowing of the gender wealth gap cannot be attributed to the MWPAs that followed. Perhaps those acts will explain the further narrowing of the gender wealth gap in the later nineteenth century, but that narrowing might better be understood as a continuation of previous trends. Our results remind that some legal reforms can better be understood as reflections than causes of social change.
Symbiosis limits establishment of legumes outside their native range at a global scale
Authors: Simonsen Anna K. , Dinnage Russell , Barrett Luke G. , Prober Suzanne M. , Thrall Peter H.
Published: April 2017

Microbial symbiosis is integral to plant growth and reproduction, but its contribution to global patterns of plant distribution is unknown. Legumes (Fabaceae) are a diverse and widely distributed plant family largely dependent on symbiosis with nitrogen-fixing rhizobia, which are acquired from soil after germination. This dependency is predicted to limit establishment in new geographic areas, owing to a disruption of compatible host-symbiont associations. Here we compare non-native establishment patterns of symbiotic and non-symbiotic legumes across over 3,500 species, covering multiple independent gains and losses of rhizobial symbiosis. We find that symbiotic legume species have spread to fewer non-native regions compared to non-symbiotic legumes, providing strong support for the hypothesis that lack of suitable symbionts or environmental conditions required for effective nitrogen-fixation are driving these global introduction patterns. These results highlight the importance of mutualisms in predicting non-native species establishment and the potential impacts of microbial biogeography on global plant distributions.
Lkb1 inactivation drives lung cancer lineage switching governed by Polycomb Repressive Complex 2
Authors: Zhang Haikuo , Fillmore Brainson Christine , Koyama Shohei , Redig Amanda J. , Chen Ting , Li Shuai , Gupta Manav , Garcia-de-Alba Carolina , Paschini Margherita , Herter-Sprie Grit S. , Lu Gang , Zhang Xin , Marsh Bryan P. , Tuminello Stephanie J. , Xu Chunxiao , Chen Zhao , Wang Xiaoen , Akbay Esra A. , Zheng Mei , Palakurthi Sangeetha , Sholl Lynette M. , Rustgi Anil K. , Kwiatkowski David J. , Diehl J Alan , Bass Adam J. , Sharpless Norman E. , Dranoff Glenn , Hammerman Peter S. , Ji Hongbin , Bardeesy Nabeel , Saur Dieter , Watanabe Hideo , Kim Carla F. , Wong Kwok-Kin
Published: April 2017

Adenosquamous lung tumours, which are extremely poor prognosis, may result from cellular plasticity. Here, we demonstrate lineage switching of KRAS+ lung adenocarcinomas (ADC) to squamous cell carcinoma (SCC) through deletion of Lkb1 (Stk11) in autochthonous and transplant models. Chromatin analysis reveals loss of H3K27me3 and gain of H3K27ac and H3K4me3 at squamous lineage genes, including Sox2, ΔNp63 and Ngfr. SCC lesions have higher levels of the H3K27 methyltransferase EZH2 than the ADC lesions, but there is a clear lack of the essential Polycomb Repressive Complex 2 (PRC2) subunit EED in the SCC lesions. The pattern of high EZH2, but low H3K27me3 mark, is also prevalent in human lung SCC and SCC regions within ADSCC tumours. Using FACS-isolated populations, we demonstrate that bronchioalveolar stem cells and club cells are the likely cells-of-origin for SCC transitioned tumours. These findings shed light on the epigenetics and cellular origins of lineage-specific lung tumours.
SUMOylation of FOXP1 regulates transcriptional repression via CtBP1 to drive dendritic morphogenesis
Authors: Rocca Daniel L. , Wilkinson Kevin A. , Henley Jeremy M.
Published: April 2017

Forkhead Box P (FOXP) transcriptional repressors play a major role in brain development and their dysfunction leads to human cognitive disorders. However, little is known about how the activity of these proteins is regulated. Here, we show that FOXP1 SUMOylation at lysine 670 is required for recruiting the co-repressor CtBP1 and transcriptional repression. FOXP1 SUMOylation is tightly controlled by neuronal activity, in which synapse to nucleus signalling, mediated via NMDAR and L-type calcium channels, results in rapid FOXP1 deSUMOylation. Knockdown of FOXP1 in cultured cortical neurons stunts dendritic outgrowth and this phenotype cannot be rescued by replacement with a non-SUMOylatable FOXP1-K670R mutant, indicating that SUMOylation of FOXP1 is essential for regulation of proper neuronal morphogenesis. These results suggest that activity-dependent SUMOylation of FOXP1 may be an important mediator of early cortical development and neuronal network formation in the brain.
Light Induced Electron-Phonon Scattering Mediated Resistive Switching in Nanostructured Nb Thin Film Superconductor
Authors: Kazim Shafaq , Sharma Alka , Yadav Sachin , Gajar Bikash , Joshi Lalit M. , Mishra Monu , Gupta Govind , Husale Sudhir , Gupta Anurag , Sahoo Sangeeta , Ojha V. N.
Published: April 2017

abstract

The elemental Nb is mainly investigated for its eminent superconducting properties. In contrary, we report of a relatively unexplored property, namely, its superior optoelectronic property in reduced dimension. We demonstrate here that nanostructured Nb thin films (NNFs), under optical illumination, behave as room temperature photo-switches and exhibit bolometric features below its superconducting critical temperature. Both photo-switch and superconducting bolometric behavior are monitored by its resistance change with light in visible and near infrared (NIR) wavelength range. Unlike the conventional photodetectors, the NNF devices switch to higher resistive states with light and the corresponding resistivity change is studied with thickness and grain size variations. At low temperature in its superconducting state, the light exposure shifts the superconducting transition towards lower temperature. The room temperature photon sensing nature of the NNF is explained by the photon assisted electron-phonon scattering mechanism while the low temperature light response is mainly related to the heat generation which essentially changes the effective temperature for the device and the device is capable of sensing a temperature difference of few tens of milli-kelvins. The observed photo-response on the transport properties of NNFs can be very important for future superconducting photon detectors, bolometers and phase slip based device applications.
Room-temperature field effect transistors with metallic ultrathin TiN-based channel prepared by atomic layer delta doping and deposition
Authors: Cheng Po-Hsien , Wang Chun-Yuan , Chang Teng-Jan , Shen Tsung-Han , Cai Yu-Syuan , Chen Miin-Jang
Published: April 2017

Metallic channel transistors have been proposed as the candidate for sub-10 nm technology node. However, the conductivity modulation in metallic channels can only be observed at low temperatures usually below 100 K. In this study, room-temperature field effect and modulation of the channel resistance was achieved in the metallic channel transistors, in which the oxygen-doped TiN ultrathin-body channels were prepared by the atomic layer delta doping and deposition (AL3D) with precise control of the channel thickness and electron concentration. The decrease of channel thickness leads to the reduction in electron concentration and the blue shift of absorption spectrum, which can be explained by the onset of quantum confinement effect. The increase of oxygen incorporation results in the increase of interband gap energy, also giving rise to the decrease in electron concentration and the blue shift of absorption spectrum. Because of the significant decrease in electron concentration, the screening effect was greatly suppressed in the metallic channel. Therefore, the channel modulation by the gate electric field was achieved at room temperature due to the quantum confinement and suppressed screening effect with the thickness down to 4.8 nm and the oxygen content up to 35% in the oxygen-doped TiN ultrathin-body channel.
Monitoring of dynamic changes in Keyhole Limpet Hemocyanin (KLH)-specific B cells in KLH-vaccinated cancer patients
Authors: Wimmers Florian , de Haas Nienke , Scholzen Anja , Schreibelt Gerty , Simonetti Elles , Eleveld Marc J. , Brouwers Huberdina M. L. M. , Beldhuis-Valkis Marjo , Joosten Irma , de Jonge Marien I. , Gerritsen Winald R. , de Vries I. Jolanda M. , Diavatopoulos Dimitri A. , Jacobs Joannes F. M.
Published: April 2017

Keyhole limpet hemocyanin (KLH) is used as an immunogenic neo-antigen for various clinical applications and during vaccine development. For advanced monitoring of KLH-based interventions, we developed a flow cytometry-based assay for the ex vivo detection, phenotyping and isolation of KLH-specific B cells. As proof-of-principle, we analyzed 10 melanoma patients exposed to KLH during anti-cancer dendritic cell vaccination. Our assay demonstrated sensitive and specific detection of KLH-specific B cells in peripheral blood and KLH-specific B cell frequencies strongly correlated with anti-KLH serum antibody titers. Profiling of B cell subsets over the vaccination course revealed that KLH-specific B cells matured from naïve to class-switched memory B cells, confirming the prototypic B cell response to a neo-antigen. We conclude that flow-cytometric detection and in-depth phenotyping of KLH-specific B cells is specific, sensitive, and scalable. Our findings provide novel opportunities to monitor KLH-specific immune responses and serve as a blueprint for the development of new flow-cytometric protocols.
Hypertension and the risk of endometrial cancer: a systematic review and meta-analysis of case-control and cohort studies
Authors: Aune Dagfinn , Sen Abhijit , Vatten Lars J.
Published: April 2017

A history of hypertension has been associated with increased risk of endometrial cancer in several studies, but the results have not been consistent. We conducted a systematic review and meta-analysis of case-control and cohort studies to clarify the association between hypertension and endometrial cancer risk. PubMed and Embase databases were searched up to 27th of February 2016. Prospective and case-control studies which reported adjusted relative risk estimates and 95% confidence intervals of endometrial cancer associated with a hypertension diagnosis were included. Summary relative risks were estimated using a random effects model. Nineteen case-control studies and 6 cohort studies were included. The summary RR was 1.61 (95% CI: 1.41–1.85, I2 = 86%) for all studies, 1.73 (95% CI: 1.45–2.06, I2 = 89%) for case-control studies and 1.32 (95% CI: 1.12–1.56, I2 = 47%) for cohort studies. The association between hypertension and endometrial cancer was weaker, but still significant, among studies with adjustment for smoking, BMI, oral contraceptive use, and parity, compared to studies without such adjustment. This meta-analysis suggest an increased risk of endometrial cancer among patients with hypertension, however, further studies with more comprehensive adjustments for confounders are warranted to clarify the association.
Computational fluid dynamics simulation of the upper airway response to large incisor retraction in adult class I bimaxillary protrusion patients
Authors: Zheng Zhe , Liu Hong , Xu Qi , Wu Wei , Du Liling , Chen Hong , Zhang Yiwen , Liu Dongxu
Published: April 2017

The changes of the upper airway after large retraction of the incisors in adult class I bimaxillary protrusion patients were assessed mainly focused on the anatomic variation and ignored the functional changes. This study aimed to investigate the changes of the upper airway in adult class I bimaxillary protrusion patients after extraction treatment using the functional images based on computational fluid dynamics (CFD). CFD was implemented after 3D reconstruction based on the CBCT of 30 patients who have completed extraction treatment. After treatment, pressure drop in the minimum area, oropharynx, and hypopharynx increased significantly. The minimum pressure and the maximum velocity mainly located in the hypopharynx in pre-treatment while they mostly occured in the oropharynx after treatment. Statistically significant correlation between pressure drop and anatomic parameters, pressure drop and treatment outcomes was found. No statistical significance changes in pressure drop and volume of nasopharynx was found. This study suggested that the risk of pharyngeal collapsing become higher after extraction treatment with maximum anchorage in bimaxillary protrusion adult patients. Those adverse changes should be taken into consideration especially for high-risk patients to avoid undesired weakening of the respiratory function in clinical treatment.
pH-Controlled Cerium Oxide Nanoparticle Inhibition of Both Gram-Positive and Gram-Negative Bacteria Growth
Authors: Alpaslan Ece , Geilich Benjamin M. , Yazici Hilal , Webster Thomas J.
Published: April 2017

Here, the antibacterial activity of dextran-coated nanoceria was examined against Pseudomonas aeruginosa and Staphylococcus epidermidis by varying the dose, the time of treatment, and the pH of the solution. Findings suggested that dextran-coated nanoceria particles were much more effective at killing P. aeruginosa and S. epidermidis at basic pH values (pH = 9) compared to acidic pH values (pH = 6) due to a smaller size and positive surface charge at pH 9. At pH 9, different particle concentrations did cause a delay in the growth of P. aeruginosa, whereas impressively S. epidermidis did not grow at all when treated with a 500 μg/mL nanoceria concentration for 24 hours. For both bacteria, a 2 log reduction and elevated amounts of reactive oxygen species (ROS) generation per colony were observed after 6 hours of treatment with nanoceria at pH 9 compared to untreated controls. After 6 hours of incubation with nanoceria at pH 9, P. aeruginosa showed drastic morphological changes as a result of cellular stress. In summary, this study provides significant evidence for the use of nanoceria (+4) for a wide range of anti-infection applications without resorting to the use of antibiotics, for which bacteria are developing a resistance towards anyway.
High Temperature Deformation Mechanism in Hierarchical and Single Precipitate Strengthened Ferritic Alloys by In Situ Neutron Diffraction Studies
Authors: Song Gian , Sun Zhiqian , Li Lin , Clausen Bjørn , Zhang Shu Yan , Gao Yanfei , Liaw Peter K.
Published: April 2017

The ferritic Fe-Cr-Ni-Al-Ti alloys strengthened by hierarchical-Ni2TiAl/NiAl or single-Ni2TiAl precipitates have been developed and received great attentions due to their superior creep resistance, as compared to conventional ferritic steels. Although the significant improvement of the creep resistance is achieved in the hierarchical-precipitate-strengthened ferritic alloy, the in-depth understanding of its high-temperature deformation mechanisms is essential to further optimize the microstructure and mechanical properties, and advance the development of the creep resistant materials. In the present study, in-situ neutron diffraction has been used to investigate the evolution of elastic strain of constitutive phases and their interactions, such as load-transfer/load-relaxation behavior between the precipitate and matrix, during tensile deformation and stress relaxation at 973 K, which provide the key features in understanding the governing deformation mechanisms. Crystal-plasticity finite-element simulations were employed to qualitatively compare the experimental evolution of the elastic strain during tensile deformation at 973 K. It was found that the coherent elastic strain field in the matrix, created by the lattice misfit between the matrix and precipitate phases for the hierarchical-precipitate-strengthened ferritic alloy, is effective in reducing the diffusional relaxation along the interface between the precipitate and matrix phases, which leads to the strong load-transfer capability from the matrix to precipitate.
In-vivo Comparison of 18F-FLT uptake, CT Number, Tumor Volume in Evaluation of Repopulation during Radiotherapy for Lung cancer
Authors: Zhang Xiaoli , Yu Jinming , Li Chengming , Sun Xindong , Meng Xue
Published: April 2017

Accelerated repopulation has been observed in various tumors. This study was aimed to evaluate the potential of 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) uptake and Computed Tomography Number (CTN) in monitoring tumor responses to radiotherapy compared with tumor volume (TV) changes. Tumor bearing nude mice were assigned to either irradiated daily or every second day group and then randomized to 6 sub-groups to receive 0Gy, 6Gy, 12Gy, 18Gy, 24Gy, 36Gy irradiation, respectively. TV was measured every 3 days. 18F-FLT micro-PET/CT scans were performed after irradiation being completed. Tumor sections were stained to calculate the immunohistochemical (Ki-67) labeling index (LI). Comparison analysis between FLT uptake parameters, CTNs, VTs and Ki-67 LI results were conducted to determine the correlation. Ki-67 LI increased significantly after 6 times of irradiation at irradiated daily group and after 3 times at irradiated every second day group, suggesting accelerated repopulation. No shrinkage of TV was noticed at two groups during irradiation delivery. Both 18F-FLT uptake and CTN increased significantly after irradiation of 12Gy/6f/6d and 6Gy/3f/6d. Comparison analysis found a significant relationship between Ki-67 LI and 18F-FLT uptake parameters as well as CTN. Both 18F-FLT PET and CT have the potential to reflect the tumor proliferative response during radiation delivery.
Characterization of the influence of chlororespiration on the regulation of photosynthesis in the glaucophyte Cyanophora paradoxa
Authors: Misumi Masahiro , Sonoike Kintake
Published: April 2017

Glaucophytes are primary symbiotic algae with unique plastids called cyanelles, whose structure is most similar to ancestral cyanobacteria among plastids in photosynthetic organisms. Here we compare the regulation of photosynthesis in glaucophyte with that in cyanobacteria in the aim of elucidating the changes caused by the symbiosis in the interaction between photosynthetic electron transfer and other metabolic pathways. Chlorophyll fluorescence measurements of the glaucophyte Cyanophora paradoxa NIES-547 indicated that plastoquinone (PQ) pool in photosynthetic electron transfer was reduced in the dark by chlororespiration. The levels of nonphotochemical quenching of chlorophyll fluorescence was high in the dark but decreased under low light, and increased again under high light. This type of concave light dependence was quite similar to that observed in cyanobacteria. Moreover, the addition of ionophore hardly affected nonphotochemical quenching, suggesting state transition as a main component of the regulatory system in C. paradoxa. These results suggest that cyanelles of C. paradoxa retain many of the characteristics observed in their ancestral cyanobacteria. From the viewpoint of metabolic interactions, C. paradoxa is the primary symbiotic algae most similar to cyanobacteria than other lineages of photosynthetic organisms.
Novel miRNA-mRNA interactions conserved in essential cancer pathways
Authors: Andrés-León Eduardo , Cases Ildefonso , Alonso Sergio , Rojas Ana M.
Published: April 2017

Cancer is a complex disease in which unrestrained cell proliferation results in tumour development. Extensive research into the molecular mechanisms underlying tumorigenesis has led to the characterization of oncogenes and tumour suppressors that are key elements in cancer growth and progression, as well as that of other important elements like microRNAs. These genes and miRNAs appear to be constitutively deregulated in cancer. To identify signatures of miRNA-mRNA interactions potentially conserved in essential cancer pathways, we have conducted an integrative analysis of transcriptomic data, also taking into account methylation and copy number alterations. We analysed 18,605 raw transcriptome samples from The Cancer Genome Atlas covering 15 of the most common types of human tumours. From this global transcriptome study, we recovered known cancer-associated miRNA-targets and importantly, we identified new potential targets from miRNA families, also analysing the phenotypic outcomes of these genes/mRNAs in terms of survival. Further analyses could lead to novel approaches in cancer therapy.
On the role of residue phosphorylation in 14-3-3 partners: AANAT as a case study
Authors: Masone Diego , Uhart Marina , Bustos Diego M.
Published: April 2017

Twenty years ago, a novel concept in protein structural biology was discovered: the intrinsically disordered regions (IDRs). These regions remain largely unstructured under native conditions and the more are studied, more properties are attributed to them. Possibly, one of the most important is their ability to conform a new type of protein-protein interaction. Besides the classical domain-to-domain interactions, IDRs follow a ‘fly-casting’ model including ‘induced folding’. Unfortunately, it is only possible to experimentally explore initial and final states. However, the complete movie of conformational changes of protein regions and their characterization can be addressed by in silico experiments. Here, we simulate the binding of two proteins to describe how the phosphorylation of a single residue modulates the entire process. 14-3-3 protein family is considered a master regulator of phosphorylated proteins and from a modern point-of-view, protein phosphorylation is a three component system, with writers (kinases), erasers (phosphatases) and readers. This later biological role is attributed to the 14-3-3 protein family. Our molecular dynamics results show that phosphorylation of the key residue Thr31 in a partner of 14-3-3, the aralkylamine N-acetyltransferase, releases the fly-casting mechanism during binding. On the other hand, the non-phosphorylation of the same residue traps the proteins, systematically and repeatedly driving the simulations into wrong protein-protein conformations.
Linoleic acid isomerase gene FgLAI12 affects sensitivity to salicylic acid, mycelial growth and virulence of Fusarium graminearum
Authors: Zhang Ya-Zhou , Wei Zhen-Zhen , Liu Cai-Hong , Chen Qing , Xu Bin-Jie , Guo Zhen-Ru , Cao Yong-Li , Wang Yan , Han Ya-Nan , Chen Chen , Feng Xiang , Qiao Yuan-Yuan , Zong Lu-Juan , Zheng Ting , Deng Mei , Jiang Qian-Tao , Li Wei , Zheng You-Liang , Wei Yu-Ming , Qi Peng-Fei
Published: April 2017

Fusarium graminearum is the major causal agent of fusarium head blight in wheat, a serious disease worldwide. Linoleic acid isomerase (LAI) catalyses the transformation of linoleic acid (LA) to conjugated linoleic acid (CLA), which is beneficial for human health. We characterised a cis-12 LAI gene of F. graminearum (FGSG_02668; FgLAI12), which was downregulated by salicylic acid (SA), a plant defence hormone. Disruption of FgLAI12 in F. graminearum resulted in decreased accumulation of cis-9,trans-11 CLA, enhanced sensitivity to SA, and increased accumulation of LA and SA in wheat spikes during infection. In addition, mycelial growth, accumulation of deoxynivalenol, and pathogenicity in wheat spikes were reduced. Re-introduction of a functional FgLAI12 gene into ΔFgLAI12 recovered the wild-type phenotype. Fluorescent microscopic analysis showed that FgLAI12 protein was usually expressed in the septa zone of conidia and the vacuole of hyphae, but was expressed in the cell membrane of hyphae in response to exogenous LA, which may be an element of LA metabolism during infection by F. graminearum. The cis-12 LAI enzyme encoded by FgLAI12 is critical for fungal response to SA, mycelial growth and virulence in wheat. The gene FgLAI12 is potentially valuable for biotechnological synthesis of cis-9,trans-11 CLA.
Lanatoside C, a cardiac glycoside, acts through protein kinase Cδ to cause apoptosis of human hepatocellular carcinoma cells
Authors: Chao Min-Wu , Chen Tzu-Hsuan , Huang Han-Li , Chang Yu-Wei , HuangFu Wei-Chun , Lee Yu-Ching , Teng Che-Ming , Pan Shiow-Lin
Published: April 2017

Recent studies have revealed that cardiac glycosides, such as digitalis and digoxin, have anticancer activity and may serve as lead compounds for the development of cancer treatments. The poor prognosis of hepatocellular carcinoma (HCC) patients reflects the development of resistance to current chemotherapeutic agents, highlighting the need for discovering new small-molecule therapeutics. Here, we found that lanatoside C, an anti-arrhythmic agent extracted from Digitalis lanata, inhibited the growth of HCC cells and dramatically decreased tumor volume as well as delayed tumor growth without obvious body weight loss. Moreover, lanatoside C triggered mitochondrial membrane potential (MMP) loss, activation of caspases and translocation of apoptosis-inducing factor (AIF) into the nucleus, which suggests that lanatoside C induced apoptosis through both caspase-dependent and -independent pathways. Furthermore, we discovered that lanatoside C activated protein kinase delta (PKCδ) via Thr505 phosphorylation and subsequent membrane translocation. Inhibition of PKCδ reversed lanatoside C-induced MMP loss and apoptosis, confirming that lanatoside C caused apoptosis through PKCδ activation. We also found that the AKT/mTOR pathway was negatively regulated by lanatoside C through PKCδ activation. In conclusion, we provide the first demonstration that the anticancer effects of lanatoside C are mainly attributable to PKCδ activation.
The low binding affinity of D-serine at the ionotropic glutamate receptor GluD2 can be attributed to the hinge region
Authors: Tapken Daniel , Steffensen Thomas Bielefeldt , Leth Rasmus , Kristensen Lise Baadsgaard , Gerbola Alexander , Gajhede Michael , Jørgensen Flemming Steen , Olsen Lars , Kastrup Jette Sandholm
Published: April 2017

Ionotropic glutamate receptors (iGluRs) are responsible for most of the fast excitatory communication between neurons in our brain. The GluD2 receptor is a puzzling member of the iGluR family: It is involved in synaptic plasticity, plays a role in human diseases, e.g. ataxia, binds glycine and D-serine with low affinity, yet no ligand has been discovered so far that can activate its ion channel. In this study, we show that the hinge region connecting the two subdomains of the GluD2 ligand-binding domain is responsible for the low affinity of D-serine, by analysing GluD2 mutants with electrophysiology, isothermal titration calorimetry and molecular dynamics calculations. The hinge region is highly variable among iGluRs and fine-tunes gating activity, suggesting that in GluD2 this region has evolved to only respond to micromolar concentrations of D-serine.