bluuebunny/crossref_metadata_2025 huggingface dataset:
English words as euphemisms in Spanish fashion
Authors: Diez–Arroyo Marisa
Published: March 2016

Euphemism is a concept closely related to taboo or embarrassing topics; classic examples include sex, religion and politics. It has been mainly studied to show how, within a given language, alternative expressions replace other unsuitable ones that, accordingly, may cause offence and discomfort to the audience. While this first approximation to the question of euphemism anticipates a key point in the use of these substitute expressions, namely the relationship between speaker-hearer in communication, the present discussion seeks to push this interdependence a bit further, framing it around English words or Anglicisms in the context of Spanish fashion. Some examples include ‘backstage’, ‘fifties’, and ‘street style’. This brings up some interesting questions: why should fashion, a clearly non-taboo topic, resort to the use of euphemistic words? How can English words qualify as good candidates to carry out the euphemistic role?
When is an /r/ not an /r/?
Authors: Davidson Keith
Published: March 2016

These notes are largely based on Lodge (2009), and the IPA transcriptions on Wells (2000).

Michael Bulley has singled out for discussion one variant in the articulation of the /r/ phoneme in British English which he characterises as ‘w-for-r’, ‘close to /w/, but distinct from it’ (Bulley, 2014: 46). The focus is on /r/ in syllable-initial position, including /r/ in initial consonant clusters. He describes this particular, not to say singular, variant as ‘/w/-like’, which begs a number of questions.
Extensive multiplex PCR diagnostics reveal new insights into the epidemiology of viral respiratory infections
Authors: NICKBAKHSH S. , THORBURN F. , VON WISSMANN B. , McMENAMIN J. , GUNSON R. N. , MURCIA P. R.
Published: March 2016

Viral respiratory infections continue to pose a major global healthcare burden. At the community level, the co-circulation of respiratory viruses is common and yet studies generally focus on single aetiologies. We conducted the first comprehensive epidemiological analysis to encompass all major respiratory viruses in a single population. Using extensive multiplex PCR diagnostic data generated by the largest NHS board in Scotland, we analysed 44230 patient episodes of respiratory illness that were simultaneously tested for 11 virus groups between 2005 and 2013, spanning the 2009 influenza A pandemic. We measured viral infection prevalence, described co-infections, and identified factors independently associated with viral infection using multivariable logistic regression. Our study provides baseline measures and reveals new insights that will direct future research into the epidemiological consequences of virus co-circulation. In particular, our study shows that (i) human coronavirus infections are more common during influenza seasons and in co-infections than previously recognized, (ii) factors associated with co-infection differ from those associated with viral infection overall, (iii) virus prevalence has increased over time especially in infants aged <1 year, and (iv) viral infection risk is greater in the post-2009 pandemic era, likely reflecting a widespread change in the viral population that warrants further investigation.
Microbiology and risk factors associated with war-related wound infections in the Middle East
Authors: SAHLI Z. T. , BIZRI A. R. , ABU-SITTAH G. S.
Published: March 2016

The Middle East region is plagued with repeated armed conflicts that affect both civilians and soldiers. Injuries sustained during war are common and frequently associated with multiple life-threatening complications. Wound infections are major consequences of these war injuries. The microbiology of war-related wound infections is variable with predominance of Gram-negative bacteria in later stages. The emergence of antimicrobial resistance among isolates affecting war-related wound injuries is a serious problem with major regional and global implications. Factors responsible for the increase in multidrug-resistant pathogens include timing and type of surgical management, wide use of antimicrobial drugs, and the presence of metallic or organic fragments in the wound. Nosocomial transmission is the most important factor in the spread of multidrug-resistant pathogens. Wound management of war-related injuries merits a multidisciplinary approach. This review aims to describe the microbiology of war-related wound infections and factors affecting their incidence from conflict areas in Iraq, Syria, Israel, and Lebanon.
Human Rights, Categorical Duties: A Dilemma for Instrumentalism
Authors: ZYLBERMAN ARIEL
Published: March 2016

Contemporary theorists tend to think that the basic justification of human rights is instrumental, as efficient means for producing the theorist's preferred ultimate value or values. Contemporary theorists also tend to think that human rights have a distinctive normative force, correlating with categorical duties. This article shows that instrumentalist accounts of human rights face a dilemma. The very structure of any instrumentalist account means that such an account faces extraordinary difficulties accommodating categorical duties to respect the human rights of others. If so, one should either reject instrumentalism about human rights or do away with categorical duties. But doing away with categorical duties comes at a high cost. The dilemma, then, should question the prevalent assumption that instrumentalist accounts of human rights can accommodate categorical duties. The dilemma should serve either to sharpen instrumentalist theories or to motivate non-instrumentalism about human rights.
How to support patients who are crying in palliative home care: an interview study from the nurses’ perspective
Authors: Rydé Kerstin , Hjelm Katarina
Published: March 2016

Aim

The aim of this study was to explore how nurses can support patients who are crying in a palliative home care context.

Background

In palliative care the nurse has a central role in the team whose duty it is to create a sense of security and trust, as well as to give comfort and support the patients. The nurse’s responsibility is to identify different needs of the patients for support and develop a relationship with them. Patients may express their pain, anxiety, fear and suffering by crying. No studies have been found which focus on how nurses can support patients who are crying in different ways and crying for different reasons.

Methods

A qualitative explorative study was performed. Semi-structured interviews were held with eight nurses aged 32–63 years (Median 40) working in Swedish palliative home care. The data were analysed using Qualitative Content analysis.

Findings

It was reported that the nurse should meet and confirm the patient during different types of crying episodes and should also be able to alternate between being close and physically touching the in such close contact with the patients, the nurse can provide emotional support by showing empathy, merely being present and letting the patients cry as much as they want. When the crying finally stops, the nurse can support the person by speaking with them, showing sensitivity, humility and respect for the patient’s wishes. A few examples of the patients’ need for information or practical support emerged. The nurse can emotionally support the person who is crying by just being present, confirming, showing empathy, offering a chance to talk and showing respect for their individual needs and the different ways they may cry.
US‒Carbon Steel (India):Multi-Product Firms and the Cumulation of Products
Authors: SPEAROT ALAN , AHN DUKGEUN
Published: March 2016

One of the key findings inUS-Carbon Steel (India)deals with the appropriate method to determine material injury when imported products are subject to simultaneous anti-dumping and countervailing duty (CVD) investigations. Along with addressing a number of legal issues concerning CVD investigations, the Appellate Body clarified restrictions on cross-cumulation of injury, essentially prohibiting the current US practice, and implicitly raising the burden of proof for parallel claims of dumping and subsidies. This decision is justified on economic grounds, where cumulation imposes a counterfactual scenario against which marginal damages of dumping and subsidies by each country cannot be properly evaluated. However, what the legal rulings by the Appellate Body did not recognize is the economic reality that many like products produced by the firms alleged to have received subsidies were selectively absent from the investigation, which more generally complicates the assessment of injury in dumping and subsidy cases.
Climate Change Reparations and the Law and Practice of State Responsibility
Authors: MAYER Benoit
Published: March 2016

It has been argued elsewhere that industrial states were legally responsible for interfering with the climate system by failing to prevent excessive greenhouse gas emissions. This paper determines the international legal principles relevant to the remedial obligations of industrial states. It assumes that climate change reparations should aim first at providing a signal for the cessation of the wrongful act (i.e. incentivizing climate change mitigation) rather than addressing the injury. A review of state practice in different fields suggests the existence of relevant exceptions to the principle of full reparation. These exceptions relate to the financial capacity of responsible states, the indirect nature of the injury, considerations of “culpability”, and the limitations of collective responsibility as “rough” justice. Accordingly, it is suggested that climate change reparations should be limited to partial compensation and symbolic measures of satisfaction prone to incentivize climate change mitigation.
Metaanalyse zur Wirksamkeit einer Förderung der phonologischen Bewusstheit in der deutschen Sprache
Authors: Wolf Katrin M. , Schroeders Ulrich , Kriegbaum Katharina
Published: March 2016

Zusammenfassung. Internationale Metaanalysen belegen bedeutsame Effekte einer Förderung der phonologischen Bewusstheit auf den Schriftspracherwerb. In der vorliegenden Metaanalyse mit 27 Primärstudien wurden die Effekte phonologischer Fördermaßnahmen auf die frühen schriftsprachlichen Kompetenzen im Deutschen quantifiziert. Die Analysen belegten generell höhere Effekte für Fördermaßnahmen, die vor der Einschulung stattfanden. Eine vorschulische Förderung besaß zwar keine signifikanten Effekte auf die Dekodierfähigkeit; jedoch konnten geringe Effekte auf die Rechtschreibkompetenz nachgewiesen werden, was auf die unterschiedliche Konsistenz der Graphem-Phonem- und Phonem-Graphem-Zuordnungen zurückzuführen sein könnte. Analysen zum Einfluss von Moderatoren ergaben, dass Kinder mit schwachen und guten Ausgangskompetenzen gleichermaßen von der Förderung profitieren, und dass die Kombination mit einem Buchstaben-Laut-Training keine inkrementellen Effekte im Vergleich zu rein phonologischen Fördermaßnahmen hat. Insgesamt fielen die metaanalytischen Trainingseffekte der deutschsprachigen Förderprogramme deutlich niedriger aus als in den internationalen Metaanalysen. Für diesen Befund werden sprachliche und methodische Erklärungen gegeben.
Erstes Vorlesen: Der frühe Vogel fängt den Wurm
Authors: Niklas Frank , Cohrssen Caroline , Tayler Collette , Schneider Wolfgang
Published: March 2016

Zusammenfassung. Da Vorlesen die Vorläuferfertigkeiten des Schriftspracherwerbs von Kindern stärkt, wird ein früher Beginn des Vorlesens als wichtig angesehen. Allerdings fehlen bislang Studien, die sich damit auseinandersetzen, ob der Vorlesebeginn ein spezifischer Prädiktor für sprachliche Fähigkeiten unter Kontrolle von Hintergrundvariablen ist. Wir untersuchten diese Fragestellung anhand einer deutschen Vorschulstichprobe (N = 746) kurz vor der Einschulung und verglichen die Ergebnisse mit Befunden einer aktuellen australischen Studie. Neben Vorlesebeginn und aktuellem Vorleseverhalten, erfasst im Elternbericht, wurden Alter und Geschlecht der Kinder, Migrationshintergrund und sozioökonomischer Status sowie sprachliche und andere kognitive Fähigkeiten berücksichtigt. Wie schon in der australischen Stichprobe zeigte sich auch für die deutsche Stichprobe, dass ein früher Vorlesebeginn die spätere Vorlesehäufigkeit sowie sprachliche Fähigkeiten im Vorschulalter unter Berücksichtigung von Kontrollvariablen vorhersagte, während dies für andere kognitive Fähigkeiten nur bedingt zutraf. Die Ergebnisse deuten an, dass der Vorlesestart ein guter Indikator für die schriftsprachliche Lernumwelt und ein spezifischer Prädiktor für schriftsprachliche Vorläuferfertigkeiten zu sein scheint.
Endometriose-Update 2016
Authors: Imesch Patrick , Fink Daniel
Published: March 2016

Zusammenfassung. Endometriose ist eine häufige benigne Erkrankung der Frau in der reproduktiven Phase. Sie manifestiert sich zumeist mit schwerer Dysmenorrhö, chronischen Unterbauchschmerzen und Dyspareunie, ist aber häufig auch mit Sterilität assoziiert. Die genaue Pathogenese ist bis heute nicht restlos geklärt, sodass therapeutisch derzeit eher symptomorientiert als kausal behandelt wird. Der folgende Artikel soll eine Übersicht über die derzeitigen Diagnose- und Behandlungsmethoden dieser rätselhaften Erkrankung geben.
Urininkontinenz beim Mann – ein Tabuthema
Authors: Kozomara-Hocke Marko , Hermanns Thomas , Poyet Cédric
Published: March 2016

Zusammenfassung. Die Urininkontinenz beim Mann ist ein unterschätztes und häufig nicht thematisiertes Problem. Sie wird in Dranginkontinenz, Belastungsinkontinenz, Mischformen und Überlaufinkontinenz unterteilt. Wegen der zunehmenden Anzahl an über 60-jährigen Männern und der Prävalenz von bis zu 40 % wird die Urininkontinenz zunehmend einen wichtigen Teil der täglichen Praxis bilden. Viele Abklärungen und auch Therapieversuche können bereits in der Hausarztpraxis durchgeführt werden. Häufig führt eine einfache Therapie zur deutlichen Verbesserung. Bei Versagen der initialen Therapie oder behandlungs- und abklärungsbedürftigen Befunden (persistierender Mikrohämaturie, rezidivierenden Infekten, erhöhten Restharnmengen usw.) sollte der Patient einem Facharzt für Urologie überwiesen werden.
Are Earthquakes Predictable?
Authors: Wheeling Kate
Published: March 2016

Researchers have been searching for precursory warning signals for decades with little success.
Topological phase transitions and chiral inelastic transport induced by the squeezing of light
Authors: Peano Vittorio , Houde Martin , Brendel Christian , Marquardt Florian , Clerk Aashish A.
Published: March 2016

There is enormous interest in engineering topological photonic systems. Despite intense activity, most works on topological photonic states (and more generally bosonic states) amount in the end to replicating a well-known fermionic single-particle Hamiltonian. Here we show how the squeezing of light can lead to the formation of qualitatively new kinds of topological states. Such states are characterized by non-trivial Chern numbers, and exhibit protected edge modes, which give rise to chiral elastic and inelastic photon transport. These topological bosonic states are not equivalent to their fermionic (topological superconductor) counterparts and, in addition, cannot be mapped by a local transformation onto topological states found in particle-conserving models. They thus represent a new type of topological system. We study this physics in detail in the case of a kagome lattice model, and discuss possible realizations using nonlinear photonic crystals or superconducting circuits.
Functional assays provide a robust tool for the clinical annotation of genetic variants of uncertain significance
Authors: Woods Nicholas T , Baskin Rebekah , Golubeva Volha , Jhuraney Ankita , De-Gregoriis Giuliana , Vaclova Tereza , Goldgar David E , Couch Fergus J , Carvalho Marcelo Alex , Iversen Edwin S , Monteiro Alvaro NA
Published: March 2016

Variants of Uncertain Significance (VUS) are genetic variants whose association with a disease phenotype has not been established. They are a common finding in sequencing-based genetic tests and pose a significant clinical challenge. The objective of this study was to assess the use of functional data to classify variants according to pathogenicity. We conduct functional analysis of a large set of BRCA1 VUS combining a validated functional assay with VarCall, a Bayesian hierarchical model to estimate the likelihood of pathogenicity given the functional data. The results from the functional assays were incorporated into a joint analysis of 214 BRCA1 VUS to predict their likelihood of pathogenicity (breast cancer). We show that applying the VarCall model (1.0 sensitivity; lower bound of 95% confidence interval (CI)=0.75 and 1.0 specificity; lower bound of 95% CI=0.83) to the current set of BRCA1 variants, use of the functional data would significantly reduce the number of VUS associated with the C-terminal region of the BRCA1 protein by ~87%. We extend this work developing yeast-based functional assays for two other genes coding for BRCT domain containing proteins, MCPH1 and MDC1. Analysis of missense variants in MCPH1 and MDC1 shows that structural inference based on the BRCA1 data set can aid in prioritising variants for further analysis. Taken together our results indicate that systematic functional assays can provide a robust tool to aid in clinical annotation of VUS. We propose that well-validated functional assays could be used for clinical annotation even in the absence of additional sources of evidence.
Influence of plasma-activated compounds on melanogenesis and tyrosinase activity
Authors: Ali Anser , Ashraf Zaman , Kumar Naresh , Rafiq Muhammad , Jabeen Farukh , Park Ji Hoon , Choi Ki Hong , Lee SeungHyun , Seo Sung-Yum , Choi Eun Ha , Attri Pankaj
Published: March 2016

Many organic chemists around the world synthesize medicinal compounds or extract multiple compounds from plants in order to increase the activity and quality of medicines. In this work, we synthesized new eugenol derivatives (ED) and then treated them with an N2 feeding gas atmospheric pressure plasma jet (APPJ) to increase their utility. We studied the tyrosinase-inhibition activity (activity test) and structural changes (circular dichroism) of tyrosinase with ED and plasma activated eugenol derivatives (PAED) in a cell-free environment. Later, we used docking studies to determine the possible interaction sites of ED and PAED compounds with tyrosinase enzyme. Moreover, we studied the possible effect of ED and PAED on melanin synthesis and its mechanism in melanoma (B16F10) cells. Additionally, we investigated the structural changes that occurred in activated ED after plasma treatment using nuclear magnetic resonance (NMR). Hence, this study provides a new perspective on PAED for the field of plasma medicine.
Severe bone marrow edema on sacroiliac joint MRI increases the risk of low BMD in patients with axial spondyloarthritis
Authors: Kim Ha Neul , Jung Joon-Yong , Hong Yeon Sik , Park Sung-Hwan , Kang Kwi Young
Published: March 2016

To determine the association between inflammatory and structural lesions on sacroiliac joint (SIJ) MRI and BMD and to identify risk factors for low BMD in patients with axial spondyloarthritis (axSpA). Seventy-six patients who fulfilled the ASAS axSpA criteria were enrolled. All underwent SIJ MRI and BMD measurement at the lumbar spine, femoral neck, and total hip. Inflammatory and structural lesions on SIJ MRI were scored. Laboratory tests and assessment of radiographic and disease activity were performed at the time of MRI. The association between SIJ MRI findings and BMD was evaluated. Among the 76 patients, 14 (18%) had low BMD. Patients with low BMD showed significantly higher bone marrow edema (BME) and deep BME scores on MRI than those with normal BMD (p < 0.047 and 0.007, respectively). Inflammatory lesions on SIJ MRI correlated with BMD at the femoral neck and total hip. Multivariate analysis identified the presence of deep BME on SIJ MRI, increased CRP, and sacroiliitis on X-ray as risk factors for low BMD (OR = 5.6, 14.6, and 2.5, respectively). The presence of deep BME on SIJ MRI, increased CRP levels, and severity of sacroiliitis on X-ray were independent risk factors for low BMD.
Tracking the migration of the Indian continent using the carbonate clumped isotope technique on Phanerozoic soil carbonates
Authors: Ghosh Prosenjit , Vasiliev Mikhail V. , Ghosh Parthasarathi , Sarkar Soumen , Ghosh Sampa , Yamada Keita , Ueno Yuichiro , Yoshida Naohiro , Poulsen Christopher J.
Published: March 2016

Approximately 140 million years ago, the Indian plate separated from Gondwana and migrated by almost 90° latitude to its current location, forming the Himalayan-Tibetan system. Large discrepancies exist in the rate of migration of Indian plate during Phanerozoic. Here we describe a new approach to paleo-latitudinal reconstruction based on simultaneous determination of carbonate formation temperature and δ18O of soil carbonates, constrained by the abundances of 13C-18O bonds in palaeosol carbonates. Assuming that the palaeosol carbonates have a strong relationship with the composition of the meteoric water, δ18O carbonate of palaeosol can constrain paleo-latitudinal position. Weighted mean annual rainfall δ18O water values measured at several stations across the southern latitudes are used to derive a polynomial equation: δ18Ow = −0.006 × (LAT)2 − 0.294 × (LAT) − 5.29 which is used for latitudinal reconstruction. We use this approach to show the northward migration of the Indian plate from 46.8 ± 5.8°S during the Permian (269 M.y.) to 30 ± 11°S during the Triassic (248 M.y.), 14.7 ± 8.7°S during the early Cretaceous (135 M.y.) and 28 ± 8.8°S during the late Cretaceous (68 M.y.). Soil carbonate δ18O provides an alternative method for tracing the latitudinal position of Indian plate in the past and the estimates are consistent with the paleo-magnetic records which document the position of Indian plate prior to 135 ± 3 M.y.
Fast generation of three-atom singlet state by transitionless quantum driving
Authors: Chen Zhen , Chen Ye-Hong , Xia Yan , Song Jie , Huang Bi-Hua
Published: March 2016

Motivated by “transitionless quantum driving”, we construct shortcuts to adiabatic passage in a three-atom system to create a singlet state with the help of quantum zeno dynamics and non-resonant lasers. The influence of various decoherence processes is discussed by numerical simulation and the results reveal that the scheme is fast and robust against decoherence and operational imperfection. We also investigate how to select the experimental parameters to control the cavity dissipation and atomic spontaneous emission which will have an application value in experiment.
Structure-based Inhibitor Design for the Intrinsically Disordered Protein c-Myc
Authors: Yu Chen , Niu Xiaogang , Jin Fan , Liu Zhirong , Jin Changwen , Lai Luhua
Published: March 2016

Intrinsically disordered proteins (IDPs) are associated with various diseases and have been proposed as promising drug targets. However, conventional structure-based approaches cannot be applied directly to IDPs, due to their lack of ordered structures. Here, we describe a novel computational approach to virtually screen for compounds that can simultaneously bind to different IDP conformations. The test system used c-Myc, an oncoprotein containing a disordered basic helix-loop-helix-leucine zipper (bHLH-LZ) domain that adopts a helical conformation upon binding to Myc-associated factor X (Max). For the virtual screen, we used three binding pockets in representative conformations of c-Myc370–409, which is part of the disordered bHLH-LZ domain. Seven compounds were found to directly bind c-Myc370–409in vitro, and four inhibited the growth of the c-Myc-overexpressing cells by affecting cell cycle progression. Our approach of IDP conformation sampling, binding site identification, and virtual screening for compounds that can bind to multiple conformations provides a useful strategy for structure-based drug discovery targeting IDPs.
Cyclophilin A (CypA) Plays Dual Roles in Regulation of Bone Anabolism and Resorption
Authors: Guo Mian , James Aaron W. , Kwak Jin Hee , Shen Jia , Yokoyama Kazunari K. , Ting Kang , Soo Chia B. , Chiu Robert H.
Published: March 2016

CypA (Cyclophilin A) is a peptidyl-prolyl isomerase previously shown to be required for chondrogenic differentiation and endochondral ossification. However, the effects of CypA on osteoclast activity and bone maintenance are entirely unknown. Here, we show that Ppia−/− mice demonstrate low bone mineral density, reduced osteoblast numbers and increased osteoclast numbers. When isolated from the calvaria, Ppia−/− osteoblasts demonstrate decreased osteogenic differentiation, whereas Ppia−/− osteoclasts derived from the long bones showed increased osteoclastic activity. Overexpression and gene silencing of CypA verified osteogenic and anti-osteoclastic effects. In osteoblasts, CypA is necessary for BMP-2 (Bone Morphogenetic Protein-2)-induced Smad phosphorylation. In osteoclasts, loss of CypA activates BtK (Bruton’s tyrosine kinase) and subsequently integrates with TRAF6 (TNF receptor-associated factor 6) and/or c-fos signaling to induce NFATc1 (nuclear factors of activated T cells, cytoplasmic 1). Collectively, CypA dually exerts pro-osteogenic and anti-osteoclastic effects. Thus, modulation of CypA may be useful in future efforts targeting osteoporosis.
Phase Conjugated and Transparent Wavelength Conversions of Nyquist 16-QAM Signals Employing a Single-Layer Graphene Coated Fiber Device
Authors: Hu Xiao , Zeng Mengqi , Long Yun , Liu Jun , Zhu Yixiao , Zou Kaiheng , Zhang Fan , Fu Lei , Wang Jian
Published: March 2016

We fabricate a nonlinear optical device based on a fiber pigtail cross-section coated with a single-layer graphene grown by chemical vapor deposition (CVD) method. Using the fabricated graphene-assisted nonlinear optical device and employing Nyquist 16-ary quadrature amplitude modulation (16-QAM) signal, we experimentally demonstrate phase conjugated wavelength conversion by degenerate four-wave mixing (FWM) and transparent wavelength conversion by non-degenerate FWM in graphene. We study the conversion efficiency as functions of the pump power and pump wavelength and evaluate the bit-error rate (BER) performance. We also compare the time-varying symbol sequence for graphene-assisted phase conjugated and transparent wavelength conversions of Nyquist 16-QAM signal.
Pharmacoproteomic analysis reveals that metapristone (RU486 metabolite) intervenes E-cadherin and vimentin to realize cancer metastasis chemoprevention
Authors: Yu Suhong , Yan Cuicui , Yang Xingtian , He Sudang , Liu Jian , Qin Chongtao , Huang Chuanzhong , Lu Yusheng , Tian Zhongping , Jia Lee
Published: March 2016

Metapristone is the most predominant biological active metabolite of mifepristone and being developed as a novel cancer metastasis chemopreventive agent by us. Despite its prominent metastasis chemopreventive effect, the underlying mechanism remains elusive. Our study, for the first time, demonstrated that metapristone had the ability to prevent breast cancer cells from migration, invasion and interfere with their adhesion to endothelial cells. To explore the underlying mechanism of metapristone, we employed the iTRAQ technique to assess the effect of metapristone on MDA-MB-231 cells. In total, 5,145 proteins were identified, of which, 311 proteins showed significant differences in metapristone-treated cells compared to the control group (P-value < 0.05). Bioinformatic analysis showed many differentially expressed proteins (DEPs) functionally associated with post-translational modification, chaperones, translation, transcription, replication, signal transduction, etc. Importantly, many of the DEPs, such as E-cadherin, vimentin, TGF-β receptor I/II, smad2/3, β-catenin, caveolin and dystroglycan were associated with TGF-β and Wnt signaling pathways, which were also linked to epithelial-to-mesenchymal transition (EMT) process. Further validation of the epithelial marker “E-caderin” and mesenchymal marker “vimetin” were carried out using immunoblot and immunofluorescence. These results have revealed a novel mechanism that metapristone-mediated metastasis chemoprevention is through intervening the EMT-related signaling pathways.
Association between Gastroesophageal Reflux Disease and Appendicitis: A Population-Based Case-Control Study
Authors: Kao Li-Ting , Tsai Ming-Chieh , Lin Herng-Ching , Lee Cha-Ze
Published: March 2016

Appendicitis and gastroesophageal reflux disease (GERD) are both prevalent diseases and might share similar pathological mechanisms. The aim of this study was to investigate the association between GERD and appendicitis using a large population-based dataset. This study used administrative claims data from the Taiwan Longitudinal Health Insurance Database 2005. We identified 7113 patients with appendicitis as cases, and 28452 matched patients without appendicitis as controls. This study revealed that GERD was found in 359 (5.05%) cases and 728 (2.56%) controls (p < 0.001). Conditional logistic regression shows that the adjusted odds ratio (OR) of GERD for cases was 2.05 (95% confidence interval (CI): 1.08~2.33) compared to controls. The adjusted ORs of prior GERD for patients aged 18~39, 40~59, and ≥60 years with appendicitis were 1.96 (95% CI: 1.56~2.47), 2.36 (95% CI: 1.94~2.88), and 1.71 (95% CI: 1.31~2.22) than controls, respectively. We concluded that patients with appendicitis had higher odds of prior GERD than those without appendicitis regardless of age group.
Facile construction of a highly sensitive DNA biosensor by in-situ assembly of electro-active tags on hairpin-structured probe fragment
Authors: Wang Qingxiang , Gao Feng , Ni Jiancong , Liao Xiaolei , Zhang Xuan , Lin Zhenyu
Published: March 2016

An ultrasensitive DNA biosensor has been developed through in-situ labeling of electroactive melamine-Cu2+ complex (Mel-Cu2+) on the end of hairpin-like probe using gold nanoparticles (AuNPs) as the signal amplification platform. The 3′-thiolated hairpin-like probe was first immobilized to the gold electrode surface by the Au-S bond. The AuNPs were then tethered on the free 5′-end of the immobilized probe via the special affinity between Au and the modified -NH2. Followed by, the Mel and Cu2+ were assembled on the AuNPs surface through Au-N bond and Cu2+-N bond, respectively. Due to the surface area and electrocatalytic effects of the AuNPs, the loading amount and electron transfer kinetic of the Mel-Cu2+ were enhanced greatly, resulting in significantly enhanced electrochemical response of the developed biosensor. Compared with the synthesis process of conventional electroactive probe DNA accomplished by homogeneous method, the method presented in this work is more reagent- and time-saving. The proposed biosensor showed high selectivity, wide linear range and low detection limit. This novel strategy could also be extended to the other bioanalysis platforms such as immunosensors and aptasensors.
Innate myeloid cell TNFR1 mediates first line defence against primary Mycobacterium tuberculosis infection.
Authors: Segueni Noria , Benmerzoug Sulayman , Rose Stéphanie , Gauthier Amandine , Bourigault Marie-Laure , Reverchon Flora , Philippeau Amandine , Erard François , Le Bert Marc , Bouscayrol Hélène , Wachter Thierry , Garcia Irène , Kollias George , Jacobs Muazzam , Ryffel Bernhard , Quesniaux Valerie F.J.
Published: March 2016

TNF is crucial for controlling Mycobacterium tuberculosis infection and understanding how will help immunomodulating the host response. Here we assessed the contribution of TNFR1 pathway from innate myeloid versus T cells. We first established the prominent role of TNFR1 in haematopoietic cells for controlling M. tuberculosis in TNFR1 KO chimera mice. Further, absence of TNFR1 specifically on myeloid cells (M-TNFR1 KO) recapitulated the uncontrolled M. tuberculosis infection seen in fully TNFR1 deficient mice, with increased bacterial burden, exacerbated lung inflammation, and rapid death. Pulmonary IL-12p40 over-expression was attributed to a prominent CD11b+ Gr1high cell population in infected M-TNFR1 KO mice. By contrast, absence of TNFR1 on T-cells did not compromise the control of M. tuberculosis infection over 6-months. Thus, the protective TNF/TNFR1 pathway essential for controlling primary M. tuberculosis infection depends on innate macrophage and neutrophil myeloid cells, while TNFR1 pathway in T cells is dispensable.
Organization and characteristics of the major histocompatibility complex class II region in the Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis)
Authors: Ruan Rui , Ruan Jue , Wan Xiao-Ling , Zheng Yang , Chen Min-Min , Zheng Jin-Song , Wang Ding
Published: March 2016

Little is known about the major histocompatibility complex (MHC) in the genome of Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis) (YFP) or other cetaceans. In this study, a high-quality YFP bacterial artificial chromosome (BAC) library was constructed. We then determined the organization and characterization of YFP MHC class II region by screening the BAC library, followed by sequencing and assembly of positive BAC clones. The YFP MHC class II region consists of two segregated contigs (218,725 bp and 328,435 bp respectively) that include only eight expressed MHC class II genes, three pseudo MHC genes and twelve non-MHC genes. The YFP has fewer MHC class II genes than ruminants, showing locus reduction in DRB, DQA, DQB and loss of DY. In addition, phylogenic and evolutionary analyses indicated that the DRB, DQA and DQB genes might have undergone birth-and-death evolution, whereas the DQB gene might have evolved under positive selection in cetaceans. These findings provide an essential foundation for future work, such as estimating MHC genetic variation in the YFP or other cetaceans. This work is the first report on the MHC class II region in cetaceans and offers valuable information for understanding the evolution of MHC genome in cetaceans.
Untargeted plasma and tissue metabolomics in rats with chronic kidney disease given AST-120
Authors: Velenosi Thomas J. , Hennop Anzel , Feere David A. , Tieu Alvin , Kucey Andrew S. , Kyriacou Polydoros , McCuaig Laura E. , Nevison Stephanie E. , Kerr Michael A. , Urquhart Bradley L.
Published: March 2016

Chronic kidney disease (CKD) results in the accumulation of metabolic waste products that are normally cleared by the kidney, known as uremia. Many of these waste products are from bacteria metabolites in the gut. Accumulation of uremic toxins in plasma and tissue, as well as the gut-plasma-tissue metabolic axis are important for understanding pathophysiological mechanisms of comorbidities in CKD. In this study, an untargeted metabolomics approach was used to determine uremic toxin accumulation in plasma, liver, heart and kidney tissue in rats with adenine-induced CKD. Rats with CKD were also given AST-120, a spherical carbon adsorbent, to assess metabolic changes in plasma and tissues with the removal of gut-derived uremic toxins. AST-120 decreased >55% of metabolites that were increased in plasma, liver and heart tissue of rats with CKD. CKD was primarily defined by 8 gut-derived uremic toxins, which were significantly increased in plasma and all tissues. These metabolites were derived from aromatic amino acids and soy protein including: indoxyl sulfate, p-cresyl sulfate, hippuric acid, phenyl sulfate, pyrocatechol sulfate, 4-ethylphenyl sulfate, p-cresol glucuronide and equol 7-glucuronide. Our results highlight the importance of diet and gut-derived metabolites in the accumulation of uremic toxins and define the gut-plasma-tissue metabolic axis in CKD.
Small Molecule Inhibited Parathyroid Hormone Mediated cAMP Response by N–Terminal Peptide Binding
Authors: Kumar Amit , Baumann Monika , Balbach Jochen
Published: March 2016

Ligand binding to certain classes of G protein coupled receptors (GPCRs) stimulates the rapid synthesis of cAMP through G protein. Human parathyroid hormone (PTH), a member of class B GPCRs, binds to its receptor via its N–terminal domain, thereby activating the pathway to this secondary messenger inside cells. Presently, GPCRs are the target of many pharmaceuticals however, these drugs target only a small fraction of structurally known GPCRs (about 10%). Coordination complexes are gaining interest due to their wide applications in the medicinal field. In the present studies we explored the potential of a coordination complex of Zn(II) and anthracenyl–terpyridine as a modulator of the parathyroid hormone response. Preferential interactions at the N–terminal domain of the peptide hormone were manifested by suppressed cAMP generation inside the cells. These observations contribute a regulatory component to the current GPCR–cAMP paradigm, where not the receptor itself, but the activating hormone is a target. To our knowledge, this is the first report about a coordination complex modulating GPCR activity at the level of deactivating its agonist. Developing such molecules might help in the control of pathogenic PTH function such as hyperparathyroidism, where control of excess hormonal activity is essentially required.
Towards an understanding of tensile deformation in Ti-based bulk metallic glass matrix composites with BCC dendrites
Authors: Kolodziejska Joanna A , Kozachkov Henry , Kranjc Kelly , Hunter Allen , Marquis Emmanuelle , Johnson William L , Flores Katharine M , Hofmann Douglas C
Published: March 2016

The microstructure and tension ductility of a series of Ti-based bulk metallic glass matrix composite (BMGMC) is investigated by changing content of the β stabilizing element vanadium while holding the volume fraction of dendritic phase constant. The ability to change only one variable in these novel composites has previously been difficult, leading to uninvestigated areas regarding how composition affects properties. It is shown that the tension ductility can range from near zero percent to over ten percent simply by changing the amount of vanadium in the dendritic phase. This approach may prove useful for the future development of these alloys, which have largely been developed experimentally using trial and error.
Polymorphisms in the 5′ upstream regulatory region of p21WAF1/CIP1 and susceptibility to oesophageal squamous cell carcinoma
Authors: Yang Wenjun , Li Yong , Ning Tao , Cai Hong , Chen Zhiqiang , Dong Ying , Ke Yang
Published: March 2016

This study aims to scan the 5′-upstream regulatory region of the p21 gene to identify all putative functional single nucleotide polymorphisms (SNPs) and to evaluate the contribution of p21 variants to oesophageal squamous cell carcinoma (ESCC) in the Chinese Han population. Common SNPs were identified, and both locus-based and haplotype-based association tests were used to evaluate the potential risk of these p21 gene polymorphisms for ESCC. Immunohistochemistry assay was further performed to detect the P21 protein expression in ESCC specimens. Twenty three SNPs were identified and seven Tagging SNPs were chosen to represent all 23 SNPs. Univariate analysis indicated that the rs3829963 C and the rs2395655 G alleles increased susceptibility to ESCC (OR = 1.606 and OR = 1.572, respectively). The rs3829963 C and rs2395655 G alleles, combined with cigarette smoking, could further increase the risk for ESCC (OR = 2.657 and OR = 2.828, respectively). Additionally, the rs2395655 G allele appeared to elevate the positive rate of P21 expression in ESCC tissues, as compared to the A allele. This report demonstrates for the first time that rs3829963 and rs2395655, in the promoter of the p21 gene are potentially functional, modulating susceptibility to ESCC among the high-risk cigarette-smoking Chinese population.
Shock Wave Response of Iron-based In Situ Metallic Glass Matrix Composites
Authors: Khanolkar Gauri R. , Rauls Michael B. , Kelly James P. , Graeve Olivia A. , Hodge Andrea M. , Eliasson Veronica
Published: March 2016

The response of amorphous steels to shock wave compression has been explored for the first time. Further, the effect of partial devitrification on the shock response of bulk metallic glasses is examined by conducting experiments on two iron-based in situ metallic glass matrix composites, containing varying amounts of crystalline precipitates, both with initial composition Fe49.7Cr17.7Mn1.9Mo7.4W1.6B15.2C3.8Si2.4. The samples, designated SAM2X5-600 and SAM2X5-630, are X-ray amorphous and partially crystalline, respectively, due to differences in sintering parameters during sample preparation. Shock response is determined by making velocity measurements using interferometry techniques at the rear free surface of the samples, which have been subjected to impact from a high-velocity projectile launched from a powder gun. Experiments have yielded results indicating a Hugoniot Elastic Limit (HEL) to be 8.58 ± 0.53 GPa for SAM2X5-600 and 11.76 ± 1.26 GPa for SAM2X5-630. The latter HEL result is higher than elastic limits for any BMG reported in the literature thus far. SAM2X5-600 catastrophically loses post-yield strength whereas SAM2X5-630, while showing some strain-softening, retains strength beyond the HEL. The presence of crystallinity within the amorphous matrix is thus seen to significantly aid in strengthening the material as well as preserving material strength beyond yielding.
Autonomy dimensions and care seeking for delivery in Zambia; the prevailing importance of cluster-level measurement
Authors: Gabrysch Sabine , McMahon Shannon A. , Siling Katja , Kenward Michael G. , Campbell Oona M. R.
Published: March 2016

It is widely held that decisions whether or when to attend health facilities for childbirth are not only influenced by risk awareness and household wealth, but also by factors such as autonomy or a woman’s ability to act upon her own preferences. How autonomy should be constructed and measured – namely, as an individual or cluster-level variable – has been less examined. We drew on household survey data from Zambia to study the effect of several autonomy dimensions (financial, relationship, freedom of movement, health care seeking and violence) on place of delivery for 3200 births across 203 rural clusters (villages). In multilevel logistic regression, two autonomy dimensions (relationship and health care seeking) were strongly associated with facility delivery when measured at the cluster level (OR 1.27 and 1.57, respectively), though not at the individual level. This suggests that power relations and gender norms at the community level may override an individual woman’s autonomy and cluster-level measurement may prove critical to understanding the interplay between autonomy and care seeking in this and similar contexts.
Tumor-induced remote ECM network orientation steers angiogenesis
Authors: Balcioglu Hayri E. , van de Water Bob , Danen Erik H. J.
Published: March 2016

Tumor angiogenesis promotes tumor growth and metastasis. Here, we use automated sequential microprinting of tumor and endothelial cells in extracellular matrix (ECM) scaffolds to study its mechanical aspects. Quantitative reflection microscopy shows that tumor spheroids induce radial orientation of the surrounding collagen fiber network up to a distance of five times their radius. Across a panel of ~20 different human tumor cell lines, remote collagen orientation is correlated with local tumor cell migration behavior. Tumor induced collagen orientation requires contractility but is remarkably resistant to depletion of collagen-binding integrins. Microvascular endothelial cells undergo directional migration towards tumor spheroids once they are within the tumor-oriented collagen fiber network. Laser ablation experiments indicate that an intact physical connection of the oriented network with the tumor spheroid is required for mechanical sensing by the endothelial cells. Together our findings indicate that, in conjunction with described activities of soluble angiogenic factors, remote physical manipulation of the ECM network by the tumor can help to steer angiogenesis.
Transcriptional regulation of miR-15b by c-Rel and CREB in Japanese encephalitis virus infection
Authors: Zhu Bibo , Ye Jing , Ashraf Usama , Li Yunchuan , Chen Huanchun , Song Yunfeng , Cao Shengbo
Published: March 2016

MicroRNAs (miRNAs) have been well known to play diverse roles in viral infection at the level of posttranscriptional repression. However, much less is understood about the mechanism by which miRNAs are regulated during viral infection. It is likely that both host and virus contain factors to modulate miRNA expression. Here we report the up-regulation of microRNA-15b (miR-15b)in vitroupon infection with Japanese encephalitis virus (JEV). Analysis of miR-15b precursor, pri-miR-15b and pre-miR-15b, suggest that the regulation occurs transcriptionally. Further, we identified the transcriptional regulatory region of miR-15b that contains consensus binding motif for NF-κB subunit c-Rel and cAMP-response element binding protein (CREB), which are known as transcription factor to regulate gene expression. By promoter fusion and mutational analyses, we demonstrated that c-Rel and CREB bind directly to the promoter elements of miR-15b, which are responsible for miR-15b transcription in response to JEV infection. Finally, we showed that pharmacological inhibition of ERK and NF-κB signaling pathway blocked induction of miR-15b in JEV infection, suggesting important roles of ERK and NF-κB pathway in the regulation of miR-15b gene. Therefore, our observations indicate that induced expression of miR-15b is modulated by c-Rel and CREB in response to JEV infection.
Population-based assessment of visual impairment among ethnic Dai adults in a rural community in China
Authors: Yang Wen-Yan , Li Jun , Zhao Chun-Hua , Qian Deng-Juan , Niu Zhiqiang , Shen Wei , Yuan Yuansheng , Zhong Hua , Pan Chen-Wei
Published: March 2016

Dai ethnicity is one of the major Chinese ethnic minorities with a population of about 1.2 million. We aimed to determine the prevalence and potential causes of visual impairment (VI) among ethnic Dai adults aged 50 years or older in a rural community in China. A population-based survey including 2163 ethnic Dai people (80.5%) was undertaken using a random cluster sampling strategy. The detailed eye examination was performed after pupil dilation by trained study ophthalmologists and optometrists. Presenting visual acuity (PVA) and best-corrected visual acuity (BCVA) was measured using the Early Treatment Diabetic Retinopathy Study logMAR chart and VI was defined as a VA of less than 20/63 in the better-seeing eye. The overall prevalence of presenting blindness and low vision was 3.0% (95% CI, 2.3–3.7) and 13.3% (95% CI, 11.9–14.8), respectively. The prevalence estimates were reduced to 2.1% (95% CI, 1.5–2.8) and 6.7% (95% CI, 5.7–7.8) when BCVA was considered. Men were more likely to be affected by low vision but less likely to be blind compared with women. Cataract accounted for 62.7% of presenting low vision and 68.8% of presenting blindness, respectively. In conclusion, VI was a significant health concern in Dai Chinese in China.