bluuebunny/crossref_metadata_2025 huggingface dataset:
Overexpression of microRNA‐542‐3p attenuates the differentiating capacity of endometriotic stromal cells
Authors: Sultana Shamima , Kajihara Takeshi , Mizuno Yumi , Sato Tomomi , Oguro Tatsuo , Kimura Machiko , Akita Masumi , Ishihara Osamu
Published: March 2017

Aim

Endometriosis is defined as the presence of endometrial glandular and stromal cells outside of the uterine cavity. A previous study reported that microRNA (miR)‐542‐3p plays a critical role in eutopic endometrial decidualization. This study aims to clarify the potential role of miR‐542‐3p and the target gene, IGFBP‐1 (insulin‐like growth factor‐binding protein 1), in the impairment of the decidualizing capacity of human ectopic endometrial stromal cells (HEcESCs).

Methods

In vitro analysis of primary undifferentiated and decidualizing human eutopic endometrial stromal cells (HEuESCs) and HEcESCs was conducted. The primary HEuESCs or HEcESCs were expanded in culture and decidualized with 8‐bromo‐cyclic adenosine monophosphate (8‐bromo‐cAMP) and medroxyprogesterone acetate (MPA).

Results

The morphological and biological differentiating capacities of the HEcESCs were markedly impaired. In contrast to the HEuESCs, the HEcESCs that were treated with the decidual stimulus retained the mesenchymal phenotype and capacity for migration. The down‐regulation of miR‐542‐3p in the HEcESCs treatment with 8‐bromo‐cAMP and MPA was much weaker than that of the HEuESCs. High expression of miR‐542‐3p led to a significant decrease in the expression of IGFBP1 in the HEcESCs.

Conclusion

Impairment of the differentiating capacity by the overexpression of miR‐542‐3p could influence the capacity for migration and invasion of endometriotic cells in an ectopic environment.
Employee‐based Innovation in Organizations: Overcoming Strategic Risks from Opportunism and Governance
Authors: Pandher Gurupdesh S. , Mutlu Gulseren , Samnani Al‐Karim
Published: March 2017

Research summary

Employees performing everyday tasks frequently acquire valuable new ideas and knowledge. Our formal analysis studies how organizations can benefit from employee‐driven innovation by using incentives to overcome strategic risk from opportunism and governance. We use a game theory framework to analyze the strategic interactions involved and identify incentives under which valuable ideas will be revealed without appropriation (in equilibrium). Our analysis considers both the short run and the long run, where governance can be adjusted to maximize expected future innovation profits. Innovation value, frequency, governance quality, and employee contestation costs are shown to play a salient role in determining the innovation incentives and equilibrium. Overall, our analysis and results provide a number of insights on how organizations can overcome frictions from strategic innovation risks to more fully mobilize their innovation potential and knowledge‐based resources.

Managerial summary

Idea theft can occur in organizations when employees find it beneficial to present a valuable idea of another employee as theirs. If employees engaged in everyday tasks believe this will likely happen or that they will not be rewarded enough, they may not reveal them. We analyze the design of appropriate innovation rewards that will prevent stealing of innovative ideas and allow organizations to capture value from employee‐driven innovation. We show that governance quality, innovation value, and costs related to contestation play a salient role in determining appropriate innovation rewards and the organization's innovation capacity. “Flatter” organizations can deter idea theft more effectively and need to pay lower innovation rewards. In the long term, we show that all organizations can become more innovative by adjusting their governance quality and reducing employee contestation costs. Further, the ones with higher innovation potential and contestation costs will move toward higher quality governance and seek more entrepreneurial employees, as this raises long‐run innovation profits. Copyright © 2017 Strategic Management Society.
Functional Substituted Phthalocyanines Bearing Ter–pyridine Complexes as Macromolecular Oxidation Catalysts for Bleaching Systems
Authors: Sen Pinar , Yildiz S. Zeki , Dege Necmi , Atakay Mehmet , Salih Bekir
Published: March 2017

The present study dealing with the oxidation catalysts using in laundry bleaching process comprises of the complexion of 4’‐(N‐2‐phthalonitrile‐N‐methylamino)‐2,2’:6’,2’’‐terpyridine (2) with the related MnCl2.4H2O and CoCl2.6H2O salts in ethanol to obtain 4’‐(N‐2‐phthalonitrile‐N‐methylamino)‐2,2’:6’,2’’‐terpyridine‐Mn (II) complex (3) and 4’‐(N‐2‐phthalonitrile‐N‐methylamino)‐2,2’:6’,2’’‐terpyridine‐Co (II) complex (4). Terpyridine metal complexes substituted Zinc phthalocyanines, Tetrakis [4’‐(N‐2‐phthalonitrile‐N‐methylamino)‐2, 2’: 6’, 2’’‐terpyridine‐Mn(II) complex] phthalocyaninato zinc(II) (5) and Tetrakis [4’‐(N‐2‐phthalonitrile‐N‐methylamino)‐2,2’:6’,2’’‐terpyridine‐Co(II) complex] phthalocyaninato zinc(II) (6) were also prepared by the tetramerization of the terpyridine‐metal complexes (3, 4) in the presence of ZnCl2. FT‐IR, 1H‐NMR, 13C‐NMR, UV‐Vis, ESI‐MS and MALDI‐MS spectra were applied to characterize the prepared compounds. 4‐nitrophthalonitrile and some other starting materials crystallized in the synthetic pathway. 4‐nitrophthalonitrile crystalizes in different morphology and 4’‐(N‐2‐ Hydroxyehyl‐N‐methylamino)‐2, 2’ : 6’, 2’’‐ terpyridine (1) crystallizes in the monoclinic, space group. The compound 2 and 3 crystallize in the monoclinic space group. The bleach performances of the prepared terpyridine complexes (3, 4) and their phthalocyanine derivatives (5, 6) were examined by the degradation of Morin dye by using online spectrophotometric method (OSM).
A Facile Regioselective Synthesis of New Class of Cyclopent[b]indole dispiro heterocycles via1,3‐Dipolar Cycloaddition protocol and in vitro Cytotoxic studies
Authors: Satheeshkumar Rajendran , Edatt Lincy , Kumar V. B. Sameer , Prasad Karnam Jayarampillai Rajendra
Published: March 2017

The construction of azomethine ylides in situ from acenaphthoquinone/isatin and secondary amino acids such as sarcosine and thiaproline with cyclopent[b]indole dipolarophilesin refluxing dioxane and methanol afforded novel class of cyclopent[b]indole dispiro heterocycles via 1,3‐dipolar cycloaddition reaction. The regio and stereochemistry of formation of the final product was concertedly assigned by proton, carbon and 2D NMR techniques. Among the synthesized dispiroheterocyclic compounds 4&7 are found to show better cytotoxic activity against HeLa and MCF‐7 with structure activity relationship (SAR) studies.
Fetal myocardial performance index in assessment and management of small‐for‐gestational‐age fetus: a cohort and nested case–control study
Authors: Henry A. , Alphonse J. , Tynan D. , Welsh A. W.
Published: March 2017

Objective

To assess the clinical utility of the fetal myocardial performance index (MPI) in assessment and management of the small‐for‐gestational‐age (SGA) fetus/growth‐restricted fetus (FGR).

Methods

This was a prospective cohort study in metropolitan Australia of patients referred in the period June 2012 to March 2015 to fetal medicine services at 24–38 weeks' gestation for suspected singleton SGA/FGR (estimated fetal weight (EFW) < 10th centile with or without abnormal umbilical artery (UA) Doppler) pregnancy. Patients had MPI assessed in addition to routine measures, and were followed through to birth. We compared MPI values against those of a local reference population and gestational age‐matched controls, and assessed the correlation with perinatal outcome and other Doppler measures.

Results

Fifty‐two cases were included, 38 diagnosed < 32 weeks and 14 diagnosed ≥ 32 weeks. None demonstrated significantly elevated left, right or delta MPI compared with the reference population or with gestational age‐matched controls at the time of first MPI evaluation. There were no consistent longitudinal patterns in MPI that would suggest its clinical utility. The mean ± SD gestational age at delivery was 34.6 ± 3.8 weeks and birth weight was 1.7 ± 0.6 kg, and the median neonatal hospital admission time was 27 days, confirming a pathological cohort. There were no significant correlations between left, right or delta‐MPI and perinatal outcome, although there were significant correlations between UA, middle cerebral artery (MCA) and ductus venosus (DV) Doppler and perinatal outcome (birth weight, gestational age at birth and length of neonatal hospital stay). Exploratory subgroup comparisons (EFW < 3rd vs 3rd–10th centile; early‐ vs late‐onset; abnormal vs normal UA Doppler) found only minor differences in MPI, reaching statistical, but not clinical, significance, only in the EFW < 3rd vs 3rd–10th centile comparison.

Conclusions

MPI did not demonstrate clinical utility in either triage or longitudinal follow‐up of an SGA/FGR cohort presenting to fetal medicine services. Given that prior research suggesting its utility originates from single‐center cohorts, while multicenter, large cohorts have suggested little utility or no additional utility if routine UA/MCA/DV Doppler is performed, publication bias may have affected previous reports. It seems unlikely that MPI has clinical utility in assessment and management of SGA/FGR fetuses. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
Antibodies from plants for bionanomaterials
Authors: Edgue Gueven , Twyman Richard M , Beiss Veronique , Fischer Rainer , Sack Markus
Published: March 2017

Antibodies are produced as part of the vertebrate adaptive immune response and are not naturally made by plants. However, antibody DNA sequences can be introduced into plants, and together with laboratory technologies that allow the design of antibodies recognizing any conceivable molecular structure, plants can be used as ‘green factories’ to produce any antibody at all. The advent of plant‐based transient expression systems in particular allows the rapid, convenient, and safe production of antibodies, ranging from laboratory‐scale expression to industrial‐scale manufacturing. The key features of plant‐based production include safety, speed, low cost, and convenience, allowing newcomers to rapidly master the technology and use it to its full advantage. Manufacturing in plants has recently achieved significant milestones and offers more than just an alternative to established microbial and mammalian cell platforms. The use of plants for product development in particular offers the power and flexibility to easily coexpress many different genes, allowing the plug‐and‐play construction of novel bionanomaterials, perfectly complementing existing approaches based on plant virus‐like particles. As well as producing single antibodies for applications in medicine, agriculture, and industry, plants can be used to produce antibody‐based supramolecular structures and scaffolds as a new generation of green bionanomaterials that promise a bright future based on clean and renewable nanotechnology applications. WIREs Nanomed Nanobiotechnol 2017, 9:e1462. doi: 10.1002/wnan.1462

This article is categorized under:

Therapeutic Approaches and Drug Discovery > Emerging Technologies

Diagnostic Tools > In Vivo Nanodiagnostics and Imaging

Biology-Inspired Nanomaterials > Protein and Virus-Based Structures
Trends in Procedures at Major Trauma Centres in New South Wales, Australia: An Analysis of State‐Wide Trauma Data
Authors: Oliver Matthew , Dinh Michael M. , Curtis Kate , Paschkewitz Royce , Rigby Oran , Balogh Zsolt J.
Published: March 2017

Objectives

To describe the trend in major trauma surgical procedures and interventional radiology in major trauma patients in Australia over the past 6 years.

Methods

This was a retrospective review of adult major trauma (Injury Severity Score greater than 15) patients using the New South Wales Statewide Trauma Registry between 2009 and 2014. Major trauma surgical procedures were classified into abdominal, neurosurgery, cardiothoracic and interventional radiology. The proportion of patients undergoing such procedures per year was the outcome of interest.

Results

There were around ten thousand cases analysed. The proportion of cases undergoing interventional radiology procedures increased from 1% in 2009 to around 6% in 2014. Other major trauma surgical procedures remained stable. Only around 100 laparotomies were performed in 2014. The predictors of having an IR procedure performed were increasing from 2009 (OR 1.5 95% CI 1.4, 1.6 p < 0.001), hypotension (OR 1.5 95% CI 1.1, 2.1 n = 0.01), severe abdominal injury (OR 4.2 95% CI 3.2, 5.3 p < 0.001) and lower limb (including pelvic) injury (OR 3.8 95% CI 3.0, 4.7 p < 0.001).

Conclusion

There has been a rapid increase in the use of interventional radiology over the past few years which will need to be addressed in future trauma service planning and models of care.
Oligomeric State and Thermal Stability of Apo- and Holo- Human Ornithine δ-Aminotransferase
Authors: Montioli Riccardo , Zamparelli Carlotta , Borri Voltattorni Carla , Cellini Barbara
Published: March 2017

Human ornithine δ-aminotransferase (hOAT) (EC 2.6.1.13) is a mitochondrial pyridoxal 5′-phosphate (PLP)-dependent aminotransferase whose deficit is associated with gyrate atrophy, a rare autosomal recessive disorder causing progressive blindness and chorioretinal degeneration. Here, both the apo- and holo-form of recombinant hOAT were characterized by means of spectroscopic, kinetic, chromatographic and computational techniques. The results indicate that apo and holo-hOAT (a) show a similar tertiary structure, even if apo displays a more pronounced exposure of hydrophobic patches, (b) exhibit a tetrameric structure with a tetramer-dimer equilibrium dissociation constant about fivefold higher for the apoform with respect to the holoform, and (c) have apparent Tm values of 46 and 67 °C, respectively. Moreover, unlike holo-hOAT, apo-hOAT is prone to unfolding and aggregation under physiological conditions. We also identified Arg217 as an important hot-spot at the dimer–dimer interface of hOAT and demonstrated that the artificial dimeric variant R217A exhibits spectroscopic properties, Tm values and catalytic features similar to those of the tetrameric species. This finding indicates that the catalytic unit of hOAT is the dimer. However, under physiological conditions the apo-tetramer is slightly less prone to unfolding and aggregation than the apo-dimer. The possible implications of the data for the intracellular stability and regulation of hOAT are discussed.
Allergic fungal sinusitis caused by Schizophyllum commune
Authors: Liu Xiang , Zou Hua , Chen Qiu‐Jian , Lu Chang‐Ming
Published: March 2017

A case of allergic fungal sinusitis (AFS) due to Schizophyllum commune was reported. The pathogen was identified using molecular bioanalysis. The patient underwent the functional endoscopic sinus surgery followed by the radical maxillary sinusotomy with canine fossa trephine. This case suggested that complete surgery allowed optimal disease clearance for AFS caused by Schizophyllum commune.
Implementation of Neurocritical Care Is Associated With Improved Outcomes in Traumatic Brain Injury
Authors: Sekhon Mypinder S. , Gooderham Peter , Toyota Brian , Kherzi Navid , Hu Vivien , Dhingra Vinay K. , Hameed Morad S. , Chittock Dean R. , Griesdale Donald E.
Published: March 2017

Background Traditionally, the delivery of dedicated neurocritical care (NCC) occurs in distinct NCC units and is associated with improved outcomes. Institution-specific logistical challenges pose barriers to the development of distinct NCC units; therefore, we developed a consultancy NCC service coupled with the implementation of invasive multimodal neuromonitoring, within a medical-surgical intensive care unit. Our objective was to evaluate the effect of a consultancy NCC program on neurologic outcomes in severe traumatic brain injury patients. Methods: We conducted a single-center quasi-experimental uncontrolled pre- and post-NCC study in severe traumatic brain injury patients (Glasgow Coma Scale ≤8). The NCC program includes consultation with a neurointensivist and neurosurgeon and multimodal neuromonitoring. Demographic, injury severity metrics, neurophysiologic data, and therapeutic interventions were collected. Glasgow Outcome Scale (GOS) at 6 months was the primary outcome. Multivariable ordinal logistic regression was used to model the association between NCC implementation and GOS at 6 months. Results: A total of 113 patients were identified: 76 pre-NCC and 37 post-NCC. Mean age was 39 years (standard deviation [SD], 2) and 87 of 113 (77%) patients were male. Median admission motor score was 3 (interquartile ratio, 1-4). Daily mean arterial pressure was higher (95 mmHg [SD, 10]) versus (88 mmHg [SD, 10], p<0.001) and daily mean core body temperature was lower (36.6°C [SD, 0.90]) versus (37.2°C [SD, 1.0], p=0.001) post-NCC compared with pre-NCC, respectively. Multivariable regression modelling revealed the NCC program was associated with a 2.5 increased odds (odds ratios, 2.5; 95% confidence interval, 1.1-5.3; p=0.022) of improved 6-month GOS. Conclusions: Implementation of a NCC program is associated with improved 6 month GOS in severe TBI patients.
Livestock Changes at the Beginning and End of the Roman Period in Britain: Issues of Acculturation, Adaptation, and ‘Improvement’
Authors: Rizzetto Mauro , Crabtree Pam J. , Albarella Umberto
Published: March 2017

This article reviews aspects of the development of animal husbandry in Roman Britain, focusing in particular on the Iron Age/Roman and Roman/early medieval transitions. By analysing the two chronological extremes of the period of Roman influence in Britain we try to identify the core characteristics of Romano-British husbandry by using case studies, in particular from south-eastern Britain, investigated from the perspective of the butchery and morphometric evidence they provide. Our aim is to demonstrate the great dynamism of Romano-British animal husbandry, with substantial changes in livestock management occurring at the beginning, the end, and during the period under study. It is suggested that such changes are the product of interactions between different cultural and social traditions, which can be associated with indigenous and external influences, but also numerous other causes, ranging from ethnic origins to environmental, geographic, political, and economic factors.
Recognizing sexual dimorphism in the fossil record: lessons from nonavian dinosaurs
Authors: Mallon Jordan C.
Published: March 2017

The demonstration of sexual dimorphism in the fossil record can provide vital information about the role that sexual selection has played in the evolution of life. However, statistically robust inferences of sexual dimorphism in fossil organisms are exceedingly difficult to establish, owing to issues of sample size, experimental control, and methodology. This is particularly so in the case of dinosaurs, for which sexual dimorphism has been posited in many species, yet quantifiable data are often lacking. This study presents the first statistical investigation of sexual dimorphism across Dinosauria. It revisits prior analyses that purport to find quantitative evidence for sexual dimorphism in nine dinosaur species. After the available morphological data were subjected to a suite of statistical tests (normality and unimodality tests and mixture modeling), no evidence for sexual dimorphism was found in any of the examined taxa, contrary to conventional wisdom. This is not to say that dinosaurs were not sexually dimorphic (phylogenetic inference suggests they may well have been), only that the available evidence precludes its detection. A priori knowledge of the sexes would greatly facilitate the assessment of sexual dimorphism in the fossil record, and it is suggested that unambiguous indicators of sex (e.g., presence of eggs, embryos, medullary bone) be used to this end.
Association between urinary metabolic profile and the intestinal effects of cocoa in rats
Authors: Massot-Cladera Malen , Mayneris-Perxachs Jordi , Costabile Adele , Swann Jonathan R. , Franch Àngels , Pérez-Cano Francisco J. , Castell Margarida
Published: March 2017

The aim of this study was to elucidate the relationship between the urinary metabolic fingerprint and the effects of cocoa and cocoa fibre on body weight, hormone metabolism, intestinal immunity and microbiota composition. To this effect, Wistar rats were fed, for 3 weeks, a diet containing 10 % cocoa (C10) or two other diets with same the proportion of fibres: one based on cocoa fibre (CF) and another containing inulin as a reference (REF) diet. The rats’ 24 h urine samples were analysed by an untargeted 1H NMR spectroscopy-based metabonomic approach. Concentrations of faecal IgA and plasma metabolic hormones were also quantified. The C10 diet decreased the intestinal IgA, plasma glucagon-like peptide-1 and glucagon concentrations and increased ghrelin levels compared with those in the REF group. Clear differences were observed between the metabolic profiles from the C10 group and those from the CF group. Urine metabolites derived from cocoa correlated with the cocoa effects on body weight, immunity and the gut microbiota. Overall, cocoa intake alters the host and bacterial metabolism concerning energy and amino acid pathways, leading to a metabolic signature that can be used as a marker for consumption. This metabolic profile correlates with body weight, metabolic hormones, intestinal immunity and microbiota composition.
Avian malaria, ecological host traits and mosquito abundance in southeastern Amazonia
Authors: FECCHIO ALAN , ELLIS VINCENZO A. , BELL JEFFREY A. , ANDRETTI CHRISTIAN B. , D'HORTA FERNANDO M. , SILVA ALLAN M. , TKACH VASYL V. , WECKSTEIN JASON D.
Published: March 2017

Avian malaria is a vector transmitted disease caused byPlasmodiumand recent studies suggest that variation in its prevalence across avian hosts is correlated with a variety of ecological traits. Here we examine the relationship between prevalence and diversity ofPlasmodiumlineages in southeastern Amazonia and: (1) host ecological traits (nest location, nest type, flocking behaviour and diet); (2) density and diversity of avian hosts; (3) abundance and diversity of mosquitoes; and (4) season. We used molecular methods to detectPlasmodiumin blood samples from 675 individual birds of 120 species. Based on cytochromebsequences, we recovered 89 lineages ofPlasmodiumfrom 136 infected individuals sampled across seven localities.Plasmodiumprevalence was homogeneous over time (dry season and flooding season) and space, but heterogeneous among 51 avian host species. Variation in prevalence among bird species was not explained by avian ecological traits, density of avian hosts, or mosquito abundance. However,Plasmodiumlineage diversity was positively correlated with mosquito abundance. Interestingly, our results suggest that avian host traits are less important determinants ofPlasmodiumprevalence and diversity in southeastern Amazonia than in other regions in which they have been investigated.
The state of the art in semantic relatedness: a framework for comparison
Authors: Feng Yue , Bagheri Ebrahim , Ensan Faezeh , Jovanovic Jelena
Published: March 2017

Semantic relatedness (SR) is a form of measurement that quantitatively identifies the relationship between two words or concepts based on the similarity or closeness of their meaning. In the recent years, there have been noteworthy efforts to compute SR between pairs of words or concepts by exploiting various knowledge resources such as linguistically structured (e.g. WordNet) and collaboratively developed knowledge bases (e.g. Wikipedia), among others. The existing approaches rely on different methods for utilizing these knowledge resources, for instance, methods that depend on the path between two words, or a vector representation of the word descriptions. The purpose of this paper is to review and present the state of the art in SR research through a hierarchical framework. The dimensions of the proposed framework cover three main aspects of SR approaches including the resources they rely on, the computational methods applied on the resources for developing a relatedness metric, and the evaluation models that are used for measuring their effectiveness. We have selected 14 representative SR approaches to be analyzed using our framework. We compare and critically review each of them through the dimensions of our framework, thus, identifying strengths and weaknesses of each approach. In addition, we provide guidelines for researchers and practitioners on how to select the most relevant SR method for their purpose. Finally, based on the comparative analysis of the reviewed relatedness measures, we identify existing challenges and potentially valuable future research directions in this domain.
TheZenne: Male Belly Dancers and Queer Modernity in Contemporary Turkey
Authors: MANSBRIDGE JOANNA
Published: March 2017

This article explores the history and contemporary revival of male belly dancers –zenneorköçek– in Turkey and in cities with large Turkish populations, such as Berlin. What does the current revival of male belly dancing tell us about the relationship between modern ideologies of sex and gender and narratives of modernity as they have taken shape in Turkey? Thezennedancer embodies the contradictions of contemporary Turkish culture, which includes a variety of same-sex practices, along with sexual taxonomies that have developed in collusion with discourses of modernity. The revival ofzennedancing can be seen as part of a series of global transformations in the visibility of gay, lesbian, and trans people in popular culture and public discourse. However, it is also an unpredicted consequence of the Justice and Development Party's (Adalet ve Kalkinma Partisi, AKP) purposeful revival and romanticization of Turkey's Ottoman past, which has been ahistorically remembered as more pious than the present. Re-emerging in the twenty-first century as an embodiment of competing definitions of sexuality and modernity in contemporary Turkey, precisely at a moment when Turkish national identity is a hotly contested issue, thezennedancer is queer ghost, returning to haunt (and seduce) the present.
Apartheid Acting Out: Trauma, Confession and the Melancholy of Theatre in Yaël Farber'sHe Left Quietly
Authors: CHARLTON ED
Published: March 2017

In 1984, Duma Kumalo was sentenced to death under the apartheid law of common purpose. He was only spared by the transitional negotiations that led to South Africa's first democratic elections in 1994. However, his suffering did not end with his release. Nor did his appearance alongside many other victims of human rights abuse at the country's Truth and Reconciliation Commission provide any measure of therapeutic relief. Instead, he continued to confess, as part of his performance in Yaël Farber'sHe Left Quietly(2002), to a trauma so overwhelming as to undo, it seems, any such a claim to healing. It has now been ten years since Kumalo passed away and this article returns to Farber's play in order to examine the theatrical form this melancholy takes, the challenge it poses to confessional orthodoxy and the ethical ends towards which such a melancholy performance might potentially drive, even still.
Collision Risk Modelling of Supply Vessels and Offshore Platforms Under Uncertainty
Authors: John Andrew , Osue Umukoro Johnson
Published: March 2017

Serious accidents in the marine and offshore industry have underscored the need for safety evaluation of maritime operations using risk and safety analysis methods which have become a powerful tool in identifying technical solutions and operational management procedures. Given that Fault Tree Analysis (FTA) is a known methodology used for analysing engineering systems, the approach is usually conducted using known failure data. But most offshore operations are conducted in a challenging and uncertain environment and the failure data of some of these systems are usually unavailable requiring a flexible and yet robust algorithm for their analysis. This paper therefore seeks to analyse the complex structure of Offshore Supply Vessel (OSV) collision with platforms by incorporating a Fuzzy Fault Tree Analysis (FFTA) method. Fuzzy set theory provides the flexibility to represent vague information from the analysis process. The methodology is structured in such a manner that diverse sets of data are integrated and synthesized for analysing the system. It is envisaged that the proposed method could provide the analyst with a framework to evaluate the risks of collision enabling informed decisions regarding the deployments of resources for system improvement.
New numerical determination of habitability in the Galaxy: the SETI connection
Authors: Ramirez Rodrigo , Gómez-Muñoz Marco A. , Vázquez Roberto , Núñez Patricia G.
Published: March 2017

In this paper, we determine the habitability of Sun-like stars in the Galaxy using Monte Carlo simulations, which are guided by the factors of the Drake Equation for the considerations on the astrophysical and biological parameters needed to generate and maintain life on a planet's surface. We used a simple star distribution, initial mass function and star formation history to reproduce the properties and distribution of stars within the Galaxy. Using updated exoplanet data from the Kepler mission, we assign planets to some of the stars, and then follow the evolution of life on the planets that met the habitability criteria using two different civilization hypotheses. We predict that around 51% of Earth-like planets in the habitable zone (HZ) are inhabited by primitive life and 4% by technological life. We apply the results to the Kepler field of view, and predicted that there should be at least six Earth-like planets in the HZ, three of them inhabited by primitive life. According to our model, non-technological life is very common if there are the right conditions, but communicative civilizations are less likely to exist and detect. Nonetheless, we predict a considerable number of detectable civilizations within our Galaxy, making it worthwhile to keep searching.
Muslim American Policy Advocacy and the Palestinian Israeli Conflict: Claims-making and the Pursuit of Group Rights
Authors: Cury Emily
Published: March 2017

Since the attacks of September 11, 2001, United States Muslims have been increasingly targeted as “others,” accused of holding dual-loyalties, and seen as potentially subversive. Nevertheless, Muslim American interest groups have not recoiled from foreign policy engagement. I argue that this is because mobilizing around symbolic foreign policy issues provides them with an opportunity to access the policy dialogue as a minority group making rights claims. To illustrate this argument, I conduct a discourse analysis of Muslim American policy engagement toward the Palestinian-Israeli conflict. I rely on primary documents produced by the Council on American Islamic Relations and the Muslim Public Affairs Council, the two leading United States Muslims organizations, as well as interviews conducted with institutional elites. I find that, through their policy advocacy, these organizations are framing their demands around United States interests and minority group rights, while positioning themselves as the legitimate representatives of the Muslim American community.

One of the most important issues to us is, of course, the Palestinian Israeli issue because this is central to what America is in the Middle East and the Muslim world.1

—Salam Al-Marayati

All I want from you, Mr. Policymaker is [for you] to listen to the other side of the story. I have a narrative that you didn't have a chance to hear, so let me give it to you and as-salamu alaykum [peace be upon you].2

—Dr. Maher Hathout
320 Übungsaufgaben zum HAM-Nat
Authors: Meinelt Philipp
Published: March 2017

Zahlreiche Universitäten setzen mittlerweile naturwissenschaftliche Tests zur Auswahl geeigneter Studierender in der Human- und Zahnmedizin ein. Um das naturwissenschaftliche Wissen der Bewerber zu prüfen, wird häufig das Hamburger Auswahlverfahren für medizinische Studiengänge – Naturwissenschaftsteil (HAM-Nat) genutzt. Dieses Buch ermöglicht es angehenden Studierenden, sich anhand der 320 Übungsfragen gezielt auf die Teilnahme am HAM-Nat vorzubereiten.
Die 320 Fragen decken den vollständigen Themenkatalog des HAM-Nat ab. Das Übungsbuch enthält jeweils 100 Aufgaben zu den Themengebieten Chemie, Physik und Biologie sowie 20 Aufgaben zum Bereich Mathematik. Es werden sowohl Definitionsfragen als auch komplexere Rechenaufgaben gestellt. Die große Vielfalt und Varianz der Fragen ermöglicht es Bewerbern, ihr Wissen nicht nur zu testen, sondern sich auch mit der Multiple-Choice-Fragetechnik vertraut zu machen. Durch die Bearbeitung der Aufgaben können angehende Studierende Routine beim Lösen der Aufgaben erlangen und so auch die Lösungsgeschwindigkeit erhöhen. Mithilfe der im Buch enthaltenen Lösungen sowie zusätzlichen Hinweisen für mögliche Lösungswege können Bewerber die Korrektheit ihrer Antworten und ihren Lernfortschritt überprüfen.
Inhibition of delta-secretase improves cognitive functions in mouse models of Alzheimer’s disease
Authors: Zhang Zhentao , Obianyo Obiamaka , Dall Elfriede , Du Yuhong , Fu Haian , Liu Xia , Kang Seong Su , Song Mingke , Yu Shan-Ping , Cabrele Chiara , Schubert Mario , Li Xiaoguang , Wang Jian-Zhi , Brandstetter Hans , Ye Keqiang
Published: March 2017

δ-secretase, also known as asparagine endopeptidase (AEP) or legumain, is a lysosomal cysteine protease that cleaves both amyloid precursor protein (APP) and tau, mediating the amyloid-β and tau pathology in Alzheimer’s disease (AD). Here we report the therapeutic effect of an orally bioactive and brain permeable δ-secretase inhibitor in mouse models of AD. We performed a high-throughput screen and identified a non-toxic and selective δ-secretase inhibitor, termed compound 11, that specifically blocks δ-secretase but not other related cysteine proteases. Co-crystal structure analysis revealed a dual active site-directed and allosteric inhibition mode of this compound class. Chronic treatment of tau P301S and 5XFAD transgenic mice with this inhibitor reduces tau and APP cleavage, ameliorates synapse loss and augments long-term potentiation, resulting in protection of memory. Therefore, these findings demonstrate that this δ-secretase inhibitor may be an effective clinical therapeutic agent towards AD.
Rational combination of oncolytic vaccinia virus and PD-L1 blockade works synergistically to enhance therapeutic efficacy
Authors: Liu Zuqiang , Ravindranathan Roshni , Kalinski Pawel , Guo Z. Sheng , Bartlett David L.
Published: March 2017

Both anti-PD1/PD-L1 therapy and oncolytic virotherapy have demonstrated promise, yet have exhibited efficacy in only a small fraction of cancer patients. Here we hypothesized that an oncolytic poxvirus would attract T cells into the tumour, and induce PD-L1 expression in cancer and immune cells, leading to more susceptible targets for anti-PD-L1 immunotherapy. Our results demonstrate in colon and ovarian cancer models that an oncolytic vaccinia virus attracts effector T cells and induces PD-L1 expression on both cancer and immune cells in the tumour. The dual therapy reduces PD-L1+ cells and facilitates non-redundant tumour infiltration of effector CD8+, CD4+ T cells, with increased IFN-γ, ICOS, granzyme B and perforin expression. Furthermore, the treatment reduces the virus-induced PD-L1+ DC, MDSC, TAM and Treg, as well as co-inhibitory molecules-double-positive, severely exhausted PD-1+CD8+ T cells, leading to reduced tumour burden and improved survival. This combinatorial therapy may be applicable to a much wider population of cancer patients.
The structure of Zika virus NS5 reveals a conserved domain conformation
Authors: Wang Boxiao , Tan Xiao-Feng , Thurmond Stephanie , Zhang Zhi-Min , Lin Asher , Hai Rong , Song Jikui
Published: March 2017

The recent outbreak of Zika virus (ZIKV) has imposed a serious threat to public health. Here we report the crystal structure of the ZIKV NS5 protein in complex with S-adenosyl-L-homocysteine, in which the tandem methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRp) domains stack into one of the two alternative conformations of flavivirus NS5 proteins. The activity of this NS5 protein is verified through a de novo RdRp assay on a subgenomic ZIKV RNA template. Importantly, our structural analysis leads to the identification of a potential drug-binding site of ZIKV NS5, which might facilitate the development of novel antivirals for ZIKV.
Crystal structure of Zika virus NS5 RNA-dependent RNA polymerase
Authors: Godoy Andre S. , Lima Gustavo M. A. , Oliveira Ketllyn I. Z. , Torres Naiara U. , Maluf Fernando V. , Guido Rafael V. C. , Oliva Glaucius
Published: March 2017

The current Zika virus (ZIKV) outbreak became a global health threat of complex epidemiology and devastating neurological impacts, therefore requiring urgent efforts towards the development of novel efficacious and safe antiviral drugs. Due to its central role in RNA viral replication, the non-structural protein 5 (NS5) RNA-dependent RNA-polymerase (RdRp) is a prime target for drug discovery. Here we describe the crystal structure of the recombinant ZIKV NS5 RdRp domain at 1.9 Å resolution as a platform for structure-based drug design strategy. The overall structure is similar to other flaviviral homologues. However, the priming loop target site, which is suitable for non-nucleoside polymerase inhibitor design, shows significant differences in comparison with the dengue virus structures, including a tighter pocket and a modified local charge distribution.
The soybean GmSNAP18 gene underlies two types of resistance to soybean cyst nematode
Authors: Liu Shiming , Kandoth Pramod K. , Lakhssassi Naoufal , Kang Jingwen , Colantonio Vincent , Heinz Robert , Yeckel Greg , Zhou Zhou , Bekal Sadia , Dapprich Johannes , Rotter Bjorn , Cianzio Silvia , Mitchum Melissa G. , Meksem Khalid
Published: March 2017

Two types of resistant soybean (Glycine max(L.) Merr.) sources are widely used against soybean cyst nematode (SCN,Heterodera glycinesIchinohe). These include Peking-type soybean, whose resistance requires both therhg1-aandRhg4alleles, and PI 88788-type soybean, whose resistance requires only therhg1-ballele. Multiple copy number of PI 88788-typeGmSNAP18,GmAAT, andGmWI12in one genomic segment simultaneously contribute torhg1-bresistance. Using an integrated set of genetic and genomic approaches, we demonstrate that therhg1-aPeking-typeGmSNAP18is sufficient for resistance to SCN in combination withRhg4. The two SNAPs (soluble NSF attachment proteins) differ by only five amino acids. Our findings suggest that Peking-typeGmSNAP18is performing a different role in SCN resistance than PI 88788-typeGmSNAP18. As such, this is an example of a pathogen resistance gene that has evolved to underlie two types of resistance, yet ensure the same function within a single plant species.
Direct amidation of esters with nitroarenes
Authors: Cheung Chi Wai , Ploeger Marten Leendert , Hu Xile
Published: March 2017

Esters are one of the most common functional groups in natural and synthetic products, and the one-step conversion of the ester group into other functional groups is an attractive strategy in organic synthesis. Direct amidation of esters is particularly appealing due to the omnipresence of the amide moiety in biomolecules, fine chemicals, and drug candidates. However, efficient methods for direct amidation of unactivated esters are still lacking. Here we report nickel-catalysed reductive coupling of unactivated esters with nitroarenes to furnish in one step a wide range of amides bearing functional groups relevant to the development of drugs and agrochemicals. The method has been used to expedite the syntheses of bio-active molecules and natural products, as well as their post-synthetic modifications. Preliminary mechanistic study indicates a reaction pathway distinct from conventional amidation methods using anilines as nitrogen sources. The work provides a novel and efficient method for amide synthesis.
A coupled human-Earth model perspective on long-term trends in the global marine fishery
Authors: Galbraith E. D. , Carozza D. A. , Bianchi D.
Published: March 2017

The global wild marine fish harvest increased fourfold between 1950 and a peak value near the end of the 20th century, reflecting interactions between anthropogenic and ecological forces. Here, we examine these interactions in a bio-energetically constrained, spatially and temporally resolved model of global fisheries. We conduct historical hindcasts with the model, which suggest that technological progress can explain most of the 20th century increase of fish harvest. In contrast, projections extending this rate of technological progress into the future under open access suggest a long-term decrease in harvest due to over-fishing. Climate change is predicted to gradually decrease the global fish production capacity, though our model suggests that this is of secondary importance to social and economic factors. Our study represents a novel way to integrate human-ecological interactions within a single model framework for long-term simulations.
Domain-dependent effects of insulin and IGF-1 receptors on signalling and gene expression
Authors: Cai Weikang , Sakaguchi Masaji , Kleinridders Andre , Gonzalez-Del Pino Gonzalo , Dreyfuss Jonathan M. , O’Neill Brian T. , Ramirez Alfred K. , Pan Hui , Winnay Jonathon N. , Boucher Jeremie , Eck Michael J. , Kahn C. Ronald
Published: March 2017

Despite a high degree of homology, insulin receptor (IR) and IGF-1 receptor (IGF1R) mediate distinct cellular and physiological functions. Here, we demonstrate how domain differences between IR and IGF1R contribute to the distinct functions of these receptors using chimeric and site-mutated receptors. Receptors with the intracellular domain of IGF1R show increased activation of Shc and Gab-1 and more potent regulation of genes involved in proliferation, corresponding to their higher mitogenic activity. Conversely, receptors with the intracellular domain of IR display higher IRS-1 phosphorylation, stronger regulation of genes in metabolic pathways and more dramatic glycolytic responses to hormonal stimulation. Strikingly, replacement of leucine973 in the juxtamembrane region of IR to phenylalanine, which is present in IGF1R, mimics many of these signalling and gene expression responses. Overall, we show that the distinct activities of the closely related IR and IGF1R are mediated by their intracellular juxtamembrane region and substrate binding to this region.
Rotiferan Hox genes give new insights into the evolution of metazoan bodyplans
Authors: Fröbius Andreas C. , Funch Peter
Published: March 2017

The phylum Rotifera consists of minuscule, nonsegmented animals with a unique body plan and an unresolved phylogenetic position. The presence of pharyngeal articulated jaws supports an inclusion in Gnathifera nested in the Spiralia. Comparison of Hox genes, involved in animal body plan patterning, can be used to infer phylogenetic relationships. Here, we report the expression of five Hox genes during embryogenesis of the rotifer Brachionus manjavacas and show how these genes define different functional components of the nervous system and not the usual bilaterian staggered expression along the anteroposterior axis. Sequence analysis revealed that the lox5-parapeptide, a key signature in lophotrochozoan and platyhelminthean Hox6/lox5 genes, is absent and replaced by different signatures in Rotifera and Chaetognatha, and that the MedPost gene, until now unique to Chaetognatha, is also present in rotifers. Collectively, our results support an inclusion of chaetognaths in gnathiferans and Gnathifera as sister group to the remaining spiralians.
Vitamin D ointment for prevention of radiation dermatitis in breast cancer patients
Authors: Nasser Nicola J. , Fenig Shlomit , Ravid Amiram , Nouriel Ariella , Ozery Naama , Gardyn Sara , Koren Ruth , Fenig Eyal
Published: March 2017

Radiation dermatitis occurs frequently during adjuvant radiation therapy for breast cancer. Prevention of radiation dermatitis by applying various creams and ointments has a limited success, and Aqua cream which has urea as one of its active ingredients is used in many institutions as a preventive treatment. The primary goal of this study is to assess the effect of vitamin D (calcipotriol) ointment in prevention of radiodermatitis in breast cancer patients compared to Aqua cream. Twenty-three women with localized breast cancer who underwent breast-conserving surgery and opted to receive adjuvant radiotherapy to breast only were enrolled in this study. A cream containing an active vitamin D analog, calcipotriol (Daivonex), was randomly applied either to the medial or to the lateral half of the irradiated breast, while Aqua cream was applied to the complimentary half of the same breast along the whole treatment days, each day, after the delivery of radiation. Skin reaction was recorded and compared between the two halves of the breast. Vitamin D was well tolerated by patients with no local or systemic allergic reactions. Radiation dermatitis was not significantly different between both treatment arms. Topical vitamin D ointment is not superior to Aqua cream for prevention of radiation-induced dermatitis in women treated with adjuvant radiation for breast cancer.
Early-onset parkinsonism in a pedigree with phosphoglycerate kinase deficiency and a heterozygous carrier: do PGK-1 mutations contribute to vulnerability to parkinsonism?
Authors: Sakaue Satoshi , Kasai Takashi , Mizuta Ikuko , Suematsu Masaya , Osone Shinya , Azuma Yumiko , Imamura Toshihiko , Tokuda Takahiko , Kanno Hitoshi , El-Agnaf Omar M. A. , Morimoto Masafumi , Nakagawa Masanori , Hosoi Hajime , Mizuno Toshiki
Published: March 2017

Phosphoglycerate kinase 1 (PGK-1) is a glycolytic enzyme encoded by PGK-1, which maps to the X chromosome. PGK-1 deficiency causes X-linked recessive hereditary chronic hemolytic anemia, myopathy, and neurological disorders due to insufficient ATP regeneration. Early-onset parkinsonism has occasionally been reported as a neurological complication of this condition. However, heterozygous carriers of PGK-1 deficiency were thought to be neurologically asymptomatic. Here, we report a boy with PGK-1 deficiency and his mother, a carrier of a heterozygous mutation in PGK-1, both of whom presented with early-onset parkinsonism. The boy developed parkinsonism at 9 years of age. His parkinsonism partially responded to levodopa treatment. 123l-metaiodobenzylguanidine (MIBG) uptake was normal. His mother, who exhibited normal PGK-1 activity in erythrocytes, developed parkinsonism at 36 years of age. Her symptoms were undistinguishable from those of Parkinson’s disease (PD), despite her normal uptake of MIBG. Neither a point mutation in nor multiplication of SNCA was found. Additionally, hotspots of LRRK2 and GBA were not mutated. To our knowledge, this report provides the first description of parkinsonism in a carrier of PGK-1 deficiency. Interestingly, PGK-1 is located within the confirmed susceptibility locus for PD known as PARK12. These observations suggest that PGK-1 mutations confer susceptibility to PD.