bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective‐area growth of doped GaN nanorods by pulsed‐mode MOCVD: Effect of Si and Mg dopants
Authors: Bae Si‐Young , Lekhal Kaddour , Lee Ho‐Jun , Min Jung‐Wook , Lee Dong‐Seon , Honda Yoshio , Amano Hiroshi
Published: April 2017

Injecting current with a uniform carrier concentration is important for applications with three‐dimensional architectures such as vertical power devices or displays. In III‐nitride nanostructures, dopants not only incorporate differently depending on the surface orientation but can also seriously affect the kinetic equilibrium shapes of the nanorods. Herein, we report selective‐area growth of doped GaN nanorods grown by pulsed‐mode metalorganic chemical vapor deposition. Two dopants, Si and Mg, were employed as donor and acceptor atoms, respectively, for a mono‐doping approach. Furthermore, a mixed flow of Si and Mg was supplied for a co‐doping approach. We compared the morphological effects and growth rates of each doped GaN nanorod array. Then, we proposed appropriate growth mechanisms for the doped GaN nanorods on the basis of our structural characterizations. These results might extend the morphological functionality of GaN nanorods by including doping and may also provide an appropriate foundation for the design of nanostructure‐based electronic or photonic devices.
Subgraph statistics in subcritical graph classes
Authors: Drmota Michael , Ramos Lander , Rué Juanjo
Published: April 2017

Let H be a fixed graph and a subcritical graph class. In this paper we show that the number of occurrences of H (as a subgraph) in a graph in of order n, chosen uniformly at random, follows a normal limiting distribution with linear expectation and variance. The main ingredient in our proof is the analytic framework developed by Drmota, Gittenberger and Morgenbesser to deal with infinite systems of functional equations [Drmota, Gittenberger, and Morgenbesser, Submitted]. As a case study, we obtain explicit expressions for the number of triangles and cycles of length 4 in the family of series‐parallel graphs. © 2017 Wiley Periodicals, Inc. Random Struct. Alg., 51, 631–673, 2017
Emerging Prototype Sodium‐Ion Full Cells with Nanostructured Electrode Materials
Authors: Ren Wenhao , Zhu Zixuan , An Qinyou , Mai Liqiang
Published: April 2017

Due to steadily increasing energy consumption, the demand of renewable energy sources is more urgent than ever. Sodium‐ion batteries (SIBs) have emerged as a cost‐effective alternative because of the earth abundance of Na resources and their competitive electrochemical behaviors. Before practical application, it is essential to establish a bridge between the sodium half‐cell and the commercial battery from a full cell perspective. An overview of the major challenges, most recent advances, and outlooks of non‐aqueous and aqueous sodium‐ion full cells (SIFCs) is presented. Considering the intimate relationship between SIFCs and electrode materials, including structure, composition and mutual matching principle, both the advance of various prototype SIFCs and the electrochemistry development of nanostructured electrode materials are reviewed. It is noted that a series of SIFCs combined with layered oxides and hard carbon are capable of providing a high specific gravimetric energy above 200 Wh kg–1, and an NaCrO2//hard carbon full cell is able to deliver a high rate capability over 100 C. To achieve industrialization of SIBs, more systematic work should focus on electrode construction, component compatibility, and battery technologies.
Dynamic Embeddedness in Chinese Firm Internationalization
Authors: Lattemann Christoph , Alon Ilan , Spigarelli Francesca , Marinova Svetla Trifonova
Published: April 2017

This article presents a multilevel framework to analyze the motivations and location choices of ChineseOFDIs. We contribute to theory‐integration on ChineseOFDIflows and patterns by suggesting a framework that combines country‐, industry‐ and firm‐level analyses and by reflecting aspects from the resource‐based view (firm‐specific advantages), institutional‐based view (push/pull home‐ and host‐­country factors), and network‐based view (network relations). We also explicitly incorporate “time” as a variable into our framework by introducing and explaining the concept ofdynamic embeddednessas an interaction dimension to reflect the inherent dynamics on all levels and actors. © 2017 Wiley Periodicals, Inc.
Serum testosterone: the why and wherefore of testing
Authors: Heald Adrian , Livingston Mark
Published: April 2017

Testosterone levels are now routinely measured in men attending endocrine and sexual medicine clinics, and increasingly in primary care, to investigate erectile and/or possible gonadal dysfunction. In this article the authors describe what to measure and when.
Successful treatment of infertility in a female Sumatran orangutan Pongo abelii
Authors: Maclachlan Neil , Hunt Gordon , Fowkes Sarah , Frost Melissa , Miller John , Purcell‐Jones Gari , Sullivan Peter , Barbon Alberto , Routh Andrew , López Francisco J. , Price Eluned C.
Published: April 2017

In 2011, a female Sumatran orangutan housed at Durrell Wildlife Conservation Trust became infertile following a massive antepartum hemorrhage in labor and the delivery of a stillborn infant. The placenta was infected with Pantoea sp. Hysterosalpingography (HSG) revealed blocked fallopian tubes, and pressurized fallopian tube perfusion was used to reverse the tubal occlusion. She subsequently conceived and following an intensive training program, we were able to measure umbilical artery waveform analysis for fetal well‐being and placental localization to exclude placenta previa, which could complicate pregnancy and lead to catastrophic hemorrhage. The female went on to deliver a healthy offspring. We suggest that these techniques should be considered for other infertile females in the global captive population.
Clinical and biochemical heterogeneity between patients with glycogen storage disease type IA: the added value of CUSUM for metabolic control
Authors: Peeks Fabian , Steunenberg Thomas A. H. , de Boer Foekje , Rubio‐Gozalbo M. Estela , Williams Monique , Burghard Rob , Rajas Fabienne , Oosterveer Maaike H. , Weinstein David A. , Derks Terry G. J.
Published: April 2017

Objective

To study heterogeneity between patients with glycogen storage disease type Ia (GSD Ia), a rare inherited disorder of carbohydrate metabolism caused by the deficiency of glucose‐6‐phosphatase (G6Pase).

Study design

Descriptive retrospective study of longitudinal clinical and biochemical data and long‐term complications in 20 GSD Ia patients. We included 11 patients with homozygous G6PC mutations and siblings from four families carrying identical G6PC genotypes. To display subtle variations for repeated triglyceride measurements with respect to time for individual patients, CUSUM‐analysis graphs were constructed.

Results

Patients with different homozygous G6PC mutations showed important differences in height, BMI, and biochemical parameters (i.e., lactate, uric acid, triglyceride, and cholesterol concentrations). Furthermore, CUSUM‐analysis predicts and displays subtle changes in longitudinal blood triglyceride concentrations. Siblings in families also displayed important differences in biochemical parameters (i.e., lactate, uric acid, triglycerides, and cholesterol concentrations) and long‐term complications (i.e., liver adenomas, nephropathy, and osteopenia/osteoporosis).

Conclusions

Differences between GSD Ia patients reflect large clinical and biochemical heterogeneity. Heterogeneity between GSD Ia patients with homozygous G6PC mutations indicate an important role of the G6PC genotype/mutations. Differences between affected siblings suggest an additional role (genetic and/or environmental) of modifying factors defining the GSD Ia phenotype. CUSUM‐analysis can facilitate single‐patient monitoring of metabolic control and future application of this method may improve precision medicine for patients both with GSD and remaining inherited metabolic diseases.
Succession of algal communities in headwaters: a comparison of pine afforested and natural grassland streams
Authors: Cibils‐Martina Luciana , Principe Romina E. , Márquez Javier A. , Gari E. Noemí , Albariño Ricardo J.
Published: April 2017

We evaluated changes in the succession process in benthic algal communities of an afforested stream by comparing them with those in a grassland stream through analysis of temporal changes in composition, structure and functional traits in a 3‐month experiment. We hypothesized that sunlight intensity reduction as a result of streamside implanted tree shading reduces the succession rate and community physiognomic complexity. We selected two streams with different riparian cover (grassland and pine afforestation) for installation of unglazed tiles as artificial substrates. The tiles were collected from each stream after 23, 45 and 73 days of exposure. Afforestation produced changes in algal succession, with lower biomass, lower diversity at the beginning of the experiment, and an increase in the proportion of small, low‐profile, tolerant, unicellular and stalked algae, coinciding with the predominance of Achnanthidium. However, the grassland stream contained a higher proportion of intermediate‐size algae, as well as a larger proportion of high‐profile algae, coinciding with the expected results. In the afforested stream, succession proceeded toward the dominance of low‐profile species, that were tolerant of low‐light conditions. However, in grassland streams with higher sunlight availability, high‐profile algae prevailed without the displacement of tolerant forms. Overall, our results indicate that algal communities in afforested stream remain structurally simpler.
Preparing medical students for clinical practice: easing the transition
Authors: Teagle Alexandra R. , George Maria , Gainsborough Nicola , Haq Inam , Okorie Michael
Published: April 2017

The transition from medical student to junior doctor is a challenge; the UK General Medical Council has issued guidance emphasizing the importance of adequate preparation of medical students for clinical practice. This study aimed to determine whether a junior doctor-led simulation-based course is an effective way of preparing final year medical students for practice as a junior doctor.

We piloted a new ‘preparation for practice’ course for final year medical students prior to beginning as Foundation Year 1 (first year of practice) doctors. The course ran over three days and consisted of four simulated stations: ward round, prescribing, handover, and lessons learnt. Quantitative and qualitative feedback was obtained.

A total of 120 students attended (40 on each day) and feedback was collected from 95 of them. Using a scale of 1 (lowest) to 5 (highest), feedback was positive, with 99% and 96% rating 4 or 5 for the overall quality of the program and the relevance of the program content, respectively. A score of 5 was awarded by 67% of students for the ward round station; 58% for the handover station; 71% for the prescribing station, and 35% for the lessons learnt station. Following the prescribing station, students reported increased confidence in their prescribing.

Preparation for practice courses and simulation are an effective and enjoyable way of easing the transition from medical student to junior doctor. Together with ‘on-the-job’ shadowing time, such programs can be used to improve students’ confidence, competence, and ultimately patient safety and quality of care.
Comparison of the excretory capacities of erythropoietin and U-74389G concerning serum creatinine levels
Authors: Tsompos Constantinos , Panoulis Constantinos , Toutouzas Konstantinos , Triantafyllou Aggeliki , Zografos George , Papalois Apostolos
Published: April 2017

Introduction This study compared the excretory effects, the erythropoietin (Epo) and antioxidant drug U-74389G exert on serum creatinine levels through kidneys. 2 preliminary studies were used for this purpose including respectively one drug used in a renal ischemia–reperfusion (IR) protocol of an animal model. The preliminary studies are part of the present work. The subjects were pretreated in preliminary studies but the results of the same subjects were simply compared in the current work.

Materials and methods The serum creatinine levels were evaluated at the 60th reperfusion min (for groups A, C and E) and at the 120th reperfusion min (for groups B, D and F) after IR in the 60 rats. Groups A and B received no drugs, rats from groups C and D were administered with Epo, whereas rats from groups E and F were administered with U-74389G.

Results The first preliminary study recommended a non-significant excretory effect of Epo (p-value = 0.4430 > 0.05) than placebo for serum creatinine levels. The second preliminary study proved a very significant excretory effect of U-74389G (p-value = 0.0005 < 0.05) than placebo for serum creatinine levels. These 2 studies were co-evaluated since they came from the same experimental setting. The outcome of the co-evaluation was that U-74389G has at least 5-fold significant excretory action (p-value = 0.0000 < 0.05) than Epo for serum creatinine levels.

Conclusions The U-74389G presents surprising effective excretory potencies for serum creatinine levels maybe of great importance in hemodialysis patients.
The Rise of Organised Brutality
Authors: Malešević Siniša
Published: April 2017

Challenging the prevailing belief that organised violence is experiencing historically continuous decline, this book provides an in-depth sociological analysis that shows organised violence is, in fact, on the rise. Malešević demonstrates that violence is determined by organisational capacity, ideological penetration and micro-solidarity, rather than biological tendencies, meaning that despite pre-modern societies being exposed to spectacles of cruelty and torture, such societies had no organisational means to systematically slaughter millions of individuals. Malešević suggests that violence should not be analysed as just an event or process, but also via changing perceptions of those events and processes, and by linking this to broader social transformations on the inter-polity and inter-group levels he makes his key argument that organised violence has proliferated. Focusing on wars, revolutions, genocides and terrorism, this book shows how modern social organisations utilise ideology and micro-solidarity to mobilise public support for mass scale violence.
The Late Sigmund Freud
Authors: Dufresne Todd
Published: April 2017

Freud is best remembered for two applied works on society, The Future of an Illusion and Civilization and its Discontents. Yet the works of the final period are routinely denigrated as merely supplemental to the earlier, more fundamental 'discoveries' of the unconscious and dream interpretation. In fact, the 'cultural Freud' is sometimes considered an embarrassment to psychoanalysis. Dufresne argues that the late Freud, as brilliant as ever, was actually revealing the true meaning of his life's work. And so while The Future of an Illusion, Civilization and its Discontents, and his final work Moses and Monotheism may be embarrassing to some, they validate beliefs that Freud always held - including the psychobiology that provides the missing link between the individual psychology of the early period and the psychoanalysis of culture of the final period. The result is a lively, balanced, and scholarly defense of the late Freud that doubles as a major reassessment of psychoanalysis of interest to all readers of Freud.
Ballasting the Hanse: Baltoscandian Erratic Cobbles in the Later Medieval Port Landscape of Bruges
Authors: De Clercq Wim , Dreesen Roland , Dumolyn Jan , Leloup Ward , Trachet Jan
Published: April 2017

The discovery of a remarkable group of vividly coloured rounded cobbles in the fields and monuments of the later medieval outports of Bruges has initiated a multi-disciplinary investigation into their function, provenance, and wider economic meaning. Geological analyses demonstrate that the stones are ballast of exotic lithological nature. A substantial number consist of glacial erratics collected from cobble beaches in the Baltoscandian area. Another group can be traced to north-eastern British coasts. The clustering of stones at Hoeke has drawn particular attention to the Hanseatic connection with Bruges and to the small harbour town of Hoeke, which hosted the staple of stockfish and various other Hanseatic activities. This article contributes to the discussion of ballast stones as a meaningful archaeological object category, especially when studied in a broader methodological context including archaeological, geological, and historical research.
Gustav Bayerle 1931–2016
Authors: Howard Douglas
Published: April 2017

Gustav Bayerle died on 12 October 2016 in San Jose, California, at the age of 85. A refugee immigrant to the United States after the 1956 Hungarian revolution, Dr. Bayerle was a longtime faculty member and department chair at Indiana University. He was respected for his scholarship, his mentoring of students, and his leadership within the Turkish Studies Association of North America.
Changes in serum phosphate and potassium and their effects on mortality in malnourished African HIV-infected adults starting antiretroviral therapy and given vitamins and minerals in lipid-based nutritional supplements: secondary analysis from the Nutritional Support for African Adults Starting Antiretroviral Therapy (NUSTART) trial
Authors: Rehman Andrea Mary , Woodd Susannah Louise , Heimburger Douglas Corbett , Koethe John Robert , Friis Henrik , PrayGod George , Kasonka Lackson , Kelly Paul , Filteau Suzanne
Published: April 2017

Malnourished HIV-infected patients starting antiretroviral therapy (ART) are at high risk of early mortality, some of which may be attributed to altered electrolyte metabolism. We used data from a randomised controlled trial of electrolyte-enriched lipid-based nutritional supplements to assess the association of baseline and time-varying serum phosphate and K concentrations with mortality within the first 12 weeks after starting ART. Baseline phosphate results were available from 1764 patients and there were 9096 subsequent serum phosphate measurements, a median of 6 per patient. For serum K there were 1701 baseline and 8773 subsequent measures, a median of 6 per patient. Abnormally high or low serum phosphate was more common than high or low serum K. Controlling for other factors found to affect mortality in this cohort, low phosphate which had not changed from the previous time interval was associated with increased mortality; the same was not true for high phosphate or for high or low K. Both increases and decreases in serum electrolytes from the previous time interval were generally associated with increased mortality, particularly in the electrolyte-supplemented group. The results suggest that changes in serum electrolytes, largely irrespective of the starting point and the direction of change, were more strongly associated with mortality than were absolute electrolyte levels. Although K and phosphate are required for tissue deposition during recovery from malnutrition, further studies are needed to determine whether specific supplements exacerbate physiologically adverse shifts in electrolyte levels during nutritional rehabilitation of ill malnourished HIV patients.
BLOOD-COLOURED SWANS: HOR.CARM.4.1.10 AND HOMER'S PURPLE DEATH
Authors: Librán-Moreno Miryam
Published: April 2017

InCarm.4.1 Horace asks Venus to stop waging war against him, who is now over fifty (1–7), and suggests that she should set her aim instead on Paulus Maximus, a young and passionate nobleman who will be happy to obey Venus' orders (9–20).
Arcus Divi Constantini: An Architectural Analysis and Chronological Proposal for the Arch of Janus in the Forum Boarium in Rome
Authors: Mateos Pedro , Pizzo Antonio , Ventura Ángel
Published: April 2017

In this article we present a new study of the Arch of Janus, analysing previously unpublished aspects of its architecture and chronology based on new data obtained from a recent research project. This study provides the first complete planimetric view of the monument, together with a stratigraphic reading of the structure, evaluating the different elements of spolia that were re-used in its construction. Also, the discovery of a new inscription that was re-used in building the arch finally confirms that it dates from the period of Constantius II (a.d. 357). Finally, we present a proposal for the reconstruction of the dedicatory inscription of the arch, preserved in the nearby church of San Giorgio al Velabro.
Surgical management of postoperative ductal aneurysm: a case report
Authors: Boutayeb Alaae , Mahfoudi Loubna , Moughil Said
Published: April 2017

We report the case of 24-year-old woman who presented with ductal aneurysm 7 years after a triple ligation of a patent ductus arteriosus. She underwent successful repair through median sternotomy and under moderate hypothermic circulatory arrest and selective cerebral perfusion.
Prevalence and composition of CHD at different altitudes in Tibet: a cross-sectional study
Authors: Zheng Jian-Yong , Qiu Yi-Gang , Li Dong-Tao , He Jiang-Chun , Chen Yu , Cao Yi , Liu Ying-Ming , Li Xian-Feng , Chi Hai-Tao , Li Tian-Chang
Published: April 2017

Background

The prevalence of CHD has been well described worldwide except in Tibet. This study aimed to illustrate the prevalence and composition of CHD in Tibetan children according to altitude.

Methods and results

In the first part, we prospectively recruited 7088 unselected Tibetan children (4–17 years) from south-west Tibet. The total prevalence of CHD increased from 4.6/1000 below 4200 m to 13.4/1000 above 4700 m, with a female-to-male ratio of 1.3:3.1. The total prevalence and female prevalence of patent ductus arteriosus increased more than 10-fold. Females living above 4700 m had exceptionally high prevalence of patent ductus arteriosus (14.9/1000). The prevalence of atrial septal defect was comparable among different altitudes (3.3–3.8/1000). The prevalence of ventricular septal defect was 1.3/1000 below 4700 m, and no cases were found above this altitude. In the second part, we retrospectively reviewed the clinical data of 383 CHD children in Tibet and 73 children at lower altitudes. The percentage of isolated ventricular septal defect decreased from 54.8 to 3.1%, and the percentage of isolated patent ductus arteriosus increased from 8.2 to 68.4% with elevation. Children living below 4200 m (10.4–13.7%) had a larger proportion of complex CHD than those above this altitude (2.0–3.1%). Of the 20 Tibetan children with complex CHD, 14 (70.0%) lived below 4200 m.

Conclusions

A wide variation in CHD prevalence and composition existed in Tibetan children among different altitudes.
Severe cardiac involvement in Gaucher type IIIC: a case report and review of the literature
Authors: Kör Yılmaz , Keskin Mehmet , Başpınar Osman
Published: April 2017

Gaucher disease is an autosomal-recessive lysosomal storage disease characterised by the accumulation of glucocerebroside in macrophages; it is caused by mutations in glucocerebrosidase gene-1 in many organ tissues such as the liver, spleen, and bone marrow. Its different clinical subtypes, according to the presence and severity of neurological symptoms, are as follows: type I, non-neuronopathic (95%); type II, acute neuronopathic; and type III, chronic neuronopathic. Type IIIC is a rare subgroup characterised by cardiovascular involvement as well as eye-movement disorders and late-onset neurological symptoms. In such cases, homozygous D409H is the most frequently detected mutation. In this article, we report the case of a patient, aged 15 years and 8 months, with complaints of syncope and a diagnosis of type IIIC Gaucher disease.
Simulation-based capital models: testing, justifying and communicating choices. A report from the life aggregation and simulation techniques working party
Authors: Androschuck T. , Gibbs S. , Katrakis N. , Lau J. , Oram S. , Raddall P. , Semchyshyn L. , Stevenson D. , Waters J.
Published: April 2017

The development of an economic capital model requires a decision to be made regarding how to aggregate capital requirements for the individual risk factors while taking into account the effects of diversification. Under the Individual Capital Adequacy Standards framework, UK life insurers have commonly adopted a correlation matrix approach due to its simplicity and ease in communication to the stakeholders involved, adjusting the result, where appropriate, to allow for non-linear interactions. The regulatory requirements of Solvency II have been one of the principal drivers leading to an increased use of more sophisticated aggregation techniques in economic capital models. This paper focusses on a simulation-based approach to the aggregation of capital requirements using copulas and proxy models. It describes the practical challenges in parameterising a copula including how allowance may be made for tail dependence. It also covers the challenges associated with fitting and validating a proxy model. In particular, the paper outlines how insurers could test, communicate and justify the choices made through the use of some examples.
The 5-Factor Disgust Scale
Authors: Eickmeier Kathrin , Hoffmann Lisa , Banse Rainer
Published: April 2017

Abstract. For years, disgust was conceptualized as a disease-avoidance mechanism. However, research shows that socio-moral or sexual transgressions elicit disgust, too. Until now, no German-language disgust scale has covered all disgust factors discussed in the literature. Here we present an economic Five-Factor Disgust Scale (5-FES; Fünf-Faktoren Ekelskala) along with empirical evidence from three studies corroborating its reliability and validity. Two well-established disgust questionnaires were combined and extended with other disgust-relevant items. Using item reduction and exploratory factor analysis, death-related, moral, food-related, sexual, and pathogen disgust emerged as distinct factors (Study 1: N = 456). Confirmatory factor analysis with two large samples (Study 2: N = 997 and N = 405) demonstrated a good fit of the correlated five-factor solution. The 5-FES correlated weakly with neuroticism, anxiety, and social desirability. A high negative correlation between sexual disgust and sexual openness emerged. Criterion validity was shown using self-reported behaviors (Study 3: N = 203). With food-related disgust comprising items about non-spoiled but exotic foods, a new disgust domain emerged. Results indicate that the 5-FES is a comprehensive and psychometrically sound German-language instrument for the differentiated assessment of disgust propensity.
Galectin-1 inhibition attenuates profibrotic signaling in hypoxia-induced pulmonary fibrosis
Authors: Kathiriya Jaymin J , Nakra Niyati , Nixon Jenna , Patel Puja S , Vaghasiya Vijay , Alhassani Ahmed , Tian Zhi , Allen-Gipson Diane , Davé Vrushank
Published: April 2017

Idiopathic pulmonary fibrosis (IPF) is characterized by lung remodeling arising from epithelial injury, aberrant fibroblast growth, and excessive deposition of extracellular matrix. Repeated epithelial injury elicits abnormal wound repair and lung remodeling, often associated with alveolar collapse and edema, leading to focal hypoxia. Here, we demonstrate that hypoxia is a physiological insult that contributes to pulmonary fibrosis (PF) and define its molecular roles in profibrotic activation of lung epithelial cells. Hypoxia increased transcription of profibrotic genes and altered the proteomic signatures of lung epithelial cells. Network analysis of the hypoxic epithelial proteome revealed a crosstalk between transforming growth factor-β1 and FAK1 (focal adhesion kinase-1) signaling, which regulated transcription of galectin-1, a profibrotic molecule. Galectin-1 physically interacted with and activated FAK1 in lung epithelial cells. We developed a novel model of exacerbated PF wherein hypoxia, as a secondary insult, caused PF in mice injured with subclinical levels of bleomycin. Hypoxia elevated expression of phosphorylated FAK1, galectin-1, and α-smooth muscle actin and reduced caspase-3 activation, suggesting aberrant injury repair. Galectin-1 inhibition caused apoptosis in the lung parenchyma and reduced FAK1 activation, preventing the development of hypoxia-induced PF. Galectin-1 inhibition also attenuated fibrosis-associated lung function decline. Further, galectin-1 transcript levels were increased in the lungs of IPF patients. In summary, we have identified a profibrotic role of galectin-1 in hypoxia signaling driving PF.
Determining the bacterial cell biology of Planctomycetes
Authors: Boedeker Christian , Schüler Margarete , Reintjes Greta , Jeske Olga , van Teeseling Muriel C. F. , Jogler Mareike , Rast Patrick , Borchert Daniela , Devos Damien P. , Kucklick Martin , Schaffer Miroslava , Kolter Roberto , van Niftrik Laura , Engelmann Susanne , Amann Rudolf , Rohde Manfred , Engelhardt Harald , Jogler Christian
Published: April 2017

Bacteria of the phylum Planctomycetes have been previously reported to possess several features that are typical of eukaryotes, such as cytosolic compartmentalization and endocytosis-like macromolecule uptake. However, recent evidence points towards a Gram-negative cell plan for Planctomycetes, although in-depth experimental analysis has been hampered by insufficient genetic tools. Here we develop methods for expression of fluorescent proteins and for gene deletion in a model planctomycete, Planctopirus limnophila, to analyse its cell organization in detail. Super-resolution light microscopy of mutants, cryo-electron tomography, bioinformatic predictions and proteomic analyses support an altered Gram-negative cell plan for Planctomycetes, including a defined outer membrane, a periplasmic space that can be greatly enlarged and convoluted, and an energized cytoplasmic membrane. These conclusions are further supported by experiments performed with two other Planctomycetes, Gemmata obscuriglobus and Rhodopirellula baltica. We also provide experimental evidence that is inconsistent with endocytosis-like macromolecule uptake; instead, extracellular macromolecules can be taken up and accumulate in the periplasmic space through unclear mechanisms.
Transient birefringence of liquids induced by terahertz electric-field torque on permanent molecular dipoles
Authors: Sajadi Mohsen , Wolf Martin , Kampfrath Tobias
Published: April 2017

Collective low-frequency molecular motions have large impact on chemical reactions and structural relaxation in liquids. So far, these modes have mostly been accessed indirectly by off-resonant optical pulses. Here, we provide evidence that intense terahertz (THz) pulses can resonantly excite reorientational-librational modes of aprotic and strongly polar liquids through coupling to the permanent molecular dipole moments. We observe a significantly enhanced response because the transient optical birefringence is up to an order of magnitude higher than obtained with optical excitation. Frequency-dependent measurements and a simple analytical model indicate that the enhancement arises from resonantly driven librations and their coupling to reorientational motion, assisted by the pump field and/or a cage translational mode. Our results open up the path to applications such as efficient molecular alignment, enhanced transient Kerr signals and systematic resonant nonlinear THz spectroscopy of the coupling between intermolecular modes in liquids.
Stability of the frequent COPD exacerbator in the general population: A Danish nationwide register-based study
Authors: Reilev Mette , Lykkegaard Jesper , Halling Anders , Vestbo Jørgen , Søndergaard Jens , Pottegård Anton
Published: April 2017

Exacerbation frequency is central in treatment strategies for chronic obstructive pulmonary disease. However, whether chronic obstructive pulmonary disease patients from the general population with frequent exacerbations continue to have frequent exacerbations over an extended period of time is currently unknown. In this study, we aimed to investigate the stability of the frequent exacerbator in a population-based setting. To this end, we conducted a nationwide register-based descriptive study with a 10-year follow-up period of chronic obstructive pulmonary disease patients with at least one medically treated exacerbation in 2003. Each subsequent year, we divided the population into frequent, infrequent and non-exacerbators and quantified the flow between categories. Further, we estimated the percentage of frequent exacerbators at baseline who stayed in this category each year during a 5-year follow-up. We identified 19,752 patients with chronic obstructive pulmonary disease and an exacerbation in 2003. Thirty percent were frequent exacerbators. Overall, the majority of exacerbators in 2003 were non-exacerbators in the following years (60% in 2004 increasing to 68% in 2012). Approximately half of frequent exacerbators in one year experienced a decrease in exacerbation frequency and had either zero or one exacerbation in the subsequent year. This pattern was stable throughout follow-up. During a 5-year follow-up period, a substantial proportion (42%) of frequent exacerbators in 2003 had no additional years as frequent exacerbators, while the minority (6%) remained in this category each year. In conclusion, the rate of exacerbations shows considerable variation over time among chronic obstructive pulmonary disease patients in the general population. This might hold implications for chronic obstructive pulmonary disease treatment guidelines and their practical application.
Progressive slowdown/prevention of cellular senescence by CD9-targeted delivery of rapamycin using lactose-wrapped calcium carbonate nanoparticles
Authors: Thapa Raj Kumar , Nguyen Hanh Thuy , Jeong Jee-Heon , Kim Jae Ryong , Choi Han-Gon , Yong Chul Soon , Kim Jong Oh
Published: April 2017

Cellular senescence, a state of irreversible growth arrest and altered cell function, causes aging-related diseases. Hence, treatment modalities that could target aging cells would provide a robust therapeutic avenue. Herein, for the first time, we utilized CD9 receptors (overexpressed in senescent cells) for nanoparticle targeting in addition to the inherent β-galactosidase activity. In our study, CD9 monoclonal antibody-conjugated lactose-wrapped calcium carbonate nanoparticles loaded with rapamycin (CD9-Lac/CaCO3/Rapa) were prepared for targeted rapamycin delivery to senescent cells. The nanoparticles exhibited an appropriate particle size (~130 nm) with high drug-loading capacity (~20%). In vitro drug release was enhanced in the presence of β-galactosidase suggesting potential cargo drug delivery to the senescent cells. Furthermore, CD9-Lac/CaCO3/Rapa exhibited high uptake and anti-senescence effects (reduced β-galactosidase and p53/p21/CD9/cyclin D1 expression, reduced population doubling time, enhanced cell proliferation and migration, and prevention of cell cycle arrest) in old human dermal fibroblasts. Importantly, CD9-Lac/CaCO3/Rapa significantly improved the proliferation capability of old cells as suggested by BrdU staining along with significant reductions in senescence-associated secretory phenotypes (IL-6 and IL-1β) (P < 0.05). Altogether, our findings suggest the potential applicability of CD9-Lac/CaCO3/Rapa in targeted treatment of senescence.
Comprehensive mapping of the Helicobacter pylori NikR regulon provides new insights in bacterial nickel responses
Authors: Vannini Andrea , Pinatel Eva , Costantini Paolo Emidio , Pelliciari Simone , Roncarati Davide , Puccio Simone , De Bellis Gianluca , Peano Clelia , Danielli Alberto
Published: April 2017

Nickel homeostasis is important for pathogenic and ureolytic bacteria, which use this metal ion as enzymatic cofactor. For example, in the human pathogen Helicobacter pylori an optimal balance between nickel uptake and incorporation in metallo-enzymes is fundamental for colonization of the host. Nickel is also used as cofactor to modulate DNA binding of the NikR regulator, which controls transcription of genes involved in nickel trafficking or infection in many bacteria. Accordingly, there is much interest in a systematic characterization of NikR regulation. Herein we use H. pylori as a model to integrate RNA-seq and ChIP-seq data demonstrating that NikR not only regulates metal-ion transporters but also virulence factors, non-coding RNAs, as well as toxin-antitoxin systems in response to nickel stimulation. Altogether, results provide new insights into the pathobiology of H. pylori and contribute to understand the responses to nickel in other bacteria.
Emergence of complex behavior in pili-based motility in early stages of P. aeruginosa surface adaptation
Authors: Brill-Karniely Yifat , Jin Fan , Wong Gerard C. L. , Frenkel Daan , Dobnikar Jure
Published: April 2017

Pseudomonas aeruginosa move across surfaces by using multiple Type IV Pili (TFP), motorized appendages capable of force generation via linear extension/retraction cycles, to generate surface motions collectively known as twitching motility. Pseudomonas cells arrive at a surface with low levels of piliation and TFP activity, which both progressively increase as the cells sense the presence of a surface. At present, it is not clear how twitching motility emerges from these initial minimal conditions. Here, we build a simple model for TFP-driven surface motility without complications from viscous and solid friction on surfaces. We discover the unanticipated structural requirement that TFP motors need to have a minimal amount of effective angular rigidity in order for cells to perform the various classes of experimentally-observed motions. Moreover, a surprisingly small number of TFP are needed to recapitulate movement signatures associated with twitching: Two TFP can already produce movements reminiscent of recently observed slingshot type motion. Interestingly, jerky slingshot motions characteristic of twitching motility comprise the transition region between different types of observed crawling behavior in the dynamical phase diagram, such as self-trapped localized motion, 2-D diffusive exploration, and super-diffusive persistent motion.
Light Control of Ferromagnetism in ZnO Films on Pt Substrate at Room Temperature
Authors: Xie Jihao , Qin Hongwei , Hao Yanming , Cheng Bin , Liu Weikang , Liu Liang , Ren Shaoqing , Zhou Guangjun , Ji Ziwu , Hu Jifan
Published: April 2017

The control of ferromagnetism by light at room temperature is essential for the development of some optical-magnetic coupling devices, data storage and quantum computation techniques. In the present work, we demonstrate that the ferromagnetism of a semiconducting ZnO film on Pt substrate can be controlled by nonpolarized ultraviolet or violet light. The illumination of light with sufficiently high frequency photons could excite photogenerated electron-hole pairs in the semiconducting ZnO film. The amount of oxygen vacancies in the ZnO film and the appearance of built-in electric field due to the heterostructured ZnO/Pt may play important roles in the light-induced changes in the ferromagnetism of the ZnO film.
Biomimetic supercontainers for size-selective electrochemical sensing of molecular ions
Authors: Netzer Nathan L. , Must Indrek , Qiao Yupu , Zhang Shi-Li , Wang Zhenqiang , Zhang Zhen
Published: April 2017

New ionophores are essential for advancing the art of selective ion sensing. Metal-organic supercontainers (MOSCs), a new family of biomimetic coordination capsules designed using sulfonylcalix[4]arenes as container precursors, are known for their tunable molecular recognition capabilities towards an array of guests. Herein, we demonstrate the use of MOSCs as a new class of size-selective ionophores dedicated to electrochemical sensing of molecular ions. Specifically, a MOSC molecule with its cavities matching the size of methylene blue (MB+), a versatile organic molecule used for bio-recognition, was incorporated into a polymeric mixed-matrix membrane and used as an ion-selective electrode. This MOSC-incorporated electrode showed a near-Nernstian potentiometric response to MB+ in the nano- to micro-molar range. The exceptional size-selectivity was also evident through contrast studies. To demonstrate the practical utility of our approach, a simulated wastewater experiment was conducted using water from the Fyris River (Sweden). It not only showed a near-Nernstian response to MB+ but also revealed a possible method for potentiometric titration of the redox indicator. Our study thus represents a new paradigm for the rational design of ionophores that can rapidly and precisely monitor molecular ions relevant to environmental, biomedical, and other related areas.
Correction: Corrigendum: Frequency-phase analysis of resting-state functional MRI
Authors: Goelman Gadi , Dan Rotem , Růžička Filip , Bezdicek Ondrej , Růžička Evžen , Roth Jan , Vymazal Josef , Jech Robert
Published: April 2017

Scientific Reports 7: Article number: 43743; published online: 08 March 2017; updated: 10 April 2017 This Article contains errors in the Acknowledgements section. “This work was supported by a Czech-Israel cooperative research grant issued by the Israel Ministry of science (grant number 3–9814) and the Czech Ministry of education (Grant LH13256 VES13-KontaktII).
Production and glyco-engineering of immunomodulatory helminth glycoproteins in plants
Authors: Wilbers Ruud H. P. , Westerhof Lotte B. , van Noort Kim , Obieglo Katja , Driessen Nicole N. , Everts Bart , Gringhuis Sonja I. , Schramm Gabriele , Goverse Aska , Smant Geert , Bakker Jaap , Smits Hermelijn H. , Yazdanbakhsh Maria , Schots Arjen , Hokke Cornelis H.
Published: April 2017

Helminth parasites control host-immune responses by secreting immunomodulatory glycoproteins. Clinical trials and mouse model studies have demonstrated the potential of helminth-derived glycoproteins for the treatment of immune-related diseases, like allergies and autoimmune diseases. Studies are however hampered by the limited availability of native parasite-derived proteins. Moreover, recombinant protein production systems have thus far been unable to reconstitute helminth-like glycosylation essential for the functionality of some helminth glycoproteins. Here we exploited the flexibility of the N-glycosylation machinery of plants to reconstruct the helminth glycoproteins omega-1 and kappa-5, two major constituents of immunomodulatory Schistosoma mansoni soluble egg antigens. Fine-tuning transient co-expression of specific glycosyltransferases in Nicotiana benthamiana enabled the synthesis of Lewis X (LeX) and LDN/LDN-F glycan motifs as found on natural omega-1 and kappa-5, respectively. In vitro and in vivo evaluation of the introduction of native LeX motifs on plant-produced omega-1 confirmed that LeX on omega-1 contributes to the glycoprotein’s Th2-inducing properties. These data indicate that mimicking the complex carbohydrate structures of helminths in plants is a promising strategy to allow targeted evaluation of therapeutic glycoproteins for the treatment of inflammatory disorders. In addition, our results offer perspectives for the development of effective anti-helminthic vaccines by reconstructing native parasite glycoprotein antigens.
Origin of reduced magnetization and domain formation in small magnetite nanoparticles
Authors: Nedelkoski Zlatko , Kepaptsoglou Demie , Lari Leonardo , Wen Tianlong , Booth Ryan A. , Oberdick Samuel D. , Galindo Pedro L. , Ramasse Quentin M. , Evans Richard F. L. , Majetich Sara , Lazarov Vlado K.
Published: April 2017

The structural, chemical, and magnetic properties of magnetite nanoparticles are compared. Aberration corrected scanning transmission electron microscopy reveals the prevalence of antiphase boundaries in nanoparticles that have significantly reduced magnetization, relative to the bulk. Atomistic magnetic modelling of nanoparticles with and without these defects reveals the origin of the reduced moment. Strong antiferromagnetic interactions across antiphase boundaries support multiple magnetic domains even in particles as small as 12–14 nm.
Involvement of a velvet protein ClVelB in the regulation of vegetative differentiation, oxidative stress response, secondary metabolism, and virulence in Curvularia lunata
Authors: Gao Jin-Xin , Yu Chuan-Jin , Wang Meng , Sun Jia-Nan , Li Ya-Qian , Chen Jie
Published: April 2017

The ortholog ofAspergillus nidulansVelB, which is known as ClVelB, was studied to gain a broader insight into the functions of a velvet protein inCurvularia lunata. With the expected common and specific functions of ClVelB, the deletion ofclvelBresults in similar though not identical phenotypes. The pathogenicity assays revealed that ΔClVelB was impaired in colonizing the host tissue, which corresponds to the finding that ClVelB controls the production of conidia and the methyl 5-(hydroxymethyl) furan-2-carboxylate toxin inC. lunata. However, the deletion ofclvelBled to the increase in aerial hyphae and melanin formation. In addition, ΔClVelB showed a decreased sensitivity to iprodione and fludioxonil fungicides and a decreased resistance to cell wall-damaging agents and osmotic stress and tolerance to H2O2. The ultrastructural analysis indicated that the cell wall of ΔClVelB became thinner, which agrees with the finding that the accumulated level of glycerol in ΔClVelB is lower than the wild-type. Furthermore, the interaction of ClVelB with ClVeA and ClVosA was identified in the present research through the yeast two-hybrid and bimolecular fluorescence complementation assays. Results indicate that ClVelB plays a vital role in the regulation of various cellular processes inC. lunata.
Association of C-Type Lectin Mincle with FcεRIβγ Subunits Leads to Functional Activation of RBL-2H3 Cells through Syk
Authors: Honjoh Chisato , Chihara Kazuyasu , Yoshiki Hatsumi , Yamauchi Shota , Takeuchi Kenji , Kato Yuji , Hida Yukio , Ishizuka Tamotsu , Sada Kiyonao
Published: April 2017

Macrophage-inducible C-type lectin (Mincle) interacts with the γ-subunit of high-affinity IgE receptor (FcεRIγ) and activates Syk by recognizing its specific ligand, trehalose-6,6′-dimycolate, a glycolipid produced byMycobacterium tuberculosis. It has been suggested that mast cells participate in the immune defense against pathogenic microbes includingM. tuberculosis, although the functions are still uncertain. In this study, we examined the Mincle-mediated signaling pathway and cellular responses using RBL-2H3 cells. Mincle formed a protein complex with not only FcεRIγ but also FcεRIβ in a stable cell line expressing myc-tagged Mincle. In addition, engagement of Mincle increased the levels of protein tyrosine phosphorylation and ERK phosphorylation. A pull-down assay demonstrated that cross-linking of Mincle induced binding of FcεRIβγ subunits to the Src homology 2 domain of Syk. Pharmacological and genetic studies indicated that activation of Syk was critical for Mincle-mediated activation of phospholipase Cγ2, leading to the activation of ERK and nuclear factor of activated T cells. Moreover, engagement of Mincle efficiently induced up-regulation of characteristic mast cell genes in addition to degranulation. Taken together, our present results suggest that mast cells contribute to Mincle-mediated immunity through Syk activation triggered by association with the FcεRIβγ complex.