bluuebunny/crossref_metadata_2025 huggingface dataset:
Analytical model for predicting the performance of arbitrary size and layout wind farms
Authors: Yang Xiaolei , Sotiropoulos Fotis
Published: August 2015

A simple engineering model for predicting wind farm performance is presented, which is applicable to wind farms of arbitrary size and turbine layout. For modeling the interaction of wind farm with the atmospheric boundary layer (ABL), the wind farm is represented as added roughness elements. The wind speed behind each turbine is calculated using a kinematic model, in which the friction velocity and the wind speed outside the turbine wake, constructed based on the wind farm‐ABL interaction model, are employed to estimate the wake expansion rate in the crosswind direction and the maximum wind speed that can be recovered within the turbine wake, respectively. Validation of the model is carried out by comparing the model predictions with the measurements from wind tunnel experiments and the Horns Rev wind farm. For all validation cases, satisfactory agreement is obtained between model predictions and experimental data. Copyright © 2015 John Wiley & Sons, Ltd.
Superposition of vortex cylinders for steady and unsteady simulation of rotors of finite tip‐speed ratio
Authors: Branlard E. , Gaunaa M.
Published: August 2015

Joukowski introduced in 1912 a helical vortex model to represent the vorticity of a rotor and its wake. For an infinite number of blades but finite tip‐speed ratio, the model consists of a vortex cylinder of longitudinal and tangential vorticity, a root vortex and a bound vortex disk. A superposition of cylinders is used in this paper to model rotors of radially varying circulation. The relations required to form a consistent system of cylinders are derived. The model contains a term which is not accounted for in the standard blade element momentum (BEM) algorithm. This term is identified as the contribution from the pressure drop due to the wake rotation. The BEM algorithm can be corrected to account for this effect. Unlike previous work on the topic, the contribution is derived for a radially varying circulation. A high‐thrust correction is also presented to extend the model. The optimal power coefficient obtained with this model for the constant circulation rotor is assessed and compared with that of existing solutions. Results from prescribed thrust distributions are compared with that of actuator disk simulations. Steady simulations are performed to compare with the BEM algorithm. The model is also applied to compute the velocity field in the entire domain and perform unsteady simulations. Results for an unsteady simulation corresponding to a pitch change of the rotor is used to compare the model with measurements and a BEM code with a dynamic inflow model. Copyright © 2015 John Wiley & Sons, Ltd.
A Randomised Assessment of Trainee Doctors’ Understanding and Interpretation of Diagnostic Test Results
Authors: Parker V. L. , Ritchie J. E. , Drake T. M. , Hookham J. , Balasubramanian S. P.
Published: August 2015

Introduction

Doctors are unfamiliar with diagnostic accuracy parameters despite routine clinical use of diagnostic tests to estimate disease probability.

Methods

Trainee doctors completed a questionnaire exploring their understanding of diagnostic accuracy parameters; ability to calculate post‐test probability of a common surgical condition (appendicitis) and their perceptions on training in this area. To determine whether the method of information provision altered interpretation, trainees were randomised to receive diagnostic test information in three ways: positive test only; positive test with specificity and sensitivity; positive test with positive likelihood ratio in layman terms.

Results

326 candidates were recruited across 30 training sessions. Trainees scored a median of three out of seven in questions concerning knowledge of diagnostic accuracy parameters. This was affected neither by training level (P = 0.737) nor by experience in acute general surgery (P = 0.738). 30 (11.8 %) candidates correctly estimated post‐test probability; with 86.6 % overestimating this value. Neither level of training (P = 0.180) nor experience (P = 0.242) influenced the accuracy of the estimate. Provision of the ultrasound scan results in different ways was not associated with likelihood of a correct response (P = 0.857).

Conclusion

This study highlights the deficiencies in trainee doctors’ understanding and application of diagnostic tests results. Most trainees over‐estimated disease probability, increasing the risk of unnecessary intervention and treatment.
CLA‐Rich Soy Oil Shortening Production and Characterization
Authors: Mayfield Sarah , Proctor Andrew , Shinn Sara E. , Dewettinck Koen , Patel Ashok R.
Published: August 2015

Conjugated linoleic acid‐rich soy oil (CLARSO) has been shown to have numerous health benefits, including anti‐obesity and anti‐carcinogenic properties. This oil was previously used to produce CLA‐rich margarine that showed physical characteristics similar to commercially available margarine. The objective of this study was to produce CLA‐rich shortening and analyze its physical properties relative to commercially available shortenings and soy oil control shortenings. The shortenings were prepared and their rheology, thermal behavior, and solid fat content (SFC) were determined and compared to the commercial samples. The CLA‐rich shortening samples showed similar rheological properties to the commercial samples and showed a better consistency (more solid‐like behavior) compared to the soy oil control samples. In addition, the CLA‐rich shortenings also have a higher SFC (% SFC) as well as higher latent heat of crystallization and melting than the soy oil controls indicating a comparatively higher crystalline fraction. Thus, CLARSO produced firmer shortenings than did conventional soy oil by interacting with the crystallizing stearin fraction and consequently increasing the crystalline mass fraction without significantly altering the microstructure kinetics of solid fat crystallization.
Changes in Volatile Compounds of Black Cumin Oil and Hazelnut Oil by Microwave Heating Process
Authors: Kiralan Mustafa , Kiralan S. Sezer
Published: August 2015

Black cumin and hazelnut oils were subjected to a heating process in a microwave oven for a duration of 2, 4, 6 and 8 min at a constant frequency of 2450 MHz and a power of 0.45 kW. The ultraviolet absorption and volatile products of the oils were investigated in detail during the processes. The experimental evidences obtained show that K232 and K270 parameters reach values of 4.69 and 1.30 for black cumin oil, 3.22 and 1.75 for hazelnut oil, respectively with the increment of heating time. The headspace SPME method was used to analyze volatile compounds extracted from black cumin and hazelnut oils being exposed to the microwave heating process. The SPME–GC/MS method allowed the detection of 17 identified volatile compounds (hexanal, α‐thujene, α‐pinene, sabinene, β‐pinene, 2‐heptenal, α‐terpinene, limonene, p‐cymene, γ‐terpinene, E‐2‐octenal, nonanal, 4‐terpineol, thymoquinone, E,E‐2,4‐decadienal, α‐longipinene and isolongifolene) in black cumin oils. Of the products, hexanal, 2‐heptenal, E‐2‐octenal, nonanal and E,E‐2,4‐decadienal were determined to be the predominant volatile oxidation products. In fact, the hexanal was found as a major volatile oxidation compound and reached a local maximum point of 7.41 × 106 AU at the end of heating. On the other hand, only 8 volatile oxidation products (hexanal, heptanal, 2‐heptenal, nonanal, E‐2‐decenal, E,Z‐2,4‐decadienal, E,E‐2,4‐decadienal and E‐2‐tridecenal) were identified in hazelnut oils as a consequence of the heating process. Based on the experimental evidence observed, it is reasonable to conclude that the nonanal content dramatically increased at the end of heating and reached a value of 9.22 × 106 AU.
Cortical thickness predicts the first onset of major depression in adolescence
Authors: Foland‐Ross Lara C. , Sacchet Matthew D. , Prasad Gautam , Gilbert Brooke , Thompson Paul M. , Gotlib Ian H.
Published: August 2015

Given the increasing prevalence of Major Depressive Disorder and recent advances in preventative treatments for this disorder, an important challenge in pediatric neuroimaging is the early identification of individuals at risk for depression. We examined whether machine learning can be used to predict the onset of depression at the individual level. Thirty‐three never‐disordered adolescents (10–15 years old) underwent structural MRI. Participants were followed for 5 years to monitor the emergence of clinically significant depressive symptoms. We used support vector machines (SVMs) to test whether baseline cortical thickness could reliably distinguish adolescents who develop depression from adolescents who remained free of any Axis I disorder. Accuracies from subsampled cross‐validated classification were used to assess classifier performance. Baseline cortical thickness correctly predicted the future onset of depression with an overall accuracy of 70% (69% sensitivity, 70% specificity; p = 0.021). Examination of SVM feature weights indicated that the right medial orbitofrontal, right precentral, left anterior cingulate, and bilateral insular cortex contributed most strongly to this classification. These findings indicate that cortical gray matter structure can predict the subsequent onset of depression. An important direction for future research is to elucidate mechanisms by which these anomalies in gray matter structure increase risk for developing this disorder.
Midterm renal functions following acute renal infarction
Authors: Ongun Sakir , Bozkurt Ozan , Demir Omer , Cimen Sertac , Aslan Guven
Published: August 2015

The aim of this study was to explore clinical features of renal infarction (RI) that may have a role in diagnosis and treatment in our patient cohort and provide data on midterm renal functions. Medical records of patients with diagnosis of acute RI, established by contrast enhanced computed tomography (CT) and at least 1 year follow‐up data, who were hospitalized in our clinic between 1998 and 2012 were retrospectively reviewed; including descriptive data, clinical signs and symptoms, etiologic factors, laboratory findings, and prescribed treatments. Patients with solitary infarct were treated with acetylsalicylic acid (ASA) only, whereas patients with atrial fibrillation (AF) or multiple or global infarct were treated with anticoagulants. Estimated Glomerular Filtration Rate (eGFR) referring to renal functions was determined by the Modification of Diet in Renal Disease (MDRD) formula. Twenty‐seven renal units of 23 patients with acute RI were identified. The mean age was 59.7 ± 15.7 years. Fourteen patients (60.8%) with RI had atrial fibrillation (AF) as an etiologic factor of which four had concomitant mesenteric ischemia at diagnosis. At presentation, 20 patients (86.9%) had elevated serum lactate dehydrogenase (LDH), 18 patients (78.2%) had leukocytosis, and 16 patients (69.5%) had microscopic hematuria. Two patients with concomitant mesenteric ischemia and AF passed away during follow up. Mean eGFR was 70.8 ± 23.2 mL/min/1.73 m2 at admission and increased to 82.3 ± 23.4 mL/min/1.73 m2 at 1 year follow up. RI should be considered in patients with persistent flank or abdominal pain, particularly if they are at high risk of thromboembolism. Antiplatelet and/or anticoagulant drugs are both effective treatment options according to the amplitude of the infarct for preserving kidney functions.
mTORC1 and DNA‐PKcs as novel molecular determinants of sensitivity to Chk1 inhibition
Authors: Massey Andrew J. , Stephens Peter , Rawlinson Rebecca , McGurk Lauren , Plummer Ruth , Curtin Nicola J.
Published: August 2015

Background:Chk1 inhibitors are currently under clinical evaluation as single agents and in combination with cytotoxic chemotherapy. Understanding determinants of sensitivity and novel combinations is critical for further clinical development.

Potentiation of mTOR inhibitor cytotoxicity by the Chk1 inhibitor V158411 was determined in p53 mutant colon cancer cells. DNA damage response, expression levels of repair proteins, cell cycle effects and the contribution of alternative DSB repair pathways were further evaluated by western blotting and high content analysis.

Results:mTOR inhibitors AZD8055, RAD‐001, rapamycin and BEZ235 induced synergistic cytotoxicity with the Chk1 inhibitor V158411 in p53 mutant colon cancer cells. Reduced FANCD2, RAD51 and RPA70, core proteins in homologous recombination repair (HRR) and interstrand crosslink repair (ICLR), following inhibition of mTOR was associated with increased V158411 induced DSBs and caspase 3‐independent cell death. Dual mTOR and Chk1 inhibition activated DNA‐PKcs. Cells defective in DNA‐PKcs exhibited increased resistance to V158411 with Chk1 expression closely correlated to DNA‐PKcs expression in various types of cancer.

Conclusions:Down regulation of proteins involved in HRR or ICLR by mTOR inhibitors is associated with increased sensitivity of human tumours to Chk1 inhibitors such as V158411. High levels of DNA‐PKcs may be a potential biomarker to stratify patients to Chk1 inhibitor therapy alone or in combination with mTOR inhibitors.
States’ Equality v States’ Power: the Euro-crisis, Inter-state Relations and the Paradox of Domination
Authors: FABBRINI Federico
Published: August 2015

This article examines how the Euro-crisis and responses to it have affected the horizontal relations of power between the EU Member States. It is argued that, whereas the EU institutional system had been designed since its foundation to strike a balance between state equality and state power, the Euro-crisis and the responses to it have increasingly upset this balance. A dynamic of inter-state domination is evidenced by the intergovernmental modes of governance within the European Council, as well as by the legal reforms in salient areas such as economic assistance, financial stabilisation and banking resolution, which have entrenched asymmetries between the states. In this article, it is argued that this dynamic constitutes a worrying development, given the anti-hegemonic nature of the EU integration project, and shows how intergovernmentalism paradoxically caters for powerful Member States. The article ends by considering options for institutional reforms, cautioning against the proposal to parliamentarise the EU and emphasising the potential of a new separation-of-powers system to restore a proper balance between the Member States.
Travauxto the EU Treaties: Preparatory Work as a Source of EU Law
Authors: MIETTINEN Samuli , KETTUNEN Merita
Published: August 2015

The Court of Justice of the European Union has historically rejected references to preparatory work in the interpretation of EU Treaties. However, the preparatory work for the EURATOM, Maastricht, and Constitutional Treaties have played a role in recent judgments. The ‘explanations’ to the Charter of Fundamental Rights are expressly approved in the current Treaties. We examine the emerging case law on preparatory work. Reference to the drafters’ intent does not necessarily support dynamic interpretation, and may potentially even ossify historical interpretations. Even if the consequence of their introduction is a conservative interpretation, their use raises questions of transparency and democracy, and complicates the already difficult task of interpreting the EU constitution.
TOPOLOGY ON COHOMOLOGY OF LOCAL FIELDS
Authors: ČESNAVIČIUS KĘSTUTIS
Published: August 2015

Arithmetic duality theorems over a local field$k$are delicate to prove if$\text{char}\,k>0$. In this case, the proofs often exploit topologies carried by the cohomology groups$H^{n}(k,G)$for commutative finite type$k$-group schemes$G$. These ‘Čech topologies’, defined using Čech cohomology, are impractical due to the lack of proofs of their basic properties, such as continuity of connecting maps in long exact sequences. We propose another way to topologize$H^{n}(k,G)$: in the key case when$n=1$, identify$H^{1}(k,G)$with the set of isomorphism classes of objects of the groupoid of$k$-points of the classifying stack$\mathbf{B}G$and invoke Moret-Bailly’s general method of topologizing$k$-points of locally of finite type$k$-algebraic stacks. Geometric arguments prove that these ‘classifying stack topologies’ enjoy the properties expected from the Čech topologies. With this as the key input, we prove that the Čech and the classifying stack topologies actually agree. The expected properties of the Čech topologies follow, and these properties streamline a number of arithmetic duality proofs given elsewhere.
Double seal technique to obliterate the eustachian tube orifice: a novel method for the treatment of recalcitrant cerebrospinal fluid leak
Authors: Taghi A S , Bentley M , Kuchai R , Saleh H A
Published: August 2015

Objective:

To demonstrate a novel and effective surgical technique for the treatment of refractory cerebrospinal fluid rhinorrhoea after skull base surgery. The novel surgical technique is described and the findings of a review of relevant world English-language publications are reported.

Case report:

A 44-year-old woman, otherwise fit and well, presented with more than a 2-year history of right-sided facial pain. A diagnosis of classical trigeminal neuralgia was made. Surgical treatment was undertaken with a retromastoid suboccipital craniotomy. Post-operatively, the patient showed signs of right-sided cerebrospinal fluid rhinorrhoea which was recalcitrant. In light of a continuous leak and several hospital admissions, a novel technique was performed whereby the eustachian tube orifice was obliterated using an endonasal endoscopic approach. The technique proved to be successful, with no further leakage.

Conclusion:

Endoscopic obliteration of the eustachian tube using a double seal technique is a simple, safe and effective procedure in the treatment of a refractory cerebrospinal fluid leak.
Squamous cell carcinoma of the lip: depth of invasion, local recurrence and regional metastases. Experience of a rural multidisciplinary head and neck unit
Authors: Pastuszek A , Hanson M , Grigg R
Published: August 2015

Background:

The internationally recognised American Joint Committee on Cancer (tumour–node–metastasis) staging system utilises tumour size to determine stage. Other factors (i.e. tumour depth) may provide additional prognostic information.

Method:

A thorough retrospective analysis was performed of 68 patients with primary lip squamous cell carcinoma operated on or discussed by the Darling Downs Health Service between 2005 and 2013.

Results:

Twelve patients developed lymphatic spread. There was a statistically significant increased risk of nodal metastasis in: patients with tumours of increased thickness (U = 103.50; degrees of freedom = 68;p < 0.001), those with a larger overall tumour size (U = 163.50; degrees of freedom = 68;p = 0.005) and patients living further from the treatment centre (U = 199.00; degrees of freedom = 68;p = 0.018).

Conclusion:

It may be reasonable that other factors are considered for staging of lip squamous cell carcinomas, in combination with tumour–node–metastasis staging. Depth of invasion may have utility in prognosis and treatment; however, larger prospective analysis needs to be performed. Patients living in a more rural setting presented with more advanced disease, suggesting an ongoing rural–metropolitan gap in healthcare.
Bank voles (Myodes glareolus) and house mice (Mus musculus musculus; M. m. domesticus) in Europe are each parasitized by their own distinct species ofAspiculuris(Nematoda, Oxyurida)
Authors: BEHNKE J. M. , STEWART A. , BAJER A. , GRZYBEK M. , HARRIS P. D. , LOWE A. , RIBAS A. , SMALES L. , VANDEGRIFT K. J.
Published: August 2015

The molecular phylogeny and morphology of the oxyuroid nematode genusAspiculurisfrom voles and house mice has been examined. Worms collected fromMyodes glareolusin Poland, Eire and the UK are identified asAspiculuris tianjinensis, previously known only from China, while worms fromMus musculusfrom a range of locations in Europe and from laboratory mice, all conformed to the description ofAspiculuris tetraptera. Worms from voles and house mice are not closely related and are not derived from each other, withA. tianjinensisbeing most closely related toAspiculuris dinnikifrom snow voles and to an isolate fromMicrotus longicaudusin the Nearctic. BothA. tianjinensisandA. tetrapteraappear to represent recent radiations within their host groups; in voles, this radiation cannot be more than 2 million years old, while in commensal house mice it is likely to be less than 10 000 years old. The potential ofAspiculurisspp. as markers of host evolution is highlighted.
The adaptive evolution of virulence: a review of theoretical predictions and empirical tests
Authors: CRESSLER CLAYTON E. , McLEOD DAVID V. , ROZINS CARLY , VAN DEN HOOGEN JOSÉE , DAY TROY
Published: August 2015

Why is it that some parasites cause high levels of host damage (i.e. virulence) whereas others are relatively benign? There are now numerous reviews of virulence evolution in the literature but it is nevertheless still difficult to find a comprehensive treatment of the theory and data on the subject that is easily accessible to non-specialists. Here we attempt to do so by distilling the vast theoretical literature on the topic into a set of relatively few robust predictions. We then provide a comprehensive assessment of the available empirical literature that tests these predictions. Our results show that there have been some notable successes in integrating theory and data but also that theory and empiricism in this field do not ‘speak’ to each other very well. We offer a few suggestions for how the connection between the two might be improved.
Ascaris and hookworm transmission in preschool children from rural Panama: role of yard environment, soil eggs/larvae and hygiene and play behaviours
Authors: KRAUSE RACHEL J. , KOSKI KRISTINE G. , PONS EMÉRITA , SANDOVAL NIDIA , SINISTERRA ODALIS , SCOTT MARILYN E.
Published: August 2015

This study explored whether the yard environment and child hygiene and play behaviours were associated with presence and intensity of Ascaris and hookworm in preschool children and with eggs and larvae in soil. Data were collected using questionnaires, a visual survey of the yard, soil samples and fecal samples collected at baseline and following re-infection. The presence of eggs/larvae in soil was associated negatively with water storage (eggs) but positively with dogs (eggs) and distance from home to latrine (larvae). Baseline and re-infection prevalences were: hookworm (28·0%, 3·4%); Ascaris (16·9%, 9·5%); Trichuris (0·9%, 0·7%). Zero-inflated negative binomial regression models revealed a higher baseline hookworm infection if yards had eggs or larvae, more vegetation or garbage, and if the child played with soil. Baseline Ascaris was associated with dirt floor, dogs, exposed soil in yard, open defecation and with less time playing outdoors, whereas Ascaris re-infection was associated with water storage, vegetation cover and garbage near the home and not playing with animals. Our results show complex interactions between infection, the yard environment and child behaviours, and indicate that transmission would be reduced if latrines were closer to the home, and if open defecation and water spillage were reduced.
An experimental Investigation of the Impact of Personality Disorder Diagnosis on Clinicians: Can We See Past the Borderline?
Authors: Lam Danny C.K. , Poplavskaya Elena V. , Salkovskis Paul M. , Hogg Lorna I. , Panting Holly
Published: August 2015

Background: There is concern that diagnostic labels for psychiatric disorders may invoke damaging stigma, stereotypes and misunderstanding. Aims: This study investigated clinicians’ reactions to diagnostic labelling by examining their positive and negative reactions to the label borderline personality disorder (BPD). Method: Mental health professionals (n = 265) viewed a videotape of a patient suffering from panic disorder and agoraphobia undergoing assessment. Prior to viewing the videotape, participants were randomly allocated to one of three conditions and were given the following information about the patient: (a) general background information; (b) additional descriptive information about behaviour corresponding to BPD; and (c) additional descriptive information about behaviour corresponding to BPD, but explicitly adding BPD as a possible comorbid diagnostic label. All participants were then asked to note things they had seen in the videotape that made them feel optimistic or pessimistic about treatment outcome. Results: Participants in the group that were explicitly informed that the patient had a BPD diagnostic label reported significantly fewer reasons to be optimistic than the other two groups. Conclusions: Diagnostic labels may negatively impact on clinicians’ judgments and perceptions of individuals and therefore clinicians should think carefully about whether, and how, they use diagnoses and efforts should be made to destigmatize diagnostic terms.
Bilingual advantage and language switch: What's the linkage?
Authors: SCALTRITTI MICHELE , PERESSOTTI FRANCESCA , MIOZZO MICHELE
Published: August 2015

Whether bilingualism affects executive functions is a topic of intense debate. While some studies have provided evidence of enhanced executive functions in bilinguals compared to monolinguals, other studies have failed to find advantages. In the present study, we investigated whether high opportunity of language switching could contribute to bilingual advantage. Advantages have been consistently found with Catalan–Spanish bilinguals who experience frequent opportunities of language switching. Fewer opportunities are experienced by speakers of Italian and one of the Italian dialects, the participants of our study. We anticipated reduced or no advantages with these participants. In Experiment 1, subjective estimates of familiarity with dialect failed to show a relationship with performances in different tasks involving executive control. In Experiment 2, we compared Italian–Venetian dialect bilinguals to Italian monolinguals in the flanker task, and no advantages were found either. Contrasting with results from Catalan–Spanish bilinguals, our results suggest that language switching plays a role in bilingual advantages.
Role of endothelial cells in bovine mammary gland health and disease
Authors: Ryman Valerie E. , Packiriswamy Nandakumar , Sordillo Lorraine M.
Published: August 2015

The bovine mammary gland is a dynamic and complex organ composed of various cell types that work together for the purpose of milk synthesis and secretion. A layer of endothelial cells establishes the blood–milk barrier, which exists to facilitate the exchange of solutes and macromolecules necessary for optimal milk production. During bacterial challenge, however, endothelial cells divert some of their lactation function to protect the underlying tissue from damage by initiating inflammation. At the onset of inflammation, endothelial cells tightly regulate the movement of plasma components and leukocytes into affected tissue. Unfortunately, endothelial dysfunction as a result of exacerbated or sustained inflammation can negatively affect both barrier integrity and the health of surrounding extravascular tissue. The objective of this review is to highlight the role of endothelial cells in supporting milk production and regulating optimal inflammatory responses. The consequences of endothelial dysfunction and sustained inflammation on milk synthesis and secretion are discussed. Given the important role of endothelial cells in orchestrating the inflammatory response, a better understanding of endothelial function during mastitis may support development of targeted therapies to protect bovine mammary tissue and mammary endothelium.
Urban Scale Shifts since the Bronze Age: Upsweeps, Collapses, and Semiperipheral Development
Authors: Inoue Hiroko , Álvarez Alexis , Anderson Eugene N. , Owen Andrew , Álvarez Rebecca , Lawrence Kirk , Chase-Dunn Christopher
Published: August 2015

This is a study of the growth and decline of cities for the purpose of identifying those events in which they significantly increased in size. Significant changes in the scale of cities are important for understanding the long-term trend toward more complex and hierarchical human societies. We report the results of an inventory of cycles, upsweeps, and collapses of settlements in five separate interpolity systems. Upsweeps are instances in which the largest settlement in a world system significantly increases in size. Collapses occur when the size of the largest settlement greatly decreases and stays down for a significant period of time rather than rebounding. We use regional interpolity systems (world systems) rather than single polities or settlements as our unit of analysis. Because the accurate designation of sweeps requires interval scale measures, we are limited to those regions and time periods for which quantitative estimates of largest settlement sizes are regularly available. We find a total of 18 upsweeps and five downsweeps, and only two instances of prolonged systemwide settlement collapse. We also investigate whether or not the rate of cycles has increased over the long run, and we find that cycles of city growth and decline have not accelerated. We also find a greater rate of urban cycles in the Western (Central) System than in the East Asian System, which supports the usual notion that the Western city system was less stable than the Eastern city system.
Uniparental disomy of the entire X chromosome in Turner syndrome patient-specific induced pluripotent stem cells
Authors: Luo Yumei , Zhu Detu , Du Rong , Gong Yu , Xie Chun , Xu Xiangye , Fan Yong , Yu Bolan , Sun Xiaofang , Chen Yaoyong
Published: August 2015

The human induced pluripotent stem cell (iPSC) technique promises to provide an unlimited, reliable source of genetically matched pluripotent cells for personalized therapy and disease modeling. Recently, it is observed that cells with ring chromosomes 13 or 17 autonomously correct the defects via compensatory uniparental disomy during cellular reprogramming to iPSCs. This breakthrough finding suggests a potential therapeutic approach to repair large-scale chromosomal aberrations. However, due to the scarceness of ring chromosome samples, the reproducibility of this approach in different individuals is not carefully evaluated yet. Moreover, the underlying mechanism and the applicability to other types of chromosomal aberrations remain unknown. Here we generated iPSCs from four 45,X chorionic villous fibroblast lines and found that only one reprogrammed line acquired 46,XX karyotype via uniparental disomy of the entire X chromosome. The karyotype correction was reproducible in the same cell line by either retroviral or episomal reprogramming. The karyotype-corrected iPSCs were subject to X chromosome inactivation and obtained better colony morphology and higher proliferation rate than other uncorrected ones. Further transcriptomic comparison among the fibroblast lines identified a distinct expression pattern of cell cycle regulators in the uncorrectable ones. These findings demonstrate that the iPSC technique holds the potential to correct X monosomy, but the correction rate is very low, probably due to differential regulation of cell cycle genes between individuals. Our data strongly suggest that more systematic investigations are needed before defining the iPSC technique as a novel means of chromosome therapy.
Metal-induced malformations in early Palaeozoic plankton are harbingers of mass extinction
Authors: Vandenbroucke Thijs R. A. , Emsbo Poul , Munnecke Axel , Nuns Nicolas , Duponchel Ludovic , Lepot Kevin , Quijada Melesio , Paris Florentin , Servais Thomas , Kiessling Wolfgang
Published: August 2015

Glacial episodes have been linked to Ordovician–Silurian extinction events, but cooling itself may not be solely responsible for these extinctions. Teratological (malformed) assemblages of fossil plankton that correlate precisely with the extinction events can help identify alternate drivers of extinction. Here we show that metal poisoning may have caused these aberrant morphologies during a late Silurian (Pridoli) event. Malformations coincide with a dramatic increase of metals (Fe, Mo, Pb, Mn and As) in the fossils and their host rocks. Metallic toxins are known to cause a teratological response in modern organisms, which is now routinely used as a proxy to assess oceanic metal contamination. Similarly, our study identifies metal-induced teratology as a deep-time, palaeobiological monitor of palaeo-ocean chemistry. The redox-sensitive character of enriched metals supports emerging ‘oceanic anoxic event’ models. Our data suggest that spreading anoxia and redox cycling of harmful metals was a contributing kill mechanism during these devastating Ordovician–Silurian palaeobiological events.
Generation of a synthetic GlcNAcylated nucleosome reveals regulation of stability by H2A-Thr101 GlcNAcylation
Authors: Lercher Lukas , Raj Ritu , Patel Nisha A. , Price Joshua , Mohammed Shabaz , Robinson Carol V. , Schofield Christopher J. , Davis Benjamin G.
Published: August 2015

O-GlcNAcylation is a newly discovered histone modification implicated in transcriptional regulation, but no structural information on the physical effect of GlcNAcylation on chromatin exists. Here, we generate synthetic, pure GlcNAcylated histones and nucleosomes and reveal that GlcNAcylation can modulate structure through direct destabilization of H2A/H2B dimers in the nucleosome, thus promoting an ‘open’ chromatin state. The results suggest that a plausible molecular basis for one role of histone O-GlcNAcylation in epigenetic regulation is to lower the barrier for RNA polymerase passage and hence increase transcription.
Contextual modulation of value signals in reward and punishment learning
Authors: Palminteri Stefano , Khamassi Mehdi , Joffily Mateus , Coricelli Giorgio
Published: August 2015

Compared with reward seeking, punishment avoidance learning is less clearly understood at both the computational and neurobiological levels. Here we demonstrate, using computational modelling and fMRI in humans, that learning option values in a relative—context-dependent—scale offers a simple computational solution for avoidance learning. The context (or state) value sets the reference point to which an outcome should be compared before updating the option value. Consequently, in contexts with an overall negative expected value, successful punishment avoidance acquires a positive value, thus reinforcing the response. As revealed by post-learning assessment of options values, contextual influences are enhanced when subjects are informed about the result of the forgone alternative (counterfactual information). This is mirrored at the neural level by a shift in negative outcome encoding from the anterior insula to the ventral striatum, suggesting that value contextualization also limits the need to mobilize an opponent punishment learning system.
A plasmonic nanorod that walks on DNA origami
Authors: Zhou Chao , Duan Xiaoyang , Liu Na
Published: August 2015

In nano-optics, a formidable challenge remains in precise transport of a single optical nano-object along a programmed and routed path toward a predefined destination. Molecular motors in living cells that can walk directionally along microtubules have been the inspiration for realizing artificial molecular walkers. Here we demonstrate an active plasmonic system, in which a plasmonic nanorod can execute directional, progressive and reverse nanoscale walking on two or three-dimensional DNA origami. Such a walker comprises an anisotropic gold nanorod as its ‘body’ and discrete DNA strands as its ‘feet’. Specifically, our walker carries optical information and can in situ optically report its own walking directions and consecutive steps at nanometer accuracy, through dynamic coupling to a plasmonic stator immobilized along its walking track. Our concept will enable a variety of smart nanophotonic platforms for studying dynamic light–matter interaction, which requires controlled motion at the nanoscale well below the optical diffraction limit.
Sialic acid catabolism drives intestinal inflammation and microbial dysbiosis in mice
Authors: Huang Yen-Lin , Chassard Christophe , Hausmann Martin , von Itzstein Mark , Hennet Thierry
Published: August 2015

Rapid shifts in microbial composition frequently occur during intestinal inflammation, but the mechanisms underlying such changes remain elusive. Here we demonstrate that an increased caecal sialidase activity is critical in conferring a growth advantage for some bacteria including Escherichia coli (E. coli) during intestinal inflammation in mice. This sialidase activity originates among others from Bacteroides vulgatus, whose intestinal levels expand after dextran sulphate sodium administration. Increased sialidase activity mediates the release of sialic acid from intestinal tissue, which promotes the outgrowth of E. coli during inflammation. The outburst of E. coli likely exacerbates the inflammatory response by stimulating the production of pro-inflammatory cytokines by intestinal dendritic cells. Oral administration of a sialidase inhibitor and low levels of intestinal α2,3-linked sialic acid decrease E. coli outgrowth and the severity of colitis in mice. Regulation of sialic acid catabolism opens new perspectives for the treatment of intestinal inflammation as manifested by E. coli dysbiosis.
Inhibition of microvesiculation sensitizes prostate cancer cells to chemotherapy and reduces docetaxel dose required to limit tumor growth in vivo
Authors: Jorfi Samireh , Ansa-Addo Ephraim A. , Kholia Sharad , Stratton Dan , Valley Shaunelle , Lange Sigrun , Inal Jameel
Published: August 2015

Microvesicles shed from cells carry constituents of the cell cytoplasm, including, of importance in multidrug resistance to cancer chemotherapy, drugs that the tumor cell attempts to efflux. To see whether such drugs could be used at lower concentrations with the same efficacy, it was first shown that microvesiculation of prostate cancer (PCa) cells, PC3, could be inhibited pharmacologically with calpeptin (calpain inhibitor) and by siRNA (CAPNS1). In cells treated with docetaxel (DTX), this inhibition resulted in a third-fold increase in intracellular concentrations of DTX. As a result, 20-fold lower concentrations of DTX (5 nM) could be used, in the presence of calpeptin (20 μM) inducing the same degree of apoptosis after 48 h in PC3 cells, as 100 nM of DTX alone. Inhibition of microvesiculation similarly improved combination chemotherapy (DTX and methotrexate). In a mouse xenograft model of PCa, DTX (0.1 mg/kg) together with calpeptin (10 mg/kg), administered i.p., significantly reduced tumor volumes compared to DTX alone (0.1 mg/kg) and brought about the same reductions in tumor growth as 10 mg/kg of DTX alone. As well as further reducing vascularization, it also increased apoptosis and reduced proliferation of PC3 cells in tumor xenografts.
Selective flow-induced vesicle rupture to sort by membrane mechanical properties
Authors: Pommella Angelo , Brooks Nicholas J. , Seddon John M. , Garbin Valeria
Published: August 2015

Vesicle and cell rupture caused by large viscous stresses in ultrasonication is central to biomedical and bioprocessing applications. The flow-induced opening of lipid membranes can be exploited to deliver drugs into cells, or to recover products from cells, provided that it can be obtained in a controlled fashion. Here we demonstrate that differences in lipid membrane and vesicle properties can enable selective flow-induced vesicle break-up. We obtained vesicle populations with different membrane properties by using different lipids (SOPC, DOPC, or POPC) and lipid:cholesterol mixtures (SOPC:chol and DOPC:chol). We subjected vesicles to large deformations in the acoustic microstreaming flow generated by ultrasound-driven microbubbles. By simultaneously deforming vesicles with different properties in the same flow, we determined the conditions in which rupture is selective with respect to the membrane stretching elasticity. We also investigated the effect of vesicle radius and excess area on the threshold for rupture and identified conditions for robust selectivity based solely on the mechanical properties of the membrane. Our work should enable new sorting mechanisms based on the difference in membrane composition and mechanical properties between different vesicles, capsules, or cells.
Comparison of four digital PCR platforms for accurate quantification of DNA copy number of a certified plasmid DNA reference material
Authors: Dong Lianhua , Meng Ying , Sui Zhiwei , Wang Jing , Wu Liqing , Fu Boqiang
Published: August 2015

Digital polymerase chain reaction (dPCR) is a unique approach to measurement of the absolute copy number of target DNA without using external standards. However, the comparability of different dPCR platforms with respect to measurement of DNA copy number must be addressed before dPCR can be classified fundamentally as an absolute quantification technique. The comparability of four dPCR platforms with respect to accuracy and measurement uncertainty was investigated by using a certified plasmid reference material. Plasmid conformation was found to have a significant effect on droplet-based dPCR (QX100 and RainDrop) not shared with chip-based QuantStudio 12k or BioMark. The relative uncertainty of partition volume was determined to be 0.7%, 0.8%, 2.3% and 2.9% for BioMark, QX100, QuantStudio 12k and RainDrop, respectively. The measurements of the certified pNIM-001 plasmid made using the four dPCR platforms were corrected for partition volume and closely consistent with the certified value within the expended uncertainty. This demonstrated that the four dPCR platforms are of comparable effectiveness in quantifying DNA copy number. These findings provide an independent assessment of this method of determining DNA copy number when using different dPCR platforms and underline important factors that should be taken into consideration in the design of dPCR experiments.
Edge states and integer quantum Hall effect in topological insulator thin films
Authors: Zhang Song-Bo , Lu Hai-Zhou , Shen Shun-Qing
Published: August 2015

The integer quantum Hall effect is a topological state of quantum matter in two dimensions and has recently been observed in three-dimensional topological insulator thin films. Here we study the Landau levels and edge states of surface Dirac fermions in topological insulators under strong magnetic field. We examine the formation of the quantum plateaux of the Hall conductance and find two different patterns, in one pattern the filling number covers all integers while only odd integers in the other. We focus on the quantum plateau closest to zero energy and demonstrate the breakdown of the quantum spin Hall effect resulting from structure inversion asymmetry. The phase diagrams of the quantum Hall states are presented as functions of magnetic field, gate voltage and chemical potential. This work establishes an intuitive picture of the edge states to understand the integer quantum Hall effect for Dirac electrons in topological insulator thin films.
Control of Dzyaloshinskii-Moriya interaction in Mn1−xFexGe: a first-principles study
Authors: Koretsune Takashi , Nagaosa Naoto , Arita Ryotaro
Published: August 2015

Motivated by the recent experiment on the size and helicity control of skyrmions in Mn1−xFexGe, we study how the Dzyaloshinskii-Moriya (DM) interaction changes its size and sign in metallic helimagnets. By means of first-principles calculations, we successfully reproduce the non-trivial sign change of the DM interaction observed in the experiment. While the DM interaction sensitively depends on the carrier density or the detail of the electronic structure such as the size of the exchange splitting, its behavior can be systematically understood in terms of the distribution of anticrossing points in the band structure. By following this guiding principle, we can even induce gigantic anisotropy in the DM interaction by applying a strain to the system. These results pave the new way for skyrmion crystal engineering in metallic helimagnets.
Hsa-miR-19a is associated with lymph metastasis and mediates the TNF-α induced epithelial-to-mesenchymal transition in colorectal cancer
Authors: Huang Lanlan , Wang Xiaoyan , Wen Chuangyu , Yang Xiangling , Song Minmin , Chen Junxiong , Wang Chenliang , Zhang Bo , Wang Lei , Iwamoto Aikichi , Wang Jianping , Liu Huanliang
Published: August 2015

Lymph node metastasis is an important factor determining the outcome of colorectal cancer. Although epithelial-to-mesenchymal transition (EMT), TNF-α and microRNA (miRNA) have been found to play important roles in lymph node metastasis, the underlying molecular mechanism remains unclear. Here we reported that high expression of microRNA-19a (miR-19a) was associated with lymph node metastasis and played an important role in TNF-α-induced EMT in colorectal cancer (CRC) cells. We analyzed miR-19a expression in surgical tissue specimens from 11 CRC patients and 275 formalin-fixed, paraffin-embedded CRC patients. We found that miR-19a was up-regulated in CRC tissues and high expression of miR-19a was significantly associated with lymph node metastasis. We further analyzed miR-19a lymph node metastasis signature in an external validation cohort of 311 CRC cases of the TCGA. MiR-19a was found to be significantly associated with lymph node metastasis in rectal cancer. In vitro, we showed that overexpression of miR-19a in human CRC cell lines promoted cell invasion and EMT. Furthermore, miR-19a was up-regulated by TNF-α and miR-19a was required for TNF-α-induced EMT and metastasis in CRC cells. Collectively, miR-19a played an important role in mediating EMT and metastatic behavior in CRC. It may serve as a potential marker of lymph node metastasis.
Integrated Transcriptomics Establish Macrophage Polarization Signatures and have Potential Applications for Clinical Health and Disease
Authors: Becker Matheus , De Bastiani Marco A. , Parisi Mariana M. , Guma Fátima T. C. R. , Markoski Melissa M. , Castro Mauro A. A. , Kaplan Mark H. , Barbé-Tuana Florencia M. , Klamt Fábio
Published: August 2015

Growing evidence defines macrophages (Mφ) as plastic cells with wide-ranging states of activation and expression of different markers that are time and location dependent. Distinct from the simple M1/M2 dichotomy initially proposed, extensive diversity of macrophage phenotypes have been extensively demonstrated as characteristic features of monocyte-macrophage differentiation, highlighting the difficulty of defining complex profiles by a limited number of genes. Since the description of macrophage activation is currently contentious and confusing, the generation of a simple and reliable framework to categorize major Mφ phenotypes in the context of complex clinical conditions would be extremely relevant to unravel different roles played by these cells in pathophysiological scenarios. In the current study, we integrated transcriptome data using bioinformatics tools to generate two macrophage molecular signatures. We validated our signatures in in vitro experiments and in clinical samples. More importantly, we were able to attribute prognostic and predictive values to components of our signatures. Our study provides a framework to guide the interrogation of macrophage phenotypes in the context of health and disease. The approach described here could be used to propose new biomarkers for diagnosis in diverse clinical settings including dengue infections, asthma and sepsis resolution.