bluuebunny/crossref_metadata_2025 huggingface dataset:
Channel-resolved subcycle interferences of electron wave packets emitted from in two-color laser fields
Authors: Xie Xinhua , Roither Stefan , Kartashov Daniil , Zhang Li , Baltuška Andrius , Kitzler Markus
Published: November 2016

We report on the observation of subcycle interferences of electron wave packets released during strong field ionization of

$\text{H}_{2}$

with cycle-shaped two-color laser fields. With a reaction microscope we measure three-dimensional momentum distributions of photoelectrons correlated with either

$\text{H}_{2}^{+}$

or protons within different energy ranges generated by dissociation of

$\text{H}_{2}^{+}$

. We refer to these different types of photoelectrons as channels. Our results show that the subcycle interference structures of electron wave packets are very sensitive to the cycle shape of the two-color laser field. We explain this behavior by the dependence of the ionization time within an optical cycle on the shape of the laser field cycle. The subcycle interference structures can be further used to obtain insight into the subcycle dynamics of molecules during strong field interaction.
Buoyant flow of through and around a semi-permeable layer of finite extent
Authors: Ngo Tri Dat , Mouche Emmanuel , Audigane Pascal
Published: November 2016

The buoyancy- and capillary-driven counter-current flow of $\text{CO}_{2}$ and brine through and around a semi-permeable layer is studied both numerically and theoretically. The continuities of the capillary pressure and the total flux at the interface between the permeable matrix and layer control the $\text{CO}_{2}$ saturation discontinuity at the interface and the balance between the buoyant and capillary diffusion fluxes on each side of the interface. This interface process is first studied in a one-dimensional (1-D) vertical column geometry using the concept of extended capillary pressure and a graphical representation of the continuity conditions in the ($S_{L}$, $S_{U}$) plane, where $S_{L}$ and $S_{U}$ are the lower and upper saturation traces at the interface, respectively. In two dimensions, we heuristically extend the two-phase gravity current model to the case where the current is bounded by a semi-permeable layer. Consequently, the current is not saturated with $\text{CO}_{2}$, and its saturation and shape are derived from the flux and capillary pressure continuity conditions at the interface. This simplified model, which depends on $\text{CO}_{2}$ saturation only, is compared to fine grid simulations in the capillary-free and gravity-dominant cases. A good agreement is obtained in the second case; the current geometrical characteristics are accurately described. In the capillary-free case, we demonstrate that the local total velocity, which is, on average, zero because the flow is counter-current, must be considered in the total flux at the interface to obtain the same level of agreement.
Sum-of-squares approach to feedback control of laminar wake flows
Authors: Lasagna Davide , Huang Deqing , Tutty Owen R. , Chernyshenko Sergei
Published: November 2016

In this paper a novel nonlinear feedback control design methodology for incompressible fluid flows aiming at the optimisation of long-time averages of flow quantities is presented. It applies to reduced-order finite-dimensional models of fluid flows, expressed as a set of first-order nonlinear ordinary differential equations with the right-hand side being a polynomial function in the state variables and in the controls. The key idea, first discussed in Chernyshenkoet al.(Phil. Trans. R. Soc. Lond. A, vol. 372, 2014, 20130350), is that the difficulties of treating and optimising long-time averages of a cost are relaxed by using the upper/lower bounds of such averages as the objective function. In this setting, control design reduces to finding a feedback controller that optimises the bound, subject to a polynomial inequality constraint involving the cost function, the nonlinear system, the controller itself and a tunable polynomial function. A numerically tractable and efficient approach to the solution of such optimisation problems, based on sum-of-squares techniques and semidefinite programming, is proposed. To showcase the methodology, the mitigation of the fluctuation kinetic energy in the unsteady wake behind a circular cylinder in the laminar regime at$Re=100$, via controlled angular motions of the surface, is numerically investigated. A compact reduced-order model that resolves the long-term behaviour of the fluid flow and the effects of actuation, is first derived using proper orthogonal decomposition and Galerkin projection. In a full-information setting, feedback controllers are then designed to reduce the long-time average of the resolved kinetic energy associated with the limit cycle. These controllers are then implemented in direct numerical simulations of the actuated flow. Control performance, total energy efficiency and the physical control mechanisms identified are analysed in detail. Key elements of the methodology, implications and future work are finally discussed.
“Contesting the Empire of Habit”: Habituation and Liberty in Lockean Education
Authors: KOGANZON RITA
Published: November 2016

Although John Locke's educational curriculum has traditionally been seen to aim at creating free citizens capable of independent thought, the centrality of habituation to his pedagogy has recently raised concerns that the Education is no more than “indoctrination” for compliant subjects. I argue here that by re-examining habituation in light of Locke's epistemology, we find that Locke's education does aim at freedom, but that this freedom requires a strong will and a cultivated skepticism. The habits which Locke asks parents to instill are aimed not at programming specific behavior and opinions, but rather at training children to “cross their desires” to strengthen their wills against the impositions of nature, custom, and fashion, which Locke argues pose an far more serious threat to independent thought than parental discipline. Locke's education aims to cultivate a skeptical mental disposition that permits individuals to resist these other sources of habit and to continually question and revise their own convictions.
Testing Civics: State-Level Civic Education Requirements and Political Knowledge
Authors: CAMPBELL DAVID E. , NIEMI RICHARD G.
Published: November 2016

Do state-level exams in civics have a positive impact on young people's civic knowledge? We hypothesize that civics exams have the biggest effect in states where they are a requirement for high school graduation—theincentivehypothesis. We further hypothesize that civics requirements have the biggest effect on young people with less exposure to information about the U.S. political system at home, specifically Latinos and, especially, immigrants—thecompensationhypothesis. We test these hypotheses with the 2006 and 2010 National Assessment of Educational Progress (NAEP) civics test administered to high school students, and with a large national survey of 18–24 year-olds. Across the two datasets, we find modest support for the incentive hypothesis and strong support for the compensation hypothesis.
Fatty acid consumption and incident type 2 diabetes: an 18-year follow-up in the female E3N (Etude Epidémiologique auprès des femmes de la Mutuelle Générale de l’Education Nationale) prospective cohort study
Authors: Dow Courtney , Mangin Marie , Balkau Beverley , Affret Aurélie , Boutron-Ruault Marie-Christine , Clavel-Chapelon Françoise , Bonnet Fabrice , Fagherazzi Guy
Published: November 2016

We evaluated the association between dietary estimates of fatty acid (FA) consumption and type 2 diabetes (T2D) risk in the French E3N (Etude Epidémiologique auprès des femmes de la Mutuelle Générale de l’Education Nationale) cohort. In total, 71 334 women without diabetes at baseline were followed up from 1993 to 2011. Diabetes was identified using questionnaires and drug-reimbursement claims, and incident cases were validated. FA consumption in 1993 was estimated from a validated dietary questionnaire. Cox regression estimated hazard ratios (HR) and 95 % CI of diabetes risk, comparing the upper tertile group with the lowest. High n-3 PUFA consumption was associated with T2D even after adjustment for confounders, including other FA and BMI (HR 1·26; 95 % CI 1·13, 1·41; upper tertile compared with lowest). Upon stratification by overweight (BMI≥25 kg/m2)/non-overweight, a positive association between total PUFA consumption and T2D was observed, but it was restricted to non-overweight women (HR 1·22; 95 % CI 1·05, 1·42), whereas n-3 PUFA consumption was associated with increased T2D risk in both BMI strata (BMI<25 kg/m2: HR 1·19; 95 % CI 1·01, 1·40 and BMI≥25 kg/m2: HR 1·38; 95 % CI 1·20, 1·59). Within the n-3 PUFA, high DPA (HR 1·41; 95 % CI 1·23, 1·63) and α-linolenic acid (ALA) intakes were associated with increased T2D risk, but the effects of ALA were restricted to overweight women (HR 1·17; 95 % CI 1·01, 1·36). Within the n-6 PUFA, only arachidonic acid (AA) intake was associated with T2D risk (HR 1·49; 95 % CI 1·33, 1·66). The associations with DPA and AA persisted even after adjustment of their principal source in this cohort, the consumption of meat. The effects of PUFA are heterogeneous within the FA group. Intake of DPA and AA may contribute to T2D development.
Effects of the Great Recession on American Attitudes Toward Trade
Authors: Mansfield Edward D. , Mutz Diana C. , Brackbill Devon
Published: November 2016

Did the American public become more protectionist during the Great Recession of 2007–09? If so, why? During this period, many observers expressed concern that rising unemployment would stimulate protectionist pressures. The results of this study indicate that although increased unemployment did not affect the trade preferences of most Americans, individuals working in import-competing industries who lost their jobs during the Great Recession did grow more hostile to trade. However, even greater hostility to trade stemmed from a variety of non-material factors. Increasing ethnocentrism and opposition to involvement in world affairs between 2007 and 2009 help account for growing antipathy toward trade. But most importantly, increasing anxiety that foreign commerce would harm people in the future, even if it had not done so thus far, contributed to mounting opposition to trade among the American public.
JAS Round Table on Amitav Ghosh,The Great Derangement: Climate Change and the Unthinkable
Authors: Thomas Julia Adeney , Parthasarathi Prasannan , Linrothe Rob , Fan Fa-ti , Pomeranz Kenneth , Ghosh Amitav
Published: November 2016

Amitav Ghosh, perhaps Asia's most prominent living author, moves among many genres and across vast territories. His fiction—The Circle of Reason(1986),The Shadow Lines(1988),The Glass Place(2000),The Hungry Tide(2004), andThe Ibistrilogy—takes us from Calcutta where he was born in 1956 to the Arabian Sea, Paris, London, and back again to the Indian Ocean, the Bay of Bengal, and beyond. His nonfiction—In an Antique Land(1992),Dancing in Cambodia and at Large in Burma(1998), andCountdown(1999)—rests on a PhD in social anthropology from Oxford. He went to Alexandria, Egypt, for his dissertation research. His science fiction,The Calcutta Chromosome, won the Arthur C. Clarke Award in 1997. His essays—published inThe New Yorker, The New Republic, andThe New York Timesand collected inThe Iman and the Indian(2002)—address major issues such as fundamentalism. Indeed, most of his work addresses big questions, exploring the nature of communal violence, the traces of love and longing across generations, manifold religious manifestations, and the systematic pain of colonial oppression. The deep and abiding theme of many works is anthropogenic environmental damage, now boldly and directly addressed inThe Great Derangement: Climate Change and the Unthinkable(2016). Married to accomplished fellow author Deborah Baker, whose work traces the Asian peregrinations of Allen Ginsberg, the literary milieu of Laura Riding, and the complexity of Islamic conversion, Ghosh has taught at Harvard, Columbia, Queens College, and Delhi University. He has won more prizes and honorary doctorates, and been a fellow at more famous institutions and a distinguished visitor in more far-flung places, than you can shake a stick at. He even has two homes: Brooklyn and Goa. In short, Ghosh's profile makes you wonder if there might not be more than one of him.
Exopolysaccharide from Lactobacillus fermentum Lf2 and its functional characterization as a yogurt additive
Authors: Ale Elisa C , Perezlindo Marcos J , Burns Patricia , Tabacman Eduardo , Reinheimer Jorge A , Binetti Ana G
Published: November 2016

Lactobacillus fermentum Lf2 is a strain which is able to produce high levels (approximately 1 g/l) of crude exopolysaccharide (EPS) when it is grown in optimised conditions. The aim of this work was to characterize the functional aspects of this EPS extract, focusing on its application as a dairy food additive. Our findings are consistent with an EPS extract that acts as moderate immunomodulator, modifying s-IgA and IL-6 levels in the small intestine when added to yogurt and milk, respectively. Furthermore, this EPS extract, in a dose feasible to use as a food additive, provides protection against Salmonella infection in a murine model, thus representing a mode of action to elicit positive health benefits. Besides, it contributes to the rheological characteristics of yogurt, and could function as a food additive with both technological and functional roles, making possible the production of a new functional yogurt with improved texture.
Effect of spring versus autumn grass/clover silage and rapeseed supplementation on milk production, composition and quality in Jersey cows
Authors: Larsen Mette Krogh , Vogdanou Stefania , Hellwing Anne Louise F. , Rybicka Iga , Weisbjerg Martin Riis
Published: November 2016

The composition of grass/clover silage varies depending on time of harvest time. In particular silage from late regrowths is expected to contain lower fibre and higher linolenic acid concentrations compared to spring growth, thereby autumn silage is expected to increase linolenic acid content of milk fat. Rapeseed supplementation is expected to increase milk production and to increase all C18 fatty acids in milk fat. An interaction between rapeseed and silage type is expected, as hydrogenation of unsaturated fatty acids in rapeseed is expected to be less when low fibre silage is fed. Thirty-six Jersey cows were used in a 4 × 4 Latin square design, for 4 periods of 3 weeks and with a 2 × 2 factorial arrangement of treatments: spring grass/clover silage from primary growth or autumn grass/clover silage which was an equal mixture of 3rd regrowth and 4th regrowth, with or without rapeseed supplementation. Dry matter intake and milk production was higher for autumn than for spring silage. Rapeseed supplementation did not affect dry matter intake, but increased milk production. The concentrations of C18 : 1cis9, C18 : 2n6 and β-carotene and C18 : 3n3 in milk were increased whereas the concentrations of C16 : 0, riboflavin and α-tocopherol were decreased with autumn silage. The majority of C18 FAs in milk and α-tocopherol concentration increased with rapeseed whereas C11 : 0 to C16 : 0 FA were reduced. Autumn silage reduced biohydrogenation of C18 : 2n6, whereas rapeseed increased biohydrogenation of C18 : 2n6 and reduced biohydrogenation of C18 : 3n3. Apparent recovery of C18 : 2n6 was reduced with rapeseed. Minor interaction effects of silage type and rapeseed addition were observed for some milk fatty acids. Feeding silage from late regrowth increased linolenic acid concentration in milk fat. Rapeseed inclusion increased milk production, and increased C18 : 0 as well as C18 : 1 fatty acids, but not C18 : 2 and C18 : 3 in milk fat. Interactions between silage type and rapeseed supplementation were minimal.
Antimicrobial activity of buttermilk and lactoferrin peptide extracts on poultry pathogens
Authors: Jean Catherine , Boulianne Martine , Britten Michel , Robitaille Gilles
Published: November 2016

Antibiotics are commonly used in poultry feed as growth promoters. This practice is questioned given the arising importance of antibiotic resistance. Antimicrobial peptides can be used as food additives for a potent alternative to synthetic or semi-synthetic antibiotics. The objective of this study was to develop a peptide production method based on membrane adsorption chromatography in order to produce extracts with antimicrobial activity against avian pathogens (Salmonella entericavar. Enteritidis,Salmonella entericavar. Typhimurium, and twoEscherichia colistrains, O78:H80 and TK3 O1:K1) as well asStaphylococcus aureus. To achieve this, buttermilk powder and purified lactoferrin were digested with pepsin. The peptide extracts (<10 kDa) were fractionated depending on their charges through high-capacity cation-exchange and anion-exchange adsorptive membranes. The yields of cationic peptide extracts were 6·3 and 15·4% from buttermilk and lactoferrin total peptide extracts, respectively. Antimicrobial activity was assessed using the microdilution technique on microplates. Our results indicate that the buttermilk cationic peptide extracts were bactericidal at less than 5 mg/ml against the selected avian strains, with losses of 1·7 log CFU/ml (Salm.Typhimurium) to 3 log CFU/ml (E. coliO78:H80); viability decreased by 1·5 log CFU/ml forStaph. aureus, a Gram-positive bacterium. Anionic and non-adsorbed peptide extracts were inactive at 5 mg/ml. These results demonstrate that membrane adsorption chromatography is an effective way to prepare a cationic peptide extract from buttermilk that is active against avian pathogens.
Effect of different fat replacers on the physicochemical and instrumental analysis of low-fat cupuassu goat milk yogurts
Authors: Costa Marion P , Frasao Beatriz S , Rodrigues Bruna L , Silva Adriana CO , Conte-Junior Carlos A
Published: November 2016

The aim of this Research Communication was to investigate the changes in physicochemical, colour, apparent viscosity and texture properties in low-fat goat milk yogurts prepared with cupuassu pulp by the addition of inulin (SI), maltodextrin (SM), whey protein (SW) and skim milk powder (SP). Three batches of each cupuassu goat milk yogurt were prepared and analysed on the 1st day of storage by pH, proximate composition, colour, apparent viscosity, and texture. In comparison to yogurts from whole (W) or skimmed milk (S), all of the fat replacers improved the physicochemical properties (P < 0·05). The addition of the carbohydrates (inulin and maltodextrin) and proteins (whey protein and skim milk powder) also influenced the colour of the low-fat cupuassu goat milk yogurt (P < 0·05). All fat replacer treatments (SI, SM, SW and SP) presented a higher (P < 0·05) apparent viscosity than W and S yogurts. However, only the addition of skim milk powder increased the texture parameters (firmness and consistency) (P < 0·05). These results suggest that skim milk powder can be used to improve the texture properties of low-fat cupuassu goat milk. Furthermore, inulin, maltodextrin, and whey protein can potentially be applied in the goat dairy industry to increase the viscosity of yogurts.
Description and experimental transmission of Tetracapsuloides vermiformis n. sp. (Cnidaria: Myxozoa) and guidelines for describing malacosporean species including reinstatement of Buddenbrockia bryozoides n. comb. (syn. Tetracapsula bryozoides)
Authors: PATRA SNEHA , HARTIGAN ASHLIE , MORRIS DAVID J. , KODÁDKOVÁ ALENA , HOLZER ASTRID S.
Published: November 2016

This paper provides the first detailed description of a Tetracapsuloides species, Tetracapsuloides vermiformis n. sp., with vermiform stages in the bryozoan host, Fredericella sultana, and its experimental transmission from F. sultana to Cyprinus carpio. The suitability of morphological, biological and 18S rDNA sequence data for discrimination between malacosporean species is reviewed and recommendations are given for future descriptions. Presently, malacosporean species cannot be differentiated morphologically due to their cryptic nature and the lack of differential characters of spores and spore-forming stages in both hosts. We examined biological, morphological and molecular characters for the present description and for revising malacosporean taxonomy in general. As a result, Buddenbrockia plumatellae was split into two species, with its sac-like stages being ascribed to Buddenbrockia bryozoides n. comb. In addition to ribosomal DNA sequences multiple biological features rather than morphological characters are considered essential tools to improve malacosporean taxonomy in the future according to our analysis of the limited traits presently available.
Incentives facing UK-listed companies to comply with the risk reporting provisions of the UK Corporate Governance Code
Authors: Klumpes P. , Ledlie C. , Fahey F. , Kakar G. , Styles S.
Published: November 2016

Recent changes made to the UK Corporate Governance Code require UK firms to report new or enhanced narrative information concerning their principal risks, their risk management processes and their future viability. This paper analyses whether the level and nature of voluntary compliance with these new requirements is consistent with alternative economic and political visibility incentives. We analyse relevant sections of financial reports produced by industry-matched samples of large-, mid- and small-cap UK-listed firms during the transitional 2013–2014 financial reporting years. Both specific and generic readability attributes of the reports are measured. We find that virtually no firm in our sample has provided any viability statement. Empirical analysis of disclosures concerning principal risk assessment and review processes appear to be primarily motivated by political visibility reasons. Examples of particularly good and cases of poor corporate risk reporting practices are also discussed. Possible implications for the actuarial profession are discussed.
Left-sided breast radiotherapy after conservative surgery: comparison of techniques between volumetric modulated arc therapy, forward-planning intensity-modulated radiotherapy and conventional technique
Authors: Giri Upendra Kumar , Sarkar Biplab , Jassal Kanan , Munshi Anusheel , Ganesh Tharmar , Mohanti Bidhu , Pradhan Anirudh
Published: November 2016

Objective

This study was conducted for comparison of techniques between volumetric modulated arc therapy (VMAT), forward-planning intensity-modulated radiotherapy (FIMRT) and conventional technique for left-sided breast radiotherapy after conservative surgery.

Methods

In all, 20 postoperative left breast carcinoma patients were included in this study. In all plans the planning target volume (PTV) was the breast tissue with appropriate margin as per our institutional protocol. The contouring was done on a Monaco Sim (V5.00.02) contouring workstation. All patient were planned using partial arc VMAT in Monaco treatment planning system (TPS) (V5.00.02) and treated on Elekta Synergy linear accelerator. The 3D conformal radiotherapy (3DCRT) and FIMRT planning were done in CMS XIO (V5.00.01.1) TPS. The 3DCRT planning consisted of conventional medial and tangential wedge portals with multileaf collimator field shaping conforming to the target volume. For all the plans generated the following metrics were scored: V105%, V100%, V95%, mean dose (for PTV), V5%, V20%, D2cc and mean dose (for organs at risk).

Results

The mean PTV volume for 20 patients was 1,074·6±405·1 cc. The highest PTV dose coverage was observed in the 3DCRT technique with 94·1±1·8% of the breast PTV receiving 95% of the prescription dose (V95%). However, it was also observed that this technique resulted in 21·3±10% of the PTV receiving more than 105% of the prescription dose (V105%), which was highest among the three techniques. In contrast, VMAT yielded lowest V95% of 93·0±1·8 and 3·3±5·5% of V105%.

Conclusion

This study concluded equivalent result between FIMRT and VMAT. However, VMAT was found to be the choice of radiotherapy technique as it produces lesser dose distribution to heart compared with any other technique.
Tense, Time, Aspect and the Ancient Greek Verb
Authors: Moran Jerome
Published: November 2016

Nearly every – no, every – Greek grammar and course book, even the most comprehensive (in English, at any rate), gives a very skimpy, perfunctory and unhelpful account — insofar as it gives any account at all – of what ‘aspect’ is and how exactly it is related to verb tense and time (which tend to be conflated). Most of the books and articles on the subject of the aspect of the Greek verb are accessible only to the professional philologist, and can't therefore be easily applied by non-specialists to the understanding of the actual usage of Greek writers or to the imitation of their usage when translating into their language. This article sets out to remedy this situation by giving a clear and (within limits) comprehensive explanation of aspect as it applies to the Greek verb.
Is Roman Britain Sexy?
Authors: Lawrence Caroline
Published: November 2016

Way back in the late 70's when I was studying Classics at Cambridge, I had to take some courses on Roman Britain. Try as my lecturers would, they could not make it sexy. Not compared to debauched Rome and sun-soaked Greece…
Ambivalent Sexism Inventory: Adaptation to Basque Population and Sexism as a Risk Factor of Dating Violence
Authors: Ibabe Izaskun , Arnoso Ainara , Elgorriaga Edurne
Published: November 2016

There is currently a consensus that sexism is one of the most important causes of intimate partner violence, but this has yet to be empirically demonstrated conclusively. The key objective of the study was to adapt Ambivalent Sexism Inventory (ASI) and to validate it to the Basque language. It also aims to analyze the prevalence of violence in dating relationships and verify if ambivalent sexism in young men and women is a valid predictor of perpetration and/or victimization in their dating relationships. Ambivalent Sexism Inventory and Dating Relationship Questionnaire were administered to 1378 undergraduate students (66% women and 45% Basque), aged between 17 and 30. The psychometric properties of the Basque and Spanish versions of the ASI are deemed to be acceptable. Sufficient guarantees are provided to be used as an instrument for measuring ambivalent sexism in adult Basque speakers. Ambivalent sexism among young men and women are both positively associated with the perpetration of violence and victimization in their dating relationships. However, ambivalent sexism or two sub-types of sexism (hostile and benevolent) are not relevant risk factors to be perpetrator or victim of violence in dating relationships, due to accounting for 3% or less of variance in dating violence.
Long-term coding of personal and universal associations underlying the memory web in the human brain
Authors: De Falco Emanuela , Ison Matias J. , Fried Itzhak , Quian Quiroga Rodrigo
Published: November 2016

Neurons in the medial temporal lobe (MTL), a critical area for declarative memory, have been shown to change their tuning in associative learning tasks. Yet, it is unclear how durable these neuronal representations are and if they outlast the execution of the task. To address this issue, we studied the responses of MTL neurons in neurosurgical patients to known concepts (people and places). Using association scores provided by the patients and a web-based metric, here we show that whenever MTL neurons respond to more than one concept, these concepts are typically related. Furthermore, the degree of association between concepts could be successfully predicted based on the neurons’ response patterns. These results provide evidence for a long-term involvement of MTL neurons in the representation of durable associations, a hallmark of human declarative memory.
Microbe-mediated host defence drives the evolution of reduced pathogen virulence
Authors: Ford Suzanne A. , Kao Damian , Williams David , King Kayla C.
Published: November 2016

Microbes that protect their hosts from pathogens are widespread in nature and are attractive disease control agents. Given that pathogen adaptation to barriers against infection can drive changes in pathogen virulence, ‘defensive microbes’ may shape disease severity. Here we show that co-evolving a microbe with host-protective properties (Enterococcus faecalis) and a pathogen (Staphylococcus aureus) withinCaenorhabditis eleganshosts drives the evolution of reduced pathogen virulence as a by-product of adaptation to the defensive microbe. Using both genomic and phenotypic analyses, we discover that the production of fewer iron-scavenging siderophores by the pathogen reduces the fitness of the defensive microbe and underpins the decline in pathogen virulence. These data show that defensive microbes can shape the evolution of pathogen virulence and that the mechanism of pathogen resistance can determine the direction of virulence evolution.
Directed transport of neutrophil-derived extracellular vesicles enables platelet-mediated innate immune response
Authors: Rossaint Jan , Kühne Katharina , Skupski Jennifer , Van Aken Hugo , Looney Mark R. , Hidalgo Andres , Zarbock Alexander
Published: November 2016

The innate immune response to bacterial infections requires the interaction of neutrophils and platelets. Here, we show that a multistep reciprocal crosstalk exists between these two cell types, ultimately facilitating neutrophil influx into the lung to eliminate infections. Activated platelets adhere to intravascular neutrophils through P-selectin/P-selectin glycoprotein ligand-1 (PSGL-1)-mediated binding, a primary interaction that allows platelets glycoprotein Ibα (GPIbα)-induced generation of neutrophil-derived extracellular vesicles (EV). EV production is directed by exocytosis and allows shuttling of arachidonic acid into platelets. EVs are then specifically internalized into platelets in a Mac1-dependent fashion, and relocated into intracellular compartments enriched in cyclooxygenase1 (Cox1), an enzyme processing arachidonic acid to synthesize thromboxane A2 (TxA2). Finally, platelet-derived-TxA2 elicits a full neutrophil response by inducing the endothelial expression of ICAM-1, intravascular crawling, and extravasation. We conclude that critical substrate–enzyme pairs are compartmentalized in neutrophils and platelets during steady state limiting non-specific inflammation, but bacterial infection triggers regulated EV shuttling resulting in robust inflammation and pathogen clearance.
Granulocyte-Colony Stimulating Factor (G-CSF) for stroke: an individual patient data meta-analysis
Authors: England Timothy J. , Sprigg Nikola , Alasheev Andrey M. , Belkin Andrey A. , Kumar Amit , Prasad Kameshwar , Bath Philip M.
Published: November 2016

Granulocyte colony stimulating factor (G-CSF) may enhance recovery from stroke through neuroprotective mechanisms if administered early, or neurorepair if given later. Several small trials suggest administration is safe but effects on efficacy are unclear. We searched for randomised controlled trials (RCT) assessing G-CSF in patients with hyperacute, acute, subacute or chronic stroke, and asked Investigators to share individual patient data on baseline characteristics, stroke severity and type, end-of-trial modified Rankin Scale (mRS), Barthel Index, haematological parameters, serious adverse events and death. Multiple variable analyses were adjusted for age, sex, baseline severity and time-to-treatment. Individual patient data were obtained for 6 of 10 RCTs comprising 196 stroke patients (116 G-CSF, 80 placebo), mean age 67.1 (SD 12.9), 92% ischaemic, median NIHSS 10 (IQR 5–15), randomised 11 days (interquartile range IQR 4–238) post ictus; data from three commercial trials were not shared. G-CSF did not improve mRS (ordinal regression), odds ratio OR 1.12 (95% confidence interval 0.64 to 1.96, p = 0.62). There were more patients with a serious adverse event in the G-CSF group (29.6% versus 7.5%, p = 0.07) with no significant difference in all-cause mortality (G-CSF 11.2%, placebo 7.6%, p = 0.4). Overall, G-CSF did not improve stroke outcome in this individual patient data meta-analysis.
An iron detection system determines bacterial swarming initiation and biofilm formation
Authors: Lin Chuan-Sheng , Tsai Yu-Huan , Chang Chih-Jung , Tseng Shun-Fu , Wu Tsung-Ru , Lu Chia-Chen , Wu Ting-Shu , Lu Jang-Jih , Horng Jim-Tong , Martel Jan , Ojcius David M. , Lai Hsin-Chih , Young John D.
Published: November 2016

Iron availability affects swarming and biofilm formation in various bacterial species. However, how bacteria sense iron and coordinate swarming and biofilm formation remains unclear. Using Serratia marcescens as a model organism, we identify here a stage-specific iron-regulatory machinery comprising a two-component system (TCS) and the TCS-regulated iron chelator 2-isocyano-6,7-dihydroxycoumarin (ICDH-Coumarin) that directly senses and modulates environmental ferric iron (Fe3+) availability to determine swarming initiation and biofilm formation. We demonstrate that the two-component system RssA-RssB (RssAB) directly senses environmental ferric iron (Fe3+) and transcriptionally modulates biosynthesis of flagella and the iron chelator ICDH-Coumarin whose production requires the pvc cluster. Addition of Fe3+, or loss of ICDH-Coumarin due to pvc deletion results in prolonged RssAB signaling activation, leading to delayed swarming initiation and increased biofilm formation. We further show that ICDH-Coumarin is able to chelate Fe3+ to switch off RssAB signaling, triggering swarming initiation and biofilm reduction. Our findings reveal a novel cellular system that senses iron levels to regulate bacterial surface lifestyle.
Protein Inhibitor of Activated STAT3 Suppresses Oxidized LDL-induced Cell Responses during Atherosclerosis in Apolipoprotein E-deficient Mice
Authors: Wang Rong , Zhang Yanjin , Xu Liran , Lin Yan , Yang Xiaofeng , Bai Liang , Chen Yulong , Zhao Sihai , Fan Jianglin , Cheng Xianwu , Liu Enqi
Published: November 2016

Atherosclerosis is a serious public health concern. Excessive inflammatory responses of vascular cells are considered a pivotal pathogenesis mechanism underlying atherosclerosis development. It is known that Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signalling plays an important role in atherosclerosis progression. Protein inhibitor of activated STAT3 (PIAS3) is the key negative regulator of JAK/STAT3 signalling. However, its effect on atherogenesis is unknown. Here, we observed that PIAS3 levels are reduced in atherosclerotic lesions and that PIAS3 expression decreases in conjunction with increases in interleukin-6 expression and atherosclerosis severity. Oxidized low-density lipoprotein (ox-LDL), an atherogenic stimulus, reduced PIAS3 expression, an effect that may be attributed to nitric oxide synthesis upregulation. In turn, PIAS3 overexpression effectively suppressed ox-LDL-induced inflammation, lipid accumulation and vascular smooth muscle cell proliferation. These results indicate that PIAS3 is a critical repressor of atherosclerosis progression. The findings of this study have contributed to our understanding on the pathogenesis of atherosclerosis and have provided us with a potential target through which we can inhibit atherosclerosis-related cellular responses.
Magnetic Modes in Rare Earth Perovskites: A Magnetic-Field-Dependent Inelastic Light Scattering study
Authors: Saha Surajit , Cao Bing-Chen , Motapothula M. , Cong Chun-Xiao , Sarkar Tarapada , Srivastava Amar , Sarkar Soumya , Patra Abhijeet , Ghosh Siddhartha , Ariando  , Coey J. M. D. , Yu Ting , Venkatesan T.
Published: November 2016

Here, we report the presence of defect-related states with magnetic degrees of freedom in crystals of LaAlO3 and several other rare-earth based perovskite oxides using inelastic light scattering (Raman spectroscopy) at low temperatures in applied magnetic fields of up to 9 T. Some of these states are at about 140 meV above the valence band maximum while others are mid-gap states at about 2.3 eV. No magnetic impurity could be detected in LaAlO3 by Proton-Induced X-ray Emission Spectroscopy. We, therefore, attribute the angular momentum-like states in LaAlO3 to cationic/anionic vacancies or anti-site defects. Comparison with the other rare earth perovskites leads to the empirical rule that the magnetic-field-sensitive transitions require planes of heavy elements (e.g. lanthanum) and oxygen without any other light cations in the same plane. These magnetic degrees of freedom in rare earth perovskites with useful dielectric properties may be tunable by appropriate defect engineering for magneto-optic applications.
Potential costs of heterospecific sexual interactions in golden orbweb spiders (Nephila spp.)
Authors: Quiñones-Lebrón Shakira G. , Kralj-Fišer Simona , Gregorič Matjaž , Lokovšek Tjaša , Čandek Klemen , Haddad Charles R. , Kuntner Matjaž
Published: November 2016

Though not uncommon in other animals, heterospecific mating is rarely reported in arachnids. We investigated sexual interactions among four closely related and syntopical African golden orbweb spiders, Nephila inaurata, N. fenestrata, N. komaci, and N. senegalensis. In two South African localities, female webs were often inhabited by heterospecific males that sometimes outnumbered conspecifics. Species association of males with females was random in nature. In subsequent laboratory choice experiments, N. inaurata males chose heterospecific females in 30% of trials. We also observed natural mating interactions between N. inaurata males and N. komaci females, and between N. komaci males and N. inaurata females in laboratory experiments. While heterospecific mating in the laboratory never produced offspring, conspecific mating did. We discuss potential ecological and evolutionary consequences of heterospecific mating interactions in Nephila that may be particularly costly to the rarer species.
Sex-Specific Effects of Testosterone on the Sexually Dimorphic Transcriptome and Epigenome of Embryonic Neural Stem/Progenitor Cells
Authors: Bramble Matthew S. , Roach Lara , Lipson Allen , Vashist Neerja , Eskin Ascia , Ngun Tuck , Gosschalk Jason E. , Klein Steven , Barseghyan Hayk , Arboleda Valerie A. , Vilain Eric
Published: November 2016

The mechanisms by which sex differences in the mammalian brain arise are poorly understood, but are influenced by a combination of underlying genetic differences and gonadal hormone exposure. Using a mouse embryonic neural stem cell (eNSC) model to understand early events contributing to sexually dimorphic brain development, we identified novel interactions between chromosomal sex and hormonal exposure that are instrumental to early brain sex differences. RNA-sequencing identified 103 transcripts that were differentially expressed between XX and XY eNSCs at baseline (FDR = 0.10). Treatment with testosterone-propionate (TP) reveals sex-specific gene expression changes, causing 2854 and 792 transcripts to become differentially expressed on XX and XY genetic backgrounds respectively. Within the TP responsive transcripts, there was enrichment for genes which function as epigenetic regulators that affect both histone modifications and DNA methylation patterning. We observed that TP caused a global decrease in 5-methylcytosine abundance in both sexes, a transmissible effect that was maintained in cellular progeny. Additionally, we determined that TP was associated with residue-specific alterations in acetylation of histone tails. These findings highlight an unknown component of androgen action on cells within the developmental CNS, and contribute to a novel mechanism of action by which early hormonal organization is initiated and maintained.
Fasting and Feeding Signals Control the Oscillatory Expression of Angptl8 to Modulate Lipid Metabolism
Authors: Dang Fabin , Wu Rong , Wang Pengfei , Wu Yuting , Azam Md. Shofiul , Xu Qian , Chen Yaqiong , Liu Yi
Published: November 2016

Emerging evidence implies a key role of angiopoietin-like protein 8 (Angptl8) in the metabolic transition between fasting and feeding, whereas much less is known about the mechanism of its own expression. Here we show that hepatic Angptl8 is rhythmically expressed, which involving the liver X receptor alpha (LXRα) and glucocorticoid receptor (GR) modulation during feeding and fasting periods, respectively. In addition, Angptl8 mRNA is very unstable, which contributes to the nature of its daily rhythmicity by rapidly responding to fasting/feeding transition. To explore its pathological function in dexamethasone (DEX)-induced fatty liver, we reversed its suppression by glucocorticoids through adenoviral delivery of Angptl8 gene in mouse liver. Surprisingly, hepatic overexpression of Angptl8 dramatically elevated plasma triglyceride (TG) and non-esterified fatty acid (NEFA) levels in DEX-treated mice, suggesting a metabolic interaction between Angptl8 and glucocorticoid signaling. Moreover, intracellular hepatic Angptl8 is implicated in the regulation of lipid homeostasis by the experiments with ectopic expression of a nonsecreted Angptl8 mutant (Δ25-Angptl8). Altogether, our data demonstrate the molecular mechanism of the diurnal rhythm of Angptl8 expression regulated by glucocorticoid signaling and LXRα pathway, and provide new evidence to understand the role of Angptl8 in maintaining plasma TG homeostasis.
Core-shell microstructured nanocomposites for synergistic adjustment of environmental temperature and humidity
Authors: Zhang Haiquan , Yuan Yanping , Zhang Nan , Sun Qingrong , Cao Xiaoling
Published: November 2016

The adjustment of temperature and humidity is of great importance in a variety of fields. Composites that can perform both functions are prepared by mixing phase change materials (PCMs) with hygroscopic materials. However, the contact area between the adsorbent and humid air is inevitably decreased in such structures, which reduces the number of mass transfer channels for water vapor. An approach entailing the increase in the mass ratio of the adsorbent is presented here to improve the adsorption capacity. A core-shell CuSO4/polyethylene glycol (PEG) nanomaterial was developed to satisfy the conflicting requirements of temperature control and dehumidification. The results show that the equilibrium adsorption capacity of the PEG coating layer was enhanced by a factor of 188 compared with that of the pure PEG powder. The coating layer easily concentrates vapor, providing better adsorption properties for the composite. Furthermore, the volume modification of the CuSO4 matrix was reduced by 80% by the PEG coated layer, a factor that increases the stability of the composite. For the phase change process, the crystallization temperature of the coating layer was adjusted between 37.2 and 46.3 °C by interfacial tension. The core-shell CuSO4/PEG composite reported here provides a new general approach for the simultaneous control of temperature and humidity.
Bacterial meningitis in diabetes patients: a population-based prospective study
Authors: van Veen Kiril E. B. , Brouwer Matthijs C. , van der Ende Arie , van de Beek Diederik
Published: November 2016

Diabetes mellitus is associated with increased infection rates. We studied clinical features and outcome of community-acquired bacterial meningitis in diabetes patients. Patients were selected from a nationwide, prospective cohort on community-acquired bacterial meningitis performed from March 2006 to October 2014. Data on patient history, symptoms and signs on admission, treatment, and outcome were prospectively collected. A total of 183 of 1447 episodes (13%) occurred in diabetes patients. The incidence of bacterial meningitis in diabetes patients was 3.15 per 100,000 patients per year and the risk of acquiring bacterial meningitis was 2.2-fold higher for diabetes patients. S. pneumoniae was the causative organism in 139 of 183 episodes (76%) and L. monocytogenes in 11 of 183 episodes (6%). Outcome was unfavourable in 82 of 183 episodes (45%) and in 43 of 183 episodes (23%) the patient died. Diabetes was associated with death with an odds ratio of 1.63 (95% CI 1.12–2.37, P = 0.011), which remained after adjusting for known predictors of death in a multivariable analysis (OR 1.98 [95% CI 1.13–3.48], P = 0.017). In conclusion, diabetes is associated with a 2-fold higher risk of acquiring bacterial meningitis. Diabetes is a strong independent risk factor for death in community-acquired adult bacterial meningitis.
Aberrant SSEA-4 upregulation mediates myofibroblast activity to promote pre-cancerous oral submucous fibrosis
Authors: Yu Cheng-Chia , Yu Chuan-Hang , Chang Yu-Chao
Published: November 2016

Oral submucous fibrosis (OSF), regarded as a precancerous condition, is characterized by juxta-epithelial inflammatory reaction followed by fibro-elastic change in the lamina properia and epithelial atrophy. The pathologic mechanisms of OSF still need to be further clarified. In the study, we investigated the functional expression of SSEA-4, which is a well-known stemness marker, in myofibroblast activity and the clinical significance in OSF tissues. The expression of SSEA-4 in OSF was evaluated by immunohistochemical staining. Functional analysis of SSEA-4 on myofibroblast activity of OSF was achieved by lentiviral silencing ST3GAL2. Immunohisitochemistry demonstrated that SSEA-4 expression was significantly higher expression in areca quid chewing-associated OSF tissues than those of normal oral mucosa tissues. From flow cytometry analysis, arecoline dose-dependently activated SSEA-4 expression in primary human normal buccal mucosal fibroblasts (BMFs). Sorted SSEA-4-positive cells from fibrotic BMFs (fBMFs) have higher colony-forming unit, collagen gel contraction, and α-smooth muscle actin (α-SMA) expression than SSEA-4-negative subset. Knockdown of ST3GAL2 in fBMFs suppressed SSEA-4 expression, collagen contraction, migration, invasiveness, and wound healing capability. Consistently, silencing ST3GAL2 was found to repress arecoline-induced myofibroblast activity in BMFs. The study highlights SSEA-4 as a critical marker for therapeutic intervention to mediate myofibroblast transdifferentiation in areca quid chewing-associated OSF.
Intrinsic K-Ras dynamics: A novel molecular dynamics data analysis method shows causality between residue pair motions
Authors: Vatansever Sezen , Gümüş Zeynep H. , Erman Burak
Published: November 2016

K-Ras is the most frequently mutated oncogene in human cancers, but there are still no drugs that directly target it in the clinic. Recent studies utilizing dynamics information show promising results for selectively targeting mutant K-Ras. However, despite extensive characterization, the mechanisms by which K-Ras residue fluctuations transfer allosteric regulatory information remain unknown. Understanding the direction of information flow can provide new mechanistic insights for K-Ras targeting. Here, we present a novel approach –conditional time-delayed correlations (CTC) – using the motions of all residue pairs of a protein to predict directionality in the allosteric regulation of the protein fluctuations. Analyzing nucleotide-dependent intrinsic K-Ras motions with the new approach yields predictions that agree with the literature, showing that GTP-binding stabilizes K-Ras motions and leads to residue correlations with relatively long characteristic decay times. Furthermore, our study is the first to identify driver-follower relationships in correlated motions of K-Ras residue pairs, revealing the direction of information flow during allosteric modulation of its nucleotide-dependent intrinsic activity: active K-Ras Switch-II region motions drive Switch-I region motions, while α-helix-3L7 motions control both. Our results provide novel insights for strategies that directly target mutant K-Ras.