bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of in-country experience on the acquisition of oral communication skills in Japanese
Authors: Atsuzawa-Windley Sonomi , Noguchi Sachiko
Published: March 2018

This study aims to investigate the effects of in-country experience on oral communication skills in Japanese. Do students who have had in-country experience in Japan have a higher level of proficiency in any area of oral communication skills than those who have not? To what extent do students with in-country experience differ from those without in their acquisition of various areas of oral communication skills? The performance of subjects in the mid-year oral examination were used as data for this study and comparisons were made between those with and without in-country experience. We believe that linguistic competence alone is not sufficient for successful communication. The results of this study provide tentative evidence that in-country experience did have positive effects on the acquisition of oral communication skills. However, the relationship between the acquisition of more than one speech style and sociolinguistic competence also emerged as a complex issue.
The teaching of Chinese and the Chinese way of thinking
Authors: Wu Guo
Published: March 2018

The teaching of Mandarin Chinese can be enhanced by the application of principles underlying the Chinese way of thinking -the Conceptual Sequence Principle (CSP) (Wu 1992:53) and the Principle of Temporal Sequence (PTS) (Tai 1985:61). These are fundamental principles motivating syntactic structures and discourse organisations in Chinese. The two principles capture the most general tendency of Chinese syntactic structures and discourse organisation. CSP accounts for various double (or multiple) nominative constructions typical of the language including Subject-Object-Verb (SOV) and Object-Subject-Verb (OSV) patterns, whereas PTS explains the relative position of verbs in verb compounds and serial verb constructions, and the position of adverbials – typically those of time and location – in relation to the verb in a sentence, as well as the because-therefore discourse pattern (Kirkpatrick 1991:183). An understanding of the two principles will not only enable students to gain insight into the Chinese language and avoid common mistakes caused by the interference of their mother tongue, but also assist them to understand the Chinese way of thinking and achieve interactive competence in the language.
Strategy choice and the target language
Authors: White Cynthia
Published: March 2018

This paper compares the strategies used by a group of English native speakers to develop competence in Japanese, a non-cognate language, and in a more familiar language, French. The participants were undergraduate students enrolled in both French and Japanese language courses. A verbal report procedure, the yoked subject technique, was used to gather data on strategy use by learners as they worked with target language materials. The data was analysed according to four dimensions of strategy use: metacognitive, cognitive, social and affective. The results indicated that the cognitive strategies learners used when learning Japanese diverged from those they used for learning French. The learning of Japanese was characterised by the use of repetition, writing out, and translation, with limited use of resourcing and no elaboration or inferencing strategies. The discussion of the results addresses the issue of the impact of language teaching methodology on cognitive strategy use, the effects of which cannot be readily separated from those of the structure of the target language.
Some examples of listening exercises in Mandarin
Authors: Lee Philip Yungkin
Published: March 2018

The developing of listening skills is one of the main problem areas of learning to speak Chinese. Beginning students are often baffled by Chinese words which they consider to be homophones, or by words differing only in tones. They need to be convinced that these problems inherent in learning the Chinese language can be overcome if they develop strategies to listen for structures meaning. Since Krashen (1980) pioneered the concept of Comprehensible Input, language teachers have tried to produce listening materials to simulate situations for students to practise authentic language. Some of these teachers include ESL teachers such as Penny Ur, Mary Underwood and Jack Richards. They have produced teachers’ resource books and conducted research on methodological issues. I have been a member of a team of teachers from the University of New South Wales who have undertaken to produce listening packages using authentic-like materials. One of the outcomes of this project is the production of Listening to Mandarin. This paper gives some examples of the strategies used and discusses problems in the teaching of listening comprehension in Mandarin.
Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA)
Authors: McDonald L Clifford , Gerding Dale N , Johnson Stuart , Bakken Johan S , Carroll Karen C , Coffin Susan E , Dubberke Erik R , Garey Kevin W , Gould Carolyn V , Kelly Ciaran , Loo Vivian , Shaklee Sammons Julia , Sandora Thomas J , Wilcox Mark H
Published: March 2018

A panel of experts was convened by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) to update the 2010 clinical practice guideline on Clostridium difficile infection (CDI) in adults. The update, which has incorporated recommendations for children (following the adult recommendations for epidemiology, diagnosis, and treatment), includes significant changes in the management of this infection and reflects the evolving controversy over best methods for diagnosis. Clostridium difficile remains the most important cause of healthcare-associated diarrhea and has become the most commonly identified cause of healthcare-associated infection in adults in the United States. Moreover, C. difficile has established itself as an important community pathogen. Although the prevalence of the epidemic and virulent ribotype 027 strain has declined markedly along with overall CDI rates in parts of Europe, it remains one of the most commonly identified strains in the United States where it causes a sizable minority of CDIs, especially healthcare-associated CDIs. This guideline updates recommendations regarding epidemiology, diagnosis, treatment, infection prevention, and environmental management.
Effects of supplemental betaine to semen extenders on semen quality in boars
Authors: Lugar D W , Krom W A , Mings P D , Stewart K R
Published: March 2018

Two experiments were conducted to evaluate the use of supplemental betaine in commercially available semen extenders. In experiment 1 (Exp1), semen was collected from six mature boars once weekly for 6 wk (3 wk in summer and 3 wk in winter) and diluted into a commercial extender with the following betaine concentrations: 0, 51, 102, and 205 mM. Semen samples were analyzed on the day of collection (D0) and after 72 h of storage (D3). In experiment 2 (Exp2), semen was collected from four mature boars for 3 wk and was diluted into three commercially available semen extenders (short term, ST; long term with bovine serum albumin, BSA; and long term without BSA, LT), with and without supplemental betaine (0 and 70 mM), and analyzed on D0 and D3. Semen was analyzed using computer-assisted sperm assessment (Ceros II, IMV) and morphology using phase contrast microscopy. In Exp1, total motility on D0 was less for 0 mM than that for 102 mM (P = 0.038) and was substantially reduced for 205 mM compared with 102 mM (P < 0.001). Supplementation with 205 mM betaine resulted in a significant reduction in the percentage of morphologically normal sperm (P < 0.001). In Exp2, 70 mM betaine reduced the total motility compared with 0 mM (P = 0.010) but did not impact percentage of normal sperm (P = 0.942). The use of supplemental betaine may partially alleviate the dilution effect on sperm, though boar genetics may impact its efficacy. Further research is needed to make a definitive conclusion.
Genomic Analysis, Sequence Diversity, and Occurrence of Apple necrotic mosaic virus, a Novel Ilarvirus Associated with Mosaic Disease of Apple Trees in China
Authors: Xing Fei , Robe Berhanu Lemma , Zhang Zhixiang , Wang Hongqing , Li Shifang
Published: March 2018

China accounts for over 50% of apple production worldwide. Very recently, a novel ilarvirus, Apple necrotic mosaic virus (ApNMV), was isolated from apple trees showing mosaic symptoms in Japan. This study compared different types of mosaic symptoms observed in apple trees in China under field conditions. Complete nucleotide sequences were obtained for six isolates of ApNMV. The genomic components varied in size from 3,378 to 3,380 nt (RNA1), 2,778 to 2,786 nt (RNA2), and 1,909 to 1,955 nt (RNA3), respectively. Although nucleotide sequence similarities with subgroup 3 ilarviruses were low (49.2 to 64.3%), results of phylogenetic analysis indicated that Chinese ApNMV isolates were clustered in subgroup 3 together with Prunus necrotic ring spot virus (PNRSV) and Apple mosaic virus (ApMV). Apple mosaic disease occurred widely in apple producing areas of China with a very high percentage (92.1%, 268 out of 291) of symptomatic trees being infected with ApNMV but not with ApMV. The data suggested that ApNMV might be the main pathogen causing apple mosaic disease in China. The genomes of the six studied Chinese ApNMV isolates demonstrated substantial sequence diversity. Here, we demonstrated a strong association of ApNMV with the mosaic disease of apple trees in China.
The solution of the sixth Hilbert problem: the ultimate Galilean revolution
Authors: D'Ariano Giacomo Mauro
Published: March 2018

I argue for a full mathematization of the physical theory, including its axioms, which must contain no physical primitives. In provocative words: ‘physics from no physics’. Although this may seem an oxymoron, it is the royal road to keep complete logical coherence, hence falsifiability of the theory. For such a purely mathematical theory the physical connotation must pertain only the interpretation of the mathematics, ranging from the axioms to the final theorems. On the contrary, the postulates of the two current major physical theories either do not have physical interpretation (as for von Neumann’s axioms for quantum theory), or contain physical primitives as ‘clock’, ‘rigid rod’, ‘force’, ‘inertial mass’ (as for special relativity and mechanics). A purely mathematical theory as proposed here, though with limited (but relentlessly growing) domain of applicability, will have the eternal validity of mathematical truth. It will be a theory on which natural sciences can firmly rely. Such kind of theory is what I consider to be the solution of the sixth Hilbert problem. I argue that a prototype example of such a mathematical theory is provided by the novel algorithmic paradigm for physics, as in the recent information-theoretical derivation of quantum theory and free quantum field theory.

This article is part of the theme issue ‘Hilbert’s sixth problem’.
A short walk in quantum probability
Authors: Hudson Robin
Published: March 2018

This is a personal survey of aspects of quantum probability related to the Heisenberg commutation relation for canonical pairs. Using the failure, in general, of non-negativity of the Wigner distribution for canonical pairs to motivate a more satisfactory quantum notion of joint distribution, we visit a central limit theorem for such pairs and a resulting family of quantum planar Brownian motions which deform the classical planar Brownian motion, together with a corresponding family of quantum stochastic areas.

This article is part of the themed issue ‘Hilbert’s sixth problem’.
The quantumN-body problem in the mean-field and semiclassical regime
Authors: Golse François
Published: March 2018

The present work discusses the mean-field limit for the quantumN-body problem in the semiclassical regime. More precisely, we establish a convergence rate for the mean-field limit which is uniform as the ratio of Planck constant to the action of the typical single particle tends to zero. This convergence rate is formulated in terms of a quantum analogue of the quadratic Monge–Kantorovich or Wasserstein distance. This paper is an account of some recent collaboration with C. Mouhot, T. Paul and M. Pulvirenti.

This article is part of the themed issue ‘Hilbert’s sixth problem’.
Derivation of regularized Grad's moment system from kinetic equations: modes, ghosts and non-Markov fluxes
Authors: Karlin Ilya
Published: March 2018

Derivation of the dynamic correction to Grad’s moment system from kinetic equations (regularized Grad’s 13 moment system, or R13) is revisited. The R13 distribution function is found as a superposition of eight modes. Three primary modes, known from the previous derivation (Karlin
et al.
1998
Phys. Rev. E
57
, 1668–1672. (
doi:10.1103/PhysRevE.57.1668
)), are extended into the nonlinear parameter domain. Three essentially nonlinear modes are identified, and two ghost modes which do not contribute to the R13 fluxes are revealed. The eight-mode structure of the R13 distribution function implies partition of R13 fluxes into two types of contributions: dissipative fluxes (both linear and nonlinear) and nonlinear streamline convective fluxes. Physical interpretation of the latter non-dissipative and non-local in time effect is discussed. A non-perturbative R13-type solution is demonstrated for a simple Lorentz scattering kinetic model. The results of this study clarify the intrinsic structure of the R13 system.

This article is part of the theme issue ‘Hilbert’s sixth problem’.
Aggregation of Markov flows I: theory
Authors: MacKay R. S. , Robinson J. D.
Published: March 2018

A Markov flow is a stationary measure, with the associated flows and mean first passage times, for a continuous-time regular jump homogeneous semi-Markov process on a discrete state space. Nodes in the state space can be eliminated to produce a smaller Markov flow which is a factor of the original one. Some improvements to the elimination methods of Wales are given. The main contribution of the paper is to present an alternative, namely a method to aggregate groups of nodes to produce a factor. The method can be iterated to make hierarchical aggregation schemes. The potential benefits are efficient computation, including recomputation to take into account local changes, and insights into the macroscopic behaviour.

This article is part of the theme issue ‘Hilbert’s sixth problem’.
Hilbert’s sixth problem: the endless road to rigour
Authors: Gorban A. N.
Published: March 2018

In this introduction, the essence of the sixth problem is discussed and the content of this issue is introduced.

This article is part of the theme issue ‘Hilbert’s sixth problem’.
Non-canonical Wnt signalling initiates scarring in biliary disease
Authors: Wilson DH , Mellin RP , Younger NT , Jarman EJ , Raven A , Chen P , Dean CH , Henderson DJ , Kendall TJ , Boulter L
Published: March 2018

Cholangiopathies, or biliary diseases, account for a significant proportion of adult and paediatric liver disease. In these pathologies, iterative cycles of damage and repair result in the development of a regenerative microenvironment surrounding the bile ducts, which orchestrates both epithelial proliferation and also biliary fibrosis. Ultimately, fibrosis at the cost of repair results in cholestasis and liver failure, necessitating liver transplantation. Whilst the fibrogenic mechanisms in hepatocellular disease have been widely studied, little is known about the processes that regulate biliary scarring. We sought to determine how the injured biliary epithelium communicates to adjacent stromal cells to regulate scar formation, and to identify therapeutically targetable pathways that could be inhibited to reduce biliary scarring, whilst maintaining the pro-regenerative stroma. Using human tissue, bile duct organoids and animal models of biliary disease, we show that non-canonical Wnt signalling is important in initiating biliary scarring. This process is driven by myeloid Wnt5a and acts through epithelial Vangl2, which is upstream of Jnk/cJun signalling. Activation of this pathway drives a pro-fibrotic signalling process which instructs portal fibroblasts to synthesise collagen. Finally, we determine that therapeutic Wnt ligand inhibition reduces biliary scarring, identifying non-canonical Wnt signalling as a novel target for anti-fibrotic therapy in cholestatic biliary disease.
Human neuroblastoma SH-SY5Y cells treated with okadaic acid express phosphorylated high molecular weight tau-immunoreactive protein species
Authors: Boban Mirta , Miškić Terezija , Babić Leko Mirjana , Hof Patrick R. , Šimić Goran
Published: March 2018

Recent data suggest that early stages of Alzheimer’s disease (AD) are characterized by an abnormally high phosphorylation of microtubule-associated protein tau and truncation of its C-terminus. Tau hyperphosphorylation may result from the downregulation of phosphatases, especially protein phosphatase 2A. In an attempt to model and analyze these molecular events we treated SH-SY5Y cells with okadaic acid (OA), an inhibitor of protein phosphatases. In addition to the low molecular weight tau, such treatment lead to the appearance of heat-stable protein species with apparent high molecular weight around 100 kDa, which were immunoreactive to tau antibodies against phosphorylated Ser202 and phosphorylated Ser396. Based on the observation that high molecular weight tau-immunoreactive proteins (HMW-TIP) correspond to the predicted size of two monomers of tau, one possibility is that HMW-TIP represent tau oligomers. The absence of HMW-TIP detection by anti-total tau antibodies used may be a consequence of epitope masking, or a combination of epitope masking and protein truncation. We noted the stability of HMW-TIP in the presence of strong denaturing agents, such as urea and guanidine, as well as upon partial dephosphorylation by the alkaline phosphatase. Moreover, as HMW-TIP did not dissociate the presence of β-mercaptoethanol, it was also independent from disulfide bonds. Taken together, these data show that OA treatment of SH-SY5Y cells induces the appearance of HMW-TIP, which may represent tau oligomer or tau-crossreactive phospho-proteins. Our findings have implications for further studies of tau under the conditions of protein phosphatase downregulation.
Effects of larval density on gene regulation inC. elegansduring routine L1 synchronization
Authors: Chan Io Long , Rando Oliver J. , Conine Colin C.
Published: March 2018

Bleaching gravidC. elegansfollowed by a short period of starvation of the L1 larvae is a routine method performed by worm researchers for generating synchronous populations for experiments. During the process of investigating dietary effects on gene regulation in L1 stage worms by single-worm RNA-Seq, we found that the density of resuspended L1 larvae affects expression of many mRNAs. Specifically, a number of genes related to metabolism and signalling are highly expressed in worms arrested at low density, but are repressed at higher arrest densities. We generated a GFP reporter strain based on one of the most density-dependent genes in our dataset –lips-15– and confirmed that this reporter was expressed specifically in worms arrested at relatively low density. Finally, we show that conditioned media from high density L1 cultures was able to downregulatelips-15even in L1 animals arrested at low density, and experiments usingdaf-22mutant animals demonstrated that this effect is not mediated by the ascaroside family of signalling pheromones. Together, our data implicate a soluble signalling molecule in density sensing by L1 stageC. elegans, and provide guidance for design of experiments focused on early developmental gene regulation.
Acute Food Deprivation Rapidly Modifies Valence-Coding Microcircuits in the Amygdala
Authors: Calhoon Gwendolyn G , Sutton Amy K , Chang Chia-Jung , Libster Avraham M , Glober Gordon F , Lévêque Clémentine L , Murphy G David , Namburi Praneeth , Leppla Christopher A , Siciliano Cody A , Wildes Craig P , Kimchi Eyal Y , Beyeler Anna , Tye Kay M
Published: March 2018

In the quest for food, we may expend effort and increase our vulnerability to potential threats. Motivation to seek food is dynamic, varying with homeostatic need. What mechanisms underlie these changes? Basolateral amygdala neurons projecting to the nucleus accumbens (BLA→NAc) preferentially encode positive valence, whereas those targeting the centromedial amygdala (BLA→CeM) preferentially encode negative valence. Longitudinal in vivo two-photon calcium imaging revealed that BLA→NAc neurons were more active, while BLA→CeM neurons were less active, following just 1 day of food deprivation. Photostimulating BLA→CeM neurons inhibited BLA→NAc neurons at baseline, but food deprivation rapidly converted this inhibition into facilitation, supporting a model wherein BLA→NAc excitability mediates invigorated food-seeking behavior after deprivation. Indeed, inhibiting BLA→NAc reduced motivation for a caloric reinforcer in food deprived animals. Taken together, negative valence overrides positive valence processing in satiety, but changing homeostatic needs alter reward value via a rapid shift in the balance between projection-defined populations of BLA neurons.
A “New Deal” for the profession
Authors: Detzen Dominic
Published: March 2018

Purpose

The purpose of this paper is to analyze how “New Deal” regulatory initiatives, primarily the Securities Acts and the Securities and Exchange Commission (SEC), changed US auditors’ professional knowledge conception, culminating in the 1938 expansion of the Committee on Accounting Procedure (CAP), the first US body to set accounting principles.

Design/methodology/approach

The paper combines Halliday’s (1985) knowledge mandates with Hancher and Moran’s (1989) regulatory space to attain a theory-based understanding of auditors’ changing knowledge conceptions amid regulatory pressure. It draws on a range of primary and secondary sources to examine the period from 1929 to 1938.

Findings

Following the stock market crash, the newly created SEC aimed to engage auditors as a means to regulate companies’ accounting practices based on a set of codified principles. While entailing increased status, this new role conflicted with the auditors’ knowledge conception, which was based on professional judgment and personal integrity. Pressure from the SEC and academics eventually made auditors agree to a codification of their professional knowledge and create the CAP as a cooperative regulatory solution.

Originality/value

The paper explores the role of auditors’ knowledge conceptions in the emergence of today’s standard setting. It is suggested that auditors’ incomplete control of their professional knowledge made standard setting a form of co-regulation, located between the actors occupying the regulatory space of accounting.
What do teachers share within Socialized Knowledge Communities: a case of Pinterest
Authors: Hu Sihua , Torphy Kaitlin T. , Opperman Amanda , Jansen Kimberly , Lo Yun-Jia
Published: March 2018

Purpose

The purpose of this paper is to examine early career teachers’ Socialized Knowledge Communities (SKCs) as they relate to the pursuit of mathematics knowledge and teaching. The authors investigate Pinterest, a living data archive, as an opportunity to view teachers’ sense-making and construction of instructional resources. Through this lens, the authors examine how teachers form and share mathematical meaning individually and collectively through professional collaboration.

Design/methodology/approach

This work characterizes teachers’ curation of mathematical resources both in the kinds of mathematics teachers are choosing and the quality therein. Finally, the authors examine through epistemic network analysis how teachers are sense-making through a statistical approach to identifying their organization of mathematics curation by typology and cognitive process demand.

Findings

Results show that sampled teachers predominantly curate instructional resources that require students to perform standard algorithm and represent mathematics relationships in visualization within Pinterest. Additionally, the authors find the resources curated by teachers have lower cognitive demand. Finally, epistemic networks show teachers make connections among instructional resources with particular types as well as with different levels of cognitive demand as they sense-make their curated curriculum. In particular, difference in teachers’ internal consideration of the quality of tasks is associated with their years of experience.

Originality/value

Twenty-first century classrooms and teachers engage frequently in curation of instructional resources online. The work contributes to an emergent understanding of teachers’ professional engagement in virtual spaces by characterizing the instructional resources being accessed, shared, and diffused. Understanding the nature of the content permeating teachers’ SKCs is essential to increase teachers’ professional capital in the digital age.
Research on Performance and Valuation of Enterprises Placarded by Others Based on the Improved Panel Vector Auto-Regression Model
Authors: Luo Na
Published: March 2018

In recent years, enterprises, which were placarded, have become a heated issue in the secondary market in China. However, there still lack researches about the performance and valuation of those enterprises which were placarded. Therefore, it seems that it is lack of persuasion to use the word “barbarians” to define the enterprises which carry out placard. For the reasons above, this paper makes the use of the improved PVAR model to give an empirical analysis on the performance and valuation of the enterprises placarded, based on the samples between 2011 and 2015. First, this paper divides the whole samples into two subsample groups by the dummy variable, according to the certain point of time whether the enterprise has been placarded. After that, it build two PVAR models combining the performance indicators and the valuation indicators. The results show that the sensitivity of the target enterprise’s performance is not as good as its valuation. Second, the two subsample groups are analyzed by the impulse response function. It explains that placard creates an incentive effect for the target enterprise in the short term. Third, by using the variance decomposition, this paper achieves a conclusion that placard reduces the dependence of the target enterprise on the aspects of its valuation, profitability, size and risk. Therefore, placard is a good signal for those target enterprises on the whole, which brings a nice momentum for the enterprises on the valuation, profitability, size and risk in the short term. In the long run, the enterprises will adjust to a stable state based on the short-term changes. From this point of view, “barbarians at the gate” bring the motivation rather than chaos.
Investigation of digital alloyed AlInSb metamorphic buffers
Authors: Dahiya Vinita , Deitz Julia I. , Hollingshead David A. , Carlin John A. , Grassman Tyler J. , Krishna Sanjay
Published: March 2018

Al1-xInxSb metamorphic step-graded buffers with Al0.6In0.4Sb terminal layers, designed to serve as a virtual substrate to support integrated InAs0.5Sb0.5 long-wave infrared absorber layers, were grown on GaSb wafers via molecular beam epitaxy. Two different structural profiles were used to define the effective composition of each buffer step: one based on digital alloys (1 nm period, ∼1.6 unit cells) and the other based on short period superlattices (10 nm period, ∼16 unit cells). Characterization via optical Nomarski microscopy, x-ray diffraction reciprocal space mapping, and transmission electron microscopy indicates that the digital alloy based structure behaves similar to that expected for a conventional bulk ternary alloy based structure, while the short period superlattice structure exhibits significantly hindered relaxation within the buffer layers.
Low-energy bismuth primary ion beams for molecular ion detection in TOF-SIMS
Authors: Miyayama Takuya , Iida Shin-ichi
Published: March 2018

Low-energy (sub-keV) bismuth primary ion beams were used for time-of-flight secondary ion mass spectrometry (ToF-SIMS) to investigate their suitability for detecting molecular ions in organic materials. In this study, a 2 keV Bi3+ (667 eV/atom) primary ion beam was compared with a 54 keV Bi3++ (18 keV/atom) beam. The 2 keV Bi3+ beam detected much less fragmentation for some organic materials compared with the 54 keV Bi3++ beam. Atomic level fragmentation was most notably suppressed by the 2 keV Bi3+ beam and deprotonated molecule [M-H+] was also significantly suppressed. As a result, intact molecule (M+) and, interestingly, bismuth-attached secondary ion [M+Bi]+ were observed instead of the protonated molecule [M+H]+ using the 2 keV Bi3+ beam. Results suggest that low-energy bismuth primary ion beams are potential candidates for molecular ion detection in ToF-SIMS.
Higher-order frequency locking of an organ pipe: A measurement study based on synchronization theory
Authors: Okada Masahiro , Kaburagi Tokihiko
Published: March 2018

Higher-order frequency locking of an organ pipe was investigated in terms of relationships between the locking phenomena and the harmonics of the pipe sound and an external force acting onto the pipe. The authors first assumed the pipe as a phase oscillator that is used in synchronization theory and predicted frequency ratios that can cause frequency locking. The authors then forced an actual pipe using a pure tone with frequency ratios of 1 : 1, 1 : 2, 2 : 1, 1 : 3, and 2 : 3. In addition, experiments were conducted using complex tones to investigate effects of higher harmonics of the external force on frequency locking. As a result, frequency locking occurred only at frequency ratios of 1 : 1, 1 : 2, and 1 : 3 in the case of the pure tone in agreement with the prediction of synchronization theory. For the complex tone, the authors succeeded in inducing 2 : 1 locking. The results show that the frequency of a harmonic component of the external force was close to that of the pipe sound when frequency locking occurred. Frequency locking of an organ pipe was therefore enhanced through the proximity of the harmonics of the pipe sound and the external force.
Depletion of Glucose Activates Catabolite Repression during Pneumonic Plague
Authors: Ritzert Jeremy T. , Lathem Wyndham W.
Published: March 2018

Bacterial pathogenesis depends on changes in metabolic and virulence gene expression in response to changes within a pathogen's environment. The plague-causing pathogen,
Yersinia pestis
, requires expression of the gene encoding the Pla protease for progression of pneumonic plague. The catabolite repressor protein Crp, a global transcriptional regulator, may serve as the activator of
pla
in response to changes within the lungs as disease progresses. By using gene reporter fusions, the spatial and temporal activation of the
crp
and
pla
promoters was measured in a mouse model of pneumonic plague. In the lungs,
crp
was highly expressed in bacteria found within large aggregates resembling biofilms, while
pla
expression increased over time independent of the aggregated state. Increased expression of
crp
and
pla
correlated with a reduction in lung glucose levels. Deletion of the glucose-specific phosphotransferase system EIIBC (PtsG) of
Y. pestis
rescued glucose levels in the lungs, resulting in reduced expression of both
crp
and
pla
. We propose that activation of
pla
expression during pneumonic plague is driven by an increase of both Crp and cAMP levels following consumption of available glucose in the lungs by
Y. pestis
. Thus, Crp operates as a sensor linking the nutritional environment of the host to regulation of virulence gene expression.

IMPORTANCE
Using
Yersinia pestis
as a model for pneumonia, we discovered that glucose is rapidly consumed, leading to a catabolite-repressive environment in the lungs. As a result, expression of the gene encoding the plasminogen activator protease, a target of the catabolite repressor protein required for
Y. pestis
pathogenesis, is activated. Interestingly, expression of the catabolite repressor protein itself was also increased in the absence of glucose but only in biofilms. The data presented here demonstrate how a bacterial pathogen senses changes within its environment to coordinate metabolism and virulence gene expression.
Nonstructural Protein 5A Impairs DNA Damage Repair: Implications for Hepatitis C Virus-Mediated Hepatocarcinogenesis
Authors: Nguyen Tram T. T. , Park Eun-Mee , Lim Yun-Sook , Hwang Soon B.
Published: March 2018

RAD51-associated protein 1 (RAD51AP1) is a member of the multiprotein complexes postulated to carry out RAD51-mediated homologous recombination and DNA repair in mammalian cells. In the present study, we showed that hepatitis C virus (HCV) NS5A directly bound RAD51AP1 and increased the protein level of RAD51AP1 through modulation of the ubiquitin-proteasome pathway. We also demonstrated that RAD51AP1 protein levels were increased in the liver tissues of HCV-infected patients and NS5A-transgenic mice. Importantly, NS5A impaired DNA repair by disrupting the RAD51/RAD51AP1/UAF1 complex and rendered HCV-infected cells more sensitive to DNA damage. Silencing of RAD51AP1 expression resulted in a decrease of viral propagation. We further demonstrated that RAD51AP1 was involved in the assembly step of the HCV life cycle by protecting viral RNA. These data suggest that HCV exploits RAD51AP1 to promote viral propagation and thus that host DNA repair is compromised in HCV-infected cells. Overall, our findings provide mechanistic insight into the pathogenesis of HCV infection.

IMPORTANCE
Chronic infection with HCV is the leading cause of hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying HCV-induced HCC are not fully understood. Here we demonstrate that the HCV NS5A protein physically interacts with RAD51AP1 and increases the RAD51AP1 protein level through modulation of the ubiquitin-proteasome pathway. HCV coopts host RAD51AP1 to protect viral RNA at an assembly step of the HCV life cycle. Note that the RAD51 protein accumulates in the cytoplasm of HCV-infected cells, and thus the RAD51/RAD51AP1/UAF1-mediated DNA damage repair system in the nucleus is compromised in HCV-infected cells. Our data may provide new insight into the molecular mechanisms of HCV-induced pathogenesis.
Atomic Structure of the Murine Norovirus Protruding Domain and Soluble CD300lf Receptor Complex
Authors: Kilic Turgay , Koromyslova Anna , Malak Virginie , Hansman Grant S.
Published: March 2018

Human noroviruses are the leading cause of acute gastroenteritis in humans. Noroviruses also infect animals, such as cows, mice, cats, and dogs. How noroviruses bind and enter host cells is still incompletely understood. Recently, the type I transmembrane protein CD300lf was identified as the murine norovirus receptor, yet it is unclear how the virus capsid and receptor interact at the molecular level. In this study, we determined the X-ray crystal structure of the soluble CD300lf (sCD300lf) and the murine norovirus capsid protruding domain complex at a 2.05-Å resolution. We found that the sCD300lf-binding site is located on the topside of the protruding domain and involves a network of hydrophilic and hydrophobic interactions. sCD300lf locked nicely into a complementary cavity on the protruding domain that is additionally coordinated with a positive surface charge on sCD300lf and a negative surface charge on the protruding domain. Five of six protruding domain residues interacting with sCD300lf were maintained between different murine norovirus strains, suggesting that sCD300lf was capable of binding to a highly conserved pocket. Moreover, a sequence alignment with other CD300 paralogs showed that the sCD300lf-interacting residues were partially conserved in CD300ld but variable in other CD300 family members, consistent with previously reported infection selectivity. Overall, these data provide insights into how a norovirus engages a protein receptor and will be important for a better understanding of selective recognition and norovirus attachment and entry mechanisms.

IMPORTANCE
Noroviruses exhibit exquisite host range specificity due to species-specific interactions between the norovirus capsid protein and host molecules. Given this strict host range restriction, it has been unclear how the viruses are maintained within a species between relatively sporadic epidemics. While much data demonstrate that noroviruses can interact with carbohydrates, recent work has shown that expression of the protein CD300lf is both necessary and sufficient for murine norovirus infection of mice and binding of the virus to permissive cells. Importantly, the expression of this murine protein by human cells renders them fully permissive for murine norovirus infection, indicating that at least in this case, host range restriction is determined by molecular events that control receptor binding and entry. Defining the atomic-resolution interactions between the norovirus capsid protein and its cognate receptor is essential for a molecular understanding of host-range restriction and norovirus tropism.
Interleukin-1β Signaling in Dendritic Cells Induces Antiviral Interferon Responses
Authors: Aarreberg Lauren D. , Wilkins Courtney , Ramos Hilario J. , Green Richard , Davis Michael A. , Chow Kwan , Gale Michael
Published: March 2018

Induction of interferon beta (IFN-β), IFN-stimulated genes (ISGs), and inflammatory responses is critical for control of viral infection. We recently identified an essential linkage of stimulation of the inflammatory cytokine interleukin-1β (IL-1β) and induction of ISGs that function as host restriction pathways against the emerging flavivirus West Nile virus (WNV)
in vivo
. Here we utilized
ex vivo
global transcriptome analysis of primary dendritic cells, known targets of WNV replication, to define gene signatures required for this IL-1β-driven antiviral response. Dendritic cells that were deficient in IL-1 receptor signaling showed dysregulation of cell-intrinsic defense genes and loss of viral control during WNV infection. Surprisingly, we found that in wild-type cells, IL-1β treatment, in the absence of infection, drove the transcription of IFN-β and ISGs at late times following treatment. Expression of these antiviral innate immune genes was dependent on the transcription factor IFN regulatory factor 3 (IRF3) and appears to reflect a general shift in IL-1β signaling from an early inflammatory response to a late IFN-mediated response. These data demonstrate that inflammatory and antiviral signals integrate to control viral infection in myeloid cells through a process of IL-1β-to-IRF3 signaling crosstalk. Strategies to exploit these cytokines in the activation of host defense programs should be investigated as novel therapeutic approaches against individual pathogens.

IMPORTANCE
West Nile virus is an emerging mosquito-borne flavivirus that can result in serious illness, neuropathology, and death in infected individuals. Currently, there are no vaccines or therapies for human use against West Nile virus. Immune control of West Nile virus infection requires inflammatory and antiviral responses, though the effect that each arm of this response has on the other is unclear. The significance of our research is in defining how virus-induced inflammatory responses regulate critical antiviral immune programs for effective control of West Nile virus infection. These data identify essential mechanisms of immune control that can inform therapeutic efforts against West Nile virus, with potential efficacy against other neuroinvasive viruses.
Understanding Microbiome Stability in a Changing World
Authors: Shade Ashley
Published: March 2018

Microbiomes underpin biogeochemical processes, sustain the bases of food webs, and recycle carbon and nutrients. Thus, microbes are frontline players in determining ecosystem responses to environmental change.
Insect Transmission of Plant Pathogens: a Systems Biology Perspective
Authors: Heck Michelle
Published: March 2018

Insect-vectored pathogens pose one of the greatest threats to plant and animal, including human, health on a global scale. Few effective control strategies have been developed to thwart the transmission of any insect-transmitted pathogen.
Can Diet Influence Our Health by Altering Intestinal Microbiota-Derived Fecal Metabolites?
Authors: Lyu Qiang , Hsu Cheng-Chih
Published: March 2018

The human gastrointestinal tract harbors a diverse, highly mutualistic microbial flora which could produce a myriad of specialized metabolites. These specialized metabolites are the chemical cellphones that gut microflora use to communicate with their human host and could potentially be used to cure diseases.
Effectiveness of blood pressure-lowering drug treatment by levels of absolute risk: post hoc analysis of the Australian National Blood Pressure Study
Authors: Ho Chau Le Bao , Breslin Monique , Doust Jenny , Reid Christopher M , Nelson Mark R
Published: March 2018

Objectives

In many current guidelines, blood pressure (BP)-lowering drug treatment for primary prevention of cardiovascular disease (CVD) is based on absolute risk. However, in clinical practice, therapeutic decisions are often based on BP levels alone. We sought to investigate which approach was superior by conducting a post hoc analysis of the Australian National Blood Pressure (ANBP) cohort, a seminal study establishing the efficacy of BP lowering in ‘mild hypertensive’ persons.

Design

A post hoc subgroup analysis of the ANBP trial results by baseline absolute risk tertile.

Setting and participants

3244 participants aged 35–69 years in a community-based randomised placebo controlled trial of blood pressure-lowering medication.

Interventions

Chlorothiazide500 mg versus placebo.

Primary outcome measures

All-cause mortality and non-fatal events (non-fatal CVD, congestive cardiac failure, renal failure, hypertensive retinopathy or encephalopathy).

Results

Treatment effects were assessed by HR, absolute risk reduction and number needed to treat. Participants had an average 5-year CVD risk in the intermediate range (10.5±6.5) with moderately elevated BP (mean 159/103 mmHg) and were middle aged (52±8 years). In a subgroup analysis, the relative effects (HR) and absolute effects (absolute risk reduction and number needed to treat) did not statistically differ across the three risk groups except for the absolute benefit in all-cause mortality (p for heterogeneity=0.04). With respect to absolute benefit, drug treatment significantly reduced the number of events in the high-risk group regarding any event with a number needed to treat of 18 (10 to 64), death from any cause with 45 (25 to 196) and major CVD events with 23 (12 to 193).

Conclusion

Our analysis confirms that the benefit of treatment was substantial only in the high-risk tertile, reaffirming the rationale of treating elevated blood pressure in the setting of all risk factors rather than in isolation.
Extra-small dual-lumen micro-balloon catheters can improve endovascular embolization: an experimental in vivo and in vitro study
Authors: Vollherbst Dominik F , Otto Ruth , Do Thuy D , von Deimling Andreas , Kauczor Hans U , Bendszus Martin , Sommer Christof M , Möhlenbruch Markus A
Published: March 2018

Background

The embolization technique can have significant impact on the success of endovascular embolization.

Objective

To evaluate the feasibility, embolization characteristics, and embolization extent with a newly developed extra-small micro-balloon catheter in an in vivo and in an in vitro embolization model in comparison with standard microcatheter embolizations.

Materials and methods

Twenty-eight embolization procedures were performed in the porcine rete mirabile (RM) and in an in vitro embolization model, using either an extra-small (distal outer diameter 1.6 F) dual-lumen micro-balloon catheter or a standard microcatheter. Precipitating hydrophobic injectable liquid (PHIL) was used as embolic agent. Procedure times, number of injections, required volume of embolic agent, and embolization extent (percentage of embolized RM in postinterventional X-ray scans or number of filled sections of the in vitro model) were assessed. Histopathological analyses were performed.

Results

Total procedure time was significantly shorter (in vivo: 123 s vs 615 s (medians), P=0.001; in vitro: 180 s vs 496 s (medians), P=0.001), number of reflux events was significantly lower (in vivo: 0 vs 9 (medians), P=0.001; in vitro: 0 vs 3 (medians), P=0.001), and embolization extent was significantly higher (in vivo: 96.9% vs 65.6% (medians), P=0.011; in vitro: 26 vs 18 filled sections (medians); P=0.041) for the micro-balloon catheter groups. There was antegrade movement of the PHIL cast after balloon deflation in one in vitro embolization procedure and spontaneous balloon deflation with subsequent reflux in one in vivo embolization procedure.

Conclusion

Extra-small dual-lumen micro-balloon catheters can improve endovascular embolization in comparison with standard microcatheter embolization.
Porcine stomachs with and without gastric ulcer differ in Lactobacillus load and strain characteristics
Authors: Almeida Luciana Ramos , Costa Patrícia Silva , Nascimento Andréa Maria Amaral , Reis Mariana de Paula , Barros Katharina Oliveira , Alvim Luige Biciati , Nunes Álvaro Cantini , Queiroz Dulciene Maria Magalhães , Rocha Gifone Aguiar , Nicoli Jacques Robert , de Moura Sílvia Beleza
Published: March 2018

Although Lactobacillus species are recognized as normal inhabitants of porcine gastric mucosa, the association of these bacteria with health status or gastric ulcer disease has never been considered. We investigated the bacterial load of Lactobacillus isolated from the antrum, corpus, and pars esophagea of stomachs with (n = 13) and without (n = 10) ulcer of the pars esophagea of slaughtered pigs. We also evaluated in vitro antagonistic properties against typical pathogens of strains isolated from stomachs without ulcer. To quantify Lactobacillus, gastric mucosa samples obtained with 5 mm biopsy punches were smeared on MRS agar and colonies were counted after 48 h of incubation under anaerobic conditions. The score of Lactobacillus was significantly greater in the antrum and corpus of stomachs without ulcer (P < 0.001 for both) when compared with stomachs with ulcer. Fingerprint profiles, obtained by repetitive sequence-based PCR using (GTG)5 primers, showed that the isolates were highly diverse. The reduction of Lactobacillus load in porcine stomachs may be a contributing factor for gastric ulcer. Strains isolated from healthy stomachs, which showed a wide spectrum of antagonistic activity against pathogens, may be viewed as an untapped source of bacteria with potential beneficial properties that deserve to be further investigated.
Open books and exact symplectic cobordisms
Authors: Klukas Mirko
Published: March 2018

Given two open books with equal pages, we show the existence of an exact symplectic cobordism whose negative end equals the disjoint union of the contact manifolds associated to the given open books, and whose positive end induces the contact manifold associated to the open book with the same page and concatenated monodromy. Using similar methods, we show the existence of strong fillings for contact manifolds associated with doubled open books, a certain class of fiber bundles over the circle obtained by performing the binding sum of two open books with equal pages and inverse monodromies. From this we conclude, following an outline by Wendl, that the complement of the binding of an open book cannot contain any local filling obstruction. Given a contact [Formula: see text]-manifold, according to Eliashberg there is a symplectic cobordism to a fibration over the circle with symplectic fibers. We extend this result to higher dimensions recovering a recent result by Dörner–Geiges–Zehmisch. Our cobordisms can also be thought of as the result of the attachment of a generalized symplectic [Formula: see text]-handle.