bluuebunny/crossref_metadata_2025 huggingface dataset:
Monitoring Costs, Credit Constraints and Entrepreneurship
Authors: Banerji Sanjay , Raj Rajesh S. N. , Sen Kunal
Published: July 2015

Access to finance is seen as a binding constraint on the growth of household enterprises in developing countries. We develop a principal agent model of a household enterprise and show that limited access to finance and monitoring costs constrain the firm size via both a direct and indirect effect. Although greater access to finance has a positive direct effect on the hiring of paid labour, firms may not choose to expand and use paid labour via an indirect route that operates through the monitoring costs of employing paid workers. We use large nationally representative surveys of household enterprises in Indian manufacturing and find support for the predictions of our theory.
Direct Written Corrective Feedback, Learner Differences, and the Acquisition of Second Language Article Use for Generic and Specific Plural Reference
Authors: STEFANOU CHARIS , RÉVÉSZ ANDREA
Published: July 2015

This article reports on a classroom‐based study that investigated the effectiveness of direct written corrective feedback in relation to learner differences in grammatical sensitivity and knowledge of metalanguage. The study employed a pretest–posttest–delayed posttest design with two treatment sessions. Eighty‐nine Greek English as a foreign language (EFL) learners were randomly assigned to 3 groups: direct feedback only, direct feedback plus metalinguistic comments, and comparison. The linguistic target was article use for specific and generic plural reference. A text summary and a truth value judgment test were employed to measure any development in learners’ ability to use articles. The results revealed an advantage for receiving direct feedback over no feedback, but provided no clear evidence for the benefit of supplying metalinguistic information. Additionally, participants with greater grammatical sensitivity and knowledge of metalanguage proved more likely to achieve gains in the direct feedback only group.
The Anatomy of Directed Motivational Currents: Exploring Intense and Enduring Periods of L2 Motivation
Authors: HENRY ALASTAIR , DAVYDENKO SOFIA , DÖRNYEI ZOLTÁN
Published: July 2015

In a series of articles Dörnyei and his colleagues (Dörnyei, Ibrahim, & Muir, 2015; Dörnyei, Muir, & Ibrahim, 2014; Muir & Dörnyei, 2013) describe the phenomenon of a period of intense and enduring motivation in pursuit of a highly desired personal goal or vision. These surges of motivational energy, which they call Directed Motivational Currents (DMCs), uniquely differ from other types of highly motivated behaviour or optimal forms of engagement that are to be found in the literature in the sense that individual learning activities form integrated parts of a coherent motivational superstructure. The current article offers the first systematic empirical investigation of this motivational phenomenon. Focusing on periods of unusually intense and enduring motivation experienced by migrant learners of Swedish as a second language, the purpose of this interview‐based study is to consider whether core characteristics of DMCs can be identified in participants’ descriptions of sustained motivated behaviour, thereby considering the validity of the DMC construct. Results reveal that motivated behaviour is characterised by features similar to those outlined by Dörnyei and colleagues, namely the presence of a salient facilitative structure, the generation of positive emotionality, and the direction of motivated behaviour toward long‐term identity investment goals. This indicates that the DMC construct captures a unique form of motivation worthy of future investigation.
Schenker's Theory of Criticism, circa 1911
Authors: BURGSTALLER GEORG
Published: July 2015

‘Art and Criticism’ (‘Kunst und Kritik’), an unpublished draft essay dating from 1911, is Schenker's theory of music criticism in all but name, revealing his wider views about the cultural practice of music journalism. As such, it can be read as the foundation for his subsequent thinking on the matter. It also offers a glimpse into how his thinking on a subject evolved: he filed the draft in a folder together with an eclectic assortment of notes with references to literary works, as well as clippings of newspaper articles on music, art and literary criticism by the foremost contributors to the public debate on criticism at the turn of the century. Through a close reading of both ‘Art and Criticism’ and its paper trail in the Schenker Archive, I seek to shed light on Schenker's thinking as a process by showing that he engaged with the thinkers of his time and demonstrating the extent to which his rejection of journalism was stimulated by the ideas of his contemporaries.
Case report: aneurysmal bone cyst of the mandibular condyle
Authors: Dunphy L. , O'Connell S. , Halsnad M. , Parmar S.
Published: July 2015

An aneurysmal bone cyst is a benign, expansive, osteolytic lesion consisting of blood‐filled cysts. It occurs rarely in the craniofacial region, more commonly affecting the long bones and the spine. We report a rare case affecting the mandibular condyle of a 65‐year‐old Caucasian male.
UnderstandingChina's Economic Engagement withNorthKorea: Realities and Problems
Authors: Lee Jong‐Woon , Hong Yi Kyung
Published: July 2015

There has not only been an escalation inSino–NorthKorean economic relations of late, but a qualitative shift has also taken place in the nature ofChina's involvement in theNorthKorean economy, as evinced by the rapid growth in bilateral trade, andChinese investment inNorthKorean natural resources and cross‐border infrastructure. In examining the recent trend in trade and investment flows, this study sheds light on the high degree ofNorthKorea's economic reliance onChina, and the effects that the growth of the latter and its strong demand for low‐cost resources and labor have had onNorthKorea. The principal finding of the article is the contradictory nature of currentSino–NorthKorean economic ties asChina expands its dominance in the midst ofNorthKorea's greater international isolation following its nuclear standoff. This contradiction is a reflection ofChina's renewed economic interest inNorthKorea as the cornerstone of its grand policy of “reaching out” to secure access to natural resources, transport infrastructure and markets.China's economic engagement carries with it benefits forNorthKorean regime survival, but also contains a potential development risk for the country associated with its economic dependency. In this regard, the emerging challenge toNorthKorea is the question of how to manage the adverse consequences of deepening economic relations withChina.
Outgrowing the Predicament? National Identity andSeoul'sDokdo Policy
Authors: Flamm Patrick
Published: July 2015

TheDokdo/Takeshima dispute between theROKandJapan remains the single biggest obstacle to an improvement ofSouthKorean–Japanese relations. The issue forcesSouthKorean foreign policy actors to constantly maneuver between engagement withJapan out of strategic interests and confrontation because of the islets' symbolic value forKorean national identity. Still, the scholarly debate has failed to comprehensively grasp the constitution ofDokdo as a political issue, while reducing it to “irrational emotions” that unnecessarily hinder urgent bilateral cooperation. Further, there prevails a one‐dimensional and fixed understanding ofKorean identity as largely post‐colonial, without acknowledging the recent research on an increasingly internationalizedKorean self‐understanding. In taking a constructivist, discourse analytical approach,Iam able to provide a sound assessment of the various active identity narratives relevant toSeoul'sDokdo policy, while considering the odds for political change.
Dismantling the Final Barrier: Transforming Japan into a “Normal Country” in the Post‐Cold‐War Era
Authors: Kim Ji Young
Published: July 2015

Since the end of the Cold War, Japan has embraced a more active security policy. While some scholars interpret the change within the context of Japan's long‐standing antimilitaristic security identity, others forewarn a fundamental shift with the potential to reorient Japan's national security policy. This article views that Japan has not stopped moving toward being a normal country, albeit “with a slight limp,” since the end of the Cold War and the speed of such movement has accelerated since the late 1990s. What, then, have been the main underlying conditions that accelerated such movement? How did changes in these conditions bring about the speedy shift in Japanese security policy? I seek to answer these questions through examining four critical periods that have exhibited significant transformations of Japan's security policy. The findings will help us to understand the shift in Japanese security norm since the end of the Cold War and its implications for East Asian security.
Competition in slow motion: the unusual case of benthic marine communities in the wake of the end‐Permian mass extinction
Authors: Hautmann Michael , Bagherpour Borhan , Brosse Morgane , Frisk Åsa , Hofmann Richard , Baud Aymon , Nützel Alexander , Goudemand Nicolas , Bucher Hugo
Published: July 2015

Changes of community structure in response to competition usually take place on timescales that are much too short to be visible in the geological record. Here we report the notable exception of a benthic marine community in the wake of the end‐Permian mass extinction, which is associated with the microbial limestone facies of the earliestTriassic ofSouthChina. The newly reported fauna is well preserved and extraordinarily rich (30 benthic macroinvertebrate species, including the new speciesAstartella?stefaniae(Bivalvia) andEucochlis obliquecostata(Gastropoda)) and stems from an environmentally stable setting providing favourable conditions for benthic organisms. Whereas changes in the taxonomic composition are negligible over the observed time interval of 10–100 ka, three ecological stages are identified, in which relative abundances of initially rare species continuously increased at the cost of previously dominant species. Concomitant with the changes of dominant species is an increase in faunal evenness and heterogeneity. In the absence of both environmental and taxonomic changes, we attribute this pattern to the long‐term effects of interspecific competition, which acted at an unusually slow pace because the number of competing species and potential immigrants was dramatically reduced by the end‐Permian mass extinction. We suggest that these non‐actualistic conditions led to decreased rates of niche differentiation and hence to the delayed rediversification of benthos that characterizes the aftermath of the greatestPhanerozoic mass extinction event. A hyperbolic diversification model is proposed, which accounts for the positive relationship between the intensity of interspecific competition and the rate of niche differentiation and resolves the conundrum of delayed rediversification at a time when niche space was largely vacated.
Biochemical Characterization of the DASH‐Type Cryptochrome CryD From Fusarium fujikuroi
Authors: Castrillo Marta , Bernhardt Adrian , Ávalos Javier , Batschauer Alfred , Pokorny Richard
Published: July 2015

Proteins from the cryptochrome/photolyase family utilize UV‐A, blue or even red light to achieve such diverse functions as repair of DNA lesions by photolyases and signaling by cryptochromes. DASH‐type cryptochromes retained the ability to repair cyclobutane pyrimidine dimers (CPDs) in single‐stranded DNA regions in vitro. However, most organisms possess conventional CPD photolyases responsible for repair of these lesions in vivo. Recent work showed that the DASH‐type cryptochrome CryD plays a regulatory role in diverse light‐dependent processes in Fusarium fujikuroi. Here, we report our in vitro studies on heterologously expressed FfCryD. The purified protein contains N5,N10‐methenyltetrahydrofolate and flavin adenine dinucleotide as cofactors. Photoreduction and DNA photorepair experiments confirmed that FfCryD is active in light‐driven electron transfer processes. However, the protein showed comparable affinities for CPD‐comprising and undamaged DNA probes. Surprisingly, after purification, full‐length FfCryD as well as a truncated version containing only the PHR domain bound RNA which influenced their behavior in vitro. Moreover, binding of FfCryD to RNA indicates a putative role in RNA metabolism or in posttranscriptional control of gene expression.
A Policy‐Oriented Electorate: Evaluations of Candidates and Parties in the Obama Elections Compared to the 1952‐1980 Period
Authors: Wattenberg Martin P. , Powell Sierra
Published: July 2015

In a replication of Miller and Wattenberg's (1985) coding of American National Election Studies open‐ended likes/dislikes questions, respondents’ evaluations of candidates and parties are found to be especially policy oriented in 2008 and 2012. Compared to earlier elections without an incumbent, prospective policy evaluations were far more prevalent in 2008. Furthermore, voters’ comments about the candidates in 2012 were more policy oriented than the elections of 1964 and 1972 in which challengers offered a stark policy choice to an incumbent president. We also find the public's likes and dislikes of the political parties focused heavily on policy considerations in the two Obama elections.
The Law: Libya, Syria, ISIS, and the Case against the Energetic Executive
Authors: Edelson Chris , Starr‐Deelen Donna G.
Published: July 2015

Dick Cheney, John Yoo, and others incorrectly claim that Alexander Hamilton's vision of an “energetic executive” contemplated a president with broad, even plenary power over the use of military force. In fact, neither Hamilton's writings nor the text of the Constitution itself embraces this notion. In practice, unilateral presidential decisions to order the use of military force have been neither wise nor necessary, outside of the limited emergency defensive context. Recent episodes involving Libya, Syria, and ISIS expose the failure of the energetic executive model.
Sexual disinhibition and dementia
Authors: Cipriani Gabriele , Ulivi Martina , Danti Sabrina , Lucetti Claudio , Nuti Angelo
Published: July 2015

To describe inappropriate sexual behaviour (ISB) observed in patients with dementia, we conducted searches using the Cochrane Library, PubMed, and Web of Science to find relevant articles, chapters, and books published from 1950 to 2014. Search terms used included ‘hypersexuality’, ‘inappropriate sexual behaviors’, and ‘dementia’. Publications found through this indexed search were reviewed for further relevant references. Sexuality is a human's need to express intimacy, but persons with dementia may not know how to appropriately meet their needs for closeness and intimacy due to their decline in cognition. Generally, the interaction among brain, physical, psychological, and environmental factors can create what we call ISB. The most likely change in the sexual behaviour of a person with dementia is indifference. However, ISB in dementia appear to be of two types—intimacy‐seeking and disinhibited—that differ in their association with dementia type, dementia severity and, possibly, other concurrent behavioural disorder. Tensions develop from uncertainties regarding which, or when, behaviours are to be considered ‘inappropriate’ (i.e. improper) or abnormal. While most ISB occur in the moderate to severe stages of Alzheimer's dementia, they may also be seen in early stages of frontotemporal dementia because of the lack of insight and disinhibition. ISB are often better managed by non‐pharmacological means, as patients may be less responsive to psychoactive therapies, but non‐pharmacological interventions do not always stop the behaviour.
Evaluation of canine‐specific minocycline and doxycycline susceptibility breakpoints for meticillin‐resistant Staphylococcus pseudintermedius isolates from dogs
Authors: Hnot Melanie L. , Cole Lynette K. , Lorch Gwendolen , Papich Mark G. , Rajala‐Schultz Paivi J. , Daniels Joshua B.
Published: July 2015

Background

Using the US Clinical and Laboratory Standards Institute (CLSI) human tetracycline breakpoints to predict minocycline and doxycycline susceptibility of Staphylococcus pseudintermedius (SP) isolates from dogs is not appropriate because they are too high to meet pharmacokinetic/pharmacodynamic data using a standard dose. New breakpoints have been approved for doxycycline and proposed for minocycline. Revised breakpoints are four dilutions lower than tetracycline breakpoints, providing a more conservative standard for classification of isolates.

Hypothesis/Objectives

The objectives of this study were to measure minimum inhibitory concentrations (MICs) of minocycline and doxycycline of 100 canine meticillin‐resistant SP clinical isolates, compare their susceptibilities to minocycline and doxycycline based on current and revised standards, and document their tetracycline resistance genes.

Methods

E‐test strips were used to determine MICs. PCR was used to identify tet genes.

Results

Using the human tetracycline breakpoint of MIC ≤ 4 μg/mL, 76 isolates were susceptible to minocycline and 36 isolates were susceptible to doxycycline. In contrast, using the proposed minocycline breakpoint (MIC ≤ 0.25 μg/mL) and approved doxycycline breakpoint (MIC ≤ 0.125 μg/mL), 31 isolates were susceptible to both minocycline and doxycycline. Thirty‐one isolates carried no tet genes, two had tet(K) and 67 had tet(M).

Conclusions and clinical importance

Use of the human tetracycline breakpoints misclassified 45 and five of the isolates as susceptible to minocycline and doxycycline, respectively. PCR analysis revealed that 43 and five of the isolates classified as susceptible to minocycline and doxycycline, respectively, possessed the tetracycline resistance gene, tet(M), known to confer resistance to both drugs. These results underscore the importance of utilizing the proposed minocycline and approved doxycycline canine breakpoints in place of human tetracycline breakpoints.
Assessment of the relationships among coagulopathy, hyperfibrinolysis, plasma lactate, and protein C in dogs with spontaneous hemoperitoneum
Authors: Fletcher Daniel J. , Rozanski Elizabeth A. , Brainard Benjamin M. , de Laforcade Armelle M. , Brooks Marjory B.
Published: July 2015

Objective

To relate coagulation and fibrinolysis derangements to shock severity as reflected by plasma lactate concentrations in dogs with spontaneous hemoperitoneum (SHP) and determine the impact on transfusions.

Design

Prospective, observational, case‐control study.

Setting

Three veterinary teaching hospitals.

Animals

Twenty‐eight client‐owned dogs with SHP and 28 breed‐ and age‐matched control dogs.

Interventions

None.

Measurements and Main Results

Blood samples for platelet counts, coagulation, and anticoagulant assays (prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin, and protein C, thromboelastography [TEG]), fibrinolysis testing (d‐dimer and TEG lysis parameters with and without the addition of 50 U/mL of tissue plasminogen activator [TEG LY30 measured with the addition of 50 U/mL of tPA to the blood sample, LY3050 and TEG LY60 measured with the addition of 50 U/mL of tPA to the blood sample, LY6050; LY30 and LY60]), and plasma lactate as an indicator of severity of shock were collected from SHP dogs at the time of diagnosis. SHP dogs were hypocoagulable (prolonged prothrombin time and activated partial thromboplastin time, decreased TEG maximum amplitude) and hyperfibrinolytic (increased LY3050 and TEG LY6050) compared to controls. The severity of hypocoagulability was related to protein C activity, while the severity of hyperfibrinolysis was related to plasma lactate concentration. Among the 18 dogs discharged from the hospital, LY3050 was significantly associated with the dose of fresh frozen plasma administered, but none of the parameters were associated with the dose of red blood cells administered.

Conclusions

Dogs with SHP have evidence of hypocoagulability, protein C deficiency, and hyperfibrinolysis. Parameters of hyperfibrinolysis were related to plasma lactate concentrations and volume of plasma transfused during hospitalization. These derangements resemble those found in people with acute coagulopathy of trauma and shock, and activation of protein C may be a common feature to both syndromes.
Parvoviral myocarditis in a 5‐week‐old Dachshund
Authors: Sime Tara A. , Powell Lisa L. , Schildt Julie C. , Olson Erik J.
Published: July 2015

Objective

To describe a case of myocarditis associated with naturally occurring canine parvovirus type 2 (CPV‐2).

Case Summary

A 5‐week‐old male intact Dachshund dog presented for acute respiratory distress. Limited diagnostic tests prior to the dog experiencing cardiopulmonary arrest included a lateral thoracic radiograph, which indicated cardiomegaly and diffuse unstructured pulmonary infiltrate. Necropsy was performed and results identified a lymphoplasmacytic myocarditis with positive CPV‐2 immunohistochemistry within the myocardium.

Unique Information Provided

This report describes the natural occurrence of CPV‐2‐associated myocarditis. In addition to highlighting this rare form of canine parvovirus, cardiomyopathy in survivors of the acute viral myocarditis phase is reviewed.
Retrospective evaluation of xylitol ingestion in dogs: 192 cases (2007–2012)
Authors: DuHadway Meghan R. , Sharp Claire R. , Meyers Katherine E. , Koenigshof Amy M.
Published: July 2015

Objective

To summarize the signalment, clinical signs, prevalence of decreased blood glucose concentration (BG), prevalence of increased liver values, treatment, and outcome in dogs known to have ingested xylitol.

Design

Retrospective study from December 2007 to February 2012

Setting

Three university teaching hospitals.

Animals

One hundred ninety‐two client‐owned dogs with known or suspected xylitol ingestion.

Interventions

None.

Measurements and Main Results

The median ingested xylitol dose was 0.32 g/kg (range 0.03–3.64 g/kg). Clinical signs were present in 39 (20%) dogs on presentation to the veterinary teaching hospitals. The most common clinical sign was vomiting (n = 25), followed by lethargy (12). The median duration of clinical signs prior to presentation was 93 minutes (range 0–5,040 minutes). Dogs that developed clinical signs ingested a significantly higher dose of xylitol than those that were asymptomatic. Thirty dogs became hypoglycemic (BG ≤ 3.3 mmol/L [60 mg/dL]) at some time point during their hospitalization. When evaluating all dogs, there was a significant difference between the initial and lowest BGs. Thirty dogs had increased alanine aminotransferase activity or total serum bilirubin concentration. Dogs with increases in alanine aminotransferase activity or total serum bilirubin concentration had a significantly lower nadir BG. All dogs survived to discharge and 158 were known to be alive at 28 days. The rest were lost to follow up.

Conclusions

The prognosis for dogs evaluated by a veterinarian that ingest lower doses of xylitol and do not develop liver failure is excellent. Dogs ingesting xylitol should be hospitalized and monitored for variations in BG, because BG drops in most dogs following presentation. Additional studies are needed in dogs ingesting higher doses of xylitol before correlations between dose and the development of clinical signs or liver failure can be established. Treatment and prognosis for these dogs warrants further investigation.
Implementation of Safe Patient Handling in the U.S. Veterans Health System: A Qualitative Study of Internal Facilitators’ Perceptions
Authors: Elnitsky C. A. , Powell‐Cope G. , Besterman‐Dahan K. L. , Rugs D. , Ullrich P. M.
Published: July 2015

Background

Although the literature has noted the positive effects of facilitation in implementation research, little is known about what facilitators do or how they increase adoption of a program. The purpose of this study was to understand internal facilitation activities in implementing a national safe patient handling program from the perspective of facility coordinators who implemented the program.

Methods

Using a qualitative descriptive design, data were collected in five focus groups at two international Safe Patient Handling and Mobility Conferences. Participants were 38 facility coordinators implementing a safe patient handling program in the Department of Veterans Affairs medical centers throughout the United States. Data were analyzed using direct content analysis to gather descriptions of internal facilitation.

Results

The internal facilitation process involved engaging multiple disciplines and levels of leadership for implementation. Fifty‐four facilitation activities were identified, including five activities not currently listed in an existing taxonomy. Key characteristics and skills of facilitators included persistence, credibility and clinical experience, and leadership and project management experience. Themes were mapped onto an existing framework and taxonomy of facilitation activities.

Linking Evidence to Action

Internal facilitation is both an implementation intervention and a process involving a wide range of activities. The findings provide an understanding of what internal facilitators are doing to support practice changes and the characteristics and skills of internal facilitators that are likely to result in long‐term organizational change. Five recommendations for action address organizations, senior leaders, and internal facilitators.
Predictors of Health Status in Mothers of Premature Infants with Implications for Clinical Practice and Future Research
Authors: Wu Chia‐Yao , Hung Chich‐Hsiu , Chang Ying‐Ju
Published: July 2015

Background

Postpartum health research has focused primarily on full‐term mothers.

Aims

To explore postpartum stress, depression, social support, health status, and predictors of health status in mothers of premature infants.

Methods

This study employed a cross‐sectional design. With convenience sampling, a total of 203 mothers of premature infants were recruited from two medical centers and four community teaching hospitals in southern Taiwan. The Hung Postpartum Stress Scale, Social Support Scale, Beck Depression Inventory, and Chinese Health Questionnaire were used to assess the mothers’ psychosocial features during the first 6 weeks postpartum.

Results

Mothers’ health status differed significantly according to levels of postpartum stress and depression. The important health status predictors were age, education, postpartum stress, and depression level.

Discussion

The concerns and needs of mothers of premature infants differed from those of full‐term mothers during the first 6 weeks postpartum; premature infants’ health status was found to be a major perceived stressor for their mothers.

Linking Evidence to Action

In the process of caring for premature infants’ mothers, healthcare providers should provide individualized care to meet their needs, thus facilitating the reduction of postpartum stress and depression levels. During premature infants’ hospitalizations, healthcare providers should hold regular faculty meetings to provide postpartum women with relevant information about their infants’ health and how to best care for them. Future studies should explore postpartum stress, social support, depression, and health status each postpartum week, which could serve as a guide for nursing interventions.
Analyzing the Correlation between Gender Traits and the Perception of Effective Leadership
Authors: Jr Phillip Neely , Muhammad Ray
Published: July 2015

As the percentage of women managers has risen in the workforce, so have questions of whether women could effectively manage corporations. This curiosity has yielded studies designed to analyze the correlation between gender and management. Additionally, the research has led to contrary views from one research project to another. In their article, Leadership, Education and Gender Roles: Think manager, Think '?'., Coder and Spiller (2013) reviewed three varying trains of thought from the 1970s through the 1990s to examine how various shortcomings in methodology might impact comprehension and remediation of gender issues and management. The article reviews research that appears to substantiate that when people think manager, they think male. This is followed by data, which suggests that when people think research, we think female and finally research endorsing the train of thought that when people think manager, there is no gender specific thought. Two Indexes developed in the 1970s greatly impacted gender and its correlation to management traits. These were the Schein Descriptive Index (SDI) and the BEM Sex Role Index (BSRI). According Coder and Spiller (20113) results of the Schein Descriptive Index, a test developed by Virginia Schein, indicated the characteristics of women managers more closely resembled males than females.
Modeling of Effective Stagnant Thermal Conductivity of Porous Media
Authors: Takatsu Yasuyuki , Masuoka Takashi , Nomura Takahiro , Yamada Yuji
Published: July 2015

Based on one-dimensional analysis of heat conduction, a general formula for the effective stagnant thermal conductivity of spatially periodic porous media is derived without assuming local thermal equilibrium. Furthermore, we discuss the contribution of the contact area between particles to the effective stagnant thermal conductivity in detail, and the modification of the formula is proposed to predict the actual effective stagnant thermal conductivity for the porous media. The present results are in good agreement with experimental results of Nozad et al. (1985, “Heat Conduction in Multi-Phase Systems I: Theory and Experiments for Two-Phase Systems,” Chem. Eng. Sci., 40(5), pp. 843–855) for a packed-sphere bed.
Evaluation of diffusion models in breast cancer
Authors: Panek Rafal , Borri Marco , Orton Matthew , O'Flynn Elizabeth , Morgan Veronica , Giles Sharon L. , deSouza Nandita , Leach Martin O. , Schmidt Maria A.
Published: July 2015

Purpose:

The purpose of this study is to investigate whether the microvascular pseudodiffusion effects resulting with non‐monoexponential behavior are present in breast cancer, taking into account tumor spatial heterogeneity. Additionally, methodological factors affecting the signal in low and high diffusion‐sensitizing gradient ranges were explored in phantom studies.

Methods:

The effect of eddy currents and accuracy of b‐value determination using a multiple b‐value diffusion‐weighted MR imaging sequence were investigated in test objects. Diffusion model selection and noise were then investigated in volunteers (n = 5) and breast tumor patients (n = 21) using the Bayesian information criterion.

Results:

54.3% of lesion voxels were best fitted by a monoexponential, 26.2% by a stretched‐exponential, and 19.5% by a biexponential intravoxel incoherent motion (IVIM) model. High correlation (0.92) was observed between diffusion coefficients calculated using mono‐ and stretched‐exponential models and moderate (0.59) between monoexponential and IVIM (medians: 0.96/0.84/0.72 × 10−3 mm2/s, respectively). Distortion due to eddy currents depended on the direction of the diffusion gradient and displacement varied between 1 and 6 mm for high b‐value images. Shift in the apparent diffusion coefficient due to intrinsic field gradients was compensated for by averaging diffusion data obtained from opposite directions.

Conclusions:

Pseudodiffusion and intravoxel heterogeneity effects were not observed in approximately half of breast cancer and normal tissue voxels. This result indicates that stretched and IVIM models should be utilized in regional analysis rather than global tumor assessment. Cross terms between diffusion‐sensitization gradients and other imaging or susceptibility‐related gradients are relevant in clinical protocols, supporting the use of geometric averaging of diffusion‐weighted images acquired with diffusion‐sensitization gradients in opposite directions.
Creatine and Caffeine: Considerations for Concurrent Supplementation
Authors: Trexler Eric T. , Smith-Ryan Abbie E.
Published: July 2015

Nutritional supplementation is a common practice among athletes, with creatine and caffeine among the most commonly used ergogenic aids. Hundreds of studies have investigated the ergogenic potential of creatine supplementation, with consistent improvements in strength and power reported for exercise bouts of short duration (≤30 s) and high intensity. Caffeine has been shown to improve endurance exercise performance, but results are mixed in the context of strength and sprint performance. Further, there is conflicting evidence from studies comparing the ergogenic effects of coffee and caffeine anhydrous supplementation. Previous research has identified independent mechanisms by which creatine and caffeine may improve strength and sprint performance, leading to the formulation of multi-ingredient supplements containing both ingredients. Although scarce, research has suggested that caffeine ingestion may blunt the ergogenic effect of creatine. While a pharmacokinetic interaction is unlikely, authors have suggested that this effect may be explained by opposing effects on muscle relaxation time or gastrointestinal side effects from simultaneous consumption. The current review aims to evaluate the ergogenic potential of creatine and caffeine in the context of high-intensity exercise. Research directly comparing coffee and caffeine anhydrous is discussed, along with previous studies evaluating the concurrent supplementation of creatine and caffeine.
Membrane contact sites promote lipid exchange
Authors: Hurtley Stella M.
Published: July 2015

The endoplasmic reticulum proteins ORP5 and ORP8 mediate PI4P-phosphatidylserine exchange at contact sites with the plasma membrane.
Keeping synaptic plasticity plastic
Authors: Hines Pamela J.
Published: July 2015

In mice, neuronal plasticity in later life depends on neuronal activity during a critical period earlier in development.
Differentiating between nutrient sources
Authors: Gough Nancy R.
Published: July 2015

Cells use the mTORC1 pathway to differentially respond to extracellular proteins or free amino acids as nutrient sources.
A Novel Y319H Substitution in CYP51C Associated with Azole Resistance in Aspergillus flavus
Authors: Paul R. A. , Rudramurthy S. M. , Meis J. F. , Mouton J. W. , Chakrabarti A.
Published: July 2015

This study aimed to explore any mutation in the
CYP51
gene conferring azole resistance in
Aspergillus flavus
. Two voriconazole-resistant and 45 voriconazole-susceptible isolates were included in the study. Sequence analysis demonstrated a T1025C nucleotide change in
CYP51C
, resulting in the Y319H amino acid substitution in one resistant isolate. However, the earlier described T788G mutation in
CYP51C
conferring voriconazole resistance in
A. flavus
isolates was present in all isolates, irrespective of their susceptibility status.
Bactericidal Activity of Ceragenin CSA-13 in Cell Culture and in an Animal Model of Peritoneal Infection
Authors: Bucki Robert , Niemirowicz Katarzyna , Wnorowska Urszula , Byfield Fitzroy J. , Piktel Ewelina , Wątek Marzena , Janmey Paul A. , Savage Paul B.
Published: July 2015

Ceragenins constitute a novel family of cationic antibiotics characterized by a broad spectrum of antimicrobial activities, which have mostly been assessedin vitro. Using a polarized human lung epithelial cell culture system, we evaluated the antibacterial activities of the ceragenin CSA-13 against two strains ofPseudomonas aeruginosa(PAO1 and Xen5). Additionally, the biodistribution and bactericidal activity of a CSA-13–IRDye 800CW derivate were assessed using an animal model of peritoneal infection after PAO1 challenge. In cell culture, CSA-13 bactericidal activities against PAO1 and Xen5 were higher than the activities of the human cathelicidin peptide LL-37. Increased CSA-13 activity was observed in polarized human lung epithelial cell cultures subjected to butyric acid treatment, which is known to increase endogenous LL-37 production. Eight hours after intravenous or intraperitoneal injection, the greatest CSA-13–IRDye 800CW accumulation was observed in mouse liver and kidneys. CSA-13–IRDye 800CW administration resulted in decreased bacterial outgrowth from abdominal fluid collected from animals subjected to intraperitoneal PAO1 infection. These observations indicate that CSA-13 may synergistically interact with antibacterial factors that are naturally present at mucosal surfaces and it maintains its antibacterial activity in the infected abdominal cavity. Cationic lipids such as CSA-13 represent excellent candidates for the development of new antibacterial compounds.
Fluconazole and Voriconazole Resistance in Candida parapsilosis Is Conferred by Gain-of-Function Mutations in
MRR1
Transcription Factor Gene
Authors: Branco Joana , Silva Ana P. , Silva Raquel M. , Silva-Dias Ana , Pina-Vaz Cidália , Butler Geraldine , Rodrigues Acácio G. , Miranda Isabel M.
Published: July 2015

Candida parapsilosis
is the second most prevalent fungal agent causing bloodstream infections. Nevertheless, there is little information about the molecular mechanisms underlying azole resistance in this species. Mutations (G1747A, A2619C, and A3191C) in the
MRR1
transcription factor gene were identified in fluconazole- and voriconazole-resistant strains. Independent expression of
MRR1
genes harboring these mutations showed that G1747A (G583R) and A2619C (K873N) are gain-of-function mutations responsible for azole resistance, the first described in
C. parapsilosis
.
Antimicrobial Susceptibility and SOS-Dependent Increase in Mutation Frequency Are Impacted by Escherichia coli Topoisomerase I C-Terminal Point Mutation
Authors: Yang Jenny , Annamalai Thirunavukkarasu , Cheng Bokun , Banda Srikanth , Tyagi Rakhi , Tse-Dinh Yuk-Ching
Published: July 2015

Topoisomerase functions are required in all organisms for many vital cellular processes, including transcription elongation. The C terminus domains (CTD) of
Escherichia coli
topoisomerase I interact directly with RNA polymerase to remove transcription-driven negative supercoiling behind the RNA polymerase complex. This interaction prevents inhibition of transcription elongation from hypernegative supercoiling and R-loop accumulation. The physiological function of bacterial topoisomerase I in transcription is especially important for a rapid network response to an antibiotic challenge. In this study,
Escherichia coli
with a
topA66
single nucleotide deletion mutation, which results in a frameshift in the TopA CTD, was shown to exhibit increased sensitivity to trimethoprim and quinolone antimicrobials. The topoisomerase I-RNA polymerase interaction and the SOS response to the antimicrobial agents were found to be significantly reduced by this
topA66
mutation. Consequently, the mutation frequency measured by rifampin selection following SOS induction was diminished in the
topA66
mutant. The increased antibiotic sensitivity for the
topA66
mutant can be reversed by the expression of recombinant
E. coli
topoisomerase I but not by the expression of recombinant
Mycobacterium tuberculosis
topoisomerase I that has a nonhomologous CTD even though the recombinant
M. tuberculosis
topoisomerase I can restore most of the plasmid DNA linking number deficiency caused by the
topA66
mutation. Direct interactions of
E. coli
topoisomerase I as part of transcription complexes are likely to be required for the rapid network response to an antibiotic challenge. Inhibitors of bacterial topoisomerase I functions and interactions may sensitize pathogens to antibiotic treatment and limit the mutagenic response.
A Simple, Efficient, and Sensitive Method for Simultaneous Detection of Anti-HIV Drugs Atazanavir, Ritonavir, and Tenofovir by Use of Liquid Chromatography-Tandem Mass Spectrometry
Authors: Koehn Josefin , Ding Yue , Freeling Jennifer , Duan Jinghua , Ho Rodney J. Y.
Published: July 2015

In the treatment of HIV infection, a combination of anti-HIV drugs is commonly used in highly active antiretroviral therapy (HAART). One such combination recommended for clinical therapy consists of the two HIV protease inhibitors atazanavir and ritonavir and the HIV nucleotide reverse transcriptase inhibitor tenofovir. The detection of plasma and cell drug concentrations provides an assessment of actual drug exposure and patient compliance. We thus developed a simple, efficient, and sensitive method to simultaneously extract and detect these three drugs in plasma and peripheral blood mononuclear cells. The use of a liquid-liquid extraction followed by protein precipitation provided a simple process, yielding a high recovery rate for all three drugs in plasma (>92%) and in cells (>86%). The liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was able to detect 0.01, 0.25, and 2.5 pg (2, 50, and 500 pg/ml, respectively) in 5 μl for atazanavir, ritonavir, and tenofovir, respectively. Validation of the method exhibited high precision and accuracy. This method was subsequently applied to a primate study to determine the concentrations of all three drugs in both plasma and cell samples. This validated method can be useful for an evaluation of drug concentrations in biological samples in an efficient and sensitive manner.
Persister Development by Borrelia burgdorferi Populations
In Vitro
Authors: Caskey John R. , Embers Monica E.
Published: July 2015

Doxycycline is an antibiotic commonly used to treat Lyme disease and other bacterial infections. The MIC and minimum bactericidal concentration (MBC) for
Borrelia burgdorferi
have been investigated by different groups but were experimentally established in this study as a function of input cell density. We demonstrated that
B. burgdorferi
treated in the stationary phase has a higher probability of regrowth following removal of antibiotic. In addition, we determined experimentally and mathematically that the spirochetes which persist posttreatment do not have a longer lag phase but exhibit a lower growth rate than untreated spirochetes. Finally, we found that treating the spirochetes by pulse-dosing did not eliminate growth or reduce the persister population
in vitro
. From these data, we propose that
B. burgdorferi
persister development is stochastic and driven by slowed growth.
The Flavonoid Isoliquiritigenin Reduces Lung Inflammation and Mouse Morbidity during Influenza Virus Infection
Authors: Traboulsi Hussein , Cloutier Alexandre , Boyapelly Kumaraswamy , Bonin Marc-André , Marsault Éric , Cantin André M. , Richter Martin V.
Published: July 2015

The host response to influenza virus infection is characterized by an acute lung inflammatory response in which intense inflammatory cell recruitment, hypercytokinemia, and a high level of oxidative stress are present. The sum of these events contributes to the virus-induced lung damage that leads to high a level of morbidity and mortality in susceptible infected patients. In this context, we identified compounds that can simultaneously reduce the excessive inflammatory response and the viral replication as a strategy to treat influenza virus infection. We investigated the anti-inflammatory and antiviral potential activities of isoliquiritigenin (ILG). Interestingly, we demonstrated that ILG is a potent inhibitor of influenza virus replication in human bronchial epithelial cells (50% effective concentration [EC50] = 24.7 μM). In addition, our results showed that this molecule inhibits the expression of inflammatory cytokines induced after the infection of cells with influenza virus. We demonstrated that the anti-inflammatory activity of ILG in the context of influenza virus infection is dependent on the activation of the peroxisome proliferator-activated receptor gamma pathway. Interestingly, ILG phosphate (ILG-p)-treated mice displayed decreased lung inflammation as depicted by reduced cytokine gene expression and inflammatory cell recruitment. We also demonstrated that influenza virus-specific CD8+effector T cell recruitment was reduced up to 60% in the lungs of mice treated with ILG-p (10 mg/kg) compared to that in saline-treated mice. Finally, we showed that administration of ILG-p reduced lung viral titers and morbidity of mice infected with the PR8/H1N1 virus.
In Vitro
and
In Vivo
Effects of the Bumped Kinase Inhibitor 1294 in the Related Cyst-Forming Apicomplexans Toxoplasma gondii and Neospora caninum
Authors: Winzer Pablo , Müller Joachim , Aguado-Martínez Adriana , Rahman Mahbubur , Balmer Vreni , Manser Vera , Ortega-Mora Luis Miguel , Ojo Kayode K. , Fan Erkang , Maly Dustin J. , Van Voorhis Wesley C. , Hemphill Andrew
Published: July 2015

We report on the
in vitro
effects of the bumped kinase inhibitor 1294 (BKI-1294) in cultures of virulent
Neospora caninum
isolates Nc-Liverpool (Nc-Liv) and Nc-Spain7 and in two strains of
Toxoplasma gondii
(RH and ME49), all grown in human foreskin fibroblasts. In these parasites, BKI-1294 acted with 50% inhibitory concentrations (IC
50
s) ranging from 20 nM (
T. gondii
RH) to 360 nM (
N. caninum
Nc-Liv), and exposure of intracellular stages to 1294 led to the nondisjunction of newly formed tachyzoites, resulting in the formation of multinucleated complexes similar to complexes previously observed in BKI-1294-treated
N. caninum
beta-galactosidase-expressing parasites. However, such complexes were not seen in a transgenic
T. gondii
strain that expressed CDPK1 harboring a mutation (G to M) in the gatekeeper residue. In
T. gondii
ME49 and
N. caninum
Nc-Liv, exposure of cultures to BKI-1294 resulted in the elevated expression of mRNA coding for the bradyzoite marker BAG1. Unlike in bradyzoites, SAG1 expression was not repressed. Immunofluorescence also showed that these multinucleated complexes expressed SAG1 and BAG1 and the monoclonal antibody CC2, which binds to a yet unidentified bradyzoite antigen, also exhibited increased labeling. In a pregnant mouse model, BKI-1294 efficiently inhibited vertical transmission in BALB/c mice experimentally infected with one of the two virulent isolates Nc-Liv or Nc-Spain7, demonstrating proof of concept that this compound protected offspring from vertical transmission and disease. The observed deregulated antigen expression effect may enhance the immune response during BKI-1294 therapy and will be the subject of future studies.
Legionella pneumophila Effector LpdA Is a Palmitoylated Phospholipase D Virulence Factor
Authors: Schroeder Gunnar N. , Aurass Philipp , Oates Clare V. , Tate Edward W. , Hartland Elizabeth L. , Flieger Antje , Frankel Gad
Published: July 2015

Legionella pneumophila
is a bacterial pathogen that thrives in alveolar macrophages, causing a severe pneumonia. The virulence of
L. pneumophila
depends on its Dot/Icm type IV secretion system (T4SS), which delivers more than 300 effector proteins into the host, where they rewire cellular signaling to establish a replication-permissive niche, the
Legionella
-containing vacuole (LCV). Biogenesis of the LCV requires substantial redirection of vesicle trafficking and remodeling of intracellular membranes. In order to achieve this, several T4SS effectors target regulators of membrane trafficking, while others resemble lipases. Here, we characterized LpdA, a phospholipase D effector, which was previously proposed to modulate the lipid composition of the LCV. We found that ectopically expressed LpdA was targeted to the plasma membrane and Rab4- and Rab14-containing vesicles. Subcellular targeting of LpdA required a C-terminal motif, which is posttranslationally modified by S-palmitoylation. Substrate specificity assays showed that LpdA hydrolyzed phosphatidylinositol, -inositol-3- and -4-phosphate, and phosphatidylglycerol to phosphatidic acid (PA)
in vitro
. In HeLa cells, LpdA generated PA at vesicles and the plasma membrane. Imaging of different phosphatidylinositol phosphate (PIP) and organelle markers revealed that while LpdA did not impact on membrane association of various PIP probes, it triggered fragmentation of the Golgi apparatus. Importantly, although LpdA is translocated inefficiently into cultured cells, an
L. pneumophila
Δ
lpdA
mutant displayed reduced replication in murine lungs, suggesting that it is a virulence factor contributing to
L. pneumophila
infection
in vivo
.