bluuebunny/crossref_metadata_2025 huggingface dataset:
The Rat Subcutaneous Air Sac Model: A Quantitative Assay of Antiangiogenesis in Induced Vessels
Authors: Lichtenberg Jens , Hjarnaa Pernille‐Julia Vig , Kristjansen Paul E. G. , Hansen Dann , Binderup Lise
Published: February 2017

Abstract:A newin vivoexperimental model ‐ the Subcutaneous Air Sac (SAS) model ‐ has recently been presented to replace a previousin vivorabbit cornea assay where neovascularisation was induced by chemical injury of the cornea or by implantation of tumour cells intracorneally, a methodology which is believed to cause severe pain to the animals. In the SAS model, an air sac is induced by injection of air subcutaneously on the back of the animal. After 10–14 days the air sac appears as an almost transparent avascular membrane in which induction of new vessels can be studied. We present recent developments of this technique: In the SAS‐tumourtechnique, vascular endothelial growth factor‐producing tumour cells are inoculated subcutaneously directly on the membrane, and the formation of new vessels is measured 8 days later. In the SAS‐pellettechnique, slow‐release pellets containing angiogenic factors, basic fibroblast growth factor or vascular endothelial growth factor are implanted on the subcutaneous membrane by a simple operation. The formation of new vessels is measured 10 days later. The ability of the SAS‐tumour‐ and SAS‐pellettechniques to detect an antiangiogenic effect of a systemically administered compound was investigated using the fumagillin analogue TNP‐470 (o‐chloro‐acetylcarbamoyl)‐fumagillol) as a positive control given subcutaneously for 7 and 9 days, respectively. At a dose of 10 mg TNP‐470/kg/day the angiogenesis was reduced by approximately 70% in the SAS‐tumourtechnique and by 40–60% in the SAS‐pellettechnique. The animals were unaffected by the SAS methodology. The SAS‐tumourand SAS‐pelletmodels are considered complementary and make use of simple and almost similar techniques which facilitate the evaluation.
Evaluation of the effect of indomethacin and piroxicam administration before embryo transfer on pregnancy rate
Authors: Kumbasar Serkan , Gül Özer , Şık Aytek
Published: February 2017

Aim

The aim of this study was to evaluate the effect of non‐steroidal anti‐inflammatory drug (NSAID) administration before embryo transfer (ET) on pregnancy rates in women undergoing in vitro fertilization/intracytoplasmic sperm injection ET.

Methods

Our study included 255 patients diagnosed with primary or secondary infertility caused by a male or tubal‐related factor, endometriosis or unexplained factors. The patients were divided randomly into three groups. Two groups were administered oral piroxicam (10 mg capsules) or 100 mg indomethacin (rectal suppository), respectively, 1–2 h before ET. As a control, the third group did not receive any form of treatment before ET. Basal levels of follicle‐stimulating hormone, luteinizing hormone, and level 17β‐estradiol on the day of human chorionic gonadotropin administration, the collected and transferred number of embryos, and the number of grade A embryos obtained were determined in all patients.

Results

The implantation, clinical pregnancy, and miscarriage rates of the groups were compared. The clinical pregnancy rate per ET and the implantation rate were 35.2% and 12.15% in the piroxicam group, 31.7% and 10.9% in the indomethacin group, and 32.9% and 12.5% in the control, respectively. The miscarriage rates of groups 1, 2 and 3 were 12%, 11.7% and 11.7%, respectively (P = 0.964). The differences in clinical pregnancy rates among the groups were not statistically significant (P = 0.887). There were also no significant differences in the implantation rates (P = 0.842).

Conclusion

These results suggest that NSAID administration before ET has no additional effect on pregnancy outcome in patients undergoing in vitro fertilization.
The Bank, the Bond, and the Bail‐out: On the Legal Construction of Market Discipline in the Eurozone
Authors: Schepel Harm
Published: February 2017

The ‘logic of the market’, so holds the Court of Justice, is the standard of legality of financial assistance to indebted member states under EU law and, ultimately, the legal justification for strict conditionality and the imposition of austerity. This logic of the market, though, is different from actual market behaviour. Austerity, it turns out, is not the inevitable response to market pressures but a function of political substitutes for market discipline (Pringle) and technocratic truth seeking about the ‘correct’ price of debt (Gauweiler) which the Court has frozen into law. The perverse consequence of making the modalities of financial assistance dependent on the ‘logic of the market’ is, moreover, to render the assistance as ineffective and expensive as possible. ‘The logic of the market’ in the Court's case law is best seen as punitive and cynical politics masquerading as inept economics.
The Growth of Debt and the Debt of Growth: Lessons from the Case of Argentina
Authors: López Pablo J. , Nahón Cecilia
Published: February 2017

Argentina's case is a ‘game changer’ in the discussion about sovereign debt across the globe, particularly regarding debt restructuring. This article reviews Argentina's sovereign debt and economic growth process over the last 25 years and draws lessons from the country's trajectory. Alternating austerity and heterodox economic policies resulted in different outcomes throughout this period. One lesson, in particular, stands out: sustainable debt has been a necessary condition for sustainable growth. Conversely, austerity policies combined with a lax approach toward debt have led to economic recession and debt unsustainability alike. Argentina's case underscores that the only way to overcome the debt‐recession trap is a timely and big‐enough debt restructuring that provides an economy with a fresh start. Neither austerity policies nor debt roll‐overs have done the job. That is why an orderly, predictable, fair, and balanced sovereign debt restructuring system is such a relevant – still pending – component of the international financial architecture.
Social Rights Constitutionalism: An Antagonistic Endorsement
Authors: Christodoulidis Emilios
Published: February 2017

The article discusses how we might understand solidarity as the organizing concept behind the institutionalization of social rights. I argue that writing solidarity into social rights constitutionalism carries productive tension into constitutional thinking because it disturbs the smooth passage from civil to political and finally to social rights. Marshall's influential argument that social rights are continuous to civil and political rights has become both the grounding assumption in constitutional theory and at the same time the most obvious lie in the constitutional practice of advanced capitalist democracies, clearly belied in EU constitutional practice under austerity. I explore the various attempts to accommodate the continuity of civil, political, and social rights in the face of the contradictory articulation of social democracy and capitalism before undertaking something of a defence of the antinomic significance of social rights constitutionalism, and probing what mileage might be left in ‘exploiting’ the contradiction between capitalist interests and social rights.
Contesting Austerity: On the Limits of EU Knowledge Governance
Authors: Bartl Marija
Published: February 2017

Lacking robust democratic foundations, EU authority is founded on output legitimacy — delivery of (economic) prosperity through rational governance. Yet current austerity policies are the epitome of irrational governance. While this volume highlights the EU's limited ability to deliver rational output through law and legal rationality, I argue that, without democracy, the EU cannot deliver the desired output through knowledge and technical rationality either. In fact, embedding expert institutions in democratic institutional settings plays a crucial epistemic role, contributing to the production of more reflective, socially inclusive knowledge. Lack of such democratic input in the EU's knowledge production is one of the root causes of its crumbling output legitimacy and the creation of many disenfranchised (internal) peripheries. Three recent challenges of Brexit, TTIP, and austerity may be seen as attempts to reclaim the democratic responsiveness of EU technocratic rule. However, the strategies of exit and voice have not been available in all these cases: in the Greek tragedy, contesting austerity ended in subjugation: a mirror image of ‘rational’ governance if unaided by inclusive democratic process.
Modified tube gastropexy using a mushroom‐tipped silicone catheter for management of gastric dilatation‐volvulus in dogs
Authors: Belch A. , Rubinos C. , Barnes D. C. , Nelissen P.
Published: February 2017

Objectives

To report the short‐ and long‐term complications and clinical outcomes of a cohort of dogs managed for gastric dilatation‐volvulus using a modified right‐sided tube gastropexy technique.

Materials and Methods

Retrospective case series.

Results

Of 31 dogs treated, 29 (93·5%) had an excellent short‐term outcome, and gastric dilatation‐volvulus did not recur in any dog. Twenty‐six dogs (84%) were initially fed via the gastrostomy tube postoperatively; three (9·7%) suffered a major complication including septic peritonitis (n=1), and premature tube removal (n=2). Fourteen dogs (45·1%) had minor complications including mild, self‐limiting discharge from the stoma site in 13.

Clinical Significance

Modified tube gastropexy using a mushroom‐tipped silicone catheter is an effective and safe surgical method for the management of gastric dilatation‐volvulus. The gastrostomy tube allowed early enteral feeding and easy administration of medications, including gastroprotectants.
The age, breed and sex pattern of diagnosis for veterinary care in insured cats in Japan
Authors: Isomura R. , Yamazaki M. , Inoue M. , Kwan N. C. L. , Matsuda M. , Sugiura K.
Published: February 2017

Objectives

To estimate the annual prevalence of different diagnostic categories by age, breed and sex in insured cats in Japan for which veterinary care claims had been made, and to identify if there is a pattern in these host factors.

Materials and Methods

Data from 48,187 cats insured for veterinary care in Japan in the period from April 2012 to March 2013 comprising 26,003 males and 22,184 females were analysed to calculate the annual prevalence of 18 diagnostic categories of disease by age, breed and sex.

Results

The prevalence was highest for urinary system disorders (12·2% for males and 10·0% for females), followed by digestive disorders (11·6% for males and 10·7% for females) and dermatological diseases (8·7% for males and 9·0% for females). The male cats had a higher prevalence than female cats for most diagnostic categories. The prevalence of cardiovascular, urinary, endocrine and neoplastic disorders increased with age; infectious and parasitic diseases had high prevalence at young ages, and the prevalence of respiratory, musculoskeletal disorders and injuries had bimodal peaks. Dermatological disorders had a high prevalence at all ages. A large variation in prevalence was observed between breeds for otic, dermatological, dental and cardiovascular disorders.

Clinical Significance

The findings can be used to increase awareness of patterns of health disorders in different categories of cat.
A modified tibial compression test for the detection of meniscal injury in dogs
Authors: Valen S. , McCabe C. , Maddock E. , Bright S. , Keeley B.
Published: February 2017

Objective

To assess diagnostic efficacy of a modified tibial compression test in predicting medial meniscal injury in dogs with cranial cruciate ligament failure.

Methods

Dogs admitted for surgical stabilisation of stifles with cranial cruciate ligament failure were examined by five preoperative physical tests to assess medial meniscal injury. Results of each physical test were compared with findings at arthrotomy and used to calculate sensitivities, specificities, positive and negative predictive values.

Results

None of the physical tests were accurate in reflecting meniscal integrity for dogs with cranial cruciate failure. Out of the five tests, the modified tibial compression test exhibited the highest concordance and sensitivity for the detection of medial meniscal tears. A palpable click during the modified tibial compression test had a sensitivity and specificity up to 63 and 77%, respectively, for the detection of medial meniscal lesions. Concordance values were up to 40% for the modified tibial compression test, followed by the range of motion test (up to 25%), while all other physical tests had concordance values below 10%.

Clinical Significance

Physical tests are highly available, affordable and can be easily performed, but their efficacy in diagnosing medical meniscal injury is low. Meniscal clicks associated with meniscal tears were more frequently elicited during the modified tibial compression test when compared with other traditional tests.
Dietary management of presumptive protein‐losing enteropathy in Yorkshire terriers
Authors: Rudinsky A. J. , Howard J. P. , Bishop M. A. , Sherding R. G. , Parker V. J. , Gilor C.
Published: February 2017

Objectives

To describe the clinical outcome of dietary management of Yorkshire terriers with protein‐losing enteropathy without immunosuppressive/anti‐inflammatory medications.

Methods

Records were searched for Yorkshire terriers with hypoalbuminaemia and a clinical diagnosis of protein‐losing enteropathy that were managed with diet and without immunosuppressive/anti‐inflammatory medications. Serum albumin changes were compared using a one‐way repeated measures ANOVA. Canine chronic enteropathy clinical activity index scores were compared using a Wilcoxon signed‐rank test.

Results

Eleven cases were identified. Clinical signs were variable including: diarrhoea, respiratory signs, vomiting, lethargy and weight loss. Diets fed included home cooked (n=5); Royal Canin Gastrointestinal Low Fat (n=4); Hill's Prescription Diet i/d Low Fat (n=1); or Purina HA Hypoallergenic (n=1). Clinical signs resolved completely in eight dogs, partially resolved in two dogs and failed to respond in one dog. In dogs that responded, albumin significantly improved from baseline (mean 14·9 g/L, sd ±3·7), at 2 to 4 weeks (mean 24·2 g/L, sd ±5·5, P=0·01), and at 3 to 4 months (mean 27·0 g/dL, sd ±5·9, P=0·01).

Clinical Significance

These results indicate that dietary management of protein‐losing enteropathy is a potential management strategy in Yorkshire terriers. Randomised clinical trials in Yorkshire terriers with protein‐losing enteropathy are necessary to compare success rate, survival and quality of life with dietary management versus combined dietary and immunosuppressive/anti‐inflammatory therapy.
The Minority Report at Trent and the Vatican Councils: Dissenting Episcopal Voices as Positive Sources for Theological Reflection
Authors: Blanchard Shaun
Published: February 2017

This paper argues that the record of theological dissent at Trent and Vatican I are positive and fruitful sources of theological reflection on the sensus fidelium. Not only do these “minority” voices (minority in the literal sense of opposing a majority group or opinion) help us to accurately interpret the drafts and final documents of these councils, but these minority figures can sometimes preserve the sensus fidelium through their calls for various concessions from the majority.

First, I revisit Trent's decree on Scripture (1546). Due to the interventions of two Italians (Nacchianti, the Bishop of Chioggia, and Bonuccio, the General of the Servites), the question of the relationship between scripture and tradition was left open – that is, the “two‐source” partim‐partim theory was not dogmatically enshrined. This was an important episode wherein a tiny minority gained a critical concession. I argue that this minority intervention bore fruit not only in a final Tridentine document that better echoed the faith of the ages, but also bore fruit centuries later at Vatican II in Dei verbum.

Second, I argue that the minority at Vatican I protected the Church from extreme ultramontanism. This relatively large and intellectually powerful minority, many of them rooted in Gallicanism, played a key role in tempering a dogmatic proclamation that was further balanced and interpreted a century later in Lumen gentium and Christus Dominus.

I conclude by suggesting theologians should look for ways in which the minority at Vatican II could serve future generations of Catholics in unforeseen ways.
Devotion, Theology and the Sensus Fidelium
Authors: Llywelyn Dorian
Published: February 2017

The potential unwieldiness of popular religiosity and devotional spirituality and their ambiguous relationship with the liturgy have made them objects of perennial ecclesiastical concern. More recently, magisterial discussion of popular religiosity has come to value more positively its cultural and anthropological value and its spiritual content. The reforms of Vatican II were followed by a significant demise in devotionalism amongst Northern European and North American Catholics, yet demographic change and other factors have resulted in the resurgence of popular religious devotions. Manifestations of grassroots faith may express valuable convictions and important insights, including the value of the collective and the non‐verbal. However, these values may be easily dismissed by social elites for aesthetic reasons, or by academic theologians for reasons of the cultural milieu and preferences of academia. Given the preference of the theological tradition for lexical intelligibility, and the symbolic and the physical nature of many kinds of popular religiosity, how the sub‐disciplines of theology may now responsibly and respectfully treat these perduring phenomena is not clear. A healthy relationship between the fides qua and the fides quae demands taking seriously the sensus fidelium, understood as a broad experience that embraces the daily lives and local circumstances of Christians as well as their worship. The contemporary construal of the discipline of Christian Spirituality, understood as the study of Christian experience, promises to provide a multidisciplinary approach that can address the topic of popular religiosity and devotional practice.
Deification: The Mariology of the Ordinary Faithful
Authors: Boss Sarah Jane
Published: February 2017

Popular devotion to the Virgin Mary can often be understood as implying a doctrine of deification, that is, of becoming perfect as our Heavenly Father is perfect. The Mother of God herself is the primary example of the deified person, and she in turn assists her devotees in their own process of becoming deified. The doctrine of deification articulated by Maximus the Confessor and John Scotus Eriugena provides an account that explains particularly well the theology implicit in much Marian devotion, and this is illustrated by two sets of examples, namely, devotional texts concerning the in partu virginity, and devotional practices at the shrine of Our Lady of Lourdes.
Sensus Fidelium and the Old Testament: Learning from the Faith of Israel
Authors: Suchhart Verena
Published: February 2017

Recent scholarship has reflected upon the relationship between sensus fidelium and scripture, but the Old Testament appears marginalized in this undertaking. This essay argues that the church can learn from Israel's faith for the concept of sensus fidelium. It presents the ‘canonical approach’ as an exegetical tool to bring the church as a reading community into conversation with many generations of believers in Israel and its own tradition. Furthermore, it provides one example of how a contemporary interpretation of an Old Testament text might deepen the understanding of the infallibility of the whole church in relation to its failures and sins.
Exploring the Facets of Empathy and Pain in Clinical Practice: A Review
Authors: Roche Jenny , Harmon Dominic
Published: February 2017

Background

Empathy is an essential element in providing quality patient care. The significance of empathy is even more striking in pain medicine, as chronic pain is notorious for the way it can compromise an individual, leaving him or her isolated and feeling misconceived. This review examines the role of empathy in pain medicine practice.

Methods

Current and past literature focusing on empathy and pain was searched for in PubMed, Science Direct, MEDLINE (Ovid), MEDLINE (Ebsco), Research Gate, and Google Scholar in July 2015. Search dates were not limited and languages included English only. Search terms were “empathy and pain,” “empathy and chronic pain,” “physician empathy and pain,” “neural mechanisms and empathy,” “empathy in clinical practice,” “empathy and stigma,” and “empathy and medical students”. To select relevant publications, the title and abstract of every publication were examined, and when in doubt, the rest of the publication was read.

Results

Four major themes were identified: (1) the neural basis for empathy and pain; (2) the value and challenges of practicing empathy pain medicine; (3) stigma and empathy for pain; and (4) empathy and physician education and training.

Conclusion

The review reveals that empathy deserves an unchallenged place in medical care, especially in pain medicine and medical education. It highlights the need to nurture empathy at all levels of professional expertise from medical student to senior doctors.
Modeling of a Three-Dimensional Single-Phase Direct Methanol Fuel Cell
Authors: Bayat Alireza , Maus Nicholas , Gordaninejad Faramarz
Published: February 2017

A three-dimensional, full-scale, single-phase finite element model has been developed for a liquid-fed direct methanol fuel cell (DMFC) with serpentine flow patterns. Equations for conservation of mass, momentum, and species are coupled with electrochemical kinetics in anode and cathode catalyst layers (CCLs). At the anode and cathode sides, only the liquid and the gas phases are considered, respectively. The significant benefit of a full-scale model is that the effect of physical parameters and distribution of the concentration of species can be realized in different channels for a desired section within the flow patterns. The model is used to study the effects of different operating parameters on fuel cell performance. Comparing numerical and experimental results demonstrate that the single-phase model slightly over-predicts the results for polarization plot. The modeling results also show that the porosity, temperature, and methanol concentration play a key role in affecting the DMFC polarization curve.
An Experimental Apparatus and Procedure for the Simulation of Thermal Stresses in Gas Turbine Combustion Chamber Panels Made of Ceramic Matrix Composites
Authors: Lebel Larry , Turenne Sylvain , Boukhili Rachid
Published: February 2017

This paper presents an experimental procedure developed to simulate the behavior of ceramic matrix composites (CMCs) under the cyclic thermal stresses of a gas turbine combustion chamber. An experimental apparatus was assembled that produces a temperature gradient across the thickness of a CMC specimen while holding the specimen at its two extremities, which simulates the bending stress that would be observed at the center of a combustor panel. Preliminary validation tests were performed in which A-N720 oxide–oxide CMC specimens were heated to a surface temperature of up to 1160 °C using an infrared heater, which allowed for the calibration of heat losses and material thermal conductivity. The specimen test conditions were compared with predicted conditions in generic annular combustor panels made of the same material. Provided that a more powerful heat source is made available to reach sufficiently high temperatures and through-thickness temperature gradients simultaneously, the proposed experiment promises to allow laboratory observation of representative deterioration modes of a CMC inside an actual combustion chamber.
Formulation of Sasol Isomerized Paraffinic Kerosene Surrogate Fuel for Diesel Engine Application Using an Ignition Quality Tester
Authors: Zheng Ziliang , Badawy Tamer , Henein Naeim , Schihl Peter , Sattler Eric
Published: February 2017

Sasol isomerized paraffinic kerosene (IPK) is a coal-derived synthetic fuel under consideration as a blending stock with jet propellant 8 (JP-8) for use in military equipment. However, Sasol IPK is a low ignition quality fuel with derived cetane number (DCN) of 31. The proper use of such alternative fuels in internal combustion engines (ICEs) requires the modification in control strategies to operate engines efficiently. With computational cycle simulation coupled with surrogate fuel mechanism, the engine development process is proved to be very effective. Therefore, a methodology to formulate Sasol IPK surrogate fuels for diesel engine application using ignition quality tester (IQT) is developed. An in-house developed matlab code is used to formulate the appropriate mixture blends, also known as surrogate fuel. And aspen hysys is used to emulate the distillation curve of the surrogate fuels. The properties of the surrogate fuels are compared to those of the target Sasol IPK fuel. The DCNs of surrogate fuels are measured in the IQT and compared with the target Sasol IPK fuel at the standard condition. Furthermore, the ignition delay, combustion gas pressure, and rate of heat release (RHR) of Sasol IPK and its formulated surrogate fuels are analyzed and compared at five different charge temperatures. In addition, the apparent activation energies derived from chemical ignition delay of the surrogate fuel and Sasol IPK are determined and compared.
Chemical Kinetic Mechanism Study on Premixed Combustion of Ammonia/Hydrogen Fuels for Gas Turbine Use
Authors: Xiao Hua , Valera-Medina Agustin
Published: February 2017

To explore the potential of ammonia-based fuel as an alternative fuel for future power generation, studies involving robust mathematical, chemical, thermofluidic analyses are required to progress toward industrial implementation. Thus, the aim of this study is to identify reaction mechanisms that accurately represent ammonia kinetics over a large range of conditions, particularly at industrial conditions. To comprehensively evaluate the performance of the chemical mechanisms, 12 mechanisms are tested in terms of flame speed, NOx emissions and ignition delay against the experimental data. Freely propagating flame calculations indicate that Mathieu mechanism yields the best agreement within experimental data range of different ammonia concentrations, equivalence ratios, and pressures. Ignition delay times calculations show that Mathieu mechanism and Tian mechanism yield the best agreement with data from shock tube experiments at pressures up to 30 atm. Sensitivity analyses were performed in order to identify reactions and ranges of conditions that require optimization in future mechanism development. The present study suggests that the Mathieu mechanism and Tian mechanism are the best suited for the further study on ammonia/hydrogen combustion chemistry under practical industrial conditions. The results obtained in this study also allow gas turbine designers and modelers to choose the most suitable mechanism for combustion studies.
Solution Stabilization and Convergence Acceleration for the Harmonic Balance Equation System
Authors: Wang Ding Xi , Huang Xiuquan
Published: February 2017

This paper presents an efficient approach for stabilizing solution and accelerating convergence of a harmonic balance equation system for an efficient analysis of turbomachinery unsteady flows due to flutter and blade row interaction. The proposed approach combines the Runge–Kutta method with the lower upper symmetric Gauss Seidel (LU-SGS) method and the block Jacobi method. The LU-SGS method, different from its original application as an implicit time marching scheme, is used as an implicit residual smoother with under-relaxation, allowing big Courant–Friedrichs–Lewy (CFL) numbers (in the order of hundreds), leading to significant convergence speedup. The block Jacobi method is introduced to implicitly integrate the time spectral source term of a harmonic balance equation system, in order to reduce the complexity of the direct implicit time integration by the LU-SGS method. The implicit treatment of the time spectral source term thus greatly augments the stability region of a harmonic balance equation system in the case of grid-reduced frequency well above ten. Validation of the harmonic balance flow solver was carried out using linear cascade test data. Flutter analysis of a transonic rotor and blade row interaction analyses for a transonic compressor stage were presented to demonstrate the stabilization and acceleration effect by the combination of the LU-SGS and the block Jacobi methods. The influence of the number of Jacobi iterations on solution stabilization is also investigated, showing that two Jacobi iterations are sufficient for stability purpose, which is much more efficient than existing methods of its kind in the open literature.
Octahedral palladium nanoparticles as excellent hosts for electrochemically adsorbed and absorbed hydrogen
Authors: Zalineeva Anna , Baranton Stève , Coutanceau Christophe , Jerkiewicz Gregory
Published: February 2017

Palladium nanoparticles develop a structure composed of core, shell, and skin, each having its unique H loading and properties.
Experimentally modeling stochastic processes with less memory by the use of a quantum processor
Authors: Palsson Matthew S. , Gu Mile , Ho Joseph , Wiseman Howard M. , Pryde Geoff J.
Published: February 2017

We simulate a random process using a photonic quantum processor with less memory than an ordinary computer would require.
High-dimensional quantum cloning and applications to quantum hacking
Authors: Bouchard Frédéric , Fickler Robert , Boyd Robert W. , Karimi Ebrahim
Published: February 2017

Quantum cloning machines are experimentally realized, giving insight into high-dimensional quantum cryptography.
IL-22 controls iron-dependent nutritional immunity against systemic bacterial infections
Authors: Sakamoto Kei , Kim Yun-Gi , Hara Hideki , Kamada Nobuhiko , Caballero-Flores Gustavo , Tolosano Emanuela , Soares Miguel P. , Puente José L. , Inohara Naohiro , Núñez Gabriel
Published: February 2017

IL-22 induces the heme scavenger hemopexin to limit iron availability to pathogens during infection. See the related Focus by
Datta.
Cross-Comparison of Human Wastewater-Associated Molecular Markers in Relation to Fecal Indicator Bacteria and Enteric Viruses in Recreational Beach Waters
Authors: Hughes B. , Beale D. J. , Dennis P. G. , Cook S. , Ahmed W.
Published: February 2017

Detection of human wastewater contamination in recreational waters is of critical importance to regulators due to the risks posed to public health. To identify such risks, human wastewater-associated microbial source tracking (MST) markers have been developed. At present, however, a greater understanding of the suitability of these markers for the detection of diluted human wastewater in environmental waters is necessary to predict risk. Here, we compared the process limit of detection (PLOD) and process limit of quantification (PLOQ) of six human wastewater-associated MST markers (
Bacteroides
HF183 [HF183],
Escherichia coli
H8 [EC H8],
Methanobrevibacter smithii
nifH
, human adenovirus [HAdV], human polyomavirus [HPyV], and pepper mild mottle virus [PMMoV]) in relation to a fecal indicator bacterium (FIB),
Enterococcus
sp. 23S rRNA (ENT 23S), and three enteric viruses (human adenovirus serotypes 40/41 [HAdV 40/41], human norovirus [HNoV], and human enterovirus [EV]) in beach water samples seeded with raw and secondary-treated wastewater. Among the six MST markers tested, HF183 was the most sensitive measure of human fecal pollution and was quantifiable up to dilutions of 10
−6
and 10
−4
for beach water samples seeded with raw and secondary-treated wastewater, respectively. Other markers and enteric viruses were detected at various dilutions (10
−1
to 10
−5
). These MST markers, FIB, and enteric viruses were then quantified in beach water (
n
= 12) and sand samples (
n
= 12) from South East Queensland (SEQ), Australia, to estimate the levels of human fecal pollution. Of the 12 sites examined, beach water and sand samples from several sites had quantifiable concentrations of HF183 and PMMoV markers. Overall, our results indicate that while HF183 is the most sensitive measure of human fecal pollution, it should be used in conjunction with a conferring viral marker to avoid overestimating the risk of gastrointestinal illness.

IMPORTANCE
MST is an effective tool to help utilities and regulators improve recreational water quality around the globe. Human fecal pollution poses significant public health risks compared to animal fecal pollution. Several human wastewater-associated markers have been developed and used for MST field studies. However, a head-to-head comparison in terms of their performance to detect diluted human fecal pollution in recreational water is lacking. In this study, we cross-compared the performance of six human wastewater-associated markers in relation to FIB and enteric viruses in beach water samples seeded with raw and secondary-treated wastewater. The results of this study will provide guidance to regulators and utilities on the appropriate application of MST markers for tracking the sources of human fecal pollution in environmental waters and confer human health risks.
Biofilm Formation on Stainless Steel by Streptococcus thermophilus UC8547 in Milk Environments Is Mediated by the Proteinase PrtS
Authors: Bassi D. , Cappa F. , Gazzola S. , Orrù L. , Cocconcelli P. S.
Published: February 2017

In
Streptococcus thermophilus
, gene transfer events and loss of ancestral traits over the years contribute to its high level of adaptation to milk environments. Biofilm formation capacity, a phenotype that is lost in the majority of strains, plays a role in persistence in dairy environments, such as milk pasteurization and cheese manufacturing plants. To investigate this property, we have studied
S. thermophilus
UC8547, a fast-acidifying dairy starter culture selected for its high capacity to form biofilm on stainless steel under environmental conditions resembling the dairy environment. Using a dynamic flow cell apparatus, it was shown that
S. thermophilus
UC8547 biofilm formation on stainless steel depends on the presence of milk proteins. From this strain, which harbors the
prtS
gene for the cell wall protease and shows an aggregative phenotype, spontaneous mutants with impaired biofilm capacity can be isolated at high frequency. These mutants lack the PrtS expendable island, as confirmed by comparison of the genome sequence of UC8547Δ3 with that of the parent strain. The
prtS
island excision occurs between two 26-bp direct repeats located in the two copies of the IS
Sth1
flanking this genomic island. The central role of PrtS was confirmed by analyzing the derivative strain UC8547Δ16, whose
prtS
gene was interrupted by an insertional mutation, thereby making it incapable of biofilm formation. PrtS, acting as a binding substance between the milk proteins adhered to stainless steel and
S. thermophilus
cell envelopes, mediates biofilm formation in dairy environments. This feature provides
S. thermophilus
with an ecological benefit for its survival and persistence in this environment.

IMPORTANCE
The increased persistence of
S. thermophilus
biofilm has consequences in the dairy environment: if, on the one hand, the release of this microorganism from biofilm can promote the fermentation of artisanal cheeses, under industrial conditions it may lead to undesirable contamination of dairy products. The study of the molecular mechanism driving
S. thermophilus
biofilm formation provides increased knowledge on how an ancestral trait affects relevant phenotypes, such as persistence in the environment and efficiency of growth in milk. This study provides insight into the genetic factors affecting biofilm formation at dairy plants.
Two Novel Fungal Phenolic UDP Glycosyltransferases from Absidia coerulea and Rhizopus japonicus
Authors: Xie Kebo , Dou Xiaoxiang , Chen Ridao , Chen Dawei , Fang Cheng , Xiao Zhiyan , Dai Jungui
Published: February 2017

In the present study, two novel phenolic UDP glycosyltransferases (P-UGTs), UGT58A1 and UGT59A1, which can transfer sugar moieties from active donors to phenolic acceptors to generate corresponding glycosides, were identified in the fungal kingdom. UGT58A1 (from
Absidia coerulea
) and UGT59A1 (from
Rhizopus japonicas
) share a low degree of homology with known UGTs from animals, plants, bacteria, and viruses. These two P-UGTs are membrane-bound proteins with an N-terminal signal peptide and a transmembrane domain at the C terminus. Recombinant UGT58A1 and UGT59A1 are able to regioselectively and stereoselectively glycosylate a variety of phenolic aglycones to generate the corresponding glycosides. Phylogenetic analysis revealed the novelty of UGT58A1 and UGT59A1 in primary sequences in that they are distantly related to other UGTs and form a totally new evolutionary branch. Moreover, UGT58A1 and UGT59A1 represent the first members of the UGT58 and UGT59 families, respectively. Homology modeling and mutational analysis implied the sugar donor binding sites and key catalytic sites, which provided insights into the catalytic mechanism of UGT58A1. These results not only provide an efficient enzymatic tool for the synthesis of bioactive glycosides but also create a starting point for the identification of P-UGTs from fungi at the molecular level.

IMPORTANCE
Thus far, there have been many reports on the glycosylation of phenolics by fungal cells. However, no P-UGTs have ever been identified in fungi. Our study identified fungal P-UGTs at the molecular level and confirmed the existence of the UGT58 and UGT59 families. The novel sequence information on UGT58A1 and UGT59A1 shed light on the exciting and new P-UGTs hiding in the fungal kingdom, which would lead to the characterization of novel P-UGTs from fungi. Molecular identification of fungal P-UGTs not only is theoretically significant for a better understanding of the evolution of UGT families but also can be applied as a powerful tool in the glycodiversification of bioactive natural products for drug discovery.
A Model for Designing Adaptive Laboratory Evolution Experiments
Authors: LaCroix Ryan A. , Palsson Bernhard O. , Feist Adam M.
Published: February 2017

The occurrence of mutations is a cornerstone of the evolutionary theory of adaptation, capitalizing on the rare chance that a mutation confers a fitness benefit. Natural selection is increasingly being leveraged in laboratory settings for industrial and basic science applications. Despite increasing deployment, there are no standardized procedures available for designing and performing adaptive laboratory evolution (ALE) experiments. Thus, there is a need to optimize the experimental design, specifically for determining when to consider an experiment complete and for balancing outcomes with available resources (i.e., laboratory supplies, personnel, and time). To design and to better understand ALE experiments, a simulator, ALEsim, was developed, validated, and applied to the optimization of ALE experiments. The effects of various passage sizes were experimentally determined and subsequently evaluated with ALEsim, to explain differences in experimental outcomes. Furthermore, a beneficial mutation rate of 10
−6.9
to 10
−8.4
mutations per cell division was derived. A retrospective analysis of ALE experiments revealed that passage sizes typically employed in serial passage batch culture ALE experiments led to inefficient production and fixation of beneficial mutations. ALEsim and the results described here will aid in the design of ALE experiments to fit the exact needs of a project while taking into account the resources required and will lower the barriers to entry for this experimental technique.

IMPORTANCE
ALE is a widely used scientific technique to increase scientific understanding, as well as to create industrially relevant organisms. The manner in which ALE experiments are conducted is highly manual and uniform, with little optimization for efficiency. Such inefficiencies result in suboptimal experiments that can take multiple months to complete. With the availability of automation and computer simulations, we can now perform these experiments in an optimized fashion and can design experiments to generate greater fitness in an accelerated time frame, thereby pushing the limits of what adaptive laboratory evolution can achieve.
RifZ (AMED_0655) Is a Pathway-Specific Regulator for Rifamycin Biosynthesis in Amycolatopsis mediterranei
Authors: Li Chen , Liu Xinqiang , Lei Chao , Yan Han , Shao Zhihui , Wang Ying , Zhao Guoping , Wang Jin , Ding Xiaoming
Published: February 2017

Rifamycin and its derivatives are particularly effective against the pathogenic mycobacteria
Mycobacterium tuberculosis
and
Mycobacterium leprae
. Although the biosynthetic pathway of rifamycin has been extensively studied in
Amycolatopsis mediterranei
, little is known about the regulation in rifamycin biosynthesis. Here, an
in vivo
transposon system was employed to identify genes involved in the regulation of rifamycin production in
A. mediterranei
U32. In total, nine rifamycin-deficient mutants were isolated, among which three mutants had the transposon inserted in
AMED_0655
(
rifZ
, encoding a LuxR family regulator). The
rifZ
gene was further knocked out via homologous recombination, and the transcription of genes in the rifamycin biosynthetic gene cluster (
rif
cluster) was remarkably reduced in the
rifZ
null mutant. Based on the cotranscription assay results, genes within the
rif
cluster were grouped into 10 operons, sharing six promoter regions. By use of electrophoretic mobility shift assay and DNase I footprinting assay, RifZ was proved to specially bind to all six promoter regions, which was consistent with the fact that RifZ regulated the transcription of the whole
rif
cluster. The binding consensus sequence was further characterized through alignment using the RifZ-protected DNA sequences. By use of bionformatic analysis, another five promoters containing the RifZ box (CTACC-N8-GGATG) were identified, among which the binding of RifZ to the promoter regions of both
rifK
and
orf18
(
AMED_0645
) was further verified. As RifZ directly regulates the transcription of all operons within the
rif
cluster, we propose that RifZ is a pathway-specific regulator for the
rif
cluster.

IMPORTANCE
To this day, rifamycin and its derivatives are still the first-line antituberculosis drugs. The biosynthesis of rifamycin has been extensively studied, and most biosynthetic processes have been characterized. However, little is known about the regulation of the transcription of the rifamycin biosynthetic gene cluster (
rif
cluster), and no regulator has been characterized. Through the employment of transposon screening, we here characterized a LuxR family regulator, RifZ, as a direct transcriptional activator for the
rif
cluster. As RifZ directly regulates the transcription of the entire
rif
cluster, it is considered a pathway-specific regulator for rifamycin biosynthesis. Therefore, as the first regulator characterized for direct regulation of
rif
cluster transcription, RifZ may provide a new clue for further engineering of high-yield industrial strains.
Identification of Peptidoglycan Hydrolase Constructs with Synergistic Staphylolytic Activity in Cow's Milk
Authors: Verbree Carolin T. , Dätwyler Steven M. , Meile Susanne , Eichenseher Fritz , Donovan David M. , Loessner Martin J. , Schmelcher Mathias
Published: February 2017

Peptidoglycan hydrolases (PGHs) have been suggested as novel therapeutics for the treatment of bovine mastitis. However, activity in the presence of cow's milk is an important requirement for drugs administered into the bovine udder. We have screened a library of >170 recombinant PGHs, including engineered bacteriophage endolysins, for enzymes with activity against
Staphylococcus aureus
in milk, using a microtiter plate-based protocol. Nine suitable PGH constructs were identified by this approach and further compared in time-kill assays for their efficacy against
S. aureus
in heat-treated milk. The three most active enzymes (lysostaphin, Ami2638A, and CHAPK_CWT-LST) reduced
S. aureus
in milk to undetectable numbers within minutes at nanomolar concentrations. Due to their different peptidoglycan cleavage sites, these PGH constructs revealed synergistic activity in most combinations, as demonstrated by checkerboard assays, spot assays, and time-kill experiments. Furthermore, they proved active against a selection of staphylococcal mastitis isolates from different geographical regions when applied individually or in synergistic combination. The most effective PGH combination completely eradicated
S. aureus
from milk, with no more bacteria being detected within 24 h after addition of the enzymes, corresponding to a reduction of >9 log units compared to the control. Efficacy was also retained at different inoculum levels (3 versus 6 log CFU/ml) and when
S. aureus
was grown in milk as opposed to broth prior to the experiments. In raw cow's milk, CHAPK_CWT-LST showed reduced efficacy, whereas both Ami2638A and lysostaphin retained their activity, reducing bacterial numbers by >3.5 log units within 3 h.

IMPORTANCE
Staphylococci and
S. aureus
in particular are a major cause of bovine mastitis, an inflammation of the mammary gland in cows associated with high costs and risks for consumers of milk products.
S. aureus
-induced mastitis, commonly treated by intramammary infusion of antibiotics, is characterized by low cure rates and increasing antibiotic resistance in bacteria. Therefore, alternative treatment options are highly desirable. PGHs, including bacteriophage endolysins, rapidly and specifically kill selected pathogens by degrading their cell wall and are refractory to resistance development, therefore holding promise as novel antibacterial agents. This study employed a screening approach to identify PGH constructs with high staphylolytic activity in cow's milk within a large collection of enzymes. Our results suggest that the most promising enzymes identified by this strategy hold potential as novel mastitis therapeutics and support their further characterization in animal models.
Dating Icelandic glacial floods using a new viscous remanent magnetization protocol
Authors: Berndt Thomas , Muxworthy Adrian R.
Published: February 2017

A new protocol using the viscous remanent magnetization (VRM) of boulders to date cataclysmic geological events such as tsunamis, glacial floods, and landslides is presented and its performance is assessed against two jökulhlaups (glacial floods) of known age in Iceland. High-intensity jökulhlaups have the ability to break off large boulders from bedrock and emplace and rotate them. These rocks originally carried a remanent magnetization parallel to the geomagnetic field during their formation. After being rotated by the flood, they acquire a VRM parallel with Earth’s magnetic field. In continuous thermal demagnetization experiments the unblocking temperature of the VRM can be determined, and subsequent rock magnetic VRM acquisition experiments can be used to establish a relationship between the unblocking temperature and the acquisition time, from which the time since the flood can be determined. The protocol was tested on 44 boulders from 2 historical jökulhlaups in Iceland and found to yield good order-of-magnitude estimates: 72 yr (confidence limits 11–360 yr) versus known 155 yr at the Sólheimajökull jökulhlaup and 290 yr (confidence limits 80–2300 yr) versus known 288 yr for the Kotarjökull jökulhlaup. The method can therefore be a valuable tool for future dating of cataclysmic events.