bluuebunny/crossref_metadata_2025 huggingface dataset:
SOMS: SurrOgate MultiStart algorithm for use with nonlinear programming for global optimization
Authors: Krityakierne Tipaluck , Shoemaker Christine A.
Published: June 2015

SOMS is a general surrogate‐based multistart algorithm, which is used in combination with any local optimizer to find global optima for computationally expensive functions with multiple local minima. SOMS differs from previous multistart methods in that a surrogate approximation is used by the multistart algorithm to help reduce the number of function evaluations necessary to identify the most promising points from which to start each nonlinear programming local search. SOMS's numerical results are compared with four well‐known methods, namely, Multi‐Level Single Linkage (MLSL), MATLAB's MultiStart, MATLAB's GlobalSearch, and GLOBAL. In addition, we propose a class of wavy test functions that mimic the wavy nature of objective functions arising in many black‐box simulations. Extensive comparisons of algorithms on the wavy test functions and on earlier standard global‐optimization test functions are done for a total of 19 different test problems. The numerical results indicate that SOMS performs favorably in comparison to alternative methods and does especially well on wavy functions when the number of function evaluations allowed is limited.
Ultra‐Wide Temperature Stable Dielectrics Based on Bi0.5Na0.5TiO3–NaNbO3 System
Authors: Xu Qi , Song Zhe , Tang Wenlin , Hao Hua , Zhang Lin , Appiah Millicent , Cao Minghe , Yao Zhonghua , He Zichen , Liu Hanxing
Published: June 2015

The microstructure, phase structure, ferroelectric, and dielectric properties of (1−x)Bi0.5Na0.5TiO3‐xNaNbO3 [(1−x)BNT‐xNN] ceramics conventionally sintered in the temperature range of 1080°C–1120°C were investigated as a candidate for capacitor dielectrics with wide temperature stability. Perovskite phase with no secondary impurity was observed by XRD measurement. With increasing NN content, (1−x)BNT‐xNN was found to gradually transform from ferroelectric (x = 0–0.05) to relaxor (x = 0.10–0.20) and then to paraelectric state (x = 0.25–0.35) at room temperature, indicated by P–I–E loops analysis, associated with greatly enhanced dielectric temperature stability. For the samples with x = 0.25–0.35, the temperature coefficient of capacitance (TCC) was found <11% in an ultra‐wide temperature range of −60°C–400°C with moderate dielectric constant and low dielectric loss, promising for temperature stable capacitor applications.
Effect of nurses' work environment on patient satisfaction: A cross‐sectional study of four hospitals in Japan
Authors: Tei‐Tominaga Maki , Sato Fusako
Published: June 2015

Aim

The Magnet Recognition Program is a system in the USA that recognizes a hospital as a magnet hospital for having a high retention rate of nurses and providing high quality patient care. The purpose of this study was to examine the effect of nurses' work environment with characteristics that are similar to those of magnet hospitals on patient satisfaction in Japan.

Methods

The authors distributed anonymous self‐administered questionnaires in August 2011 to all nurses via the directors of the nursing departments of four private hospitals. The response rates were 91% (n = 425) for nurses and 51% (n = 379) for patients. In the questionnaire for nurses, the items addressed basic attributes and a scale of work environment characteristics of a magnet hospital (the Japanese version of the Practice Environment Scale of the Nursing Work Index [PES‐NWI]). The questionnaire for patients addressed basic attributes, information about their hospitalization, and items to assess patient satisfaction. To examine the effects of the PES‐NWI subscales on patient satisfaction, the authors conducted multivariate logistic regression analysis for groups, which were dichotomized by 75 percentile of the scores of patient satisfaction.

Results

The result of model 1 in the multivariate logistic regression analysis demonstrated that collegial nurse–physician relations showed significant relationships with low patient satisfaction (odds ratio = 0.144, P < 0.05), while the significance was diminished in model 2, in which dummy variables of hospitals were entered into the equation.

Conclusion

These findings suggested that a favorable work environment for nurses, which is similar to that of magnet hospitals, may influence patient satisfaction in hospitals in Japan.
Evolution of host‐inclusion systems: a visco‐elastic model
Authors: Zhukov V. P. , Korsakov A. V.
Published: June 2015

A visco‐elastic model is suggested to recover the P−T−t paths of spherically symmetrical host‐inclusion systems from residual pressure patterns. For a coesite–garnet, aragonite–garnet and diamond–garnet system with partial transition of high pressure polymorphs to low pressure ones, the model predicts that the exhumation history of ultra‐high pressure metamorphic rocks from depths below 90 km began with pressure decrease to ∼1 GPa (∼40 km depth), while the temperature remained high (>800 C); then the system cooled and decompressed to ambient conditions. Non‐spherical inclusion shapes in the 3‐D model lead to heterogeneities in residual pressure and shear stress distributions as well as to significant gradients of shear stress, which may affect the kinetics and thermodynamics of phase transformation in the inclusions.
Planning for Agricultural Change and Economic Transformation in Tanzania?
Authors: Wuyts Marc , Kilama Blandina
Published: June 2015

Recently, Tanzania witnessed a revival of economic planning that explicitly aimed to combine rapid economic growth with accelerated structural transformation of the economy. To achieve these planning targets would require a relatively modest drop in the share of agriculture in GDP, but a dramatic fall in its share in employment by 2025. Tanzanian planners assume that labour is locked in agriculture because agricultural productivity is low, from which they conclude that, to release labour to fuel the expansion of manufacturing, it is imperative to raise agricultural productivity by appropriate land policies, leveraging private investment and developing public–private partnerships. We argue that, analytically, this planning argument leaves out the possibility that causality may run the other way – from high labour retention in agriculture to low agricultural productivity – and that, empirically, the observed patterns inherent in actual processes of economic transformation in Tanzania do not tally well with the assumptions of planners. More specifically, in so far as labour flows out of agriculture, it flows towards informal‐sector activities, both rural and urban, rather than towards formal manufacturing.
Melatonin promotes adipogenesis and mitochondrial biogenesis in 3T3‐L1 preadipocytes
Authors: Kato Hisashi , Tanaka Goki , Masuda Shinya , Ogasawara Junetsu , Sakurai Takuya , Kizaki Takako , Ohno Hideki , Izawa Tetsuya
Published: June 2015

Melatonin is synthesized in the pineal gland, but elicits a wide range of physiological responses in peripheral target tissues. Recent advances suggest that melatonin controls adiposity, resulting in changes in body weight. The aim of this study was to investigate the effect of melatonin on adipogenesis and mitochondrial biogenesis in 3T3‐L1 mouse embryo fibroblasts. Melatonin significantly increased the expression of peroxisome proliferator‐activated receptor‐γ (PPAR‐γ), a master regulator of adipogenesis, and promoted differentiation into adipocytes. Melatonin‐treated cells also formed smaller lipid droplets and abundantly expressed several molecules associated with lipolysis, including adipose triglyceride lipase, perilipin, and comparative gene identification‐58. Moreover, the hormone promoted biogenesis of mitochondria, as indicated by fluorescent staining, elevated the citrate synthase activity, and upregulated the expression of PPAR‐γ coactivator 1α, nuclear respiratory factor‐1, and transcription factor A. The expression of uncoupling protein 1 was also observable both at mRNA and at protein level in melatonin‐treated cells. Finally, adiponectin secretion and the expression of adiponectin receptors were enhanced. These results suggest that melatonin promotes adipogenesis, lipolysis, mitochondrial biogenesis, and adiponectin secretion. Thus, melatonin has potential as an anti‐obesity agent that may reverse obesity‐related disorders.
Identification of quantitative trait loci influencing inflammation‐mediated alveolar bone loss: insights into polygenic inheritance of host–biofilm disequilibria in periodontitis
Authors: Sima C. , Cheng Q. , Rautava J. , Levesque C. , Sherman P. , Glogauer M.
Published: June 2015

Background and Objective

The relative contribution of genetic and environmental factors to the onset and progression of periodontitis is inconclusive. Despite the high prevalence, phenotypic heterogeneity and significant local and systemic implications of this disease, early detection and individualized therapy are problematic. Using a murine model of periodontitis in a panel of 17 recombinant inbred mice, the current study addressed the heritability of, and oral dysbiosis associated with, inflammation‐mediated alveolar bone loss (iABL), the hallmark of periodontitis.

Material and Methods

Quantitative trait locus (QTL) genomics and quantitative PCR for over 99% of known murine oral microbiota were used.

Results

It was found that iABL is a polygenic trait with 32.7% heritability. One suggestive QTL, nicknamed inflammation‐mediated alveolar bone loss locus (iABLL), was identified on chromosome 2. Eleven genes involved in innate immune responses and bone metabolism, particularly related to macrophage and osteoblast function, namely Etl4, Pdss1, Cobll1, 9330158F14Rik, Xirp2, Stk39, Mettl5, Metapl1, Itga6, Pdk1 and Sp3, were found in the iABLL using cis expression QTL and nonsynonymous single nucleotide polymorphism analyses. Specific oral microbiome shifts in saliva and tongue mucosa are associated with disease in this model.

Conclusion

Our results indicate that complex host–biofilm interactions generate pathogenic states that extend beyond subgingival biofilms and periodontal tissues. Although no temporal relationship between the onset of iABL and microbiome changes were established, our findings suggest that host factors may be responsible for pathogenic shifts in subgingival biofilms when persistent and undisturbed.
Quantitation of the Regional Lymph Node Metastatic Burden and Prognosis in Malignant Mammary Tumors of Dogs
Authors: de Araújo M.R. , Campos L.C. , Ferreira E. , Cassali G.D.
Published: June 2015

Background

As in women, regional lymph node status impacts survival in dogs with malignant mammary tumors. However, few studies have evaluated regional lymph node metastases in dogs with malignant mammary gland tumors.

Objectives

To estimate overall survival based on the assessments of the lymph node status and the morphologic and morphometric features in female dogs with malignant mammary gland tumors.

Materials and Methods

In total, 178 lymph nodes from 97 female dogs were assessed and reviewed, and after confirmation by immunohistochemistry (IHC), 161 lymph nodes were selected for analysis of metastases. Animals were considered metastasis‐free (negative lymph nodes) only after IHC analysis for cytokeratin AE1/AE3. The number of positive lymph nodes, the number of metastatic foci, the maximum diameter and the area of metastasis were analyzed, and estimates of overall survival were made.

Results

Dogs with metastasis had lower mean survival than those with metastasis‐free regional lymph nodes, showing a direct relationship between the number of affected lymph nodes and shorter survival. However, histologic analysis of the lymph nodes identified lower survival rates in animals with macrometastases and isolated tumor cells, areas of metastasis >20.11 mm², and metastatic diameters >7.32 mm.

Conclusion

The identification of ≥1 lymph nodes positive for metastasis and morphometric characterization of lymphatic metastases indicate the prognostic relevance of lymph nodes status in dogs with mammary tumors.
Eurasian lynx natal den site and maternal home‐range selection in multi‐use landscapes of Norway
Authors: White S. , Briers R. A. , Bouyer Y. , Odden J. , Linnell J. D. C.
Published: June 2015

In carnivores, securing suitable den sites with associated early maternal home ranges is important for successful reproduction, and understanding natal den site selection is essential to ensure that these habitats are protected from human disturbance. This study investigated Eurasian lynx Lynx lynx natal den site selection across multiple use landscapes in Norway and explores whether the selection of early maternal home ranges across southern Norway involved a trade‐off of security for access to their preferred prey species, roe deer Capreolus capreolus. The characteristics of natal dens and home ranges from 33 reproductive events were quantified across south‐eastern and northern Norway. Natal dens were located in terrain further from the most accessible and disturbed areas (public roads) and in terrain more rugged than generally available. Early maternal home ranges were characterized by low human and low road density in rugged terrain and a selection for areas associated with higher or lower roe deer densities was not important in our analysis. Humans are the dominant cause of lynx mortality throughout Norway and our findings suggest that female lynx primarily chose areas that limited their interaction with people during the denning period.
APPROXIMATE HEDGING PROBLEM WITH TRANSACTION COSTS IN STOCHASTIC VOLATILITY MARKETS
Authors: Nguyen Thai Huu , Pergamenshchikov Serguei
Published: June 2015

This paper studies the problem of option replication in general stochastic volatility markets with transaction costs, using a new specification for the volatility adjustment in Leland's algorithm. We prove several limit theorems for the normalized replication error of Leland's strategy, as well as that of the strategy suggested by Lépinette. The asymptotic results obtained not only generalize the existing results, but also enable us to fix the underhedging property pointed out by Kabanov and Safarian. We also discuss possible methods to improve the convergence rate and to reduce the option price inclusive of transaction costs.
On a so‐Called Solution to a Paradox
Authors: Veber Michael
Published: June 2015

The mooronic solution to the surprise quiz paradox says students know there will be a surprise quiz one day this week but they lose this knowledge on the penultimate day. This is because ‘there will be a surprise quiz one day this week’ then becomes an instance of Moore's paradox. This view has surprising consequences. Furthermore, even though the surprise quiz announcement becomes an instance of Moore's paradox on the penultimate day, this does not prevent the students from knowing the quiz is coming. I conclude that the first stage of the paradoxical argument succeeds and the mooronic solution fails.
Taxonomic re‐examination of Japanese Halimeda species using genetic markers, and proposal of a new species Halimeda ryukyuensis (Bryopsidales, Chlorophyta)
Authors: Kojima Rei , Hanyuda Takeaki , Kawai Hiroshi
Published: June 2015

In order to elucidate the biodiversity of Japanese Halimeda species, we investigated molecular phylogenetic relationships using tufA and rbcL DNA sequences, and the occurrence of 9 of the 11 species previously reported in Japan was confirmed (i.e., H. borneensis, H. cuneata, H. discoidea, H. distorta, H. kanaloana, H. macroloba, H. opuntia, H. renschii and H. velasquezii). In addition, H. minima, which has not been recorded in Japan, as well as an undescribed taxon, were noticed at Okinawa Island, Okinawa, Japan. The undescribed taxon was genetically closest to H. lacunalis, but distinct from that species in having much smaller thalli, with elliptical segments and turbinate peripheral utricles. It appears to belong to the section Halimeda in the morphology of the segments, but differs from related taxa such as H. taenicola and H. tuna in its considerably smaller size and in showing fusion between the adjacent peripheral utricles. Therefore, we describe a new species Halimeda ryukyuensis sp. nov. In addition, based on morphological re‐examination of the type specimen of H. lacunalis, we suggest emendation of the description of the species as having siphons completely fused in pairs or triplets at the nodes.
Sputum matrix metalloproteinase‐8 and ‐9 and tissue inhibitor of metalloproteinase‐1 in bronchiectasis: Clinical correlates and prognostic implications
Authors: Guan Wei‐jie , Gao Yong‐hua , Xu Gang , Lin Zhi‐ya , Tang Yan , Gu Ying‐ying , Liu Gui‐hong , Li Hui‐min , Chen Rong‐chang , Zhong Nan‐shan
Published: June 2015

Background and objective

The triplet of airway infection, inflammation and bronchial wall destruction associated with excessive matrix metalloproteinases (MMP) release and imbalance of tissue inhibitor metalloproteinase‐1 (TIMP‐1) is implicated in bronchiectasis. We sought to determine the associations between sputum MMP (MMP‐8, MMP‐9) and TIMP‐1 and the severity of bronchiectasis; the utility of MMP in predicting risks of future bronchiectasis exacerbations (BE); and the changes in MMP levels during BE.

Methods

We recruited 102 patients with stable bronchiectasis and 22 healthy subjects. For bronchiectasis patients, baseline measurements consisted of sputum inflammation and MMP measurements, bacterial culture, spirometry and chest high‐resolution computed tomography (HRCT). Bronchiectasis patients were followed up for 1 year to determine the frequency of BE. Changes in MMP levels during BE were assessed in 36 bronchiectasis patients.

Results

Sputum MMP‐8, MMP‐9 and MMP‐9/TIMP‐1 ratio in bronchiectasis patients were significantly increased compared with healthy subjects. MMP‐8 and MMP‐9 levels, but not TIMP‐1, were positively correlated with clinical measures, including HRCT scores, spirometry and Bronchiectasis Severity Index. Seventy‐nine bronchiectasis patients were included in survival analyses of BE. Lower levels of baseline MMP‐9 were associated with reduced risks of and a longer time to the first BE during follow‐up. MMP‐8 and MMP‐9, but not TIMP‐1 or MMP‐9/TIMP‐1 ratio, were significantly heightened during BE.

Conclusions

Sputum MMP might be useful biomarkers for the assessment of bronchiectasis severity and the prediction of future risks of BE. Our results provide the rationales for the future clinical application of MMP inhibitors.
Longitudinal relationships between gratitude, deliberate rumination, and posttraumatic growth in adolescents following the Wenchuan earthquake in China
Authors: Zhou Xiao , Wu Xinchun
Published: June 2015

To examine the longitudinal relationship between gratitude, deliberate rumination and posttraumatic growth (PTG) in the adolescent survivors after the Wenchuan earthquake, 217 adolescent survivors were randomly selected from several primary and secondary schools in the county of Wenchuan, and were assessed by questionnaires at three and a half years (T1), four and a half years (T2), five and a half years (T3) after the Wenchuan earthquake, respectively. The results found that there was a one‐way predictive relationship of gratitude onto PTG from T1 to T3, and gratitude predicted deliberate rumination from T1 to T2 but not T2 to T3. Deliberate rumination only had a significant positive effect on PTG from T2 to T3, and PTG only predicted deliberate rumination from T1 to T2. These results indicated that gratitude could be a stable predictive factor for the development of PTG, and gratitude could also affect PTG by deliberate rumination. In addition, the predictive effect between deliberate rumination and PTG is unstable with time change.
HLA‐B*59:09, a novel allele identified by sequence‐based typing in a cord blood donated by a Korean woman
Authors: Hong S. S. , Han O. J. , Kang M. S. , Huh J. Y.
Published: June 2015

The new allele B*59:09 showed two nucleotide differences with B*59:01:01:01 in exon 3.
enviroCar: A Citizen Science Platform for Analyzing and Mapping Crowd‐Sourced Car Sensor Data
Authors: Bröring Arne , Remke Albert , Stasch Christoph , Autermann Christian , Rieke Matthes , Möllers Jakob
Published: June 2015

This article presents the enviroCar platform for collecting geographic data acquired from automobile sensors and openly providing those data for further processing and analysis. By plugging a low‐cost On‐Board Diagnostics (OBD‐II) adapter into a car and using an Android smartphone, various kinds of sensor data measured by today's cars can be collected and uploaded on to the Web. Once available on the Web, these data can be used to monitor traffic and related environmental parameters. We analyse the OBD‐II interface and its potential usage for environmental monitoring, e.g. to estimate fuel consumption and resulting emissions, noise emission, and standing times. Next, we present the main contribution of this article, the system design of the enviroCar platform. This system design consists of the enviroCar app and the enviroCar server, which allows for flexible geoprocessing of the uploaded data. We focus in this article on the description of the spatiotemporal RESTful Web Service interface and underlying data model specifically designed for handling the mobile sensor data. Finally, we present application scenarios in which the enviroCar platform can act as a powerful tool, e.g. regarding traffic monitoring and smarter cities (e.g. the detection of pollutant emission hotspots in the city), or towards applications for a quantified self (e.g. monitoring fuel consumption). We started the enviroCar project in 2013 and have been able to attract a growing number of participants since then. In a crowd‐funding initiative, enviroCar was successfully funded by volunteers, demonstrating the interest in this platform.
Sweat osmolarity shows intra‐animal regional variation in the horse
Authors: Potts Samantha , Thatcher Rhys , Jones Arwel W. , Warren Lori K. , Tenbroeck Saundra H. , Nottage Florence , McEwan Neil R.
Published: June 2015

Background

Sweating is important in regulating body temperature but can be a source of loss of both fluids and electrolytes. Although the process has been studied in horses, the variation in sweat osmolarity across the body has not.

Objectives

This work describes an investigation to determine if there is regional variation in the osmolarity of sweat across different anatomical regions of the horse.

Animals

Ten horses were used in the study and were animals either stabled for riding lessons or had livery on‐site.

Methods

Sweat samples were collected from five regions on each horse following exercise and the osmolarity measurements were made using an Osmomat 030 (Gonotec, Berlin, Germany). Values were analysed by paired t‐tests and analysis of variance.

Results

Samples from the back and ears had statistically (P < 0.05) lower osmolarity values than those seen for the neck and forelimb, with thigh values intermediate between the other two sets of values.

Conclusions and clinical importance

Previous studies have used osmolarity values based on the sweat collected from the horse's back. The current work demonstrates that these values are probably an underestimation of electrolyte loss, which may have implications for the composition and administration of rehydration compounds.
Adsorption characteristics of clay adsorbents – sepiolite, kaolin and synthetic talc – for removal of Reactive Yellow 138:1
Authors: Rahman Ari , Kishimoto Naoyuki , Urabe Takeo
Published: June 2015

Adsorption characteristics of three clay adsorbents – sepiolite, kaolin and synthetic talc – were investigated to determine their applicability to remove an anionic reactive dye – Reactive Yellow 138:1 – from a water stream. Results showed that synthetic talc had the highest maximum monolayer adsorption capacity of 10.07 mg/g, followed by kaolin (3.73 mg/g) and sepiolite (3.23 mg/g), for the removal of Reactive Yellow 138:1. Synthetic talc and sepiolite removed dyes from aqueous solutions mainly through physical adsorption depending on the surface area. By contrast, the adsorption mechanism of kaolin was strongly influenced by the anion exchange mechanism. Zeta potential analysis revealed that the adsorption capacity of clay adsorbents increased under acidic rather than alkaline conditions, owing to protonation of the clay surface. Moreover, synthetic talc was successfully regenerated by heating at more than 400°C, effectively restoring its original adsorption capacity.
Arachidonic acid‐derived signaling lipids and functions in impaired healing
Authors: Dhall Sandeep , Wijesinghe Dayanjan Shanaka , Karim Zubair A. , Castro Anthony , Vemana Hari Priya , Khasawneh Fadi T. , Chalfant Charles E. , Martins‐Green Manuela
Published: June 2015

Very little is known about lipid function during wound healing, and much less during impaired healing. Such understanding will help identify what roles lipid signaling plays in the development of impaired/chronic wounds. We took a lipidomics approach to study the alterations in lipid profile in the LIGHT−/− mouse model of impaired healing which has characteristics that resemble those of impaired/chronic wounds in humans, including high levels of oxidative stress, excess inflammation, increased extracellular matrix degradation and blood vessels with fibrin cuffs. The latter suggests excess coagulation and potentially increased platelet aggregation. We show here that in these impaired wounds there is an imbalance in the arachidonic acid (AA) derived eicosonoids that mediate or modulate inflammatory reactions and platelet aggregation. In the LIGHT−/− impaired wounds there is a significant increase in enzymatically derived breakdown products of AA. We found that early after injury there was a significant increase in the eicosanoids 11‐, 12‐, and 15‐hydroxyeicosa‐tetranoic acid, and the proinflammatory leukotrienes (LTD4 and LTE) and prostaglandins (PGE2 and PGF2α). Some of these eicosanoids also promote platelet aggregation. This led us to examine the levels of other eicosanoids known to be involved in the latter process. We found that thromboxane (TXA2/B2), and prostacyclins 6kPGF1α are elevated shortly after wounding and in some cases during healing. To determine whether they have an impact in platelet aggregation and hemostasis, we tested LIGHT−/− mouse wounds for these two parameters and found that, indeed, platelet aggregation and hemostasis are enhanced in these mice when compared with the control C57BL/6 mice. Understanding lipid signaling in impaired wounds can potentially lead to development of new therapeutics or in using existing nonsteroidal anti‐inflammatory agents to help correct the course of healing.
Vanishing of the higher direct images of the structure sheaf
Authors: Chatzistamatiou Andre , Rülling Kay
Published: June 2015

We prove that the higher direct images of the structure sheaf under a birational and projective morphism between excellent and regular schemes vanish.
Electrochromic properties of iridium oxide thin films prepared by reactive sputtering in O2 or H2O atmosphere
Authors: Ito Satoshi , Abe Yoshio , Kawamura Midori , Kim Kyung Ho
Published: June 2015

Iridium oxide is an electrochromic (EC) material, i.e., it shows reversible and persistent changes in optical properties. In this study, the authors investigated the effects of substrate temperature and sputtering gas on the structures and EC properties of iridium oxide thin films prepared by reactive radio-frequency magnetron sputtering. An Ir metal target was sputtered in an O2 or H2O atmosphere at substrate temperatures between −30 and 130 °C. The crystal structures and chemical bonding states of the films were examined using x-ray diffraction and Fourier-transform infrared (IR) spectroscopy, respectively, and their EC properties were studied in 0.5 M aqueous H2SO4 electrolyte solution. IrO2 films were deposited at 70 and 130 °C, and amorphous films were formed at 20 and −30 °C in both O2 and H2O atmospheres. IR absorption peaks from hydrogen-bonded OH groups were clearly observed for films deposited in an H2O atmosphere at substrate temperatures of −30 and 20 °C, which indicates that iridium oxyhydroxide or hydrated iridium oxide films were deposited. The amorphous iridium oxyhydroxide or hydrated iridium oxide films showed large variations in transmittance and high bleached-state transmittances, and they are considered to be suitable for use in EC devices.
WNK1-regulated inhibitory phosphorylation of the KCC2 cotransporter maintains the depolarizing action of GABA in immature neurons
Authors: Friedel Perrine , Kahle Kristopher T. , Zhang Jinwei , Hertz Nicholas , Pisella Lucie I. , Buhler Emmanuelle , Schaller Fabienne , Duan JingJing , Khanna Arjun R. , Bishop Paul N. , Shokat Kevan M. , Medina Igor
Published: June 2015

Immature neurons need WNK1-dependent phosphorylation of KCC2 to prevent a premature switch in the Cl
−
gradient and the effect of GABA.
Science Signaling
Podcast: 30 June 2015
Authors: Kahle Kristopher T. , VanHook Annalisa M.
Published: June 2015

WNK1-dependent phosphorylation of an ion transporter ensures that immature neurons are stimulated, rather than inhibited, by the neurotransmitter GABA.
Adequacy of High-Dose Cefepime Regimen in Febrile Neutropenic Patients with Hematological Malignancies
Authors: Sime Fekade Bruck , Roberts Michael S. , Tiong Ing Soo , Gardner Julia H. , Lehman Sheila , Peake Sandra L. , Hahn Uwe , Warner Morgyn S. , Roberts Jason A.
Published: June 2015

While guidelines recommend empirical cefepime therapy in febrile neutropenia, the mortality benefit of cefepime has been controversial. In light of this, recent reports on pharmacokinetic changes for several antibiotics in febrile neutropenia and the consequent suboptimal exposure call for a pharmacokinetic/pharmacodynamic evaluation of current dosing. This study aimed to assess pharmacokinetic/pharmacodynamic target attainment from a 2-g intravenous (i.v.) every 8 h (q8h) cefepime regimen in febrile neutropenic patients with hematological malignancies. Cefepime plasma concentrations were measured in the 3rd, 6th, and 9th dosing intervals at 60% of the interval and/or trough point. The selected pharmacokinetic/pharmacodynamic targets were the proportion of the dosing interval (60% and 100%) for which the free drug concentration remains above the MIC (
f
T
>MIC
). Target attainment was assessed in reference to the MIC of isolated organisms if available or empirical breakpoints if not. The percentage of
f
T
>MIC
was also estimated by log-linear regression analysis. All patients achieved >60%
f
T
>MIC
in the 3rd and 6th dosing intervals. A 100%
f
T
>MIC
was not attained in 6/12, 4/10, and 4/9 patients in the 3rd, 6th, and 9th dose intervals, respectively, or in 14/31 (45%) of the dosing intervals investigated. On the other hand, 29/31 (94%) of trough concentrations were at or above 4 mg/liter. In conclusion, for patients with normal renal function, a high-dose 2-g i.v. q8h cefepime regimen appears to provide appropriate exposure if the MIC of the organism is ≤4 mg/liter but may fail to cover less susceptible organisms.
Meropenem Population Pharmacokinetics in Critically Ill Patients with Septic Shock and Continuous Renal Replacement Therapy: Influence of Residual Diuresis on Dose Requirements
Authors: Ulldemolins Marta , Soy Dolors , Llaurado-Serra Mireia , Vaquer Sergi , Castro Pedro , Rodríguez Alejandro H. , Pontes Caridad , Calvo Gonzalo , Torres Antoni , Martín-Loeches Ignacio
Published: June 2015

Meropenem dosing in critically ill patients with septic shock and continuous renal replacement therapy (CRRT) is complex, with the recommended maintenance doses being 500 mg to 1,000 mg every 8 h (q8h) to every 12 h. This multicenter study aimed to describe the pharmacokinetics (PKs) of meropenem in this population to identify the sources of PK variability and to evaluate different dosing regimens to develop recommendations based on clinical parameters. Thirty patients with septic shock and CRRT receiving meropenem were enrolled (153 plasma samples were tested). A population PK model was developed with data from 24 patients and subsequently validated with data from 6 patients using NONMEM software (v.7.3). The final model was characterized by CL = 3.68 + 0.22 · (residual diuresis/100) and
V
= 33.00 · (weight/73)
2.07
, where CL is total body clearance (in liters per hour), residual diuresis is the volume of residual diuresis (in milliliters per 24 h), and
V
is the apparent volume of distribution (in liters). CRRT intensity was not identified to be a CL modifier. Monte Carlo simulations showed that to maintain concentrations of the unbound fraction (

f
u

) of drug above the MIC of the bacteria for 40% of dosing interval
T
(referred to as 40% of the ƒ

u
T

>MIC
), a meropenem dose of 500 mg q8h as a bolus over 30 min would be sufficient regardless of the residual diuresis. If 100% of the ƒ

u
T

>MIC
was chosen as the target, oligoanuric patients would require 500 mg q8h as a bolus over 30 min for the treatment of susceptible bacteria (MIC < 2 mg/liter), while patients with preserved diuresis would require the same dose given as an infusion over 3 h. If bacteria with MICs close to the resistance breakpoint (2 to 4 mg/liter) were to be treated with meropenem, a dose of 500 mg every 6 h would be necessary: a bolus over 30 min for oligoanuric patients and an infusion over 3 h for patients with preserved diuresis. Our results suggest that residual diuresis may be an easy and inexpensive tool to help with titration of the meropenem dose and infusion time in this challenging population.
Imidazolium Salts as Small-Molecule Urinary Bladder Exfoliants in a Murine Model
Authors: Wagers Patrick O. , Tiemann Kristin M. , Shelton Kerri L. , Kofron William G. , Panzner Matthew J. , Wooley Karen L. , Youngs Wiley J. , Hunstad David A.
Published: June 2015

We present a novel family of small-molecule urinary bladder exfoliants that are expected to be of great value in preclinical studies of urologic conditions and have improved potential for translation compared with prior agents. There is broad urologic interest in the therapeutic potential of such exfoliating agents. The primary agent used in preclinical models, the cationic peptide protamine sulfate (PS), has limited translational potential due to concerns including systemic adverse reactions and bladder tissue injury. Intravesical application of a safe, systemically nontoxic exfoliant would have potential utility in the eradication of
Escherichia coli
and other uropathogens that reside in the bladder epithelium following cystitis, as well as in chronic bladder pain and bladder cancer. Here, we introduce a family of imidazolium salts with potent and focused exfoliating activity on the bladder epithelium. Synthesis and purification were straightforward and scalable, and the compounds exhibited prolonged stability in lyophilized form. Most members of the compound family were cytotoxic to cultured uroepithelial cells, with >10-fold differences in potency across the series. Upon topical (intravesical) administration of selected compounds to the murine bladder, complete epithelial exfoliation was achieved with physiologically relevant imidazolium concentrations and brief contact times. The exfoliative activity of these compounds was markedly improved in comparison to PS, as assessed by microscopy, immunofluorescence, and immunoblotting for uroplakins. Bladder uroepithelium regenerated within days to yield a histologically normal appearance, and no toxicity was observed. Finally, the chemical scaffold offers an opportunity for inclusion of antimicrobials or conjugation with chemotherapeutic or other moieties.
In Vitro
Study of the Variable Effects of Proton Pump Inhibitors on Voriconazole
Authors: Niece Krista L. , Boyd Natalie K. , Akers Kevin S.
Published: June 2015

Voriconazole is a broad-spectrum antifungal agent used for the treatment of severe fungal infections. Maintaining therapeutic concentrations of 1 to 5.5 μg/ml is currently recommended to maximize the exposure-response relationship of voriconazole. However, this is challenging, given the highly variable pharmacokinetics of the drug, which includes metabolism by cytochrome P450 (CYP450) isotypes CYP2C19, CYP3A4, and CYP2C9, through which common metabolic pathways for many medications take place and which are also expressed in different isoforms with various metabolic efficacies. Proton pump inhibitors (PPIs) are also metabolized through these enzymes, making them competitive inhibitors of voriconazole metabolism, and coadministration with voriconazole has been reported to increase total voriconazole exposure. We examined the effects of five PPIs (rabeprazole, pantoprazole, lansoprazole, omeprazole, and esomeprazole) on voriconazole concentrations using four sets of human liver microsomes (HLMs) of different CYP450 phenotypes. Overall, the use of voriconazole in combination with any PPI led to a significantly higher voriconazole yield compared to that achieved with voriconazole alone in both pooled HLMs (77% versus 59%;
P
< 0.001) and individual HLMs (86% versus 76%;
P
< 0.001). The mean percent change in the voriconazole yield from that at the baseline after PPI exposure in pooled microsomes ranged from 22% with pantoprazole to 51% with esomeprazole. Future studies are warranted to confirm whether and how the deliberate coadministration of voriconazole and PPIs can be used to boost voriconazole levels in patients with difficult-to-treat fungal infections.
Role of CD4+Foxp3+Regulatory T Cells in Protection Induced by a Live Attenuated, Replicating Type I Vaccine Strain of Toxoplasma gondii
Authors: Akbar Haroon , Dimier-Poisson Isabelle , Moiré Nathalie
Published: June 2015

Vaccination with the live attenuatedToxoplasma gondiiMic1.3KO strain induced long-lasting immunity against challenge withToxoplasma gondiitype I and type II strains. The involvement of regulatory T cells (Tregs) in the protection mechanism was investigated. Intraperitoneal injection of Mic1.3KO induced a weak and transient influx of CD4+Foxp3+T regulatory cells followed by recruitment/expansion of CD4+Foxp3−CD25+effector cells and control of the parasite at the site of infection. The local and systemic cytokine responses associated with this recruitment of Tregs were of the TH1/Treg-like type. In contrast, injection of RH, the wild-type strain from which the vaccinal strain is derived, induced a low CD4+Foxp3+cell influx and uncontrolled multiplication of the parasites at this local site, followed by death of the mice. The associated local and systemic cytokine responses were of the TH1/TH17-like type. In addition,in vivoTreg induction in RH-infected mice with interleukin-2 (IL-2)/anti-IL-2 complexes induced control of the parasite and a TH1/Treg cytokine response similar to the response after Mic1.3KO vaccination. These results suggest that Tregs may contribute to the protective response after vaccination with Mic1.3KO.
Structural Characterization of the Fla2 Flagellum of Rhodobacter sphaeroides
Authors: de la Mora Javier , Uchida Kaoru , del Campo Ana Martínez , Camarena Laura , Aizawa Shin-Ichi , Dreyfus Georges
Published: June 2015

Rhodobacter sphaeroides
is a free-living alphaproteobacterium that contains two clusters of functional flagellar genes in its genome: one acquired by horizontal gene transfer (fla1) and one that is endogenous (fla2). We have shown that the Fla2 system is normally quiescent and under certain conditions produces polar flagella, while the Fla1 system is always active and produces a single flagellum at a nonpolar position. In this work we purified and characterized the structure and analyzed the composition of the Fla2 flagellum. The number of polar filaments per cell is 4.6 on average. By comparison with the Fla1 flagellum, the prominent features of the ultra structure of the Fla2 HBB are the absence of an H ring, thick and long hooks, and a smoother zone at the hook-filament junction. The Fla2 helical filaments have a pitch of 2.64 μm and a diameter of 1.4 μm, which are smaller than those of the Fla1 filaments. Fla2 filaments undergo polymorphic transitions
in vitro
and showed two polymorphs: curly (right-handed) and coiled. However,
in vivo
in free-swimming cells, we observed only a bundle of filaments, which should probably be left-handed. Together, our results indicate that Fla2 cell produces multiple right-handed polar flagella, which are not conventional but exceptional.

IMPORTANCE
R. sphaeroides
possesses two functional sets of flagellar genes. The fla1 genes are normally expressed in the laboratory and were acquired by horizontal transfer. The fla2 genes are endogenous and are expressed in a Fla1
−
mutant grown phototrophically and in the absence of organic acids. The Fla1 system produces a single lateral or subpolar flagellum, and the Fla2 system produces multiple polar flagella. The two kinds of flagella are never expressed simultaneously, and both are used for swimming in liquid media. The two sets of genes are certainly ready for responding to specific environmental conditions. The characterization of the Fla2 system will help us to understand its role in the physiology of this microorganism.
Is social deprivation an independent predictor of outcomes following cardiac surgery? An analysis of 240 221 patients from a national registry
Authors: Barnard James , Grant Stuart W , Hickey Graeme L , Bridgewater Ben
Published: June 2015

Objectives

Social deprivation impacts on healthcare outcomes but is not included in the majority of cardiac surgery risk prediction models. The objective was to investigate geographical variations in social deprivation of patients undergoing cardiac surgery and identify whether social deprivation is an independent predictor of outcomes.

Methods

National Adult Cardiac Surgery Audit data for coronary artery bypass graft (CABG), or valve surgery performed in England between April 2003 and March 2013, were analysed. Base hospitals in England were divided into geographical regions. Social deprivation was measured by quintile groups of the index of multiple deprivation (IMD) score with the first quintile group (Q1) being the least, and the last quintile group (Q5) the most deprived group. In-hospital mortality and midterm survival were analysed using mixed effects logistic, and stratified Cox proportional hazards regression models respectively.

Results

240 221 operations were analysed. There was substantial regional variation in social deprivation with the proportion of patients in IMD Q5 ranging from 34.5% in the North East to 6.5% in the East of England. Following adjustment for preoperative risk factors, patients undergoing all cardiac surgery in IMD Q5 were found to have an increased risk of in-hospital mortality relative to IMD Q1 (OR=1.13; 95%CI 1.03 to 1.24), as were patients undergoing isolated CABG (OR=1.19; 95%CI 1.03 to 1.37). For midterm survival, patients in IMD Q5 had an increased hazard in all groups (HRs ranged between 1.10 (valve+CABG) and 1.26 (isolated CABG)). For isolated CABG, the median postoperative length of stay was 6 and 7 days, respectively, for IMD Q1–Q4 and Q5.

Conclusions

Significant regional variation exists in the social deprivation of patients undergoing cardiac surgery in England. Social deprivation is associated with an increased risk of in-hospital mortality and reduced midterm survival. These findings have implications for health service provision, risk prediction models and analyses of surgical outcomes.
Surgical treatment of a retropharyngeal abscess in a bull
Authors: Williams Helen J , Townsend Neil , Rubio Martinez Luis
Published: June 2015

A 12‐month‐old bull with chronic respiratory stridor and dysphagia was presented. Endoscopic evaluation of the upper airway revealed a large swelling of the dorsal pharynx, partially obstructing the airway. The swelling was investigated further with the bull anaesthetised. A hand was advanced through the mouth to the level of the mass while an endoscope was placed via the nasopharyngeal route to visualise the swelling. Needle aspiration revealed thick purulent material. The wall of the abscess was digitally broken down, and the endoscope was advanced into the cavity of the abscess to allow flushing with normal saline. Immediately following surgery, there was a noticeable reduction in respiratory noise. Two days following surgery, appetite had returned to normal, and by four days following surgery, minimal respiratory noise was present at rest. Four months after being discharged, the owner reported the animal to be completely normal.
Yersinia pseudotuberculosis infection in an adult Boer goat
Authors: Helmer C , Eibach R , Kleinschmidt S , Ganter M
Published: June 2015

This case report describes a Yersinia pseudotuberculosis infection in an adult, female single pet goat kept on a dairy cattle farm. The doe showed the habitus of a chronically ill animal, with poor body condition and chronic diarrhoea, when presented at the clinic. The animal displayed a grave manifestation of the disease with severe enteritis and typhlocolitis, lymphadenitis and some up to 10 cm in diameter pyogranulomatous inflammation in the liver, spleen, pancreas, omasum and the intestinal lymph nodes. All other causative agents that might explain the described signs were ruled out (Corynebacterium pseudotuberculosis, Mycobacterium avium subspecies paratuberculosis, tuberculosis, tumorous alterations, foreign bodies, caprine arthritis encephalitis). Goats seem to be vulnerable for yersiniosis, but in contrast to this case report, in most cases, Yersinia enterocolitica, and not Y. pseudotuberculosis, can be proved as infectious cause of yersiniosis.
Intracellular survival ofBurkholderia cepaciacomplex in phagocytic cells
Authors: Valvano Miguel A.
Published: June 2015

Burkholderia cepacia complex (Bcc) species are a group of Gram-negative opportunistic pathogens that infect the airways of cystic fibrosis patients, and occasionally they infect other immunocompromised patients. Bcc bacteria display high-level multidrug resistance and chronically persist in the infected host while eliciting robust inflammatory responses. Studies using macrophages, neutrophils, and dendritic cells, combined with advances in the genetic manipulation of these bacteria, have increased our understanding of the molecular mechanisms of virulence in these pathogens and the molecular details of cell-host responses triggering inflammation. This article discusses our current view of the intracellular survival of Burkholderia cenocepacia within macrophages.
Deciding Determinism with Fairness for Simple Transducer Networks
Authors: Ameloot Tom J.
Published: June 2015

A distributed database system often operates in an asynchronous communication model where messages can be arbitrarily delayed. This communication model causes nondeterministic effects like unpredictable arrival orders of messages. Nonetheless, in general we want the distributed system to be deterministic; the system should produce the same output despite the nondeterministic effects on messages.

Previously, two interpretations of determinism have been proposed. The first says that all infinite fair computation traces produce the same output. The second interpretation is a confluence notion, saying that all finite computation traces can still be extended to produce the same output. A decidability result for the confluence notion was previously obtained for so-called simple transducer networks, a model from the field of declarative networking. In the current article, we also present a decidability result for simple transducer networks, but this time for the first interpretation of determinism, with infinite fair computation traces. We also compare the expressivity of simple transducer networks under both interpretations.