bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors Associated with the Adoption and Use of Management Accounting Techniques in Developing Countries: The Case of Romania
Authors: Albu Nadia , Albu Cătălin Nicolae
Published: October 2012

The purpose of this article is to investigate and analyze through the lens of contingency theory the existence and use of management accounting techniques in Romanian entities, with an in‐depth consideration of the institutional factors characterizing the environment of this country. Using a sample of 109 respondents, we identify factors associated with the existence and use of management accounting techniques in a context where organizational practices are subject to variations, resource and training scarcity, and uncertainty. Our findings indicate that the most important factors are the type of capital and size. The adoption and use of management accounting techniques are mostly associated with the presence of foreign capital as a defining feature of the Romanian environment. However, we find limited statistical support for the importance of the environment and competition, factors usually related to the use of such techniques in other developing countries.
On composite likelihood estimation of a multivariate INAR(1) model
Authors: Pedeli Xanthi , Karlis Dimitris
Published: October 2012

In several circumstances the collected data are counts observed in different time points, while the counts at each time point are correlated. Current models are able to account for serial correlation but usually fail to account for cross‐correlation. Motivated by the lack of appropriate tools for handling such type of data, we define a multivariate integer‐valued autoregressive process of order 1 (MINAR(1)) and examine its basic statistical properties. Apart from the general specification of the MINAR(1) process, we also study two specific parametric cases that arise under the assumptions of a multivariate Poisson and a multivariate negative binomial distribution for the innovations of the process. To overcome the computational difficulties of the maximum likelihood approach we suggest the method of composite likelihood. The performance of the two methods of estimation, that is, maximum likelihood and composite likelihood, is compared through a small simulation experiment. Extensions of the time‐invariant model to a regression model are also discussed. The proposed model is applied to a trivariate data series related to daily traffic accidents in three areas in the Netherlands.
Restricted distribution and limited gene flow in the model ciliate Tetrahymena thermophila
Authors: Zufall Rebecca A. , Dimond Kristen L. , Doerder F. Paul
Published: October 2012

The biogeography of microbial eukaryotes has long been debated, but few phylogeographic data have been available to assess whether protists tend to have ubiquitous or endemic distributions. We addressed this issue in the ciliate Tetrahymena thermophila, a highly successful model system in cell and molecular biology. We found that this species has a distribution that is restricted to the Eastern United States, with high diversity in the northeast and low diversity across the rest of its distribution. We find high levels of population subdivision, low rates of migration and significant isolation by distance, supporting the moderate endemicity model of protist biogeography. This restricted gene flow may be a result of small population size, which would reduce the probability of migration events, or the inability to establish after migration. This work lays the foundation for T. thermophila to become a valuable model system for studying population biology.
Mosaic structure of native ant supercolonies
Authors: Seppä P. , Johansson H. , Gyllenstrand N. , Pálsson S. , Pamilo P.
Published: October 2012

According to the inclusive fitness theory, some degree of positive relatedness is required for the evolution and maintenance of altruism. However, ant colonies are sometimes large interconnected networks of nests, which are genetically homogenous entities, causing a putative problem for the theory. We studied spatial structure and genetic relatedness in two supercolonies of the antFormica exsecta, using nuclear and mitochondrial markers. We show that there may be multiple pathways to supercolonial social organization leading to different spatial genetic structures. One supercolony formed a genetically homogenous population dominated by a single mtDNAhaplotype, as expected if founded by a small number of colonizers, followed by nest propagation by budding and domination of the habitat patch. The other supercolony had several haplotypes, and the spatial genetic structure was a mosaic of nuclear and mitochondrial clusters. Genetic diversity probably originated from long‐range dispersal, and the mosaic population structure is likely a result of stochastic short‐range dispersal of individuals. Such a mosaic spatial structure is apparently discordant with the current knowledge about the integrity of ant colonies. Relatedness was low in both populations when estimated among nestmates, but increased significantly when estimated among individuals sharing the same genetic cluster or haplogroup. The latter association indicates the important historical role of queen dispersal in the determination of the spatial genetic structure.
Vascular binding of a pathogen under shear force through mechanistically distinct sequential interactions with host macromolecules
Authors: Moriarty Tara J. , Shi Meiqing , Lin Yi‐Pin , Ebady Rhodaba , Zhou Hong , Odisho Tanya , Hardy Pierre‐Olivier , Salman‐Dilgimen Aydan , Wu Jing , Weening Eric H. , Skare Jon T. , Kubes Paul , Leong John , Chaconas George
Published: October 2012

Systemic dissemination of microbial pathogens permits microbes to spread from the initial site of infection to secondary target tissues and is responsible for most mortality due to bacterial infections. Dissemination is a critical stage of disease progression by the Lyme spirochaete, Borrelia burgdorferi. However, many mechanistic features of the process are not yet understood. A key step is adhesion of circulating microbes to vascular surfaces in the face of the shear forces present in flowing blood. Using real‐time microscopic imaging of the Lyme spirochaete in living mice we previously identified the first bacterial protein (B. burgdorferi BBK32) shown to mediate vascular adhesion in vivo. Vascular adhesion is also dependent on host fibronectin (Fn) and glycosaminoglycans (GAGs). In the present study, we investigated the mechanisms of BBK32‐dependent vascular adhesion in vivo. We determined that BBK32–Fn interactions (tethering) function as a molecular braking mechanism that permits the formation of more stable BBK32–GAG interactions (dragging) between circulating bacteria and vascular surfaces. Since BBK32‐like proteins are expressed in a variety of pathogens we believe that the vascular adhesion mechanisms we have deciphered here may be critical for understanding the dissemination mechanisms of other bacterial pathogens.
Epigenetics and chromatin dynamics: a review and a paradigm for functional disorders
Authors: Ordog T. , Syed S. A. , Hayashi Y. , Asuzu D. T.
Published: October 2012

Background  Motility and functional gastrointestinal disorders have high prevalence in the community, cause significant morbidity, and represent a major health care burden. Despite major advances in our understanding of the cellular and molecular basis of gastrointestinal neuromuscular functions, many of these diseases still defy mechanistic explanations. The biopsychosocial model underlying the current classification of functional gastrointestinal disorders recognizes and integrates the pathogenetic role of genetic, environmental, and psychosocial factors but has not been associated with specific molecular mechanisms.

Purpose  Here, we propose that this integrative function is encoded in the chromatin, composed of the DNA and associated histone and non‐histone proteins and non‐coding RNA. By establishing epigenetically heritable ‘molecular memories’ of past stimuli including environmental challenges, the chromatin determines an individual’s responses to future insults and translates them into high‐order outputs such as symptoms and illness behavior. Thus, surveying epigenetic signatures throughout the genome of affected cells in individual patients may make it possible to better understand and ultimately control the phenomena described by the biopsychosocial model. In this review, we provide a high‐level but comprehensive description of the concepts and mechanisms underlying epigenetics and chromatin dynamics, describe the mechanisms whereby the environment can alter the epigenome and identify aspects of functional gastrointestinal and motility disorders where epigenetic mechanisms are most likely to play important roles.
Roux‐en‐Y gastric bypass surgery increases number but not density of CCK‐, GLP‐1‐, 5‐HT‐, and neurotensin‐expressing enteroendocrine cells in rats
Authors: Mumphrey M. B. , Patterson L. M. , Zheng H. , Berthoud H.‐R.
Published: October 2012

Background  Roux‐en‐Y gastric bypass (RYGB) surgery is very effective in reducing excess body weight and improving glucose homeostasis in obese subjects. Changes in the pattern of gut hormone secretion are thought to play a major role, but the mechanisms leading to both changed hormone secretion and beneficial effects remain unclear. Specifically, it is not clear whether changes in the number of hormone‐secreting enteroendocrine cells, or changes in the releasing stimuli, or both, are important.

Methods  We estimated numbers of enteroendocrine cells after immunohistochemical staining in fixed tissue samples from rats at 10–11 months after RYGB.

Key Results  Numbers of glucagon‐like peptide‐1 (GLP‐1) (L‐cells, co‐expressing peptide YY (PYY)), cholecystokinin (CCK), neurotensin, and 5‐HT‐immunoreactive cells were significantly increased in the Roux and common limbs, but not the biliopancreatic limb in RYGB rats compared with sham‐operated, obese rats fed high‐fat diet, and chow‐fed controls. This increase was mostly accounted for by general hyperplasia of all intestinal wall layers of the nutrient‐perfused Roux and common limbs, and less to increased density of expression. The number of ghrelin cells in the bypassed stomach was not different among the three groups.

Conclusions & Inferences  The findings suggest that the number of enteroendocrine cells increases passively as the gut adapts, and that the increased total number of L‐ and I‐cells is likely to contribute to the higher circulating levels of GLP‐1, PYY, and CCK, potentially leading to suppression of food intake and stimulation of insulin secretion. Whether changes in releasing stimuli also contribute to altered circulating levels will have to be determined in future studies.
Patient Satisfaction in an Academic Chronic Pain Clinic
Authors: Trentman Terrence L. , Cornidez Eric G. , Wilshusen Laurie L. , Chang Yu‐Hui H. , Seamans David P. , Rosenfeld David M. , Freeman John A. , Chien James J.
Published: October 2012

Objectives

Patient perception of healthcare quality is of growing interest. It has been shown that patient satisfaction is associated with compliance with medical advice and clinical outcome. The 3‐fold purpose of this study was to identify which attributes of the patient–physician interaction most strongly correlated with patients' perceptions of provider quality of care, to identify key drivers that move patients' perception of overall provider quality from “very good” to “excellent,” and to identify features of the pain clinic experience that were most important to patients but were simultaneously perceived as lacking.

Methods

Randomized patient satisfaction survey conducted via telephone approximately 3 weeks after the patient's pain clinic visit.

Results

A total of 999 patients participated in the survey over 5 years (estimated response rate 60.2%). Thoroughness, listening, and time spent with the provider were the 3 attributes most strongly associated with the patients' perceptions of provider quality of care, while thoroughness, listening, punctuality, and clear instructions were the drivers of “very good” vs. “excellent” patient perceived overall provider quality. Areas identified for clinic improvement include thoroughness, providing adequate explanations and instructions, and including patient preferences in decision making.

Conclusions

These results may guide pain clinic physicians as they seek to improve patient perceptions of their care and ultimately patient outcomes.
OsNAC5 overexpression enlarges root diameter in rice plants leading to enhanced drought tolerance and increased grain yield in the field
Authors: Jeong Jin Seo , Kim Youn Shic , Redillas Mark C. F. R. , Jang Geupil , Jung Harin , Bang Seung Woon , Choi Yang Do , Ha Sun‐Hwa , Reuzeau Christophe , Kim Ju‐Kon
Published: October 2012

Drought conditions are among the most serious challenges to crop production worldwide. Here, we report the results of field evaluations of transgenic rice plants overexpressing OsNAC5, under the control of either the root‐specific (RCc3) or constitutive (GOS2) promoters. Field evaluations over three growing seasons revealed that the grain yield of the RCc3:OsNAC5 and GOS2:OsNAC5 plants were increased by 9%–23% and 9%–26% under normal conditions, respectively. Under drought conditions, however, RCc3:OsNAC5 plants showed a significantly higher grain yield of 22%–63%, whilst the GOS2:OsNAC5 plants showed a reduced or similar yield to the nontransgenic (NT) controls. Both the RCc3:OsNAC5 and GOS2:OsNAC5 plants were found to have larger roots due to an enlarged stele and aerenchyma at flowering stage. Cell numbers per cortex layer and stele of developing roots were higher in both transgenic plants than NT controls, contributing to the increase in root diameter. The root diameter was enlarged to a greater extent in the RCc3:OsNAC5, suggesting the importance of this phenotype for enhanced drought tolerance. Microarray experiments identified 25 up‐regulated genes by more than three‐fold (P < 0.01) in the roots of both transgenic lines. Also identified were 19 and 18 up‐regulated genes that are specific to the RCc3:OsNAC5 and GOS2:OsNAC5 roots, respectively. Of the genes specifically up‐regulated in the RCc3:OsNAC5 roots, GLP, PDX, MERI5 and O‐methyltransferase were implicated in root growth and development. Our present findings demonstrate that the root‐specific overexpression of OsNAC5 enlarges roots significantly and thereby enhances drought tolerance and grain yield under field conditions.
Emerging molecular targets in melanoma invasion and metastasis
Authors: Orgaz Jose L. , Sanz‐Moreno Victoria
Published: October 2012

Metastatic cutaneous melanoma accounts for the majority of skin cancer deaths due to its aggressiveness and high resistance to current therapies. To efficiently metastasize, invasive melanoma cells need to change their cytoskeletal organization and alter contacts with the extracellular matrix and the surrounding stromal cells. Melanoma cells can use different migratory strategies depending on varying environments to exit the primary tumour mass and invade surrounding and later distant tissues. In this review, we have focused on tumour cell plasticity or the interconvertibility that melanoma cells have as one of the factors that contribute to melanoma metastasis. This has been an area of very intense research in the last 5 yr yielding a vast number of findings. We have therefore reviewed all the possible clinical opportunities that this new knowledge offers to both stratify and treat cutaneous malignant melanoma patients.
Accuracy of Adults' Perception of Childhood Obesity in a Military Environment
Authors: West Gordon F. , Hayden Megan R. , Benjamin Carla R.
Published: October 2012

Objectives

The aim of this study was to determine how accurately adults in a military environment identified images of children within four different categories: underweight, normal weight, overweight, and obese.

Design and Sample

For this descriptive correlational research study, the sample was composed of 1,016 adults.

Measures

Chi‐square analysis of participant's demographic characteristics and accuracy of identification of six different images of children was conducted.

Results

Statistical significance was demonstrated with participant's self‐image and accuracy of identification in four of the six images.

Conclusions

This research supports the conclusion that individuals who classify themselves as overweight or obese are very accurate in correctly classifying images of children in these categories. While this is true our findings demonstrate that a large number of participants do not correctly self‐identify themselves. This suggests that educational campaigns need to include educational components to increase awareness of what children are considered overweight or obese. Without this, the potential exists for the message to be missed as the parent could potentially perceive the overweight or obese child as normal.
The Strategies of Japanese Public Health Nurses in Medication Support for High‐Risk Tuberculosis Patients
Authors: Shimamura Tamae , Taguchi Atsuko , Kobayashi Sayuri , Nagata Satoko , Magilvy Joan Kathy , Murashima Sachiyo
Published: October 2012

Objective

The purpose of this study was to describe the support provided by Japanese public health nurses (PHNs) to high‐risk tuberculosis (TB) patients, focusing specifically on the support aimed at preventing interruptions in treatment.

Design and Sample

A qualitative descriptive approach was used with a convenience sample of 11 PHNs in Japan who cared for TB patients at highest risk for medication adherence problems.

Measures

Semi‐structured interviews were conducted to learn the scope and practice of PHNs with high‐risk TB patients. Data were analyzed using a qualitative descriptive analysis process.

Results

One main theme was identified: “Supporting the patients in overcoming tuberculosis, regaining health, and living a healthier life.” Three categories with five subcategories described the nurses' activities: (1) empathetic and reliable support, (2) motivational strategies for medication adherence, and (3) developing a foundation for healthier life.

Conclusions

The nurses interviewed described creative and extraordinary strategies used to promote medication adherence and facilitate development of a healthy posttreatment lifestyle. Their approach was patient‐centered and culturally congruent. Findings may be transferrable to PHN practice in other regions as care for this economically disadvantaged and marginalized population is a critical need.
Pyrazole‐substituted Near‐infrared Cyanine Dyes Exhibit pH‐dependent Fluorescence Lifetime Properties
Authors: Lee Hyeran , Berezin Mikhail Y. , Tang Rui , Zhegalova Natalia , Achilefu Samuel
Published: October 2012

Near‐infrared heptamethine cyanine dye is functionalized with pyrazole derivatives at the meso‐position to induce pH‐dependent photophysical properties. The presence of pyrazole unsubstituted at 1N‐position is essential to induce pH‐dependent fluorescence intensity and lifetime changes in these dyes. Replacement of meso‐chloro group of cyanine dye IR820 with 1N‐unsubstituted pyrazole resulted in the pH‐dependent fluorescence lifetime changes from 0.93 ns in neutral media to 1.27 ns in acidic media in DMSO. Time‐resolved emission spectra (TRES) revealed that at lower pH, the pyrazole consists of fluorophores with two distinct lifetimes, which cor‐responds to pH‐sensitive and non‐pH‐sensitive species. In contrast, 1N‐substituted pyrazoles do not exhibit pH response, suggesting excited state electron transfer as the mechanism of pH‐dependent fluorescence lifetime sensitivity for this class of compounds.
Solvent‐Dependent Fluorescence Lifetimes of Estrone, 17β‐Estradiol and 17α‐Ethinylestradiol
Authors: Chan Kara Y. , Courtois Benoît , Loose Krista , Hare Patrick M.
Published: October 2012

The fluorescence lifetimes of the estrogens, estrone, 17β‐estradiol and 17α‐ethinylestradiol, were studied in various solvents. The fluorescence lifetimes of 17β‐estradiol and 17α‐ethinylestradiol decreased from 4.7 to 0.9 ns as the solvent hydrogen bond accepting ability increased, in good agreement with other phenolic molecules. Estrone's two fluorescence bands had distinct lifetimes, with the 304 nm band having a lifetime shorter than 200 ps, reflecting efficient energy transfer to the carbonyl group, which had lifetimes ranging from 4.4 to 4.9 ns depending on the solvent. Solvent effects on the 1ππ*, 1πσ* and 1nπ* states that are relevant to estrogen photophysics can adequately explain these trends. The solvent dependence on the excited states of these potent endocrine disruptors has significant implications for their photochemistry.
The Ability of Cyanobacterial Cells to Restore UV‐B Radiation Induced Damage to Photosystem II is Influenced by Photolyase Dependent DNA Repair
Authors: Vass István‐Zoltán , Kós Péter B. , Sass László , Nagy Csaba I. , Vass Imre
Published: October 2012

Damage of DNA and Photosystem‐II are among the most significant effects of UV‐B irradiation in photosynthetic organisms. Both damaged DNA and Photosystem‐II can be repaired, which represent important defense mechanisms against detrimental UV‐B effects. Correlation of Photosystem‐II damage and repair with the concurrent DNA damage and repair was investigated in the cyanobacterium Synechocystis PCC6803 using its wild type and a photolyase deficient mutant, which is unable to repair UV‐B induced DNA damages. A significant amount of damaged DNA accumulated during UV‐B exposure in the photolyase mutant concomitant with decreased Photosystem‐II activity and D1 protein amount. The transcript level of psbA3, which is a UV‐responsive copy of the psbA gene family encoding the D1 subunit of the Photosystem‐II reaction center, is also decreased in the photolyase mutant. The wild‐type cells, however, did not accumulate damaged DNA during UV‐B exposure, suffered smaller losses of Photosystem‐II activity and D1 protein, and maintained higher level of psbA3 transcripts than the photolyase mutant. It is concluded that the repair capacity of Photosystem‐II depends on the ability of cells to repair UV‐B‐damaged DNA through maintaining the transcription of genes, which are essential for protein synthesis‐dependent repair of the Photosystem‐II reaction center.
In vitro modelling of rat mucosal mast cell function in Trichinella spiralis infection
Authors: Thrasher S. M. , Scalfone L. K. , Holowka D. , Appleton J. A.
Published: October 2012

Intestinal infection with the parasitic nematode, Trichinella spiralis, provides a robust context for the study of mucosal mast cell function. In rats, mucosal mast cells are exposed to parasites during the earliest stage of infection, affording an opportunity for mast cells to contribute to an innate response to infection. During secondary infection, degranulation of rat mucosal mast cells coincides with expulsion of challenge larvae from the intestine. The goal of this study was to evaluate the rat bone marrow‐derived mast cells (BMMC) and the rat basophilic leukaemia cell line (RBL‐2H3) as models for mucosal mast cells, using parasite glycoproteins and antibody reagents that have been tested extensively in rats in vivo. We found that BMMC displayed a more robust mucosal phenotype. Although T. spiralis glycoproteins bound to mast cell surfaces in the absence of antibodies, they did not stimulate degranulation, nor did they inhibit degranulation triggered by immune complexes. Parasite glycoproteins complexed with specific monoclonal IgGs provoked release of rat mast cell protease II (RMCPII) and β‐hexosaminidase from both cell types in a manner that replicated results observed previously in passively immunized rats. Our results document that RBL‐2H3 cells and BMMC model rat mucosal mast cells in the contexts of innate and adaptive responses to T. spiralis.
Comparison of Procedure Cost for Thrombectomy of Arteriovenous Fistulas and Grafts
Authors: Schon Donald , DeLozier Tammy , Patel Nina
Published: October 2012

Expenditures on dialysis vascular access now exceed $2.5 Billion annually in the US. Studies suggest that significant savings could be achieved by increasing arteriovenous fistula (AVF) prevalence to >65%. It is common but unsubstantiated opinion that AVF have lower maintenance costs than arteriovenous grafts (AVG). This manuscript tests this hypothesis by direct comparison. Equipment utilization time and supply utilization on 110 thrombectomy procedures on AVF and 258 on AVG were compared. Procedures techniques were standardized within one facility and procedures performed by a multiple but limited number of operators. There were no significant differences in demographic variables and comorbid factors between groups. Time to complete AVF thrombectomy was 1.7 times that for AVG. In addition, major supplies used such as wires and balloons were also significantly greater. Interventionists who took longer than average to thrombectomize AVF took longer than average to thrombectomize AVG. The prevalence of arterial inflow lesions was 1.5 greater in thrombosed AVF versus Thrombosed AVG. Procedure costs when analyzed in terms of procedure time, room utilization, staff, and equipment are significantly greater for thrombosed AVF than thrombosed AVG.
Serological survey of HIV and syphilis in pregnant women in Madagascar
Authors: Frickmann Hagen , Schwarz Norbert G. , Girmann Mirko , Hagen Ralf M. , Poppert Sven , Crusius Sabine , Podbielski Andreas , Heriniaina Jean N. , Razafindrabe Tsiriniaina , Rakotondrainiarivelo Jean P. , May Jürgen , Rakotozandrindrainy Raphaël
Published: October 2012

Objectives  Peripartal transmission of human immunodeficiency virus (HIV) and Treponema pallidum, the causative agent of syphilis, leads to severe consequences for newborns. Preventive measures require awareness of the maternal infection. Although HIV and syphilis testing in Madagascar could be theoretically carried out within the framework of the national pregnancy follow‐up scheme, the required test kits are rarely available at peripheral health centres. In this study, we screened blood samples of pregnant Madagascan women for HIV and syphilis seroprevalence to estimate the demand for systemic screening in pregnancy.

Methods  Retrospective anonymous serological analysis for HIV and syphilis was performed in plasma samples from 1232 pregnant women that were taken between May and July 2010 in Ambositra, Ifanadiana, Manakara, Mananjary, Moramanga and Tsiroanomandidy (Madagascar) during pregnancy follow‐up. Screening was based on Treponema pallidum haemagglutination tests for syphilis and rapid tests for HIV, with confirmation of positive screening results on line assays.

Results  Out of 1232 pregnant women, none were seropositive for HIV and 37 (3%) were seropositive for Treponema pallidum.

Conclusions  Our findings are in line with previous studies that describe considerable syphilis prevalence in the rural Madagascan population. The results suggest a need for screening to prevent peripartal Treponema pallidum transmission, while HIV is still rare. If they are known, Treponema pallidum infections can be easily, safely and inexpensively treated even in pregnancy to reduce the risk of transmission.
Fast Thermal Cycling of Acetanilide as a Storage Material for Solar Energy Applications
Authors: El-Sebaii A. A. , Al-Agel F.
Published: October 2012

The melting temperature of acetanilide C8H9NO equals 116 °C which lies in the range of solar cooking (boiling cooking) of most kinds of food. Acetanilide was used in previous studies as a storage medium integrated within box type solar cookers. However, detailed studies of melting and/or solidification behavior of acetanilide were not reported. Therefore, the main aim of this work was to study the effect of fast thermal melting/solidification cycling of commercial grade acetanilide on its melting point and latent heat of fusion. One thousand thermal cycles had been performed and the thermophysical properties of acetanilide were measured using the differential scanning calorimetric technique. It was indicated that acetanilide solidifies with ∼15 °C of supercooling; consequently, it is recommended to overcome the supercooling problem before using acetanilide as a thermal storage material for solar energy applications.
Performance Analysis of 15 kW Closed Cycle Ocean Thermal Energy Conversion System With Different Working Fluids
Authors: Gong Jianying , Gao Tieyu , Li Guojun
Published: October 2012

Closed cycle ocean thermal energy conversion (CC-OTEC) is a way to generate electricity by the sea water temperature difference from the upper surface to the different depth. This paper presents the performance of a 15 kW micropower CC-OTEC system under different working fluids. The results show that both butane and isobutane are not proper working fluids for the CC-OTEC system because the inlet stable operating turbine pressure is in a very narrow range. R125, R143a, and R32, especially R125, are suggested to be the transitional working fluids for CC-OTEC system for their better comprehensive system performance. Moreover, it is recommended that propane should be a candidate for the working fluid because of its excellent comprehensive properties and environmental friendliness. However, propane has inflammable and explosive characteristics. As for the natural working fluid ammonia, almost all performance properties are not satisfactory except the higher net output per unit sea water mass flow rate. But ammonia has relative broader range of the stable operating turbine inlet pressure, which has benefits for the practical plant operation.
Modeling and Predicting Gas-Solid Fluidized Bed Dynamics to Capture Nonuniform Inlet Conditions
Authors: Kanholy Santhip K. , Chodak Jillian , Lattimer Brian Y. , Battaglia Francine
Published: October 2012

The hydrodynamics of fluidized beds involving gas-solids interactions are very complex, and modeling such a system using computational fluid dynamics (CFD) modeling is even more challenging for mixtures composed of nonuniform particle characteristics such as diameter or density. Another issue is the presence of dead-zones, regions of particles that do not fluidize and accumulate at the bottom of the bed, affecting uniform fluidization of the material. The dead zones typically form between the gas jets and depend on the spacing of the distributor holes and gas velocity. Conventionally, in Eulerian–Eulerian modeling for gas-solid mixtures, the solid phase is assumed to behave like a fluid, and the presence of dead zones are not typically captured in a CFD simulation. Instead, the entire bed mass present in an experiment is usually modeled in the simulations assuming complete fluidization of the bed mass. A different modeling approach was presented that accounts for only the fluidizing mass by adjusting the initial mass present in the bed using the measured pressure drop and minimum fluidization velocity from the experiments. In order to demonstrate the fidelity of the new modeling approach, three different bed materials were examined that can be classified as Geldart B particles. Glass beads and ceramic beads of the same mean particle diameter were used, as well as larger-sized ceramic particles. Binary mixture models were also validated for two types of bed mixtures consisting of glass-ceramic and ceramic-ceramic compositions. It was found that adjusting the amount of fluidizing mass in the modeling of fluidized beds best predicted the fluidization dynamics of an experiment for both single phase and binary mixture fluidized beds.
Building a Life Sciences Innovation Ecosystem
Authors: Harrison Kenneth D. , Kadaba Neena S. , Kelly Regis B. , Crawford Douglas
Published: October 2012

Universities should support research with commercial potential, provide a supportive environment for start-ups, and partner enthusiastically with the private sector.
Unmasking Interferon Pathways in Autoimmune Disease
Authors: Anandasabapathy Niroshana
Published: October 2012

Distinct patterns of interferon signaling correlate with different autoimmune disorders and may lead to disease-specific targeted treatments.
SINES of a New Leukemia Treatment
Authors: Tanhehco Yvette
Published: October 2012

Selective inhibitors of nuclear export may be a promising target for treatment of chronic lymphocytic leukemia.
High β-Lactamase Levels Change the Pharmacodynamics of β-Lactam Antibiotics in Pseudomonas aeruginosa Biofilms
Authors: Hengzhuang Wang , Ciofu Oana , Yang Liang , Wu Hong , Song Zhijun , Oliver Antonio , Høiby Niels
Published: October 2012

Resistance to β-lactam antibiotics is a frequent problem in
Pseudomonas aeruginosa
lung infection of cystic fibrosis (CF) patients. This resistance is mainly due to the hyperproduction of chromosomally encoded β-lactamase and biofilm formation. The purpose of this study was to investigate the role of β-lactamase in the pharmacokinetics (PK) and pharmacodynamics (PD) of ceftazidime and imipenem on
P. aeruginosa
biofilms.
P. aeruginosa
PAO1 and its corresponding β-lactamase-overproducing mutant, PAΔDDh2Dh3, were used in this study. Biofilms of these two strains in flow chambers, microtiter plates, and on alginate beads were treated with different concentrations of ceftazidime and imipenem. The kinetics of antibiotics on the biofilms was investigated
in vitro
by time-kill methods. Time-dependent killing of ceftazidime was observed in PAO1 biofilms, but concentration-dependent killing activity of ceftazidime was observed for β-lactamase-overproducing biofilms of
P. aeruginosa
in all three models. Ceftazidime showed time-dependent killing on planktonic PAO1 and PAΔDDh2Dh3. This difference is probably due to the special distribution and accumulation in the biofilm matrix of β-lactamase, which can hydrolyze the β-lactam antibiotics. The PK/PD indices of the AUC/MBIC and
C
max
/MBIC (AUC is the area under concentration-time curve, MBIC is the minimal biofilm-inhibitory concentration, and
C
max
is the maximum concentration of drug in serum) are probably the best parameters to describe the effect of ceftazidime in β-lactamase-overproducing
P. aeruginosa
biofilms. Meanwhile, imipenem showed time-dependent killing on both PAO1 and PAΔDDh2Dh3 biofilms. An inoculum effect of β-lactams was found for both planktonic and biofilm
P. aeruginosa
cells. The inoculum effect of ceftazidime for the β-lactamase-overproducing mutant PAΔDDh2Dh3 biofilms was more obvious than for PAO1 biofilms, with a requirement of higher antibiotic concentration and a longer period of treatment.
Inhibition of Chikungunya Virus Replication by Harringtonine, a Novel Antiviral That Suppresses Viral Protein Expression
Authors: Kaur Parveen , Thiruchelvan Meerra , Lee Regina Ching Hua , Chen Huixin , Chen Karen Caiyun , Ng Mah Lee , Chu Justin Jang Hann
Published: October 2012

Chikungunya virus (CHIKV) is a mosquito-transmitted virus that has reemerged as a significant public health threat in the last decade. Since the 2005-2006 chikungunya fever epidemic in the Indian Ocean island of La Réunion, millions of people in more than 40 countries have been infected. Despite this, there is currently no antiviral treatment for chikungunya infection. In this study, an immunofluorescence-based screening platform was developed to identify potential inhibitors of CHIKV infection. A primary screen was performed using a highly purified natural product compound library, and 44 compounds exhibiting ≥70% inhibition of CHIKV infection were identified as positive hits. Among these, four were selected for dose-dependent inhibition assays to confirm their anti-CHIKV activity. Harringtonine, a cephalotaxine alkaloid, displayed potent inhibition of CHIKV infection (50% effective concentration [EC
50
] = 0.24 μM) with minimal cytotoxicity and was selected for elucidation of its antiviral mechanism. Time-of-addition studies, cotreatment assays, and direct transfection of viral genomic RNA indicated that harringtonine inhibited an early stage of the CHIKV replication cycle which occurred after viral entry into cells. In addition, quantitative reverse transcription-PCR (qRT-PCR) and Western blot analyses indicated that harringtonine affects CHIKV RNA production as well as viral protein expression. Treatment of harringtonine against Sindbis virus, a related alphavirus, suggested that harringtonine could inhibit other alphaviruses. This study suggests for the first time that harringtonine exerts its antiviral effects by inhibiting CHIKV viral protein synthesis.
Increased Survival of Antibiotic-Resistant Escherichia coli inside Macrophages
Authors: Miskinyte Migla , Gordo Isabel
Published: October 2012

Mutations causing antibiotic resistance usually incur a fitness cost in the absence of antibiotics. The magnitude of such costs is known to vary with the environment. Little is known about the fitness effects of antibiotic resistance mutations when bacteria confront the host's immune system. Here, we study the fitness effects of mutations in the
rpoB
,
rpsL
, and
gyrA
genes, which confer resistance to rifampin, streptomycin, and nalidixic acid, respectively. These antibiotics are frequently used in the treatment of bacterial infections. We measured two important fitness traits—growth rate and survival ability—of 12
Escherichia coli
K-12 strains, each carrying a single resistance mutation, in the presence of macrophages. Strikingly, we found that 67% of the mutants survived better than the susceptible bacteria in the intracellular niche of the phagocytic cells. In particular, all
E. coli
streptomycin-resistant mutants exhibited an intracellular advantage. On the other hand, 42% of the mutants incurred a high fitness cost when the bacteria were allowed to divide outside of macrophages. This study shows that single nonsynonymous changes affecting fundamental processes in the cell can contribute to prolonged survival of
E. coli
in the context of an infection.
In Vitro
Activity of Daclatasvir on Hepatitis C Virus Genotype 3 NS5A
Authors: Wang Chunfu , Valera Lourdes , Jia Lingling , Kirk Melissa J. , Gao Min , Fridell Robert A.
Published: October 2012

The NS5A replication complex inhibitor daclatasvir (DCV; BMS-790052) inhibits hybrid replicons containing hepatitis C virus (HCV) genotype 3a (HCV3a) NS5A genes with 50% effective concentrations (EC
50
s) ranging from 120 to 870 pM. Selection studies with a hybrid HCV3a replicon identified NS5A residues 31 and 93 as sites for DCV-selected resistance. Our results support the potential use of DCV as a component in combination therapies for HCV3a chronic infection.
Cytotoxic Necrotizing Factor 1 and Hemolysin from Uropathogenic Escherichia coli Elicit Different Host Responses in the Murine Bladder
Authors: Garcia Tamako A. , Ventura Christy L. , Smith Mark A. , Merrell D. Scott , O'Brien Alison D.
Published: October 2012

Cytotoxic necrotizing factor 1 (CNF1) and hemolysin (HlyA1) are toxins produced by uropathogenicEscherichia coli(UPEC). We previously showed that these toxins contribute to the inflammation and tissue damage seen in a mouse model of ascending urinary tract infection. CNF1 constitutively activates small Rho GTPases by deamidation of a conserved glutamine residue, and HlyA1 forms pores in eukaryotic cell membranes. In this study, we used cDNA microarrays of bladder tissue isolated from mice infected intraurethrally with wild-type CP9, CP9cnf1, or CP9ΔhlyAto further evaluate the role that each toxin plays in the host response to UPEC. Regardless of the strain used, we found that UPEC itself elicited a significant change in host gene expression 24 h after inoculation. The largest numbers of upregulated genes were in the cytokine and chemokine signaling and Toll-like receptor signaling pathways. CNF1 exerted a strong positive influence on expression of genes involved in innate immunity and signal transduction and a negative impact on metabolism- and transport-associated genes. HlyA1 evoked an increase in expression of genes that encode innate immunity factors and a decrease in expression of genes involved in cytoskeletal and metabolic processes. Multiplex cytokine and myeloperoxidase assays corroborated our finding that a strong proinflammatory response was elicited by all strains tested. Bladders challenged intraurethrally with purified CNF1 displayed pathology similar to but significantly less intense than the pathology that we observed in CP9-challenged mice. Our data demonstrate substantial roles for CNF1 and HlyA1 in initiation of a strong proinflammatory response to UPEC in the bladder.
Role of YopK in Yersinia pseudotuberculosis Resistance against Polymorphonuclear Leukocyte Defense
Authors: Thorslund Sara E. , Ermert David , Fahlgren Anna , Erttmann Saskia F. , Nilsson Kristina , Hosseinzadeh Ava , Urban Constantin F. , Fällman Maria
Published: October 2012

The enteropathogenYersinia pseudotuberculosiscan survive in the harsh environment of lymphoid compartments that abounds in immune cells. This capacity is dependent on the plasmid-encodedYersiniaouter proteins (Yops) that are delivered into the host cell via a mechanism involving theYersiniatype III secretion system. We show that the virulence protein YopK has a role in the mechanism by whichY. pseudotuberculosisavoids the polymorphonuclear leukocyte or neutrophil (PMN) defense. AyopKmutant, which is attenuated in the mouse infection model, where it fails to cause systemic infection, was found to colonize Peyer's patches and mesenteric lymph nodes more rapidly than the wild-type strain. Further, in mice lacking PMNs, theyopKmutant caused full disease with systemic spread and typical symptoms. Analyses of effects on PMNs revealed that both the wild-type strain and theyopKmutant inhibited internalization and reactive oxygen species production, as well as neutrophil extracellular trap formation by PMNs. However, the wild-type strain effectively avoided induction of PMN death, whereas the mutant caused a necrosis-like PMN death. Taken together, our results indicate that YopK is required for the ability ofYersiniato resist the PMN defense, which is critical for the virulence of the pathogen. We suggest a mechanism whereby YopK functions to prevent unintended Yop delivery and thereby PMN disruption, resulting in necrosis-like cell death, which would enhance the inflammatory response favoring the host.
Inactivation of Epidermal Growth Factor by Porphyromonas gingivalis as a Potential Mechanism for Periodontal Tissue Damage
Authors: Pyrc Krzysztof , Milewska Aleksandra , Kantyka Tomasz , Sroka Aneta , Maresz Katarzyna , Kozieł Joanna , Nguyen Ky-Anh , Enghild Jan J. , Knudsen Anders Dahl , Potempa Jan
Published: October 2012

Porphyromonas gingivalis
is a Gram-negative bacterium associated with the development of periodontitis. The evolutionary success of this pathogen results directly from the presence of numerous virulence factors, including peptidylarginine deiminase (PPAD), an enzyme that converts arginine to citrulline in proteins and peptides. Such posttranslational modification is thought to affect the function of many different signaling molecules. Taking into account the importance of tissue remodeling and repair mechanisms for periodontal homeostasis, which are orchestrated by ligands of the epidermal growth factor receptor (EGFR), we investigated the ability of PPAD to distort cross talk between the epithelium and the epidermal growth factor (EGF) signaling pathway. We found that EGF preincubation with purified recombinant PPAD, or a wild-type strain of
P. gingivalis
, but not with a PPAD-deficient isogenic mutant, efficiently hindered the ability of the growth factor to stimulate epidermal cell proliferation and migration. In addition, PPAD abrogated EGFR-EGF interaction-dependent stimulation of expression of suppressor of cytokine signaling 3 and interferon regulatory factor 1. Biochemical analysis clearly showed that the PPAD-exerted effects on EGF activities were solely due to deimination of the C-terminal arginine. Interestingly, citrullination of two internal Arg residues with human endogenous peptidylarginine deiminases did not alter EFG function, arguing that the C-terminal arginine is essential for EGF biological activity. Cumulatively, these data suggest that the PPAD-activity-abrogating EGF function in gingival pockets may at least partially contribute to tissue damage and delayed healing within
P. gingivalis
-infected periodontia.
Vitamin D and the Human Antimicrobial Peptide LL-37 Enhance Group AStreptococcusResistance to Killing by Human Cells
Authors: Love John F. , Tran-Winkler Hien J. , Wessels Michael R.
Published: October 2012

The CsrRS two-component regulatory system of group AStreptococcus(GAS;Streptococcus pyogenes) responds to subinhibitory concentrations of the human antimicrobial peptide LL-37. LL-37 signaling through CsrRS results in upregulation of genes that direct synthesis of virulence factors, including the hyaluronic acid capsule and streptolysin O (SLO). Here, we demonstrate that a consequence of this response is augmented GAS resistance to killing by human oropharyngeal keratinocytes, neutrophils, and macrophages. LL-37-induced upregulation of SLO and hyaluronic acid capsule significantly reduced internalization of GAS by keratinocytes and phagocytic killing by neutrophils and macrophages. Because vitamin D induces LL-37 production by macrophages, we tested its effect on macrophage killing of GAS. In contrast to the reported enhancement of macrophage function in relation to other pathogens, treatment of macrophages with 1α,25-dihydroxy-vitamin D3 paradoxically reduced the ability of macrophages to control GAS infection. These observations demonstrate that LL-37 signals through CsrRS to induce a virulence phenotype in GAS characterized by heightened resistance to ingestion and killing by both epithelial cells and phagocytes. By inducing LL-37 production in macrophages, vitamin D may contribute to this paradoxical exacerbation of GAS infection.

IMPORTANCEIt remains poorly understood why group AStreptococcus(GAS) causes asymptomatic colonization or localized throat inflammation in most individuals but rarely progresses to invasive infection. The human antimicrobial peptide LL-37, which is produced as part of the innate immune response to GAS infection, signals through the GAS CsrRS two-component regulatory system to upregulate expression of multiple virulence factors. This study reports that two CsrRS-regulated GAS virulence factors—streptolysin O and the hyaluronic acid capsule—are critical in LL-37-induced resistance of GAS to killing by human throat epithelial cells and by neutrophils and macrophages. Vitamin D, which increases LL-37 production in macrophages, has the paradoxical effect of increasing GAS resistance to macrophage-mediated killing. In this way, the human innate immune response may promote the transition from GAS colonization to invasive infection.
Chiari malformation and central sleep apnoea: successful therapy with adaptive pressure support servo-ventilation following surgical treatment
Authors: Fahim Ahmed , Johnson Anthony OC
Published: October 2012

Sleep apnoea is a common disorder with significant morbidity. It is categorised into obstructive and central sleep apnoea. There are a variety of conditions associated with central sleep apnoea ranging from cardiac failure to structural brain anomalies. We herein report a case of 57-year-old woman with Chiari malformation associated with significant sleep-disordered breathing. There was a family history of Chiari malformation. Although neurosurgical intervention had a significant impact on apnoea hypopnoea index (AHI) with a reduction from 81/h preoperatively to 22.1/h after the surgical treatment, it failed to cure the sleep disorder breathing completely and adaptive non-invasive servo-ventilation had a dramatic effect on symptoms and normalised the AHI. Although, central sleep apnoea is associated with a number of common disorders, this case illustrates that there may be an unusual cause. Moreover, adaptive pressure support servo-ventilation may provide a promising treatment option following surgical correction of Chiari malformation.