bluuebunny/crossref_metadata_2025 huggingface dataset:
Patterned atomic layer epitaxy of Si/Si(001):H
Authors: Owen James H. G. , Ballard Joshua , Randall John N. , Alexander Justin , Von Ehr James R.
Published: August 2011

We aim to develop techniques for the building of atomically precise structures. On the H-terminated Si(001) surface, H atoms can be selectively removed using an STM tip with appropriate lithography conditions, creating arbitrary patterns of reactive dangling bonds with atomic precision. The exposed patterns are used as templates for the growth of Si and Ge by gas-source epitaxy, using disilane and digermane as the precursor gases. The quality of the epitaxy, in terms of island size and defect density of the second and subsequent monolayer (ML), is dependent upon the electron exposure. Good-quality growth of the second and following MLs requires a multiple of the exposure required for good-quality growth of the first ML. This is interpreted in terms of remanent hydrogen in island sites in the first ML.
Shotgun Isotope Array for Rapid, Substrate-Specific Detection of Microorganisms in a Microbial Community
Authors: Tobino Tomohiro , Kurisu Futoshi , Kasuga Ikuro , Furumai Hiroaki
Published: August 2011

The shotgun isotope array method has been proposed to be an effective new tool for use in substrate-specific microbe exploration without any prior knowledge of the community composition. Proof of concept was demonstrated by detection of acetate-degrading microorganisms in activated sludge and further verified by independent stable isotope probing (SIP).
Spontaneous Gac Mutants of Pseudomonas Biological Control Strains: Cheaters or Mutualists?
Authors: Driscoll William W. , Pepper John W. , Pierson Leland S. , Pierson Elizabeth A.
Published: August 2011

Bacteria rely on a range of extracellular metabolites to suppress competitors, gain access to resources, and exploit plant or animal hosts. The GacS/GacA two-component regulatory system positively controls the expression of many of these beneficial external products in pseudomonad bacteria. Natural populations often contain variants with defective Gac systems that do not produce most external products. These mutants benefit from a decreased metabolic load but do not appear to displace the wild type in nature. How could natural selection maintain the wild type in the presence of a mutant with enhanced growth? One hypothesis is that Gac mutants are “cheaters” that do not contribute to the public good, favored within groups but selected against between groups, as groups containing more mutants lose access to ecologically important external products. An alternative hypothesis is that Gac mutants have a mutualistic interaction with the wild type, so that each variant benefits by the presence of the other. In the biocontrol bacterium
Pseudomonas chlororaphis
strain 30-84, Gac mutants do not produce phenazines, which suppress competitor growth and are critical for biofilm formation. Here, we test the predictions of these alternative hypotheses by quantifying interactions between the wild type and the phenazine- and biofilm-deficient Gac mutant within growing biofilms. We find evidence that the wild type and Gac mutants interact mutualistically in the biofilm context, whereas a phenazine-defective structural mutant does not. Our results suggest that the persistence of alternative Gac phenotypes may be due to the stabilizing role of local mutualistic interactions.
Groundwater Seeps Facilitate Exposure to Burkholderia pseudomallei
Authors: Baker Anthony , Tahani Donald , Gardiner Christopher , Bristow Keith L. , Greenhill Andrew R. , Warner Jeffrey
Published: August 2011

Burkholderia pseudomallei
is a saprophytic bacterium which is the causative agent of melioidosis, a common cause of fatal bacterial pneumonia and sepsis in the tropics. The incidence of melioidosis is clustered spatially and temporally and is heavily linked to rainfall and extreme weather events. Clinical case clustering has recently been reported in Townsville, Australia, and has implicated Castle Hill, a granite monolith in the city center, as a potential reservoir of infection. Topsoil and water from seasonal groundwater seeps were collected around the base of Castle Hill and analyzed by quantitative real-time PCR targeting the type III secretion system genes for the presence of
B. pseudomallei
. The organism was identified in 65% (95% confidence interval [CI], 49.5 to 80.4) of soil samples (
n
= 40) and 92.5% (95% CI, 83.9 to 100) of seasonal groundwater samples (
n
= 40). Further sampling of water collected from roads and gutters in nearby residential areas after an intense rainfall event found that 88.2% (95% CI, 72.9 to 100) of samples (
n
= 16) contained viable
B. pseudomallei
at concentrations up to 113 CFU/ml. Comparison of isolates using multilocus sequence typing demonstrated clinical matches and close associations between environmental isolates and isolates derived from clinical samples from patients in Townsville. This study demonstrated that waterborne
B. pseudomallei
from groundwater seeps around Castle Hill may facilitate exposure to
B. pseudomallei
and contribute to the clinical clustering at this site. Access to this type of information will advise the development and implementation of public health measures to reduce the incidence of melioidosis.
Improvement in the Thermostability of
d
-Psicose 3-Epimerase from Agrobacterium tumefaciens by Random and Site-Directed Mutagenesis
Authors: Choi Jin-Geun , Ju Yo-Han , Yeom Soo-Jin , Oh Deok-Kun
Published: August 2011

The S213C, I33L, and I33L S213C variants of
d
-psicose 3-epimerase from
Agrobacterium tumefaciens
, which were obtained by random and site-directed mutagenesis, displayed increases of 2.5, 5, and 7.5°C in the temperature for maximal enzyme activity, increases of 3.3-, 7.2-, and 29.9-fold in the half-life at 50°C, and increases of 3.1, 4.3, and 7.6°C in apparent melting temperature, respectively, compared with the wild-type enzyme. Molecular modeling suggests that the improvement in thermostability in these variants may have resulted from increased putative hydrogen bonds and formation of new aromatic stacking interactions. The immobilized wild-type enzyme with and without borate maintained activity for 8 days at a conversion yield of 70% (350 g/liter psicose) and for 16 days at a conversion yield of 30% (150 g/liter psicose), respectively. After 8 or 16 days, the enzyme activity gradually decreased, and the conversion yields with and without borate were reduced to 22 and 9.6%, respectively, at 30 days. In contrast, the activities of the immobilized I33L S213C variant with and without borate did not decrease during the operation time of 30 days. These results suggest that the I33L S213C variant may be useful as an industrial producer of
d
-psicose.
The Microbial Carbon Pump: from Genes to Ecosystems
Authors: Jiao Nianzhi , Zheng Qiang
Published: August 2011

The majority of marine dissolved organic carbon (DOC) is resistant to biological degradation and thus can remain in the water column for thousands of years, constituting carbon sequestration in the ocean. To date the origin of such recalcitrant DOC (RDOC) is unclear. A recently proposed conceptual framework, the microbial carbon pump (MCP), emphasizes the microbial transformation of organic carbon from labile to recalcitrant states. The MCP is concerned with both microbial uptakes and outputs of DOC compounds, covering a wide range from gene to ecosystem levels. In this minireview, the ATP binding cassette (ABC) transporter is used as an example for the microbial processing of DOC at the genetic level. The compositions of the ABC transporter genes of the two major marine bacterial clades
Roseobacter
and SAR11 demonstrate that they have distinct patterns in DOC utilization:
Roseobacter
strains have the advantage of taking up carbohydrate DOC, while SAR11 bacteria prefer nitrogen-containing DOC. At the ecosystem level, bacterially derived RDOC based on
d
-amino acid biomarkers is reported to be responsible for about a quarter of the total marine RDOC pool. Under future global warming scenarios, partitioning of primary production into DOC could be enhanced, and thus the MCP could play an even more important role in carbon sequestration by the ocean. Joint efforts to study the MCP from multiple disciplines are required to obtain a better understanding of ocean carbon cycle and its coupling with global change.
Evolution of Secondary Metabolite Genes in Three Closely Related Marine Actinomycete Species
Authors: Freel Kelle C. , Nam Sang-Jip , Fenical William , Jensen Paul R.
Published: August 2011

The marine actinomycete genus
Salinispora
is composed of three closely related species. These bacteria are a rich source of secondary metabolites, which are produced in species-specific patterns. This study examines the distribution and phylogenetic relationships of genes involved in the biosynthesis of secondary metabolites in the salinosporamide and staurosporine classes, which have been reported for
S. tropica
and
S. arenicola
, respectively. The focus is on “
Salinispora pacifica
,” the most recently discovered and phylogenetically diverse member of the genus. Of 61
S. pacifica
strains examined, 15 tested positive for a ketosynthase (KS) domain linked to the biosynthesis of salinosporamide K, a new compound in the salinosporamide series. Compound production was confirmed in two strains, and the domain phylogeny supports vertical inheritance from a common ancestor shared with
S. tropica
, which produces related compounds in the salinosporamide series. There was no evidence for interspecies recombination among
salA
KS sequences, providing further support for the geographic isolation of these two salinosporamide-producing lineages. In addition, staurosporine production is reported for the first time for
S. pacifica
, with 24 of 61 strains testing positive for
staD
, a key gene involved in the biosynthesis of this compound. High levels of recombination were observed between
staD
alleles in
S. pacifica
and the cooccurring yet more distantly related
S. arenicola
, which produces a similar series of staurosporines. The distributions and phylogenies of the biosynthetic genes examined provide insight into the complex processes driving the evolution of secondary metabolism among closely related bacterial species.
Efficient one-pot synthesis of polysubstituted 6-[(1H-1,2,3-triazol-1-yl)methyl]uracils through the “click” protocol
Authors: Jansa Petr , Špaček Petr , Votruba Ivan , Břehová Petra , Dračínský Martin , Klepetářová Blanka , Janeba Zlatko
Published: August 2011

The preparation of several triazolo acyclic nucleosides and triazolo acyclic nucleoside phosphonates is described. The synthetic methodology has been developed as an efficient one-pot Cu(I)-catalyzed azide alkyne Huisgen “click” cycloaddition. A novel Cu(I)-catalyzed decarboxylation reaction of 1-substituted 1H-1,2,3-triazole-4-carboxylic acids at room temperature was observed and used for the preparation of 1-substituted 1H-1,2,3-triazoles. As congeners of TPI (Taiho pharmaceutical inhibitor), the prepared compounds were screened as potential inhibitors of human thymidine phosphorylase, but no inhibitory activity was observed.
Opinions of patients with cancer on the relative importance of place of death in the context of a ‘good death’
Authors: Waghorn Melanie , Young Holly , Davies Andrew
Published: August 2011

Objective

The primary objective of the study was to determine the relative importance of place of death to patients with advanced cancer being treated at a cancer centre in England.

Methods

Demographic data were collected from the electronic patient record system, with additional information obtained from the patients themselves. Patients were questioned about a variety of end of life issues, including preferred place of death (PPD), and ‘acceptable’ places of death. They were also asked to rank the importance of factors previously linked to a ‘good death’.

Results

120 patients participated in the study. 51 (42.5%) patients stated that ‘home’ was their PPD, while 80 (67%) patients stated that home was an acceptable place of death. Patients from areas with worse deprivation scores were less likely to want to die at home than patients from areas with better deprivation scores (p=0.03). The most important factors associated with a good death were ‘to have my pain/symptoms well controlled’, ‘to not be a burden to my family’ and ‘to have sorted out my personal affairs’ respectively. Place of death was ranked as the seventh most important factor.

Discussion

Place of death is undoubtedly an important factor in achieving a good death for some patients and carers. However, for others a home death is either unimportant or to be avoided. The results of this study, and the results of similar studies, suggest that place of death may not be a good marker of the quality of end of life care.
Patients with pancreatic cancer and relatives talk about preferred place of death and what influenced their preferences: a qualitative study: Table 1
Authors: Chapple Alison , Evans Julie , McPherson Ann , Payne Sheila
Published: August 2011

Objective

To explore reasons why people with pancreatic cancer, who are reaching the end of their lives, say they wish to die at home or elsewhere, and why preferences may change.

Design

Qualitative study using semistructured interviews followed by thematic analysis.

Setting

Respondents recruited from different parts of the UK during 2009/2010.

Participants

16 people with experience of pancreatic cancer (8 patients and 8 bereaved relatives) who discussed place of death in detail during an in-depth interview (from a total sample of 32 people with pancreatic cancer and eight relatives of others who had died of this disease).

Results

People's preferences were affected by their perceptions and previous experiences of care available at home, in a hospice or hospital. Preferences were also shaped by fears about possible loss of dignity, or fears of becoming a burden. Some people thought that a home death might leave bad memories for other members of the family. People with pancreatic cancer and their relatives were aware that preferences might change (or had changed) as death approached.

Conclusions

The National Health Service End of Life Care Strategy for England seeks to meet the needs of people who are dying and promotes better support for home deaths. More information is needed about why patients hold different views about place of care and place of death, why patients' preferences change and what importance patients attach to place of death. Health professionals should bear this in mind if the subject is raised during advance care planning.
Proximity to vacant buildings is associated with increased fire risk in Baltimore, Maryland, homes
Authors: Schachterle Stephen E , Bishai David , Shields Wendy , Stepnitz Rebecca , Gielen Andrea C
Published: August 2011

Background

Fires and burns are a leading cause of unintentional injury death in the USA. Although it has been anecdotally reported that vacant dwellings are at a higher risk for fire, the association between vacancy and fire risk at the individual household level has not been empirically measured.

Methods

In this cross-sectional study, geocoded residential vacant properties (VP) and fire events are analysed in Baltimore City at the census tract level and the individual household level.

Results

On average, a 10% increase in the proportion of vacancies in a census tract was associated with a 9.9% increase in fires (95% CI: 5% to 15%). Random-effects Poisson models, controlling for housing and neighbourhood conditions, found contagion effects. The risk of fire in an occupied dwelling increased by 8% (95% CI: 1% to 10%) for every vacant structure within 10 m, and the risk of fire decreased by half (95% CI: 45% to 62%) for every km between an occupied dwelling and vacant building. Close proximity to VP was associated with trash fires within dwellings (p=0.039) and structure fires (p=0.012).

Conclusions

We believe that this is the first study to demonstrate increased risk posed by nearby VP at the household level, confirming earlier ecological analyses of the role of VP as strong correlates of home fires. Measurement of this risk can motivate property owners, policy makers and insurers to invest in risk reduction measures that include building maintenance and trash removal.
Prevalence of helmet use by users of bicycles, push scooters, inline skates and skateboards in Toronto and the surrounding area in the absence of comprehensive legislation: an observational study
Authors: Page Jessica L , Macpherson Alison K , Middaugh-Bonney Tara , Tator Charles H
Published: August 2011

Background

Legislation in the province of Ontario, Canada, mandates users under the age of 18 to wear a helmet when they ride a bicycle, and legislation has been shown to significantly increase rates of bicycle helmet use. Legislation does not exist in Ontario for older bicyclists or for users of other non-motorised modes of transportation, and there are no current data available regarding rates of helmet use in these categories. This study was designed to determine the prevalence of helmet use among users of bicycles, skateboards, push scooters and inline skates in Toronto, Ontario, and the surrounding area. Further analysis was performed to examine factors associated with helmet use.

Methods

We performed a cross-sectional, observational study. Three trained, stationary observers captured 6038 users of bicycles (5783), skateboards (77), inline skates (165) and push scooters (13) in the summer of 2009. Observations were separated into three time periods capturing commuters, midday users and recreational users. A general linear model was used to assess the factors associated with helmet use among bicyclists.

Results

Helmets were worn by 48.9% of all users observed and 50.0% of all bicyclists. Among bicyclists, females were more likely to wear helmets than males (prevalence ratio 1.27, 95% CI 1.17 to 1.36), while children were significantly more likely to wear helmets than adults (prevalence ratio 1.17, 95% CI 1.37 to 2.15). Significant behavioural variation was observed among users during the three observation periods (p<0.001), with commuters being the most likely to wear a helmet.

Conclusion

In the absence of comprehensive legislation encompassing all ages of users, only half of users of non-motorised, wheeled transportation devices are choosing to wear a helmet to protect against traumatic brain injury. Implementation of evidence-based strategies to increase helmet use, such as the introduction of legislation encompassing all ages and all equipment, is required.
Association of cardiac and non-cardiac chronic disease comorbidity on glycaemic control in a multi-ethnic population with type 1 and type 2 diabetes
Authors: Mehta R L , Davies M J , Ali S , Taub N A , Stone M A , Baker R , McNally P G , Lawrence I G , Khunti K
Published: August 2011

Aims

To determine the prevalence of chronic disease comorbidity in south Asians (SAs) and white Europeans (WEs) with diabetes and to quantify the relationship of cardiac disease comorbidity (CDCM) and non-cardiac disease comorbidity (NCCM) to glycaemic control in SAs and WEs with type 1 and type 2 diabetes mellitus.

Methods

A cross-sectional study using a database of patients of SA (25.5%) and WE (74.5%) origin attending a specialist diabetes clinic in the UK between 2003 and 2005 (n=5664).

Results

The prevalence of SAs and WEs with type 1 diabetes was 12% and 88%, respectively; for those with type 2 diabetes the prevalence was 30% and 70%, respectively. Overall, the prevalence of comorbidity in people with type 1 diabetes was 25.5% and with type 2 diabetes was 47%. NCCM was more prevalent in WEs than SAs (17.6% vs 12.8%, p<0.001). In type 2 diabetes, the prevalence of suboptimal glycaemic control was significantly greater in SAs compared to WEs with NCCM and CDCM (79% vs 62%, p<0.001; 78% vs 65%, p<0.001, respectively). SAs with type 2 diabetes and comorbidity had excess odds of suboptimal glycaemic control compared to WEs: OR 2.27 (95% CI 1.50 to 3.43) for those with NCCM and OR 1.91 (95% CI 1.49 to 2.44) for those with CDCM.

Conclusions

The prevalence of CDCM is higher in SAs compared to WEs with type 2 diabetes, whereas the prevalence of NCCM is higher in WEs compared to SAs. Taking into account comorbidities, SAs (compared to WEs) with type 2 diabetes had an excess risk of having HbA1c ≥7% ranging from 1.86- to 2.27-fold. Further research is needed to identify the reasons for unfavourable metabolic conditions in SAs and also develop and evaluate interventions.
ADAPTABLE MULTI-AGENT SYSTEMS: THE CASE OF THE GAIA METHODOLOGY
Authors: CERNUZZI LUCA , MOLESINI AMBRA , OMICINI ANDREA , ZAMBONELLI FRANCO
Published: August 2011

Changes and adaptations are always necessary after the deployment of a multi-agent system (MAS), as well as of any other type of software systems. Some of these changes may be simply perfective and have local impact only. However, adaptive changes to meet new situations in the operational environment of the MAS may impact globally on the overall design. More specifically, those changes usually affect the organizational structure of the MAS. In this paper we analyze the issue of design change/adaptation in a MAS organization, and the specific problem of how to properly model/design a MAS so as to make it ready for adaptation. Special attention is paid to the Gaia methodology, whose suitability in dealing with adaptable MAS organizations is also discussed with the help of an illustrative application example.
PROBLEMS IN ADDITIVE NUMBER THEORY, IV: NETS IN GROUPS AND SHORTEST LENGTH g-ADIC REPRESENTATIONS
Authors: NATHANSON MELVYN B.
Published: August 2011

The number theoretic analog of a net in metric geometry suggests new problems and results in combinatorial and additive number theory. For example, for a fixed integer g ≥ 2, the study of h-nets in the additive group of integers with respect to the generating set Ag = {0} ∪ {± gi : i = 0, 1, 2, …} requires a knowledge of the word lengths of integers with respect to Ag. A g-adic representation of an integer is described that algorithmically produces a representation of shortest length. Additive complements and additive asymptotic complements are also discussed, together with their associated minimality problems.
$\mathbb{Q}(\sqrt{2}, \sqrt{35})$ HAS A NON-PRINCIPAL EUCLIDEAN IDEAL
Authors: GRAVES HESTER
Published: August 2011

This paper introduces a totally real quartic number field with a non-principal Euclidean ideal.
A GENERALIZATION OF THE CONGRUENT NUMBER PROBLEM
Authors: ROLEN LARRY
Published: August 2011

We study a certain generalization of the classical Congruent Number Problem. Specifically, we study integer areas of rational triangles with an arbitrary fixed angle θ. These numbers are called θ-congruent. We give an elliptic curve criterion for determining whether a given integer n is θ-congruent. We then consider the "density" of integers n which are θ-congruent, as well as the related problem giving the "density" of angles θ for which a fixed n is congruent. Assuming the Shafarevich–Tate conjecture, we prove that both proportions are at least 50% in the limit. To obtain our result we use the recently proven p-parity conjecture due to Monsky and the Dokchitsers as well as a theorem of Helfgott on average root numbers in algebraic families.
Early subclinical increase in pulmonary water content in athletes performing sustained heavy exercise at sea level: ultrasound lung comet-tail evidence
Authors: Pingitore Alessandro , Garbella Erika , Piaggi Paolo , Menicucci Danilo , Frassi Francesca , Lionetti Vincenzo , Piarulli Andrea , Catapano Giosuè , Lubrano Valter , Passera Mirko , Di Bella Gianluca , Castagnini Cinzia , Pellegrini Silvia , Metelli Maria Rosa , Bedini Remo , Gemignani Angelo , L′Abbate Antonio
Published: August 2011

Whether prolonged strenuous exercise performed by athletes at sea level can produce interstitial pulmonary edema is under debate. Chest sonography allows to estimate extravascular lung water, creating ultrasound lung comet-tail (ULC) artifacts. The aim of the study was to determine whether pulmonary water content increases in Ironmen ( n = 31) during race at sea level and its correlation with cardiopulmonary function and systemic proinflammatory and cardiac biohumoral markers. A multiple factor analysis approach was used to determine the relations between systemic modifications and ULCs by assessing correlations among variables and groups of variables showing significant pre-post changes. All athletes were asymptomatic for cough and dyspnea at rest and after the race. Immediately after the race, a score of more than five comet tail artifacts, the threshold for a significant detection, was present in 23 athletes (74%; 16.3 ± 11.2; P < 0.01 ULC after the race vs. rest) but decreased 12 h after the end of the race (13 athletes; 42%; 6.3 ± 8.0; P < 0.01 vs. soon after the race). Multiple factor analysis showed significant correlations between ULCs and cardiac-related variables and NH2-terminal pro-brain natriuretic peptide. Healthy athletes developed subclinical increase in pulmonary water content immediately after an Ironman race at sea level, as shown by the increased number of ULCs related to cardiac changes occurring during exercise. Hemodynamic changes are one of several potential factors contributing to the mechanisms of ULCs.
Temporal and spatial correlation of platelet-activating factor-induced increases in endothelial [Ca2+]i, nitric oxide, and gap formation in intact venules
Authors: Zhou Xueping , He Pingnian
Published: August 2011

We have previously demonstrated that platelet-activating factor (PAF)-induced increases in microvessel permeability were associated with endothelial gap formation and that the magnitude of peak endothelial intracellular Ca2+ concentration ([Ca2+]i) and nitric oxide (NO) production at the single vessel level determines the degree of the permeability increase. This study aimed to examine whether the magnitudes of PAF-induced peak endothelial [Ca2+]i, NO production, and gap formation are correlated at the individual endothelial cell level in intact rat mesenteric venules. Endothelial gaps were quantified by the accumulation of fluorescent microspheres at endothelial clefts using confocal imaging. Endothelial [Ca2+]i was measured on fura-2- or fluo-4-loaded vessels, and 4,5-diaminofluorescein (DAF-2) was used for NO measurements. The results showed that increases in endothelial [Ca2+]i, NO production, and gap formation occurred in all endothelial cells when vessels were exposed to PAF but manifested a spatial heterogeneity in magnitudes among cells in each vessel. PAF-induced peak endothelial [Ca2+]i preceded the peak NO production by 0.6 min at the cellular level, and the magnitudes of NO production and gap formation linearly correlated with that of the peak endothelial [Ca2+]i in each cell, suggesting that the initial levels of endothelial [Ca2+]i determine downstream NO production and gap formation. These results provide direct evidence from intact venules that inflammatory mediator-induced increases in microvessel permeability are associated with the generalized formation of endothelial gaps around all endothelial cells. The spatial differences in the molecular signaling that were initiated by the heterogeneous endothelial Ca2+ response contribute to the heterogeneity in permeability increases along the microvessel wall during inflammation.
TAK1 plays a major role in growth factor-induced phenotypic modulation of airway smooth muscle
Authors: Pera Tonio , Sami Riham , Zaagsma Johan , Meurs Herman
Published: August 2011

Increased airway smooth muscle (ASM) mass is a major feature of airway remodeling in asthma and chronic obstructive pulmonary disease. Growth factors induce a proliferative ASM phenotype, characterized by an increased proliferative state and a decreased contractile protein expression, reducing contractility of the muscle. Transforming growth factor-β-activated kinase 1 (TAK1), a mitogen-activated protein kinase kinase kinase, is a key enzyme in proinflammatory signaling in various cell types; however, its function in ASM is unknown. The aim of this study was to investigate the role of TAK1 in growth factor-induced phenotypic modulation of ASM. Using bovine tracheal smooth muscle (BTSM) strips and cells, as well as human tracheal smooth muscle cells, we investigated the role of TAK1 in growth factor-induced proliferation and hypocontractility. Platelet-derived growth factor- (PDGF; 10 ng/ml) and fetal bovine serum (5%)-induced increases in DNA synthesis and cell number in bovine and human cells were significantly inhibited by pretreatment with the specific TAK1 inhibitor LL-Z-1640-2 (5 Z-7-oxozeaenol; 100 nM). PDGF-induced DNA synthesis and extracellular signal-regulated kinase-1/2 phosphorylation in BTSM cells were strongly inhibited by both LL-Z-1640-2 pretreatment and transfection of dominant-negative TAK1. In addition, LL-Z-1640-2 inhibited PDGF-induced reduction of BTSM contractility and smooth muscle α-actin expression. The data indicate that TAK1 plays a major role in growth factor-induced phenotypic modulation of ASM.
Regulation of monocyte subset proinflammatory responses within the lung microvasculature by the p38 MAPK/MK2 pathway
Authors: O'Dea Kieran P. , Dokpesi Justina O. , Tatham Kate C. , Wilson Michael R. , Takata Masao
Published: August 2011

Margination and activation of monocytes within the pulmonary microcirculation contribute substantially to the development of acute lung injury in mice. The enhanced LPS-induced TNF expression exhibited by Gr-1highcompared with Gr-1lowmonocytes within the lung microvasculature suggests differential roles for these subsets. We investigated the mechanisms responsible for such heterogeneity of lung-marginated monocyte proinflammatory response using a combined in vitro and in vivo approach. The monocyte subset inflammatory response was studied in vitro in mouse peripheral blood mononuclear cell-lung endothelial cell coculture and in vivo in a two-hit model of intravenous LPS-induced monocyte margination and lung inflammation in mice, by flow cytometry-based quantification of proinflammatory genes and intracellular phospho-kinases. With LPS stimulation in vitro, TNF expression was consistently higher in Gr-1highthan Gr-1lowmonocytes, markedly enhanced by coculture with endothelial cells, and abrogated by p38 MAPK inhibitors. Expression of IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) was only detectable under coculture conditions, was substantially higher in Gr-1highmonocytes, and was attenuated by p38 inhibition. Consistent with these differential responses, phosphorylation of p38 and its substrate MAPK-activated protein kinase 2 (MK2) was significantly higher in the Gr-1highsubset. In vivo, p38 inhibitor treatment significantly attenuated LPS-induced TNF expression in “lung-marginated” Gr-1highmonocytes. LPS-induced p38/MK2 phosphorylation was higher in lung-marginated Gr-1highthan Gr-1lowmonocytes and neutrophils, mirroring TNF expression. These results indicate that the p38/MK2 pathway is a critical determinant of elevated Gr-1highsubset responsiveness within the lung microvasculature, producing a coordinated proinflammatory response that places Gr-1highmonocytes as key orchestrators of pulmonary microvascular inflammation and injury.
Airway remodeling in murine asthma correlates with a defect in PGE2synthesis by lung fibroblasts
Authors: Stumm Camila Leindecker , Wettlaufer Scott H. , Jancar Sonia , Peters-Golden Marc
Published: August 2011

Asthma is a chronic lung disease characterized by local inflammation that can result in structural alterations termed airway remodeling. One component of airway remodeling involves fibroblast accumulation and activation, resulting in deposition of collagen I around small bronchi. Prostaglandin E2(PGE2) is the main eicosanoid lipid mediator produced by lung fibroblasts, and it exerts diverse anti-fibrotic actions. Dysregulation of the PGE2synthesis/response axis has been identified in human pulmonary fibrotic diseases and implicated in the pathogenesis of animal models of lung parenchymal fibrosis. Here we investigated the relationship between the fibroblast PGE2axis and airway fibrosis in an animal model of chronic allergic asthma. Airway fibrosis increased progressively as the number of airway challenges with antigen increased from 3 to 7 to 12. Compared with cells from control lungs, fibroblasts grown from the lungs of asthmatic animals, regardless of challenge number, exhibited no defect in the ability of PGE2or its analogs to inhibit cellular proliferation and collagen I expression. This correlated with intact expression of the EP2receptor, which is pivotal for PGE2responsiveness. However, cytokine-induced upregulation of PGE2biosynthesis as well as expression of cyclooxygenase-2 (COX-2) and microsomal PGE synthase-1 declined with increasing numbers of antigen challenges. In addition, treatment with the COX-2-selective inhibitor nimesulide potentiated the degree of airway fibrosis following repeated allergen challenge. Because endogenous COX-2-derived PGE2acts as a brake on airway fibrosis, the inability of fibroblasts to upregulate PGE2generation in the inflammatory milieu presented by repeated allergen exposure could contribute to the airway remodeling and fibrosis observed in chronic asthma.
Intrauterine growth restriction decreases pulmonary alveolar and vessel growth and causes pulmonary artery endothelial cell dysfunction in vitro in fetal sheep
Authors: Rozance Paul J. , Seedorf Gregory J. , Brown Alicia , Roe Gates , O'Meara Meghan C. , Gien Jason , Tang Jen-Ruey , Abman Steven H.
Published: August 2011

Intrauterine growth restriction (IUGR) increases the risk for bronchopulmonary dysplasia (BPD). Abnormal lung structure has been noted in animal models of IUGR, but whether IUGR adversely impacts fetal pulmonary vascular development and pulmonary artery endothelial cell (PAEC) function is unknown. We hypothesized that IUGR would decrease fetal pulmonary alveolarization, vascular growth, and in vitro PAEC function. Studies were performed in an established model of severe placental insufficiency and IUGR induced by exposing pregnant sheep to elevated temperatures. Alveolarization, quantified by radial alveolar counts, was decreased 20% ( P < 0.005) in IUGR fetuses. Pulmonary vessel density was decreased 44% ( P < 0.01) in IUGR fetuses. In vitro, insulin increased control PAEC migration, tube formation, and nitric oxide (NO) production. This response was absent in IUGR PAECs. VEGFA stimulated tube formation, and NO production also was absent. In control PAECs, insulin increased cell growth by 68% ( P < 0.0001). Cell growth was reduced in IUGR PAECs by 29% at baseline ( P < 0.01), and the response to insulin was attenuated ( P < 0.005). Despite increased basal and insulin-stimulated Akt phosphorylation in IUGR PAECs, endothelial NO synthase (eNOS) protein expression as well as basal and insulin-stimulated eNOS phosphorylation were decreased in IUGR PAECs. Both VEGFA and VEGFR2 also were decreased in IUGR PAECs. We conclude that fetuses with IUGR are characterized by decreased alveolar and vascular growth and PAEC dysfunction in vitro. This may contribute to the increased risk for adverse respiratory outcomes and BPD in infants with IUGR.
Mechanisms of lung endothelial barrier disruption induced by cigarette smoke: role of oxidative stress and ceramides
Authors: Schweitzer Kelly S. , Hatoum Hadi , Brown Mary Beth , Gupta Mehak , Justice Matthew J. , Beteck Besem , Van Demark Mary , Gu Yuan , Presson Robert G. , Hubbard Walter C. , Petrache Irina
Published: August 2011

The epithelial and endothelial cells lining the alveolus form a barrier essential for the preservation of the lung respiratory function, which is, however, vulnerable to excessive oxidative, inflammatory, and apoptotic insults. Whereas profound breaches in this barrier function cause pulmonary edema, more subtle changes may contribute to inflammation. The mechanisms by which cigarette smoke (CS) exposure induce lung inflammation are not fully understood, but an early alteration in the epithelial barrier function has been documented. We sought to investigate the occurrence and mechanisms by which soluble components of mainstream CS disrupt the lung endothelial cell barrier function. Using cultured primary rat microvascular cell monolayers, we report that CS induces endothelial cell barrier disruption in a dose- and time-dependent manner of similar magnitude to that of the epithelial cell barrier. CS exposure triggered a mechanism of neutral sphingomyelinase-mediated ceramide upregulation and p38 MAPK and JNK activation that were oxidative stress dependent and that, along with Rho kinase activation, mediated the endothelial barrier dysfunction. The morphological changes in endothelial cell monolayers induced by CS included actin cytoskeletal rearrangement, junctional protein zonula occludens-1 loss, and intercellular gap formation, which were abolished by the glutathione modulator N-acetylcysteine and ameliorated by neutral sphingomyelinase inhibition. The direct application of ceramide recapitulated the effects of CS, by disrupting both endothelial and epithelial cells barrier, by a mechanism that was redox and apoptosis independent and required Rho kinase activation. Furthermore, ceramide induced dose-dependent alterations of alveolar microcirculatory barrier in vivo, measured by two-photon excitation microscopy in the intact rat. In conclusion, soluble components of CS have direct endothelial barrier-disruptive effects that could be ameliorated by glutathione modulators or by inhibitors of neutral sphingomyelinase, p38 MAPK, JNK, and Rho kinase. Amelioration of endothelial permeability may alleviate lung and systemic vascular dysfunction associated with smoking-related chronic obstructive lung diseases.
Phosphatidylinositol 4,5-bisphosphate stimulates alveolar epithelial fluid clearance in male and female adult rats
Authors: Kooijman Edgar E. , Kuzenko Stephanie R. , Gong Denghuang , Best Michael D. , Folkesson Hans G.
Published: August 2011

Cell membrane phospholipids, like phosphatidylinositol 4,5-bisphosphate [PI( 4 , 5 )P2], can regulate epithelial Na channel (ENaC) activity. Gender differences in lung ENaC expression have also been demonstrated. However, the effects in vivo on alveolar fluid clearance are uncertain. Thus PI( 4 , 5 )P2 effects on alveolar fluid clearance were studied in male and female rats. An isosmolar 5% albumin solution was intrapulmonary instilled; alveolar fluid clearance was studied for 1 h. Female rats had a 37 ± 19% higher baseline alveolar fluid clearance than male rats. Bilateral ovariectomy attenuated this gender difference. Compared with controls, PI( 4 , 5 )P2 instillation (300 μM) increased alveolar fluid clearance by ∼93% in both genders. Amiloride or the specific αENaC small-interfering RNA inhibited baseline and PI( 4 , 5 )P2-stimulated alveolar fluid clearance in both genders, indicating a dependence on amiloride-sensitive pathways. The fraction of amiloride inhibition was greater in PI( 4 , 5 )P2-instilled rats (male: 64 ± 10%; female: 70 ± 11%) than in controls (male: 30 ± 6%; female: 44 ± 8%). PI( 4 , 5 )P2 instillation lacked additional alveolar fluid clearance stimulation above that of terbutaline, nor did propranolol inhibit alveolar fluid clearance after PI( 4 , 5 )P2 instillation, indicating that PI( 4 , 5 )P2 stimulation was not secondary to endogenous β-adrenoceptor activation. PI( 4 , 5 )P2 amine instillation resulted in an intermediate alveolar fluid clearance stimulation, suggesting that, to reach maximal alveolar fluid clearance stimulation, PI( 4 , 5 )P2 must reside in cell membranes. In summary, PI( 4 , 5 )P2 instillation upregulated in vivo alveolar fluid clearance similar to short-term β-adrenoceptor upregulation of alveolar fluid clearance. PI( 4 , 5 )P2 stimulation was mediated partly by increased amiloride-sensitive Na transport. There exist important gender-related effects suggesting a female advantage that may have clinical implications for resolution of acute lung injury.
The Coevolution of Phycobilisomes: Molecular Structure Adapting to Functional Evolution
Authors: Shi Fei , Qin Song , Wang Yin-Chu
Published: August 2011

Phycobilisome is the major light-harvesting complex in cyanobacteria and red alga. It consists of phycobiliproteins and their associated linker peptides which play key role in absorption and unidirectional transfer of light energy and the stability of the whole complex system, respectively. Former researches on the evolution among PBPs and linker peptides had mainly focused on the phylogenetic analysis and selective evolution. Coevolution is the change that the conformation of one residue is interrupted by mutation and a compensatory change selected for in its interacting partner. Here, coevolutionary analysis of allophycocyanin, phycocyanin, and phycoerythrin and covariation analysis of linker peptides were performed. Coevolution analyses reveal that these sites are significantly correlated, showing strong evidence of the functional and structural importance of interactions among these residues. According to interprotein coevolution analysis, less interaction was found between PBPs and linker peptides. Our results also revealed the correlations between the coevolution and adaptive selection in PBS were not directly related, but probably demonstrated by the sites coupled under physical-chemical interactions.
Planting Date and Seeding Rate Effects on Sunn Hemp Biomass and Nitrogen Production for a Winter Cover Crop
Authors: Balkcom Kipling S. , Massey Jessica M. , Mosjidis Jorge A. , Price Andrew J. , Enloe Stephen F.
Published: August 2011

Sunn hemp (Crotalaria junceaL.) is a tropical legume that produces plant biomass and nitrogen (N) quickly. Our objectives were to assess the growth of a new sunn hemp cultivar breed to produce seed in a temperate climate and determine the residual N effect on a rye (Secale cerealeL.) cover crop in east-central Alabama from 2007 to 2009. Plant populations, plant height, stem diameter, biomass production, and N content were determined for two sunn hemp planting dates, following corn (Zea maysL.) and wheat (Triticum aestivumL.) harvest, across different seeding rates (17, 34, 50, and 67 kg/ha). Rye biomass was measured the following spring. Sunn hemp biomass production was inconsistent across planting dates, but did relate to growing degree accumulation. Nitrogen concentrations were inversely related to biomass production, and subsequent N contents corresponded to biomass levels. Neither planting date nor seeding rate affected rye biomass production, but rye biomass averaged over both planting dates following wheat/sunn hemp averaged 43% and 33% greater than rye following fallow. Rye biomass following corn/sunn hemp was equivalent to fallow plots. Early planting dates are recommended for sunn hemp with seeding rates between 17 and 34 kg/ha to maximize biomass and N production.
Improving Antigenicity of the Recombinant Hepatitis C Virus Core Protein via Random Mutagenesis
Authors: Huang Chen-Ji , Peng Hwei-Ling , Cheng Chih-Yu
Published: August 2011

In order to enhance the sensitivity of diagnosis, a recombinant clone containing domain I of HCV core (amino acid residues 1 to 123) was subjected to random mutagenesis. Five mutants with higher sensitivity were obtained by colony screening of 616 mutants using reverse ELISA. Sequence analysis of these mutants revealed alterations focusing on W84, P95, P110, or V129. The inclusion bodies of these recombinant proteins overexpressed in E. coli BL21(DE3) were subsequently dissolved using 6 M urea and then refolded by stepwise dialysis. Compared to the unfolded wild‐type antigen, the refolded M3b antigen (W84S, P110S and V129L) exhibited an increase of 66% antigenicity with binding capacity of 0.96 and affinity of 113 μM−1. Moreover, the 33% decrease of the production demand suggests that M3b is a potential substitute for anti‐HCV antibody detection.
Depressive Symptom Clusters and Neuropsychological Performance in Mild Alzheimer's and Cognitively Normal Elderly
Authors: Hall James R. , O'Bryant Sid E. , Johnson Leigh A. , Barber Robert C.
Published: August 2011

Objectives. Determine the relationship between depressive symptom clusters and neuropsychological test performance in an elderly cohort of cognitively normal controls and mild Alzheimer's disease (AD).Design. Cross-sectional analysis.Setting. Four health science centers in Texas.Participants. 628 elderly individuals (272 diagnosed with mild AD and 356 controls) from ongoing longitudinal study of Alzheimer's disease.Measurements. Standard battery of neuropsychological tests and the 30-item Geriatric Depression Scale with regressions model generated on GDS-30 subscale scores (dysphoria, apathy, meaninglessness and cognitive impairment) as predictors and neuropsychological tests as outcome variables. Follow-up analyses by gender were conducted.Results. For AD, all symptom clusters were related to specific neurocognitive domains; among controls apathy and cognitive impairment were significantly related to neuropsychological functioning. The relationship between performance and symptom clusters was significantly different for males and females in each group.Conclusion. Findings suggest the need to examine disease status and gender when considering the impact of depressive symptoms on cognition.
Bit Error Rate Performance of a MIMO-CDMA System Employing Parity-Bit-Selected Spreading in Frequency Nonselective Rayleigh Fading
Authors: D'Amours Claude , Dahmane Adel Omar
Published: August 2011

We analytically derive the upper bound for the bit error rate (BER) performance of a single user multiple input multiple output code division multiple access (MIMO-CDMA) system employing parity-bit-selected spreading in slowly varying, flat Rayleigh fading. The analysis is done for spatially uncorrelated links. The analysis presented demonstrates that parity-bit-selected spreading provides an asymptotic gain of10log(Nt)dB over conventional MIMO-CDMA when the receiver has perfect channel estimates. This analytical result concurs with previous works where the (BER) is determined by simulation methods and provides insight into why the different techniques provide improvement over conventional MIMO-CDMA systems.
Prevalence of Epithelial Ovarian Cancer Stem Cells Correlates with Recurrence in Early-Stage Ovarian Cancer
Authors: Steffensen Karina Dahl , Alvero Ayesha B. , Yang Yang , Waldstrøm Marianne , Hui Pei , Holmberg Jennie C. , Silasi Dan-Arin , Jakobsen Anders , Rutherford Thomas , Mor Gil
Published: August 2011

Epithelial ovarian cancer stem cells (EOC stem cells) have been associated with recurrence and chemoresistance. CD44 and CK18 are highly expressed in cancer stem cells and function as tools for their identification and characterization. We investigated the association between the number of CD44+ EOC stem cells in ovarian cancer tumors and progression-free survival. EOC stem cells exist as clusters located close to the stroma forming the cancer stem cell “niche”. 17.1% of the samples reveled high number of CD44+ EOC stem cells (>20% positive cells). In addition, the number of CD44+ EOC stem cells was significantly higher in patients with early-stage ovarian cancer (FIGO I/II), and it was associated with shorter progression-free survival (P=0.026). This study suggests that quantification of the number of EOC stem cells in the tumor can be used as a predictor of disease and could be applied for treatment selection in early-stage ovarian cancer.
Oscillation of Second‐Order Nonlinear Delay Dynamic Equations on Time Scales
Authors: Agwa H. A. , Khodier A. M. M. , Hassan Heba A.
Published: August 2011

In this work, we use the generalized Riccati transformation and the inequality technique to establish some new oscillation criteria for the second‐order nonlinear delay dynamic equation , on a time scale 𝕋, where γ is the quotient of odd positive integers and p(t) and q(t) are positive right‐dense continuous (rd‐continuous) functions on 𝕋. Our results improve and extend some results established by Sun et al. 2009. Also our results unify the oscillation of the second‐order nonlinear delay differential equation and the second‐order nonlinear delay difference equation. Finally, we give some examples to illustrate our main results.