bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating the Lived Experience of People with Down Syndrome with Dementia: Overcoming Methodological and Ethical Challenges
Authors: Watchman Karen
Published: June 2016

Adults with Down syndrome are at increased risk of dementia at a significantly younger age and remain under‐represented as participants in dementia‐related research. Because little is known about their personal experiences either immediately postdiagnosis or as dementia progresses, there is little opportunity that shared individual experiences can shape future policy and practice. To remedy this omission, the author examined methodological and ethical challenges identified as part of a research study that included people with Down syndrome affected by dementia. It has been contended that traditional qualitative approaches are less effective when participants are affected by changing cognitive functioning and reduced verbal communication. To counteract this contention overt participant observation and an adapted narrative research method were used as part of a three‐year longitudinal study to help better understand the lived experiences of three adults with Down syndrome affected by dementia. Methodological and ethical challenges were shown to collide, and factors contributing to this effect included identifying process consent, accurate representation of participants, the role of and relationship with the researcher, participants, lack of awareness of their diagnosis of dementia, and need to recognize the importance of social interaction while maintaining academic rigor. Reflections are proffered on two conceptual and practice issues, with a call for both to be recognized and addressed in terms of future policy and practice. First is a lack of awareness of a sense of “self” or identity, resulting in individuals with Down syndrome and dementia being defined by their situation rather than individual preference or need. Second is the lack of information postdiagnosis about dementia being shared with people who have Down syndrome.
Information Frictions in Uncertain Regulatory Environments: Evidence from U.S. Commercial Banks
Authors: Wilson Kristin , Veuger Stan
Published: June 2016

Information frictions between firms and regulators are typically seen as a means by which firms evade enforcement. In contrast, we argue that information frictions between firms and regulators can reduce the efficiency of firms’ compliance efforts when the interpretation of regulatory standards is uncertain. We exploit plausibly exogenous variation in distance between firms and their regulators to demonstrate this for a panel of community banks in the US. We find that banks located at greater distance from regulatory field offices face significantly higher administrative costs, at a rate of 20% of administrative costs per hour of travel time. These differences do not come with reduced compliance, are not driven by endogenous regulator choice, and are stable over time. Further, the costs borne by distant firms are negatively related to the scale of the jurisdiction in which they operate, suggesting that information spillovers between firms limit uncertainty about regulatory expectations.
Genomic agonism and phenotypic antagonism between estrogen and progesterone receptors in breast cancer
Authors: Singhal Hari , Greene Marianne E. , Tarulli Gerard , Zarnke Allison L. , Bourgo Ryan J. , Laine Muriel , Chang Ya-Fang , Ma Shihong , Dembo Anna G. , Raj Ganesh V. , Hickey Theresa E. , Tilley Wayne D. , Greene Geoffrey L.
Published: June 2016

Individual and concerted actions of ER and PR highlight the prognostic and therapeutic value of PR in ER
+
/PR
+
breast cancers.
High functional diversity stimulates diversification in experimental microbial communities
Authors: Jousset Alexandre , Eisenhauer Nico , Merker Monika , Mouquet Nicolas , Scheu Stefan
Published: June 2016

High biodiversity promotes the evolution of more biodiversity by selecting for new species exploiting resources more thoroughly.
A strongly robust type II Weyl fermion semimetal state in Ta
3
S
2
Authors: Chang Guoqing , Xu Su-Yang , Sanchez Daniel S. , Huang Shin-Ming , Lee Chi-Cheng , Chang Tay-Rong , Bian Guang , Zheng Hao , Belopolski Ilya , Alidoust Nasser , Jeng Horng-Tay , Bansil Arun , Lin Hsin , Hasan M. Zahid
Published: June 2016

A new methodology is used to design robust Weyl semimetals and to identify the most robust and ideal Weyl semimetal candidate in Ta
3
S
2
.
Diverse rupture processes in the 2015 Peru deep earthquake doublet
Authors: Ye Lingling , Lay Thorne , Kanamori Hiroo , Zhan Zhongwen , Duputel Zacharie
Published: June 2016

The nearby
M
w
7.5 and
M
w
7.6 events in a deep earthquake doublet under Peru have diverse stress drops and radiation efficiency.
The anatomical placode in reptile scale morphogenesis indicates shared ancestry among skin appendages in amniotes
Authors: Di-Poï Nicolas , Milinkovitch Michel C.
Published: June 2016

Researchers show that scales, feathers, and hairs of reptiles, birds, and mammals evolved from the scales of their common reptilian ancestor.
Production of Manganese Oxide Nanoparticles by Shewanella Species
Authors: Wright Mitchell H. , Farooqui Saad M. , White Alan R. , Greene Anthony C.
Published: June 2016

Several species of the bacterial genus
Shewanella
are well-known dissimilatory reducers of manganese under anaerobic conditions. In fact,
Shewanella oneidensis
is one of the most well studied of all metal-reducing bacteria. In the current study, a number of
Shewanella
strains were tested for manganese-oxidizing capacity under aerobic conditions. All were able to oxidize Mn(II) and to produce solid dark brown manganese oxides.
Shewanella
loihica
strain PV-4 was the strongest oxidizer, producing oxides at a rate of 20.3 mg/liter/day and oxidizing Mn(II) concentrations of up to 9 mM. In contrast,
S. oneidensis
MR-1 was the weakest oxidizer tested, producing oxides at 4.4 mg/liter/day and oxidizing up to 4 mM Mn(II). Analysis of products from the strongest oxidizers, i.e.,
S
.
loihica
PV-4 and
Shewanella putrefaciens
CN-32, revealed finely grained, nanosize, poorly crystalline oxide particles with identical Mn oxidation states of 3.86. The biogenic manganese oxide products could be subsequently reduced within 2 days by all of the
Shewanella
strains when culture conditions were made anoxic and an appropriate nutrient (lactate) was added. While
Shewanella
species were detected previously as part of manganese-oxidizing consortia in natural environments, the current study has clearly shown manganese-reducing
Shewanella
species bacteria that are able to oxidize manganese in aerobic cultures.

IMPORTANCE
Members of the genus
Shewanella
are well known as dissimilatory manganese-reducing bacteria. This study shows that a number of species from
Shewanella
are also capable of manganese oxidation under aerobic conditions. Characterization of the products of the two most efficient oxidizers,
S. loihica
and
S. putrefaciens
, revealed finely grained, nanosize oxide particles. With a change in culture conditions, the manganese oxide products could be subsequently reduced by the same bacteria. The ability of
Shewanella
species both to oxidize and to reduce manganese indicates that the genus plays a significant role in the geochemical cycling of manganese. Due to the high affinity of manganese oxides for binding other metals, these bacteria may also contribute to the immobilization and release of other metals in the environment.
Factors Associated with Shiga Toxin-Producing Escherichia coli Shedding by Dairy and Beef Cattle
Authors: Venegas-Vargas Cristina , Henderson Scott , Khare Akanksha , Mosci Rebekah E. , Lehnert Jonathan D. , Singh Pallavi , Ouellette Lindsey M. , Norby Bo , Funk Julie A. , Rust Steven , Bartlett Paul C. , Grooms Daniel , Manning Shannon D.
Published: June 2016

Shiga toxin-producing
Escherichia coli
(STEC) is an important foodborne pathogen that can cause hemorrhagic colitis and hemolytic-uremic syndrome. Cattle are the primary reservoir for STEC, and food or water contaminated with cattle feces is the most common source of infections in humans. Consequently, we conducted a cross-sectional study of 1,096 cattle in six dairy herds (
n =
718 animals) and five beef herds (
n =
378 animals) in the summers of 2011 and 2012 to identify epidemiological factors associated with shedding. Fecal samples were obtained from each animal and cultured for STEC. Multivariate analyses were performed to identify risk factors associated with STEC positivity. The prevalence of STEC was higher in beef cattle (21%) than dairy cattle (13%) (odds ratio [OR], 1.76; 95% confidence interval [CI], 1.25, 2.47), with considerable variation occurring across herds (range, 6% to 54%). Dairy cattle were significantly more likely to shed STEC when the average temperature was >28.9°C 1 to 5 days prior to sampling (OR, 2.5; 95% CI, 1.25, 4.91), during their first lactation (OR, 1.8; 95% CI, 1.1, 2.8), and when they were <30 days in milk (OR, 3.9; 95% CI, 2.1, 7.2). These data suggest that the stress or the negative energy balance associated with lactation may result in increased STEC shedding frequencies in Michigan during the warm summer months. Future prevention strategies aimed at reducing stress during lactation or isolating high-risk animals could be implemented to reduce herd-level shedding levels and avoid transmission of STEC to susceptible animals and people.

IMPORTANCE
STEC shedding frequencies vary considerably across cattle herds in Michigan, and the shedding frequency of strains belonging to non-O157 serotypes far exceeds the shedding frequency of O157 strains, which is congruent with human infections in the state. Dairy cattle sampled at higher temperatures, in their first lactation, and early in the milk production stage were significantly more likely to shed STEC, which could be due to stress or a negative energy balance. Future studies should focus on the isolation of high-risk animals to decrease herd shedding levels and the potential for contamination of the food supply.
Phage Therapy Is Effective in a Mouse Model of Bacterial Equine Keratitis
Authors: Furusawa Takaaki , Iwano Hidetomo , Hiyashimizu Yutaro , Matsubara Kazuki , Higuchi Hidetoshi , Nagahata Hajime , Niwa Hidekazu , Katayama Yoshinari , Kinoshita Yuta , Hagiwara Katsuro , Iwasaki Tomohito , Tanji Yasunori , Yokota Hiroshi , Tamura Yutaka
Published: June 2016

Bacterial keratitis of the horse is mainly caused by staphylococci, streptococci, and pseudomonads. Of these bacteria,Pseudomonas aeruginosasometimes causes rapid corneal corruption and, in some cases, blindness. Antimicrobial resistance can make treatment very difficult. Therefore, new strategies to control bacterial infection are required. A bacteriophage (phage) is a virus that specifically infects and kills bacteria. Since phage often can lyse antibiotic-resistant bacteria because the killing mechanism is different, we examined the use of phage to treat horse bacterial keratitis. We isolatedMyoviridaeorPodoviridaephages, which together have a broad host range. They adsorb efficiently to host bacteria; more than 80% of the ΦR18 phage were adsorbed to host cells after 30 s. In our keratitis mouse model, the administration of phage within 3 h also could kill bacteria and suppress keratitis. A phage multiplicity of infection of 100 times the host bacterial number could kill host bacteria effectively. A cocktail of two phages suppressed bacteria in the keratitis model mouse. These data demonstrated that the phages in this study could completely prevent the keratitis caused byP. aeruginosain a keratitis mouse model. Furthermore, these results suggest that phage may be a more effective prophylaxis for horse keratitis than the current preventive use of antibiotics. Such treatment may reduce the use of antibiotics and therefore antibiotic resistance. Further studies are required to assess phage therapy as a candidate for treatment of horse keratitis.

IMPORTANCEAntibiotic-resistant bacteria are emerging all over the world. Bacteriophages have great potential for resolution of this problem. A bacteriophage, or phage, is a virus that infects bacteria specifically. As a novel therapeutic strategy against racehorse keratitis caused byPseudomonas aeruginosa, we propose the application of phages for treatment. Phages isolated in this work hadin vitroeffectiveness for a broad range ofP. aeruginosastrains. Indeed, a great reduction of bacterial proliferation was shown in phage therapy for mouse models ofP. aeruginosakeratitis. Therefore, to reduce antibiotic usage, phage therapy should be investigated and developed further.
Wolbachia Endosymbionts Modify Drosophila Ovary Protein Levels in a Context-Dependent Manner
Authors: Christensen Steen , Pérez Dulzaides Ricardo , Hedrick Victoria E. , Momtaz A. J. M. Zehadee , Nakayasu Ernesto S. , Paul Lake N. , Serbus Laura R.
Published: June 2016

Endosymbiosis is a unique form of interaction between organisms, with one organism dwelling inside the other. One of the most widespread endosymbionts isWolbachia pipientis, a maternally transmitted bacterium carried by insects, crustaceans, mites, and filarial nematodes. Although candidate proteins that contribute to maternal transmission have been identified, the molecular basis for maternalWolbachiatransmission remains largely unknown. To investigate transmission-related processes in response toWolbachiainfection, ovarian proteomes were analyzed fromWolbachia-infectedDrosophila melanogasterandD. simulans.Endogenous and variant host-strain combinations were investigated. Significant and differentially abundant ovarian proteins were detected, indicating substantial regulatory changes in response toWolbachia. VariantWolbachiastrains were associated with a broader impact on the ovary proteome than endogenousWolbachiastrains. TheD. melanogasterovarian environment also exhibited a higher level of diversity of proteomic responses toWolbachiathanD. simulans.Overall, manyWolbachia-responsive ovarian proteins detected in this study were consistent with expectations from the experimental literature. This suggests that context-specific changes in protein abundance contribute toWolbachiamanipulation of transmission-related mechanisms in oogenesis.

IMPORTANCEMillions of insect species naturally carry bacterial endosymbionts calledWolbachia. Wolbachiabacteria are transmitted by females to their offspring through a robust egg-loading mechanism. The molecular basis forWolbachiatransmission remains poorly understood at this time, however. This proteomic study identified specific fruit fly ovarian proteins as being upregulated or downregulated in response toWolbachiainfection. The majority of these protein responses correlated specifically with the type of host andWolbachiastrain involved. This work corroborates previously identified factors and mechanisms while also framing the broader context of ovarian manipulation byWolbachia.
Disruption of the Reductive 1,3-Propanediol Pathway Triggers Production of 1,2-Propanediol for Sustained Glycerol Fermentation by Clostridium pasteurianum
Authors: Pyne Michael E. , Sokolenko Stanislav , Liu Xuejia , Srirangan Kajan , Bruder Mark R. , Aucoin Marc G. , Moo-Young Murray , Chung Duane A. , Chou C. Perry
Published: June 2016

Crude glycerol, the major by-product of biodiesel production, is an attractive bioprocessing feedstock owing to its abundance, low cost, and high degree of reduction. In line with the advent of the biodiesel industry,
Clostridium pasteurianum
has gained prominence as a result of its unique capacity to convert waste glycerol into
n
-butanol, a high-energy biofuel. However, no efforts have been directed at abolishing the production of 1,3-propanediol (1,3-PDO), the chief competing product of
C. pasteurianum
glycerol fermentation. Here, we report rational metabolic engineering of
C. pasteurianum
for enhanced
n
-butanol production through inactivation of the gene encoding 1,3-PDO dehydrogenase (
dhaT
). In spite of current models of anaerobic glycerol dissimilation, culture growth and glycerol utilization were unaffected in the
dhaT
disruption mutant (
dhaT
::Ll.LtrB). Metabolite characterization of the
dhaT
::Ll.LtrB mutant revealed an 83% decrease in 1,3-PDO production, encompassing the lowest
C. pasteurianum
1,3-PDO titer reported to date (0.58 g liter
−1
). With 1,3-PDO formation nearly abolished, glycerol was converted almost exclusively to
n
-butanol (8.6 g liter
−1
), yielding a high
n
-butanol selectivity of 0.83 g
n
-butanol g
−1
of solvents compared to 0.51 g
n
-butanol g
−1
of solvents for the wild-type strain. Unexpectedly, high-performance liquid chromatography (HPLC) analysis of
dhaT
::Ll.LtrB mutant culture supernatants identified a metabolite peak consistent with 1,2-propanediol (1,2-PDO), which was confirmed by nuclear magnetic resonance (NMR). Based on these findings, we propose a new model for glycerol dissimilation by
C. pasteurianum
, whereby the production of 1,3-PDO by the wild-type strain and low levels of both 1,3-PDO and 1,2-PDO by the engineered mutant balance the reducing equivalents generated during cell mass synthesis from glycerol.

IMPORTANCE
Organisms from the genus
Clostridium
are perhaps the most notable native cellular factories, owing to their vast substrate utilization range and equally diverse variety of metabolites produced. The ability of
C. pasteurianum
to sustain redox balance and glycerol fermentation despite inactivation of the 1,3-PDO pathway is a testament to the exceptional metabolic flexibility exhibited by clostridia. Moreover, identification of a previously unknown 1,2-PDO-formation pathway, as detailed herein, provides a deeper understanding of fermentative glycerol utilization in clostridia and will inform future metabolic engineering endeavors involving
C. pasteurianum
. To our knowledge, the
C. pasteurianum dhaT
disruption mutant derived in this study is the only organism that produces both 1,2- and 1,3-PDOs. Most importantly, the engineered strain provides an excellent platform for highly selective production of
n
-butanol from waste glycerol.
A New Catabolic Plasmid in Xanthobacter and
Starkeya
spp. from a 1,2-Dichloroethane-Contaminated Site
Authors: Munro Jacob E. , Liew Elissa F. , Ly Mai-Anh , Coleman Nicholas V.
Published: June 2016

1,2-Dichloroethane (DCA) is a problematic xenobiotic groundwater pollutant. Bacteria are capable of biodegrading DCA, but the evolution of such bacteria is not well understood. In particular, the mechanisms by which bacteria acquire the key dehalogenase genes
dhlA
and
dhlB
have not been well defined. In this study, the genomic context of
dhlA
and
dhlB
was determined in three aerobic DCA-degrading bacteria (
Starkeya novella
strain EL1,
Xanthobacter autotrophicus
strain EL4, and
Xanthobacter flavus
strain EL8) isolated from a groundwater treatment plant (GTP). A haloalkane dehalogenase gene (
dhlA
) identical to the canonical
dhlA
gene from
Xanthobacter
sp. strain GJ10 was present in all three isolates, and, in each case, the
dhlA
gene was carried on a variant of a 37-kb circular plasmid, which was named pDCA. Sequence analysis of the
repA
replication initiator gene indicated that pDCA was a member of the pTAR plasmid family, related to catabolic plasmids from the
Alphaproteobacteria
, which enable growth on aromatics, dimethylformamide, and tartrate. Genes for plasmid replication, mobilization, and stabilization were identified, along with two insertion sequences (IS
Xa1
and IS
Pme1
) which were likely to have mobilized
dhlA
and
dhlB
and played a role in the evolution of aerobic DCA-degrading bacteria. Two haloacid dehalogenase genes (
dhlB1
and
dhlB2
) were detected in the GTP isolates;
dhlB1
was most likely chromosomal and was similar to the canonical
dhlB
gene from strain GJ10, while
dhlB2
was carried on pDCA and was not closely related to
dhlB1
. Heterologous expression of the DhlB2 protein confirmed that this plasmid-borne dehalogenase was capable of chloroacetate dechlorination.

IMPORTANCE
Earlier studies on the DCA-degrading
Xanthobacter
sp. strain GJ10 indicated that the key dehalogenases
dhlA
and
dhlB
were carried on a 225-kb linear plasmid and on the chromosome, respectively. The present study has found a dramatically different gene organization in more recently isolated DCA-degrading
Xanthobacter
strains from Australia, in which a relatively small circular plasmid (pDCA) carries both
dhlA
and
dhlB
homologs. pDCA represents a true organochlorine-catabolic plasmid, first because its only obvious metabolic phenotype is dehalogenation of organochlorines, and second because acquisition of this plasmid provides both key enzymes required for carbon-chlorine bond cleavage. The discovery of the alternative haloacid dehalogenase
dhlB2
in pDCA increases the known genetic diversity of bacterial chloroacetate-hydrolyzing enzymes.
Microbial Antimony Biogeochemistry: Enzymes, Regulation, and Related Metabolic Pathways
Authors: Li Jingxin , Wang Qian , Oremland Ronald S. , Kulp Thomas R. , Rensing Christopher , Wang Gejiao
Published: June 2016

Antimony (Sb) is a toxic metalloid that occurs widely at trace concentrations in soil, aquatic systems, and the atmosphere. Nowadays, with the development of its new industrial applications and the corresponding expansion of antimony mining activities, the phenomenon of antimony pollution has become an increasingly serious concern. In recent years, research interest in Sb has been growing and reflects a fundamental scientific concern regarding Sb in the environment. In this review, we summarize the recent research on bacterial antimony transformations, especially those regarding antimony uptake, efflux, antimonite oxidation, and antimonate reduction. We conclude that our current understanding of antimony biochemistry and biogeochemistry is roughly equivalent to where that of arsenic was some 20 years ago. This portends the possibility of future discoveries with regard to the ability of microorganisms to conserve energy for their growth from antimony redox reactions and the isolation of new species of “antimonotrophs.”
Centrality dependence of total disintegration of target nuclei in high energy nucleus–nucleus interactions
Authors: Bhattacharyya Swarnapratim , Haiduc Maria , Neagu Alina Tania , Firu Elena
Published: June 2016

A study of centrality dependence of target fragmentation and multiparticle production has been carried out in 16O–AgBr, 22Ne–AgBr, and 28Si–AgBr interactions at 4.1–4.5 AGeV/c for the total disintegrated (TD) events. Average multiplicity of black particles increases linearly with decreasing centrality while average multiplicity of grey and shower particles decreases with decreasing centrality for the TD events. The decrease of average multiplicity of grey particles is linear; on the other hand, in the case of shower particles, the increase is nonlinear. With the increase of the mass of the projectile beam, the average multiplicity of black particles decreases and the average multiplicity of grey particles increases for the TD events. This observation has been explained on the basis of the fireball model; however, in the case of shower particles, average multiplicity increases with increase of projectile mass.
WEAR BEHAVIOR OF NANOSTRUCTURED HYPOEUTECTIC Fe–B ALLOY
Authors: FU LICAI , YANG JUN , ZHOU LINGPING , LIU WEIMIN
Published: June 2016

The wear behavior of nanostructured hypoeutectic Fe[Formula: see text]B[Formula: see text] alloy was investigated in comparison with coarse grained counterpart. The friction coefficient of the Fe[Formula: see text]B[Formula: see text] alloy changed slightly with grain size. While the wear rate decreased as the grain size decreased to nano scale. Both Fe2O3 and Fe2SiO4 oxides were found on the worn surfaces in the nanostructured Fe[Formula: see text]B[Formula: see text] alloy, but only a few oxide films were observed for the coarse grained counterpart. These results suggested that the nanostructured eutectic was conducive to forming oxide films on the worn surface of the Fe[Formula: see text]B[Formula: see text] alloy, and improved the wear resistance.
Chaplygin-gas solutions of f(R) gravity
Authors: Elmardi Maye , Abebe Amare , Tekola Abiy
Published: June 2016

We explore exact [Formula: see text] gravity solutions that mimic Chaplygin-gas inspired [Formula: see text]CDM cosmology. Starting with the original, generalized and modified Chaplygin-gas (MCG) equations of state (EoS), we reconstruct the forms of [Formula: see text] Lagrangians. The resulting solutions are generally quadratic in the Ricci scalar, but have appropriate [Formula: see text]CDM solutions in limiting cases. These solutions, given appropriate initial conditions, can be potential candidates for scalar field-driven early universe expansion (inflation) and dark energy-driven late-time cosmic acceleration.
m-Eternal total domination in graphs
Authors: Roushini Leely Pushpam P. , Shanthi PA.
Published: June 2016

Eternal domination of a graph requires the vertices of the graph to be protected, against infinitely long sequences of attacks, by guards located at vertices, with the requirement that the configuration of guards induces a dominating set at all times. Klostermeyer and Mynhardt studied some variations of this concept in which the configuration of guards induces total dominating sets (TDSs). They considered two models of the problem, one in which only one guard moves at a time and one in which more than one guard may move simultaneously. In this paper, we consider the model in which all guards move simultaneously when the configuration of guards induces TDSs and we study this model for some classes of graphs.
Tyrosine kinase inhibitor BIBF1000 does not hamper right ventricular pressure adaptation in rats
Authors: de Raaf Michiel Alexander , Herrmann Franziska Elena , Schalij Ingrid , de Man Frances S. , Vonk-Noordegraaf Anton , Guignabert Christophe , Wollin Lutz , Bogaard Harm Jan
Published: June 2016

BIBF1000 is a small molecule tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), and platelet-derived growth factor receptor (PDGFR) and is a powerful inhibitor of fibrogenesis. BIBF1000 is very similar to BIBF1120 (nintedanib), a drug recently approved for the treatment of idiopathic pulmonary fibrosis (IPF). A safety concern pertaining to VEGFR, FGFR, and PDGFR inhibition is the possible interference with right ventricular (RV) responses to an increased afterload, which could adversely affect clinical outcome in patients with IPF who developed pulmonary hypertension. We tested the effect of BIBF1000 on the adaptation of the RV in rats subjected to mechanical pressure overload. BIBF1000 was administered for 35 days in pulmonary artery-banded (PAB) rats. RV adaptation was assessed by echocardiography, pressure volume loop analysis, histology, and determination of atrial natriuretic peptide (ANP) expression. BIBF1000 treatment resulted in growth attenuation but had no effects on RV function after PAB, given absence of changes in cardiac index, end-systolic elastance, connective tissue disposition, and capillary density. We conclude that, in this experimental model of increased afterload, combined VEGFR, FGFR, and PDGFR inhibition does not hamper RV adaptation to pressure overload.
Dose dependency of outcomes of intrapleural fibrinolytic therapy in new rabbit empyema models
Authors: Komissarov Andrey A. , Florova Galina , Azghani Ali O. , Buchanan Ann , Boren Jake , Allen Timothy , Rahman Najib M. , Koenig Kathleen , Chamiso Mignote , Karandashova Sophia , Henry James , Idell Steven
Published: June 2016

The incidence of empyema (EMP) is increasing worldwide; EMP generally occurs with pleural loculation and impaired drainage is often treated with intrapleural fibrinolytic therapy (IPFT) or surgery. A number of IPFT options are used clinically with empiric dosing and variable outcomes in adults. To evaluate mechanisms governing intrapleural fibrinolysis and disease outcomes, models of Pasteurella multocida and Streptococcus pneumoniae were generated in rabbits and the animals were treated with either human tissue (tPA) plasminogen activator or prourokinase (scuPA). Rabbit EMP was characterized by the development of pleural adhesions detectable by chest ultrasonography and fibrinous coating of the pleura. Similar to human EMP, rabbits with EMP accumulated sizable, 20- to 40-ml fibrinopurulent pleural effusions associated with extensive intrapleural organization, significantly increased pleural thickness, suppression of fibrinolytic and plasminogen-activating activities, and accumulation of high levels of plasminogen activator inhibitor 1, plasminogen, and extracellular DNA. IPFT with tPA (0.145 mg/kg) or scuPA (0.5 mg/kg) was ineffective in rabbit EMP ( n = 9 and 3 for P. multocida and S. pneumoniae, respectively); 2 mg/kg tPA or scuPA IPFT ( n = 5) effectively cleared S. pneumoniae-induced EMP collections in 24 h with no bleeding observed. Although intrapleural fibrinolytic activity for up to 40 min after IPFT was similar for effective and ineffective doses of fibrinolysin, it was lower for tPA than for scuPA treatments. These results demonstrate similarities between rabbit and human EMP, the importance of pleural fluid PAI-1 activity, and levels of plasminogen in the regulation of intrapleural fibrinolysis and illustrate the dose dependency of IPFT outcomes in EMP.
Brief mechanical ventilation causes differential epithelial repair along the airways of fetal, preterm lambs
Authors: Deptula Nicole , Royse Emily , Kemp Matthew W. , Miura Yuichiro , Kallapur Suhas G. , Jobe Alan H. , Hillman Noah H.
Published: June 2016

Mechanical ventilation of preterm lambs causes lung inflammation and injury to the airway epithelium, which is repaired by 15 days after ventilation. In mice, activated basal cells (p63+, KRT14+, KRT8+) initiate injury repair to the trachea, whereas club cells coordinate distal airway repair. In both human and sheep, basal cells line the pseudostratified airways to the distal bronchioles with club cells only present in terminal bronchioles. Mechanical ventilation causes airway epithelial injury that is repaired through basal cell activation in the fetal lung. Ewes at 123 ± 1 day gestational age had the head and chest of the fetus exteriorized and tracheostomy placed. With placental circulation intact, fetal lambs were mechanically ventilated with up to 15 ml/kg for 15 min with 95% N2/5% CO2. Fetal lambs were returned to the uterus for up to 24 h. The trachea, left mainstem bronchi, and peripheral lung were evaluated for epithelial injury and cellular response consistent with repair. Peripheral lung tissue had inflammation, pro-inflammatory cytokine production, epithelial growth factor receptor ligand upregulation, increased p63 expression, and proliferation of pro-SPB, TTF-1 positive club cells. In bronchi, KRT14 and KRT8 mRNA increased without increases in Notch pathway mRNA or proliferation. In trachea, mRNA increased for Notch ligands, SAM pointed domain-containing Ets transcription factor and mucin 5B, but not for basal cell markers. A brief period of mechanical ventilation causes differential epithelial activation between trachea, bronchi, and peripheral lung. The repair mechanisms identified in adult mice occur at different levels of airway branching in fetal sheep with basal and club cell activation.
Using cultured endothelial cells to study endothelial barrier dysfunction: Challenges and opportunities
Authors: Aman Jurjan , Weijers Ester M. , van Nieuw Amerongen Geerten P. , Malik Asrar B. , van Hinsbergh Victor W. M.
Published: June 2016

Despite considerable progress in the understanding of endothelial barrier regulation and the identification of approaches that have the potential to improve endothelial barrier function, no drug- or stem cell-based therapy is presently available to reverse the widespread vascular leak that is observed in acute respiratory distress syndrome (ARDS) and sepsis. The translational gap suggests a need to develop experimental approaches and tools that better mimic the complex environment of the microcirculation in which the vascular leak develops. Recent studies have identified several elements of this microenvironment. Among these are composition and stiffness of the extracellular matrix, fluid shear stress, interaction of endothelial cells (ECs) with pericytes, oxygen tension, and the combination of toxic and mechanic injurious stimuli. Development of novel cell culture techniques that integrate these elements would allow in-depth analysis of EC biology that closely approaches the (patho)physiological conditions in situ. In parallel, techniques to isolate organ-specific ECs, to define EC heterogeneity in its full complexity, and to culture patient-derived ECs from inducible pluripotent stem cells or endothelial progenitor cells are likely to advance the understanding of ARDS and lead to development of therapeutics. This review 1) summarizes the advantages and pitfalls of EC cultures to study vascular leak in ARDS, 2) provides an overview of elements of the microvascular environment that can directly affect endothelial barrier function, and 3) discusses alternative methods to bridge the gap between basic research and clinical application with the intent of improving the translational value of present EC culture approaches.
Hyperoxia-induced p47phoxactivation and ROS generation is mediated through S1P transporter Spns2, and S1P/S1P1&2signaling axis in lung endothelium
Authors: Harijith Anantha , Pendyala Srikanth , Ebenezer David L. , Ha Alison W. , Fu Panfeng , Wang Yue-Ting , Ma Ke , Toth Peter T. , Berdyshev Evgeny V. , Kanteti Prasad , Natarajan Viswanathan
Published: June 2016

Hyperoxia-induced lung injury adversely affects ICU patients and neonates on ventilator assisted breathing. The underlying culprit appears to be reactive oxygen species (ROS)-induced lung damage. The major contributor of hyperoxia-induced ROS is activation of the multiprotein enzyme complex NADPH oxidase. Sphingosine-1-phosphate (S1P) signaling is known to be involved in hyperoxia-mediated ROS generation; however, the mechanism(s) of S1P-induced NADPH oxidase activation is unclear. Here, we investigated various steps in the S1P signaling pathway mediating ROS production in response to hyperoxia in lung endothelium. Of the two closely related sphingosine kinases (SphKs)1 and 2, which synthesize S1P from sphingosine, only Sphk1−/−mice conferred protection against hyperoxia-induced lung injury. S1P is metabolized predominantly by S1P lyase and partial deletion of Sgpl1 ( Sgpl1+/−) in mice accentuated lung injury. Hyperoxia stimulated S1P accumulation in human lung microvascular endothelial cells (HLMVECs), and downregulation of S1P transporter spinster homolog 2 (Spns2) or S1P receptors S1P1&2, but not S1P3, using specific siRNA attenuated hyperoxia-induced p47phoxtranslocation to cell periphery and ROS generation in HLMVECs. These results suggest a role for Spns2 and S1P1&2in hyperoxia-mediated ROS generation. In addition, p47phox(phox:phagocyte oxidase) activation and ROS generation was also reduced by PF543, a specific SphK1 inhibitor in HLMVECs. Our data indicate a novel role for Spns2 and S1P1&2in the activation of p47phoxand production of ROS involved in hyperoxia-mediated lung injury in neonatal and adult mice.
Non-deposit system option for waste management on small islands
Authors: Vilms Monica , Voronova Viktoria
Published: June 2016

This paper analyses waste management on small islands (on a global scale these are micro-islands). In the context of the paper, small islands are islands that have an area less than 50 km2. The study presents an overview of the problems connected with waste transport from islands to the mainland. Waste generation on islands is very much related to tourists. If tourists do not handle waste properly, it will cause problems. Four small Estonian islands in the range of 3–19 km2 are studied in detail. For these and other small islands, the main problem is the waste produced by tourists, or related to tourists and waste transport to the mainland. Currently, the local municipality has to arrange and finance waste transport. In fact, and based on the polluter-pays principle, the tourists should bear the cost of waste management. There are different tax options available in order to collect the money from tourists – waste tax, harbour tax, tourist tax, donations, environmental tax and others. The study results revealed that the best possible solution for Estonian islands may be a non-deposit system – including an additional charge on ferry ticket prices. The extra money should cover the costs of waste management and waste shipping. The tourists arriving in their own boats should pay a harbour tax, which includes a waste tax to compensate for the cost of waste management.
Developing a University-Based Interprofessional Education Diagnostic Team to Identify Children With Possible Autism Spectrum Disorder
Authors: Self Trisha L. , Mitchell Linda M. , Hess Sean , Marble Karissa J. , Swails Jeffrey
Published: June 2016

Upon entering the workplace, speech-language pathologists (SLPs) are required to work on interprofessional teams, yet many of these professionals have not received adequate preservice instruction on how to collaborate. Furthermore, collaborating to provide services for children with autism spectrum disorder (ASD) has been found to improve developmental outcomes; however, many SLPs are not prepared to engage in this type of collaborative practice. Based on the American Speech-Language-Hearing Association’s (ASHA) recommendation that university programs include interprofessoinal education (IPE) into Communication Sciences and Disorders programs, coupled with the need to prepare students to provide interprofessional services for children with ASD, Wichita State University developed a field-based interprofessional diagnostic team for SLP students. The process used to develop this team followed Pickering and Embry’s recommended steps for cultivating interprofessional collaboration within a university environment. The purpose of this article is to describe the procedures used to develop the team and activities used to target competencies for interprofessional collaborative practice.
Whistle While You Work
Authors: Manz Charles C. , Houghton Jeffery D. , Neck Christopher P. , Fugate Mel , Pearce Craig
Published: June 2016

There has been a growing interest in leader emotion in organizational scholarship. Concomitantly, the body of research on self-leadership continues to expand. Nonetheless, relatively little work has focused on emotional self-leadership. We address this void by exploring intrapersonal and interpersonal aspects of emotional self-leadership and its inherent challenges and opportunities. Specifically, we examine how emotional self-leadership strategies can be used to shape emotional experiences, emotional authenticity, and other work-related outcomes. We offer an emotional self-leadership model, research propositions, and implications for research and practice.
Moving Hearts: Cultivating Patriotic Affect in Rousseau’s Considerations on the Government of Poland
Authors: Gallagher Megan
Published: June 2016

Rousseau’s embrace of ceremony and festivals in his Considerations on the Government of Poland demonstrates one way for republican political thought to develop a substantive treatment of civic virtue. Differentiating the narcissism of spectacle and theater that Rousseau critiques in the Letter to d’Alembert from the Considerations’ call for a generous affect, I demonstrate that the latter is compatible with a republican ethos premised on civic virtue and patriotic attachment to the nation-state. Rousseau argues for the instantiation of political practices that constantly cultivate political virtue and their associated affective orientations. His treatment of civic ceremonies in the Considerations should be read as an attempt to inculcate patriotic affect in republican citizens via constitutional measures.
Advanced Placement and Rural Schools
Authors: Gagnon Douglas J. , Mattingly Marybeth J.
Published: June 2016

Completing Advanced Placement (AP) coursework is an important part of the selective college admissions process, and access to AP coursework can be viewed as a measure of equal opportunity. Relatively little research has fully examined how access to AP coursework is mediated by school characteristics. Rural schools are at a particular disadvantage in promoting AP success due to a lack of sufficiently prepared students, teaching constraints, and other logistical challenges. This study uses regression to analyze AP access, enrollment, and success across a rich data set of U.S. school districts. We find that remote, small, and poor rural schools are considerably less likely to offer any AP courses. Even for rural schools that do offer AP coursework, enrollment and success rates lag well behind more urban and affluent schools. We explore potential policy solutions and examine alternative advanced coursework options for those rural schools that do not offer AP.
The potential of gene therapy approaches for the treatment of hemoglobinopathies: achievements and challenges
Authors: Goodman Michael A. , Malik Punam
Published: June 2016

Hemoglobinopathies, including β-thalassemia and sickle cell disease (SCD), are a heterogeneous group of commonly inherited disorders affecting the function or levels of hemoglobin. Disease phenotype can be severe with substantial morbidity and mortality. Bone marrow transplantation is curative, but limited to those patients with an appropriately matched donor. Genetic therapy, which utilizes a patient’s own cells, is thus an attractive therapeutic option. Numerous therapies are currently in clinical trials or in development, including therapies utilizing gene replacement therapy using lentiviruses and the latest gene editing techniques. In addition, methods are being developed that may be able to expand gene therapies to those with poor access to medical care, potentially significantly decreasing the global burden of disease.
Acute Care Utilization in Patients With Concurrent Mental Health and Complex Chronic Medical Conditions
Authors: Abernathy Karen , Zhang Jingwen , Mauldin Patrick , Moran William , Abernathy Mac , Brownfield Elisha , Davis Kimberly
Published: June 2016

Objectives: Patients with coexisting mental health disorder and chronic disease are more at risk for poor outcomes, including increased acute care utilization. This study was performed to assess the association of mental health disorders on acute care utilization (emergency department [ED] use, hospitalization, and rehospitalization within 30 days) using disease clustering. Methods: A retrospective cohort analysis was performed on 10 408 patients. Adult patients >18 years of age were included in the study if they were seen at least twice in University Internal Medicine primary care clinic at the Medical University of South Carolina from October 10, 2010 through September 30, 2013. The main outcome measure was a count of acute care use (hospital or ED). A linear regression model was used to fit a predictive model for ED and hospital utilization, and agglomerative hierarchical clustering was used to identify patients with similar comorbidities. Results: Covariates associated with increased risk of ED and hospital utilization include non-white race (rate ratio [RR] = 1.35, P < .0001), resident physician (RR = 1.30, P < .0001), and public insurance (RR = 1.56, P < .0001). Patients within the multiple chronic conditions (MCC), chronic obstructive pulmonary disease (COPD)/asthma, or renal disease clusters had 1.80 ( P < .0001), 1.50 ( P < .0001), and 2.57 ( P < .0001) times, respectively, the amount of predicted utilization compared with healthy patients, whereas patients with a mental health diagnosis had 1.41 ( P < .0001) times the predicted utilization. There was a significant association with increased utilization in patients with coexisting mental health disorder and chronic disease within the COPD/asthma (RR = 1.20, P = .0038), renal disease (RR = 1.27, P < .0001), and MCC (RR = 1.34, P < .0001) clusters. Conclusions: Patients with co-occurring chronic medical conditions and mental health disorders have higher rates of acute care utilization compared with patients with chronic medical conditions alone. Improving access to mental health care at the primary care clinic may have a positive impact on utilization.
Corrected Maximum Likelihood Estimators in Linear Heteroskedastic Regression Models
Authors: Cordeiro Gauss M.
Published: June 2016

The linear heteroskedastic regression model, for which the variance of the response is given by a suitable function of a set of linear exogenous variables, is very useful in econometric applications. We derive a simple matrix formula for the n^−1 biases of the maximum likelihood estimators of the parameters in the variance of the response, where n is the sample size. These biases are easily obtained as a vector of regression coeﬃcients in a simple weighted least squares regression. We use simulation to compare the uncorrected estimators with the bias-corrected ones to conclude the superiority of the corrected estimators over the uncorrected ones with regard to the normal approximation. The practical use of such biases is illustrated in two applications to real data sets.
Extracting Default Probabilities from Sovereign Bonds
Authors: Meres Bernardo , Almeida Caio
Published: June 2016

Sovereign risk analysis is central in debt markets. Considering diﬀerent bonds and countries, there are numerous measures aiming to identify the way risk is perceived by market participants. In such environment, probabilities of default play a central role in investors’ decisions. This article contributes by providing a parametric arbitrage-free dynamic model to estimate defaultable term structures of sovereign bonds. The proposed model builds on Duﬃe and Singleton’s (1999) general reduced-form model by proposing a piecewise constant structure for the conditional probabilities of defaults. Once an average recovery rate value is ﬁxed for the whole market, the proposed model estimates implied probabilities of defaults from bond prices, working as a parsimonious tool to quantify investor’s perception of credit risk. We apply this methodology to analyze the behavior of default probabilities within the Brazilian sovereign ﬁxed income market at three diﬀerent recent economic moments.
The Revealed Social Welfare Function: USA X Brazil
Authors: Mattos Enlinson
Published: June 2016

This paper proposes the use of the optimal nonlinear tax formula to derive the social welfare function of policymakers. In particular, it uses PSID and PNAD for 1990 to estimate the implicit social welfare functions associated with income tax imposition for the USA and Brazil. Under assumptions on the household preferences, the estimations suggest that both U.S. and Brazilian social welfare functions are concave and Paretian, but that only the Brazilian function is utilitarian, i.e., the Brazilian social planner is less inequity-averse than her U.S. counterpart.
A Back-of-the-Envelope Rule to Identify Atheoretical VARs
Authors: Urzúa Carlos M.
Published: June 2016

Vector autoregressive models are often used in Macroeconomics to draw conclusions about the eﬀects of policy innovations. However, those results depend on the researcher’s priors about the particular ordering of the variables. As an alternative, this paper presents a very simple rule based on the maximum entropy principle that can be used to ﬁnd the “most likely” ordering. The proposal is illustrated in the case of a VAR model of the U.S. economy. It is found that monetary policy shocks are better represented by innovations in the federal funds rate rather than in non-borrowed reserves.