bluuebunny/crossref_metadata_2025 huggingface dataset:
Antimicrobial and Biophysical Properties of Surfactant Supplemented with an Antimicrobial Peptide for Treatment of Bacterial Pneumonia
Authors: Banaschewski Brandon J. H. , Veldhuizen Edwin J. A. , Keating Eleonora , Haagsman Henk P. , Zuo Yi Y. , Yamashita Cory M. , Veldhuizen Ruud A. W.
Published: March 2015

Antibiotic-resistant bacterial infections represent an emerging health concern in clinical settings, and a lack of novel developments in the pharmaceutical pipeline is creating a “perfect storm” for multidrug-resistant bacterial infections. Antimicrobial peptides (AMPs) have been suggested as future therapeutics for these drug-resistant bacteria, since they have potent broad-spectrum activity, with little development of resistance. Due to the unique structure of the lung, bacterial pneumonia has the additional problem of delivering antimicrobials to the site of infection. One potential solution is coadministration of AMPs with exogenous surfactant, allowing for distribution of the peptides to distal airways and opening of collapsed lung regions. The objective of this study was to test various surfactant-AMP mixtures with regard to maintaining pulmonary surfactant biophysical properties and bactericidal functions. We compared the properties of four AMPs (CATH-1, CATH-2, CRAMP, and LL-37) suspended in bovine lipid-extract surfactant (BLES) by assessing surfactant-AMP mixture biophysical and antimicrobial functions. Antimicrobial activity was tested against methillicin-resistant
Staphylococcus aureus
and
Pseudomonas aeruginosa
. All AMP/surfactant mixtures exhibited an increase of spreading compared to a BLES control. BLES+CATH-2 mixtures had no significantly different minimum surface tension versus the BLES control. Compared to the other cathelicidins, CATH-2 retained the most bactericidal activity in the presence of BLES. The BLES+CATH-2 mixture appears to be an optimal surfactant-AMP mixture based on
in vitro
assays. Future directions involve investigating the potential of this mixture in animal models of bacterial pneumonia.
Ceftobiprole- and Ceftaroline-Resistant Methicillin-Resistant Staphylococcus aureus
Authors: Chan Liana C. , Basuino Li , Diep Binh , Hamilton Stephanie , Chatterjee Som S. , Chambers Henry F.
Published: March 2015

The role of
mecA
mutations in conferring resistance to ceftobiprole and ceftaroline, cephalosporins with anti-methicillin-resistant
Staphylococcus aureus
(MRSA) activity, was determined with MRSA strains COL and SF8300. The SF8300 ceftaroline-passaged mutant carried a single
mecA
mutation, E447K (E-to-K change at position 447), and expressed low-level resistance. This mutation in COL conferred high-level resistance to ceftobiprole but only low-level resistance to ceftaroline. The COL ceftaroline-passaged mutant, which expressed high-level resistance to ceftobiprole and ceftaroline, had mutations in
pbp2
,
pbp4
, and
gdpP
but not
mecA
.
Activity of Ceftazidime-Avibactam against Fluoroquinolone-Resistant Enterobacteriaceae and Pseudomonas aeruginosa
Authors: Pitart C. , Marco F. , Keating T. A. , Nichols W. W. , Vila J.
Published: March 2015

Ceftazidime-avibactam and comparator antibiotics were tested by the broth microdilution method against 200
Enterobacteriaceae
and 25
Pseudomonas aeruginosa
strains resistant to fluoroquinolones (including strains with the extended-spectrum β-lactamase [ESBL] phenotype and ceftazidime-resistant strains) collected from our institution. The MICs and mechanisms of resistance to fluoroquinolone were also studied. Ninety-nine percent of fluoroquinolone-resistant
Enterobacteriaceae
strains were inhibited at a ceftazidime-avibactam MIC of ≤4 mg/liter (using the susceptible CLSI breakpoint for ceftazidime alone as a reference). Ceftazidime-avibactam was very active against ESBL
Escherichia coli
(MIC
90
of 0.25 mg/liter), ESBL
Klebsiella pneumoniae
(MIC
90
of 0.5 mg/liter), ceftazidime-resistant AmpC-producing species (MIC
90
of 1 mg/liter), non-ESBL
E. coli
(MIC
90
of ≤0.125 mg/liter), non-ESBL
K. pneumoniae
(MIC
90
of 0.25 mg/liter), and ceftazidime-nonresistant AmpC-producing species (MIC
90
of ≤0.5 mg/liter). Ninety-six percent of fluoroquinolone-resistant
P. aeruginosa
strains were inhibited at a ceftazidime-avibactam MIC of ≤8 mg/liter (using the susceptible CLSI breakpoint for ceftazidime alone as a reference), with a MIC
90
of 8 mg/liter. Additionally, fluoroquinolone-resistant mutants from each species tested were obtained
in vitro
from two strains, one susceptible to ceftazidime and the other a β-lactamase producer with a high MIC against ceftazidime but susceptible to ceftazidime-avibactam. Thereby, the impact of fluoroquinolone resistance on the activity of ceftazidime-avibactam could be assessed. The MIC
90
values of ceftazidime-avibactam for the fluoroquinolone-resistant mutant strains of
Enterobacteriaceae
and
P. aeruginosa
were ≤4 mg/liter and ≤8 mg/liter, respectively. We conclude that the presence of fluoroquinolone resistance does not affect
Enterobacteriaceae
and
P. aeruginosa
susceptibility to ceftazidime-avibactam; that is, there is no cross-resistance.
Impact of Antimalarial Treatment and Chemoprevention on the Drug Sensitivity of Malaria Parasites Isolated from Ugandan Children
Authors: Tumwebaze Patrick , Conrad Melissa D. , Walakira Andrew , LeClair Norbert , Byaruhanga Oswald , Nakazibwe Christine , Kozak Benjamin , Bloome Jessica , Okiring Jaffer , Kakuru Abel , Bigira Victor , Kapisi James , Legac Jennifer , Gut Jiri , Cooper Roland A. , Kamya Moses R. , Havlir Diane V. , Dorsey Grant , Greenhouse Bryan , Nsobya Samuel L. , Rosenthal Philip J.
Published: March 2015

Changing treatment practices may be selecting for changes in the drug sensitivity of malaria parasites. We characterized
ex vivo
drug sensitivity and parasite polymorphisms associated with sensitivity in 459
Plasmodium falciparum
samples obtained from subjects enrolled in two clinical trials in Tororo, Uganda, from 2010 to 2013. Sensitivities to chloroquine and monodesethylamodiaquine varied widely; sensitivities to quinine, dihydroartemisinin, lumefantrine, and piperaquine were generally good. Associations between
ex vivo
drug sensitivity and parasite polymorphisms included decreased chloroquine and monodesethylamodiaquine sensitivity and increased lumefantrine and piperaquine sensitivity with
pfcrt
76T, as well as increased lumefantrine sensitivity with
pfmdr1
86Y, Y184, and 1246Y. Over time,
ex vivo
sensitivity decreased for lumefantrine and piperaquine and increased for chloroquine, the prevalences of
pfcrt
K76 and
pfmdr1
N86 and D1246 increased, and the prevalences of
pfdhfr
and
pfdhps
polymorphisms associated with antifolate resistance were unchanged. In recurrent infections, recent prior treatment with artemether-lumefantrine was associated with decreased
ex vivo
lumefantrine sensitivity and increased prevalence of
pfcrt
K76 and
pfmdr1
N86, 184F, and D1246. In children assigned chemoprevention with monthly dihydroartemisinin-piperaquine with documented circulating piperaquine, breakthrough infections had increased the prevalence of
pfmdr1
86Y and 1246Y compared to untreated controls. The noted impacts of therapy and chemoprevention on parasite polymorphisms remained significant in multivariate analysis correcting for calendar time. Overall, changes in parasite sensitivity were consistent with altered selective pressures due to changing treatment practices in Uganda. These changes may threaten the antimalarial treatment and preventive efficacies of artemether-lumefantrine and dihydroartemisinin-piperaquine, respectively.
Ethanol Impairs Mucosal Immunity against Streptococcus pneumoniae Infection by Disrupting Interleukin 17 Gene Expression
Authors: Trevejo-Nunez Giraldina , Chen Kong , Dufour Jason P. , Bagby Gregory J. , Horne William T. , Nelson Steve , Kolls Jay K.
Published: March 2015

Acute ethanol intoxication suppresses the host immune responses againstStreptococcus pneumoniae. As interleukin 17 (IL-17) is a critical cytokine in host defense against extracellular pathogens, includingS. pneumoniae, we hypothesized that ethanol impairs mucosal immunity against this pathogen by disrupting IL-17 production or IL-17 receptor (IL-17R) signaling. A chronic ethanol feeding model in simian immunodeficiency virus (SIV)-infected rhesus macaques and acute ethanol intoxication in a murine model were used. Transcriptome analysis of bronchial brushes in the nonhuman primate model showed downregulation of the expression of IL-17-regulated chemokines in ethanol-fed animals, a finding also replicated in the murine model. Surprisingly, recombinant CXCL1 and CXCL5 but not IL-17 or IL-23 plus IL-1β rescued bacterial burden in the ethanol group to control levels. Taken together, the results of this study suggest that ethanol impairs IL-17-mediated chemokine production in the lung. Thus, exogenous luminal restoration of IL-17-related chemokines, CXCL1 and CXCL5, improves host defenses againstS. pneumoniae.
Interleukin-6-Driven Inflammatory Response Induces Retinal Pathology in a Model of Ocular Toxoplasmosis Reactivation
Authors: Rochet Élise , Brunet Julie , Sabou Marcela , Marcellin Luc , Bourcier Tristan , Candolfi Ermanno , Pfaff Alexander W.
Published: March 2015

Ocular inflammation is one of the consequences of infection with the protozoan parasite
Toxoplasma gondii
. Even if lesions are self-healing in immunocompetent persons, they pose a lifetime risk of reactivation and are a serious threat to vision. As there are virtually no immunological data on reactivating ocular toxoplasmosis, we established a model of direct intravitreal injection of parasites in previously infected mice with a homologous type II strain. Two different mouse strains with variable ability to control retinal infection were studied in order to describe protective and deleterious reaction patterns. In Swiss-Webster mice, which are already relatively resistant to primary infection, no peak of parasite load was observed upon reinfection. In contrast, the susceptible inbred strain C57BL/6 showed high parasite loads after 7 days, as well as marked deterioration of retinal architecture. Both parameters were back to normal on day 21. C57BL/6 mice also reacted with a strong local production of inflammatory and Th1-type cytokines, like interleukin-6 (IL-6), IL-17A, and gamma interferon (IFN-γ), while Swiss-Webster mice showed only moderate expression of the Th2 cytokine IL-31. Interestingly, rapid intraocular production of anti-
Toxoplasma
antibodies was observed in Swiss-Webster but not in C57BL/6 mice. We then localized the cellular source of different immune mediators within the retina by immunofluorescence. Finally, neutralization experiments of IFN-γ or IL-6 demonstrated the respective protective and deleterious roles of these cytokines for parasite control and retinal integrity during reinfection. In conclusion, we developed and immunologically characterized a promising mouse model of reactivating ocular toxoplasmosis.
Characterization of a Novel Antisense RNA in the Major Pilin Locus of Neisseria meningitidis Influencing Antigenic Variation
Authors: Tan Felicia Y. Y. , Wörmann Mirka E. , Loh Edmund , Tang Christoph M. , Exley Rachel M.
Published: March 2015

Expression of type four pili (Tfp) is essential for virulence in
Neisseria meningitidis
. Pili mediate adhesion, bacterial aggregation, and DNA uptake. In
N. meningitidis
, the major pilin subunit is encoded by the
pilE
gene. In some strains, PilE is subject to phase and antigenic variation, which can alter Tfp properties and together offer a possible mechanism of immune escape. Pilin expression and antigenic variation can be modulated in response to environmental cues; however, the precise mechanisms of such regulation remain unclear. We identified a promoter in the
pilE
locus, 3′ of the
pilE
coding sequence, on the antisense (AS) strand which is conserved in meningococci. We show that this promoter directs transcription of an AS RNA that is expressed during specific growth phases and in response to salt stress. Furthermore, we demonstrate that the transcript encompasses sequences complementary to the entire
pilE
coding sequence and 5′ untranslated region. AS RNAs can regulate the gene on the sense strand by altering transcript stability or translation. However, by using Northern blotting, quantitative reverse transcription-PCR (RT-PCR), and Western blotting, we found no significant AS RNA-dependent changes in
pilE
transcript or protein level. Instead, our data indicate that the AS RNA influences pilin antigenic variation. This work provides further insights into the complex regulation of pilin expression and variation in pathogenic
Neisseria
.

IMPORTANCE
Pathogenic
Neisseria
spp. express type four pili (Tfp) which are important for adhesion, aggregation and transformation. Some strains of
N. meningitidis
are able to vary the sequence of the major subunit (PilE) of the Tfp. The mechanisms underlying this variation are not fully defined, but the process requires several noncoding elements that are found adjacent to the
pilE
gene. In this work, we identified a
cis-
encoded RNA antisense to
pilE
in
N. meningitidis
. By using Northern blotting and RT-PCR analysis, we found that the RNA is expressed in stationary phase or following salt stress. Our work also indicates that this RNA does not significantly affect
pilE
or pilin expression levels but instead appears to modulate pilin variation.
Revisiting the Gram-Negative Lipoprotein Paradigm
Authors: LoVullo Eric D. , Wright Lori F. , Isabella Vincent , Huntley Jason F. , Pavelka Martin S.
Published: March 2015

The processing of lipoproteins (Lpps) in Gram-negative bacteria is generally considered an essential pathway. Mature lipoproteins in these bacteria are triacylated, with the final fatty acid addition performed by Lnt, an apolipoprotein N-acyltransferase. The mature lipoproteins are then sorted by the Lol system, with most Lpps inserted into the outer membrane (OM). We demonstrate here that the
lnt
gene is not essential to the Gram-negative pathogen
Francisella tularensis
subsp.
tularensis
strain Schu or to the live vaccine strain LVS. An LVS Δ
lnt
mutant has a small-colony phenotype on sucrose medium and increased susceptibility to globomycin and rifampin. We provide data indicating that the OM lipoprotein Tul4A (LpnA) is diacylated but that it, and its paralog Tul4B (LpnB), still sort to the OM in the Δ
lnt
mutant. We present a model in which the Lol sorting pathway of
Francisella
has a modified ABC transporter system that is capable of recognizing and sorting both triacylated and diacylated lipoproteins, and we show that this modified system is present in many other Gram-negative bacteria. We examined this model using
Neisseria gonorrhoeae
, which has the same Lol architecture as that of
Francisella
, and found that the
lnt
gene is not essential in this organism. This work suggests that Gram-negative bacteria fall into two groups, one in which full lipoprotein processing is essential and one in which the final acylation step is not essential, potentially due to the ability of the Lol sorting pathway in these bacteria to sort immature apolipoproteins to the OM.

IMPORTANCE
This paper describes the novel finding that the final stage in lipoprotein processing (normally considered an essential process) is not required by
Francisella tularensis
or
Neisseria gonorrhoeae
. The paper provides a potential reason for this and shows that it may be widespread in other Gram-negative bacteria.
Large rhinolith causing nasal obstruction
Authors: Dincer Kose Onur , Kose Taha Emre , Erdem Mehmet Ali , Cankaya Abdulkadir Burak
Published: March 2015

Rhinoliths are calcified masses located in the nasal cavity and may cause symptoms such as nasal obstruction, fetid odour and facial pain. They are usually diagnosed incidentally on radiographic examinations or depending on the symptoms. In this paper we report a 27-year-old Caucasian woman with a calcified mass in the right nasal cavity causing nasal obstruction, anosmia and facial pain. The calcified mass was removed by endonasal approach.
Anonymisation of address coordinates for microlevel analyses of the built environment: a simulation study
Authors: Buck Christoph , Dreger Steffen , Pigeot Iris
Published: March 2015

Background

Data privacy is a major concern in spatial epidemiology because exact residential locations or parts of participants’ addresses such as street or zip codes are used to perform geospatial analyses. To overcome this concern, different levels of aggregation such as census districts or zip code areas are mainly used, though any spatial aggregation leads to a loss of spatial variability. For the assessment of urban opportunities for physical activity that was conducted in the IDEFICS (Identification and prevention of dietary- and lifestyle-induced health effects in children and infants) study, macrolevel analyses were performed, but the use of exact residential addresses for micro-level analyses was not permitted by the responsible office for data protection. We therefore implemented a spatial blurring to anonymise address coordinates depending on the underlying population density.

Methods

We added a standard Gaussian distributed error to individual address coordinates with the variancedepending on the population density and on the chosen k-anonymity. 1000 random point locations were generated and repeatedly blurred 100 times to obtain anonymised locations. For each location 1 km network-dependent neighbourhoods were used to calculate walkability indices. Indices of blurred locations were compared to indices based on their sampling origins to determine the effect of spatial blurring on the assessment of the built environment.

Results

Spatial blurring decreased with increasing population density. Similarly, mean differences in walkability indices also decreased with increasing population density. In particular for densely-populated areas with at least 1500 residents per km², differences between blurred locations and their sampling origins were small and did not affect the assessment of the built environment after spatial blurring.

Conclusions

This approach allowed the investigation of the built environment at a microlevel using individual network-dependent neighbourhoods, while ensuring data protection requirements. Minor influence of spatial blurring on the assessment of walkability was found that slightly affected the assessment of the built environment in sparsely-populated areas.
Regorafenib assessment in refractory advanced colorectal cancer: RegARd-C study protocol
Authors: Hendlisz Alain , Deleporte Amélie , Vandeputte Caroline , Charette Nicolas , Paesmans Marianne , Guiot Thomas , Garcia Camilo , Flamen Patrick
Published: March 2015

Introduction

Regorafenib was recently approved for patients with pretreated advanced colorectal cancer (aCRC), despite a moderate improvement of the patients’ outcome, and significant toxicities. Based on previous studies showing that early fluorodeoxyglucose-positron emission tomography (FDG-PET)-based metabolic response assessment (MRA) might adequately select patients unlikely to benefit from treatment, the RegARd-C trial uses early MRA to identify likely non-responders to regorafenib in a population of patients with aCRC and guide a comprehensive evaluation of genomic and epigenetic determinants of resistance to treatment.

Methods and analysis

RegARd-C is a multicentric prospective study. Its primary objective is to identify non-benefitters from regorafenib given at 160 mg/day, 3 weeks out of 4 in a population of patients with pretreated aCRC. Baseline PET is repeated at day 14 of the first treatment course. MRA is blinded for the investigators. Overall survival (OS) is the primary end point and will be correlated with metabolic parameters and (epi)genetic alterations assessed from tumour and serial blood samples. A target sample size of 105 evaluable patients (70 as derivation set and 35 as validation set), is considered as sufficient to validate an expected HR for OS of metabolic responders compared to metabolic non-responders significantly <1 (with 80% power and 1-sided 5% α in case of a true HR≤0.59 and a responders rate of 47%).

Ethics and dissemination

The study was approved by the Institut Jules Bordet's competent ethics committee and complies with the Helsinki declaration or the Belgian laws and regulations, whichever provides the greatest protection for the patient, and follows the International Conference on Harmonisation E 6 (R1) Guideline for Good Clinical Practice, reference number CPMP/ICH/135/95. The protocol and the trials results, even inconclusive, will be presented at international oncology congresses, and published in peer-reviewed journals. Genomic and epigenetic data will be made available in public open data sets.

Trial registration numbers

EudraCT number: 2012-005655-16; ClinicalTrials.gov number:NCT01929616.
Reducing stress and burnout in junior doctors: the impact of debriefing sessions
Authors: Gunasingam Nishmi , Burns Kharis , Edwards James , Dinh Michael , Walton Merrilyn
Published: March 2015

Background

Internship and residency are difficult times with novice practitioners facing new challenges and stressors. Junior doctors may experience burnout, a syndrome that encompasses three dimensions: emotional exhaustion, depersonalisation and reduced personal accomplishment. While there is some existing literature on the prevalence of burnout in junior doctors, there are few studies on interventional strategies.

Aims

This study aimed to examine the prevalence of burnout in a cohort of junior doctors and whether debriefing sessions reduced levels of burnout.

Methods

A prospective randomised controlled study of a convenience sample of postgraduate year 1 doctors in a single hospital was undertaken during a rotation term in 2011. All participants completed a questionnaire using a validated tool, the Maslach Burnout Inventory, to determine the prevalence of burnout. They were then randomly assigned to a group who were to receive four debriefing sessions over 2 months, or, to the control group, who had no debriefing sessions. Quantitative and qualitative analyses were conducted.

Results

Thirty-one postgraduate year 1 doctors participated in the study, with 13 being assigned to the group receiving debriefing sessions and 18 assigned to the control group. At baseline, 21/31 (68%) participants displayed evidence of burnout in at least one domain as measured by the Maslach Burnout Inventory. Burnout was significantly higher in women. There was no significant difference in burnout scores with debriefing. The intervention was well received with 11/18 (61%) suggesting they would recommend the strategy to future junior doctors and 16/18 (89%) found that the sessions were a source of emotional and social support.

Conclusions

Burnout is prevalent among postgraduate year 1 doctors, and they value the emotional and social support from attending debriefing sessions. A larger study is required to determine if debriefing can reduce the incidence of burnout in junior doctors.
Response of ionospheric disturbance dynamo and electromagnetic induction during geomagnetic storm
Authors: Falayi E.O. , Rabiu A.B. , Bolaji O.S. , Fayose R.S.
Published: March 2015

During geomagnetic storms, the direct penetration of magnetospheric convection electric field and the ionospheric disturbance dynamo (IDD) take place in the ionosphere. In this paper, we studied variability of IDD and electromagnetic induction (EMI) at different latitudinal sectors during the geomagnetic storms on 7 and 8 September 2002 and 20 and 21 November 2003 with high solar wind speed due to coronal mass ejection. This investigation employs geomagnetic field components (H and Z), the geomagnetic indices (Dst, AL, and AU), solar wind speed (Vx), and interplanetary magnetic field (Bz). It was observed that the H component of geomagnetic field decreases across latitudes, and varies with Vx, Bz, Dst, AL, and AU indices throughout the difference phases of the storm. Our result demonstrated the dominance of the IDD during the nighttime compared to the daytime. This implies that neutral dynamic wind is greater at night than during the day. Higher ratio ΔZ/ΔH is observed at nighttime because of the reduction on the E region conductivity, which allowed F region electric fields to dominate.
Diet composition of Steller sea lions (Eumetopias jubatus) in Frederick Sound, southeast Alaska: a comparison of quantification methods using scats to describe temporal and spatial variabilities
Authors: Tollit D.J. , Wong M.A. , Trites A.W.
Published: March 2015

We compared eight dietary indices used to describe the diet of Steller sea lions (Eumetopias jubatus (Schreber, 1776)) from 2001 to 2004 in Frederick Sound, southeast Alaska. Remains (n = 9666 items) from 59+ species categories were identified from 1684 fecal samples (scats) from 14 collection periods. The most frequently occurring prey were walleye pollock (Theragra chalcogramma (Pallas, 1814) = Gadus chalcogrammus Pallas, 1814; 95%), Pacific herring (Clupea pallasii Valenciennes in Cuvier and Valenciennes, 1847; 30%), Pacific hake (Merluccius productus (Ayres, 1855); 29%), and arrowtooth flounder (Atheresthes stomias (Jordan and Gilbert, 1880) = Reinhardtius stomias (Jordan and Gilbert, 1880); 21%). These species, along with Pacific salmon (genus Oncorhynchus Suckley, 1861) and skate (genus Raja L., 1758), accounted for 80%–90% of the reconstructed biomass and energy contribution, with pollock contributing 37%–60%. Overall, 80% of fish were 14–42 cm long and mainly pelagic, though 40% of scats contained benthic-associated prey. Steller sea lions switched from adult pollock to strong cohorts of juvenile pollock, and took advantage of spawning concentrations of salmon in autumn and herring in late spring and summer, as well as a climate-driven increase in hake availability. Observed temporal and site differences in diet confirm the need for robust long-term scat sampling protocols. All major indices similarly tracked key temporal changes, despite differences in occurrence and biomass-energy-based diet estimates linked to prey size and energy-density effects and the application of correction factors.
RISK SEEKING, NONCONVEX REMUNERATION AND REGIME SWITCHING
Authors: BARUCCI EMILIO , MARAZZINA DANIELE
Published: March 2015

We investigate asset management in a regime switching framework when the fund manager aims to beat a certain target for the assets under management over an infinite horizon or over a finite horizon. We consider both a full information and a partial information setting. In a full information setting, the asset manager tends to take more risk in the good state and less risk in the bad state with respect to the constant parameter environment. Confidence risk induces the agent to increase his risk exposure.
Fabrication and characterization of environmental-friendly Ni1-xRxTiO3 nanopigments with high NIR reflectance
Authors: Tong Yu-Ping , Chen Zheng , Wang Hui-Xian , Zhang Xu-Fang , Ma Jun-Tao , Chen Xi
Published: March 2015

A series of novel high dispersed environmental-friendly nanopigments based on NiTiO 3 doped with rare earth ion such as Y , La , Eu , Sm have been developed. The products were characterized by X-ray diffractometer (XRD), scanning electron microscopy (SEM), commission internationale de l'Eclairage (CIE) 1976 L*α*b* color scales and UV-Vis-near-infrared radiation (NIR) reflectance spectroscopy. The substitution of R 3+ for Ni 2+ in NiTiO 3 can improve the yellowness of pigments, especially for Eu 3+ substitution. The sample with the substitution of Eu 3+ for Ni 2+ processes the highest NIR reflectance and enhances the NIR reflectance to 89.0%. SEM results revealed that the obtained pigments were composed of well-dispersed spherical-like particles with the range of 40–60 nm. EDS results indicated that the distribution of Ni , Ti , R , O element was considerably uniform with no chemical segregation phenomenon.
Factors Facilitating Cultural Learning in Virtual Architectural Heritage Environments
Authors: Ibrahim Nazrita , Mohamad Ali Nazlena , Mohd Yatim Noor Faezah
Published: March 2015

Besides being a medium for exhibiting three-dimensional heritage objects, the design and development of virtual heritage environments could also facilitate cultural learning. The aim of this article is to present some consideration on factors that could facilitate cultural learning in virtual heritage environment. Cultural learning in the context of this study refers to the acquisition of knowledge that encourages cultural awareness and appreciation. In this study, we explore virtual heritage environment design features, and cultural information characteristics and presentation formats that are important to facilitate cultural learning, from the casual user's perspective. We conducted experiments that required users to explore virtual heritage environments (focusing on architectural heritage) from selected heritage-related websites, followed by interview sessions. Four contributing factors were identified: information design, information presentation, navigation mechanism, and environment setting. The results suggest the need to reduce users’ cognitive load when exploring virtual heritage environments while simultaneously presenting information that adds value to their understanding. The results also suggest that the inclusion of cultural information in virtual heritage environments is essential for cultural learning to take place.
Quantum Oscillations in Hole-Doped Cuprates
Authors: Sebastian Suchitra E. , Proust Cyril
Published: March 2015

One of the leading challenges of condensed matter physics in the past few decades is an understanding of the high-temperature copper-oxide superconductors. Although the d-wave character of the superconducting state is well understood, the normal state in the underdoped regime has eluded understanding. Here, we review the past few years of quantum oscillation measurements performed in the underdoped cuprates that have culminated in an understanding of the normal ground state of these materials. A nodal electron pocket created by charge order is found to characterize the normal ground state in YBa2Cu3O6+δand is likely universal to a majority of the cuprate superconductors. An open question remains regarding the origin of the suppression of the antinodal density of states at the Fermi energy in the underdoped normal state, either from mainly charge correlations or, more likely, from mainly pairing and/or magnetic correlations that precede charge order.
Napoleon Is in Equilibrium
Authors: Phillips Rob
Published: March 2015

It has been said that the cell is the test tube of the twenty-first century. If so, the theoretical tools needed to quantitatively and predictively describe what goes on in such test tubes lag sorely behind the stunning experimental advances in biology seen in the decades since the molecular biology revolution began. Perhaps surprisingly, one of the theoretical tools that has been used with great success on problems ranging from how cells communicate with their environment and each other to the nature of the organization of proteins and lipids within the cell membrane is statistical mechanics. A knee-jerk reaction to the use of statistical mechanics in the description of cellular processes is that living organisms are so far from equilibrium that one has no business even thinking about it. But such reactions are probably too hasty given that there are many regimes in which, because of a separation of timescales, for example, such an approach can be a useful first step. In this article, we explore the power of statistical mechanical thinking in the biological setting, with special emphasis on cell signaling and regulation. We show how such models are used to make predictions and describe some recent experiments designed to test them. We also consider the limits of such models based on the relative timescales of the processes of interest.
n-Tupled Fixed Points Theorem in Fuzzy Metric Spaces with Application
Authors: Murthy P. P. , Kenvat Rashmi
Published: March 2015

We will introduce the concept ofn-tupled fixed points (for positive integern) in fuzzy metric space by mild modification of the concept ofn-tupled fixed points (for even positive intergern) introduced by Imdad et al. (2013) in metric spaces. As application of the above-mentioned concept, we will establish somen-tupled fixed point theorems for contractive type mappings in fuzzy metric space which extends the result of Roldán et al. (2013). Also we have given an application to solve a kind of Lipschitzian systems fornvariables and an integral system.
Management of Pruritus in Chronic Liver Disease
Authors: Bhalerao Angeline , Mannu Gurdeep S.
Published: March 2015

Background.There continues to be uncertainty on the ideal treatment of pruritus in chronic liver disease. The aim of this study was to gather the latest information on the evidence-based management of pruritus in chronic liver disease.Methodology.A literature search for pruritus in chronic liver disease was conducted using Pubmed and Embase database systems using the MeSH terms “pruritus,” “chronic liver disease,” “cholestatic liver disease,” and “treatment.”Results.The current understanding of the pathophysiology of pruritus is described in addition to detailing research into contemporary treatment options of the condition. These medical treatments range from bile salts, rifampicin, and opioid receptor antagonists to antihistamines.Conclusion.The burden of pruritus in liver disease patients persists and, although it is a common symptom, it can be difficult to manage. In recent years there has been greater study into the etiology and treatment of the condition. Nonetheless, pruritus remains poorly understood and many patients continue to suffer, reiterating the need for further research to improve our understanding of the etiology and treatment for the condition.
Quasi-Optimal Elimination Trees for 2D Grids with Singularities
Authors: Paszyńska A. , Paszyński M. , Jopek K. , Woźniak M. , Goik D. , Gurgul P. , AbouEisha H. , Moshkov M. , Calo V. M. , Lenharth A. , Nguyen D. , Pingali K.
Published: March 2015

We construct quasi-optimal elimination trees for 2D finite element meshes with singularities. These trees minimize the complexity of the solution of the discrete system. The computational cost estimates of the elimination process model the execution of the multifrontal algorithms in serial and in parallel shared-memory executions. Since the meshes considered are a subspace of all possible mesh partitions, we call these minimizers quasi-optimal. We minimize the cost functionals using dynamic programming. Finding these minimizers is more computationally expensive than solving the original algebraic system. Nevertheless, from the insights provided by the analysis of the dynamic programming minima, we propose a heuristic construction of the elimination trees that has costONelog⁡Ne, whereNeis the number of elements in the mesh. We show that this heuristic ordering has similar computational cost to the quasi-optimal elimination trees found with dynamic programming and outperforms state-of-the-art alternatives in our numerical experiments.
An Adaptive Linearized Method for Localizing Video Endoscopic Capsule Using Weighted Centroid Algorithm
Authors: Hany Umma , Wahid Khan A.
Published: March 2015

Video Capsule Endoscope (VCE) sends images of abnormalities in the gastrointestinal (GI) tract. While the physicians receive these images, they have little idea of their exact location which is needed for proper treatment. The proposed localization system consists of a 3D antenna array (with 8 receiver sensors) and one transmitter embedded inside the electronic capsule. We propose an adaptive linearized method of localization using Weighted Centroid Localization (WCL) where the position is calculated by averaging the weighted sum of the reference positions. In our proposed system, first we identify the path loss attenuation exponents using linear least square regression of the collected data (RSSI versus distance). Then the path loss model is linearized to minimize the path loss deviation which is mainly caused due to the nonhomogeneous environment of radio propagation. Then the instantaneous path loss (PL) measured by the sensors is attenuated to the above linearized model and considered as the weight of the sensors to find the location of the capsule using WCL. Finally a calibration process is applied using linear least square regression. To assess the performance, we model the path loss and implement the algorithm in Matlab for 2,530 possible positions with a resolution of 1 mm. The results show that the algorithm achieves high localization accuracy compared with other related methods when simulated using a 3D small intestine model.
Equilibrium Configurations of the Noncircular Cross-Section Elastic Rod Model with the Elliptic KB Method
Authors: Wang Yongzhao , Zhang Qichang , Wang Wei
Published: March 2015

The mechanical deformation of DNA is very important in many biological processes. In this paper, we consider the reduced Kirchhoff equations of the noncircular cross-section elastic rod characterized by the inequality of the bending rigidities. One family of exact solutions is obtained in terms of rational expressions for classical Jacobi elliptic functions. The present solutions allow the investigation of the dynamical behavior of the system in response to changes in physical parameters that concern asymmetry. The effects of the factor on the DNA conformation are discussed. A qualitative analysis is also conducted to provide valuable insight into the topological configuration of DNA segments.
Surgical Resection for a Second Primary Lung Cancer Originating Close to the Initial Surgical Margin for Lung Squamous Cell Carcinoma
Authors: Sato Seijiro , Koike Terumoto , Hashimoto Takehisa , Tsuchida Masanori
Published: March 2015

Few reports have described surgical resection for second primary lung cancers originating close to the initial surgical margin for lung cancer. A 64-year-old man had undergone left segmentectomy with lymph node dissection for small peripheral squamous cell lung cancer using video-assisted thoracic surgery, with pathology confirming a small tumor 12 mm in diameter identified about 3 cm from the surgical margin. Eighteen months after initial surgery, computed tomography revealed a 30 mm pulmonary nodule close to the initial surgical margin in the residual left upper lobe and the serum level of carcinoembryonic antigen was found to be increased. Local recurrence on the staple-line of the surgical margin was suspected, and completion left upper lobectomy was performed. Histological examination identified not only a squamous cell carcinoma component but also a small cell carcinoma component. The immunohistochemical staining pattern of the second tumor differed from that of the initial resected lung squamous cell carcinoma. The final pathological diagnosis was a second primary tumor with mixed small cell carcinoma and squamous cell carcinoma histology.
Approximate State Transition Matrix and Secular Orbit Model
Authors: Ramachandran M. P.
Published: March 2015

The state transition matrix (STM) is a part of the onboard orbit determination system. It is used to control the satellite’s orbital motion to a predefined reference orbit. Firstly in this paper a simple orbit model that captures the secular behavior of the orbital motion in the presence of all perturbation forces is derived. Next, an approximate STM to match the secular effects in the orbit due to oblate earth effect and later in the presence of all perturbation forces is derived. Numerical experiments are provided for illustration.
A Microarray Study of Middle Cerebral Occlusion Rat Brain with Acupuncture Intervention
Authors: Zhang Chao , Wen Yan , Fan Xiaonong , Yang Sha , Tian Guang , Zhou Xueyi , Chen Yaqiong , Meng Zhihong
Published: March 2015

Microarray analysis was used to investigate the changes of gene expression of ischemic stroke and acupuncture intervention in middle cerebral artery occlusion (MCAo) rat brain. Results showed that acupuncture intervention had a remarkable improvement in neural deficit score, cerebral blood flow, and cerebral infarction volume of MCAo rats. Microarray analysis showed that a total of 627 different expression genes were regulated in ischemic stroke. 417 genes were upregulated and 210 genes were downregulated. A total of 361 different expression genes were regulated after acupuncture intervention. Three genes were upregulated and 358 genes were downregulated. The expression of novel genes after acupuncture intervention, includingTph1andOlr883, was further analyzed by Real-Time Quantitative Polymerase Chain Reaction (RT-PCR). Upregulation ofTph1and downregulation ofOlr883indicated that the therapeutic effect of acupuncture for ischemic stroke may be closely related to the suppression of poststroke depression and regulation of olfactory transduction. In conclusion, the present study may enrich our understanding of the multiple pathological process of ischemic brain injury and indicate possible mechanisms of acupuncture on ischemic stroke.
Microrelief-Controlled Overland Flow Generation: Laboratory and Field Experiments
Authors: Chu Xuefeng , Padmanabhan G. , Bogart Daniel
Published: March 2015

Surface microrelief affects overland flow generation and the related hydrologic processes. However, such influences vary depending on other factors such as rainfall characteristics, soil properties, and initial soil moisture conditions. Thus, in-depth research is needed to better understand and evaluate the combined effects of these factors on overland flow dynamics. The objective of this experimental study was to examine how surface microrelief, in conjunction with the factors of rainfall, soil, and initial moisture conditions, impacts overland flow generation and runoff processes in both laboratory and field settings. A series of overland flow experiments were conducted for rough and smooth surfaces that represented distinct microtopographic characteristics and the experimental data were analyzed and compared. Across different soil types and initial moisture conditions, both laboratory and field experiments demonstrated that a rough soil surface experienced a delayed initiation of runoff and featured a stepwise threshold flow pattern due to the microrelief-controlled puddle filling-spilling-merging dynamics. It was found from the field experiments that a smooth plot surface was more responsive to rainfall variations especially during an initial rainfall event. However, enhanced capability of overland flow generation and faster puddle connectivity of a rough field plot occurred during the subsequent rain events.
Thermal Properties of Light Tensor Mesons via QCD Sum Rules
Authors: Azizi K. , Türkan A. , Veli Veliev E. , Sundu H.
Published: March 2015

The thermal properties off2(1270),a2(1320), andK2*(1430) light tensor mesons are investigated in the framework of QCD sum rules at finite temperature. In particular, the masses and decay constants of the light tensor mesons are calculated taking into account the new operators appearing at finite temperature. The numerical results show that, at the point at which the temperature-dependent continuum threshold vanishes, the decay constants decrease with amount of (70–85)% compared to their vacuum values, while the masses diminish about (60–72)% depending on the kinds of the mesons under consideration. The results obtained at zero temperature are in good consistency with the experimental data as well as the existing theoretical predictions.
Focus on Diffusion MR Investigations of Musculoskeletal Tissue to Improve Osteoporosis Diagnosis: A Brief Practical Review
Authors: Capuani Silvia , Manenti Guglielmo , Iundusi Riccardo , Tarantino Umberto
Published: March 2015

Nowadays, a huge number of papers have documented the ability of diffusion magnetic resonance imaging (D-MRI) to highlight normal and pathological conditions in a variety of cerebral, abdominal, and cardiovascular applications. To date, however, the role of D-MRI to investigate musculoskeletal tissue, specifically the cancellous bone, has not been extensively explored. In order to determine potentially useful applications of diffusion techniques in musculoskeletal investigation, D-MRI applications to detect osteoporosis disease were reviewed and further explained.
Elucidation of Acquired Resistance to Bcl-2 and MDM2 Inhibitors in Acute Leukemia In Vitro and In Vivo
Authors: Hoffman-Luca C. Gianna , Ziazadeh Daniel , McEachern Donna , Zhao Yujun , Sun Wei , Debussche Laurent , Wang Shaomeng
Published: March 2015

Purpose: Two clinical-stage anticancer drugs, the Bcl-2 inhibitor ABT-263, and the MDM2 inhibitor SAR405838 achieve complete tumor regression in animal models of leukemia but also induce acquired resistance. Elucidation of acquired resistance mechanisms and development of strategies to overcome the resistance are critical for their successful clinical development.

Experimental Design: We employed RS4;11 and MV4;11 cell lines, two acute leukemia models, to investigate acquired resistance mechanisms for both drugs in vitro and in vivo and evaluated several treatment regimens in xenograft mouse models to improve long-term, complete tumor regression.

Results: Resistance to either SAR405838 or ABT-263 (or its analogue ABT-737) develops in acute leukemia models in vitro and in vivo. RS4;11 and MV4;11 tumors treated with SAR405838 acquire resistance to the drug by mutation of the TP53 gene or compromise of p53 protein function. RS4;11 tumors treated with either ABT-263 or ABT-737 acquire resistance primarily through downregulation of BAX but not BAK. When acute leukemia cells become highly resistant to the MDM2 inhibitor, they retain their sensitivity to the Bcl-2 inhibitors, or vice versa. Certain sequential or combination treatment of SAR405838 and ABT-263 can achieve longer-term tumor regression than treatment with either agent alone.

Conclusions: Our study provides new insights into the mechanisms of acquired resistance of Bcl-2 and MDM2 inhibitors in acute leukemia models and suggests that certain sequential or combination treatment of these two distinct classes of apoptosis-inducing agents should be tested as new treatment strategies for acute leukemia in the clinic. Clin Cancer Res; 21(11); 2558–68. ©2015 AACR.
Is This the Time to Introduce Minimal Residual Disease in Multiple Myeloma Clinical Practice?
Authors: Paiva Bruno , Puig Noemi , García-Sanz Ramón , San Miguel Jesús F.
Published: March 2015

Increasing therapeutic options and prolonged survival in multiple myeloma have raised interest in the concept of depth of response and its importance to predict patients' outcomes. Although the efficacy of current treatment approaches has greatly improved in the past decade, the definition of complete response (CR) remains unaltered and continues to use conventional serological and morphologic techniques. That notwithstanding, there is growing interest in minimal residual disease (MRD) monitoring, which has emerged in recent years as one of the most relevant prognostic factors in multiple myeloma. MRD can be assessed both inside (e.g., immunophenotypic and molecular techniques) and outside the bone marrow (e.g., PET/CT). Here, we focus on flow- and molecular-based assays by which different cooperative groups have demonstrated the efficacy of MRD assessment to predict outcomes even among patients in CR, and irrespectively of disease risk. Although further standardization is still required, the time has come to implement MRD monitoring in prospective clinical trials as a sensitive tool to evaluate treatment efficacy and for risk-adapted treatment, particularly in the consolidation and maintenance settings. Here, we present a comprehensive and critical review on the methodologic aspects, specific characteristics, and clinical significance of MRD monitoring by flow cytometry, PCR, and next-generation sequencing. Clin Cancer Res; 21(9); 2001–8. ©2015 AACR.