bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteomic Analyses of Intracellular Salmonella enterica Serovar Typhimurium Reveal Extensive Bacterial Adaptations to Infected Host Epithelial Cells
Authors: Liu Yanhua , Zhang Qiufeng , Hu Mo , Yu Kaiwen , Fu Jiaqi , Zhou Fan , Liu Xiaoyun
Published: May 2015

Salmonella
species can gain access into nonphagocytic cells, where the bacterium proliferates in a unique membrane-bounded compartment. In order to reveal bacterial adaptations to their intracellular niche, here we conducted the first comprehensive proteomic survey of
Salmonella
isolated from infected epithelial cells. Among ∼3,300 identified bacterial proteins, we found that about 100 proteins were significantly altered at the onset of
Salmonella
intracellular replication. In addition to substantially increased iron-uptake capacities, bacterial high-affinity manganese and zinc transporters were also upregulated, suggesting an overall limitation of metal ions in host epithelial cells. We also found that
Salmonella
induced multiple phosphate utilization pathways. Furthermore, our data suggested upregulation of the two-component PhoPQ system as well as of many downstream virulence factors under its regulation. Our survey also revealed that intracellular
Salmonella
has increased needs for certain amino acids and biotin. In contrast,
Salmonella
downregulated glycerol and maltose utilization as well as chemotaxis pathways.
Synergistic Costimulatory Effect of Chlamydia pneumoniae with Carbon Nanoparticles on NLRP3 Inflammasome-Mediated Interleukin-1β Secretion in Macrophages
Authors: Matsuo Junji , Nakamura Shinji , Takeda Seiji , Ishida Kasumi , Yamazaki Tomohiro , Yoshida Mitsutaka , Chiba Hitoshi , Hui Shu-Ping , Yamaguchi Hiroyuki
Published: May 2015

The obligate intracellular bacterium
Chlamydia pneumoniae
is not only a causative agent of community-acquired pneumonia but is also associated with a more serious chronic disease, asthma, which might be exacerbated by air pollution containing carbon nanoparticles. Although a detailed mechanism of exacerbation remains unknown, the proinflammatory cytokine interleukin-1β (IL-1β) is a critical player in the pathogenesis of asthma.
C. pneumoniae
induces IL-1β in macrophages via NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome activation and Toll-like receptor 2/4 (TLR2/4) stimulation. Carbon nanoparticles, such as carbon nanotubes (CNTs), can also evoke the NLRP3 inflammasome to trigger IL-1β secretion from lipopolysaccharide-primed macrophages. This study assessed whether costimulation of
C. pneumoniae
with CNTs synergistically enhanced IL-1β secretion from macrophages, and determined the molecular mechanism involved. Enhanced IL-1β secretion from
C. pneumoniae
-infected macrophages by CNTs was dose and time dependent. Transmission electron microscopy revealed that
C. pneumoniae
and CNTs were engulfed concurrently by macrophages. Inhibitors of actin polymerization or caspase-1, a component of the inflammasome, significantly blocked IL-1β secretion. Gene silencing using small interfering RNA (siRNA) targeting the NLRP3 gene also abolished IL-1β secretion. Other inhibitors (K
+
efflux inhibitor, cathepsin B inhibitor, and reactive oxygen species-generating inhibitor) also blocked IL-1β secretion. Taken together, these findings demonstrated that CNTs synergistically enhanced IL-1β secretion from
C. pneumoniae
-infected macrophages via the NLRP3 inflammasome and caspase-1 activation, providing novel insight into our understanding of how
C. pneumoniae
infection can exacerbate asthma.
CpsA, a LytR-CpsA-Psr Family Protein in Mycobacterium marinum, Is Required for Cell Wall Integrity and Virulence
Authors: Wang Qinglan , Zhu Lin , Jones Victoria , Wang Chuan , Hua Yifei , Shi Xujun , Feng Xia , Jackson Mary , Niu Chen , Gao Qian
Published: May 2015

LytR-CpsA-Psr family proteins play an important role in bacterial cell wall integrity. Although the pathogenic relevance of LytR-CpsA-Psr family proteins has been studied in a few bacterial pathogens, their function in mycobacteria remains uncharacterized. In this work, a transposon insertion mutant (
cpsA
::Tn) of
Mycobacterium marinum
was studied. We found that inactivation of CpsA altered bacterial colony morphology, sliding motility, cell surface hydrophobicity, and cell wall permeability. Besides, the
cpsA
mutant exhibited a decreased arabinogalactan content, indicating that CpsA plays a role in cell wall assembly. Moreover, the mutant shows impaired growth within macrophage cell lines and is severely attenuated in zebrafish larvae and adult zebrafish. Taken together, our results indicated that CpsA, a previously uncharacterized protein, is important for mycobacterial cell wall integrity and is required for mycobacterial virulence.
Identification of SlpB, a Cytotoxic Protease from Serratia marcescens
Authors: Shanks Robert M. Q. , Stella Nicholas A. , Hunt Kristin M. , Brothers Kimberly M. , Zhang Liang , Thibodeau Patrick H.
Published: May 2015

The Gram-negative bacterium and opportunistic pathogen
Serratia marcescens
causes ocular infections in healthy individuals. Secreted protease activity was characterized from 44 ocular clinical isolates, and a higher frequency of protease-positive strains was observed among keratitis isolates than among conjunctivitis isolates. A positive correlation between protease activity and cytotoxicity to human corneal epithelial cells
in vitro
was determined. Deletion of
prtS
in clinical keratitis isolate K904 reduced, but did not eliminate, cytotoxicity and secreted protease production. This indicated that PrtS is necessary for full cytotoxicity to ocular cells and implied the existence of another secreted protease(s) and cytotoxic factors. Bioinformatic analysis of the
S. marcescens
Db11 genome revealed three additional open reading frames predicted to code for serralysin-like proteases noted here as
slpB
,
slpC
, and
slpD
. Induced expression of
prtS
and
slpB
, but not
slpC
and
slpD
, in strain PIC3611 rendered the strain cytotoxic to a lung carcinoma cell line; however, only
prtS
induction was sufficient for cytotoxicity to a corneal cell line. Strain K904 with deletion of both
prtS
and
slpB
genes was defective in secreted protease activity and cytotoxicity to human cell lines. PAGE analysis suggests that SlpB is produced at lower levels than PrtS. Purified SlpB demonstrated calcium-dependent and AprI-inhibited protease activity and cytotoxicity to airway and ocular cell lines
in vitro
. Lastly, genetic analysis indicated that the type I secretion system gene,
lipD
, is required for SlpB secretion. These genetic data introduce SlpB as a new cytotoxic protease from
S. marcescens
.
The All-Alpha Domains of Coupling Proteins from the Agrobacterium tumefaciens VirB/VirD4 and Enterococcus faecalis pCF10-Encoded Type IV Secretion Systems Confer Specificity to Binding of Cognate DNA Substrates
Authors: Whitaker Neal , Chen Yuqing , Jakubowski Simon J. , Sarkar Mayukh K. , Li Feng , Christie Peter J.
Published: May 2015

Bacterial type IV coupling proteins (T4CPs) bind and mediate the delivery of DNA substrates through associated type IV secretion systems (T4SSs). T4CPs consist of a transmembrane domain, a conserved nucleotide-binding domain (NBD), and a sequence-variable helical bundle called the all-alpha domain (AAD). In the T4CP structural prototype, plasmid R388-encoded TrwB, the NBD assembles as a homohexamer resembling RecA and DNA ring helicases, and the AAD, which sits at the channel entrance of the homohexamer, is structurally similar to N-terminal domain 1 of recombinase XerD. Here, we defined the contributions of AADs from the
Agrobacterium tumefaciens
VirD4 and
Enterococcus faecalis
PcfC T4CPs to DNA substrate binding. AAD deletions abolished DNA transfer, whereas production of the AAD in otherwise wild-type donor strains diminished the transfer of cognate but not heterologous substrates. Reciprocal swaps of AADs between PcfC and VirD4 abolished the transfer of cognate DNA substrates, although strikingly, the VirD4-AAD
PcfC
chimera (VirD4 with the PcfC AAD) supported the transfer of a mobilizable plasmid. Purified AADs from both T4CPs bound DNA substrates without sequence preference but specifically bound cognate processing proteins required for cleavage at origin-of-transfer sequences. The soluble domains of VirD4 and PcfC lacking their AADs neither exerted negative dominance
in vivo
nor specifically bound cognate processing proteins
in vitro
. Our findings support a model in which the T4CP AADs contribute to DNA substrate selection through binding of associated processing proteins. Furthermore, MOBQ plasmids have evolved a docking mechanism that bypasses the AAD substrate discrimination checkpoint, which might account for their capacity to promiscuously transfer through many different T4SSs.

IMPORTANCE
For conjugative transfer of mobile DNA elements, members of the VirD4/TraG/TrwB receptor superfamily bind cognate DNA substrates through mechanisms that are largely undefined. Here, we supply genetic and biochemical evidence that a helical bundle, designated the all-alpha domain (AAD), of T4SS receptors functions as a substrate specificity determinant. We show that AADs from two substrate receptors,
Agrobacterium tumefaciens
VirD4 and
Enterococcus faecalis
PcfC, bind DNA without sequence or strand preference but specifically bind the cognate relaxases responsible for nicking and piloting the transferred strand through the T4SS. We propose that interactions of receptor AADs with DNA-processing factors constitute a basis for selective coupling of mobile DNA elements with type IV secretion channels.
Characterization of the Dynamic Germination of Individual Clostridium difficile Spores Using Raman Spectroscopy and Differential Interference Contrast Microscopy
Authors: Wang Shiwei , Shen Aimee , Setlow Peter , Li Yong-qing
Published: May 2015

The Gram-positive spore-forming anaerobe
Clostridium difficile
is a leading cause of nosocomial diarrhea. Spores of
C. difficile
initiate infection when triggered to germinate by bile salts in the gastrointestinal tract. We analyzed germination kinetics of individual
C. difficile
spores using Raman spectroscopy and differential interference contrast (DIC) microscopy. Similar to
Bacillus
spores, individual
C. difficile
spores germinating with taurocholate plus glycine began slow leakage of a ∼15% concentration of a chelate of Ca
2+
and dipicolinic acid (CaDPA) at a heterogeneous time
T
1
, rapidly released CaDPA at
T
lag
, completed CaDPA release at
T
release
, and finished peptidoglycan cortex hydrolysis at
T
lysis
.
T
1
and
T
lag
values for individual spores were heterogeneous, but Δ
T
release
periods (
T
release
−
T
lag
) were relatively constant. In contrast to
Bacillus
spores, heat treatment did not stimulate spore germination in the two
C. difficile
strains tested.
C. difficile
spores did not germinate with taurocholate or glycine alone, and different bile salts differentially promoted spore germination, with taurocholate and taurodeoxycholate being best. Transient exposure of spores to taurocholate plus glycine was sufficient to commit individual spores to germinate.
C. difficile
spores did not germinate with CaDPA, in contrast to
B. subtilis
and
C. perfringens
spores. However, the detergent dodecylamine induced
C. difficile
spore germination, and rates were increased by spore coat removal although cortex hydrolysis did not follow
T
release
, in contrast with
B. subtilis
.
C. difficile
spores lacking the cortex-lytic enzyme, SleC, germinated extremely poorly, and cortex hydrolysis was not observed in the few
sleC
spores that partially germinated. Overall, these findings indicate that
C. difficile
and
B. subtilis
spore germination exhibit key differences.

IMPORTANCE
Spores of the Gram-positive anaerobe
Clostridium difficile
are responsible for initiating infection by this important nosocomial pathogen. When exposed to germinants such as bile salts,
C. difficile
spores return to life through germination in the gastrointestinal tract and cause disease, but their germination has been studied only with population-wide measurements. In this work we used Raman spectroscopy and DIC microscopy to monitor the kinetics of germination of individual
C. difficile
spores, the commitment of spores to germination, and the effect of germinant type and concentration, sublethal heat shock, and spore decoating on germination. Our data suggest that the order of germination events in
C. difficile
spores differs from that in
Bacillus
spores and provide new insights into
C. difficile
spore germination.
Novel Transcriptional Regulons for Autotrophic Cycle Genes in Crenarchaeota
Authors: Leyn Semen A. , Rodionova Irina A. , Li Xiaoqing , Rodionov Dmitry A.
Published: May 2015

Autotrophic microorganisms are able to utilize carbon dioxide as their only carbon source, or, alternatively, many of them can grow heterotrophically on organics. Different variants of autotrophic pathways have been identified in various lineages of the phylum
Crenarchaeota
. Aerobic members of the order
Sulfolobales
utilize the hydroxypropionate-hydroxybutyrate cycle (HHC) to fix inorganic carbon, whereas anaerobic
Thermoproteales
use the dicarboxylate-hydroxybutyrate cycle (DHC). Knowledge of transcriptional regulation of autotrophic pathways in
Archaea
is limited. We applied a comparative genomics approach to predict novel autotrophic regulons in the
Crenarchaeota
. We report identification of two novel DNA motifs associated with the autotrophic pathway genes in the
Sulfolobales
(HHC box) and
Thermoproteales
(DHC box). Based on genome context evidence, the HHC box regulon was attributed to a novel transcription factor from the TrmB family named HhcR. Orthologs of HhcR are present in all
Sulfolobales
genomes but were not found in other lineages. A predicted HHC box regulatory motif was confirmed by
in vitro
binding assays with the recombinant HhcR protein from
Metallosphaera yellowstonensis
. For the DHC box regulon, we assigned a different potential regulator, named DhcR, which is restricted to the order
Thermoproteales
. DhcR in
Thermoproteus neutrophilus
(Tneu_0751) was previously identified as a DNA-binding protein with high affinity for the promoter regions of two autotrophic operons. The global HhcR and DhcR regulons reconstructed by comparative genomics were reconciled with available omics data in
Metallosphaera
and
Thermoproteus
spp. The identified regulons constitute two novel mechanisms for transcriptional control of autotrophic pathways in the
Crenarchaeota
.

IMPORTANCE
Little is known about transcriptional regulation of carbon dioxide fixation pathways in
Archaea
. We previously applied the comparative genomics approach for reconstruction of DtxR family regulons in diverse lineages of
Archaea
. Here, we utilize similar computational approaches to identify novel regulatory motifs for genes that are autotrophically induced in microorganisms from two lineages of
Crenarchaeota
and to reconstruct the respective regulons. The predicted novel regulons in archaeal genomes control the majority of autotrophic pathway genes and also other carbon and energy metabolism genes. The HhcR regulon was experimentally validated by DNA-binding assays in
Metallosphaera
spp. Novel regulons described for the first time in this work provide a basis for understanding the mechanisms of transcriptional regulation of autotrophic pathways in
Archaea
.
Retinoblastoma: diagnosis and management—the UK perspective
Authors: Jenkinson Helen
Published: May 2015

In the developed world, retinoblastoma is an uncommon yet highly curable ocular malignancy of childhood affecting 40–50 children in the UK each year. The presenting signs, most commonly leukocoria and squint, should alert the primary care physician or secondary care physician to examine for the red reflex, the absence of which is an indication for urgent ophthalmology assessment. Diagnosis is made by clinical examination and staging may include bone marrow sampling, lumbar puncture and MRI scanning. CT should be avoided to reduce radiation exposure in a population of whom a proportion are at considerable risk of second malignancies. Although enucleation is necessary for many children, over recent years there has been a growing emphasis on conservative management in an attempt to reduce the need for enucleation and avoid the adverse late effects associated with external beam radiotherapy. This review will describe approaches to treatment in the UK and how the stage, laterality and position of the tumour within the eye influence treatment choices.
Acute Care QUAliTy in chronic Kidney disease (ACQUATIK): a prospective cohort study exploring outcomes of patients with chronic kidney disease
Authors: Arnold Julia J , Hayer Manvir , Sharif Adnan , Begaj Irena , Tabriez Mohammed , Bagnall David , Ray Daniel , Hoye Ciaron , Nazir Masood , Dutton Mary , Fifer Lesley , Kirkham Katie , Sims Don , Townend Jonathan N , Gill Paramjit S , Dasgupta Indranil , Cockwell Paul , Ferro Charles J
Published: May 2015

Introduction

Chronic kidney disease (CKD) is common and carries a high risk of morbidity, including hospital admissions and readmissions and mortality. This is largely attributed to an increased risk of cardiovascular disease. Patients with CKD are less likely to receive evidence-based treatments for cardiovascular disease. However, these treatments are based on trials which generally exclude patients with CKD. It is therefore unclear whether this patient group derives the same benefits without an increased risk of adverse effects.

Methods and analysis

The Acute Care QUAliTy in chronic Kidney disease (ACQUATIK) study is a prospective, observational, multicentre cohort study. Over 4000 patients will be recruited with an enrolment period of 2 years and a follow-up period of 2–4 years. Patients under follow-up by a renal team will be excluded. Data will be obtained from patient and hospital records during the index admission. Preadmission data will be extracted from general practice records based on the Quality and Outcomes Framework. Diagnosis, comorbidities and procedure data pertaining to the index and subsequent admissions will be extracted from the Hospital Episode Statistics database and long-term mortality data will be tracked using the Office of National Statistics. This information will allow us to examine a complete patient journey through primary and secondary care, providing unequalled levels of information on treatment and outcomes of patients with CKD. The combined data set will be used to compare outcomes and treatments among patients with CKD versus patients without CKD. The primary end point is hospital readmission rates. The relationship between age, sex, ethnicity, socioeconomic status and concurrent comorbidities will be analysed to determine their influence on outcomes and treatments.

Ethics and dissemination

The ACQUATIK study has been approved by the NRES Committee West Midlands—South Birmingham—Reference 13/WM/0317. The results from ACQUATIK will be submitted for publication in peer-reviewed journals and presented at primary and secondary care conferences.

Trial registration number

ISRCTN37237454.
Local food environment interventions to improve healthy food choice in adults: a systematic review and realist synthesis protocol
Authors: Penney Tarra L , Brown Helen Elizabeth , Maguire Eva R , Kuhn Isla , Monsivais Pablo
Published: May 2015

Introduction

Local food environments have been linked with dietary intake and obesity in adults. However, overall evidence remains mixed with calls for increased theoretical and conceptual clarity related to how availability of neighbourhood food outlets, and within-outlet food options, influence food purchasing and consumption. The purpose of this work is to develop a programme theory of food availability, supported by empirical evidence from a range of local food environment interventions.

Methods and analysis

A systematic search of the literature will be followed by duplicate screening and quality assessment (using the Effective Public Health Practice Project tool). Realist synthesis will then be conducted according to the Realist And Meta-narrative Evidence Syntheses: Evolving Standards (RAMESES) publication standards, including transparent appraisal, synthesis and drawing conclusions via consensus.

Dissemination

The final synthesis will propose an evidence-based programme theory of food availability, including evidence mapping to demonstrate contextual factors, pathways of influence and potential mechanisms. With the paucity of empirically supported programme theories used in current local food environment interventions to improve food availability, this synthesis may be used to understand how and why interventions work, and thus inform the development of theory-driven, evidence-based interventions to improve healthy food choice and future empirical work.

Trial registration number

PROSPERO CRD42014009808.
Direct targeting of risk factors significantly increases the detection of liver cirrhosis in primary care: a cross-sectional diagnostic study utilising transient elastography
Authors: Harman David J , Ryder Stephen D , James Martin W , Jelpke Matthew , Ottey Dominic S , Wilkes Emilie A , Card Timothy R , Aithal Guruprasad P , Guha Indra Neil
Published: May 2015

Objectives

To assess the feasibility of a novel diagnostic algorithm targeting patients with risk factors for chronic liver disease in a community setting.

Design

Prospective cross-sectional study.

Setting

Two primary care practices (adult patient population 10 479) in Nottingham, UK.

Participants

Adult patients (aged 18 years or over) fulfilling one or more selected risk factors for developing chronic liver disease: (1) hazardous alcohol use, (2) type 2 diabetes or (3) persistently elevated alanine aminotransferase (ALT) liver function enzyme with negative serology.

Interventions

A serial biomarker algorithm, using a simple blood-based marker (aspartate aminotransferase:ALT ratio for hazardous alcohol users, BARD score for other risk groups) and subsequently liver stiffness measurement using transient elastography (TE).

Main outcome measures

Diagnosis of clinically significant liver disease (defined as liver stiffness ≥8 kPa); definitive diagnosis of liver cirrhosis.

Results

We identified 920 patients with the defined risk factors of whom 504 patients agreed to undergo investigation. A normal blood biomarker was found in 62 patients (12.3%) who required no further investigation. Subsequently, 378 patients agreed to undergo TE, of whom 98 (26.8% of valid scans) had elevated liver stiffness. Importantly, 71/98 (72.4%) patients with elevated liver stiffness had normal liver enzymes and would be missed by traditional investigation algorithms. We identified 11 new patients with definite cirrhosis, representing a 140% increase in the number of diagnosed cases in this population.

Conclusions

A non-invasive liver investigation algorithm based in a community setting is feasible to implement. Targeting risk factors using a non-invasive biomarker approach identified a substantial number of patients with previously undetected cirrhosis.

Trial registration number

The diagnostic algorithm utilised for this study can be found on clinicaltrials.gov (NCT02037867), and is part of a continuing longitudinal cohort study.
How does acupuncture affect insulin sensitivity in women with polycystic ovary syndrome and insulin resistance? Study protocol of a prospective pilot study
Authors: Zheng Yanhua , Stener-Victorin Elisabet , Ng Ernest H Y , Li Juan , Wu Xiaoke , Ma Hongxia
Published: May 2015

Introduction

Hyperinsulinaemia and insulin resistance (IR) are key features of polycystic ovary syndrome (PCOS) and metabolic syndrome. The effect of 5 weeks of acupuncture treatment has been investigated in a completed prospective pilot trial (Clinicaltrials.gov:NCT01457209), and acupuncture with electrical stimulation applied to insulin-resistant rats with dihydrotestosterone-induced PCOS was shown to improve insulin sensitivity. Therefore, we now aim to conduct a prospective pilot study to evaluate whether using the same acupuncture treatment protocol given over a longer period of time (6 months) than in the previous pilot trial will improve insulin sensitivity in women with PCOS and IR. Our hypothesis is that acupuncture with combined manual and low-frequency electrical stimulation of the needles will improve insulin sensitivity in women with PCOS and IR.

Methods/analysis

This is a prospective pilot trial. A total of 112 women with PCOS and IR will be recruited and categorised according to their body mass index (BMI) as normal weight (BMI=18.5−23 kg/m2) or as overweight/obese (BMI>23 kg/m2). Acupuncture will be applied three times per week for 6 months at 30 min per treatment. The primary outcome will be the change in insulin sensitivity before and after 6 months of acupuncture treatment, as measured by an oral glucose tolerance test.

Ethics/dissemination

Ethical approval of this study has been granted from the ethics committee of the First Affiliated Hospital of Guangzhou Medical University (No. 2013039). Written and informed consent will be obtained from each patient before any study procedure is performed, according to good clinical practice. The results of this trial will be disseminated in a peer-reviewed journal and presented at international congresses.

Trial registration numbers

NCT02026323 and ChiCTR-OCH-13003921.
A multisource feedback tool to assess ward round leadership skills of senior paediatric trainees: (2) Testing reliability and practicability
Authors: Goodyear Helen M , Lakshminarayana Indumathy , Wall David , Bindal Taruna
Published: May 2015

Background

A five-domain multisource feedback (MSF) tool was previously developed in 2009–2010 by the authors to assess senior paediatric trainees’ ward round leadership skills.

Objectives

To determine whether this MSF tool is practicable and reliable, whether individuals’ feedback varies over time and trainees’ views of the tool.

Methods

The MSF tool was piloted (April–July 2011) and field tested (September 2011–February 2013) with senior paediatric trainees. A focus group held at the end of field testing obtained trainees’ views of the tool.

Results

In field testing, 96/115 (84%) trainees returned 633 individual assessments from three different ward rounds over 18 months. The MSF tool had high reliability (Cronbach's α 0.84, G coefficient 0.8 for three raters). In all five domains, data were shifted to the right with scores of 3 (good) and 4 (excellent). Consultants gave significantly lower scores (p<0.001), as did trainees for self–assessment (p<0.001). There was no significant change in MSF scores over 18 months but comments showed that trainees’ performance improved. Trainees valued these comments and the MSF tool but had concerns about time taken for feedback and confusion about tool use and the paediatric assessment strategy.

Conclusions

A five-domain MSF tool was found to be reliable on pilot and field testing, practicable to use and liked by trainees. Comments on performance were more helpful than scores in giving trainees feedback.
Incidence of and mortality from kidney disease in over 600,000 insured Swedish dogs
Authors: Pelander L. , Ljungvall I. , Egenvall A. , Syme H. , Elliott J. , Häggström J.
Published: May 2015

Kidney disease is an important cause of morbidity and mortality in dogs. Knowledge about the epidemiology of kidney disease in the dog population is valuable and large‐scale epidemiological studies are needed. The aim of the present study was to use insurance data to estimate kidney‐related morbidity and mortality in the Swedish dog population. Insurance company data from insured dogs during the years 1995–2006 were studied retrospectively. Incidence and mortality were calculated for the whole group of dogs as well as divided by sex and breed. The total number of veterinary care insured dogs was 665,245. The total incidence of kidney disease in this group of dogs was 15.8 (15.3–16.2) cases/10,000 dog‐years at risk. The number of dogs in the life insurance was 548,346 and in this group the total kidney‐related mortality was 9.7 (9.3–10.2) deaths/10,000 dog‐years at risk. The three breeds with the highest incidence of kidney disease were the Bernese mountain dog, miniature schnauzer and boxer. The three breeds with the highest mortality caused by kidney disease were the Bernese mountain dog, Shetland sheepdog and flat‐coated retriever. In conclusion, the epidemiological information provided in this study concerning kidney disease in dogs can provide valuable information for future research.
A tale of two horizons
Authors: Stotyn Sean
Published: May 2015

I revisit the fate of coinciding horizons and the volume between them in the extremal limit of spherically symmetric black holes in four space–time dimensions, focusing on the Schwarzschild – de Sitter black hole for concreteness. The two Killing horizons in the limit space–time that are traditionally identified with the limiting event horizons of the non-extremal black hole are shown to instead be generated by an enhanced symmetry of the near horizon geometry (NHG). This dismantles the interpretation of the four-volume between the horizons remaining finite in the extremal limit. The NHG is reinterpreted as a tangent space–time to the degenerate black hole horizon, and geometrical objects, such as Killing vectors and Killing horizons, are carefully mapped between the bulk and the NHG. The implications for extremal black hole entropy are then discussed.
Vitamin D, phosphate, and vasculotoxicity
Authors: Brown Ronald B. , Haq Afrozul , Stanford Charles F. , Razzaque Mohammed S.
Published: May 2015

Vascular calcification is a complex process that results in the ectopic deposition of calcium-phosphate hydroxyapatite. Medial and intimal vascular calcification is frequently present in patients with diabetes mellitus and chronic kidney disease (CKD), and markedly increases the morbidity and mortality of these patients. Increased serum levels of calcium and phosphate, along with the use of active vitamin D metabolites, are commonly implicated in the evolvement of vascular wall mineralization in CKD patients. Because CKD patients have lower serum levels of vitamin D, they are routinely prescribed vitamin D supplements that exert a dualistic role that is both healthful and harmful in these patients, perhaps protecting bone health, but at the expense of promoting vascular pathology. This review briefly explains how reducing the phosphate burden in CKD patients could minimize vitamin-D-associated vascular wall calcification.
Effect of pion versus kaon interferometry on the chaotic parameter
Authors: Liu Jie , Zhao Li-Dong , Xu Xiao-Zhao , Yin Hui-Zeng
Published: May 2015

In this paper, the advantages of pion versus kaon interferometry as a measure to probe the degree of source coherence are studied by a expanding boson gas model with a harmonic oscillator potential. We investigate the conditions about occurrence of Bose–Einstein condensation and analyze its impacts on the chaotic parameter λ. The results indicate that this finite condensation for pion system decreases the value of λ, but influence slightly for kaon system.
Energy-dependent existence of soliton in the synthesis of chemical elements
Authors: Iwata Yoritaka
Published: May 2015

Light chemical elements are, for instance, produced through ion collisions taking place in the core of stars, where fusion is particularly important to the synthesis of chemical elements. Meanwhile soliton provides transparency leading to the hindrance of fusion cross-section. In order to explain high fusion cross-section actually observed in low incident energies, it is necessary to discover the suppression mechanism of soliton propagation. In this paper, based on a systematic three-dimensional time-dependent density functional calculation, the existence of soliton is examined for ion collisions with some incident energies, impact parameters, and nuclear force parameter sets. As a result, solitons are suggested to exist highly depending on the energy. The suppression of soliton is consequently due to the spin-orbit force and the momentum-dependent components of the nuclear force.
Generic off-diagonal solutions and solitonic hierarchies in (modified) gravity
Authors: Vacaru Sergiu I.
Published: May 2015

We have summarized our recent results on encoding exact solutions of field equations in Einstein and modified gravity theories into solitonic hierarchies derived for nonholonomic curve flows with associated bi-Hamilton structure. We argue that there is a canonical distinguished connection for which the fundamental geometric/physical equations decouple in general form. This allows us to construct very general classes of generic off-diagonal solutions determined by corresponding types of generating and integration functions depending on all (spacetime) coordinates. If the integral varieties are constrained to zero torsion configurations, we can extract solutions for the general relativity (GR) theory. We conclude that the geometric and physical data for various classes of effective/modified Einstein spaces can be encoded into multi-component versions of the sine-Gordon, or modified Korteweg–de Vries equations.
Approximate symmetries in atomic nuclei from a large-scale shell-model perspective
Authors: Launey K. D. , Draayer J. P. , Dytrych T. , Sun G.-H. , Dong S.-H.
Published: May 2015

In this paper, we review recent developments that aim to achieve further understanding of the structure of atomic nuclei, by capitalizing on exact symmetries as well as approximate symmetries found to dominate low-lying nuclear states. The findings confirm the essential role played by the Sp(3, ℝ) symplectic symmetry to inform the interaction and the relevant model spaces in nuclear modeling. The significance of the Sp(3, ℝ) symmetry for a description of a quantum system of strongly interacting particles naturally emerges from the physical relevance of its generators, which directly relate to particle momentum and position coordinates, and represent important observables, such as, the many-particle kinetic energy, the monopole operator, the quadrupole moment and the angular momentum. We show that it is imperative that shell-model spaces be expanded well beyond the current limits to accommodate particle excitations that appear critical to enhanced collectivity in heavier systems and to highly-deformed spatial structures, exemplified by the second 0+ state in 12 C (the challenging Hoyle state) and 8 Be . While such states are presently inaccessible by large-scale no-core shell models, symmetry-based considerations are found to be essential.
USING EPSILON HULLS TO CHARACTERIZE AND CLASSIFY TOTALLY DISCONNECTED SIERPIŃSKI RELATIVES
Authors: TAYLOR T. D.
Published: May 2015

This paper presents an investigation of the use of ϵ-hulls to characterize and classify the totally disconnected Sierpiński relatives. These fractals all have the same fractal dimension, and the same topologies, but the ϵ-hulls provide ways to distinguish between such relatives. Examples of specific relatives are presented to illustrate the theory.
PERISTALTIC FLOW OF COUPLE-STRESS FLUID WITH HEAT AND MASS TRANSFER: AN APPLICATION IN BIOMEDICINE
Authors: HINA S. , MUSTAFA M. , HAYAT T. , ALSAEDI A.
Published: May 2015

Analysis is performed for the simultaneous effects of heat and mass transfer on the peristaltic transport of an electrically conducting couple-stress fluid in a compliant walls channel. The study may be useful in understanding the physiological flow of blood through micro-circulatory system in the presence of particle-size effect. Long wavelength and low Reynolds number aspects are taken into consideration. Exact solutions for stream function, temperature and concentration are derived. Impact of pertinent parameters like the couple-stress fluid parameter (γ), Hartman number (M), amplitude ratio (ϵ), elastic parameters (E1, E2, E3, E4, E5), Brinkman number (Br) and Schmidt number (Sc). It is observed that velocity and temperature distributions are greater for couple stress fluid when compared with the Newtonian fluid.
New optimal quantum convolutional codes
Authors: Zhu Shixin , Wang Liqi , Kai Xiaoshan
Published: May 2015

One of the most challenges to prove the feasibility of quantum computers is to protect the quantum nature of information. Quantum convolutional codes are aimed at protecting a stream of quantum information in a long distance communication, which are the correct generalization to the quantum domain of their classical analogs. In this paper, we construct some classes of quantum convolutional codes by employing classical constacyclic codes. These codes are optimal in the sense that they attain the Singleton bound for pure convolutional stabilizer codes.
Synthesis, antiviral, cytotoxicity and antitumor evaluations of A4 type of porphyrin derivatives
Authors: Fadda Ahmed A. , El-Mekawy Rasha E. , El-Shafei Ahmed I.
Published: May 2015

This manuscript describes the synthesis of a new series of porphyrin structures 4a–4m, 7, 9, 12 and 14. These structures were investigated against two types of viruses such as HIV-1 and HSV-1. Also they were screened for their antitumor activity. Among all tested compounds, it was found that compound 4b showed a high activity against HIV-1 and HSV-1 and against four different tumor cell lines. Most of the tested compounds showed a moderate degree of a potent antimicrobial activity. The structure of these compounds was confirmed on the basis of their analytical and spectral data such as UV-vis, IR, 13 C NMR, 1 H NMR spectroscopy and mass spectral data.
AVIAN INFLUENZA AND ITS MASS DEPOPULATION STRATEGIES IN INFECTED POULTRY BIRDS
Authors: Tahir Rabia , Anjum Aftab Ahmed , Muhammad Khushi , Rasool Asfa , Khan Farah
Published: May 2015

Avian influenza (AI) is a highly contagious and zoonotic viral disease that affects several animal species. It causes heavy economic losses in the domestic poultry. A quick response is always desired in the event of any disease outbreak. The principal approach to control a contagious disease involves the killing of diseased animals along with the bio containment of infectious agent. Mass depopulation of the infected birds plays an important role in the eradication of the disease. The possible strategies for mass depopulation include maceration, electrocution, cervical dislocation, gassing and foaming. All of these procedures are much intensive and time consuming because it involves a lot of man power, biosecurity risks, applicability for all house types and suitability for large-scale emergency implementation. The basic objectives of these strategies include (1) To reduce pain and suffering to the birds, (2) To minimize disease spread and (3) To ensure of protection to human operators from potential biohazards. A suitable depopulation technique can only be suggested keeping in view the species and type of bird involved, and differences in husbandry practices like management, housing and stocking density. Mass depopulation is an important tool to control the spread of any disease but the selection of procedure depends upon the prevailing circumstances. In this paper, various mass depopulation strategies and their selection in different conditions is reviewed and discussed.
CoEx
Authors: Eusse Juan Fernando , Williams Christopher , Leupers Rainer
Published: May 2015

Application-Specific Instruction Set Processors (ASIPs) provide the adequate performance/efficiency tradeoff for their particular application domain. Nevertheless, their design methodologies have stagnated during the past decade and are still based on a series of manual and time-consuming iterative steps. Furthermore, there exists a
productivity gap
between the point where an application is given as the target for processor customization and the time a customized architecture is available. Therefore, new tools are required that reduce the number of design iterations and bridge the aforementioned productivity gap. This can be achieved by (1) profiling technologies that, by adapting to the designer’s needs, help to gain insight into application specifications, and (2) prearchitectural design technologies that give early yet accurate feedback on the impact of algorithmic/architectural design decisions. The first requirement is addressed in this article by proposing the
multigrained profiling
approach, which identifies the profiling needs at each step of ASIP design and lets the designer tailor the level of detail for application inspection. CoEx, a practical implementation of the approach, is also introduced. The second requirement is addressed by creating a
prearchitectural estimation engine
. This engine couples CoEx reports for an application with an abstract processor model and generates an estimate of the achievable performance. Both CoEx and the performance estimation engine are respectively evaluated for instrumentation-induced execution overhead and accuracy. Finally, the development of an ASIP architecture for an augmented reality computer vision application is presented. The ASIP achieves a gain of six times compared to the original application performance, after being developed in only 2 days.
Execution Trace--Driven Energy-Reliability Optimization for Multimedia MPSoCs
Authors: Das Anup , Singh Amit Kumar , Kumar Akash
Published: May 2015

Multiprocessor systems-on-chip (MPSoCs) are becoming a popular design choice in current and future technology nodes to accommodate the heterogeneous computing demand of a multitude of applications enabled on these platform. Streaming multimedia and other communication-centric applications constitute a significant fraction of the application space of these devices. The mapping of an application on an MPSoC is an NP-hard problem. This has attracted researchers to solve this problem both as stand-alone (best-effort) and in conjunction with other optimization objectives, such as energy and reliability. Most existing studies on energy-reliability joint optimization are static—that is, design time based. These techniques fail to capture runtime variability such as resource unavailability and dynamism associated with application behaviors, which are typical of multimedia applications. The few studies that consider dynamic mapping of applications do not consider throughput degradation, which directly impacts user satisfaction. This article proposes a runtime technique to analyze the execution trace of an application modeled as Synchronous Data Flow Graphs (SDFGs) to determine its mapping on a multiprocessor system with heterogeneous processing units for different fault scenarios. Further, communication energy is minimized for each of these mappings while satisfying the throughput constraint. Experiments conducted with synthetic and real SDFGs demonstrate that the proposed technique achieves significant improvement with respect to the state-of-the-art approaches in terms of throughput and storage overhead with less than 20% energy overhead.
A Pólya Urn Document Language Model for Improved Information Retrieval
Authors: Cummins Ronan , Paik Jiaul H. , Lv Yuanhua
Published: May 2015

The multinomial language model has been one of the most effective models of retrieval for more than a decade. However, the multinomial distribution does not model one important linguistic phenomenon relating to term dependency—that is, the tendency of a term to repeat itself within a document (i.e., word burstiness). In this article, we model document generation as a random process with reinforcement (a multivariate Pólya process) and develop a Dirichlet compound multinomial language model that captures word burstiness directly.

We show that the new reinforced language model can be computed as efficiently as current retrieval models, and with experiments on an extensive set of TREC collections, we show that it significantly outperforms the state-of-the-art language model for a number of standard effectiveness metrics. Experiments also show that the tuning parameter in the proposed model is more robust than that in the multinomial language model. Furthermore, we develop a constraint for the verbosity hypothesis and show that the proposed model adheres to the constraint. Finally, we show that the new language model essentially introduces a measure closely related to idf, which gives theoretical justification for combining the term and document event spaces in tf-idf type schemes.
TSG (2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside) from the Chinese HerbPolygonum multiflorumIncreases Life Span and Stress Resistance ofCaenorhabditis elegans
Authors: Büchter Christian , Zhao Liang , Havermann Susannah , Honnen Sebastian , Fritz Gerhard , Proksch Peter , Wätjen Wim
Published: May 2015

2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG) was isolated fromPolygonum multiflorum, a plant which is traditionally used as an anti-ageing drug. We have analysed ageing-related effects of TSG in the model organismC. elegansin comparison to resveratrol. TSG exerted a high antioxidative capacity both in a cell-free assay and in the nematode. The antioxidative capacity was even higher compared to resveratrol. Presumably due to its antioxidative effects, treatment with TSG decreased the juglone-mediated induction of the antioxidative enzyme SOD-3; the induction of the GST-4 by juglone was diminished slightly. TSG increased the resistance ofC. elegansagainst lethal thermal stress more prominently than resveratrol (50 μM TSG increased mean survival by 22.2%). The level of the ageing pigment lipofuscin was decreased after incubation with the compound. TSG prolongs the mean, median, and maximum adult life span ofC. elegansby 23.5%, 29.4%, and 7.2%, respectively, comparable to the effects of resveratrol. TSG-mediated extension of life span was not abolished in a DAF-16 loss-of-function mutant strain showing that this ageing-related transcription factor is not involved in the effects of TSG. Our data show that TSG possesses a potent antioxidative capacity, enhances the stress resistance, and increases the life span of the nematodeC. elegans.
The Balanced Scorecard and the Strategic Learning Process: A System Dynamics Modeling Approach
Authors: Nielsen Steen , Nielsen Erland H.
Published: May 2015

The main purpose of this paper is to improve on the conceptual as well as the methodological aspects of BSC as a quantitative model by combining elements from traditional balanced scorecard (BSC) thinking with the Systems Thinking. This is done by combining short and long term aspects of measurements. The result is then used to build and construct a balanced scorecard model for strategic learning with the specific aim to maintain satisfied customers and motivated employees. Strategic planning, operational execution, feedback, and learning are some of the most important key features of any performance measurement model. This paper aims to address not only the conceptual domain related to BSC, that is, learning and system dynamics causality and feedback, but also the methodological domain concept of precision solved by differential equations. Our results show how a potential move from a static strategic vision map to a linked and dynamic understanding may be not fully realistic but very useful for learning purposes. The new knowledge obtained from the learning feedbacks fertilizes both decision discussion and decision-making and what may be required in order to move to the next level of BSC and system dynamics integration.