bluuebunny/crossref_metadata_2025 huggingface dataset:
IRGM3 Contributes to Immunopathology and Is Required for Differentiation of Antigen-Specific Effector CD8+T Cells in Experimental Cerebral Malaria
Authors: Guo Jintao , McQuillan James A. , Yau Belinda , Tullo Gregory S. , Long Carole A. , Bertolino Patrick , Roediger Ben , Weninger Wolfgang , Taylor Gregory A. , Hunt Nicholas H. , Ball Helen J. , Mitchell Andrew J.
Published: February 2015

Gamma interferon (IFN-γ) drives antiparasite responses and immunopathology during infection withPlasmodiumspecies. Immunity-related GTPases (IRGs) are a class of IFN-γ-dependent proteins that are essential for cell autonomous immunity to numerous intracellular pathogens. However, it is currently unknown whether IRGs modulate responses during malaria. We have used thePlasmodium bergheiANKA (PbA) model in which mice develop experimental cerebral malaria (ECM) to study the roles of IRGM1 and IRGM3 in immunopathology. Induction of mRNA forIrgm1andIrgm3was found in the brains and spleens of infected mice at times of peak IFN-γ production.Irgm3−/−but notIrgm1−/−mice were completely protected from the development of ECM, and this protection was associated with the decreased induction of inflammatory cytokines, as well as decreased recruitment and activation of CD8+T cells within the brain. Although antigen-specific proliferation of transferred CD8+T cells was not diminished compared to that of wild-type recipients following PbA infection, T cells transferred intoIrgm3−/−recipients showed a striking impairment of effector differentiation. Decreased induction of several inflammatory cytokines and chemokines (interleukin-6, CCL2, CCL3, and CCL4), as well as enhanced mRNA expression of type-I IFNs, was found in the spleens ofIrgm3−/−mice at day 4 postinfection. Together, these data suggest that protection from ECM pathology inIrgm3−/−mice occurs due to impaired generation of CD8+effector function. This defect is nonintrinsic to CD8+T cells. Instead, diminished T cell responses most likely result from defective initiation of inflammatory responses in myeloid cells.
Mutant Brucella abortus Membrane Fusogenic Protein Induces Protection against Challenge Infection in Mice
Authors: de Souza Filho Job Alves , Martins Vicente de Paulo , Campos Priscila Carneiro , Alves-Silva Juliana , Santos Nathalia V. , de Oliveira Fernanda Souza , Menezes Gustavo B. , Azevedo Vasco , Cravero Silvio Lorenzo , Oliveira Sergio Costa
Published: February 2015

Brucellaspecies can cause brucellosis, a zoonotic disease that causes serious livestock economic losses and represents a public health threat. The mechanism of virulence ofBrucellaspp. is not yet fully understood. Therefore, it is crucial to identify new molecules that serve as virulence factors to better understand this host-pathogen interplay. Here, we evaluated the role of theBrucellamembrane fusogenic protein (Mfp) and outer membrane protein 19 (Omp19) in bacterial pathogenesis. In this study, we showed thatB. abortusΔmfp::kanand Δomp19::kandeletion mutant strains have reduced persistencein vivoin C57BL/6 and interferon regulatory factor 1 (IRF-1) knockout (KO) mice. Additionally, 24 h after macrophage infection with a Δmfp::kanor Δomp19::kanstrain expressing green fluorescent protein (GFP) approximately 80% or 65% ofBrucella-containing vacuoles (BCVs) retained the late endosomal/lysosomal marker LAMP-1, respectively, whereas around 60% of BCVs containing wild-type S2308 were found in LAMP-1-negative compartments.B. abortusΔomp19::kanwas attenuatedin vivobut had a residual virulence in C57BL/6 and IRF-1 KO mice, whereas the Δmfp::kanstrain had a lower virulence in these same mouse models. Furthermore, Δmfp::kanand Δomp19::kanstrains were used as live vaccines. Challenge experiments revealed that in C57BL/6 and IRF-1 KO mice, the Δmfp::kanstrain induced greater protection than the vaccine RB51 and protection similar that of vaccine S19. However, a Δomp19::kanstrain induced protection similar to that of RB51. Thus, these results demonstrate thatBrucellaMfp and Omp19 are critical for full bacterial virulence and that the Δmfp::kanmutant may serve as a potential vaccine candidate in future studies.
Dendritic Cell-Based Immunization Ameliorates Pulmonary Infection with Highly Virulent Cryptococcus gattii
Authors: Ueno Keigo , Kinjo Yuki , Okubo Yoichiro , Aki Kyoko , Urai Makoto , Kaneko Yukihiro , Shimizu Kiminori , Wang Dan-Ni , Okawara Akiko , Nara Takuya , Ohkouchi Kayo , Mizuguchi Yuki , Kawamoto Susumu , Kamei Katsuhiko , Ohno Hideaki , Niki Yoshihito , Shibuya Kazutoshi , Miyazaki Yoshitsugu
Published: February 2015

Cryptococcosis due to a highly virulent fungus,
Cryptococcus gattii
, emerged as an infectious disease on Vancouver Island in Canada and surrounding areas in 1999, causing deaths among immunocompetent individuals. Previous studies indicated that
C. gattii
strain R265 isolated from the Canadian outbreak had immune avoidance or immune suppression capabilities. However, protective immunity against
C. gattii
has not been identified. In this study, we used a gain-of-function approach to investigate the protective immunity against
C. gattii
infection using a dendritic cell (DC)-based vaccine. Bone marrow-derived dendritic cells (BMDCs) efficiently engulfed acapsular
C. gattii
(Δ
cap60
strain), which resulted in their expression of costimulatory molecules and inflammatory cytokines. This was not observed for BMDCs that were cultured with encapsulated strains. When Δ
cap60
strain-pulsed BMDCs were transferred to mice prior to intratracheal R265 infection, significant amelioration of pathology, fungal burden, and the survival rate resulted compared with those in controls. Multinucleated giant cells (MGCs) that engulfed fungal cells were significantly increased in the lungs of immunized mice. Interleukin 17A (IL-17A)-, gamma interferon (IFN-γ)-, and tumor necrosis factor alpha (TNF-α)-producing lymphocytes were significantly increased in the spleens and lungs of immunized mice. The protective effect of this DC vaccine was significantly reduced in IFN-γ knockout mice. These results demonstrated that an increase in cytokine-producing lymphocytes and the development of MGCs that engulfed fungal cells were associated with the protection against pulmonary infection with highly virulent
C. gattii
and suggested that IFN-γ may have been an important mediator for this vaccine-induced protection.
Uncoupling of Pro- and Anti-Inflammatory Properties of Staphylococcus aureus
Authors: Peres Adam G. , Stegen Camille , Li Junbin , Xu An Qi , Levast Benoit , Surette Michael G. , Cousineau Benoit , Desrosiers Martin , Madrenas Joaquín
Published: February 2015

Staphylococcus aureusis a Gram-positive bacterium that is carried by a quarter of the healthy human population and that can cause severe infections. This pathobiosis has been linked to a balance between Toll-like receptor 2 (TLR2)-dependent pro- and anti-inflammatory responses. The relationship between these two types of responses is unknown. Analysis of 16 nasal isolates ofS. aureusshowed heterogeneity in their capacity to induce pro- and anti-inflammatory responses, suggesting that these two responses are independent of each other. Uncoupling of these responses was corroborated by selective signaling through phosphoinositol 3-kinase (PI3K)-Akt-mTOR and extracellular signal-regulated kinase (ERK) for the anti-inflammatory response and through p38 for the proinflammatory response. Uncoupling was also observed at the level of phagocytosis and phagosomal processing ofS. aureus, which were required solely for the proinflammatory response. Importantly, the anti-inflammatory properties of anS. aureusisolate correlated with its ability to modulate T cell immunity. Our results suggest the presence of anti-inflammatory TLR2 ligands in the staphylococcal cell wall, whose identification may provide templates for novel immunomodulatory drugs.
Identification and Characterization of Clostridium perfringens Beta Toxin Variants with Differing Trypsin Sensitivity and
In Vitro
Cytotoxicity Activity
Authors: Theoret James R. , Uzal Francisco A. , McClane Bruce A.
Published: February 2015

By producing toxins,
Clostridium perfringens
causes devastating diseases of both humans and animals.
C. perfringens
beta toxin (CPB) is the major virulence determinant for type C infections and is also implicated in type B infections, but little is known about the CPB structure-function relationship. Amino acid sequence comparisons of the CPBs made by 8 randomly selected isolates identified two natural variant toxins with four conserved amino acid changes, including a switch of E to K at position 168 (E168K) that introduces a potential trypsin cleavage site into the CPB protein of strain JGS1076. To investigate whether this potential trypsin cleavage site affects sensitivity to trypsin, a primary host defense against this toxin, the two CPB variants were assayed for their trypsin sensitivity. The results demonstrated a significant difference in trypsin sensitivity, which was linked to the E168K switch by using site-directed recombinant CPB (rCPB) mutants. The natural CPB variants also displayed significant differences in their cytotoxicity to human endothelial cells. This cytotoxicity difference was mainly attributable to increased host cell binding rather than the ability to oligomerize or form functional pores. Using rCPB site-directed mutants, differences in cytotoxicity and host cell binding were linked to an A300V amino acid substitution in the strain JGS1076 CPB variant that possessed more cytotoxic activity. Mapping of sequence variations on a CPB structure modeled using related toxins suggests that the E168K substitution is surface localized and so can interact with trypsin and that the A300V substitution is located in a putative binding domain of the CPB toxin.
Rab14 Regulates Maturation of Macrophage Phagosomes Containing the Fungal Pathogen Candida albicans and Outcome of the Host-Pathogen Interaction
Authors: Okai Blessing , Lyall Natalie , Gow Neil A. R. , Bain Judith M. , Erwig Lars-Peter
Published: February 2015

Avoidance of innate immune defense is an important mechanism contributing to the pathogenicity of microorganisms. The fungal pathogen
Candida albicans
undergoes morphogenetic switching from the yeast to the filamentous hyphal form following phagocytosis by macrophages, facilitating its escape from the phagosome, which can result in host cell lysis. We show that the intracellular host trafficking GTPase Rab14 plays an important role in protecting macrophages from lysis mediated by
C. albicans
hyphae. Live-cell imaging of macrophages expressing green fluorescent protein (GFP)-tagged Rab14 or dominant negative Rab14, or with small interfering RNA (siRNA)-mediated knockdown of Rab14, revealed the temporal dynamics of this protein and its influence on the maturation of macrophage phagosomes following the engulfment of
C. albicans
cells. Phagosomes containing live
C. albicans
cells became transiently Rab14 positive within 2 min following engulfment. The duration of Rab14 retention on phagosomes was prolonged for hyphal cargo and was directly proportional to hyphal length. Interference with endogenous Rab14 did not affect the migration of macrophages toward
C. albicans
cells, the rate of engulfment, the overall uptake of fungal cells, or early phagosome processing. However, Rab14 depletion delayed the acquisition of the late phagosome maturation markers LAMP1 and lysosomal cathepsin, indicating delayed formation of a fully bioactive lysosome. This was associated with a significant increase in the level of macrophage killing by
C. albicans
. Therefore, Rab14 activity promotes phagosome maturation during
C. albicans
infection but is dysregulated on the phagosome in the presence of the invasive hyphal form, which favors fungal survival and escape.
Binding of Complement Factor H to PorB3 and NspA Enhances Resistance of Neisseria meningitidis to Anti-Factor H Binding Protein Bactericidal Activity
Authors: Giuntini Serena , Pajon Rolando , Ram Sanjay , Granoff Dan M.
Published: February 2015

Among 25 serogroup BNeisseria meningitidisclinical isolates, we identified four (16%) with high factor H binding protein (FHbp) expression that were resistant to complement-mediated bactericidal activity of sera from mice immunized with recombinant FHbp vaccines. Two of the four isolates had evidence of human FH-dependent complement downregulation independent of FHbp. Since alternative complement pathway recruitment is critical for anti-FHbp bactericidal activity, we hypothesized that in these two isolates binding of FH to ligands other than FHbp contributes to anti-FHbp bactericidal resistance. Knocking out NspA, a known meningococcal FH ligand, converted both resistant isolates to anti-FHbp susceptible isolates. The addition of a nonbactericidal anti-NspA monoclonal antibody to the bactericidal reaction also increased anti-FHbp bactericidal activity. To identify a role for FH ligands other than NspA or FHbp in resistance, we created double NspA/FHbp knockout mutants. Mutants from both resistant isolates bound 10-fold more recombinant human FH domains 6 and 7 fused to Fc than double knockout mutants prepared from two sensitive meningococcal isolates. In light of recent studies showing functional FH-PorB2 interactions, we hypothesized that PorB3 from the resistant isolates recruited FH. Allelic exchange ofporB3from a resistant isolate to a sensitive isolate increased resistance of the sensitive isolate to anti-FHbp bactericidal activity (and vice versa). Thus, some PorB3 variants functionally bind human FH, which in the presence of NspA enhances anti-FHbp resistance. Combining anti-NspA antibodies with anti-FHbp antibodies can overcome resistance. Meningococcal vaccines that target both NspA and FHbp are likely to confer greater protection than either antigen alone.
Protein A Is Released into the Staphylococcus aureus Culture Supernatant with an Unprocessed Sorting Signal
Authors: O'Halloran Dara P. , Wynne Kieran , Geoghegan Joan A.
Published: February 2015

The immunoglobulin binding protein A (SpA) of
Staphylococcus aureus
is synthesized as a precursor with a C-terminal sorting signal. The sortase A enzyme mediates covalent attachment to peptidoglycan so that SpA is displayed on the surface of the bacterium. Protein A is also found in the extracellular medium, but the processes involved in its release are not fully understood. Here, we show that a portion of SpA is released into the supernatant with an intact sorting signal, indicating that it has not been processed by sortase A. Release of SpA was reduced when the native sorting signal of SpA was replaced with the corresponding region of another sortase-anchored protein (SdrE). Similarly, a reporter protein fused to the sorting signal of SpA was released to a greater extent than the same polypeptide fused to the SdrE sorting signal. Released SpA protected bacteria from killing in human blood, indicating that it contributes to immune evasion.
The Bacteroides thetaiotaomicron Protein Bacteroides Host Factor A Participates in Integration of the Integrative Conjugative Element CTnDOT into the Chromosome
Authors: Ringwald Kenneth , Gardner Jeffrey
Published: February 2015

CTnDOT is a conjugative transposon found in
Bacteroides
species. It encodes multiple antibiotic resistances and is stimulated to transfer by exposure to tetracycline. CTnDOT integration into the host chromosome requires IntDOT and a previously unknown host factor. We have identified a protein, designated BHFa (
Bacteroides
host factor A), that participates in integrative recombination. BHFa is the first host factor identified for a site-specific recombination reaction in the CTnDOT family of integrative and conjugative elements. Based on the amino acid sequence of BHFa, the ability to bind specifically to 4 sites in the
attDOT
DNA, and its activity in the integration reaction, BHFa is a member of the IHF/HU family of nucleoid-associated proteins. Other DNA bending proteins that bind DNA nonspecifically can substitute for BHFa in the integration reaction.

IMPORTANCE
Bacteroides
species are normal members of the human colonic microbiota. These species can harbor and spread self-transmissible genetic elements (integrative conjugative elements [ICEs]) that contain antibiotic resistance genes. This work describes the role of a protein, BHFa, and its importance in the integration reaction required for the element CTnDOT to persist in
Bacteroides
host cells.
The Enhancer Binding Protein Nla6 Regulates Developmental Genes That Are Important for Myxococcus xanthus Sporulation
Authors: Giglio Krista M. , Zhu Chengjun , Klunder Courtney , Kummer Shelley , Garza Anthony G.
Published: February 2015

In the bacteriumMyxococcus xanthus, starvation triggers the formation of multicellular fruiting bodies containing thousands of stress-resistant spores. Recent work showed that fruiting body development is regulated by a cascade of transcriptional activators called enhancer binding proteins (EBPs). The EBP Nla6 is a key component of this cascade; it regulates the promoters of other EBP genes, including a downstream-functioning EBP gene that is crucial for sporulation. In recent expression studies, hundreds of Nla6-dependent genes were identified, suggesting that the EBP gene targets of Nla6 may be part of a much larger regulon. The goal of this study was to identify and characterize genes that belong to the Nla6 regulon. Accordingly, a direct repeat [consensus, C(C/A)ACGNNGNC] binding site for Nla6 was identified usingin vitroandin vivomutational analyses, and the sequence was subsequently used to find 40 potential developmental promoter (88 gene) targets. We showed that Nla6 binds to the promoter region of four new targets (asgE,exo, MXAN2688, and MXAN3259)in vitroand that Nla6 is important for their normal expressionin vivo. Phenotypic studies indicate that all of the experimentally confirmed targets of Nla6 are primarily involved in sporulation. These targets include genes involved in transcriptional regulation, cell-cell signal production, and spore differentiation and maturation. Although sporulation occurs late in development, all of the developmental loci analyzed here show an Nla6-dependent burst in expression soon after starvation is induced. This finding suggests that Nla6 starts preparing cells for sporulation very early in the developmental process.

IMPORTANCEBacterial development yields a remarkable array of complex multicellular forms. One such form, which is commonly found in nature, is a surface-associated aggregate of cells known as a biofilm. Mature biofilms are structurally complex and contain cells that are highly resistant to antibacterial agents. When starving, the model bacteriumMyxococcus xanthusforms a biofilm containing a thin mat of cells and multicellular structures that house a highly resistant cell type called a myxospore. Here, we identify the promoter binding site of the transcriptional activator Nla6, identify genes in the Nla6 regulon, and show that several of the genes in the Nla6 regulon are important for production of stress-resistant spores in starvation-inducedM. xanthusbiofilms.
Ugp and PitA Participate in the Selection of PHO-Constitutive Mutants
Authors: Iglesias Neves Henrique , Pereira Tuanny Fernanda , Yagil Ezra , Spira Beny
Published: February 2015

Mutations that cause the constitutive expression of the PHO regulon of
Escherichia coli
occur either in the
pst
operon or in the
phoR
gene, which encode, respectively, a high-affinity P
i
transport system and a histidine kinase sensor protein. These mutations are normally selected on glycerol-2-phosphate (G2P) as the carbon source in the presence of excess P
i
. The emergence of early PHO-constitutive mutants, which appear after growth for up to 48 h on selective medium, depends on the presence of
phoA
, which codes for a periplasmic alkaline phosphatase, while late mutants, which appear after 48 h, depend both on
phoA
and on the
ugp
operon, which encodes a glycerophosphodiester transport system. The emergence of the late mutants hints at an adaptive mutation process. PHO-constitutive
phoR
mutants appear only in a host that is mutated in
pitA
, which encodes an alternative P
i
transport system that does not belong to the PHO regulon. The conserved Thr
217
residue in the PhoR protein is essential for PHO repression.

IMPORTANCE
One of the principal ways in which bacteria adapt to new nutrient sources is by acquiring mutations in key regulatory genes. The inability of
E. coli
to grow on G2P as a carbon source is used to select mutations that derepress the PHO regulon, a system of genes involved in the uptake of phosphorus-containing molecules. Mutations in the
pst
operon or in
phoR
result in the constitutive expression of the entire PHO regulon, including alkaline phosphatase, which hydrolyzes G2P. Here we demonstrate that the
ugp
operon, another member of the PHO regulon, is important for the selection of PHO-constitutive mutants under prolonged nutritional stress and that
phoR
mutations can be selected only in bacteria lacking
pitA
, which encodes a secondary P
i
transport system.
Injuries in World Cup telemark skiing: a 5-year cohort study
Authors: Johansen Melissa Woll , Steenstrup Sophie E , Bere Tone , Bahr Roald , Nordsletten Lars
Published: February 2015

Background

There are limited data on injuries in World Cup (WC) telemark skiing.

Objective

To describe the injury incidence and injury pattern seen among WC telemark skiers during the competitive season.

Methods

We interviewed all WC athletes (or their coach, if the athlete was not present) at the end of five winter seasons from 2008 until 2013. All acute injuries occurring in the competitive season that required the attention of medical personnel were registered. Exposure was calculated based on the official International Ski Federation (FIS) results database.

Results

149 acute injuries were registered during 565 WC skier seasons. The absolute injury incidence was 26.4 injuries per 100 athletes per season (95% CI 22.1 to 30.6), higher for females than males (risk ratio (RR) 1.49, 95% CI 1.07 to 2.08). During the FIS WC competitions, 69 injuries were registered, corresponding to a relative incidence of 8.2 injuries per 1000 runs (95% CI 6.3 to 10.1). The most frequently injured body part was the knee (21%) followed by the hand-finger-thumb (20%), ankle (13%) and shoulder/clavicle (13%). The absolute risk of knee and shoulder/clavicle injuries was higher for females versus males (RR for knee injuries 2.72, 95% CI 1.35 to 5.51; RR for shoulder/clavicle injuries 2.55, 95% CI 1.06 to 6.14). No differences were detected in the injury incidence between disciplines.

Conclusions

Female telemark skiers are at 1.5 times greater risk of injury than male skiers. The most commonly injured body part was the knee. The risk of knee and shoulder/clavicle injuries was higher for female athletes than for male athletes.
Association between sense of coherence in adolescence and social benefits later in life: a 12-year follow-up study
Authors: Würtz Else Toft , Fonager Kirsten , Mortensen Jens Tølbøll
Published: February 2015

Objectives

Local government concerns over expenditure on social and healthcare are growing. The aim of the present study was to explore the association between a weak ‘sense of coherence’ (SOC) in teens and their subsequent risk of receiving social and healthcare benefits during young adulthood, and to monitor how SOC developed during this period.

Design

Prospective cohort study.

Setting

North Denmark Region.

Participants

773 Pupils from seventh and eighth forms who answered a questionnaire in 1998.

Outcome measures

Different social benefits (from the Danish DREAM database embracing disbursed public social benefits). Change in SOC score from 1998 to 2010.

Results

722 had answered seven items of the original SOC-13 questionnaire (denoted by SOC-7). Girls with a weak SOC-7 (the lowest 1st quartile) in 1998 had a significantly increased risk of receiving unemployment benefits (RR 1.3 (1.1 to 1.6)), social assistance (RR 1.8 (1.3 to 2.5)) and sickness benefits (RR 1.5 (1.2 to 2.0)) compared with girls with a strong SOC-7. For boys, only minor protective and non-significant differences were found. The SOC answers from 1998 and 2010 were compared (n=394). SOC increased significantly and mostly in girls.

Conclusions

SOC-7 may serve as a predictor for social life event outcomes and hence facilitate an early identification and a selective approach to support teenage girls with a weak SOC. From adolescence to young adulthood, SOC-7 was of a relatively unstable nature.
Sleep and use of electronic devices in adolescence: results from a large population-based study
Authors: Hysing Mari , Pallesen Ståle , Stormark Kjell Morten , Jakobsen Reidar , Lundervold Astri J , Sivertsen Børge
Published: February 2015

Objectives

Adolescents spend increasingly more time on electronic devices, and sleep deficiency rising in adolescents constitutes a major public health concern. The aim of the present study was to investigate daytime screen use and use of electronic devices before bedtime in relation to sleep.

Design

A large cross-sectional population-based survey study from 2012, the youth@hordaland study, in Hordaland County in Norway.

Setting

Cross-sectional general community-based study.

Participants

9846 adolescents from three age cohorts aged 16–19. The main independent variables were type and frequency of electronic devices at bedtime and hours of screen-time during leisure time.

Outcomes

Sleep variables calculated based on self-report including bedtime, rise time, time in bed, sleep duration, sleep onset latency and wake after sleep onset.

Results

Adolescents spent a large amount of time during the day and at bedtime using electronic devices. Daytime and bedtime use of electronic devices were both related to sleep measures, with an increased risk of short sleep duration, long sleep onset latency and increased sleep deficiency. A dose–response relationship emerged between sleep duration and use of electronic devices, exemplified by the association between PC use and risk of less than 5 h of sleep (OR=2.70, 95% CI 2.14 to 3.39), and comparable lower odds for 7–8 h of sleep (OR=1.64, 95% CI 1.38 to 1.96).

Conclusions

Use of electronic devices is frequent in adolescence, during the day as well as at bedtime. The results demonstrate a negative relation between use of technology and sleep, suggesting that recommendations on healthy media use could include restrictions on electronic devices.
Cohort differences in the levels and trajectories of frailty among older people in England
Authors: Marshall Alan , Nazroo James , Tampubolon Gindo , Vanhoutte Bram
Published: February 2015

Background

The level of frailty in the older population across age cohorts and how this changes is a factor in determining future care costs and may also influence the extent of socioeconomic and gender inequalities in frailty.

Methods

We model cohort-specific trajectories in frailty among the community dwelling population older than 50 years, using five waves (2002–2010) of the English Longitudinal Study of Ageing. We stratify our analysis by wealth and gender and use a frailty index, based on accumulation of ‘deficits’.

Results

For males and females between the ages of 50 and 70 in 2002, frailty trajectories for adjacent age cohorts converge. However, levels of frailty are higher in recent compared with earlier cohorts at the older ages (for cohorts aged over 70 in 2002). These cohort differences are largest in the poorest wealth group, while for the most affluent, frailty trajectories overlap across all adjacent cohorts suggesting no change across cohorts.

Conclusions

A key driver of the cohort differences in frailty that we observe is likely to be increased survival of frail individuals. Importantly, this paper illustrates that the social conditions experienced across the wealth distribution impacts on the rate of deficit accumulation in older populations. Our results on trajectories of frailty between 2002 and 2010 are pessimistic and, in the context of rising life expectancies, suggest that poorer older people in particular spend additional years of life in a frail state.
Antifreeze proteins as gas hydrate inhibitors
Authors: Walker Virginia K. , Zeng Huang , Ohno Hiroshi , Daraboina Nagu , Sharifi Hassan , Bagherzadeh S. Alireza , Alavi Saman , Englezos Peter
Published: February 2015

Certain organisms survive low temperatures using a range of physiological changes including the production of antifreeze proteins (AFPs), which have evolved to adsorb to ice crystals. Several of these proteins have been purified and shown to also inhibit the crystallization of clathrate hydrates. They have been found to be effective against structure II (sII) hydrates formed from the liquid tetrahydrofuran, sI and sII gas hydrates formed from single gases, as well as sII natural gas hydrates using a mixture of three gases, as assessed using a variety of instrumentation including stirred reactors, differential scanning calorimetry, nuclear magnetic resonance, Raman spectroscopy, and X-ray powder diffraction. For the most part, AFPs are equal to or more effective than the commercial kinetic hydrate inhibitor (KHI) polyvinylpyrolidone, even under field conditions where saline and liquid hydrocarbons are present. Enclathrated gas analysis has revealed that the adsorption of AFPs to the hydrate surface is distinct from tested commercial KHIs and results in properties that should make these proteins more valuable in some field applications. Efforts to overcome the difficulties of recombinant protein production are ongoing, but in silico models of AFP adsorption to hydrates may offer the opportunity to design commercial KHIs for hydrocarbon recovery and transport with all the attributes of these AFP ”green inhibitors”, including their benefits for human and environmental safety.
Dynamics of spherical stars with structure scalars and R + ϵRn cosmology
Authors: Sharif M. , Yousaf Z.
Published: February 2015

We study the role of the R + ϵRn model on the dynamical evolution of radiating anisotropic and shearing viscous relativistic spherical stellar structures. In this context, we calculate modified versions of scalar functions (previously defined by L. Herrera et al. Phys. Rev. D, 79, 064025 (2009). doi:10.1103/PhysRevD.79.064025 ) for the problem under consideration and then associate them with the physical parameters. The Weyl tensor as well as other matter variables with extra curvature terms coming from the model are related and find shear and expansion evolution equations. We conclude that structure scalars along with f(R) degrees of freedom have vital importance in the dynamics of spherical compact systems.
Identification of nuclear low-copy genes and their phylogenetic utility in rosids
Authors: Wang Baohua , Zhang Yan , Wei Peipei , Sun Miao , Ma Xiaofei , Zhu Xinyu
Published: February 2015

By far, the interordinal relationships in rosids remain poorly resolved. Previous studies based on chloroplast, mitochondrial, and nuclear DNA has produced conflicting phylogenetic resolutions that has become a widely concerned problem in recent phylogenetic studies. Here, a total of 96 single-copy nuclear gene loci were identified from the KOG (eukaryotic orthologous groups) database, most of which were first used for phylogenetic analysis of angiosperms. The orthologous sequence datasets from completely sequenced genomes of rosids were assembled for the resolution of the position of the COM (Celastrales–Oxalidales–Malpighiales) clade in rosids. Our analysis revealed strong and consistent support for CM topology (the COM clade as sister to the malvids). Our results will contribute to further exploring the underlying cause of conflict between chloroplast, mitochondrial, and nuclear data. In addition, our study identified a few novel nuclear molecular markers with potential to investigate the deep phylogenetic relationship of plants or other eukaryotic taxonomical groups.
Green Tea Polyphenol Epigallocatechin-3-Gallate Attenuates TNF-α-Induced Intercellular Adhesion Molecule-1 Expression and Monocyte Adhesion to Retinal Pigment Epithelial Cells
Authors: Thichanpiang Peeradech , Wongprasert Kanokpan
Published: February 2015

Epigallocatechin-3-gallate (EGCG) is a major polyphenol component of green tea (Camellia sinensis) and demonstrates anti-oxidant, anticancer and anti-inflammatory properties. EGCG has been shown to protect retinal pigment epithelium (RPE) against oxidative stress-induced cell death. The pathogenesis of diseases in the retina is usually initiated by local inflammation at the RPE cell layer, and inflammation is mostly associated with leukocyte migration and the secretion of pro-inflammatory cytokines. Whether EGCG can modulate the cytokine-induced inflammatory response of RPE, particularly leukocyte migration, has not been clearly elucidated, and was therefore the objective of this study. ARPE-19 cells were cultured with different concentrations of TNF-α in the presence or absence of EGCG to different time points. Intracellular reactive oxygen species (ROS) levels were determined. Intercellular adhesion molecule (ICAM)-1 and phosphor-NF-κB and IκB expression were determined by Western blot analysis. Phosphor-NF-κB nuclear translocation and monocyte–RPE adhesion were investigated using immunofluorescence confocal laser scanning microscopy. Scanning electron microscopy (SEM) was carried out to further determine the ultrastructure of monocyte–RPE adhesion. The results demonstrated that TNF-α modulated inflammatory effects in ARPE-19 by induction of ROS and up-regulation of ICAM-1 expression. Moreover, TNF-α-induced phosphor-NF-κB nuclear translocation, increased phosphor-NF-κB expression and IκB degradation, and increased the degree of monocyte–RPE adhesion. Pretreating the cells with EGCG ameliorated the inflammatory effects of TNF-α. The results indicated that EGCG significantly exerts anti-inflammatory effects in ARPE-19 cells, partly as a suppressor of TNF-α signaling and that the inhibition was mediated via the NF-κB pathway.
Probing CP violation at LBNE with reactor experiments
Authors: Dutta Debajyoti , Bora Kalpana
Published: February 2015

In this work, we have explored the possibilities of improving CP violation (CPV) discovery potential of newly planned Long-Baseline Neutrino Experiment (LBNE), USA, by combining with data from reactors. The third mixing angle θ13 is now very precisely measured and this precise measurement of θ13 helps in the measurement of CPV. Here, CPV is studied with and without data from reactors. The impact of placing a neutrino data (ND) is also studied. It is found that CPV discovery potential of LBNE with ND increases when combined with data from reactors. With a far detector of 35 kt, it is possible to obtain 5σ sensitivity of CPV when run for 5 years in ν and 5 years in [Formula: see text] mode. When normal hierarchy is assumed, CPV sensitivity is maximum. CPV discovery is possible by combining 5 years neutrino data from LBNE with 3 years anti-neutrino data from reactors. This study reveals that CPV can also be discovered at 5σ cl in inverted mass hierarchy (IH) mode when appearance measurement of LBNE is combined with reactors.
Analysis of longitudinal momentum distribution data of core fragment coming from 9Be(11Be, 10Be+n)9Be stripping reaction
Authors: Singh Monika , Kharab Rajesh , Singh Ram Mehar
Published: February 2015

Here we investigate the effects of first-order correction to eikonal approximation in the analysis of longitudinal momentum distribution (LMD) data of outgoing core fragment 10 Be coming from 9 Be (11 Be , 10 Be + n )9 Be stripping reaction at 60 MeV/A incident energy. It is found that the inclusion of first-order correction term alters the tail region significantly which in turn improves matching between the data and prediction.
Research on Wind-Induced Reliability of Double Column Suspended Guyed Tower in Strong Wind Area
Authors: Xiao Zheng-Zhi , Liu Hai-Lin , Li Zheng-Liang , Yu Deng-Ke , Li Ying-Gang
Published: February 2015

The ultra-high voltage transmission line is long, which needs to pass through the various complex terrains. In order to ensure the safe structural system, understanding and grasping the wind-induced response and reliability of double column suspended guyed tower (DCSGT) in strong wind area of Gobi Desert are basic requirements. Through combining the conditional probability density of wind speed and frequency function of wind direction, the successive-type joint distribution model of wind speed and direction is obtained by multiplication theorem. In accordance with the principle of equivalent extreme value event, through utilizing the statistical moment point estimation method, the first four-order statistical moment information of equivalent extreme value variables is solved. The probability density function (PDF) of DCSGT response is calculated in accordance with these statistical moments. The dynamic reliability index and failure probability of DCSGT are solved by the moment method.
A Two-stage Parametric Identification of Strong Nonlinear Structural Systems with Incomplete Response Measurements
Authors: Liu Lijun , Lei Ying , He Mingyu
Published: February 2015

Compared with the identification of linear structural parameters, it is more difficult to conduct parametric identification of strong nonlinear structural systems, especially when only incomplete structural responses are available. Although the extended Kalman filter (EKF) is useful for structural identification with partial measurements of structural responses and can be extended for the identification of nonlinear structures, EKF approximates nonlinear system through Taylor series expansion and is therefore not effective for the identification of strong nonlinear structural systems. Other approaches such as the unscented Kalman filter (UKF) have been proposed for the identification of strong nonlinear problems. Based on the fact that nonlinearities exist in local areas of structures, a straightforward two-stage identification approach is proposed in this paper for the identification of strong nonlinear structural parameters with incomplete response measurements. In the first stage, the locations of nonlinearities are identified based on the EKF for the identification of the equivalent linear structures. In the second stage, the UKF is utilized to identify the parameters of strong nonlinear structural systems. Therefore, the parametric identification of strong nonlinear structural parameters is simplified by the proposed approach. Several numerical examples with different nonlinear models and locations are used to validate the proposed approach.
Trapping of buoyant fluids in fault-bound structures
Authors: Yielding Graham
Published: February 2015

Structural traps comprise surfaces having high capillary threshold pressure for fluid phases such as hydrocarbon or CO
2
. Traps may include top-seal, bottom-seal and side-seal surfaces, the latter commonly being faults. Faults may form seals by juxtaposition or by fault-rock. The first step in fault characterization is mapping the distribution of offset layers at the fault surface. This pattern (‘Allan diagram’) comprises the separation polygons. These same lines define the displacement distribution on the fault, and so can also be used as a quality-check of the interpretation. They are also a fundamental part of horizon maps. Despite their central role in subsurface mapping, construction of fault polygons remains a weak step in the workflow in many E&P companies. To characterize fault-rock effects, it is usual to consider an upscaled proxy such as shale gouge ratio (SGR), with the assumption that high SGR represents clay smears and low SGR represents clay-poor fault rock. Suitable estimates of hydraulic properties can then be applied to different parts of the fault surface. The property distribution on the fault side-seals allows an estimate of the maximum hydrocarbon column height that the trap might contain, by comparing the multiple potential leak-points and finding which predicts the shallowest contact.
To govern IT, or not to govern IT?
Authors: Juiz Carlos , Toomey Mark
Published: February 2015

Business leaders may bemoan the burdens of governing IT, but the alternative could be much worse.
Online privacy
Authors: Kugler Logan
Published: February 2015

How do the U.S., Europe, and Japan differ in their approaches to data protection --- and what are they doing about it?
Far-sighted thinking about deleterious computer-related events
Authors: Neumann Peter G.
Published: February 2015

Considerably more anticipation is needed for what might seriously go wrong.
What's the best way to teach computer science to beginners?
Authors: Guzdial Mark
Published: February 2015

The
Communications
Web site, http://cacm.acm.org, features more than a dozen bloggers in the BLOG@CACM community. In each issue of
Communications
, we'll publish selected posts or excerpts.

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Mark Guzdial questions the practice of teaching programming to new CS students by having them practice programming largely on their own.
Papers everyone should read
Authors: Gropp Bill
Published: February 2015

Are there papers that you think everyone should read? An old favorite or a new result? In each issue of SIGHPC Connect, we present papers suggested by our membership.
Bard College
Authors: Shuai Xiangyin
Published: February 2015

The workshop was very successful because the participants (about 25 people) consisted of Bard students, staff members, professors, and senior citizens from the Bard College Lifetime Learning Institute. We started the workshop by showing the participants a YouTube video of President Obama kicking off the Hour of Code. Everyone was encouraged and ready to learn. We then used the MIT App Inventor and taught everyone how to make the HelloPurr and Digital Doodle apps. Everyone successfully finished creating the two apps, and some participants even tried to come up with new ones.
U.S. Air Force Academy
Authors: Hadfield Steve
Published: February 2015

One of the two USAFA CS Ed Week events was a school-wide Hour of Code led by Tess Livingston and Matt Kiser at Woodmen-Roberts Elementary School in Colorado Springs, Colorado. The event kicked off with a visit from a Nao robot and his human friends from the Department of Computer Science at the United States Air Force Academy. With the help of Cadet Lilly Warner, the Nao robot demonstrated its dexterity with a Tai Chi Chuan exercise, sang "Let it go" from the Frozen soundtrack, danced to "Happy" from Despicable Me, and conversed with the children motivating them to learn how to write code. Follow on activities in the computer lab with Mr. Kiser focused on the Hour of Code tutorials from code.org and tynker.com. The children from grades K through 5 all had a great time.
Drexel University
Authors: Boland Kerry
Published: February 2015

As part of Drexel's annual celebration of National Computer Science Education Week (November 17 -- 21, 2014), Drexel student tech volunteer organization DUCSTeach (Drexel University Computer Science Teachers) visited middle school students at St. Francis de Sales School on Wednesday, Nov. 17, 2014 to lead an "Hour of Code," where volunteers gave introductory computer science activities designed to demystify coding, and show students that anyone can learn the basics to be a maker, a creator or an innovator
SIGCSE symposium preview
Authors: Decker Adrienne , Eiselt Kurt
Published: February 2015

And now for a word about the upcoming SIGCSE 2015 Symposium. In order not to disturb the symposium chairs (Adrienne Decker and Kurt Eiselt) while they are busy preparing for the conference, we have installed an app that allows us to listen in on their weekly Skype meeting, already in progress…
Broadening participation and RESPECT
Authors: Barnes Tiffany , Thiruvathukal George
Published: February 2015

In computing and STEM fields, broadening participation is both a matter of driving creativity and innovation and a matter of equity. It is critical that we, as the CS education community, improve inclusion of diverse people, especially those from underrepresented populations. Globally, underrepresentation differs regionally and culturally by gender, race, ethnicity, socio-economic advantage, physical, mental, and cognitive ability, and LGBT status. Lest we think that this is a minority-only issue, consider developing countries or the poor of every nation, where computing could help build the economy, health, education, and financial systems.
ACM education council report
Authors: Fitzgerald Sue
Published: February 2015

At the ACM Education Council meeting in mid-September, 2014, issues of importance to those interested in computing education were discussed. In a brainstorming activity, Education Council members were asked to suggest topics of emerging importance. Among other ideas, members discussed ACM's international membership growth, the establishment of cybersecurity education curriculum guidelines, encouraging the study of computing in K-12 and promoting diversity.
MPEG column
Authors: Timmerer Christian
Published: February 2015

The 110th MPEG meeting was held at the Strasbourg Convention and Conference Centre featuring the following highlights:

• The future of video coding standardization

• Workshop on media synchronization

• Standards at FDIS: Green Metadata and CDVS

• What's happening in MPEG-DASH?

Additional details about MPEG's 110th meeting can be also found here including the official press release and all publicly available documents.
Raw Networking
Authors: Neville-Neil George
Published: February 2015

Dear KV, The company I work for has decided to use a wireless network link to reduce latency, at least when the weather between the stations is good. It seems to me that for transmission over lossy wireless links we’ll want our own transport protocol that sits directly on top of whatever the radio provides, instead of wasting bits on IP and TCP or UDP headers, which, for a point-to-point network, aren’t really useful.
Use of the Blacksea Water Containing Hydrogen Sulfide (H2s) as a Fuel Cell Fuel
Authors: Sanli Ayse Elif , Canan Belkis , AytaÇ Aylin
Published: February 2015

Black Seawater is a hydrogen source because of high hydrogen sulfide (H2S) content. H2S is the chemical electron donor. Energy can be generated from H2S by the oxidation or by the electro-oxidation. Electrochemical systems such as fuel cells are the powerful alternative to recovery of sulfur and to generate energy. In the present study Black seawater with H2S content has been investigated as a fuel cell fuel. The electrochemical behaviors of metal sulfides have been performed in the solution containing H2S. NiS has showed the catalytic effect towards the electro-oxidation of HS- ions. A fuel cell constructed with Ni anode and Pt cathode has provided the maximum power density of 23 mWcm-2 at the potential of 300 mV and 75 mAcm-2.
Analysis of Porosity and Tortuosity in a 2D Selected Region of Solid Oxide Fuel Cell Cathode Using the Lattice Boltzmann Method
Authors: Espinoza Mayken , Sundén Bengt , Andersson Martin , Yuan Jinliang
Published: February 2015

The solid oxide fuel cell (SOFC) is one of the most promising devices for getting electrical energy. There are a lot of advantages in the use of SOFCs such as their efficiency, higher electrical and thermal power production and reduction of the emission of polluting gases. Modeling the SOFC at downscale is one of the most important challenges in fuel cell (FC) research. Knowing the behavior of materials to this scale is a helpful tool to predict the physical and chemical phenomena within the FCs, improve their efficiency and reduce material costs. At micro- and mesoscale, Lattice Boltzmann Method (LBM) appears as a powerful tool for modeling fuel cells. LBM has been proven suitable for solving several physical phenomena in complex geometries such as porous media. Using the D2Q9 LBM scheme, the velocity field for a selected section of an SOFC cathode is determined. This velocity field is shown in 2D and 3D graphics. The porosity and tortuosity for this selected region are calculated and compared with previous results.