bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphological and molecular phylogenetic analysis of the high triglyceride‐producing marine diatom, Fistulifera solaris sp. nov. (Bacillariophyceae)
Authors: Matsumoto Mitsufumi , Mayama Shigeki , Nemoto Michiko , Fukuda Yorikane , Muto Masaki , Yoshino Tomoko , Matsunaga Tadashi , Tanaka Tsuyoshi
Published: September 2014

Fistulifera sp. strain JPCC DA0580, a marine pennate diatom, contains extremely high levels of intracellular triglyceride and has been suggested as a promising source of feedstock for biodiesel fuels. JPCC DA0580 was isolated from a mangrove swamp located in Sumiyo Bay below the mouths of the Sumiyo and Yakugachi Rivers in Amami‐Ohshima, Kagoshima, Japan. In this study, the morphology and the 18S rDNA sequence of JPCC DA0580 were compared with those of other Fistulifera strains. JPCC DA0580 possesses morphological characters of the genus Fistulifera, namely lightly silicified frustules, a distinct median costa (raphe sternum), and a wart‐like central pore (fistula). Morphometric analysis revealed that JPCC DA0580 differs from other Fistulifera species by the presence of a valve with coarser striation and coarser areolation. On the basis of 18S rDNA phylogeny, JPCC DA0580 formed a well‐supported clade with other members of the Fistulifera species complex, although the number of nucleotide substitutions was highest in JPCC DA0580. Our results led us to propose the taxonomic name Fistulifera solaris sp. nov. for JPCC DA0580.
Homeownership and Housing Displacement After Hurricane Katrina Among Low‐Income African‐American Mothers in New Orleans
Authors: Fussell Elizabeth , Harris Elizabeth
Published: September 2014

Objective

We evaluate the effect of pre‐Katrina housing tenure and postdisaster financial resources on the odds of housing displacement after Hurricane Katrina for a sample of low‐income African‐American mothers.

Methods

Using longitudinal data from a sample of low‐income African‐American mothers with pre‐Katrina measures of housing tenure and individual characteristics and post‐Katrina indicators of disaster impacts, we estimate a multinomial logistic regression model predicting post‐Katrina housing outcomes.

Results

Among low‐income African‐American mothers, homeowners’ odds of being in their pre‐Katrina home rather than a new home are greater than those of renters, while renters’ odds of being in a pre‐Katrina home are greater than those of subsidized housing residents, ceteris paribus. The difference in homeowners’ and renters’ odds is reduced to insignificance when access to private insurance is added to the model, although the difference for subsidized housing residents remains.

Conclusion

Homeownership and disaster assistance protect against housing displacement. Renters, especially those in subsidized housing, were more vulnerable to housing loss after this disaster.
Arabidopsis RAV1 transcription factor, phosphorylated by SnRK2 kinases, regulates the expression of ABI3,ABI4, and ABI5 during seed germination and early seedling development
Authors: Feng Cui‐Zhu , Chen Yun , Wang Cun , Kong You‐Han , Wu Wei‐Hua , Chen Yi‐Fang
Published: September 2014

The phytohormone abscisic acid (ABA) modulates a number of processes during plant growth and development. In this study, the molecular mechanism of Arabidopsis RAV (Related to ABI3/VP1) transcription factor RAV1 involving ABA signaling was investigated. RAV1‐underexpressing lines were more sensitive to ABA than wild‐type plants during seed germination and early seedling development, whereas RAV1‐overexpressing lines showed strong ABA‐insensitive phenotypes. Overexpression of RAV1 repressed ABI3, ABI4, and ABI5 expression, and RAV1 bound to the ABI3, ABI4, and ABI5 promoters in vitro and in vivo, indicating that RAV1 directly down‐regulates the expression of ABI3, ABI4, and ABI5. The interruption of ABI5 function in RAV1‐U abi5 plants abolished the ABA‐hypersensitive phenotype of RAV1‐U plants, demonstrating that ABI5 is epistatic to RAV1. RAV1 interacted with SNF1‐RELATED PROTEIN KINASE SnRK2.2, SnRK2.3 and SnRK2.6 in the nucleus. In vitro kinase assays showed that SnRK2.2, SnRK2.3 and SnRK2.6 phosphorylated RAV1. Transient expression assays revealed that SnRK2.2, SnRK2.3 and SnRK2.6 reduced the RAV1‐dependent repression of ABI5, and the ABA‐insensitive phenotype of the RAV1‐overexpressing line was impaired by overexpression of SnRK2.3 in the RAV1 OE3 plants. Together, these results demonstrated that the Arabidopsis RAV1 transcription factor plays an important role in ABA signaling by modulating the expression of ABI3, ABI4, and ABI5, and that its activity is negatively affected by SnRK2s.
Bounding Lagrangian widths via geodesic paths
Authors: Borman Matthew Strom , McLean Mark
Published: September 2014

The width of a Lagrangian is the largest capacity of a ball that can be symplectically embedded into the ambient manifold such that the ball intersects the Lagrangian exactly along the real part of the ball. Due to Dimitroglou Rizell, finite width is an obstruction to a Lagrangian admitting an exact Lagrangian cap in the sense of Eliashberg–Murphy. In this paper we introduce a new method for bounding the width of a Lagrangian$Q$by considering the Lagrangian Floer cohomology of an auxiliary Lagrangian$L$with respect to a Hamiltonian whose chords correspond to geodesic paths in$Q$. This is formalized as a wrapped version of the Floer–Hofer–Wysocki capacity and we establish an associated energy–capacity inequality with the help of a closed–open map. For any orientable Lagrangian$Q$admitting a metric of non-positive sectional curvature in a Liouville manifold, we show the width of$Q$is bounded above by four times its displacement energy.
Spectral theory for the -Boson particle system
Authors: Borodin Alexei , Corwin Ivan , Petrov Leonid , Sasamoto Tomohiro
Published: September 2014

We develop spectral theory for the generator of the $q$-Boson (stochastic) particle system. Our central result is a Plancherel type isomorphism theorem for this system. This theorem has various implications. It proves the completeness of the Bethe ansatz for the $q$-Boson generator and consequently enables us to solve the Kolmogorov forward and backward equations for general initial data. Owing to a Markov duality with $q$-TASEP ($q$-deformed totally asymmetric simple exclusion process), this leads to moment formulas which characterize the fixed time distribution of $q$-TASEP started from general initial conditions. The theorem also implies the biorthogonality of the left and right eigenfunctions. We consider limits of our $q$-Boson results to a discrete delta Bose gas considered previously by van Diejen, as well as to another discrete delta Bose gas that describes the evolution of moments of the semi-discrete stochastic heat equation (or equivalently, the O’Connell–Yor semi-discrete directed polymer partition function). A further limit takes us to the delta Bose gas which arises in studying moments of the stochastic heat equation/Kardar–Parisi–Zhang equation.
Jordan property for groups of birational selfmaps
Authors: Prokhorov Yuri , Shramov Constantin
Published: September 2014

Assuming a particular case of the Borisov–Alexeev–Borisov conjecture, we prove that finite subgroups of the automorphism group of a finitely generated field over $\mathbb{Q}$ have bounded orders. Further, we investigate which algebraic varieties have groups of birational selfmaps satisfying the Jordan property. Unless explicitly stated otherwise, all varieties are assumed to be algebraic, geometrically irreducible and defined over an arbitrary field $\Bbbk$ of characteristic zero.
Numerical Study of Turbulent Flow and Convective Heat Transfer Characteristics in Helical Rectangular Ducts
Authors: Xing Yunfei , Zhong Fengquan , Zhang Xinyu
Published: September 2014

Three-dimensional turbulent forced convective heat transfer and its flow characteristics in helical rectangular ducts are simulated using SST k–ω turbulence model. The velocity field and temperature field at different axial locations along the axial direction are analyzed for different inlet Reynolds numbers, different curvatures, and torsions. The causes of heat transfer differences between the inner and outer wall of the helical rectangular ducts are discussed as well as the differences between helical and straight duct. A secondary flow is generated due to the centrifugal effect between the inner and outer walls. For the present study, the flow and thermal field become periodic after the first turn. It is found that Reynolds number can enhance the overall heat transfer. Instead, torsion and curvature change the overall heat transfer slightly. But the aspect ratio of the rectangular cross section can significantly affect heat transfer coefficient.
Surface Topography of Additive Manufacturing Parts Using a Finite Difference Approach
Authors: Jamiolahmadi Saeed , Barari Ahmad
Published: September 2014

Inspection of surface integrity in additive manufacturing (AM) parts essentially needs a detailed understanding of their actual surface topography. Today's optical surface topography and roughness measurement sensors only provide information of the discrete points measured from the manufactured surface and not a detailed reconstruction of the surface topography. This paper presents a finite difference approach for reconstruction of the surface topography using sample measured data points. The developed methodology can be used in the surface quality inspection of the additive manufactured parts, their surface texture modeling, surface integrity analysis, and in planning for the required postprocessing or down-stream surface finish processes suitable for them. The methodology is fully implemented, and variety of experiments is conducted. The results show that the developed methodology is successful to reconstructed surface topography of the AM parts.
Development of plasma etching processes to pattern sub-15 nm features with PS-b-PMMA block copolymer masks: Application to advanced CMOS technology
Authors: Delalande Michaël , Cunge Gilles , Chevolleau Thierry , Bézard Philippe , Archambault Sophie , Joubert Olivier , Chevalier Xavier , Tiron Raluca
Published: September 2014

The best strategies to transfer nanoholes formed from the self-assembly of Polystyren/Polymethylmethacrylate (PS/PMMA) based block copolymers into a silicon substrate are investigated. The authors show that specific issues are associated with the plasma etching of materials through the PS masks obtained from self-assembly. Indeed, due to the nanometric size of sub-15 nm contact holes and to their inherently high aspect ratio (>5), plasma etching processes typically used to etch SiO2 and silicon in the microelectronic industry must be revisited. In particular, processes where the etching anisotropy relies on the formation of passivation layer on the feature's sidewalls are not adapted to nanometric dimensions because these layers tend to fill the holes leading to etch stop issues. At the same time, the ion bombarding energy must be increased as compared to a typical process to overcome differential charging effects in high aspect-ratio nanoholes. However, by developing appropriate processes—such as synchronized pulsed plasmas—the authors show that it is possible to etch 70 nm deep holes into silicon by using block copolymers and a hard mask strategy. Another interesting observation resulting from these experiments is that for sub-15 nm holes, a critical dimension (CD)-dispersion of few nm leads to strong aspect ratio dependent etch rates. In addition, a careful analysis of the dispersion of the holes' CD after each plasma steps shows that the CD control is far from satisfying advanced CMOS technology requirements. A critical issue comes from the uncompleted PMMA removal from the PS/PMMA matrix during our self-assembly process: variable amount of PMMA remains in the PS holes, leading to microloading effects during the etching steps, which in turn generates CD-control loss. This problem perhaps can be solved by combining UV exposure to acetic acid treatment to provide PS masks free of PMMA residues before plasma etching.
Large area infrared frequency selective surface with dimensions reproducible by optical lithography
Authors: D' Archangel Jeffrey A. , Shelton David J. , Hudgins Robert , Poutous Menelaos K. , Boreman Glenn D.
Published: September 2014

An infrared frequency selective surface (FSS) with absorptive resonance near 6.5 μm was fabricated by electron-beam lithography using a patch design with dimensions reproducible by optical-projection lithography. By selective wet etching along with reactive-ion etching, the sample was divided into miniature FSS particles, which were released from the substrate. A large number of such particles could be implemented as a large area, conformal coating. Spectral reflectivity of the full FSS array as well as the FSS particles was measured and compared to electromagnetic simulations. To show the feasibility of this approach, the full array FSS design was fabricated using a g-line (λ = 436 nm) 5× projection lithography stepper and compared to the array fabricated by electron-beam lithography using scanning electron microscopy and Fourier transform infrared spectroscopy. Even though the resolution of the g-line stepper led to a poor fabrication output, the optical resonance was found to be robust, with only slight detuning attributed to the changes in unit cell geometry. This work highlights the utility of optical-projection lithography, coupled with the releasable particle fabrication procedure, to create a large area, conformal coating with specific infrared spectral properties.
Impact of the Steepness of the Slope on the Biomechanics of World Cup Slalom Skiers
Authors: Supej Matej , Hébert-Losier Kim , Holmberg Hans-Christer
Published: September 2014

Purpose:

Numerous environmental factors can affect alpine-ski-racing performance, including the steepness of the slope. However, little research has focused on this factor. Accordingly, the authors’ aim was to determine the impact of the steepness of the slope on the biomechanics of World Cup slalom ski racers.

Methods:

The authors collected 3-dimensional kinematic data during a World Cup race from 10 male slalom skiers throughout turns performed on a relatively flat (19.8°) and steep (25.2°) slope under otherwise similar course conditions.

Results:

Kinematic data revealed differences between the 2 slopes regarding the turn radii of the skis and center of gravity, velocity, acceleration, and differential specific mechanical energy (all P < .001). Ground-reaction forces (GRFs) also tended toward differences (P = .06). Examining the time-course behaviors of variables during turn cycles indicated that steeper slopes were associated with slower velocities but greater accelerations during turn initiation, narrower turns with peak GRFs concentrated at the midpoint of steering, more pronounced lateral angulations of the knees and hips at the start of steering that later became less pronounced, and overall slower turns that involved deceleration at completion. Consequently, distinct energy-dissipation-patterns were apparent on the 2 slope inclines, with greater pregate and lesser postgate dissipation on the steeper slope. The steepness of the slope also affected the relationships between mechanical skiing variables.

Conclusions:

The findings suggest that specific considerations during training and preparation would benefit the race performance of slalom skiers on courses involving sections of varying steepness.
Acute Effects of Static Active or Dynamic Active Stretching on Eccentric-Exercise-Induced Hamstring Muscle Damage
Authors: Chen Che-Hsiu , Chen Trevor C. , Jan Mei-Hwa , Lin Jiu-Jenq
Published: September 2014

Objectives:

To examine whether an acute bout of active or dynamic hamstring-stretching exercises would reduce the amount of muscle damage observed after a strenuous eccentric task and to determine whether the stretching protocols elicit similar responses.

Design:

A randomized controlled clinical trial.

Methods:

Thirty-six young male students performed 5 min of jogging as a warm-up and were allocated to 1 of 3 groups: 3 min of static active stretching (SAS), 3 min of dynamic active stretching (DAS), or control (CON). All subjects performed eccentric exercise immediately after stretching. Heart rate, core temperature, maximal voluntary isometric contraction, passive hip flexion, passive hamstring stiffness (PHS), plasma creatine kinase activity, and myoglobin were recorded at prestretching, at poststretching, and every day after the eccentric exercises for 5 d.

Results:

After stretching, the change in hip flexion was significantly higher in the SAS (5°) and DAS (10.8°) groups than in the CON (–4.1°) group. The change in PHS was significantly higher in the DAS (5.6%) group than in the CON (–5.7%) and SAS (–6.7%) groups. Furthermore, changes in muscle-damage markers were smaller in the SAS group than in the DAS and CON groups.

Conclusions:

Prior active stretching could be useful for attenuating the symptoms of muscle damage after eccentric exercise. SAS is recommended over DAS as a stretching protocol in terms of strength, hamstring range of motion, and damage markers.
Detecting a Pathogenic Activity, Not a Pathogenic Molecule
Authors: Foley John F.
Published: September 2014

The putative pattern-recognition receptor pyrin detects the activity of microbial toxins that inactivate Rho family GTPases in infected cells.
Inhibiting HIF with Fructose-1,6-Bisphosphastase
Authors: Gough Nancy R.
Published: September 2014

An enzyme involved in gluconeogenesis inhibits HIF activity through a noncatalytic mechanism.
Anti–CTLA-4 therapy broadens the melanoma-reactive CD8
+
T cell response
Authors: Kvistborg Pia , Philips Daisy , Kelderman Sander , Hageman Lois , Ottensmeier Christian , Joseph-Pietras Deborah , Welters Marij J. P. , van der Burg Sjoerd , Kapiteijn Ellen , Michielin Olivier , Romano Emanuela , Linnemann Carsten , Speiser Daniel , Blank Christian , Haanen John B. , Schumacher Ton N.
Published: September 2014

Anti–CTLA-4 treatment increases the diversity of the melanoma-specific CD8 T cell response.
Susceptibility to
Campylobacter
Infection Is Associated with the Species Composition of the Human Fecal Microbiota
Authors: Dicksved Johan , Ellström Patrik , Engstrand Lars , Rautelin Hilpi
Published: September 2014

The gut microbiota is essential for human health, but very little is known about how the composition of this ecosystem can influence and respond to bacterial infections. Here we address this by prospectively studying the gut microbiota composition before, during, and after natural
Campylobacter
infection in exposed poultry abattoir workers. The gut microbiota composition was analyzed with 16S amplicon sequencing of fecal samples from poultry abattoir workers during the peak season of
Campylobacter
infection in Sweden. The gut microbiota compositions were compared between individuals who became culture positive for
Campylobacter
and those who remained negative. Individuals who became
Campylobacter
positive had a significantly higher abundance of
Bacteroides
(
P
= 0.007) and
Escherichia
(
P
= 0.002) species than those who remained culture negative. Furthermore, this group had a significantly higher abundance of
Phascolarctobacterium
(
P
= 0.017) and
Streptococcus
(
P
= 0.034) sequences than the
Campylobacter
-negative group, which had an overrepresentation of
Clostridiales
(
P
= 0.017), unclassified
Lachnospiraceae
(
P
= 0.008), and
Anaerovorax
(
P
= 0.015) sequences. Intraindividual comparisons of the fecal microbiota compositions yielded small differences over time in
Campylobacter
-negative participants, but significant long-term changes were found in the
Campylobacter
-positive group (
P
< 0.005). The results suggest that the abundance of specific genera in the microbiota reduces resistance to
Campylobacter
colonization in humans and that
Campylobacter
infection can have long-term effects on the composition of the human fecal microbiota.

IMPORTANCE
Studies using mouse models have made important contributions to our understanding of the role of the gut microbiota in resistance to bacterial enteropathogen colonization. The relative abundances of
Escherichia coli
and
Bacteroides
species have been pointed out as important determinants of susceptibility to Gram-negative pathogens in general and
Campylobacter
infection in particular. In this study, we assessed the role of the human gut microbiota in resistance to
Campylobacter
colonization by studying abattoir workers that are heavily exposed to these bacteria. Individuals with a certain composition of the gut microbiota became culture positive for
Campylobacter
. As their microbiotas were characterized by high abundances of
Bacteroides
spp. and
E. coli
, well in line with the findings with mouse models, these bacterial species likely play an important role in colonization resistance also in humans.
Streptolysin O and NAD-Glycohydrolase Prevent Phagolysosome Acidification and Promote Group A
Streptococcus
Survival in Macrophages
Authors: Bastiat-Sempe Benedicte , Love John F. , Lomayesva Natalie , Wessels Michael R.
Published: September 2014

Group A
Streptococcus
(GAS,
Streptococcus pyogenes
) is an ongoing threat to human health as the agent of streptococcal pharyngitis, skin and soft tissue infections, and life-threatening conditions such as necrotizing fasciitis and streptococcal toxic shock syndrome. In animal models of infection, macrophages have been shown to contribute to host defense against GAS infection. However, as GAS can resist killing by macrophages
in vitro
and induce macrophage cell death, it has been suggested that GAS intracellular survival in macrophages may enable persistent infection. Using isogenic mutants, we now show that the GAS pore-forming toxin streptolysin O (SLO) and its cotoxin NAD-glycohydrolase (NADase) mediate GAS intracellular survival and cytotoxicity for macrophages. Unexpectedly, the two toxins did not inhibit fusion of GAS-containing phagosomes with lysosomes but rather prevented phagolysosome acidification. SLO served two essential functions, poration of the phagolysosomal membrane and translocation of NADase into the macrophage cytosol, both of which were necessary for maximal GAS intracellular survival. Whereas NADase delivery to epithelial cells is mediated by SLO secreted from GAS bound to the cell surface, in macrophages, the source of SLO and NADase is GAS contained within phagolysosomes. We found that transfer of NADase from the phagolysosome to the macrophage cytosol occurs not by simple diffusion through SLO pores but rather by a specific translocation mechanism that requires the N-terminal translocation domain of NADase. These results illuminate the mechanisms through which SLO and NADase enable GAS to defeat macrophage-mediated killing and provide new insight into the virulence of a major human pathogen.

IMPORTANCE
Macrophages constitute an important element of the innate immune response to mucosal pathogens. They ingest and kill microbes by phagocytosis and secrete inflammatory cytokines to recruit and activate other effector cells. Group A
Streptococcus
(GAS,
Streptococcus pyogenes
), an important cause of pharyngitis and invasive infections, has been shown to resist killing by macrophages. We find that GAS resistance to macrophage killing depends on the GAS pore-forming toxin streptolysin O (SLO) and its cotoxin NAD-glycohydrolase (NADase). GAS bacteria are internalized by macrophage phagocytosis but resist killing by secreting SLO, which damages the phagolysosome membrane, prevents phagolysosome acidification, and translocates NADase from the phagolysosome into the macrophage cytosol. NADase augments SLO-mediated cytotoxicity by depleting cellular energy stores. These findings may explain the nearly universal production of SLO by GAS clinical isolates and the association of NADase with the global spread of a GAS clone implicated in invasive infections.
Synthetic Lethality Reveals Mechanisms of Mycobacterium tuberculosis Resistance to β-Lactams
Authors: Lun Shichun , Miranda David , Kubler Andre , Guo Haidan , Maiga Mariama C. , Winglee Kathryn , Pelly Shaaretha , Bishai William R.
Published: September 2014

Most β-lactam antibiotics are ineffective against
Mycobacterium tuberculosis
due to the microbe’s innate resistance. The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains has prompted interest to repurpose this class of drugs. To identify the genetic determinants of innate β-lactam resistance, we carried out a synthetic lethality screen on a transposon mutant library for susceptibility to imipenem, a carbapenem β-lactam antibiotic. Mutations in 74 unique genes demonstrated synthetic lethality. The majority of mutations were in genes associated with cell wall biosynthesis. A second quantitative real-time PCR (qPCR)-based synthetic lethality screen of randomly selected mutants confirmed the role of cell wall biosynthesis in β-lactam resistance. The global transcriptional response of the bacterium to β-lactams was investigated, and changes in levels of expression of cell wall biosynthetic genes were identified. Finally, we validated these screens
in vivo
using the
MT1616
transposon mutant, which lacks a functional acyl-transferase gene. Mice infected with the mutant responded to β-lactam treatment with a 100-fold decrease in bacillary lung burden over 4 weeks, while the numbers of organisms in the lungs of mice infected with wild-type bacilli proliferated. These findings reveal a road map of genes required for β-lactam resistance and validate synthetic lethality screening as a promising tool for repurposing existing classes of licensed, safe, well-characterized antimicrobials against tuberculosis.

IMPORTANCE
The global emergence of multidrug-resistant and extensively drug-resistant
M. tuberculosis
strains has threatened public health worldwide, yet the pipeline of new tuberculosis drugs under development remains limited. One strategy to cope with the urgent need for new antituberculosis agents is to repurpose existing, approved antibiotics. The carbapenem class of β-lactam antibiotics has been proposed as one such class of drugs. Our study identifies molecular determinants of innate resistance to β-lactam drugs in
M. tuberculosis
, and we demonstrate that functional loss of one of these genes enables successful treatment of
M. tuberculosis
with β-lactams in the mouse model.
Vesicular Trafficking of Incoming Human Papillomavirus 16 to the Golgi Apparatus and Endoplasmic Reticulum Requires γ-Secretase Activity
Authors: Zhang Wei , Kazakov Teymur , Popa Andreea , DiMaio Daniel
Published: September 2014

The route taken by papillomaviruses from the cell surface to the nucleus during infection is incompletely understood. Here, we developed a novel human papillomavirus 16 (HPV16) pseudovirus in which the carboxy terminus of the minor capsid protein L2 is exposed on the exterior of the intact capsid prior to cell binding. With this pseudovirus, we used the proximity ligation assay immune detection technique to demonstrate that during entry HPV16 L2 traffics into and out of the early endosome prior to Golgi localization, and we demonstrated that L2 enters the endoplasmic reticulum during entry. The cellular membrane-associated protease, γ-secretase, is required for infection by HPV16 pseudovirus and authentic HPV16. We also showed that inhibition of γ-secretase does not interfere substantively with virus internalization, initiation of capsid disassembly, entry into the early endosome, or exit from this compartment, but γ-secretase is required for localization of L2 and viral DNA to the Golgi apparatus and the endoplasmic reticulum. These results show that incoming HPV16 traffics sequentially from the cell surface to the endosome and then to the Golgi apparatus and the endoplasmic reticulum prior to nuclear entry.

IMPORTANCE
The human papillomaviruses are small nonenveloped DNA viruses responsible for approximately 5% of all human cancer deaths, but little is known about the process by which these viruses transit from the cell surface to the nucleus. Here we show that incoming HPV16, the most common high-risk HPV, traffics though a series of vesicular compartments during infectious entry, including the endosome, Golgi apparatus, and endoplasmic reticulum. Furthermore, we show that γ-secretase, a cellular membrane-associated protease, is required for entry of the L2 minor capsid protein and viral DNA into the Golgi apparatus and endoplasmic reticulum. These studies reveal a new pathway of cell entry by DNA viruses and suggest that components of this pathway are candidate antiviral targets.
Paracetamol-associated acute liver failure in Australian and New Zealand children: high rate of medication errors
Authors: Rajanayagam J , Bishop J R , Lewindon P J , Evans Helen M
Published: September 2014

Background

In children, paracetamol overdose due to deliberate self-poisoning, accidental exposure or medication errors can lead to paediatric acute liver failure and death. In Australia and New Zealand, the nature of ingestion and outcomes of paracetamol-associated paediatric acute liver failure have not been described.

Objective

To describe the nature and outcomes of paracetamol-associated paediatric acute liver failure.

Design

Retrospective analysis of paracetamol-associated paediatric acute liver failure cases presenting 2002–2012.

Setting

New Zealand and Queensland Paediatric Liver Transplant Services.

Results

14 of 54 cases of paediatric acute liver failure were attributed to paracetamol, the majority were secondary to medication errors. 12 of the 14 children were under the age of 5 years. Seven children received doses in excess of 120 mg/kg/day. Many of the other children received either a double dose, too frequent administration, coadministration of other medicines containing paracetamol or regular paracetamol for up to 24 days. Three children underwent transplant. One of these and one other child died.

Conclusions

In Australia and New Zealand, paracetamol overdose secondary to medication errors is the leading cause of paediatric acute liver failure. A review of regional safety practices surrounding paracetamol use in children is indicated.
The cost-effectiveness and public health benefit of nalmefene added to psychosocial support for the reduction of alcohol consumption in alcohol-dependent patients with high/very high drinking risk levels: a Markov model
Authors: Laramée Philippe , Brodtkorb Thor-Henrik , Rahhali Nora , Knight Chris , Barbosa Carolina , François Clément , Toumi Mondher , Daeppen Jean-Bernard , Rehm Jürgen
Published: September 2014

Objectives

To determine whether nalmefene combined with psychosocial support is cost-effective compared with psychosocial support alone for reducing alcohol consumption in alcohol-dependent patients with high/very high drinking risk levels (DRLs) as defined by the WHO, and to evaluate the public health benefit of reducing harmful alcohol-attributable diseases, injuries and deaths.

Design

Decision modelling using Markov chains compared costs and effects over 5 years.

Setting

The analysis was from the perspective of the National Health Service (NHS) in England and Wales.

Participants

The model considered the licensed population for nalmefene, specifically adults with both alcohol dependence and high/very high DRLs, who do not require immediate detoxification and who continue to have high/very high DRLs after initial assessment.

Data sources

We modelled treatment effect using data from three clinical trials for nalmefene (ESENSE 1 (NCT00811720), ESENSE 2 (NCT00812461) and SENSE (NCT00811941)). Baseline characteristics of the model population, treatment resource utilisation and utilities were from these trials. We estimated the number of alcohol-attributable events occurring at different levels of alcohol consumption based on published epidemiological risk-relation studies. Health-related costs were from UK sources.

Main outcome measures

We measured incremental cost per quality-adjusted life year (QALY) gained and number of alcohol-attributable harmful events avoided.

Results

Nalmefene in combination with psychosocial support had an incremental cost-effectiveness ratio (ICER) of £5204 per QALY gained, and was therefore cost-effective at the £20 000 per QALY gained decision threshold. Sensitivity analyses showed that the conclusion was robust. Nalmefene plus psychosocial support led to the avoidance of 7179 alcohol-attributable diseases/injuries and 309 deaths per 100 000 patients compared to psychosocial support alone over the course of 5 years.

Conclusions

Nalmefene can be seen as a cost-effective treatment for alcohol dependence, with substantial public health benefits.

Trial registration numbers

This cost-effectiveness analysis was developed based on data from three randomised clinical trials: ESENSE 1 (NCT00811720), ESENSE 2 (NCT00812461) and SENSE (NCT00811941).
A prospective cohort study characterising the role of anogenital warts in HIV acquisition among men who have sex with men: a study protocol
Authors: Brown Brandon , Davtyan Mariam , Leon Segundo R , Sanchez Hugo , Calvo Gino , Klausner Jeffrey D , Galea Jerome
Published: September 2014

Introduction

The HIV epidemic in Latin America is concentrated among men who have sex with men (MSM) and transgender women (TGW) with transmission predominately occurring during unprotected anal intercourse. This mode of transmission is also responsible for other sexually transmitted infections (STIs) such as herpes simplex, chlamydia and gonorrhoea, human papillomavirus (HPV)/genital warts and syphilis. Studies assessing the prevalence of HIV and HPV among MSM have not addressed the role of genital warts and HPV-related diseases in the acquisition of HIV infection. Community-based testing programmes are a potentially important way to remove barriers including stigma for individuals to learn about their STI status.

Methods and analysis

The prospective cohort study will recruit 600 MSM/TGW at a community centre in Lima, Peru, named Epicentro. Half of the participants will have a history of or have current anogenital warts (AGW), and the other half will have no history of AGW. We will measure the prevalence and acquisition of STIs including syphilis, HPV, chlamydia and gonorrhoea and the HIV-incidence in the two groups. To the best of our knowledge, it will be the first study that specifically examines the impact of genital warts on incident HIV infection. This study will help to understand the relationship between AGW and HIV infection among MSM/TGW in Peru. Furthermore, it may facilitate the development of preventive intervention strategies to reduce the prevalence of AGW and prevent incident HIV infection. HPV-related manifestations may be a good proxy for HIV risk.

Ethics and dissemination

This study was approved by institutional review boards at the University of California, Los Angeles (UCLA) in the USA and Impacta in Peru. Study findings will be shared with the Peruvian Ministry of Health as well as other international and national public health organisations. Study results will be translated into Spanish for participants.

Trial registration number

The Clinicaltrials.gov registration number isNCT01387412
Serial characterisation of monocyte and neutrophil function after lung resection
Authors: Jones Richard O , Brittan Mairi , Anderson Niall H , Conway Morris Andrew , Murchison John T , Walker William S , Simpson A John
Published: September 2014

Objectives

The primary aim of this prospective study was to perform a comprehensive serial characterisation of monocyte and neutrophil function, circulating monocyte subsets, and bronchoalveolar lavage (BAL) fluid after lung resection. A secondary aim was to perform a pilot, hypothesis-generating evaluation of whether innate immune parameters were associated with postoperative pneumonia.

Methods

Forty patients undergoing lung resection were studied in detail. Blood monocytes and neutrophils were isolated preoperatively and at 6, 24 and 48 h postoperatively. BAL was performed preoperatively and immediately postoperatively. Monocyte subsets, monocyte responsiveness to lipopolysaccharide (LPS) and neutrophil phagocytic capacity were quantified at all time points. Differential cell count, protein and cytokine concentrations were measured in BAL. Pneumonia evaluation at 72 h was assessed using predefined criteria.

Results

After surgery, circulating subsets of classical and intermediate monocytes increased significantly. LPS-induced release of proinflammatory cytokines from monocytes increased significantly and by 48 h a more proinflammatory profile was found. Neutrophil phagocytosis demonstrated a small but significant fall. Factors associated with postoperative pneumonia were: increased release of specific proinflammatory and anti-inflammatory cytokines from monocytes; preoperative neutrophilia; and preoperative BAL cell count.

Conclusions

We conclude that postoperative lung inflammation is associated with specific changes in the cellular innate immune response, a better understanding of which may improve patient selection and prediction of complications in the future.
Sarcoidosis: the links between epidemiology and aetiology
Authors: Dubrey Simon , Shah Shreena , Hardman Timothy , Sharma Rakesh
Published: September 2014

Sarcoidosis is a multisystem inflammatory disease, the aetiology of which has still to be resolved. The proposed mechanism is that a susceptible genotype is exposed to one or more potential antigens. A sustained inflammatory response follows, which ultimately results in pathognomonic granuloma formation. Various clinical phenotypes exist with specific genetic associations influencing disease susceptibility, protection, and clinical progression. Occupational and environmental factors, including microbial elements, may then effect the development of this disease. Sarcoidosis is a heterogeneous disease, showing geographic and racial variation in clinical presentation. It demonstrates a familial tendency and clear genotype associations. Additionally, it appears to cluster within closely associated populations (eg, work colleagues) and appears to be related to selected occupations and environmental exposures. Frequently occult, but occasionally fatal, this disease has a very variable prognosis. It is also unusual in having no specific biomarker. The epidemiology and multiple factors that appear to influence the aetiology of sarcoidosis illustrate why this disease state is frequently described as a clinical enigma.
The influence of nighttime feeding of carbohydrate or protein combined with exercise training on appetite and cardiometabolic risk in young obese women
Authors: Ormsbee Michael J. , Kinsey Amber W. , Eddy Wyatt R. , Madzima Takudzwa A. , Arciero Paul J. , Figueroa Arturo , Panton Lynn B.
Published: September 2014

Single macronutrient intake prior to sleep reduces appetite but may negatively impact insulin sensitivity in sedentary obese women. The present study examined the additive impact of nighttime feeding of whey (WH), casein (CAS), or carbohydrate (CHO) combined with exercise training on appetite, cardiometabolic health, and strength in obese women. Thirty-seven sedentary obese women (WH, n = 13, body mass index (BMI) 34.4 ± 1.3 kg/m2; CAS, n = 14, BMI 36.5 ± 1.8 kg/m2; CHO, n = 10, BMI 33.1 ± 1.7 kg/m2) consumed WH, CAS, or CHO (140–150 kcal/serving), every night of the week, within 30 min of sleep, for 4 weeks. Supervised exercise training (2 days of resistance training and 1 day of high-intensity interval training) was completed 3 days per week. Pre- and post-testing measurements included appetite ratings, mood state, resting metabolic rate, fasting lipids, glucose, and hormonal responses (insulin, leptin, adiponectin, hs-CRP, IGF-1, and cortisol), body composition, and strength. Nighttime intake of CAS significantly (p < 0.05) increased morning satiety (pretraining, 25 ± 5; post-training 41 ± 6) more than WH (pretraining, 34 ± 5; post-training, 35 ± 6) or CHO (pre 40 ± 8, post 43 ± 7). Exercise training increased lean mass and strength, decreased body fat, and improved mood state in all groups. No other differences were noted. Nighttime feeding of CAS combined with exercise training increased morning satiety more than WH or CHO. Nighttime feeding for 4 weeks did not impact insulin sensitivity (assessed via homeostatic model assessment of insulin resistance) when combined with exercise training in obese women. ClinicalTrial.gov: NCT01830946.
Paracellular calcium transport across renal and intestinal epithelia
Authors: Alexander R. Todd , Rievaj Juraj , Dimke Henrik
Published: September 2014

Calcium (Ca2+) is a key constituent in a myriad of physiological processes from intracellular signalling to the mineralization of bone. As a consequence, Ca2+is maintained within narrow limits when circulating in plasma. This is accomplished via regulated interplay between intestinal absorption, renal tubular reabsorption, and exchange with bone. Many studies have focused on the highly regulated active transcellular transport pathways for Ca2+from the duodenum of the intestine and the distal nephron of the kidney. However, comparatively little work has examined the molecular constituents creating the paracellular shunt across intestinal and renal epithelium, the transport pathway responsible for the majority of transepithelial Ca2+flux. More specifically, passive paracellular Ca2+absorption occurs across the majority of the intestine in addition to the renal proximal tubule and thick ascending limb of Henle’s loop. Importantly, recent studies demonstrated that Ca2+transport through the paracellular shunt is significantly regulated. Therefore, we have summarized the evidence for different modes of paracellular Ca2+flux across renal and intestinal epithelia and highlighted recent molecular insights into both the mechanism of secondarily active paracellular Ca2+movement and the identity of claudins that permit the passage of Ca2+through the tight junction of these epithelia.
Effects of natural resource development on the terrestrial biodiversity of Canadian boreal forests
Authors: Venier L.A. , Thompson I.D. , Fleming R. , Malcolm J. , Aubin I. , Trofymow J.A. , Langor D. , Sturrock R. , Patry C. , Outerbridge R.O. , Holmes S.B. , Haeussler S. , De Grandpré L. , Chen H.Y.H. , Bayne E. , Arsenault A. , Brandt J.P.
Published: September 2014

Much of Canada’s terrestrial biodiversity is supported by boreal forests. Natural resource development in boreal forests poses risks to this biodiversity. This paper reviews the scientific literature to assess the effects of natural resource development on terrestrial biodiversity in Canadian boreal forests. We address four questions: (1) To what extent have Canadian boreal forests changed due to natural resource development? (2) How has biodiversity responded to these changes? (3) Will the biodiversity of second-growth forests converge with that of primary boreal forests? (4) Are we losing species from boreal forests? We focus on trees, understory plants, insects, fungi, selected mammals, and songbirds because these groups have been most studied. We review more than 600 studies and found that changes in community composition are prevalent in response to large-scale conversion of forest types, changes in stand structures and age distributions, and altered landscape structure resulting from forest management and habitat loss associated with other developments such as oil and gas, hydroelectric, and mining. The southern boreal forest has been more highly impacted than the north due to more extensive forest management and the cumulative effects of multiple forms of development. There is abundant evidence that most species are not in danger of being extirpated from the boreal forest due to these anthropogenic changes. A few species, including woodland caribou (Rangifer tarandus) and grizzly bear (Ursus arctos), have, however, undergone long-term range contractions. Significant gaps in our ability to assess the effects of natural resource development on biodiversity in the boreal zone are the lack of long-term spatial and population data to monitor the impact of forest changes on ecosystems and species.
AN ACCURATE CALIBRATION METHOD FOR THE MEASUREMENT OF ARTERIAL OXYGEN SATURATION USING PHOTOPLETHYSMOGRAPHY
Authors: WANG YONGJIAN , PU LINA , WU DAN , LIN WAN-HUA , WONG KELVIN KIAN LOONG , ZHANG HEYE
Published: September 2014

The monitoring of arterial oxygen saturation (SaO2) is a common practice in both clinical and home environments, and the process of monitoring can be exercised invasively or non-invasively. In the past decades, the pulse oximeter is one of the most popular non-invasive devices that use photoplethysmography (PPG) to measure SaO 2. As the pulse oximeter requires calibration prior to application in clinical practice, a significant number of calibration methods have been proposed based on experimental data collected from human volunteers. Alternatively, models may be derived from the Lambert–Beer law or the photon diffusion equation (PDE). However, most of such calibrated oximeter can only provide accurate readings of SaO 2 at high versus the low levels. We propose to apply an extra-boundary condition to solve the PDE, and then to develop a model-based calibration method that relate optical measurements to the level of SaO 2 in this work. Then, we validate our method against previous model-based methods and an oximeter simulator with higher accuracy when the level of SaO 2 is greater than 90%. In practice, our model-based method can still maintain a good performance when the level of SaO 2 decreases to 60%, thereby demonstrating high potential in the accurate evaluation of the oxygen level of patients by PPG.
Experimental study of the Kirchhoff-Law-Johnson-Noise secure key exchange
Authors: Mingesz Robert
Published: September 2014

The Kirchhoff-Law-Johnson-Noise (KLJN) secure key distribution system provides a way of exchanging secure keys by using classical physics (electricity and thermodynamics). Several theoretical studies have addressed the performance and applicability of the communication protocol, and they have indicated that it is protected against all known types of attacks. However, until now, there have been very few real physical implementations and experimental tests of the protocol. With our work, we continue filling this gap. Details of implementing a KLJN based system are presented using a dedicated hardware and an off-the-shelf solution as well. Furthermore, the results of experimental tests and analysis of the performance will be presented.
Model-Based Count Series Clustering for Bike Sharing System Usage Mining: A Case Study with the Vélib’ System of Paris
Authors: Etienne Côme , Latifa Oukhellou
Published: September 2014

Today, more and more bicycle sharing systems (BSSs) are being introduced in big cities. These transportation systems generate sizable transportation data, the mining of which can reveal the underlying urban phenomenon linked to city dynamics. This article presents a statistical model to automatically analyze the trip data of a bike sharing system. The proposed solution partitions (i.e., clusters) the stations according to their usage profiles. To do so, count series describing the stations’s usage through departure/arrival counts per hour throughout the day are built and analyzed. The model for processing these count series is based on Poisson mixtures and introduces a station scaling factor that handles the differences between the stations’s global usage. Differences between weekday and weekend usage are also taken into account. This model identifies the latent factors that shape the geography of trips, and the results may thus offer insights into the relationships between station neighborhood type (its amenities, its demographics, etc.) and the generated mobility patterns. In other words, the proposed method brings to light the different functions in different areas that induce specific patterns in BSS data. These potentials are demonstrated through an in-depth analysis of the results obtained on the Paris Vélib’ large-scale bike sharing system.