bluuebunny/crossref_metadata_2025 huggingface dataset:
Measurement of gastric emptying by radiopaque markers in patients with diabetes: correlation with scintigraphy and upper gastrointestinal symptoms
Authors: Olausson E. A. , Brock C. , Drewes A. M. , Grundin H. , Isaksson M. , Stotzer P. , Abrahamsson H. , Attvall S. , Simrén M.
Published: January 2013

Background  Scintigraphy, the gold standard to measure gastric emptying, is expensive and not widely available. Therefore, we compared emptying of radiopaque markers (ROM) from the stomach, by use of fluoroscopy, with scintigraphy in patients with insulin‐treated diabetes.

Methods  On the same day we measured gastric emptying of 20 ROM using fluoroscopy and scintigraphic emptying of a standard solid meal. The subjects also completed a validated gastrointestinal (GI) symptom questionnaire.

Key Results  We included 115 patients with insulin‐treated diabetes (median age 53, range 21–69 years; 59 women). A moderately strong correlation was demonstrated between scintigraphic (% retained at 2 h) and ROM emptying (markers retained at 6 h) (r = 0.47; P < 0.0001). Eighty‐three patients had delayed gastric emptying with scintigraphy, whereas only 29 patients had delayed emptying of ROM. Of the 29 patients with delayed emptying of ROM, 28 also had delayed scintigraphic emptying. The sensitivity and specificity of the ROM test was 34% and 97%, respectively. Significant correlations were only noted between scintigraphic gastric emptying and GI symptom severity, with the strongest correlations for fullness/early satiety (r = 0.34; P < 0.001) and nausea/vomiting (r = 0.30; P < 0.001).

Conclusions & Inferences  A gastric emptying test with ROM is a widely available screening method to detect delayed gastric emptying in patients with diabetes, where a positive result seems reliable. However, a normal ROM test does not exclude delayed gastric emptying, and if the clinical suspicion of gastroparesis remains, scintigraphy should be performed. Results from scintigraphy also correlate with GI symptom severity, which ROM test did not.
Treatment of Infantile Hemangiomas with Sirolimus in a Patient with PHACE Syndrome
Authors: Kaylani Samer , Theos Amy J. , Pressey Joseph G.
Published: January 2013

Infantile hemangiomas (IHs) are common benign tumors of childhood. IHs often regress satisfactorily without intervention, but a subset of IHs may lead to functional or cosmetic morbidity necessitating therapy. PHACE syndrome is characterized by a variety of neurocutaneous and vascular anomalies that typically include segmental hemangiomas. We present an infant with PHACE syndrome and segmental IH that failed conventional first‐line therapies. Treatment with sirolimus provided benefit with regression of the cutaneous IH. As an inhibitor of the mammalian target of rapamycin (mTOR) pathway, the effective use of sirolimus may shed light on the emerging role of mTOR signaling in the development and pathogenesis of IHs.
Changes in Perceived Supervisor Embeddedness: Effects on Employees’ Embeddedness, Organizational Trust, and Voice Behavior
Authors: Ng Thomas W. H. , Feldman Daniel C.
Published: January 2013

Guided by social information processing theory, this study examines how perceived supervisor embeddedness relates to employees’ own affect toward, attachment to, and behavior within the firm. Data were collected from 338 employees at 3 points in time over a 10‐month period. The results supported the proposed model in 3 key ways. First, perceived supervisor embeddedness was directly related to employees’ own embeddedness over time. Second, organizational trust mediated the relationship between perceived supervisor embeddedness and employees’ own embeddedness over time. Third, organizational trust and employee embeddedness were both related to employees’ voice behavior over time.
Sound‐induced perturbations of the brain network in non‐REM sleep, and network oscillations in wake
Authors: Wu Weiwei , Sheth Bhavin R.
Published: January 2013

During sleep, the brain network processes sensory stimuli without awareness. Stimulation must affect differently brain networks in sleep versus wake, but these differences have yet to be quantified. We recorded cortical activity in stage 2 (SII) sleep and wake using EEG while a tone was intermittently played. Zero‐lag correlation measured input to pairs of sensors in the network; cross‐correlation and phase‐lag index measured pairwise corticocortical connectivity. Our analysis revealed that under baseline conditions, the cortical network, in particular the central regions of the frontoparietal cortex, interact at a characteristic latency of 50 ms, but only during wake, not sleep. Nonsalient auditory stimulation causes far greater perturbation of connectivity from baseline in sleep than wake, both in the response to common input and corticocortical connectivity. The findings have key implications for sensory processing.
The evolutionary origin of the vertebrate basal ganglia and its role in action selection
Authors: Grillner Sten , Robertson Brita , Stephenson‐Jones Marcus
Published: January 2013

Abstract  The group of nuclei within the basal ganglia of the forebrain is central to the control of movement. We present data showing that the structure and function of the basal ganglia have been conserved throughout vertebrate evolution over some 560 million years. The interaction between the different nuclei within the basal ganglia is conserved as well as the cellular and synaptic properties and transmitters. We consider the role of the conserved basal ganglia circuitry for basic patterns of motor behaviour controlled via brainstem circuits. The output of the basal ganglia consists of tonically active GABAergic neurones, which target brainstem motor centres responsible for different patterns of behaviour, such as eye and locomotor movements, posture, and feeding. A prerequisite for activating or releasing a motor programme is that this GABAergic inhibition is temporarily reduced. This can be achieved through activation of GABAergic projection neurons from striatum, the input level of the basal ganglia, given an appropriate synaptic drive from cortex, thalamus and the dopamine system. The tonic inhibition of the motor centres at rest most likely serves to prevent the different motor programmes from becoming active when not intended. Striatal projection neurones are subdivided into one group with dopamine 1 receptors that provides increased excitability of the direct pathway that can initiate movements, while inhibitory dopamine 2 receptors are expressed on neurones that instead inhibit movements and are part of the ‘indirect loop’ in mammals as well as lamprey. We review the evidence showing that all basic features of the basal ganglia have been conserved throughout vertebrate phylogeny, and discuss these findings in relation to the role of the basal ganglia in selection of behaviour.
Nitric oxide‐mediated cutaneous microvascular function is impaired in polycystic ovary sydrome but can be improved by exercise training
Authors: Sprung V. S. , Cuthbertson D. J. , Pugh C. J. A. , Daousi C. , Atkinson G. , Aziz N. F. , Kemp G. J. , Green D. J. , Cable N. T. , Jones H.
Published: January 2013

Key points

Polycystic ovary syndrome (PCOS) is associated with cardiovascular disease.

Nitric oxide (NO) is a naturally occurring molecule that possesses anti‐atherogenic properties.

The contribution of NO to the dilatation of microvessels in the skin is currently unknown in women with PCOS.

In this study, it was found that women with PCOS display impaired NO bioavailability compared with obese matched control women.

Exercise training improves the microvascular dysfunction displayed in women with PCOS, via the upregulation of NO.

These findings suggest exercise training can be a preventive strategy in women with PCOS.

Abstract  Polycystic ovary syndrome (PCOS) is associated with cardiovascular disease. The contribution of the nitric oxide (NO) dilator system to cutaneous endothelial dysfunction is currently unknown in PCOS. Our aim was to examine whether women with PCOS demonstrate impaired cutaneous microvascular NO function and whether exercise training can ameliorate any impairment. Eleven women with PCOS (age, 29 ± 7 years; body mass index, 34 ± 6 kg m−2) were compared with six healthy obese control women (age, 29 ± 7 years; body mass index, 34 ± 5 kg m−2). Six women with PCOS (30 ± 7 years; 31 ± 6 kg m−2) then completed 16 weeks of exercise training. Laser Doppler flowmetry, combined with intradermal microdialysis of l‐NG‐monomethyl‐l‐arginine, a nitric oxide antagonist, in response to incremental local heating of the forearm was assessed in women with PCOS and control women, and again in women with PCOS following exercise training. Cardiorespiratory fitness, homeostasis model assessment for insulin resistance, hormone and lipid profiles were also assessed. Differences between women with PCOS and control women and changes with exercise were analysed using Student's unpaired t tests. Differences in the contribution of NO to cutaneous blood flow [expressed as a percentage of maximal cutaneous vasodilatation (CVCmax)] were analysed using general linear models. At 42°C heating, cutaneous NO‐mediated vasodilatation was attenuated by 17.5%CVCmax (95% confidence interval, 33.3, 1.7; P = 0.03) in women with PCOS vs. control women. Exercise training improved cardiorespiratory fitness by 5.0 ml kg−1 min−1 (95% confidence interval, 0.9, 9.2; P = 0.03) and NO‐mediated cutaneous vasodilatation at 42°C heating by 19.6% CVCmax (95% confidence interval, 4.3, 34.9; P = 0.02). Cutaneous microvascular NO function is impaired in women with PCOS compared with obese matched control women but can be improved with exercise training.
Repeated in vivo exposure of cocaine induces long‐lasting synaptic plasticity in hypocretin/orexin‐producing neurons in the lateral hypothalamus in mice
Authors: Rao Yan , Mineur Yann S. , Gan Geliang , Wang Alex Hanxiang , Liu Zhong‐Wu , Wu Xinyuan , Suyama Shigetomo , de Lecea Luis , Horvath Tamas L. , Picciotto Marina R. , Gao Xiao‐Bing
Published: January 2013

Key points

Repeated, but not single, in vivo cocaine exposure leads to an experience‐dependent potentiation of glutamatergic synapses on hypocretin‐producing neurons (hypocretin neurons) in mice.

The locus of synaptic potentiation is at the postsynaptic site of glutamatergic synapses on hypocretin neurons and the up‐regulation of AMPA‐type glutamate receptors may be involved.

Cocaine‐induced synaptic potentiation is long‐lasting and exists during the abstinence of cocaine.

The expression of tetanus‐induced long‐term potentiation is facilitated in hypocretin neurons in cocaine‐treated mice.

These results may help us better understand the role of the hypocretin system in behavioural changes related to cocaine addiction in animals and humans.

Abstract  Hypocretin (orexin), a neuropeptide synthesized exclusively in the perifornical/lateral hypothalamus, is critical for drug seeking and relapse, but it is not clear how the circuitry centred on hypocretin‐producing neurons (hypocretin neurons) is modified by drugs of abuse and how changes in this circuit might alter behaviours related to drug addiction. In this study, we show that repeated, but not single, in vivo cocaine administration leads to a long‐lasting, experience‐dependent potentiation of glutamatergic synapses on hypocretin neurons in mice following a cocaine‐conditioned place preference (CPP) protocol. The synaptic potentiation occurs postsynaptically and probably involves up‐regulation of AMPA‐type glutamate receptors on hypocretin neurons. Phosphorylation of cAMP response element‐binding protein (CREB) is also significantly increased in hypocretin neurons in cocaine‐treated animals, suggesting that CREB‐mediated pathways may contribute to synaptic potentiation in these cells. Furthermore, the potentiation of synaptic efficacy in hypocretin neurons persists during cocaine withdrawal, but reverses to baseline levels after prolonged abstinence. Finally, the induction of long‐term potentiation (LTP) triggered by a high‐frequency stimulation is facilitated in hypocretin neurons in cocaine‐treated mice, suggesting that long‐lasting changes in synapses onto hypocretin neurons would probably be further potentiated by other stimuli (such as concurrent environmental cues) paired with the drug. In summary, we show here that hypocretin neurons undergo experience‐dependent synaptic potentiation that is distinct from that reported in other reward systems, such as the ventral tegmental area, following exposure to cocaine. These findings support the idea that the hypocretin system is important for behavioural changes associated with cocaine administration in animals and humans.
Direct inhibition of arcuate proopiomelanocortin neurons: a potential mechanism for the orexigenic actions of dynorphin
Authors: Zhang Xiaobing , van den Pol Anthony N.
Published: January 2013

Key points

In conjunction with fast amino acid transmitters, neuropeptides such as dynorphin play key roles in regulating energy homeostasis.

Dynorphin immunoreactive axons are abundant in the hypothalamic arcuate nucleus and terminate near or on proopiomelanocortin (POMC) neurons.

Dynorphin directly inhibits POMC cells by a mechanism based on activation of GIRK channels, mediated by kappa‐2 opioid receptors.

Dynorphin indirectly modulates the activity of POMC neurons by depressing afferent glutamate and GABA synaptic neurotransmission.

These data suggest that dynorphin‐containing neurons could modulate food intake and energy homeostasis by directly attenuating the activity of the anorexigenic POMC cell.

Abstract  Dynorphin, an endogenous ligand of kappa (κ) opioid receptors, has multiple roles in the brain, and plays a positive role in energy balance and food intake. However, the mechanism for this is unclear. With immunocytochemistry, we find that axonal dynorphin immunoreactivity in the arcuate nucleus is strong, and that a large number of dynorphin‐immunoreactive boutons terminate on or near anorexigenic proopiomelanocortin (POMC) cells. Here we provide evidence from whole‐cell patch‐clamp recording that dynorphin‐A (Dyn‐A) directly and dose‐dependently inhibits arcuate nucleus POMC neurons. Dyn‐A inhibition was eliminated by the κ opioid receptor antagonist nor‐BNI, but not by the μ receptor antagonist CTAP. The inhibitory effect was mimicked by the κ2 receptor agonist GR89696, but not by the κ1 receptor agonist U69593. No presynaptic effect of κ2 agonists was found. These results suggest that Dyn‐A inhibits POMC neurons through activation of the κ2 opioid receptor. In whole‐cell voltage clamp, Dyn‐A opened G‐protein‐coupled inwardly rectifying potassium (GIRK)‐like channels on POMC neurons. Dynorphin attenuated glutamate and GABA neurotransmission to POMC neurons. In contrast to the strong inhibition of POMC neurons by Dyn‐A, we found a weaker direct inhibitory effect of Dyn‐A on arcuate nucleus neuropeptide Y (NPY) neurons mediated by both κ1 and κ2 receptors. Taken together, these results indicate a direct inhibitory effect of Dyn‐A on POMC neurons through activation of the κ2 opioid receptor and GIRK channels. A number of orexigenic hypothalamic neurons release dynorphin along with other neuropeptides. The inhibition of anorexigenic POMC neurons may be one mechanism underlying the orexigenic actions of dynorphin.
Focus Issue: Understanding Mechanisms of Inflammation
Authors: Foley John F.
Published: January 2013

Inflammatory responses can be both beneficial and detrimental.
From Indolent to Metastatic
Authors: Wong Wei
Published: January 2013

A transcription factor promotes the metastasis of nonaggressive PTEN-null prostate tumors through a nontranscriptional mechanism.
Tapping Lines of Communication
Authors: VanHook Annalisa M.
Published: January 2013

Carnivorous fungi identify prey by intercepting pheromone communication.
N152G, -S, and -T Substitutions in CMY-2 β-Lactamase Increase Catalytic Efficiency for Cefoxitin and Inactivation Rates for Tazobactam
Authors: Skalweit Marion J. , Li Mei , Conklin Benjamin C. , Taracila Magdalena A. , Hutton Rebecca A.
Published: January 2013

Class C cephalosporinases are a growing threat, and clinical inhibitors of these enzymes are currently unavailable. Previous studies have explored the role of Asn152 in the
Escherichia coli
AmpC and P99 enzymes and have suggested that interactions between C-6′ or C-7′ substituents on penicillins or cephalosporins and Asn152 are important in determining substrate specificity and enzymatic stability. We sought to characterize the role of Asn152 in the clinically important CMY-2 cephalosporinase with substrates and inhibitors. Mutagenesis of CMY-2 at position 152 yields functional mutants (N152G, -S, and -T) that exhibit improved penicillinase activity and retain cephamycinase activity. We also tested whether the position 152 substitutions would affect the inactivation kinetics of tazobactam, a class A β-lactamase inhibitor with
in vitro
activity against CMY-2. Using standard assays, we showed that the N152G, -S, and -T variants possessed increased catalytic activity against cefoxitin compared to the wild type. The 50% inhibitory concentration (IC
50
) for tazobactam improved dramatically, with an 18-fold reduction for the N152S mutant due to higher rates of enzyme inactivation. Modeling studies have shown active-site expansion due to interactions between Y150 and S152 in the apoenzyme and the Michaelis-Menten complex with tazobactam. Substitutions at N152 might become clinically important as new class C β-lactamase inhibitors are developed.
Defining the Timing of Action of Antimalarial Drugs against Plasmodium falciparum
Authors: Wilson Danny W. , Langer Christine , Goodman Christopher D. , McFadden Geoffrey I. , Beeson James G.
Published: January 2013

Most current antimalarials for treatment of clinical
Plasmodium falciparum
malaria fall into two broad drug families and target the food vacuole of the trophozoite stage. No antimalarials have been shown to target the brief extracellular merozoite form of blood-stage malaria. We studied a panel of 12 drugs, 10 of which have been used extensively clinically, for their invasion, schizont rupture, and growth-inhibitory activity using high-throughput flow cytometry and new approaches for the study of merozoite invasion and early intraerythrocytic development. Not surprisingly, given reported mechanisms of action, none of the drugs inhibited merozoite invasion
in vitro
. Pretreatment of erythrocytes with drugs suggested that halofantrine, lumefantrine, piperaquine, amodiaquine, and mefloquine diffuse into and remain within the erythrocyte and inhibit downstream growth of parasites. Studying the inhibitory activity of the drugs on intraerythrocytic development, schizont rupture, and reinvasion enabled several different inhibitory phenotypes to be defined. All drugs inhibited parasite replication when added at ring stages, but only artesunate, artemisinin, cycloheximide, and trichostatin A appeared to have substantial activity against ring stages, whereas the other drugs acted later during intraerythrocytic development. When drugs were added to late schizonts, only artemisinin, cycloheximide, and trichostatin A were able to inhibit rupture and subsequent replication. Flow cytometry proved valuable for
in vitro
assays of antimalarial activity, with the free merozoite population acting as a clear marker for parasite growth inhibition. These studies have important implications for further understanding the mechanisms of action of antimalarials, studying and evaluating drug resistance, and developing new antimalarials.
Daptomycin versus Vancomycin in Treatment of Methicillin-Resistant Staphylococcus aureus Meningitis in an Experimental Rabbit Model
Authors: Bardak-Ozcem Selin , Turhan Tuncer , Sipahi Oguz Resat , Arda Bilgin , Pullukcu Husnu , Yamazhan Tansu , Isikgoz-Tasbakan Meltem , Sipahi Hilal , Ulusoy Sercan
Published: January 2013

In this study, we aimed to compare the antibacterial activities of daptomycin and vancomycin in the treatment of methicillin-resistant
Staphylococcus aureus
(MRSA) meningitis (induced by MRSA strain ATCC 43300) in an experimental rabbit meningitis model. After an 8-h period of treatment, bacterial counts decreased significantly in both treatment groups compared to the control group (
P
< 0.05). However, there was no statistically significant difference between treatment groups. Our results suggest that the antibacterial activity of daptomycin is similar to vancomycin for treatment in the experimental MRSA meningitis model in rabbits.
Solithromycin Inhibition of Protein Synthesis and Ribosome Biogenesis in Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae
Authors: Rodgers Ward , Frazier Ashley D. , Champney W. Scott
Published: January 2013

The continuing increase in antibiotic-resistant microorganisms is driving the search for new antibiotic targets and improved antimicrobial agents. Ketolides are semisynthetic derivatives of macrolide antibiotics, which are effective against certain resistant organisms. Solithromycin (CEM-101) is a novel fluoroketolide with improved antimicrobial effectiveness. This compound binds to the large 50S subunit of the ribosome and inhibits protein biosynthesis. Like other ketolides, it should impair bacterial ribosomal subunit formation. This mechanism of action was examined in strains of
Streptococcus pneumoniae
,
Staphylococcus aureus
, and
Haemophilus influenzae
. The mean 50% inhibitory concentrations (IC
50
s) for solithromycin inhibition of cell viability, protein synthesis, and growth rate were 7.5, 40, and 125 ng/ml for
Streptococcus pneumoniae
,
Staphylococcus aureus
, and
Haemophilus influenzae
, respectively. The net formation of the 50S subunit was reduced in all three organisms, with IC
50
s similar to those given above. The rates of 50S subunit formation measured by a pulse-chase labeling procedure were reduced by 75% in cells growing at the IC
50
of solithromycin. Turnover of 23S rRNA was stimulated by solithromycin as well. Solithromycin was found to be a particularly effective antimicrobial agent, with IC
50
s comparable to those of telithromycin and significantly better than those of azithromycin and clarithromycin in these three microorganisms.
Antibodies to Escherichia coli-Expressed C-Terminal Domains of Plasmodium falciparum Variant Surface Antigen 2-Chondroitin Sulfate A (VAR2CSA) Inhibit Binding of CSA-Adherent Parasites to Placental Tissue
Authors: Saveria Tracy , Oleinikov Andrew V. , Wiliamson Kathryn , Chaturvedi Richa , Lograsso Joe , Keitany Gladys J. , Fried Michal , Duffy Patrick
Published: January 2013

Placental malaria (PM) is characterized by infected erythrocytes (IEs) that selectively bind to chondroitin sulfate A (CSA) and sequester in placental tissue. Variant surface antigen 2-CSA (VAR2CSA), a
Plasmodium falciparum
erythrocyte membrane protein 1 (PfEMP1) protein family member, is expressed on the surface of placental IEs and mediates adherence to CSA on the surface of syncytiotrophoblasts. This transmembrane protein contains 6 Duffy binding-like (DBL) domains which might contribute to the specific adhesive properties of IEs. Here, we use laboratory isolate 3D7 VAR2CSA DBL domains expressed in
Escherichia coli
to generate antibodies specific for this protein. Flow cytometry results showed that antibodies generated against DBL4ε, DBL5ε, DBL6ε, and tandem double domains of DBL4-DBL5 and DBL5-DBL6 all bind to placental parasite isolates and to lab strains selected for CSA binding but do not bind to children's parasites. Antisera to DBL4ε and to DBL5ε inhibit maternal IE binding to placental tissue in a manner comparable to that for plasma collected from multigravid women. These antibodies also inhibit binding to CSA of several field isolates derived from pregnant women, while antibodies to double domains do not enhance the functional immune response. These data support DBL4ε and DBL5ε as vaccine candidates for pregnancy malaria and demonstrate that
E. coli
is a feasible tool for the large-scale manufacture of a vaccine based on these VAR2CSA domains.
Intestinal Microbiota Containing Barnesiella Species Cures Vancomycin-Resistant Enterococcus faecium Colonization
Authors: Ubeda Carles , Bucci Vanni , Caballero Silvia , Djukovic Ana , Toussaint Nora C. , Equinda Michele , Lipuma Lauren , Ling Lilan , Gobourne Asia , No Daniel , Taur Ying , Jenq Robert R. , van den Brink Marcel R. M. , Xavier Joao B. , Pamer Eric G.
Published: January 2013

Bacteria causing infections in hospitalized patients are increasingly antibiotic resistant. Classical infection control practices are only partially effective at preventing spread of antibiotic-resistant bacteria within hospitals. Because the density of intestinal colonization by the highly antibiotic-resistant bacterium vancomycin-resistant
Enterococcus
(VRE) can exceed 10
9
organisms per gram of feces, even optimally implemented hygiene protocols often fail. Decreasing the density of intestinal colonization, therefore, represents an important approach to limit VRE transmission. We demonstrate that reintroduction of a diverse intestinal microbiota to densely VRE-colonized mice eliminates VRE from the intestinal tract. While oxygen-tolerant members of the microbiota are ineffective at eliminating VRE, administration of obligate anaerobic commensal bacteria to mice results in a billionfold reduction in the density of intestinal VRE colonization. 16S rRNA gene sequence analysis of intestinal bacterial populations isolated from mice that cleared VRE following microbiota reconstitution revealed that recolonization with a microbiota that contains
Barnesiella
correlates with VRE elimination. Characterization of the fecal microbiota of patients undergoing allogeneic hematopoietic stem cell transplantation demonstrated that intestinal colonization with
Barnesiella
confers resistance to intestinal domination and bloodstream infection with VRE. Our studies indicate that obligate anaerobic bacteria belonging to the
Barnesiella
genus enable clearance of intestinal VRE colonization and may provide novel approaches to prevent the spread of highly antibiotic-resistant bacteria.
BtaE, an Adhesin That Belongs to the Trimeric Autotransporter Family, Is Required for Full Virulence and Defines a Specific Adhesive Pole of Brucella suis
Authors: Ruiz-Ranwez Verónica , Posadas Diana M. , Van der Henst Charles , Estein Silvia M. , Arocena Gastón M. , Abdian Patricia L. , Martín Fernando A. , Sieira Rodrigo , De Bolle Xavier , Zorreguieta Angeles
Published: January 2013

Brucella
is responsible for brucellosis, one of the most common zoonoses worldwide that causes important economic losses in several countries. Increasing evidence indicates that adhesion of
Brucella
spp. to host cells is an important step to establish infection. We have previously shown that the BmaC unipolar monomeric autotransporter mediates the binding of
Brucella suis
to host cells through cell-associated fibronectin. Our genome analysis shows that the
B. suis
genome encodes several additional potential adhesins. In this work, we characterized a predicted trimeric autotransporter that we named BtaE. By expressing
btaE
in a nonadherent
Escherichia coli
strain and by phenotypic characterization of a
B. suis
Δ
btaE
mutant, we showed that BtaE is involved in the binding of
B. suis
to hyaluronic acid. The
B. suis
Δ
btaE
mutant exhibited a reduction in the adhesion to HeLa and A549 epithelial cells compared with the wild-type strain, and it was outcompeted by the wild-type strain in the binding to HeLa cells. The knockout
btaE
mutant showed an attenuated phenotype in the mouse model, indicating that BtaE is required for full virulence. BtaE was immunodetected on the bacterial surface at one cell pole. Using old and new pole markers, we observed that both the BmaC and BtaE adhesins are consistently associated with the new cell pole, suggesting that, in
Brucella
, the new pole is functionally differentiated for adhesion. This is consistent with the inherent polarization of this bacterium, and its role in the invasion process.
Influenza-Induced Inflammation Drives Pneumococcal Otitis Media
Authors: Short Kirsty R. , Reading Patrick C. , Brown Lorena E. , Pedersen John , Gilbertson Brad , Job Emma R. , Edenborough Kathryn M. , Habets Marrit N. , Zomer Aldert , Hermans Peter W. M. , Diavatopoulos Dimitri A. , Wijburg Odilia L.
Published: January 2013

Influenza A virus (IAV) predisposes individuals to secondary infections with the bacterium
Streptococcus pneumoniae
(the pneumococcus). Infections may manifest as pneumonia, sepsis, meningitis, or otitis media (OM). It remains controversial as to whether secondary pneumococcal disease is due to the induction of an aberrant immune response or IAV-induced immunosuppression. Moreover, as the majority of studies have been performed in the context of pneumococcal pneumonia, it remains unclear how far these findings can be extrapolated to other pneumococcal disease phenotypes such as OM. Here, we used an infant mouse model, human middle ear epithelial cells, and a series of reverse-engineered influenza viruses to investigate how IAV promotes bacterial OM. Our data suggest that the influenza virus HA facilitates disease by inducing a proinflammatory response in the middle ear cavity in a replication-dependent manner. Importantly, our findings suggest that it is the inflammatory response to IAV infection that mediates pneumococcal replication. This study thus provides the first evidence that inflammation drives pneumococcal replication in the middle ear cavity, which may have important implications for the treatment of pneumococcal OM.
Chlamydia trachomatis Plasmid-Encoded Pgp4 Is a Transcriptional Regulator of Virulence-Associated Genes
Authors: Song Lihua , Carlson John H. , Whitmire William M. , Kari Laszlo , Virtaneva Kimmo , Sturdevant Daniel E. , Watkins Heather , Zhou Bing , Sturdevant Gail L. , Porcella Stephen F. , McClarty Grant , Caldwell Harlan D.
Published: January 2013

Chlamydia trachomatiscauses chronic inflammatory diseases of the eye and genital tract and has global medical importance. The chlamydial plasmid plays an important role in the pathophysiology of these diseases, as plasmid-deficient organisms are highly attenuated. The cryptic plasmid carries noncoding RNAs and eight conserved open reading frames (ORFs). To understand plasmid gene function, we generated plasmid shuttle vectors with deletions in each of the eight ORFs. The individual deletion mutants were used to transform chlamydiae and the transformants were characterized phenotypically and at the transcriptional level. We show thatpgp1, -2, -6, and -8are essential for plasmid maintenance, while the other ORFs can be deleted and the plasmid stably maintained. We further show that apgp4knockout mutant exhibits anin vitrophenotype similar to its isogenic plasmidless strain, in terms of abnormal inclusion morphology and lack of glycogen accumulation. Microarray and qRT-PCR analysis revealed that Pgp4 is a transcriptional regulator of plasmid-encodedpgp3and multiple chromosomal genes, including the glycogen synthase geneglgA, that are likely important in chlamydial virulence. Our findings have major implications for understanding the plasmid's role in chlamydial pathogenesis at the molecular level.
A comparative geochemical study of Mars and Earth basalt petrogenesis
Authors: Greenough John D. , Ya’acoby Avee
Published: January 2013

Geochemical data, from the Mars Meteorite Compendium web site, for 13 basaltic meteorites, possibly from only four localities on Mars, are used to study Martian petrogenetic processes. To achieve this goal, an exploratory data analysis technique, multidimensional scaling (MDS), is used to quantitatively assess the relative behavior (measured with correlation coefficients) of 160 incompatible element ratios involving 25 “trace” elements. The ratios behave as in Earth basalts, suggesting that relative element incompatibility is similar in both planets. Because mineralogy controls incompatibility, the mineralogy of Earth and Mars mantles appears similar. In addition, results suggest that ratios involving elements with highly different incompatibility (e.g., La/Yb) are dominantly controlled by % melting. Plots of SiO2 (pressure proxy; decreases with increasing pressure) versus La/Yb and Nb/Y (decrease as melting increases) imply that Mars basalts, like Earth tholeiites, reflect high percentages of melting, but opposite to Earth, % melting appears to increase with increasing pressure. The moderately correlated, positive, SiO2–La/Yb Mars relationship parallels highly correlated Lunar KREEP data and contrasts with Earth’s negative correlation. The positive relationships may reflect restricted mantle convection in some (Mars and the Moon are smaller) planetary bodies. Using similarly incompatible element ratios that are sensitive to source composition, to compare Mars and Earth with MDS, Mars sources most resemble depleted Earth mantle. Additionally, these ratios group Mars sources into enriched, depleted, and intermediate types. The groupings are the same as those suggested by isotopes, and we conclude that trace element data support the hypothesis that chemical variation in Mars may reflect crystallization of a Mars magma ocean. The natural patterns in ratios and samples revealed using MDS, which has no a priori information about relationships, support integrity of the geochemical data set, despite potential shortcomings such as small sample sizes, alteration, and weathering. However, whether the meteorites are representative of Mars as a whole is unknown.
The Paint Pots, Kootenay National Park, Canada — a natural acid spring analogue for Mars
Authors: Grasby Stephen E. , Richards Barry C. , Sharp Christine E. , Brady Allyson L. , Jones Gareth M. , Dunfield Peter F.
Published: January 2013

The Paint Pots are a natural Fe–SO4acid spring system along the Kicking Horse Rim, a major geological feature that has controlled fluid flow and mineralization over geologic time. The very low pH (∼3) and extremely high trace metal concentrations of the springs are anomalous and greatly exceed health limits (Zn = 35.8 mg/L, Pb = 0.461 mg/L, As = 82.7 ppb). Sulphur isotopes (δ34S and δ18O in sulphate equal to +11.4 and –12.1 ‰, respectively) are consistent with sulphide oxidation. Mass balance calculations indicate that the springs must have derived their acidity and metal content from natural weathering of a pyrite-rich ore deposit in the vicinity. Several ore deposit types occur along the Kicking Horse Rim, with the Mississippi Valley Type (MVT) style being the most consistent with the source of the spring waters. At the spring outlet, Fe-rich waters oxidize, forming large cone features of Fe–O precipitates, predominantly goethite. A diverse microbial community has been identified in the site that is distinct from those found at acid mine drainage sites. At one site, there was a high proportion of the bacterial candidate division WPS-2, the first time that this group has been detected as the predominant phylum in a community. Compared with anthropogenically influenced acid mine drainage sites that have been studied to date as Mars analogues, the unique uncultured organisms found in the Paint Pots provide a distinct analogue site that can offer insights into the diversity of extremophilic organisms in more natural environments.
SURFACE-ACOUSTIC-WAVE FIELD AND ACOUSTO-OPTIC INTERACTION IN AlN/128-DEG-ROTATED Y-CUT X-PROPAGATION LiNbO3
Authors: WANG JUNTAO , HAN QUN , NING JIPING , HE YANG
Published: January 2013

The efficiency of guided-wave acousto-optic (AO) interaction in AlN /128-deg-rotated Y-cut X-propagation lithium niobate (128-deg YX- LiNbO 3) structure is analyzed theoretically for the first time by determining the overlap integral between the optical and the surface acoustic wave (SAW) field distribution. The results show that the use of an AlN film can increase the phase velocity of SAW, the electromechanical coupling coefficient and the diffraction efficiency of AO interaction. A maximum of 9.33% for the electromechanical coupling coefficient is obtained when the normalized thickness of AlN film equals 0.09. The diffraction efficiency has a significant improvement when the normalized thickness of AlN film is increased from 0 to 0.05. And, the improvement for the TM polarization is more evident than that for the TE polarization. However, for a well-concentrated optical waveguide, the use of an AlN film reduces the diffraction efficiency of the TM polarization when the SAW frequency is low.
REALIZATION OF FIRST-ORDER CURRENT-MODE FILTERS WITH LOW NUMBER OF MOS TRANSISTORS
Authors: YUCE ERKAN , MINAEI SHAHRAM , HERENCSAR NORBERT , KOTON JAROSLAV
Published: January 2013

In this paper, a new current-mode (CM) circuit for realizing all of the first-order filter responses is suggested. The proposed configuration contains low number of components, only two NMOS transistors both operating in saturation region, two capacitors and two resistors. Major advantages of the presented circuit are low voltage, low noise and high linearity. The proposed filter circuit can simultaneously provide both inverting and non-inverting first-order low-pass, high-pass and all-pass filter responses. Computer simulation results achieved through SPICE tool and experimental results are given as examples to demonstrate performance and effectiveness of the proposed topology.
CONVENTIONAL AND EXTENDED TIME-DELAYED FEEDBACK CONTROLLED ZERO-CROSSING DIGITAL PHASE LOCKED LOOP
Authors: BANERJEE TANMOY , SARKAR B. C.
Published: January 2013

This article investigates the effect of the conventional and extended time-delayed feedback control techniques of chaos control on a first-order positive zero-crossing digital phase locked loop (ZC1-DPLL) using local stability analysis, two-parameter bifurcation studies and two-parameter Lyapunov exponent spectrum. Starting from the nonlinear dynamics of a ZC1-DPLL, we at first explore the time-delayed feedback control (TDFC) algorithm on a ZC1-DPLL in the parameter space. A condition for the optimum value of the system control parameter is derived analytically for a TDFC based ZC1-DPLL. Next, the extended time-delayed feedback control (ETDFC) technique on a ZC1-DPLL is described. It is observed that the application of the delayed feedback control (DFC) technique on the sampled values of the incoming signal inside the loop finally results in the nonlinear DFC of the phase error dynamics. We prove that, for some suitably chosen control parameters, an ETDFC based ZC1-DPLL has a broader stability zone in comparison with a ZC1-DPLL and its TDFC version.
CHAOS IN COUPLED CLOCKS
Authors: PERLIKOWSKI P. , KAPITANIAK M. , CZOLCZYNSKI K. , STEFANSKI A. , KAPITANIAK T.
Published: January 2013

We consider the dynamics of two pendulum clocks (with pendulums of the same length but different masses) suspended on the same beam. We give evidence that besides the complete and phase synchronizations, the considered system can exhibit long period synchronization and chaotic behavior. We argue that the observed phenomena are robust.
SYNCHRONIZING CONTINUOUS TIME CHAOTIC SYSTEMS OVER NONDETERMINISTIC NETWORKS WITH PACKET DROPOUTS
Authors: SOUZA FERNANDO O. , PALHARES REINALDO M. , MENDES EDUARDO M. A. M. , TORRES LEONARDO A. B.
Published: January 2013

The problem of control synthesis for master–slave synchronization of continuous time chaotic systems of Lur'e type using sampled feedback control subject to sampling time random fluctuation and data packet dropouts is investigated. New stability and stabilization conditions are proposed based on Linear Matrix Inequalities (LMIs). The idea is to connect two very efficient approaches to deal with delayed systems: the discretized Lyapunov functional for systems with pointwise delay and the convex analysis for systems with time-varying delay. Simulation examples based on synchronizing coupled Chua's circuits are used to illustrate the effectiveness of the proposed methodology.
GEOMETRIC LIMITS OF MANDELBROT AND JULIA SETS UNDER DEGREE GROWTH
Authors: BOYD SUZANNE HRUSKA , SCHULZ MICHAEL J.
Published: January 2013

First, for the family Pn,c(z) = zn + c, we show that the geometric limit of the Mandelbrot sets Mn(P) as n → ∞ exists and is the closed unit disk, and that the geometric limit of the Julia sets J(Pn,c) as n tends to infinity is the unit circle, at least when |c| ≠ 1. Then, we establish similar results for some generalizations of this family; namely, the maps z ↦ zt + c for real t ≥ 2 and the rational maps z ↦ zn + c + a/zn.
DELAYED BIFURCATION IN FIRST-ORDER SINGULARLY PERTURBED PROBLEMS WITH A NONGENERIC TURNING POINT
Authors: SHEN JIANHE , HAN MAOAN
Published: January 2013

In this paper, based on the method of upper and lower solutions, delayed bifurcation in first-order singularly perturbed problems with a nongeneric turning point is studied. The asymptotic behavior of the solutions is understood by constructing the upper and lower solutions with the desired dynamical properties. As an application of the obtained results, delayed phenomenon of degenerate Hopf bifurcation in a planar polynomial differential system with a slowly varying parameter is discussed in detail and the maximal delay is calculated. Numerical simulations are carried out to verify the theoretical results.
BIFURCATIONS AND EXACT TRAVELING WAVE SOLUTIONS OF THE GENERALIZED TWO-COMPONENT CAMASSA–HOLM EQUATION
Authors: LI JIBIN , QIAO ZHIJUN
Published: January 2013

In this paper, we apply the method of dynamical systems to a generalized two-component Camassa–Holm system. Through analysis, we obtain solitary wave solutions, kink and anti-kink wave solutions, cusp wave solutions, breaking wave solutions, and smooth and nonsmooth periodic wave solutions. To guarantee the existence of these solutions, we give constraint conditions among the parameters associated with the generalized Camassa–Holm system. Choosing some special parameters, we obtain exact parametric representations of the traveling wave solutions.
BIFURCATION ANALYSIS OF THE QUASI-PERIODIC SOLUTION WITH THREE-PHASE SYNCHRONIZED ENVELOPES IN A RING OF THREE-COUPLED, BISTABLE OSCILLATORS
Authors: KAMIYAMA KYOHEI , KOMURO MOTOMASA , ENDO TETSURO
Published: January 2013

In this study, we investigate the bifurcation of the quasi-periodic solution in a ring of three-coupled, bistable oscillators. The quasi-periodic solution under study is a propagating wave solution with three-phase synchronized envelope, and we name it "ICC3ϕ" which means invariant closed curve for which time waveforms have three-phase synchronized envelope. We obtain the two-parameter bifurcation diagram of ICC3ϕ with respect to the coupling factor α versus the nonlinear strength ϵ. Consequently, we detect several Arnold tongues showing various periodic solutions of ICC3ϕ. By investigating the bifurcation on the boundary of these Arnold tongues, we clarify the transition from periodic to quasi-periodic solution of ICC3ϕ or the inverse. Specifically, the transition of the period-4, period-5, and period-7 solutions to ICC3ϕ is due to a saddle-node bifurcation, which has no hysteresis. In contrast, the transition from the period-3 solution to ICC3ϕ is a combination of subcritical pitchfork and heteroclinic bifurcations; hence, it has hysteresis. We draw diagrams showing the connection of unstable manifolds of heteroclinic bifurcation.
Design of energy-efficient, adaptable throughput systems at near/sub-threshold voltage
Authors: Srivastav Meeta , Henry M. B. , Nazhandali Leyla
Published: January 2013

Voltage scaling has been a prevalent method of saving energy for energy-constrained applications. However, current technology trends which shrink transistors sizes exacerbate process variation effects in voltage-scaled systems. Large variations in transistor parameters result in high variation in performance and power across the chip. These effects, if ignored at the design, stage, will result in unpredictable behavior when deployed in the field. In this article, we leverage the benefits of voltage scaling methodology for obtaining energy efficiency and compensate for the loss in throughput by exploiting parallelism present in the various DSP designs. We show that such a hybrid method consumes 8%--77% less power, compared to simple dynamic voltage scaling over different throughputs. We study this system architecture in two different workload environments: static and dynamic. We show that to achieve the highest level of energy efficiency, the number of cores and the operating voltages vary widely between a BASE design versus a process variation-aware (PVA) design. We further demonstrate that the PVA design enjoys an average of 26.9% and 51.1% reduction in energy consumption for the static and dynamic designs, respectively. Since different cores will have a wide range of speeds at operating voltages close to near/sub-thresholds due to process variation, we gather characteristic behavior of each core. With knowledge of the core speeds, we can further increase the energy efficiency. Furthermore, in this article, we show that of this methodology will be 49.3% more energy efficient, compared to that building the system with no knowledge about the characteristics of each core.
Improving performance per watt of asymmetric multi-core processors via online program phase classification and adaptive core morphing
Authors: Rodrigues Rance , Annamalai Arunachalam , Koren Israel , Kundu Sandip
Published: January 2013

Asymmetric multi-core processors (AMPs) have been shown to outperform symmetric ones in terms of performance and performance/watt. Improved performance and power efficiency are achieved when the program threads are matched to their most suitable cores. Since the computational needs of a program may change during its execution, the best thread to core assignment will likely change with time. We have, therefore, developed an online program phase classification scheme that allows the swapping of threads when the current needs of the threads justify a change in the assignment.

The architectural differences among the cores in an AMP can never match the diversity that exists among different programs and even between different phases of the same program. Consider, for example, a program (or a program phase) that has a high instruction-level parallelism (ILP) and will exhibit high power efficiency if executed on a powerful core. We can not, however, include such powerful cores in the designed AMP, since they will remain underutilized most of the time, and they are not power efficient when the programs do not exhibit a high degree of ILP. Thus, we must expect to see program phases where the designed cores will be unable to support the ILP that the program can exhibit. We, therefore, propose in this article a dynamic morphing scheme. This scheme will allow a core to gain control of a functional unit that is ordinarily under the control of a neighboring core during periods of intense computation with high ILP. This way, we dynamically adjust the hardware resources to the current needs of the application.

Our results show that combining online phase classification and dynamic core morphing can significantly improve the performance/watt of most multithreaded workloads.