bluuebunny/crossref_metadata_2025 huggingface dataset:
Cysteine modification reveals which subunits form the ligand binding site in human heteromeric 5‐HT3AB receptors
Authors: Thompson A. J. , Price K. L. , Lummis S. C. R.
Published: June 2011

Non‐technical summary  Nerve signals are transmitted across cell membranes by receptors that can consist of multiple different subunits. The 5‐HT3 receptor is a pentamer which can function with A subunits alone, or with a mixture of A and B subunits. As 5‐HT activates the receptor by binding at the interface of adjacent subunits, it is important to know which subunits are adjacent. Here we show that in both A‐only and A+B receptors there is at least one A–A interface, without which the receptor cannot function. This knowledge is important for understanding the receptor mechanism, and also will allow the design of more specific drugs that act at the 5‐HT binding site.
Cerebral blood flow alteration in neuroprotection following cerebral ischaemia
Authors: Sutherland Brad A. , Papadakis Michalis , Chen Ruo‐Li , Buchan Alastair M.
Published: June 2011

Abstract  The best neuroprotectant for acute ischaemic stroke would always be the rapid return of oxygen and glucose to physiological levels. This is currently provided by thrombolysis which restores blood flow to the ischaemic region. The attempt to confer neuroprotection by targeting the brain parenchyma has shown promise in experimental stroke models, but has unequivocally failed to translate to the clinic. Neuroprotective therapy primarily targets the biochemical cascade that produces cell death following cerebral ischaemia. However, these agents may also alter signal transduction that controls cerebral blood flow, for example glutamate, which may affect the outcome after ischaemia. In these cases, neuroprotection may potentially be due to the improved access to oxygen and glucose rather than biochemical prevention of cell death. Improvement in cerebral blood flow is an important but often overlooked effect of neuroprotective therapy, analogous to the protective effects of drug‐induced hypothermia. This short review will discuss cerebral blood flow alteration and protection of the brain in the context of ischaemic preconditioning, oxygen sensing and thrombolysis. Future neuroprotection studies in cerebral ischaemia require stringent monitoring of cerebral blood flow, plus other physiological parameters. This will increase the chances that any protection observed may be able to translate to human therapy.
Switching control of sympathetic activity from forebrain to hindbrain in chronic dehydration
Authors: Colombari Débora S. A. , Colombari Eduardo , Freiria‐Oliveira Andre H. , Antunes Vagner R. , Yao Song T. , Hindmarch Charles , Ferguson Alastair V. , Fry Mark , Murphy David , Paton Julian F. R.
Published: June 2011

Non‐technical summary  Dehydration, a life‐threatening condition, occurs when the body does not replace adequate water lost through urination, sweating or when ill with diarrhoea. This presents the body with a major challenge of maintaining blood pressure – essential for consciousness that is dependent on the degree of body hydration, which dictates blood volume. We know that a major control mechanism involves a brain region called the hypothalamus that automatically maintains blood pressure. Our study has described the gene networks in key brain regions involved in the response to dehydration. We reveal a new structure in the brain that regulates blood pressure in dehydration and a unique genetic mechanism that exists within it. Moreover, our study unearths a remarkable form of flexibility within the brain during dehydration that involves switching control of blood pressure between two spatially distinct structures. We have provided new mechanistic insight to explain how the brain maintains body stability in face of the significant challenge of low water content.
Numerical Investigations of the Efficiency of Circulation Control in a Compressor Stator
Authors: Vorreiter Arne , Fischer Susanne , Saathoff Horst , Radespiel Rolf , Seume Joerg R.
Published: June 2011

Airfoil active flow control has been attempted in the past in order to increase the permissible loading of boundary layers in gas turbine components. The present paper presents a stator with active flow control for a high-speed compressor using a Coanda surface near the trailing edge in order to inhibit boundary layer separation. The design intent is to reduce the number of vanes while—in order to ensure a good matching with the downstream rotor—the flow turning angle is kept constant. In a first step, numerical simulations of a linear compressor cascade with circulation control are conducted. The Coanda surface is located behind an injection slot on the airfoil suction side. Small blowing rates lead to a gain in efficiency associated with a rise in static pressure. In a second step, this result is transferred to a four-stage high-speed research compressor, where the circulation control is applied in the first stator. The design method and the first results are based on steady numerical calculations. The analysis of these results shows performance benefits of the concept. For both the cascade and the research compressor, the pressure gain and efficiency are shown as a function of blowing rate and jet power ratio. The comparison is performed based on a dimensionless efficiency, which takes into account the change in power loss.
A template‐based approach to semi‐quantitative SPECT myocardial perfusion imaging: Independent of normal databases
Authors: Hughes Tyler , Shcherbinin Sergey , Celler Anna
Published: June 2011

Purpose:

Normal patient databases (NPDs) are used to distinguish between normal and abnormal perfusion in SPECT myocardial perfusion imaging (MPI) and have gained wide acceptance in the clinical environment, yet there are limitations to this approach. This study introduces a template‐based method for semi‐quantitative MPI, which attempts to overcome some of the NPD limitations.

Methods:

Our approach involves the construction of a 3D digital healthy heart template from the delineation of the patient's left ventricle in the SPECT image. This patient‐specific template of the heart, filled with uniform activity, is then analytically projected and reconstructed using the same algorithm as the original image. Subsequent to generating bulls‐eye maps for the patient image (PB) and the template image (TB), a ratio (PB/TB) is calculated, which produces a reconstruction‐artifact corrected image (CB). Finally, a threshold is used to define defects within CB enabling measurements of the perfusion defect extent (EXT). The SPECT‐based template (TS) measurements were compared to those of a CT‐based “ideal” template (TI). Twenty digital phantoms were simulated: male and female, each with one healthy heart and nine hearts with various defects. Four physical phantom studies were performed modeling a healthy heart and three hearts with different defects. The phantom represented a thorax with spine, lung, and left ventricle inserts. Images were acquired on General Electric's (GE) Infinia Hawkeye SPECT/CT camera using standard clinical MPI protocol. Finally, our method was applied to 14 patient MPI rest/stress studies acquired on the GE Infinia Hawkeye SPECT/CT camera and compared to the results obtained from Cedars‐Sinai's QPS software.

Results:

In the simulation studies, the true EXT correlated well with the TI (slope = 1.08; offset = −0.40%; r = 0.99) and TS (slope = 0.90; offset = 0.27%; r = 0.99) methods with no significant differences between them. Similarly, strong correlations were measured for EXT obtained from QPS and the template method for patient studies (slope = 0.91; offset = 0.45%; r = 0.98). Mean errors in extent for the TS method using simulation, physical phantom, and patient data were 2.7% ± 2.4%, 0.9% ± 0.5%, 2.0% ± 2.7%, respectively.

Conclusions:

The authors introduced a method for semi‐quantitative SPECT MPI, which offers a patient‐specific approach to define the perfusion defect regions within the heart, as opposed to the patient‐averaged NPD methodology.
Control of intravascular catheters using an array of active steering coils
Authors: Gudino N. , Heilman J. A. , Derakhshan J. J. , Sunshine J. L. , Duerk J. L. , Griswold M. A.
Published: June 2011

Purpose: To extend the concept of deflecting the tip of a catheter with the magnetic force created in an MRI system through the use of an array of independently controllable steering coils located in the catheter tip, and to present methods for visualization of the catheter and/or surrounding areas while the catheter is deflected.Methods: An array of steering coils made of 42‐gauge wire was built over a 2.5 Fr (0.83 mm) fiber braided microcatheter. Two of the coils were 70 turn axial coils separated by 1 cm, and the third was a 15‐turn square side coil that was 2 × 4 mm2. Each coil was driven independently by a pulse width modulation (PWM) current source controlled by a microprocessor that received commands from a matlab routine that dynamically set current amplitude and direction for each coil. The catheter was immersed in a water phantom containing 1% Gd‐DTPA that was placed at the isocenter of a 1.5 T MRI scanner. Deflections of the catheter tip were measured from image‐based data obtained with a real‐time radio frequency (RF) spoiled gradient echo sequence (GRE). The small local magnetic fields generated by the steering coils were exploited to generate a hyperintense signal at the catheter tip by using a modified GRE sequence that did not include slice‐select rewinding gradients. Imaging and excitation modes were implemented by synchronizing the excitation of the steering coil array with the scanner by ensuring that no current was driven through the coils during the data acquisition window; this allowed visualization of the surrounding tissue while not affecting the desired catheter position.Results: Deflections as large as 2.5 cm were measured when exciting the steering coils sequentially with a 100 mA maximum current per coil. When exciting a single axial coil, the deflection was half this value with 30% higher current. A hyperintense catheter tip useful for catheter tracking was obtained by imaging with the modified GRE sequence. Clear visualization of the areas surrounding the catheter was obtained by using the excitation and imaging mode even with a repetition time (TR) as small as 10 ms.Conclusions: A new system for catheter steering is presented that allows large deflections through the use of an integrated array of steering coils. Additionally, two imaging techniques for tracking the catheter tip and visualization of surrounding areas, without interference from the active catheter, were shown. Together the demonstrated steerable catheter, control system and the imaging techniques will ultimately contribute to the development of a steerable system for interventional MRI procedures.
Dosimetric and mechanical characteristics of a commercial dynamic μMLC used in SRS
Authors: Galal Mohamed M. , Keogh Sinéad , Khalil Sultan
Published: June 2011

Purpose: The aim of this work is to carry out mechanical and dosimetric assessments on a commercial dynamic micromulti leaf collimator system to be used for stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT). Mechanical parameters such as leaf position accuracy with different gantry angles and leaf position reproducibility were measured. Also dosimetric measurements of the interleaf leakage, intraleaf transmission, penumbra width, and light field alignment were carried out. Furthermore, measurements of output factors (Scp) and in‐air factors (Sc) for the μMLC system will be reported.Methods: EBT2 films were used to assess the leaf position error with gantry angle and after stress test, penumbra width and light field alignment. Leaf leakage was quantified using both EBT2 film and a pinpoint ion chamber. With regard to output factors, the pinpoint chamber was placed in a water phantom at 10 cm depth and 100 cm SSD. For in‐air output factor measurements, 0.2 cm of brass was placed above the photon diode as build‐up.Results: Measurements of mechanical parameters gave values of 0.05 cm (SD 0.035) for the average leaf position accuracy for different gantry angles and after stress test. Dosimetric measurements, yielded values of 0.22 ± 0.01 and 0.24 ± 0.01 cm, respectively, for side and head leaf penumbras. Also, average leaf abutting, leakage and transmission were found to be 0.65, 0.91, and 0.20%, respectively.Conclusions: (a) The add‐on μMLC system in combination with our LINAC has been commissioned to be used for clinical purposes and showed good agreement with published results for different μMLC types. (b) This work has lead to the recommendation that leaves should be recalibrated after ten static beams or after each dynamic arc.
Quantitative Phosphoproteomics Identifies Substrates and Functional Modules of Aurora and Polo-Like Kinase Activities in Mitotic Cells
Authors: Kettenbach Arminja N. , Schweppe Devin K. , Faherty Brendan K. , Pechenick Dov , Pletnev Alexandre A. , Gerber Scott A.
Published: June 2011

Combining quantitative phosphoproteomics and selective kinase inhibition yields previously unknown substrates and functions of two families of mitotic kinases and refinement of their recognition motifs.
Science Signaling
Podcast: 28 June 2011
Authors: Hauf Silke , Winey Mark , Jones Michele H. , Keck Jamie M. , VanHook Annalisa M.
Published: June 2011

Two studies shed light on cell cycle–dependent protein phosphorylation during mitosis in yeast.
Focus Issue: Choreographing the Dance of the Mitotic Kinases
Authors: Gough Nancy R.
Published: June 2011

Research into the phosphoproteome targeted by mitotic kinases reveals insight into the coordination of the activity of these kinases during cell division.
Shaping the Gradient
Authors: Adler Elizabeth M.
Published: June 2011

The Pom1 cortical concentration gradient depends on its autophosphorylation and its dephosphorylation by Dis2.
Food as Antibiotic?
Authors: Gough Nancy R.
Published: June 2011

The yolk protein phosvitin acts as a pattern recognition receptor to help developing fish fend off bacterial infection.
Acetylation for Autophagy
Authors: Wong Wei
Published: June 2011

Acetylation of pyruvate kinase M2 inhibits its activity and triggers its autophagic degradation, leading to increased tumor cell proliferation.
Light Control
Authors: Vinson Valda
Published: June 2011

An implanted device using blue-light–triggered expression of the glucagon-like peptide 1 attenuates diabetes in mice.
Determination of Pentapeptide Repeat Units in Qnr Proteins by the Structure-Based Alignment Approach
Authors: Park Kwang Seung , Lee Jung Hun , Jeong Da Un , Lee Jae Jin , Wu Xing , Jeong Byeong Chul , Kang Choong-Min , Lee Sang Hee
Published: June 2011

The Qnr proteins belong to the pentapeptide repeat protein family. Despite each pentapeptide repeat unit being an important structural determinant, accurately determining pentapeptide repeat units in the Qnr proteins through sequence-based alignments has been challenging. In the present study, the pentapeptide repeat units of the nine representative Qnr proteins have been precisely determined via the structure-based alignment approach using homology modeling and superposition of their best models.
A Small Amount of Fat Does Not Affect Piperaquine Exposure in Patients with Malaria
Authors: Annerberg Anna , Lwin Khin Maung , Lindegardh Niklas , Khrutsawadchai Sakchai , Ashley Elizabeth , Day Nicholas P. J. , Singhasivanon Pratap , Tarning Joel , White Nicholas J. , Nosten François
Published: June 2011

Dihydroartemisinin-piperaquine is a new, highly effective, and well-tolerated combination treatment for uncomplicated falciparum malaria. The lipophilic characteristic of piperaquine suggests that administration together with fat will increase the oral bioavailability of the drug, and this has been reported for healthy volunteers. This pharmacokinetic study monitored 30 adult patients with uncomplicated falciparum malaria for 4.5 months to evaluate the effects of the concomitant intake of fat on the total piperaquine exposure. The fixed-drug combination of dihydroartemisinin-piperaquine was given with water to fasting patients (
n
= 15) or was coadministered with 200 ml milk containing 6.4 g fat (
n
= 15). The drug combination was generally well tolerated, and there were no severe adverse effects reported for either group during the study. Total piperaquine exposure (area under the concentration-time curve from zero to infinity [AUC
0-∞
]; results are given as medians [ranges]) were not statistically different between fed (29.5 h · μg/ml [20.6 to 58.7 h · μg/ml]) and fasting (23.9 h · μg/ml [11.9 to 72.9 h · μg/ml]) patients, but the interindividual variation was reduced in the fed group. Overall, none of the pharmacokinetic parameters differed statistically between the groups. Total piperaquine exposure correlated well with the day 7 concentrations in the fasted group, but the fed group showed a poor correlation. In conclusion, the coadministration of 6.4 g fat did not have any significant effect on piperaquine pharmacokinetics in the treatment of uncomplicated malaria.
A High-Throughput Screening Assay for Inhibitors of Bacterial Motility Identifies a Novel Inhibitor of the Na+-Driven Flagellar Motor and Virulence Gene Expression in Vibrio cholerae
Authors: Rasmussen Lynn , White E. Lucile , Pathak Ashish , Ayala Julio C. , Wang Hongxia , Wu Jian-He , Benitez Jorge A. , Silva Anisia J.
Published: June 2011

Numerous bacterial pathogens, particularly those that colonize fast-flow areas in the bladder and gastrointestinal tract, require motility to establish infection and spread beyond the initially colonized tissue.Vibrio choleraestrains of serogroups O1 and O139, the causative agents of the diarrheal illness cholera, express a single polar flagellum powered by sodium motive force and require motility to colonize and spread along the small intestine. Therefore, motility may be an attractive target for small molecules that can prevent and/or block the infective process. In this study, we describe a high-throughput screening (HTS) assay to identify small molecules that selectively inhibit bacterial motility. The HTS assay was used to screen an ∼8,000-compound structurally diverse chemical library for inhibitors ofV. choleraemotility. The screen identified a group of quinazoline-2,4-diamino analogs that completely suppressed motility without affecting the growth rate in broth. A further study on the effects of one analog, designated Q24DA, showed that it induces a flagellated but nonmotile (Mot−) phenotype and is specific for the Na+-driven flagellar motor of pathogenicVibriospecies. A mutation conferring phenamil-resistant motility did not eliminate inhibition of motility by Q24DA. Q24DA diminished the expression of cholera toxin and toxin-coregulated pilus as well as biofilm formation and fluid secretion in the rabbit ileal loop model. Furthermore, treatment ofV. choleraewith Q24DA impacted additional phenotypes linked to Na+bioenergetics, such as the function of the primary Na+pump, Nqr, and susceptibility to fluoroquinolones. The above results clearly show that the described HTS assay is capable of identifying small molecules that specifically block bacterial motility. New inhibitors such as Q24DA may be instrumental in probing the molecular architecture of the Na+-driven polar flagellar motor and in studying the role of motility in the expression of other virulence factors.
Increasing Chloramphenicol Resistance in Streptococcus pneumoniae Isolates from Papua New Guinean Children with Acute Bacterial Meningitis
Authors: Manning Laurens , Laman Moses , Greenhill Andrew R. , Michael Audrey , Siba Peter , Mueller Ivo , Davis Timothy M. E.
Published: June 2011

In Papua New Guinean (PNG) children with acute bacterial meningitis (ABM), all
Haemophilus influenzae
isolates were resistant to chloramphenicol. Although
Streptococcus pneumoniae
isolates had a median chloramphenicol MIC of 3 μg/ml, it was ≥4 μg/ml in 42.8%, and the likelihood of an area under the 24-hour concentration-time curve/MIC ratio of >100 h at a MIC of ≥4 μg/ml was approximately 50%. All isolates were ceftriaxone sensitive. These data support ceftriaxone rather than conventional chloramphenicol for all PNG children with suspected ABM.
Characterization of Salmonella enterica Serovar Typhimurium Isolates Harboring a Chromosomally Encoded CMY-2 β-Lactamase Gene Located on a Multidrug Resistance Genomic Island
Authors: Shahada Francis , Sekizuka Tsuyoshi , Kuroda Makoto , Kusumoto Masahiro , Ohishi Daiki , Matsumoto Atsuko , Okazaki Hizuru , Tanaka Kiyoshi , Uchida Ikuo , Izumiya Hidemasa , Watanabe Haruo , Tamamura Yukino , Iwata Taketoshi , Akiba Masato
Published: June 2011

Since 2004, extended-spectrum cephalosporin (ESC)-resistant
Salmonella enterica
serovar Typhimurium (
S
. Typhimurium) isolates have been detected from cattle in the northern major island of Japan, Hokkaido. Resistance to ESCs was found to be mediated by CMY-2 type β-lactamase among 22 epidemiologically unrelated isolates showing indistinguishable pulsed-field gel electrophoresis patterns. Southern blot analysis using I-CeuI-digested genomic DNA demonstrated that the CMY-2 β-lactamase gene (
bla
CMY-2
) was integrated in a 2.5-Mb chromosomal fragment. Genetic analysis of
S
. Typhimurium isolate L-3553 indicated that
bla
CMY-2
was located on a unique 125-kb genomic island, GI-VII-6, which consists of 140 open reading frames. Pairwise alignment of GI-VII-6 and
Escherichia coli
plasmid pAR060302 (size, 167 kb) revealed that a large proportion of GI-VII-6 (99%) shows a high sequence similarity (>99%) with pAR060302. GI-VII-6 contains 11 antimicrobial resistance genes including
sul1
,
qacE
Δ
1
,
aadA2
, and
dfrA12
in the
aadA2
region;
sugE1
and
bla
CMY-2
in the
bla
CMY-2
region; and
sul2
,
strA
,
strB
,
tet
(A), and
floR
in the
floR
region. Two directly repeated IS
26
copies were present at both ends of GI-VII-6. Junction regions of GI-VII-6 were flanked by an 8-bp direct repeat, indicating that GI-VII-6 was acquired by transposition involving IS
26
transposase. PCR scanning revealed that the overall structure of GI-VII-6 was almost identical in the 22 isolates. Phylogenetic analysis suggested that
S
. Typhimurium isolates harboring GI-VII-6 belong to a different genomic lineage than other whole-genome-sequenced
S
. Typhimurium strains. These data indicate that a particular clone of
S
. Typhimurium harboring GI-VII-6 has spread among the cattle population in Hokkaido, Japan.
Lack of an Effect of Standard and Supratherapeutic Doses of Linezolid on QTc Interval Prolongation
Authors: Damle Bharat , LaBadie Robert R. , Cuozzo Cheryl , Alvey Christine , Choo Heng Wee , Riley Steve , Kirby Deborah
Published: June 2011

A double-blind, placebo-controlled, four-way crossover study was conducted in 40 subjects to assess the effect of linezolid on corrected QT (QTc) interval prolongation. Time-matched, placebo-corrected QT intervals were determined predose and at 0.5, 1 (end of infusion), 2, 4, 8, 12, and 24 h after intravenous dosing of linezolid 600 and 1,200 mg. Oral moxifloxacin at 400 mg was used as an active control. The pharmacokinetic profile of linezolid was also evaluated. At each time point, the upper bound of the 90% confidence interval (CI) for placebo-corrected QTcF values (i.e., QTc values adjusted for ventricular rate using the correction methods of Fridericia) for linezolid 600 and 1,200-mg doses were <10 ms, which indicates an absence of clinically significant QTc prolongation. At 2 and 4 h after the moxifloxacin dose, corresponding to the population
T
max
, the lower bound of the two-sided 90% CI for QTcF when comparing moxifloxacin to placebo was >5 ms, indicating that the study was adequately sensitive to assess QTc prolongation. The pharmacokinetic profile of linezolid at 600 mg was consistent with previous observations. Systemic exposure to linezolid increased in a slightly more than dose-proportional manner at supratherapeutic doses, but the degree of nonlinearity was small. At a supratherapeutic single dose of 1,200 mg of linezolid, no treatment-related increase in adverse events was seen compared to 600 mg of linezolid, and no clinically meaningful effects on vital signs and safety laboratory evaluations were noted.
Infection of Polarized Airway Epithelial Cells by Normal and Small-Colony Variant Strains of Staphylococcus aureus Is Increased in Cells with Abnormal Cystic Fibrosis Transmembrane Conductance Regulator Function and Is Influenced by NF-κB
Authors: Mitchell Gabriel , Grondin Gilles , Bilodeau Ginette , Cantin André M. , Malouin François
Published: June 2011

The infection of nonphagocytic host cells by
Staphylococcus aureus
and more particularly by small-colony variants (SCVs) may contribute to the persistence of this pathogen in the lungs of cystic fibrosis (CF) patients. The development of chronic infections is also thought to be facilitated by the proinflammatory status of CF airways induced by an activation of NF-κB. The aim of this study was to compare the infection of non-CF and CF-like airway epithelial cells by
S. aureus
strains (normal and SCVs) and to determine the impact of the interaction between cystic fibrosis transmembrane conductance regulator (CFTR) and NF-κB on the infection level of these cells by
S. aureus
. We developed an
S. aureus
infection model using polarized airway epithelial cells grown at the air-liquid interface and expressing short hairpin RNAs directed against CFTR to mimic the CF condition. A pair of genetically related CF coisolates with the normal and SCV phenotypes was characterized and used. Infection of both cell lines (non-CF and CF-like) was more productive with the SCV strain than with its normal counterpart. However, both normal and SCV strains infected more CF-like than non-CF cells. Accordingly, inhibition of CFTR function by CFTR
inh
-172 increased the
S. aureus
infection level. Experimental activation of NF-κB also increased the level of infection of polarized pulmonary epithelial cells by
S. aureus
, an event that could be associated with that observed when CFTR function is inhibited or impaired. This study supports the hypothesis that the proinflammatory status of CF tissues facilitates the infection of pulmonary epithelial cells by
S. aureus
.
Allelic Variation of the Lyme Disease Spirochete Adhesin DbpA Influences Spirochetal Binding to Decorin, Dermatan Sulfate, and Mammalian Cells
Authors: Benoit Vivian M. , Fischer Joshua R. , Lin Yi-Pin , Parveen Nikhat , Leong John M.
Published: June 2011

After transmission by an infected tick, the Lyme disease spirochete,
Borrelia burgdorferi
sensu lato, colonizes the mammalian skin and may disseminate systemically. The three major species of Lyme disease spirochete—
B. burgdorferi
sensu stricto,
B. garinii
, and
B. afzelii
—are associated with different chronic disease manifestations. Colonization is likely promoted by the ability to bind to target tissues, and Lyme disease spirochetes utilize multiple adhesive molecules to interact with diverse mammalian components. The allelic variable surface lipoprotein decorin binding protein A (DbpA) promotes bacterial binding to the proteoglycan decorin and to the glycosaminoglycan (GAG) dermatan sulfate. To assess allelic variation of DbpA in GAG-, decorin-, and cell-binding activities, we expressed
dbpA
alleles derived from diverse Lyme disease spirochetes in
B. burgdorferi
strain B314, a noninfectious and nonadherent strain that lacks
dbpA
. Each DbpA allele conferred upon
B. burgdorferi
strain B314 the ability to bind to cultured kidney epithelial (but not glial or endothelial) cells, as well as to purified decorin and dermatan sulfate. Nevertheless, allelic variation of DbpA was associated with dramatic differences in substrate binding activity. In most cases, decorin and dermatan sulfate binding correlated well, but DbpA of
B. afzelii
strain VS461 promoted differential binding to decorin and dermatan sulfate, indicating that the two activities are separable. DbpA from a clone of
B. burgdorferi
strain N40 that can cause disseminated infection in mice displayed relatively low adhesive activity, indicating that robust DbpA-mediated adhesive activity is not required for spread in the mammalian host.
Discrepancy between participants' understanding and desire to know in informed consent: are they informed about what they really want to know?
Authors: Koh Jiwon , Goh Eurah , Yu Kyung-Sang , Cho Belong , Yang Jeong Hee
Published: June 2011

Background

Participants' understanding of clinical trials is important in informed consent. However, little is known about what information participants really want to know.

Aims

To demonstrate the existence of a discrepancy between participants' understanding and their desire to know.

Methods

The participants in clinical trials at Seoul National University Hospital were surveyed. The survey consisted of 11 statements based on the essential elements of informed consent. The participants gave two responses to each statement on a five-point Likert scale to rate their subjective understanding and desire to know, respectively. Information discrepancy was defined as the difference between these two ratings: if understanding exceeded desire to know for a particular item, it was defined as ‘over-informed’; if desire to know exceeded understanding for a particular item, it was defined as ‘under-informed’.

Results

Participants reported good understanding of ‘voluntariness’, ‘duration’, ‘study involves research’ and poor understanding of ‘confidentiality’, ‘compensation’, ‘benefits’, ‘procedures’ and ‘risks or discomforts’. For ‘risks or discomforts’, ‘who to contact’, ‘voluntariness’, ‘duration’ and ‘procedures’, participants reported high desire to know compared with ‘confidentiality’, ‘purpose’, ‘study involves research’ and ‘benefits’. The elements ‘study involves research’, ‘voluntariness’, ‘duration’, ‘purpose’ and ‘who to contact’ were over-informed, while ‘compensation’, ‘risks or discomforts’, ‘procedures’, ‘confidentiality’ and ‘benefits’ were under-informed. Participants over 50 years of age, those without a college education and those whose participation was less voluntary were relatively less informed about the clinical trials.

Conclusions

An information discrepancy was observed between the participants' understanding and their desire to know. By putting more emphasis on under-informed elements, the quality of informed consent could be improved.
Risk of disclosure of participating in an internet-based HIV behavioural risk study of men who have sex with men
Authors: Khosropour Christine M , Sullivan Patrick S
Published: June 2011

As the frequency of internet-based research has increased, it is important for researchers to consider how the conditions in which data are collected may influence the risks to participants. In particular, because internet-based data collection often occurs outside a clinical or research setting, there may be unintentional disclosures of a participant's involvement in a research study of which the researcher is unaware. The current analysis examined the responses of men who have sex with men participating in an internet-based HIV behavioural risk study when queried about the possible disclosure of their participation in the study. Fewer than 2% of participants indicated that their participation in the research study was disclosed, and all but one indicated no negative outcomes associated with the disclosure. As the field of online research continues to expand, it is important to consider risks that are unique to internet-based research, and to monitor these risks to ensure that the confidentiality of research subjects is maintained.
Moral duties and euthanasia: why to kill is not necessarily the same as to let die
Authors: McLachlan Hugh
Published: June 2011

David Shaw's response to Hugh McLachlan's criticism of his proposed new perspective on euthanasia is ineffectual, mistaken and unfair. It is false to say that the latter does not present an argument to support his claim that there is a moral difference between killing and letting die. It is not the consequences alone of actions that constitute their moral worth. It can matter too what duties are breached or fulfilled by the particular moral agents who are involved.
Characteristics of epileptic episodes in UK dog breeds: an epidemiological approach
Authors: Short A. D. , Dunne A. , Lohi H. , Boulton S. , Carter S. D. , Timofte D. , Ollier W. E. R.
Published: June 2011

In this study, previously unreported cohort characteristics and seizure patterns for canine epilepsy were identified from a series of UK‐based epileptic dogs containing 1260 cases from 79 known pedigree breeds and a group of crossbreed dogs.
SEESAW AND LEPTOGENESIS: A TRIANGULAR ANSATZ
Authors: FALCONE D.
Published: June 2011

A triangular ansatz for the seesaw mechanism and baryogenesis via leptogenesis is explored. In a basis where both the charged lepton and the Majorana mass matrix are diagonal, the Dirac mass matrix can generally be written as the product of a unitary times a triangular matrix. We assume the unitary matrix to be the identity and then an upper triangular Dirac matrix. Constraints from bilarge lepton mixing and leptogenesis are studied.
NO-BOUNDARY COSMOLOGY
Authors: WU ZHONG CHAO
Published: June 2011

We present a brief summary of the developments of no-boundary quantum cosmology for the last three decades.
EFFECTS OF NOISE ON CYCLIC COMPETITIONS AMONG THREE SPECIES
Authors: NIE LINRU , GONG AILING , MEI DONGCHENG
Published: June 2011

The Lotka–Volterra model of cyclic competitions among three species with noise was investigated by numerical simulations. Our results indicate that the multiplicative noise is responsible for the alternately sinusoidal competitive oscillations of species, the optimizations of response of the system via stochastic resonance, the spatial patterns and the temporal oscillations of the spatial correlation coefficients.
COHERENCE RESONANCE–INDUCED STOCHASTIC NEURAL FIRING AT A SADDLE-NODE BIFURCATION
Authors: GU HUAGUANG , ZHANG HUIMIN , WEI CHUNLING , YANG MINGHAO , LIU ZHIQIANG , REN WEI
Published: June 2011

Coherence resonance at a saddle-node bifurcation point and the corresponding stochastic firing patterns are simulated in a theoretical neuronal model. The characteristics of noise-induced neural firing pattern, such as exponential decay in histogram of interspike interval (ISI) series, independence and stochasticity within ISI series are identified. Firing pattern similar to the simulated results was discovered in biological experiment on a neural pacemaker. The difference between this firing and integer multiple firing generated at a Hopf bifurcation point is also given. The results not only revealed the stochastic dynamics near a saddle-node bifurcation, but also gave practical approaches to identify the saddle-node bifurcation and to distinguish it from the Hopf bifurcation in neuronal system. In addition, many previously observed firing patterns can be attribute to stochastic firing pattern near such a saddle-node bifurcation.
COVERING A POINT SET BY TWO DISJOINT RECTANGLES
Authors: KIM SANG-SUB , BAE SANG WON , AHN HEE-KAP
Published: June 2011

Given a set S of n points in the plane, the disjoint two-rectangle covering problem is to find a pair of disjoint rectangles such that their union contains S and the area of the larger rectangle is minimized. In this paper we consider two variants of this optimization problem: (1) the rectangles are allowed to be reoriented freely while restricting them to be parallel to each other, and (2) one rectangle is restricted to be axis-parallel but the other rectangle is allowed to be reoriented freely. For both of the problems, we present O(n2 log n)-time algorithms using O(n) space.
GREEDY CONSTRUCTION OF 2-APPROXIMATE MINIMUM MANHATTAN NETWORKS
Authors: GUO ZEYU , SUN HE , ZHU HONG
Published: June 2011

Given a set T of n points in ℝ2, a Manhattan network on T is a graph G = (V,E) with the property that all the edges in E are vertical or horizontal line segments connecting points in V ⊇ T and for all p, q ∈ T, the graph contains a path having the length exactly L1 distance between p and q. The Minimum Manhattan Network problem is to find a Manhattan network of minimum length, i.e. minimizing the total length of the line segments of the network. In this paper we present a 2-approximation algorithm with time complexity O(n log n), which improves over a recent combinatorial 2-approximation algorithm with running time O(n2). Moreover, compared with other 2-approximation algorithms using linear programming or dynamic programming techniques, we show that a greedy strategy suffices to obtain a 2-approximation algorithm.
RELIABILITY BOUNDS OF A 3-DIMENSIONAL CONSECUTIVE-k-OUT-OF-n : F SYSTEM
Authors: BOUSHABA MAHMOUD , AZOUZ ZINEB
Published: June 2011

A 3-dimensional consecutive k-out-of-n : F system consists of n3 components disposed on a cubic grid of size n; it fails if and only if all the components of at least one cube of size k (1 < k < n) fail (k3 components). Although introduced as early as in 1992 by Salvia and Lasher7 as a better model for problems in medical imaging, few results are known about it.1 In this paper, we propose, in the the independent and not-necessarily-identical case, a new lower bound which has the advantage of being calculated directly from the reliability of a one dimensional consecutive-k-out-of-n:F system. To do this, we derive an intermediate system2 which behaves like a one dimensional consecutive k-out-of-n and is less reliable than the initial 3-dimensional system, hence its suitability as the lower bound. The proposed approach converts a three-dimensional system into a one-dimensional system directly. It can be extended to the three-dimensional versions of the k-within-connected-(r,s,t)-out-of-(m,n,p):F system and the m-consecutive-k-out-of-n : F system.
SWITCHING RATES AND THE ASYMPTOTIC BEHAVIOR OF HERDING MODELS
Authors: IRLE ALBRECHT , KAUSCHKE JONAS , LUX THOMAS , MILAKOVIĆ MISHAEL
Published: June 2011

Markov chains have experienced a surge of economic interest in the form of behavioral agent-based models that aim at explaining the statistical regularities of financial returns. We review some of the relevant mathematical facts and show how they apply to agent-based herding models, with the particular goal of establishing their asymptotic behavior since several studies have pointed out that the ability of such models to reproduce the stylized facts hinges crucially on the size of the agent population (typically denoted by N), a phenomenon that is also known as N-dependence. Our main finding is that N-(in)dependence traces back to both the topology and the velocity of information transmission among heterogeneous financial agents.
SHARED BICYCLES IN A CITY: A SIGNAL PROCESSING AND DATA ANALYSIS PERSPECTIVE
Authors: BORGNAT PIERRE , ABRY PATRICE , FLANDRIN PATRICK , ROBARDET CÉLINE , ROUQUIER JEAN-BAPTISTE , FLEURY ERIC
Published: June 2011

Community shared bicycle systems, such as the Vélo'v program launched in Lyon in May 2005, are public transportation programs that can be studied as a complex system composed of interconnected stations that exchange bicycles. They generate digital footprints that reveal the activity in the city over time and space, making possible a quantitative analysis of movements using bicycles in the city. A careful study relying on nonstationary statistical modeling and data mining allows us to first model the time evolution of the dynamics of movements with Vélo'v, that is mostly cyclostationary over the week with nonstationary evolutions over larger time-scales, and second to disentangle the spatial patterns to understand and visualize the flows of Vélo'v bicycles in the city. This study gives insights on the social behaviors of the users of this intermodal transportation system, the objective being to help in designing and planning policy in urban transportation.
THE DIVERSITY IN THE DECISION FACILITATES COOPERATION IN THE SEQUENTIAL PRISONER'S DILEMMA GAME
Authors: OHDAIRA TETSUSHI , TERANO TAKAO
Published: June 2011

The condition of cooperation in social conflicts of interest has been an interesting topic. On the one hand people usually desire to make their own profit. On the other hand, they mutually cooperate. This fact has motivated many researchers. Some solutions for this question have been proposed, and particular studies indicate that the diversity in decision-making or relationships promotes cooperation. In this research, we achieve the diversity by utilizing the novel method that refers to the mechanism of correction regarding each probability that every strategy comes to the representative by decision-making of group. This mechanism works when difference between the probability of the first and others becomes quite large. If once every group adopts this corrected decision, he/she achieves mutual cooperation of high level in the sequential prisoner's dilemma game in case the number of strategies (= players) is within the definite range. We also note that this game can effectively describe the property of evolution of strategy only with a small number of players. When each group has many players, in contrast to previous research, the decision with correction also has an effect on the suppression of prevalence of defection. In addition, we also show that the decision of this model is analogous to the system of redistribution of revenue, which provides balance of strength between several teams in professional sports.
EVOLUTIONARY GAMES ON VISIBILITY GRAPHS
Authors: MURKS ALEKSANDRA , PERC MATJAŽ
Published: June 2011

We show that time series of different complexities can be transformed into networks that host individuals playing evolutionary games. The irregularity of the time series is thereby faithfully reflected in the fraction of cooperators surviving the evolutionary process, thus effectively linking time series with evolutionary games. Pivotal to the linkage is a simple visibility algorithm that transforms time series into networks. More specifically, periodic series yield regular networks, chaotic series yield random networks, while fractal series yield scale-free networks. As an example, we use a chaotic time series from the Logistic map and a fractal time series of Brownian motion, yielding an interaction network with an exponential and a power-law degree distribution, respectively. By employing the prisoner's dilemma and the snowdrift game, we demonstrate that such heterogeneous interaction networks facilitate the evolution of cooperation if compared to the traditional square lattice topology. Due to the simplicity of the employed methodology, newcomers with a basic command of nonlinear dynamics or stochastic processes can become easily acquainted with evolutionary games, and moreover, integrate these interesting and vibrant subfields of physics more effectively into their research.
NETWORK AUTOMATA: COUPLING STRUCTURE AND FUNCTION IN DYNAMIC NETWORKS
Authors: SMITH DAVID M. D. , ONNELA JUKKA-PEKKA , LEE CHIU FAN , FRICKER MARK D. , JOHNSON NEIL F.
Published: June 2011

We introduce Network Automata, a framework which couples the topological evolution of a network to its structure. To demonstrate its implementation we describe a simple model which exhibits behavior similar to the "Game of Life" before recasting some simple, well-known network models as Network Automata. We then introduce Functional Network Automata which are useful for dealing with networks in which the topology evolves according to some specified microscopic rules and, simultaneously, there is a dynamic process taking place on the network that both depends on its structure but is also capable of modifying it. It is a generic framework for modeling systems in which network structure, dynamics, and function are interrelated. At the practical level, this framework allows for precise, unambiguous implementation of the microscopic rules involved in such systems. To demonstrate the approach, we develop a family of simple biologically inspired models of fungal growth.
A MODEL FOR THE EMERGENCE OF SOCIAL ORGANIZATION IN PRIMATES
Authors: KUPERMAN M. N.
Published: June 2011

Recent studies have established a relationship between the repertoire of signals used for communication and neocortex size of different species of primates and the topology of the social network formed by the interactions between individuals. Inspired by these results, we have developed a model that qualitatively reproduces these observations. The model presents the social organization as a self-organized process where the size of the repertoire in one case and of the neocortex in another play a highly relevant role.
OSCILLATORY DYNAMICS INDUCED BY MULTI-DELAYS IN GENE EXPRESSION
Authors: WANG QI , LIU BO , YAN SHIWEI
Published: June 2011

We discuss the existence of Hopf bifurcation, the dynamical stability breaking of the molecular concentrations of two generic biochemical reaction systems and their sensitivity to the changes of the parameters incorporated in the model equations. It is found that the oscillatory dynamics can be expected for the systems due to the inclusion of time delays. The chaotic dynamics and the periodic windows in the chaotic domains can exist in the case of the system with two time delays. The proposed mathematical method may have the significance in the problems where the negative and/or positive feedback dynamics, as well as the time delays have the characteristic physical and biological background.
Palaeozoic–Mesozoic history of SE Asia
Authors: Metcalfe Ian
Published: June 2011

SE Asia comprises a collage of Gondwana-derived continental blocks assembled by the closure of multiple Tethyan and back-arc ocean basins now represented by suture zones. Two major biogeographical boundaries, the Late Palaeozoic Gondwana–Cathaysia divide and the Cenozoic-Recent Australia–Asia divide (Wallace Line) are present. Palaeozoic and Mesozoic evolution involved the rifting and separation of three collages of continental terranes from eastern Gondwana and the opening and closure of three successive ocean basins, the Palaeo-Tethys (Devonian–Triassic), Meso-Tethys (Permian–Cretaceous) and Ceno-Tethys (Late Triassic–Cenozoic). This led to the opening and closing of ocean gateways and provision of shallow-marine and terrestrial land bridges and stepping-stones for biotic migration. The SE Asia core (Sundaland) comprises a western Sibumasu block, an eastern Indochina–East Malaya block, and the Sukhothai Island Arc terrane between. The Jinghong, Nan-Uttaradit and Sra Kaeo sutures represent the Sukhothai closed back-arc basin. The Palaeo-Tethys is represented by the Changning-Menglian, Chiang Mai/Inthanon and Bentong-Raub suture zones. The West Sumatra and West Burma blocks were accreted to the Sundaland core in the Late Permian–Early Triassic. SW Borneo and/or East Java–West Sulawesi are now identified as the missing ‘Argoland’ that separated from NW Australia in the Jurassic and accreted to SE Sundaland in the Cretaceous.
Automotive autonomy
Authors: Wright Alex
Published: June 2011

Self-driving cars are inching closer to the assembly line, thanks to promising new projects from Google and the European Union.
The status of women of color in computer science
Authors: Ong Maria (Mia)
Published: June 2011

Addressing the challenges of increasing the number of women of color in computing and ensuring their success.
Passing a language through the eye of a needle
Authors: Ierusalimschy Roberto , De Figueiredo Luiz Henrique , Celes Waldemar
Published: June 2011

How the embeddability of Lua impacted its design.
DSL for the uninitiated
Authors: Ghosh Debasish
Published: June 2011

Domain-specific languages bridge the semantic gap in programming.
Microsoft's protocol documentation program
Authors: CACM Staff
Published: June 2011

A discussion with Nico Kicillof, Wolfgang Grieskamp, and Bob Binder.
A decade of software model checking with SLAM
Authors: Ball Thomas , Levin Vladimir , Rajamani Sriram K.
Published: June 2011

SLAM is a program-analysis engine used to check if clients of an API follow the API's stateful usage rules.