bluuebunny/crossref_metadata_2025 huggingface dataset:
Ectopic Expression of Rice OsBIANK1, Encoding an Ankyrin Repeat‐Containing Protein, in Arabidopsis Confers Enhanced Disease Resistance to Botrytis cinerea and Pseudomonas syringae
Authors: Li Dayong , Wang Fengrang , Liu Bo , Zhang Yafen , Huang Lei , Zhang Huijuan , Song Fengming
Published: September 2012

Ankyrin repeat‐containing proteins comprise a large family whose members have been shown to play important roles in various aspects of biological processes in plant growth and development as well as in responses to biotic and abiotic stresses. We previously identified a rice gene, OsBIANK1, encoding an ankyrin repeat‐containing protein and found that expression of OsBIANK1 can be induced by defence signalling molecules and by infection of Magnaporthe oryzae, the causal agent of blast disease. To better understand the possible function of OsBIANK1 in disease resistance, we generated transgenic Arabidopsis plants that constitutively overexpress the OsBIANK1 gene. Results from disease assays revealed that the OsBIANK1‐overexpressing plants display increased resistance against Botrytis cinerea and Pseudomonas syringae pv. tomato DC3000 as compared with the wild‐type plants. In OsBIANK1‐overexpressing plants, expression of some of well‐known defence genes (e.g. PR‐1, PR‐2 and PDF1.2) was up‐regulated after infection with B. cinerea or P. syringae pv. tomato DC3000. Furthermore, the OsBIANK1‐overexpressing plants showed decreased levels of reactive oxygen species (i.e. superoxide anion and H2O2) after Botrytis infection. Thus, our present results further support the role of OsBIANK1 in regulation of defence responses against different types of pathogens.
Is dispersal guided by the environment? A comparison of interspecific gene flow estimates among differentiated regions of a newt hybrid zone
Authors: Espregueira Themudo G. , Nieman A. M. , Arntzen J. W.
Published: September 2012

How frequently genes pass through a hybrid zone may be influenced by the environment. Accordingly, in long hybrid zones that span more than one environmental setting, different patterns may emerge. The varied conditions allow testing of hypotheses on dispersal as a function of the environment. We reconstruct the amount and direction of gene flow across a heterogeneous hybrid zone of two species of marbled newts (Triturus marmoratusandTriturus pygmaeus), in four widely separated areas of theIberianPeninsula from one mitochondrial and three nuclear genes. The main variables associated with the position of the contact zone are precipitation, rivers, altitude and relief. In some sections of the contact zone, however, its position is not correlated with any environmental factor and is instead determined by the shortest geographical distance between fixed positions at either side (mountains in theEast and river in theWest). In areas where the position of the zone is stable, gene flow was bidirectional. External data show thatT. pygmaeushas supersededT. marmoratusover a large area and here gene flow was unidirectional. The prediction that a major river would reduce gene flow was not confirmed.
Asexual reproduction in introduced and native populations of the ant Cerapachys biroi
Authors: Kronauer Daniel J. C. , Pierce Naomi E. , Keller Laurent
Published: September 2012

Asexual reproduction is particularly common among introduced species, probably because it helps to overcome the negative effects associated with low population densities during colonization. The ant Cerapachys biroi has been introduced to tropical and subtropical islands around the world since the beginning of the last century. In this species, workers can reproduce via thelytokous parthenogenesis. Here, we use genetic markers to reconstruct the history of anthropogenic introductions of C. biroi, and to address the prevalence of female parthenogenesis in introduced and native populations. We show that at least four genetically distinct lineages have been introduced from continental Asia and have led to the species' circumtropical establishment. Our analyses demonstrate that asexual reproduction dominates in the introduced range and is also common in the native range. Given that C. biroi is the only dorylomorph ant that has successfully become established outside of its native range, this unusual mode of reproduction probably facilitated the species' worldwide spread. On the other hand, the rare occurrence of haploid males and at least one clear case of sexual recombination in the introduced range show that C. biroi has not lost the potential for sex. Finally, we show that thelytoky in C. biroi probably has a genetic rather than an infectious origin, and that automixis with central fusion is the most likely underlying cytological mechanism. This is in accordance with what is known for other thelytokous eusocial Hymenoptera.
Splenocyte apoptosis in Plasmodium berghei ANKA infection: possible role of TNF‐α and TGF‐β
Authors: Keswani T. , Bhattacharyya A.
Published: September 2012

Cerebral malaria is associated with the circulating levels of tumour necrosis factor alpha (TNF‐α) and transforming growth factor β (TGF‐β), but association between these two cytokines and implications in splenocyte apoptosis remain largely obscured. We have evaluated the outcome of TGF‐β and TNF‐α production in the context of splenocyte apoptosis during Plasmodium berghei ANKA (PbA) infection. Blood‐stage PbA infection confirmed blood–brain barrier disruption, disarray of white pulp, increase in percentage of sub‐G0/G1 and splenocyte apoptosis. Flow cytometric analysis reveals up‐regulation of Fas‐L followed by caspase‐8 and caspase‐3 activation and signifies possible involvement of Fas‐L‐mediated splenocyte apoptosis. We have observed down‐regulation of TGF‐β and up‐regulation of TNF‐α in tissue and serum level, respectively, during PbA infection. Association between the production of TGF‐β and the severity of malaria infection in splenocytes was verified with TGF‐β inhibitor that exacerbated the apoptotic process. In contrary, TNF‐α inhibitor causes significant delay in apoptotic process, but could not alter the lethality of parasite. Thus, results from this study suggest that the critical balance between TGF‐β and TNF‐α might have a key role on Fas‐L‐mediated splenocyte apoptosis during experimental cerebral malaria.
The antiapoptotic activity of Heligmosomoides polygyrus antigen fractions
Authors: Doligalska M. , Brodaczewska K. , Donskow‐ Łysoniewska K.
Published: September 2012

Our study identified Heligmosomoides polygyrus antigen factors with potential activity for regulation of T‐cell proliferation and surviving of CD4+CD25−, CD4+CD25hi and CD3+CD8+ cell populations. The antiapoptotic activity of antigenic fractions separated by HPLC was evaluated in vitro after exposure of cells to DEX and rTNF‐α. Different populations of cells responded to antigen fractions in distinct pattern; the most sensitive population of cells to H. polygyrus products were CD4+CD25hi after exposure to DEX and CD3+CD8+ T cells after exposure to rTNF‐α. H. polygyrus antigens may influence survival of CD8+ T cells by regulation of c‐FLIP rather than Bcl‐2, which affects survival of CD4+CD25hi Treg cells and CD4+ T cells. Activation of NF‐κB subunits, for example, p50 and p65 was essential for resistance of cells to apoptosis, and antigenic fractions F9 and F17 exerted different effect to F13. The most active fraction in inhibition of apoptosis was F9, which includes Hsp‐60, calumenin, ferritin, galectin and thrombospondin. This study may provide new clues for recognition of factors that regulate the immune response during infection and which engage the TNF‐α receptor‐mediated and the mitochondria‐mediated death pathway.
Cardiac damage induced by immunization with heat‐killed Trypanosoma cruzi is not antibody mediated
Authors: Bonney K. M. , Gifford K. M. , Taylor J. M. , Chen C.‐I. , Engman D. M.
Published: September 2012

Cardiac inflammation that develops during infection with Trypanosoma cruzi may result in part from autoimmunity, which may occur after bystander activation, after parasite‐induced cardiomyocyte damage, or molecular mimicry. A/J mice infected with T. cruzi or immunized with heat‐killed T. cruzi (HKTC) develop strong autoimmunity accompanied by cardiac damage. To determine whether this cardiac damage occurs via an antibody‐dependent mechanism, we analysed T. cruzi‐infected and HKTC‐immunized mice for the presence of autoantibodies, cardiac antibody deposition, and serum cardiac troponin I as a measure of cardiac damage. We also performed a serum transfer experiment in which sera from T. cruzi‐infected and T. cruzi‐immunized mice (and controls) were transferred into naïve recipients, which were then analysed for the presence of antibodies and serum troponin. Unlike T. cruzi‐infected mice, T. cruzi‐immunized mice did not show significant antibody deposition in the myocardium. These results indicate that antibody deposition does not precede cardiac damage and inflammation in mice immunized with or infected with T. cruzi. Serum adoptive transfer did not induce cardiac damage in any recipients. Based on these findings, we conclude that the cardiac damage induced by immunization with HKTC is not mediated by antibodies.
Analysis of serum cytokine levels in children with chronic cough associated with Toxocara canis infection
Authors: Nagy D. , Bede O. , Danka J. , SzÉnási Z. , Sipka S.
Published: September 2012

Toxocara infection is associated with an increased prevalence of airway symptoms and may be a possible aetiologic agent of chronic cough. The occurrence of toxocariasis in Hungary is mild and/or sporadic. The purpose of this study was to investigate the levels of serum cytokines (IL‐1, IL‐2, IL‐4, IL‐5, IL‐6, IL‐10, IL‐13, IFN‐gamma and TNF‐alpha) and total IgE, the blood eosinophil count, the results of skin prick and non‐specific bronchus provocation tests in Toxocara‐seropositive children with chronic cough relative to those in healthy controls. The patients exhibited moderate eosinophilia, significantly elevated levels of serum total IgE, IL‐6, IL‐10, IL‐13 and IFN‐gamma, and higher skin reactivity to common allergens, whereas the bronchial hyperreactivity was similar in the two groups. The protective proinflammatory cytokines (IL‐6, IFN‐gamma and IL‐13) in association with the anti‐inflammatory cytokine (IL‐10) were simultaneously increased in Toxocara‐infected children with chronic cough. During infections, the activation and suppression of immune processes occur simultaneously and cytokines of Th1/Th2 and regulatory T cells contribute to the regulation of the immune response evoked by helminth infections (depending on the parasite load, the timing and duration of the infection and the status of the host immune system).
Modeling Embryo Transfer into a Closed Uterine Cavity
Authors: Yaniv Sarit , Jaffa Ariel J. , Elad David
Published: September 2012

Embryo transfer (ET) is the last manual intervention after extracorporeal fertilization. After the ET procedure is completed, the embryos are conveyed in the uterus for another two to four days due to spontaneous uterine peristalsis until the window time for implantation. The role of intrauterine fluid flow patterns in transporting the embryos to their implantation site during and after ET was simulated by injection of a liquid bolus into a two-dimensional liquid-filled channel with a closed fundal end via a liquid-filled catheter inserted in the channel. Numerical experiments revealed that the intrauterine fluid field and the embryos transport pattern were strongly affected by the closed fundal end. The embryos re-circulated in small loops around the vicinity where they were deposited from the catheter. The transport pattern was controlled by the uterine peristalsis factors, such as amplitude and frequency of the uterine walls motility, as well as the synchronization between the onset of catheter discharge and uterine peristalsis. The outcome of ET was also dependent on operating parameters such as placement of the catheter tip within the uterine cavity and the delivery speed of the catheter load. In conclusion, this modeling study highlighted important parameters that should be considered during ET procedures in order to increase the potential for pregnancy success.
Experimental Characterization and Finite Element Implementation of Soft Tissue Nonlinear Viscoelasticity
Authors: Troyer Kevin L. , Shetye Snehal S. , Puttlitz Christian M.
Published: September 2012

Finite element (FE) models of articular joint structures do not typically implement the fully nonlinear viscoelastic behavior of the soft connective tissue components. Instead, contemporary whole joint FE models usually represent the transient soft tissue behavior with significantly simplified formulations that are computationally tractable. The resultant fidelity of these models is greatly compromised with respect to predictions under temporally varying static and dynamic loading regimes. In addition, models based upon experimentally derived nonlinear viscoelastic coefficients that do not account for the transient behavior during the loading event(s) may further reduce the model’s predictive accuracy. The current study provides the derivation and validation of a novel, phenomenological nonlinear viscoelastic formulation (based on the single integral nonlinear superposition formulation) that can be directly inputted into FE algorithms. This formulation and an accompanying experimental characterization technique, which incorporates relaxation manifested during the loading period of stress relaxation experiments, is compared to a previously published characterization method and validated against an independent analytical model. The results demonstrated that the static and dynamic FE approximations are in good agreement with the analytical solution. Additionally, the predictive accuracy of these approximations was observed to be highly dependent upon the experimental characterization technique. It is expected that implementation of the novel, computationally tractable nonlinear viscoelastic formulation and associated experimental characterization technique presented in the current study will greatly improve the predictive accuracy of the individual connective tissue components for whole joint FE simulations subjected to static and dynamic loading regimes.
A Multiplanar Radiography Method for Assessing Cup Orientation in Total Hip Arthroplasty
Authors: Amiri Shahram , Masri Bassam A. , Garbuz Donald , Anglin Carolyn , Wilson David R.
Published: September 2012

Correct orientation of the acetabular cup considering patient-specific functional pelvic angles is an important factor for improving outcomes and avoiding complications after total hip arthroplasty. This study introduces a new, noninvasive radiographic tool for accurately determining a patient’s specific pelvic tilt angle preoperatively, as well as accurately assessing acetabular cup orientation with respect to bony landmarks intraoperatively and postoperatively. The method was validated by imaging a bone replica model of the pelvis with implanted hip components, in comparison to digitized references, and verified with a cadaveric specimen. Pelvic tilt was measured with an accuracy of 0.1 deg and SD of 0.4 deg. Operative cup inclination and anteversion showed accuracies of 0.6 deg and 2.5 deg, with SD of 0.4 deg and 0.6 deg, respectively; these could be improved further by subtracting systematic bias. The method shows accuracy advantages over existing radiographic and fluoroscopic methods and exposes the subjects to a lower radiation dose compared to the similar computed tomography methods. These results suggest that the proposed method is feasible for assessing cup placement with reference to the functional and anatomical references. Furthermore, the ability to reference the same bony landmarks preoperatively, intraoperatively, and postoperatively has important research and clinical advantages.
A New Unconditionally Stable Time Integration Method for Analysis of Nonlinear Structural Dynamics
Authors: Akbar Gholampour Ali , Ghassemieh Mehdi , Karimi-Rad Mahdi
Published: September 2012

A new time integration scheme is presented for solving the differential equation of motion with nonlinear stiffness. In this new implicit method, it is assumed that the acceleration varies quadratically within each time step. By increasing the order of acceleration, more terms of the Taylor series are used, which are expected to have responses with better accuracy than the classical methods. By considering this assumption and employing two parameters δ and α, a new family of unconditionally stable schemes is obtained. The order of accuracy, numerical dissipation, and numerical dispersion are used to measure the accuracy of the proposed method. Second order accuracy is achieved for all values of δ and α. The proposed method presents less dissipation at the lower modes in comparison with Newmark's average acceleration, Wilson-θ, and generalized-α methods. Moreover, this second order accurate method can control numerical damping in the higher modes. The numerical dispersion of the proposed method is compared with three unconditionally stable methods, namely, Newmark's average acceleration, Wilson-θ, and generalized-α methods. Furthermore, the overshooting effect of the proposed method is compared with these methods. By evaluating the computational time for analysis with similar time step duration, the proposed method is shown to be faster in comparison with the other methods.
Design of an effective vibration isolation system for measurements sensitive to low-frequency vibrations
Authors: Iwaya Katsuya , Shimizu Ryota , Teramura Akira , Sasaki Seiji , Itagaki Toru , Hitosugi Taro
Published: September 2012

We constructed an effective vibration isolation system that employed an active vibration isolation system on top of a thick base-slab foundation and evaluated the performance by comparing the resultant vibration levels with the most stringent criterion of architectural standards (VC-E). The effect of the thick base slab on reducing vibrations was systematically investigated by comparing vibration levels at the bedrock with those at the base slab. The vibration spectra measured on the active vibration isolation table achieved an overall 1/100–1/200 of the VC-E in the range of 1–100 Hz, except at 5–25 Hz in the vertical direction. In addition, these vibration spectra were compared with those from another vibration isolation system based on a separate foundation. These comparative studies of vibration isolation, including details of the entire systems, can provide useful information for designing an effective vibration isolation system for various experiments that are highly sensitive to low-frequency vibration noise, such as scanning probe microscopy, electron microscopy, and ultrafine patterning.
A method of dose reconstruction for moving targets compatible with dynamic treatments
Authors: Poulsen Per Rugaard , Schmidt Mai Lykkegaard , Keall Paul , Worm Esben Schjødt , Fledelius Walther , Hoffmann Lone
Published: September 2012

Purpose:

To develop a method that allows a commercial treatment planning system (TPS) to perform accurate dose reconstruction for rigidly moving targets and to validate the method in phantom measurements for a range of treatments including intensity modulated radiation therapy (IMRT), volumetric arc therapy (VMAT), and dynamic multileaf collimator (DMLC) tracking.

Methods:

An in‐house computer program was developed to manipulate Dicom treatment plans exported from a TPS (Eclipse, Varian Medical Systems) such that target motion during treatment delivery was incorporated into the plans. For each treatment, a motion including plan was generated by dividing the intratreatment target motion into 1 mm position bins and construct sub‐beams that represented the parts of the treatment that were delivered, while the target was located within each position bin. For each sub‐beam, the target shift was modeled by a corresponding isocenter shift. The motion incorporating Dicom plans were reimported into the TPS, where dose calculation resulted in motion including target dose distributions. For experimental validation of the dose reconstruction a thorax phantom with a moveable lung equivalent rod with a tumor insert of solid water was first CT scanned. The tumor insert was delineated as a gross tumor volume (GTV), and a planning target volume (PTV) was formed by adding margins. A conformal plan, two IMRT plans (step‐and‐shoot and sliding windows), and a VMAT plan were generated giving minimum target doses of 95% (GTV) and 67% (PTV) of the prescription dose (3 Gy). Two conformal fields with MLC leaves perpendicular and parallel to the tumor motion, respectively, were generated for DMLC tracking. All treatment plans were delivered to the thorax phantom without tumor motion and with a sinusoidal tumor motion. The two conformal fields were delivered with and without portal image guided DMLC tracking based on an embedded gold marker. The target dose distribution was measured with a radiochromic film in the moving rod and compared with the reconstructed doses using gamma tests.

Results:

Considerable interplay effects between machine motion and target motion were observed for the treatments without tracking. For nontracking experiments, the mean 2 mm/2% gamma pass rate over all investigated scenarios was 99.6% between calculated and measured doses. For tracking experiments, the mean gamma pass rate was 99.4%.

Conclusions:

A method for accurate dose reconstruction for moving targets with dynamic treatments was developed and experimentally validated in a variety of delivery scenarios. The method is suitable for integration into TPSs, e.g., for reconstruction of the dose delivered to moving tumors or calculation of target doses delivered with DMLC tracking.
Phosphorylation of Cytohesin-1 by Fyn Is Required for Initiation of Myelination and the Extent of Myelination During Development
Authors: Yamauchi Junji , Miyamoto Yuki , Torii Tomohiro , Takashima Shou , Kondo Kazumi , Kawahara Katsumasa , Nemoto Noriko , Chan Jonah R. , Tsujimoto Gozoh , Tanoue Akito
Published: September 2012

Transgenic and knockout mice reveal a pathway that controls the extent of myelination by Schwann cells.
The Tumor Suppressor PTEN Is Exported in Exosomes and Has Phosphatase Activity in Recipient Cells
Authors: Putz Ulrich , Howitt Jason , Doan Anh , Goh Choo-Peng , Low Ley-Hian , Silke John , Tan Seong-Seng
Published: September 2012

A tumor suppressor protein with lipid phosphatase activity is carried to target cells in microvesicles.
Genome Sequence of Lactobacillus ingluviei, a Bacterium Associated with Weight Gain in Animals
Authors: Merhej Vicky , Armougom Fabrice , Robert Catherine , Raoult Didier
Published: September 2012

We report the draft genome sequence of
Lactobacillus ingluviei
strain Autruche 4 (CSURP209) isolated from an ostrich.
L. ingluviei
is associated with weight gain in mice. This genome sequence may help us understand the obesity-induced mechanisms of intestinal bacteria.
Complete Genome Sequence of Amycolatopsis mediterranei S699 Based on
De Novo
Assembly via a Combinatorial Sequencing Strategy
Authors: Tang Biao , Zhao Wei , Zheng Huajun , Zhuo Ying , Zhang Lixin , Zhao Guo-Ping
Published: September 2012

The genome of
Amycolatopsis mediterranei
S699 was resequenced and assembled
de novo
. By comparing the sequences of S699 previously released and that of
A. mediterranei
U32, about 10 kb of major indels was found to differ between the two S699 genomes, and the differences are likely attributable to their different assembly strategies.
Genome Sequence of the Alkaliphilic Bacterium Nitritalea halalkaliphila Type Strain LW7, Isolated from Lonar Lake, India
Authors: Jangir Pramod Kumar , Singh Ajit , Shivaji S. , Sharma Rakesh
Published: September 2012

An alkaliphilic bacterium,
Nitritalea halalkaliphila
LW7, which belongs to the family
Cyclobacteriacae
in the phylum
Bacteroidetes
, was isolated from Lonar Lake in Maharastra, India. Here we announce the draft genome sequence of the type strain LW7, which contains 3,633,701 bp with a G+C content of 48.58%.
Draft Genome Sequences of Two Campylobacter jejuni Clinical Isolates, NW and D2600
Authors: Jerome John P. , Klahn Brian D. , Bell Julia A. , Barrick Jeffrey E. , Brown C. Titus , Mansfield Linda S.
Published: September 2012

The
Campylobacter jejuni
human clinical isolates NW and D2600 colonized C57BL/6 interleukin-10-deficient (IL-10
−/−
) mice without inducing a robust inflammatory response (J. A. Bell et al., BMC Microbiol. 9:57, 2009). We announce draft genome sequences of NW and D2600 to facilitate comparisons with strains that induce gastrointestinal inflammation in this mouse model.
Complete Genome Sequence of Helicobacter cinaedi Type Strain ATCC BAA-847
Authors: Miyoshi-Akiyama Tohru , Takeshita Nozomi , Ohmagari Norio , Kirikae Teruo
Published: September 2012

Here we report the completely annotated genome sequence of the
Helicobacter cinaedi
type strain (ATCC BAA-847), which is an emerging pathogen that causes cellulitis and bacteremia. The genome sequence will provide new insights into the diagnosis, pathogenic mechanisms, and drug resistance of
H. cinaedi
.
Draft Genome Sequence of Weissella koreensis KCTC 3621T
Authors: Lee Je Hee , Bae Jin-Woo , Chun Jongsik
Published: September 2012

Weissella koreensisis a Gram-positive, rod-shaped, nonmotile, and facultative anaerobic species belonging to the lactic acid bacteria (LAB). The members of this species have been repeatedly isolated from kimchi (a traditional Korean fermented food) and are known for their beneficial effects on human and animal intestinal microflora through producing various clinically important amino acids such as γ-aminobutyric acid and ornithine. Here we report the genome sequence of the type strain ofW. koreensis(KCTC 3621T) to provide taxonomic and functional insights into the species.
Genome Sequence of Enterococcus sp. Strain C1, an Azo Dye Decolorizer
Authors: Chan Giek Far , Gan Han Ming , Rashid Noor Aini Abdul
Published: September 2012

Enterococcus
sp. strain C1 is a facultative anaerobe which was coisolated with
Citrobacter
sp. strain A1 from a sewage oxidation pond. Strain C1 could degrade azo dyes very efficiently via azo reduction and desulfonation in a microaerophilic environment. Here the draft genome sequence of
Enterococcus
sp. C1 is reported.
Draft Genome Sequence of Klebsiella pneumoniae subsp. pneumoniae DSM 30104
T
Authors: Lee Je Hee , Cheon In Su , Shim Byoung-Shik , Kim Dong Wook , Kim Suhng Wook , Chun Jongsik , Song Manki
Published: September 2012

Klebsiella pneumoniae
is a Gram-negative, rod-shaped, nonmotile, and opportunistic pathogenic species with clinical importance. It is a part of natural flora of humans and animals. Here we report the draft genome sequence of the type strain of
Klebsiella pneumoniae
subsp.
pneumoniae
(DSM 30104
T
) to provide taxonomic and functional insights into the species.
MetR-Regulated Vibrio cholerae Metabolism Is Required for Virulence
Authors: Bogard Ryan W. , Davies Bryan W. , Mekalanos John J.
Published: September 2012

LysR-type transcriptional regulators (LTTRs) are the largest, most diverse family of prokaryotic transcription factors, with regulatory roles spanning metabolism, cell growth and division, and pathogenesis. Using a sequence-defined transposon mutant library, we screened a panel of
V. cholerae
El Tor mutants to identify LTTRs required for host intestinal colonization. Surprisingly, out of 38 LTTRs, only one severely affected intestinal colonization in the suckling mouse model of cholera: the methionine metabolism regulator, MetR. Genetic analysis of genes influenced by MetR revealed that
glyA1
and
metJ
were also required for intestinal colonization. Chromatin immunoprecipitation of MetR and quantitative reverse transcription-PCR (qRT-PCR) confirmed interaction with and regulation of
glyA1
, indicating that misregulation of
glyA1
is likely responsible for the colonization defect observed in the
metR
mutant. The
glyA1
mutant was auxotrophic for glycine but exhibited wild-type trimethoprim sensitivity, making folate deficiency an unlikely cause of its colonization defect. MetJ regulatory mutants are not auxotrophic but are likely altered in the regulation of amino acid-biosynthetic pathways, including those for methionine, glycine, and serine, and this misregulation likely explains its colonization defect. However, mutants defective in methionine, serine, and cysteine biosynthesis exhibited wild-type virulence, suggesting that these amino acids can be scavenged in vivo. Taken together, our results suggest that glycine biosynthesis may be required to alleviate an in vivo nutritional restriction in the mouse intestine; however, additional roles for glycine may exist. Irrespective of the precise nature of this requirement, this study illustrates the importance of pathogen metabolism, and the regulation thereof, as a virulence factor.

IMPORTANCE
Vibrio cholerae
continues to be a severe cause of morbidity and mortality in developing countries. Identification of
V. cholerae
factors critical to disease progression offers the potential to develop or improve upon therapeutics and prevention strategies. To increase the efficiency of virulence factor discovery, we employed a regulator-centric approach to multiplex our in vivo screening capabilities and allow whole regulons in
V. cholerae
to be interrogated for pathogenic potential. We identified MetR as a new virulence regulator and serine hydroxymethyltransferase GlyA1 as a new MetR-regulated virulence factor, both required by
V. cholerae
to colonize the infant mouse intestine. Bacterial metabolism is a prerequisite to virulence, and current knowledge of in vivo metabolism of pathogens is limited. Here, we expand the known role of amino acid metabolism and regulation in virulence and offer new insights into the in vivo metabolic requirements of
V. cholerae
within the mouse intestine.
β-1,3-Glucan, Which Can Be Targeted by Drugs, Forms a Trabecular Scaffold in the Oocyst Walls ofToxoplasmaandEimeria
Authors: Bushkin G. Guy , Motari Edwin , Magnelli Paula , Gubbels Marc-Jan , Dubey Jitender P. , Miska Katarzyna B. , Bullitt Esther , Costello Catherine E. , Robbins Phillips W. , Samuelson John
Published: September 2012

The walls of infectious pathogens, which are essential for transmission, pathogenesis, and diagnosis, contain sugar polymers that are defining structural features, e.g., β-1,3-glucan and chitin in fungi, chitin inEntamoebacysts, β-1,3-GalNAc inGiardiacysts, and peptidoglycans in bacteria. The goal here was to determine in which of three walled forms ofToxoplasma gondii(oocyst, sporocyst, or tissue cyst) is β-1,3-glucan, the product of glucan synthases and glucan hydrolases predicted by whole-genome sequences of the parasite. The three most important discoveries were as follows. (i) β-1,3-glucan is present in oocyst walls ofToxoplasmaandEimeria(a chicken parasite that is a model for intestinal stages ofToxoplasma) but is absent from sporocyst and tissue cyst walls. (ii) Fibrils of β-1,3-glucan are part of a trabecular scaffold in the inner layer of the oocyst wall, which also includes a glucan hydrolase that has a novel glucan-binding domain. (iii) Echinocandins, which target the glucan synthase and kill fungi, arrest development of theEimeriaoocyst wall and prevent release of the parasites into the intestinal lumen. In summary, β-1,3-glucan, which can be targeted by drugs, is an important component of oocyst walls ofToxoplasmabut is not a component of sporocyst and tissue cyst walls.

IMPORTANCEWe show here that walls ofToxoplasmaoocysts, the infectious stage shed by cats, contain β-1,3-glucan, a sugar polymer that is a major component of fungal walls. In contrast to fungi, β-1,3-glucan is part of a trabecular scaffold in the inner layer of the oocyst wall that is independent of the permeability barrier formed by the outer layer of the wall. While glucan synthase inhibitors kill fungi, these inhibitors arrest the development of the oocyst walls ofEimeria(an important chicken pathogen that is a surrogate forToxoplasma) and block release of oocysts into the intestinal lumen. The absence of β-1,3-glucan in tissue cysts ofToxoplasmasuggests that drugs targeted at the glucan synthase might be used to treatEimeriain chickens but not to treatToxoplasmain people.
Cardiac testing and outcomes in infants after an apparent life-threatening event
Authors: Hoki Robert , Bonkowsky Joshua L , Minich L LuAnn , Srivastava Rajendu , Pinto Nelangi M
Published: September 2012

Objectives

We sought to determine the yield of cardiac testing and to identify predictors of cardiac disease in infants with an apparent life-threatening event (ALTE).

Design

Retrospective longitudinal cohort study.

Setting

Paediatric hospital providing primary and tertiary care that is part of an integrated healthcare system.

Patients

Infants hospitalised for an ALTE from 1999 to 2003.

Main exposures

Cardiac testing used at time of ALTE and results, and clinical risk factors for cardiac disease.

Outcome measures

Short-term (during hospitalisation) and long-term (through November 2009) follow-up for any diagnosis of significant cardiac anatomic or rhythm abnormality.

Results

Study criteria were met by 485 infants (mean age 1.9, SD±2.2 months; 49% boys). Cardiac testing was performed on 219 (45%) patients during ALTE hospitalisation, identifying two patients with significant cardiac disease (cardiomyopathy, ventricular pre-excitation). During 7.7 years of follow-up, three additional significant cardiac diagnoses (ventricular pre-excitation, frequent ventricular ectopy, moderate aortic stenosis) were identified. All cardiac tests had low positive predictive value (PPV). Significant cardiac disease was associated with prematurity (22% vs 80%, p=0.002), but not age, gender, prior ALTE or rescue breaths.

Conclusions

This longitudinal study of an ALTE cohort revealed significant cardiac disease in <1% of patients. Prematurity was the only clinical predictor identified. ECG was sensitive for identifying significant cardiac disease, but routine testing warrants further investigation because of the low PPV.
Responsiveness of the VISA-P scale for patellar tendinopathy in athletes
Authors: Hernandez-Sanchez Sergio , Hidalgo Ma Dolores , Gomez Antonia
Published: September 2012

Background

Patient-reported outcome measures are increasingly used in sports medicine to assess results after treatment, but interpretability of change for many instruments remains unclear.

Objective

To define the minimum clinically important difference (MCID) for the Victorian Institute of Sport Assessment scale (VISA-P) in athletes with patellar tendinopathy (PT) who underwent conservative treatment.

Methods

Ninety-eight athletes with PT were enrolled in the study. Each participant completed the VISA-P at admission, after 1 week, and at the final visit. Athletes also assessed their clinical change at discharge on a 15-point Likert scale. We equated important change with a score of ≥3 (somewhat better). Receiver-operating characteristic (ROC) curve analysis and mean change score were used to determine MCID. Minimal detectable change was calculated. The effect of baseline scores on MCID and different criteria used to define important change were investigated. A Bayesian analysis was used to establish the posterior probability of reporting clinical changes related to MCID value.

Results

Athletes with PT who showed an absolute change greater than 13 points in the VISA-P score or 15.4–27% of relative change achieved a minimal important change in their clinical status. This value depended on baseline scores. The probability of a clinical change in a patient was 98% when this threshold was achieved and 45% when MCID was not achieved.

Conclusions

Definition of the MCID will enhance the interpretability of changes in the VISA-P score in the athletes with PT, but caution is required when these values are used.
Disseminating results to clinical trial participants: a qualitative review of patient understanding in a post-trial population
Authors: Darbyshire Julie Lorraine , Price Hermione Clare
Published: September 2012

Objective

To identify the most appropriate format for results dissemination to maximise understanding of trial results.

Design

Qualitative.

Setting

Of the original 58 4-T trial centres, 34 agreed to take part in this ancillary research.

Participants

All participants from these centres were eligible. All 343 participants were sent questionnaires.

Primary and secondary outcome measures

The low response rate meant that we were unable to make any firm conclusions about the patients' preferred method of dissemination; however, we were able to comment on the level of understanding demonstrated by the trial participants.

Results

All 40 (12%) returned questionnaires were received from 15 centres. We received no questionnaires from over half of the centres. The questionnaires which were returned demonstrated broad satisfaction with the results letter, general enthusiasm for the trial and a variable level of understanding of the results; however, there was a high proportion of responders who were not clear on why the research was undertaken or what the results meant.

Conclusions

The low response rate may be related to delays during the trial set-up process suggesting that interest in a study quickly wanes for both patients and centres. From this we deduce that rapid dissemination of results is needed if it is to have any impact at all. The responders are likely to reflect a biased cohort who were both enthusiastic about the research and who had a good experience during their 3 years in the 4-T trial. It is perhaps not surprising therefore that the overview is positive. That this population was still not fully informed about the purpose of the research would seem to confirm a low level of understanding among the general public which we suggest should be addressed during the consent process.
Using ‘amenable mortality’ as indicator of healthcare effectiveness in international comparisons: results of a validation study
Authors: Mackenbach Johan P , Hoffmann Rasmus , Khoshaba Bernadette , Plug Iris , Rey Grégoire , Westerling Ragnar , Pärna Kersti , Jougla Eric , Alfonso José , Looman Caspar , McKee Martin
Published: September 2012

Background and study aims

There is widespread consensus on the need for better indicators of the effectiveness of healthcare. We carried out an analysis of the validity of amenable mortality as an indicator of the effectiveness of healthcare, focusing on the potential use in routine surveillance systems of between-country variations in rates of mortality. We assessed whether the introduction of specific healthcare innovations coincided with declines in mortality from potentially amenable causes in seven European countries. In this paper, we summarise the main results of this study and illustrate them for four conditions.

Data and methods

We identified 14 conditions for which considerable declines in mortality have been observed and for which there is reasonable evidence in the literature of the effectiveness of healthcare interventions to lower mortality. We determined the time at which these interventions were introduced and assessed whether the innovations coincided with favourable changes in the mortality trends from these conditions, measured using Poisson linear spline regression. All the evidence was then presented to a Delphi panel.

Main results

The timing of innovation and favourable change in mortality trends coincided for only a few conditions. Other reasons for mortality decline are likely to include diffusion and improved quality of interventions and in incidence of diseases and their risk factors, but there is insufficient evidence to differentiate these at present. For most conditions, a Delphi panel could not reach consensus on the role of current mortality levels as measures of effectiveness of healthcare.

Discussion and conclusions

Improvements in healthcare probably lowered mortality from many of the conditions that we studied but occurred in a much more diffuse way than we assumed in the study design. Quantification of the contribution of healthcare to mortality requires adequate data on timing of innovation and trends in diffusion and quality and in incidence of disease, none of which are currently available. Given these gaps in knowledge, between-country differences in levels of mortality from amenable conditions should not be used for routine surveillance of healthcare performance. The timing and pace of mortality decline from amenable conditions may provide better indicators of healthcare performance.
Improving outcome in severe trauma: trauma systems and initial management—intubation, ventilation and resuscitation
Authors: Harris Tim , Davenport Ross , Hurst Tom , Jones Jonathan
Published: September 2012

Severe trauma is an increasing global problem mainly affecting fit and healthy younger adults. Improvements in the entire pathway of trauma care have led to improvements in outcome. Development of a regional trauma system based around a trauma centre is associated with a 15–50% reduction in mortality. Trauma teams led by senior doctors provide better care. Although intuitively advantageous, the involvement of doctors in the pre-hospital care of trauma patients currently lacks clear evidence of benefit. Poor airway management is consistently identified as a cause of avoidable morbidity and mortality. Rapid sequence induction/intubation is frequently indicated but the ideal drugs have yet to be identified. The benefits of cricoid pressure are not clear cut. Dogmas in the management of pneumothoraces have been challenged: chest x-ray has a role in the diagnosis of tension pneumothoraces, needle aspiration may be ineffective, and small pneumothoraces can be managed conservatively. Identification of significant haemorrhage can be difficult and specific early resuscitation goals are not easily definable. A hypotensive approach may limit further bleeding but could worsen significant brain injury. The ideal initial resuscitation fluid remains controversial. In appropriately selected patients early aggressive blood product resuscitation is beneficial. Hypothermia can exacerbate bleeding and the benefit in traumatic brain injury is not adequately studied for firm recommendations.
Laboratory evaluation on the high temperature rheological properties of rubber asphalt: a preliminary study
Authors: Wang Hainian , You Zhanping , Goh Shu Wei , Hao Peiwen , Huang Xiaoming
Published: September 2012

Crumb rubber is the recycled rubber particle obtained from mechanical shearing or grinding scrap tires into small particle sizes less than 6.3 mm (or approximately 1/4”). The rheological properties of asphalt binder have an important effect on the field performance of asphalt mixtures and the long-term serviceability of asphalt pavement. The objective of this research is to evaluate the high temperature rheological performance of rubber asphalt binder based on the complex shear modulus (|G*|) and the phase angle (δ) values using the dynamic shear rheometer. Five rubber asphalt dosages at 0, 10, 15, 20, and 25% by weight of asphalt (Superpave PG 64-22), respectively, were used to modify asphalt binder; and three rubber particle meshes, 20#, 30#, and 40#, were utilized in this research. The |G*| at various temperatures and frequencies were tested on each sample, including original and short-term aging binder using the rolling thin-film over. The master curves of |G*|/sin(δ) for each type of rubber asphalt was generated to investigate its rheological properties over a broad range of temperatures and frequencies. Based on the testing results, it was found that the addition of crumb rubber significantly increases the |G*| of asphalt binder, which is desirable to potentially improve the anti-rutting performance of asphalt mixtures. It was also found that the addition of 10% mesh crumb rubbers bumps up the high temperature grade of asphalt, from PG64 to PG76 in this case. The master curve using the |G*|/sin(δ) of rubber asphalt shows a substantial improvement in rutting resistant at each testing temperature and loading frequency. However, it was noteworthy that the rutting resistance enhancement of crumb rubber was affected by the percentage of rubber used, the rubber particle size and its aging condition.
Passenger car equivalents of trucks on four-lane rural freeways under lane restriction and different traffic conditions
Authors: Alecsandru Ciprian , Ishak Sherif , Qi Yan
Published: September 2012

Truck lane restriction and differential speed limits for trucks and passenger cars are becoming more common policies to improve freeway operations and safety. The most recent edition of the Highway Capacity Manual (HCM) recognizes that the passenger car equivalent (ET) values may differ with various traffic conditions, but does not explicitly address how ET values may be impacted by truck lane restrictions or differential speed limit policies. This study developed a flow-based methodology to determine ET for trucks under truck lane restriction policies and different levels of demand and traffic composition. A simulation model (VISSIM) was calibrated to reproduce ET in HCM on a level terrain freeway segment and then used to simulate various scenarios to capture the effect of demand flow rate, truck percentage, and compliance ratio to lane restriction, all under the enforcement of differential speed limit policy. The results showed that ET increases as the compliance ratio increases, regardless of the truck percentage and demand flow rate. For a given traffic flow rate, ET decreases as the truck percentage increases. Moreover, regardless of the compliance ratio to lane restriction and the truck percentage, ET increases with the demand flow rate. The statistical analysis revealed that the truck percentage has a significant effect on ET for most cases, except when the truck percentage exceeds 30%. The results also showed significant differences in ET for all demand flow rates at 95% confidence level. The study also developed linear regression models for each level of service to estimate the value of ET as a function of the truck percentage and compliance ratio.
EFFECT OF GATE-ALL-AROUND TRANSISTOR GEOMETRY ON THE HIGH-FREQUENCY NOISE: ANALYTICAL DISCUSSION
Authors: BENALI A. , TRAVERSA F. L. , ALBAREDA G. , ALARCÓN A. , AGHOUTANE M. , ORIOLS X.
Published: September 2012

By means of the Ramo–Shockley–Pellegrini theorem, an analytical discussion on how different geometries of gate-all-around 1D ballistic transistors affect their time-dependent current and their (intrinsic) high-frequency noise spectrum is presented. In particular, it is shown that the frequency range where the high-frequency noise spectrum is meaningful increases when the lateral area is decreased.
EFFECT OF MARKOV AND NON-MARKOV CLASSICAL NOISE ON ENTANGLEMENT DYNAMICS
Authors: BORDONE PAOLO , BUSCEMI FABRIZIO , BENEDETTI CLAUDIA
Published: September 2012

We analyze the effect of a classical noise into the entanglement dynamics between two particles, initially entangled, subject to continuous time quantum walks in a one-dimensional lattice. The noise is modeled by randomizing the transition amplitudes from one site to another. Both Markovian and non-Markovian environments are considered. For the Markov regime an exponential decay of the initial quantum correlation is found, while the loss of coherence of the quantum state increases monotonically with time up to a saturation value depending upon the degrees of freedom of the system. For the non-Markov regime the presence or absence of entanglement revival and entanglement sudden death phenomena is found or deduced depending on the peculiar characteristics of the noise. Our results indicate that the entanglement dynamics in the non-Markovian regime is affected by the persistence of the memory effects of the environment and by its intrinsic features.