bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Clinical Research Training Programs Using the Clinical Research Appraisal Inventory
Authors: Lipira Lauren , Jeffe Donna B. , Krauss Melissa , Garbutt Jane , Piccirillo Jay , Evanoff Bradley , Fraser Victoria
Published: October 2010

The purpose of this study was to measure change in clinical research self‐efficacy after participating in KL2, postdoctoral and predoctoral clinical research training programs at Washington University School of Medicine. We surveyed program participants using a 76‐item version of the Clinical Research Appraisal Inventory (CRAI). Principal components analysis (PCA) examined the CRAI’s underlying factor structure; Cronbach alpha measured the internal consistency of items on each subscale and the overall CRAI. CRAI score changes from baseline to 1‐year follow‐up were assessed using repeated‐measures analysis of variance. All 29 KL2, 47 postdoctoral, and 31 TL1 scholars enrolled 2006–2009 (mean age 31.6 years, range 22–44; 59.6% female; 65.4% white) completed baseline surveys. Of these participants, 22 KL2, 17 postdoctoral, and 21 TL1 scholars completed the 1‐year follow‐up assessment. PCA resulted in a seven‐factor solution with 69 items (alphas > 0.849 for each subscale and 69‐item CRAI). Significant improvements at 1‐year follow‐up were observed across all programs for Study Design/Data Analysis (p= .016), Interpreting/Reporting/Presenting (p= .034), and overall CRAI (p= .050). Differences between programs were observed for all but one subscale (each p < .05). Clinical research self‐efficacy increased 1 year after clinical research training. Whether this short‐term outcome correlates with long‐term clinical research productivity, requires further study. Clin Trans Sci 2010; Volume 3: 243–248.
Facilitating Research Faculty Participation in CBPR: Development of a Model Based on Key Informant Interviews
Authors: Allen Michele L. , Culhane‐Pera Kathleen A. , Pergament Shannon L. , Call Kathleen T.
Published: October 2010

Community‐based participatory research (CBPR) may enhance the translational research process; however, this would require increased institutional capacity for community engaged research. In this paper, we first present results of key informant interviews with academic health center faculty regarding facilitators to faculty participation in CBPR partnerships and then propose a model arising from these results describing how increased capacity may be achieved. Participants were 13 key informant faculty of varying levels of expertise in CBPR at a large university academic health center. Interviews were recorded and transcribed. A thematic content analysis of each interview was conducted by research team members. Facilitators reported by faculty representing five health science schools were grouped into five thematic areas: (1) researcher personal attributes including an innate orientation toward working with community, (2) positive attitudes toward collaboration, (3) a partnership‐building skill set, (4) community partners who are ready and eager to collaborate, and (5) supportive institutional policies and procedures. We propose a model describing the relationship between personal attributes, learned/environmental factors, and community facilitators that may be utilized to promote increased institutional capacity for CBPR and thus increase the likelihood of the successful translation of research findings into community settings. Clin Trans Sci 2010; Volume 3: 233–238.
The prevalence of rheumatoid factor isotypes and anti‐cyclic citrullinated peptides in Malaysian rheumatoid arthritis patients
Authors: GOMEZ Edmund Luke , GUN Suk Chyn , SOMNATH Sushela Devi , D’SOUZA Beryl , LIM Ai Lee , CHINNA Karuthan , RADHAKRISHNAN Ammu K
Published: October 2010

Aim:  The purpose of this study is to compare the prevalence of rheumatoid factor (RF) isotypes and second generation anti‐cyclic citrullinated peptides (anti‐CCP) in Malaysian rheumatoid arthritis (RA) patients.

Methods:  In this cross‐sectional study, 147 established RA patients from three ethnic groups were recruited from a major rheumatology clinic in Malaysia. Enzyme‐linked immunosorbent assays (ELISA) for serum RF isotypes IgA, IgG and IgM as well as second‐generation anti‐CCP were performed and the prevalence of each auto‐antibody was compared in the three ethnic groups.

Results:  The anti‐CCP was the most prevalent auto‐antibody in each of the ethnic groups, followed closely by RF IgM and RF IgG. Rheumatoid factor IgA was the least prevalent across all three ethnic groups. The anti‐CCP–RF IgM combination provided the best test sensitivity. Seroprevalence of anti‐CCP was strongly associated with the presence of each of the RF isotypes. The seroprevalence of RF and anti‐CCP did not increase or decrease with advancing age, age at onset and disease duration.

Conclusion:  When used alone, anti‐CCP provides a diagnostic advantage over RF IgM on the basis of test sensitivity. Considering the high cost of the anti‐CCP assay, step‐wise serum testing with IgM RF followed by anti‐CCP may provide a more economically sensible option to optimize test sensitivity for RA.
Molecular typing of Escherichia coli strains associated with threatened sea ducks and near‐shore marine habitats of south‐west Alaska
Authors: Hollmén Tuula E. , DebRoy Chitrita , Flint Paul L. , Safine David E. , Schamber Jason L. , Riddle Ann E. , Trust Kimberly A.
Published: October 2010

In Alaska, sea ducks winter in coastal habitats at remote, non‐industrialized areas, as well as in proximity to human communities and industrial activity. We evaluated prevalence and characteristics of Escherichia coli strains in faecal samples of Steller's eiders (Polysticta stelleri; n = 122) and harlequin ducks (Histrionicus histrionicus; n = 21) at an industrialized site and Steller's eiders (n = 48) at a reference site, and compared these strains with those isolated from water samples from near‐shore habitats of ducks. The overall prevalence of E. coli was 16% and 67% in Steller's eiders and harlequin ducks, respectively, at the industrialized study site, and 2% in Steller's eiders at the reference site. Based on O and H antigen subtyping and genetic characterization by enterobacterial repetitive intergenic consensus polymerase chain reaction and pulsed‐field gel electrophoresis, we found evidence of avian pathogenic E. coli (APEC) strains associated with both species and detected E. coli strains carrying virulence genes associated with mammals in harlequin ducks. Steller's eiders that carried APEC had lower serum total protein and albumin concentrations, providing further evidence of pathogenicity. The genetic profile of two E. coli strains from water matched an isolate from a Steller's eider providing evidence of transmission between near‐shore habitats and birds.
Mesalamine‐induced B7‐H1 expression on hepatic stellate cells attenuates autoimmune liver injury
Authors: Lee Jeong‐Hoon , Yoon Jung‐Hwan , Lee Yu‐Jeong , Yang Jong In , Kwak Min‐Sun , Cho Eun Ju , Jang Eun Sun , Yu Su Jong , Choi Dae Hee , Jung Eun Uk , Kim Hwi Young , Kim Bo Hyun , Chung Goh Eun , Kim Yoon Jun , Jang Ja‐June , Kim Chung Yong , Lee Hyo‐Suk
Published: October 2010

Aim:  Hepatic stellate cells (HSCs) have immune regulatory functions. Mesalamine is an effective immune regulatory drug for inflammatory bowel disease. Thus, we hypothesized that mesalamine may also modulate the immune regulatory functions of HSCs. Since B7‐H1 plays a crucial role in regulating T‐cell apoptosis, we evaluated if mesalamine induces B7‐H1 expression on HSCs, and if so, whether mesalamine attenuates autoimmune liver injury in vivo.

Methods:  LX‐2 cells, an immortalized human HSC cell line, and human peripheral T‐cells were used in this study. B7‐H1 expression on LX‐2 cells following mesalamine treatment was examined by using flow cytometry. Cell viability was analyzed by MTS assay. Concanavalin‐A (ConA) mice hepatitis model was used for in vivo study.

Results:  Flow cytometry showed that mesalamine treatment increased the B7‐H1‐expressing LX‐2 cell fraction from 45.4% to 88.2%, of which increment is equivalent to that of positive control (29.9%, interferon γ‐treated cells). Human T‐cells incubated with LX‐2 cells showed significantly less cell viability in the presence of mesalamine than cells without mesalamine treatment (P < 0.001). Histological examination revealed that hepatic necroinflammation was significantly attenuated by mesalamine pretreatment (P = 0.019), although serum levels of aminotransferases were not significantly reduced. During the 24‐h period following ConA injection, 1 of 10 mice pretreated with mesalamine and 3 of 10 mice without pretreatment died.

Conclusion:  These results demonstrate that mesalamine enhances B7‐H1 expression on HSCs, and thus, induces T‐cell apoptosis and attenuates autoimmune liver injury.
A fourth dimension in decision making in hepatology
Authors: Ilan Yaron
Published: October 2010

Today, the assessment of liver function in patients suffering from acute or chronic liver disease is based on liver biopsy and blood tests including synthetic function, liver enzymes and viral load, most of which provide only circumstantial evidence as to the degree of hepatic impairment. Most of these tests lack the degree of sensitivity to be useful for follow‐up of these patients at the frequency that is needed for decision making in clinical hepatology. Accurate assessment of liver function is essential to determine both short‐ and long‐term prognosis, and for making decisions about liver and non‐liver surgery, TIPS, chemoembolization or radiofrequency ablation in patients with chronic liver disease. Liver function tests can serve as the basis for accurate decision‐making regarding the need for liver transplantation in the setting of acute failure or in patients with chronic liver disease. The liver metabolic breath test relies on measuring exhaled 13C tagged methacetin, which is metabolized only by the liver. Measuring this liver‐specific substrate by means of molecular correlation spectroscopy is a rapid, non‐invasive method for assessing liver function at the point‐of‐care. The 13C methacetin breath test (MBT) is a powerful tool to aid clinical hepatologists in bedside decision‐making. Our recent findings regarding the ability of point‐of‐care 13C MBT to assess the hepatic functional reserve in patients with acute and chronic liver disease are reviewed along with suggested treatment algorithms for common liver disorders.
Electron beam induced etching of silicon with SF6
Authors: Vanhove N. , Lievens P. , Vandervorst W.
Published: October 2010

Electron beam induced etching (EBIE) with SF6 precursor molecules has been demonstrated as an approach to induce localized etching of Si with an etch yield of approximately 0.003 atoms/incoming electron. Further understanding of the EBIE mechanisms is presented through an analysis of the influence of the different electron beam parameters (beam energy and electron flux) and the effect of the sample bias on the EBIE rate. It is demonstrated that the etch rate increases with decreasing beam energy and with increasing electron flux to a saturation value. The latter is explained by a transition from an electron flux density limited process (at low current densities) to a gas supply limited process (at high current densities). The authors also demonstrate that a large etch rate enhancement is obtained by applying a positive sample bias. This is explained within the frame of a model outlining the role of the low secondary energy electrons in the electron stimulated etching process.
PI3K Signaling Through the Dual GTPase–Activating Protein ARAP3 Is Essential for Developmental Angiogenesis
Authors: Gambardella Laure , Hemberger Myriam , Hughes Bethany , Zudaire Enrique , Andrews Simon , Vermeren Sonja
Published: October 2010

The guanosine triphosphatase–activating protein ARAP3 may be a target for antiangiogenic therapies.
Regional Variations
Authors: VanHook Annalisa M.
Published: October 2010

Intrinsic differences in mTORC2-dependent Akt activation underlie the region-specific effects of neurofibromatosis-1 on glial progenitor cell development.
The Toll of Stress on Vessels
Authors: Foley John F.
Published: October 2010

Activation of Toll-like receptor 2 by the products of lipid oxidation promotes angiogenesis independently of vascular endothelial growth factor.
The Differences That Bind
Authors: Wong Wei
Published: October 2010

Bacterial chemoreceptors can be classified on the basis of whether ligands bind directly or indirectly.
PIAS1 Repression
Authors: Mueller Kristen L.
Published: October 2010

A ligase regulates repression of the Foxp3 promoter to restrict differentiation of natural regulatory T cells.
Three’s the Charm
Authors: Hurtley Stella M.
Published: October 2010

Membrane fusion proteins cooperate to promote rapid secretory vesicle exocytosis from neuroendocrine cells.
Purification and Biochemical Characterization of IMP-13 Metallo-β-Lactamase
Authors: Santella Gisela , Docquier Jean-Denis , Gutkind Gabriel , Rossolini Gian Maria , Radice Marcela
Published: October 2010

The IMP-13 metallo-β-lactamase was overproduced in
Escherichia coli
BL21(DE3) and purified by chromatography. Analysis of kinetic parameters revealed some notable differences with other IMP-type enzymes, noteworthily a higher catalytic efficiency toward ticarcillin and piperacillin and a marked preference for imipenem over meropenem.
Regulation of
mprF
by Antisense RNA Restores Daptomycin Susceptibility to Daptomycin-Resistant Isolates of
Staphylococcus aureus
Authors: Rubio Aileen , Conrad Mary , Haselbeck Robert J. , G. C. Kedar , Brown-Driver Vickie , Finn John , Silverman Jared A.
Published: October 2010

Mutations in
mprF
have been shown to result in reduced susceptibility to daptomycin and other cationic antibacterials. An
mprF
antisense-inducible plasmid was constructed and used to demonstrate that depletion of
mprF
can reestablish susceptibility to daptomycin. Inducing antisense to
mprF
also resulted in increased susceptibility to vancomycin and gentamicin but, paradoxically, decreased susceptibility to oxacillin. These results suggest that
mprF
mutations that reduce susceptibility to cationic antibacterials result in a gain-of-function phenotype.
Profiling the
Aspergillus fumigatus
Proteome in Response to Caspofungin
Authors: Cagas Steven E. , Jain Mohit Raja , Li Hong , Perlin David S.
Published: October 2010

The proteomic response of
Aspergillus fumigatus
to caspofungin was evaluated by gel-free isobaric tagging for relative and absolute quantitation (iTRAQ) as a means to determine potential biomarkers of drug action. A cell fractionation approach yielding 4 subcellular compartment fractions was used to enhance the resolution of proteins for proteomic analysis. Using iTRAQ, a total of 471 unique proteins were identified in soluble and cell wall/plasma membrane fractions at 24 and 48 h of growth in rich media in a wild-type drug-susceptible strain. A total of 122 proteins showed at least a 2-fold change in relative abundance following exposure to caspofungin (CSF) at just below the minimum effective concentration (0.12 μg/ml). The largest changes were seen in the mitochondrial hypoxia response domain protein (AFUA_1G12250), the level of which decreased >16-fold in the secreted fraction, and ChiA1, the level of which decreased 12.1-fold in the cell wall/plasma membrane fraction. The level of the major allergen and cytotoxin AspF1 was also shown to decrease by 12.1-fold upon the addition of drug. A subsequent iTRAQ analysis of an echinocandin-resistant strain (fks1-S678P) was used to validate proteins specific to drug action. A total of 103 proteins in the 2 fractions tested by iTRAQ were differentially expressed in the wild-type susceptible strain but not significantly changed in the resistant strain. Of these potential biomarkers, 11 had levels that changed at least 12-fold. Microarray analysis of the susceptible strain was performed to evaluate the correlation between proteomics and genomics, with a total of 117 genes found to be changing at least 2-fold. Of these, a total of 22 proteins with significant changes identified by iTRAQ also showed significant gene expression level changes by microarray. Overall, these data have the potential to identify biomarkers that assess the relative efficacy of echinocandin drug therapy.
Immunocytochemistry for Amoxicillin and Its Use for Studying Uptake of the Drug in the Intestine, Liver, and Kidney of Rats
Authors: Fujiwara Kunio , Shin Masashi , Miyazaki Tsubasa , Maruta Yasuhiro
Published: October 2010

Specific transport systems for penicillins have been recognized, but theirin vivorole in the context of other transporters remains unclear. We produced a serum against amoxicillin (anti-AMPC) conjugated to albumin with glutaraldehyde. The antiserum was specific for AMPC and ampicillin (ABPC) but cross-reacted weakly with cephalexin. This enabled us to develop an immunocytochemical (ICC) method for detecting the uptake of AMPC in the rat intestine, liver, and kidney. Three hours after a single oral administration of AMPC, the ICC method revealed that AMPC distributed to a high degree in the microvilli, nuclei, and cytoplasm of the absorptive epithelial cells of the intestine. AMPC distributed in the cytoplasm and nuclei of the hepatocytes in a characteristic granular morphology on the bile capillaries, and in addition, AMPC adsorption was observed on the luminal surface of the capillaries, intercalated portions, and interlobular bile ducts on the bile flow. Almost no AMPC could be detected 6 h postadministration in either the intestine or the liver. Meanwhile, in the kidney, AMPC persisted until 12 h postadministration to a high degree in the proximal tubules, especially in the S3 segment cells in the tubular lumen, in which numerous small bodies that strongly reacted with the antibody were observed. All these sites of AMPC accumulation correspond well to specific sites where certain transporter systems for penicillins occur, suggesting that AMPC is actually and actively absorbed, eliminated, or excreted at these sites, possibly through such certain penicillin transporters.
Evaluation of Hepatotoxicity with Off-Label Oral-Treatment Doses of Voriconazole for Invasive Fungal Infections
Authors: Gorski Elizabeth , Esterly John S. , Postelnick Michael , Trifilio Steven , Fotis Michael , Scheetz Marc H.
Published: October 2010

The approved treatment dose of intravenous voriconazole is a weight-based dose of 4 mg/kg of body weight twice daily; the approved oral dosing is fixed at 200 mg twice daily. In our institution, patients frequently receive oral high-dose voriconazole at 4 mg/kg twice daily. It is unknown if higher doses are associated with increased hepatotoxicity. A retrospective cohort study of patients treated with oral voriconazole for presumed invasive fungal infection for ≥7 days was completed. Patients receiving a fixed dose (i.e., labeled dose) were frequency matched and compared to those receiving a weight-based dose (i.e., high dose). The primary endpoint of hepatotoxicity was evaluated by using NCI Common Terminology Criteria (CTC) and components of liver enzymes measuring >3× the upper limit of normal (ULN) and >5× baseline measurements. Secondary endpoints included an incidence of other adverse drug events. Twenty-five labeled-dose and 84 high-dose voriconazole patients were studied. Liver enzyme abnormalities were similar between groups, with the exception of labeled-dose patients experiencing more alkaline phosphatase (ALP) CTC >2× the baseline (
P
= 0.02) and ALP levels >3× the ULN (
P
= 0.02). Treatment with high dose was associated with the discontinuation of voriconazole for practitioner attribution of adverse drug events (
P
= 0.03), although reasons varied and no commonality of biomarker abnormality was identified. Multivariate analysis revealed that the duration of therapy and higher mg/kg total daily doses as interval variables were predictive of some hepatotoxicity outcomes. No difference existed in liver abnormalities for high-dose voriconazole; however, higher mg/kg doses and a longer duration of therapy may be associated with hepatotoxicity.
Interleukin-1 Receptor Signaling Is Required To Overcome the Effects of Pertussis Toxin and for Efficient Infection- or Vaccination-Induced Immunity against
Bordetella pertussis
Authors: Zhang Xuqing , Hester Sara E. , Kennett Mary J. , Karanikas Alexia T. , Bendor Liron , Place David E. , Harvill Eric T.
Published: October 2010

Interleukin-1 receptor-deficient (IL-1R
−/−
) mice are healthy despite being colonized by commensal microbes but are defective in defenses against specific pathogens, suggesting that IL-1R-mediated effects contribute to immune responses against specific pathogenic mechanisms. To better define the role of IL-1R in immunity to respiratory infections, we challenged IL-1R
−/−
mice with
Bordetella pertussis
and
Bordetella parapertussis
, the causative agents of whooping cough. Following inoculation with
B. pertussis
, but not
B. parapertussis
, IL-1R
−/−
mice showed elevated bacterial numbers and more extensive inflammatory pathology than wild-type mice. Acellular
B. pertussis
vaccines were not efficiently protective against
B. pertussis
in IL-1R
−/−
mice.
B. pertussis
-stimulated dendritic cells from IL-1R
−/−
mice produced higher levels of tumor necrosis factor alpha (TNF-α) and IL-6 than wild-type cells. Moreover, elevated levels of gamma interferon (IFN-γ) and TNF-α but lower levels of IL-10 were detected during
B. pertussis
infection in IL-1R
−/−
mice. Since
B. parapertussis
did not cause severe disease in IL-1R
−/−
mice, we hypothesized that the extreme requirement for IL-1R involves pertussis toxin (Ptx), which is expressed only by
B. pertussis
. An isogenic Ptx-deficient
B. pertussis
strain had only a modest phenotype in wild-type mice but was completely defective in causing lethal disease in IL-1R
−/−
mice, indicating that the particular virulence of
B. pertussis
in these mice requires Ptx. Ptx contributes to IL-1β induction by
B. pertussis
, which is involved in IL-10 induction through IL-1R signaling. IL-10 treatment reduced
B. pertussis
numbers in IL-1R
−/−
mice, suggesting that the lower IL-10 responses partially account for the uncontrolled inflammation and bacterial growth in these mice.
Lipoproteins of Bacterial Pathogens
Authors: Kovacs-Simon A. , Titball R. W. , Michell S. L.
Published: October 2010

Bacterial lipoproteins are a set of membrane proteins with many different functions. Due to this broad-ranging functionality, these proteins have a considerable significance in many phenomena, from cellular physiology through cell division and virulence. Here we give a general overview of lipoprotein biogenesis and highlight examples of the roles of lipoproteins in bacterial disease caused by a selection of medically relevant Gram-negative and Gram-positive pathogens:Mycobacterium tuberculosis,Streptococcus pneumoniae,Borrelia burgdorferi, andNeisseria meningitidis. Lipoproteins have been shown to play key roles in adhesion to host cells, modulation of inflammatory processes, and translocation of virulence factors into host cells. As such, a number of lipoproteins have been shown to be potential vaccines. This review provides a summary of some of the reported roles of lipoproteins and of how this knowledge has been exploited in some cases for the generation of novel countermeasures to bacterial diseases.
Exposure to Cigarette Smoke Inhibits the Pulmonary T-Cell Response to Influenza Virus andMycobacterium tuberculosis
Authors: Feng Yan , Kong Ying , Barnes Peter F. , Huang Fang-Fang , Klucar Peter , Wang Xisheng , Samten Buka , Sengupta Mayami , Machona Bruce , Donis Ruben , Tvinnereim Amy R. , Shams Homayoun
Published: October 2010

Smoking is associated with increased susceptibility to tuberculosis and influenza. However, little information is available on the mechanisms underlying this increased susceptibility. Mice were left unexposed or were exposed to cigarette smoke and then infected withMycobacterium tuberculosisby aerosol or influenza A by intranasal infection. Some mice were given a DNA vaccine encoding an immunogenicM. tuberculosisprotein. Gamma interferon (IFN-γ) production by T cells from the lungs and spleens was measured. Cigarette smoke exposure inhibited the lung T-cell production of IFN-γ during stimulationin vitrowith anti-CD3, after vaccination with a construct expressing an immunogenic mycobacterial protein, and during infection withM. tuberculosisand influenza A virusin vivo. Reduced IFN-γ production was mediated through the decreased phosphorylation of transcription factors that positively regulate IFN-γ expression. Cigarette smoke exposure increased the bacterial burden in mice infected withM. tuberculosisand increased weight loss and mortality in mice infected with influenza virus. This study provides the first demonstration that cigarette smoke exposure directly inhibits the pulmonary T-cell response toM. tuberculosisand influenza virus in a physiologically relevant animal model, increasing susceptibility to both pathogens.
Identification of a Genetic Locus Responsible for Antimicrobial Peptide Resistance in
Clostridium difficile
Authors: McBride Shonna M. , Sonenshein Abraham L.
Published: October 2010

Clostridium difficile
causes chronic intestinal disease, yet little is understood about how the bacterium interacts with and survives in the host. To colonize the intestine and cause persistent disease, the bacterium must circumvent killing by host innate immune factors, such as cationic antimicrobial peptides (CAMPs). In this study, we investigated the effect of model CAMPs on growth and found that
C. difficile
is not only sensitive to these compounds but also responds to low levels of CAMPs by expressing genes that lead to CAMP resistance. By plating the bacterium on medium containing the CAMP nisin, we isolated a mutant capable of growing in three times the inhibitory concentration of CAMPs. This mutant also showed increased resistance to the CAMPs gallidermin and polymyxin B, demonstrating tolerance to different types of antimicrobial peptides. We identified the mutated gene responsible for the resistance phenotype as CD1352. This gene encodes a putative orphan histidine kinase that lies adjacent to a predicted ABC transporter operon (CD1349 to CD1351). Transcriptional analysis of the ABC transporter genes revealed that this operon was upregulated in the presence of nisin in wild-type cells and was more highly expressed in the CD1352 mutant. The insertional disruption of the CD1349 gene resulted in significant decreases in resistance to the CAMPs nisin and gallidermin but not polymyxin B. Because of their role in cationic antimicrobial peptide resistance, we propose the designation
cprABC
for genes CD1349 to CD1351 and
cprK
for the CD1352 gene. These results provide the first evidence of a
C. difficile
gene associated with antimicrobial peptide resistance.
Vaccination with Outer Membrane Complexes Elicits Rapid Protective Immunity to Multidrug-Resistant
Acinetobacter baumannii
Authors: McConnell Michael J. , Domínguez-Herrera Juan , Smani Younes , López-Rojas Rafael , Docobo-Pérez Fernando , Pachón Jerónimo
Published: October 2010

Acinetobacter baumannii
causes pneumonias, bacteremias, and skin and soft tissue infections, primarily in the hospitalized setting. The incidence of infections caused by
A. baumannii
has increased dramatically over the last 30 years, while at the same time the treatment of these infections has been complicated by the emergence of antibiotic-resistant strains. Despite these trends, no vaccines or antibody-based therapies have been developed for the prevention of
A. baumannii
infection. In this study, an outer membrane complex vaccine consisting of multiple surface antigens from the bacterial membrane of
A. baumannii
was developed and tested in a murine sepsis model. Immunization elicited humoral and cellular responses that were able to reduce postinfection bacterial loads, reduce postinfection proinflammatory cytokine levels in serum, and protect mice from infection with human clinical isolates of
A. baumannii
. A single administration of the vaccine was able to elicit protective immunity in as few as 6 days postimmunization. In addition, vaccine antiserum was used successfully to therapeutically rescue naïve mice with established infection. These results indicate that prophylactic vaccination and antibody-based therapies based on an outer membrane complex vaccine may be viable approaches to preventing the morbidity and mortality caused by this pathogen.
Mycobacterium
ulcerans
Triggers T-Cell Immunity followed by Local and Regional but Not Systemic Immunosuppression
Authors: Fraga Alexandra G. , Cruz Andrea , Martins Teresa G. , Torrado Egídio , Saraiva Margarida , Pereira Daniela R. , Meyers Wayne M. , Portaels Françoise , Silva Manuel T. , Castro António G. , Pedrosa Jorge
Published: October 2010

Buruli ulcer is a neglected infectious disease caused by
Mycobacterium ulcerans
and is characterized by necrotic cutaneous lesions induced by the exotoxin mycolactone. Despite evidence of Th1-mediated protective immunity,
M. ulcerans
infection has been associated with systemic immunosuppression. We show that early during mouse infection with either mycolactone-positive or negative strains, pathogen-specific gamma interferon (IFN-γ)-producing T cells developed in the draining lymph node (DLN). CD4
+
cells migrated to the infection foci, but progressive infection with virulent
M. ulcerans
led to the local depletion of recruited cells. Moreover, dissemination of virulent
M. ulcerans
to the DLN was accompanied by extensive DLN apoptotic cytopathology, leading to depletion of CD4
+
T cells and abrogation of IFN-γ expression. Advanced footpad infection with virulent
M. ulcerans
did not induce increased susceptibility to systemic coinfection by
Listeria monocytogenes
. These results show that infection with
M. ulcerans
efficiently triggers a mycobacterium-specific T-cell response in the DLN and that progression of infection with highly virulent
M. ulcerans
leads to a local and regional suppression of that immune response, but without induction of systemic immunosuppression. These results suggest that prophylactic and/or therapeutic interventions to prevent dissemination of
M. ulcerans
to DLN during the early phase of infection would contribute for the maintenance of protective immunity and disease control.
Probiotic
Lactobacillus reuteri
Ameliorates Disease Due to Enterohemorrhagic
Escherichia coli
in Germfree Mice
Authors: Eaton Kathryn A. , Honkala Alexander , Auchtung Thomas A. , Britton Robert A.
Published: October 2010

Strains of enterohemorrhagic
Escherichia coli
(EHEC) are a group of Shiga toxin-producing food-borne pathogens that cause severe hemorrhagic colitis and can lead to hemolytic-uremic syndrome (HUS), a life-threatening condition that principally affects children and for which there is no effective treatment. We used a germfree mouse model of renal and enteric disease due to EHEC to determine if probiotic
Lactobacillus reuteri
ATCC PTA 6475 is effective in suppressing disease symptoms caused by EHEC. When germfree Swiss Webster mice are monocolonized with EHEC, they develop disease characterized by weight loss, cecal luminal fluid accumulation, and renal tubular necrosis. When
L. reuteri
was administered 1 day prior to EHEC challenge and every other day thereafter, EHEC colonization was suppressed and mice were significantly protected from the manifestations of disease. Protection from disease did not require the induction of the antimicrobial compound reuterin in
L. reuteri
prior to treatment. The twice-daily administration of
L. reuteri
appeared more effective than every-other-day administration. These data indicated that
L. reuteri
partially protects mice from disease manifestations of EHEC.
MyD88-Dependent Signaling Protects against Anthrax Lethal Toxin-Induced Impairment of Intestinal Barrier Function
Authors: Okugawa Shu , Moayeri Mahtab , Eckhaus Michael A. , Crown Devorah , Miller-Randolph Sharmina , Liu Shihui , Akira Shizuo , Leppla Stephen H.
Published: October 2010

MyD88-deficient mice were previously shown to have increased susceptibility to
Bacillus anthracis
infection relative to wild-type animals. To determine the mechanism by which MyD88 protects against
B. anthracis
infection, knockout mice were challenged with nonencapsulated, toxigenic
B. anthracis
or with anthrax toxins. MyD88-deficient mice had increased susceptibility to
B. anthracis
and anthrax lethal toxin but not to edema toxin. Lethal toxin alone induced marked multifocal intestinal ulcers in the knockout animals, compromising the intestinal epithelial barrier. The resulting enteric bacterial leakage in the knockout animals led to peritonitis and septicemia. Focal ulcers and erosion were also found in MyD88-heterozygous control mice but with far lower incidence and severity.
B. anthracis
infection also induced a similar enteric bacterial septicemia in MyD88-deficient mice but not in heterozygous controls. We show that lethal toxin and
B. anthracis
challenge induce bacteremia as a result of intestinal damage in MyD88-deficient mice. These results suggest that loss of the intestinal epithelial barrier and enteric bacterial septicemia may contribute to sensitizing MyD88-deficient mice to
B. anthracis
and that MyD88 plays a protective role against lethal toxin-induced impairment of intestinal barrier.
Role of the HefC Efflux Pump inHelicobacter pyloriCholesterol-Dependent Resistance to Ceragenins and Bile Salts
Authors: Trainor Elizabeth A. , Horton Katherine E. , Savage Paul B. , Testerman Traci L. , McGee David J.
Published: October 2010

The human gastric pathogenHelicobacter pylorimodifies host cholesterol via glycosylation and incorporates the glycosylated cholesterol into its membrane; however, the benefits of cholesterol toH. pyloriare largely unknown. We speculated that cholesterol in theH. pylorimembrane might alter the susceptibility of these organisms to membrane-disrupting antibacterial compounds. To test this hypothesis,H. pyloristrains were cultured in Ham's F-12 chemically defined medium in the presence or absence of cholesterol. The two cultures were subjected to overnight incubations with serial 2-fold dilutions of 10 bile salts and four ceragenins, which are novel bile salt derivatives that mimic membrane-disrupting activity of antimicrobial peptides.H. pyloricultured with cholesterol was substantially more resistant to seven of the bile salts and three ceragenins thanH. pyloricultured without cholesterol. In most cases, these cholesterol-dependent differences ranged from 2 to 7 orders of magnitude; this magnitude depended on concentration of the agent. Cholesterol is modified by glycosylation using Cgt, a cholesteryl glycosyltransferase. Surprisingly, acgtknockout strain still maintained cholesterol-dependent resistance to bile salts and ceragenins, indicating that cholesterol modification was not involved in resistance. We then tested whether three putative, paralogous inner membrane efflux pumps, HefC, HefF, or HefI, played a role. While HefF and HefI appeared unimportant, HefC was shown to play a critical role in the resistance to bile salts and ceragenins by multiple methods in multiple strain backgrounds. Thus, both cholesterol and the putative bile salt efflux pump HefC play important roles inH. pyloriresistance to bile salts and ceragenins.
Infectivity Acts asIn VivoSelection for Maintenance of the Chlamydial Cryptic Plasmid
Authors: Russell Marsha , Darville Toni , Chandra-Kuntal Kumar , Smith Bennett , Andrews Charles W. , O'Connell Catherine M.
Published: October 2010

Chlamydia trachomatiscontains a conserved ∼7.5-kb plasmid. Loss of the plasmid results in reduced glycogen accumulation, failure to activate TLR2, and reduced infectivity. We hypothesized that reduced infectivity functions as a means of selection for plasmid maintenance. We directly examined the biological significance of the reduced infectivity associated with plasmid deficiency by determining the relative fitness of plasmid-deficient CM972 versus that of wild-typeC. muridarumNigg in mixed inoculain vitroandin vivo.C. muridarumNigg rapidly out-competed its plasmid-cured derivative CM972in vitrobut was not competitive with CM3.1, a derivative of CM972 that has reverted to a normal infectivity phenotype.C. muridarumNigg also effectively competed with CM972 during lower and upper genital tract infection in the mouse, demonstrating that strong selective pressure for plasmid maintenance occurs during infection. The severity of oviduct inflammation and dilatation resulting from these mixed infections correlated directly with the amount ofC. muridarumNigg in the initial inoculum, confirming the role of the plasmid in virulence. Genetic characterization of CM972 and CM3.1 revealed no additional mutations (other than loss of the plasmid) to account for the reduced infectivity of CM972 and detected a single base substitution in TC_0236 in CM3.1 that may be responsible for its restored infectivity. These data demonstrate that a chlamydial strain that differs genetically from its wild-type parent only with respect to the lack of the chlamydial plasmid is unable to competein vitroandin vivo, likely explaining the rarity of plasmid-deficient isolates in nature.
Associations of low-level urine cadmium with kidney function in lead workers
Authors: Weaver Virginia M , Kim Nam-Soo , Jaar Bernard G , Schwartz Brian S , Parsons Patrick J , Steuerwald Amy J , Todd Andrew C , Simon David , Lee Byung-Kook
Published: October 2010

Objectives

Low-level cadmium exposure, resulting in, for example, urinary cadmium <2.0 μg/g creatinine, is widespread; recent data suggest nephrotoxicity even at these low levels. Few studies have examined the impact of low-level cadmium exposure in workers who are occupationally exposed to other nephrotoxicants such as lead.

Methods

We evaluated associations of urine cadmium, a measure of cumulative dose, with four glomerular filtration measures and N-acetyl-β-D-glucosaminidase (NAG) in lead workers. Recent and cumulative lead doses were assessed via blood and tibia lead, respectively.

Results

In 712 lead workers, mean (SD) blood and tibia lead values, urine cadmium values and estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease equation were 23.1 (14.1) μg/dl, 26.6 (28.9) μg Pb/g bone mineral, 1.15 (0.66) μg/g creatinine and 97.4 (19.2) ml/min/1.73 m2, respectively. After adjustment for age, sex, body mass index, urine creatinine, smoking, alcohol, education, annual income, diastolic blood pressure, current or former lead worker job status, new or returning study participant, and blood and tibia lead, higher ln-urine cadmium was associated with higher calculated creatinine clearance, eGFR (β=8.7 ml/min/1.73 m2; 95% CI 5.4 to 12.1) and ln-NAG but lower serum creatinine.

Conclusions

Potential explanations for these results include a normal physiological response in which urine cadmium levels reflect renal filtration, the impact of adjustment for urine dilution with creatinine in models of kidney outcomes, and cadmium-related hyperfiltration.
TORSION INSTEAD OF TECHNICOLOR
Authors: ZUBKOV M. A.
Published: October 2010

We consider the model, which contains a nonminimal coupling of Dirac spinors to torsion. Due to the action for torsion that breaks parity, the left–right asymmetry of the spinors appears. This construction is used in order to provide dynamical electroweak symmetry breaking. Namely, we arrange all Standard Model fermions in the left-handed spinors. The additional technifermions are arranged in right-handed spinors. Due to the interaction with torsion, the technifermions are condensed and, therefore, cause appearance of the gauge boson masses. In order to provide all fermions with masses, we consider two possibilities. The first one is related to an additional coupling of a real massive scalar field to the considered spinors. The second possibility is to introduce the explicit mass term for the mentioned Dirac spinors composed of the Standard Model fermions and the technifermions.
CAUSAL TRANSFORMATION OF GÖDEL-TYPE SPACETIMES IN CONFORMAL FIELD THEORY
Authors: GUSIN PAWEL
Published: October 2010

The Gödel-type metrics are considered as backgrounds of the sigma-models. In the conformal field theory such backgrounds are deformed by the exactly marginal operators. We examine, how the closed timelike curves (CTCs) transform under such deformations.
AN ABELIAN MODEL OF GRAVITY AND CANONICAL QUANTIZATION BY MEANS OF PATH INTEGRALS
Authors: BRACKEN PAUL
Published: October 2010

An Abelian model of gravity is introduced and its constraint structure is obtained. The main task is to show that the model with constraints can be canonically quantized by means of the canonical path integral formalism using the Faddeev–Popov approach. It is shown how the path integral can be simplified by carrying out the integrals over those variables for which the integrals can be computed.
SCALE INVARIANCE VS CONFORMAL INVARIANCE FROM HOLOGRAPHY
Authors: NAKAYAMA YU
Published: October 2010

The relation between scale invariance and conformal invariance is a subtle but important unsolved problem in the quantum field theory. We study a holographic approach to this problem and show that the null energy condition in the bulk effective gravitational theories guarantees the equivalence between the scale invariance and conformal invariance of the boundary theories. We also investigate the higher-dimensional compactification, where the warping can generate additional possible violation of the conformal invariance. Our discussion is applicable in any dimension, and suggests a generalization of Zamolodchikov–Polchinski theorem that states the equivalence in (1+1) dimension from the purely field theory viewpoint.
CONTROL OF ABSORPTION AND KERR NONLINEARITY BASED ON QUANTUM COHERENCE WITHOUT DRIVING FIELD
Authors: HUANG ZHONGHUA , CHEN AIXI , CHEN ZHAOCHU , DENG LI
Published: October 2010

In a three-level atomic system, the influences of spontaneously generated coherence on the linear absorption and the Kerr nonlinearity are investigated. Our studies show that properties of linear absorption can be dramatically affected by the effect of spontaneously generated coherence. With increase of intensities of spontaneously generated coherence, absorption inhibition will occur, and finally the atomic medium becomes transparent. Furthermore, we find that the Kerr nonlinearity can be obviously enhanced under the action of effects of spontaneously generated coherence. Comparing with traditional scheme of the electromagnetically induced transparency, absorption and Kerr nonlinearity can be controlled without need another driving field in our scheme.
REVIEW OF PARALLEL TECHNIQUES AND ITS IMPLICATION FOR JAVA
Authors: YU SUN , ZHANG WEI
Published: October 2010

This paper surveys the state-of-the-art parallel techniques for multiprocessor architectures, and studies its implication for Java programs, which are typically compiled at run-time. First, this paper overviews basic techniques of program parallelization in traditional static compilers, followed by a survey of successful parallelizing compilers. Then this paper introduces the latest research topics in this area, particularly focusing on the efforts of combining parallelizing techniques with Java virtual machines, including parallel compilation and parallel real-time garbage collection. Finally, this paper summaries the opportunities and challenges of parallelizing Java computing on multicore platforms.
PREDICATE GATES, COMPONENTS AND A PROCESSOR FOR SPATIAL LOGIC
Authors: KOUZAEV GUENNADI A. , KOSTADINOV ATANAS N.
Published: October 2010

Predicate logic gates, components and a processor are proposed for space–time signals and computing. Voltage impulses are transmitted along two wires and the signals are considered as predicate expressions. The developed simple gates and components perform the predicate logical operations AND, NOT, and OR with these expressions. For design and verification of all components and the processor, the CPLD and FPGA boards and corresponding software are used. The designed processor is compatible with classical computers and applicable in the area of artificial intelligence as well as linguistic calculations, database machines, SQL servers, etc.
CRITICAL-PATH DRIVEN ROUTERS FOR ON-CHIP NETWORKS
Authors: HU WEI , CHEN TIANZHOU , SHI QINGSONG , LIU SHA
Published: October 2010

Multithreaded programming has become the dominant paradigm in computer architecture, mainly in the form of multi-core processors. The performance bottleneck of a multithreaded program is its critical path, whose length is its total execution time. As the number of cores within a processor increases, Network-on-Chip (NoC) has been proposed as a promising approach for inter-core communication. In order to optimize the performance of a multithreaded program running on an NoC based multi-core platform, we design and implement the critical-path driven router, which prioritizes inter-thread communication on the critical path when routing packets. The experimental results show that the critical-path driven router improves the execution time of the test case by 14.8% compared to the ordinary router.
HIGH SPEED MULTI-RESOURCE ARBITER WITH ACTIVE VIRTUAL CHANNEL ALLOCATION FOR NETWORK ON CHIPS
Authors: GUAN XUGUANG , ZHU ZHANGMING , ZHOU DUAN , YANG YINTANG
Published: October 2010

To improve the shortcomings of long arbitration–allocation time and large power consumption in conventional network on chips, this paper proposes a high speed multi-resource arbiter with active virtual channel allocation. Through arbitrating the acknowledgement signals of virtual channels, the virtual channels can attend the arbitration–allocation process actively. Thus reduces the virtual channel allocation time. Furthermore, the proposed multi-resource arbiter has integrated the function of virtual channel allocation, which improves the performance and simplifies the design process simultaneously. Null convention logic units are used to make the circuit quasi-delay insensitive and high robustness. The proposed multi-resource arbiter is implemented based on SMIC 0.18 μm standard CMOS technology. Results have shown that the arbitration–allocation time of the arbiter is only 824.1 ps, which reduced 25.1% compared with the conventional one. The power consumption and the area are slightly larger than the conventional ones. The proposed high speed multi-resource arbiter is suitable for high performance and high robustness interconnections of on chip networks.
A LOW-POWER UWB TRANSCEIVER BY USE OF TRIGGER RECEIVING METHOD
Authors: ZHANG SHENG , LI ZHENG , LIU MENGMENG , LIN XIAOKANG
Published: October 2010

This paper presents a novel non-coherent receiving algorithm termed trigger receiving algorithm. In comparison with conventional coherent receiving method, the trigger receiving algorithm needs neither local template nor correlation operation, thus both circuit complexity and power consumption are drastically reduced. Based on the proposed algorithm, a fully integrated transceiver was implemented in a 0.18 μ m CMOS process. It occupies an area of 0.44 mm2 and achieves a maximum chip rate of 40 Mbps with 7 mW energy consumption provided by a 1.8 V power supply.
CORRELATION IDENTIFICATION IN BIPARTITE PAULI CHANNELS
Authors: FREY MICHAEL R. , COFFEY LAURA E. , MENTCH LUCAS K. , MILLER AMY L. , RUBIN STEVEN S.
Published: October 2010

The classical communication capacities of quantum Pauli channels with memory (correlation) are known to exhibit a transition effect. We revisit this phenomenon from the standpoint of the functionally analogous task of Pauli channel correlation identification. We treat the complete class of Pauli channels with correlation and determine the maximum quantum Fisher information achievable both with pure separable channel probe states and with maximally entangled bipartite probe states. A comparison of these Fisher informations reveals four distinct classes of Pauli channels and shows that only those channels that exceed a certain parametric threshold exhibit a transition effect. For those Pauli channels that exhibit this effect, the threshold at which it occurs has a simple analytic expression.