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Porphyromonas gingivalis Resistance to Polymyxin B Is Determined by the Lipid A 4’-Phosphatase, PGN_0524

International Journal of Oral Science 2009年第3期1卷 126-135页

作者： Stephen R. Coats Thao T. To Sumita Jain pamela H. Braham Richard P. Darveau Department of Periodontics School of Dentistry University of Washington Seattle USA

Aim To elucidate the genetic basis for the pronounced resistance that the oral pathogen, Porphyromonas gingivalis （P. gingivalis）, exhibits towards the cationic antimicrobial peptide, polymyxin B. Methodology A genetic screen of P. gingivalis clones generated by a Tn4400-based random insertion mutagenesis strategy was performed to identify bacteria harboring novel genetic mutations that render P. gingivalis susceptible to killing by the cationic antimicrobial peptide, polymyxin B （PMB, 50μg·mL^-1）. Results P. gingivalis （ATCC 33277） is unusually resistant to the cationic antimicrobial peptide, PMB at relatively high concentrations （200μg·mL^-1）. Approximately 2,700 independent Tn4400 ＇-derived mutants ofP. gingivalis were examined for increased sensitivity to PMB killing at a relatively low dose （50 μg·mL^-1）. A single PMB-sensitive mutant was obtained in this phenotypic screen. We determined that the Tn4400＇ transposon was integrated into the gene encoding the lipid A 4＇-phosphatase, PGN 0524, demonstrating that this insertion event was responsible for its increased susceptibility of this clone to PMB-dependent killing. The resulting mutant strain, designated 0524-Tn4400＇, was highly sensitive to PMB killing relative to wild-type P. gingivalis, and exhibited the same sensitivity as the previously characterized strain, 0524KO, which bears a genetically engineered deletion in the PGN_0524 locus. Positive ion mass spectrometric structural （MALDI-TOF MS） analyses revealed that lipid A isolates from 0524-Tn4400＂ and 0524KO strains displayed strikingly similar MALDI-TOF MS spectra that were substantially different from the wildtype P gingivalis lipid A spectrum. Finally, intact 0524- Tn4400＇ and 0524KO mutant bacteria, as well as their corresponding LPS isolates, were significantly more potent in stimulating Toll-like receptor 4 （TLR4）-dependent E-selectin expression in human endothelial cells relative to intact wild-type P.. gingivalis or its corresponding LPS isolate.

关键词： P. gingivalis antimicrobial peptide lipid A phosphatase polymyxin B transposon lipopolysaccharide

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Emerging Challenges in the Completion of Construction Projects through Public Private Partnerships: Empirical Literature Review

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Journal of Building Construction and Planning Research 2020年第4期8卷 263-272页

作者： pamela Akinyi Oyieyo School of Open and Distance eLearning University of Nairobi Nairobi Kenya

The process of engaging private sector in the provision of public infrastructure can improve economic value in service delivery and enable the government to utilize the capabilities and expertise held by private sector. This has a positive impact on the public in terms of improving their well-being. This literature review attempts to compare the challenges encountered in implementation of PPP projects across the world, with a view to determining cross cutting challenges and recommendations for developing countries. A literature review was conducted for empirical studies focusing on construction projects. The studies are reviewed by analyzing the methodology used and conclusions made to identify the geographical study area, Public Private Partnership project financing model, emerging challenges and recommendation for future project management. The literature search was based on four keywords: construction projects, completion of construction projects, public private partnership, challenges in construction projects. Thus, a total of 11 empirical studies were identified for review in Europe, Asia and Africa. The review revealed that most risk factors affecting project completion can be categorized as human and organizational factors and unknown geotechnical conditions that were not known beforehand. Specifically, project owners’ interference was also attributable to delays with the delays having significant implications for project execution. Risks have great impact on the performance of construction projects because they affect their quality, time and cost. The general remedy to such potential risk factors is adoption of reliable prediction mechanisms which would estimate those factors using a probabilistic model that does not rely on expert judgments as they tend to be unreliable.

关键词： Construction Projects Completion of Construction Projects Public Private Partnership Challenges in Construction Projects

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Measures of empathy in children and adolescents:A systematic review of questionnaires

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World Journal of Psychiatry 2021年第10期11卷 876-896页

作者： Gianluca Sesso Giulio Emilio Brancati pamela Fantozzi Emanuela Inguaggiato Annarita Milone Gabriele Masi Department of Clinical and Experimental Medicine University of PisaPisa 56100Italy IRCCS Fondazione Stella Maris Scientific Institute of Child Neurology and PsychiatryCalambrone 56128Italy

BACKGROUND Empathy has long been considered a multidimensional construct,encompassing cognitive,affective and behavioral *** in empathic competences in early childhood contribute to psychopathology,and have been variably implicated in several clinical conditions,such as autism spectrum disorders(ASD)and conduct *** To identify and describe empirically validated questionnaires assessing empathy in children and adolescents and to provide a summary of related theoretical perspectives on empathy definitional *** A systematic review of the literature was *** bibliographic databases were searched.A total of 47 studies were selected for final analysis and 16 distinct measures were identified and *** Questionable to excellent levels of internal consistency were observed,while few studies assessed test-retest *** construct definitions only partially overlapped,affective and cognitive domains of empathy were the commonest internal factors that were often separately *** facets of the construct(i.e.,somatic empathy and sympathy)and specific clinical populations(i.e.,ASD)could be specifically addressed through more recent *** The combination of different assessment methods is recommended in order to foresee further improvements in this field and try to overcome the problem of limited convergence with more objective measures.

关键词： Empathy Assessment Child Adolescent Autistic disorder Conduct disorder

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Mast cells as rapid innate sensors of cytomegalovirus by TLR3/TRIF signaling-dependent and -independent mechanisms

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Cellular & Molecular Immunology 2015年第2期12卷 192-201页

作者： Marc Becker Niels AW Lemmermann Stefan Ebert pamela Baars Angelique Renzaho Jurgen Podlech Michael Stassen Matthias J Reddehase Institute for Immunology Research Center for Immunotherapy (FZI) at the University Medical Center of the Johannes Gutenberg University Mainz Germany Institute for Virology Research Center for Immunotherapy (FZI) at the University Medical Center of the Johannes Gutenberg University Mainz Germany These authors contributed equally to this work Co-senior authors

The succinct metaphor,‘the immune system＇s loaded gun＇, has been used to describe the role of mast cells （MCs） due to their storage of a wide range of potent pro-inflammatory and antimicrobial mediators in secretory granules that can be released almost instantly on demand to fight invaders. Located at host-environment boundaries and equipped with an arsenal of pattern recognition receptors, MCs are destined to be rapid innate sensors of pathogens penetrating endothelial and epithelial surfaces. Although the importance of MCs in antimicrobial and antiparasitic defense has long been appreciated, their role in raising the alarm against viral infections has been noted only recently. Work on cytomegalovirus （CMV） infection in the murine model has revealed MCs as players in a novel cross-talk axis between innate and adaptive immune surveillance of CMV, in that infection of MCs, which is associated with MC degranulation and release of the chemokine CCL5, enhances the recruitment of protective CD8 T cells to extravascular sites of virus replication, specifically to lung interstitium and alveolar epithelium. Here, we have expanded on these studies by investigating the conditions for MC activation and the consequent degranulation in response to host infection. Surprisingly, the data revealed two temporally and mechanistically distinct waves of MC activation： an almost instant indirect activation that depended on TLR3/TRIF signaling and delayed activation by direct infection of MCs that did not involve TLR3/rRIF signaling. Cell type-specific Cre-recombination that yielded eGFP-expressing reporter virus selectively originating from MCs identified MC as a new in vivo, first-hit target cell of productive murine CMV infection.

关键词： cytomegalovirus innate immunity mast cells mast cell-specific Cre-recombination TLR3FrRIF-signaling

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Early testing of insulin resistance: a tale of two lipid ratios in a group of 5th graders screened by the Coronary Artery Risk Detection in Appalachian Communities Project (CARDIAC Project)

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World Journal of Pediatrics 2019年第4期15卷 398-404页

作者： Charles Ituka Mosimah Christa Lilly Awung-Njia Forbin pamela J.Murray Lee Pyles Elloise Elliot William Neal West Virginia University MorgantownUSA University of Yaounde I YaoundeCameroon

Background In West Virginia (WV),47% of fifth-grade children are either overweight or *** is no clear consensus regarding the definition of insulin resistance in children,and directly measuring insulin on the population level is *** proposed measures examined further in this study include triglyceride (TRIG)/high-density lipoprotein cholesterol (HDL-C) ratio and TRIG/low-density lipoprotein (LDL-C) *** purpose of this study is to examine the relationship between TRIG/HDL-C ratio,TRIG/LDL-C ratio and insulin resistance in fifth-graders with acanthosis nigricans (AN).Methods Between 2007 and 2016,52,545 fifth-grade students in WV were assessed for *** glucose and insulin levels were collected only for a sub-group of students who were AN-positive and was used to determine insulin resistance using the Homeostatic Model for Insulin Resistance (HOMA-IR) *** analysis included t tests and logistic regression with receiver operating characteristic *** Of the students assessed for AN,4.5% (n =2360) tested *** prevalence of insulin resistance was 79% (n =814) among 1030 with AN and complete ***/HDL-C ratio and TRIG/LDL-C ratio were significantly associated with insulin resistance (TRIG/HDL-C:Est.=0.36,P < 0.0001,AUC =0.68;TRIG/LDL-C:Est.=0.87,P < 0.0001,AUC =0.69).Multivariate analysis showed that increased body mass index (Est.=0.05,P < 0.0001),gender (Est.=0.49,p < 0.0001) and TRIG/HDL-C ratio (Est.=0.21,P < 0.0001) were significantly associated with insulin *** TRIG/HDL-C is a better surrogate marker of insulin resistance in AN-positive children compared to TRIG/ LDL-C ratio;so,on a population-level,cholesterol rather than insulin may be obtained for preliminary testing of early insulin resistance in children.

关键词： Acanthosis nigricans CARDIAC Project High-density lipoprotein cholesterol Insulin resistance Low-density lipoprotein cholesterol

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AIAP: A Quality Control and Integrative Analysis Package to Improve ATAC-seq Data Analysis

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Genomics, Proteomics & Bioinformatics 2021年第4期19卷 641-651页

作者： Shaopeng Liu Daofeng Li Cheng Lyu Paul MGontarz Benpeng Miao pamela A.F.Madden Ting Wang Bo Zhang Department of Developmental Biology Center of Regenerative MedicineWashington University School of MedicineSt.LouisMO 63108USA Department of Genetics Center for Genomic Sciences and Systems BiologyWashington University School of MedicineSt.LouisMO 63108USA Department of Psychiatry Washington University School of MedicineSt.LouisMO 63108USA

Assay for transposase-accessible chromatin with high-throughput sequencing(ATAC-seq) is a technique widely used to investigate genome-wide chromatin accessibility. The recently published Omni-ATAC-seq protocol substantially improves the signal/noise ratio and reduces the input cell number. High-quality data are critical to ensure accurate *** tools have been developed for assessing sequencing quality and insertion size distribution for ATAC-seq data;however, key quality control(QC) metrics have not yet been established to accurately determine the quality of ATAC-seq data. Here, we optimized the analysis strategy for ATAC-seq and defined a series of QC metrics for ATAC-seq data,including reads under peak ratio(RUPr), background(BG), promoter enrichment(Pro En), subsampling enrichment(Sub En), and other measurements. We incorporated these QC tests into our recently developed ATAC-seq Integrative Analysis Package(AIAP) to provide a complete ATAC-seq analysis system, including quality assurance, improved peak calling, and downstream differential analysis. We demonstrated a significant improvement of sensitivity(20%–60%) in both peak calling and differential analysis by processing paired-end ATAC-seq datasets using AIAP. AIAP is compiled into Docker/Singularity, and it can be executed by one command line to generate a comprehensive QC report. We used ENCODE ATAC-seq data to benchmark and generate QC recommendations, and developed q ATACViewer for the userfriendly interaction with the QC report. The software, source code, and documentation of AIAP are freely available at https://***/Zhang-lab/ATAC-seq_QC_analysis.

关键词： ATAC-seq Quality control Chromatin accessibility Differential analysis Data visualization

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Patient perceptions of stool DNA testing for pan-digestive cancer screening:A survey questionnaire

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World Journal of Gastroenterology 2014年第17期20卷 4972-4979页

作者： Dennis Yang Shauna L Hillman Ann M Harris pamela S Sinicrope Mary E Devens David A Ahlquist Department of Internal Medicine Mayo ClinicRochesterMN 55902United States Division of Biostatistics Mayo ClinicRochesterMN 55902United States Survey Research Center Mayo ClinicRochesterMN 55902United States Division of Gastroenterology and Hepatology Mayo ClinicRochesterMN 55902United States

AIM: To explore patient interest in a potential multi-organ stool-DNA test (MUST) for pan-digestive cancer screening.

关键词： Stool-DNA testing Colorectal cancer screening Gastrointestinal cancer screening Patient perceptions

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AIDS AWARENESS PROMOTION-BETTER LATE THAN NEVER

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China Today 2003年第3期52卷 50-52页

作者： pamela LORD

“People need to know that they can be testedwithout shame;that if they are infected they will betreated;that if they fall ill,they can live safe fromdiscrimination” -Kofi Annan,Hangzhou,China,October

关键词：爱滋病中国艺术身体检测

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The Last Masters

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Beijing Review 2019年第49期62卷 44-45页

作者： pamela Tobey 不详

On a cool weekend in mid-October,an eager group of 12 boarded a small bus for a four-hour drive to the western edge of Hebei a province neighboring *** destination was Nuanquan Town,or Warm Spring Town,with its ancient walled villages dating from the Ming(1368-1644)and Qing(1644-1911)dynasties,relatively untouched by the influence of modem redevelopment They were traveling for a weekend of learning how to make traditional paper lanterns.

关键词： modem lights town

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Multi-detector CT angiography for the assessment of anterior spinal artery and artery of Adamkiewicz patency in patients suspected of having thoracic aortic pathology

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Journal of Geriatric Cardiology 2006年第1期3卷 52-56页

作者： Laura Logan pamela Schraedley Geoffrey D.Rubin Department of Radiology Stanford University Medical Center Room S-072B Stanford CA 94305-5105 USA.

Objective To evaluate the visualization of the anterior spinal artery (ASA) and the artery of Adamkiewicz (AKA) as well as the affecting factors for the detection rate using multidetector row CT (MDCT). Methods Ninety-nine consecutive patients (31 women and 68 men; age range, 25-90 years; average age 61.3 years) with suspicion for thoracic aortic lesions necessitating surgical intervention (31 aortic aneurysm, 45 dissection, 5 intramural hematoma, and 18 normal), underwent 16-slice MDCT angiography from the aortic arch to the aortic bifurcation. Transverse sections, multiplanar reformations (MPR) and thin maximum intensity projections (MIP) were used to assess the ASA and AKA. The level of the ASA and AKA origins and CT acquisition parameters were recorded. The contrast-to-noise ratio (CNR) of the image, an index of the mass of the T11 body (vertebral mass index), the subcutaneous fat thickness,and the CT value within the aortic arch and at the T11 level were measured. The detection of the ASA and AKA was evaluated relative to the acquisition parameters, scan characteristics, and aortic lesion type. Differences were assessed with Wilcoxon rank-sum and t tests. Results The ASA was visualized in 51 patients (52%) and the AKA in 18 patients (18 %). The ASA was identified in 36/67 (54%)patients with 1.25 mm thickness and in15/32 (47%) patients with 2.5-3.0 mm thickness. This difference did not achieve significance (P=0.13). The detection rate of the ASA and the AKA was influenced by vertebral mass index and the CNR (P＜0.05). The amount of subcutaneous fat affected the detection rate of the ASA (P＜0.05) but not the AKA. In CT scans with ASA detection, the mean CT values in the aorta at the arch and at T11 were 360 and 358 HU, respectively; whereas in CT scans without ASA detection, the CT values in the aorta at the arch and at T11 were lower (297 and 317 HU, respectively; both P＜0.05). Conclusion The ASA and AKA were less frequently detected in our cohorts than previous

关键词： Aneurysm, aortic arteries, Adamkiewicz arteries, spinal computed tomography (CT) angiography

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