is a nosocomial pathogen that frequently causes healthcare-acquired infections. The global spread of multidrug-resistant (MDR) strains with its ability to survive in the environment for extended ...periods imposes a pressing public health threat. Two MDR
outbreaks occurred in 2012 and 2014 in a companion animal intensive care unit (caICU) in the Netherlands. Whole-genome sequencing (WGS) was performed on dog clinical isolates (
= 6), environmental isolates (
= 5), and human reference strains (
= 3) to investigate if the isolates of the two outbreaks were related. All clinical isolates shared identical resistance phenotypes displaying multidrug resistance. Multi-locus Sequence Typing (MLST) revealed that all clinical isolates belonged to sequence type ST2. The core genome MLST (cgMLST) results confirmed that the isolates of the two outbreaks were not related. Comparative genome analysis showed that the outbreak isolates contained different gene contents, including mobile genetic elements associated with antimicrobial resistance genes (ARGs). The time-measured phylogenetic reconstruction revealed that the outbreak isolates diverged approximately 30 years before 2014. Our study shows the importance of WGS analyses combined with molecular clock investigations to reduce transmission of MDR
infections in companion animal clinics.
BackgroundWe conducted a phase I clinical trial that infused CCR5 gene-edited CD4+ T cells to determine how these T cells can better enable HIV cure strategies.MethodsThe aim of trial was to develop ...RNA-based approaches to deliver zinc finger nuclease (ZFN), evaluate the effect of CCR5 gene-edited CD4+ T cells on the HIV-specific T cell response, test the ability of infused CCR5 gene-edited T cells to delay viral rebound during analytical treatment interruption, and determine whether individuals heterozygous for CCR5 Δ32 preferentially benefit. We enrolled 14 individuals living with HIV whose viral load was well controlled by antiretroviral therapy (ART). We measured the time to viral rebound after ART withdrawal, the persistence of CCR5-edited CD4+ T cells, and whether infusion of 10 billion CCR5-edited CD4+ T cells augmented the HIV-specific immune response.ResultsInfusion of the CD4+ T cells was well tolerated, with no serious adverse events. We observed a modest delay in the time to viral rebound relative to historical controls; however, 3 of the 14 individuals, 2 of whom were heterozygous for CCR5 Δ32, showed post-viral rebound control of viremia, before ultimately losing control of viral replication. Interestingly, only these individuals had substantial restoration of HIV-specific CD8+ T cell responses. We observed immune escape for 1 of these reinvigorated responses at viral recrudescence, illustrating a direct link between viral control and enhanced CD8+ T cell responses.ConclusionThese findings demonstrate how CCR5 gene-edited CD4+ T cell infusion could aid HIV cure strategies by augmenting preexisting HIV-specific immune responses.REGISTRATIONClinicalTrials.gov NCT02388594.FundingNIH funding (R01AI104400, UM1AI126620, U19AI149680, T32AI007632) was provided by the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute on Drug Abuse (NIDA), the National Institute of Mental Health (NIMH), and the National Institute of Neurological Disorders and Stroke (NINDS). Sangamo Therapeutics also provided funding for these studies.
BACKGROUND. We conducted a phase I clinical trial that infused CCR5 gene-edited CD4+ T cells to determine how these T cells can better enable HIV cure strategies. METHODS. The aim of trial was to ...develop RNA-based approaches to deliver zinc finger nuclease (ZFN), evaluate the effect of CCR5 gene-edited CD4+ T cells on the HIV-specific T cell response, test the ability of infused CCR5 gene-edited T cells to delay viral rebound during analytical treatment interruption, and determine whether individuals heterozygous for CCR5 Д32 preferentially benefit. We enrolled 14 individuals living with HIV whose viral load was well controlled by antiretroviral therapy (ART). We measured the time to viral rebound after ART withdrawal, the persistence of CCR5-edited CD4+ T cells, and whether infusion of 10 billion CCR5-edited CD4+ T cells augmented the HIV-specific immune response. RESULTS. Infusion of the CD4+ T cells was well tolerated, with no serious adverse events. We observed a modest delay in the time to viral rebound relative to historical controls; however, 3 of the 14 individuals, 2 of whom were heterozygous for CCR5 Д32, showed post-viral rebound control of viremia, before ultimately losing control of viral replication. Interestingly, only these individuals had substantial restoration of HIV-specific CD8+ T cell responses. We observed immune escape for 1 of these reinvigorated responses at viral recrudescence, illustrating a direct link between viral control and enhanced CD8+ T cell responses. CONCLUSION. These findings demonstrate how CCR5 gene-edited CD4+ T cell infusion could aid HIV cure strategies by augmenting preexisting HIV-specific immune responses. REGISTRATION. ClinicalTrials.gov NCT02388594. FUNDING. NIH funding (R01AI104400, UM1AI126620, U19AI149680, T32AI007632) was provided by the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute on Drug Abuse (NIDA), the National Institute of Mental Health (NIMH), and the National Institute of Neurological Disorders and Stroke (NINDS). Sangamo Therapeutics also provided funding for these studies.
Staphylococcus schleiferi is an opportunistic pathogen in humans and dogs. Recent taxonomic reassignment of its subspecies (
subsp.
and
subsp.
) into two separate species (
and
) lacks supporting ...data for diagnostic implications and clinical relevance. We aimed to confirm the reclassification of
by using genomic and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) data for a large set of isolates from humans and animals to investigate their molecular epidemiology and clinical relevance. Routine MALDI-TOF analysis and Illumina sequencing were performed on 165
isolates from the Netherlands. With 33 publicly available genomes, the study included 198 genomes from 149 dogs, 34 humans, and 15 other sources. The Type Strain Genome Server was used to identify species in the genomes, and the MALDI-TOF MS database was extended to improve species differentiation. MALDI-TOF did not discriminate between
and
Genome phylogeny distinguished the two species in two monophyletic clusters.
isolates originated from humans, while
isolates were found in animals and three human isolates clustering with the animal isolates. The sialidase B gene (
) was a unique marker gene for
, whereas the
gene was exclusive for
. The
gene was exclusively detected in
, as were the
(A),
,
(B/C),
(O/M), and
(6')-
(2'') genes. The MALDI-TOF database extension did not improve differentiation between the two species. Even though our whole-genome sequencing-based approach showed clear differentiation between these two species, it remains critical to identify
and
correctly in routine diagnostics.
This study clearly shows that
is a concern in human hospital settings, whereas
predominantly causes infections in animals.
is more resistant to antibiotics and can sometimes transmit to humans via exposure to infected dogs. Even though genome-based methods can clearly differentiate the two species, current diagnostic methods used routinely in clinical microbiology laboratories cannot distinguish the two bacterial species.
RPCF Algorithm for Multi-Agent Tourism System Soe Yu Maw; Myo Myo Naing; Ni Lar Thein
2006 IEEE International Symposium on MicroNanoMechanical and Human Science,
2006-Nov.
Conference Proceeding
Nowadays, there is a vast and ever growing amount of information in the Web. The users are in need of more powerful tools to collect the vast amount of heterogeneous information. To address the ...problem of information overload Agents have widely been proposed as a solution to these problems. One possible system approach is to personalize the Web page and create the system which responds to the user request by potentially aggregating information from several information sources in a manner which is dependent on who the user is. Personalization is a process of gathering and storing information about users, analyzing the information and based on this analysis, delivering the information to each user at the right time. Generally, Web personalization has three categories, rule-based filtering, collaborative filtering, and content-based filtering. This paper proposes the RPCF Algorithm, which aims to identify users that have relevant interest by calculating similarity between user's profiles. In our system, we use the rule-based personalization with collaborative filtering technique for evaluating the RPCF algorithm. Our system aims at creating a personalized agent system that automatically tailors the relevant information of the users' request from the Web sites to produce the best recommendation. We illustrate this technique in the tourism domain
Spray drying is a widely used method of converting liquid material (aqueous or organic solutions, emulsions and suspensions) into a dry powder. Good flowability, narrow size distribution, and ...controllable morphology are inherent in powders produced by spray drying. This review considers the granulation factors that influence the final properties of the silicon nitride dried powders. The first group includes the types of atomizers, manifolds, and drying chamber configurations. The process parameters fall into the second group and include the following: inlet temperature, atomizing air flow, feed flow rate, drying gas flow rate, outlet temperature, and drying time. Finally, the last group, feedstock parameters, includes many factors such as feed surface tension, feed viscosity, solvent type, solid particle concentration, and additives. Given the large number of factors affecting morphology, particle size and moisture, optimizing the spray drying process is usually achieved by the “trial and error” approach. Nevertheless, some factors such as the effect of a solvent, dispersant, binder, and sintering additives considered in the literature that affect the Si3N4 granulation process were reviewed in the work. By summarizing the data available on silicon nitride powder production, the authors attempt to tackle the problem of its emerging demand in science and industry.
Reduced insecticide spray in crop fields due to the widespread adoption of Bacillus thuringiensis (Bt) crops has favored the population increases of mirid bugs. Cry51Aa proteins are new types of Bt ...proteins that belong to aerolysin-like β pore-forming proteins with insecticidal activity against hemipteran and coleopteran pests. Here, we studied the activity of Bt Cry51Aa1 and Cry51Aa2 against Apolygus lucorum, an emerging pest in cotton, and their mechanism of action. Cry51Aa1 exhibited almost 5-fold higher toxicity than Cry51Aa2 with LC50 of 11.87 and 61.34 μg/mL, respectively. Protoxins could be activated both in vitro, by trypsin and midgut contents, and in vivo, by A. lucorum midgut. Both Cry51Aa protoxins were processed in two steps, producing pre-activated (∼30 kDa) and final activated (∼25–28 kDa) proteins. Cry51Aa proteins bound to a 25 kDa midgut protein, and Cry51Aa2 showed 2 times higher binding affinity than Cry51Aa1. Incubating Cry51Aa proteins with midgut homogenate resulted in toxin oligomers of 150–200 kDa. Our findings provide a theoretical basis for using Cry51Aa proteins to control A. lucorum and a better understanding of their mode of action.
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