328 research outputs found

    UniTune: Text-Driven Image Editing by Fine Tuning a Diffusion Model on a Single Image

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    Text-driven image generation methods have shown impressive results recently, allowing casual users to generate high quality images by providing textual descriptions. However, similar capabilities for editing existing images are still out of reach. Text-driven image editing methods usually need edit masks, struggle with edits that require significant visual changes and cannot easily keep specific details of the edited portion. In this paper we make the observation that image-generation models can be converted to image-editing models simply by fine-tuning them on a single image. We also show that initializing the stochastic sampler with a noised version of the base image before the sampling and interpolating relevant details from the base image after sampling further increase the quality of the edit operation. Combining these observations, we propose UniTune, a novel image editing method. UniTune gets as input an arbitrary image and a textual edit description, and carries out the edit while maintaining high fidelity to the input image. UniTune does not require additional inputs, like masks or sketches, and can perform multiple edits on the same image without retraining. We test our method using the Imagen model in a range of different use cases. We demonstrate that it is broadly applicable and can perform a surprisingly wide range of expressive editing operations, including those requiring significant visual changes that were previously impossible.Comment: SIGGRAPH 202

    An arginine deprivation response pathway is induced in Leishmania during macrophage invasion

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    Amino acid sensing is an intracellular function that supports nutrient homeostasis, largely through controlled release of amino acids from lysosomal pools. The intracellular pathogen Leishmania resides and proliferates within human macrophage phagolysosomes. Here we describe a new pathway in Leishmania that specifically senses the extracellular levels of arginine, an amino acid that is essential for the parasite. During infection, the macrophage arginine pool is depleted due to its use to produce metabolites (NO and polyamines) that constitute part of the host defense response and its suppression, respectively. We found that parasites respond to this shortage of arginine by up-regulating expression and activity of the Leishmania arginine transporter (LdAAP3), as well as several other transporters. Our analysis indicates the parasite monitors arginine levels in the environment rather than the intracellular pools. Phosphoproteomics and genetic analysis indicates that the arginine-deprivation response is mediated through a mitogen-activated protein kinase-2-dependent signaling cascade

    Development of a multiplex PCR assay for simultaneous detection of Theileria annulata, Babesia bovis and Anaplasma marginale in cattle

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    Tropical theileriosis, bovine babesiosis and anaplasmosis are tick-borne protozoan diseases that impose serious constraints on the health and productivity of domestic cattle in tropical and sub-tropical regions of the world. A common feature of these diseases is that, following recovery from primary infection, animals become persistent carriers of the pathogen and continue to play a critical role in disease epidemiology, acting as reservoirs of infection. This study describes development and evaluation of multiplex and single PCR assays for simultaneous detection of Theileria annulata, Babesia bovis and Anaplasma marginale in cattle. Following in silico screening for candidate target genes representing each of the pathogens, an optimised multiplex PCR assay was established using three primer sets, cytob1, MAR1bB2 and bovar2A, for amplification of genomic DNA of T. annulata, A. marginale and B. bovis respectively. The designed primer sets were found to be species-specific, generating amplicons of 312, 265 and 166 base pairs, respectively and were deemed suitable for the development of a multiplex assay. The sensitivity of each primer pair was evaluated using serial dilutions of parasite DNA, while specificity was confirmed by testing for amplification from DNA of different stocks of each pathogen and other Theileria, Babesia and Anaplasma species. Additionally, DNA preparations derived from field samples were used to evaluate the utility of the single and multiplex PCRs for determination of infection status. The multiplex PCR was found to detect each pathogen species with the same level of sensitivity, irrespective of whether its DNA was amplified in isolation or together with DNA representing the other pathogens. Moreover, single and multiplex PCRs were able to detect each species with equal sensitivity in serially diluted DNA representing mixtures of T. annulata, B. bovis and A. marginale, and no evidence of non-specific amplification from non-target species was observed. Validation that the multiplex PCR efficiently detects single and mixed infections from field samples was demonstrated. The developed assay represents a simple and efficient diagnostic for co-detection of tropical theileriosis, bovine babesiosis and anaplasmosis, and may be a valuable tool for epidemiological studies aimed at assessing the burden of multiple infection with tick-borne pathogens and improving control of the associated diseases in endemic regions

    Methotrexate enhances the anti-inflammatory effect of CF101 via up-regulation of the A(3 )adenosine receptor expression

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    Methotrexate (MTX) exerts an anti-inflammatory effect via its metabolite adenosine, which activates adenosine receptors. The A(3 )adenosine receptor (A(3)AR) was found to be highly expressed in inflammatory tissues and peripheral blood mononuclear cells (PBMCs) of rats with adjuvant-induced arthritis (AIA). CF101 (IB-MECA), an A(3)AR agonist, was previously found to inhibit the clinical and pathological manifestations of AIA. The aim of the present study was to examine the effect of MTX on A(3)AR expression level and the efficacy of combined treatment with CF101 and MTX in AIA rats. AIA rats were treated with MTX, CF101, or both agents combined. A(3)AR mRNA, protein expression and exhibition were tested in paw and PBMC extracts from AIA rats utilizing immunohistochemistry staining, RT-PCR and Western blot analysis. A(3)AR level was tested in PBMC extracts from patients chronically treated with MTX and healthy individuals. The effect of CF101, MTX and combined treatment on A(3)AR expression level was also tested in PHA-stimulated PBMCs from healthy individuals and from MTX-treated patients with rheumatoid arthritis (RA). Combined treatment with CF101 and MTX resulted in an additive anti-inflammatory effect in AIA rats. MTX induced A(2A)AR and A(3)AR over-expression in paw cells from treated animals. Moreover, increased A(3)AR expression level was detected in PBMCs from MTX-treated RA patients compared with cells from healthy individuals. MTX also increased the protein expression level of PHA-stimulated PBMCs from healthy individuals. The increase in A(3)AR level was counteracted in vitro by adenosine deaminase and mimicked in vivo by dipyridamole, demonstrating that receptor over-expression was mediated by adenosine. In conclusion, the data presented here indicate that MTX induces increased A(3)AR expression and exhibition, thereby potentiating the inhibitory effect of CF101 and supporting combined use of these drugs to treat RA

    Methotrexate enhances the anti-inflammatory effect of CF101 via up-regulation of the A(3 )adenosine receptor expression

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    Methotrexate (MTX) exerts an anti-inflammatory effect via its metabolite adenosine, which activates adenosine receptors. The A(3 )adenosine receptor (A(3)AR) was found to be highly expressed in inflammatory tissues and peripheral blood mononuclear cells (PBMCs) of rats with adjuvant-induced arthritis (AIA). CF101 (IB-MECA), an A(3)AR agonist, was previously found to inhibit the clinical and pathological manifestations of AIA. The aim of the present study was to examine the effect of MTX on A(3)AR expression level and the efficacy of combined treatment with CF101 and MTX in AIA rats. AIA rats were treated with MTX, CF101, or both agents combined. A(3)AR mRNA, protein expression and exhibition were tested in paw and PBMC extracts from AIA rats utilizing immunohistochemistry staining, RT-PCR and Western blot analysis. A(3)AR level was tested in PBMC extracts from patients chronically treated with MTX and healthy individuals. The effect of CF101, MTX and combined treatment on A(3)AR expression level was also tested in PHA-stimulated PBMCs from healthy individuals and from MTX-treated patients with rheumatoid arthritis (RA). Combined treatment with CF101 and MTX resulted in an additive anti-inflammatory effect in AIA rats. MTX induced A(2A)AR and A(3)AR over-expression in paw cells from treated animals. Moreover, increased A(3)AR expression level was detected in PBMCs from MTX-treated RA patients compared with cells from healthy individuals. MTX also increased the protein expression level of PHA-stimulated PBMCs from healthy individuals. The increase in A(3)AR level was counteracted in vitro by adenosine deaminase and mimicked in vivo by dipyridamole, demonstrating that receptor over-expression was mediated by adenosine. In conclusion, the data presented here indicate that MTX induces increased A(3)AR expression and exhibition, thereby potentiating the inhibitory effect of CF101 and supporting combined use of these drugs to treat RA

    Genetic diversity of Anaplasma species major surface proteins and implications for anaplasmosis serodiagnosis and vaccine development

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    The genus Anaplasma (Rickettsiales: Anaplasmataceae) includes several pathogens of veterinary and human medical importance. An understanding of the diversity of Anaplasma major surface proteins (MSPs), including those MSPs that modulate infection, development of persistent infections, and transmission of pathogens by ticks, is derived in part, by characterization and phylogenetic analyses of geographic strains. Information concerning the genetic diversity of Anaplasma spp. MSPs will likely influence the development of serodiagnostic assays and vaccine strategies for the control of anaplasmosi

    ps4 80 hydroxychloroquine in lupus pregnancy a meta analysis of individual participant data

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    Purpose Our current knowledge about how to treat lupus in pregnancy derives from small prospective or retrospective cohorts. The goal of this individual participant meta-analysis was to pool data from multiple prospective cohorts to answer the clinical question of whether hydroxychloroquine (HCQ) treatment affects pregnancy outcomes Methods The literature was searched for prospective cohorts of pregnancies among women with lupus. HCQ use was defined as use any time during pregnancy. Outcomes of interest included fetal loss, preterm birth, high disease, and preeclampsia. Data from each cohort were collected and analysed individually. Pooled ORs were calculated by random-effect models in Review Manager. Due to multiple pregnancies per patient, one pregnancy was randomly selected per patient. Primary analysis included only women with first trimester visits (6 cohorts). Subgroup analyses were stratified by a history of nephritis, APS, and disease activity at first clinic visit. Results The current analysis included 591 pregnancies from six cohorts, of which 73% were exposed to HCQ during pregnancy. Fetal loss: Overall, there was a 51% decrease in the risk of fetal loss among patients taking HCQ during pregnancy (OR: 0.49; 95% CI: 0.24 to 1.00). Among patients with a history of lupus nephritis, taking HCQ during pregnancy reduced the risk of fetal loss by 76% (OR: 0.24; 95% CI: 0.07 to 0.83; table 1). Preterm birth: There was no evidence that HCQ decreased the risk of preterm birth. Disease activity: Although not significant, among patients with a history of lupus nephritis, HCQ use during pregnancy may reduce the risk of having high disease activity during pregnancy (OR: 0.47; 95% CI: 0.21 to 1.09). Preeclampsia: Overall, there was no evidence that HCQ decreased the risk of. Among patients with APS, there may be a protective effect of HCQ, but the precision of the estimate was limited (OR: 0.55; 95% CI: 0.12 to 2.45). Conclusion Our results suggest that among patients with lupus nephritis, HCQ use may decrease the risk of fetal loss and decrease high disease activity during pregnancy. The heterogeneity of data collection suggests the need for a unified approach to identify larger cohorts of lupus pregnancies
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