| 1. |
- Ali, Abukar, 1988, et al.
(författare)
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CTLA4-Ig but not anti-TNF therapy promotes staphylococcal septic arthritis in mice.
- 2015
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Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 212:8, s. 1308-1316
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Tidskriftsartikel (refereegranskat)abstract
- The development of biologics has greatly increased the quality of life as well as the life expectancy of many RA patients. However, a large number of these patients are at an increased risk of developing serious infections. The aim of this study was to examine differential effects of anti-TNF versus CTLA4-Ig treatment on both immunological response and host defense in a murine model of septic arthritis.
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| 2. |
- Ali, Abukar, 1988, et al.
(författare)
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IL-1 Receptor Antagonist Treatment Aggravates Staphylococcal Septic Arthritis and Sepsis in Mice.
- 2015
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin-1 receptor antagonist (IL-1Ra) is the primary therapy against autoinflammatory syndromes with robust efficacy in reducing systemic inflammation and associated organ injury. However, patients receiving IL-1Ra might be at increased risk of acquiring serious infections.
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| 3. |
- Baranwal, Gaurav, et al.
(författare)
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Impact of cell wall peptidoglycan O-acetylation on the pathogenesis of Staphylococcus aureus in septic arthritis.
- 2017
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Ingår i: International journal of medical microbiology : IJMM. - : Elsevier BV. - 1618-0607 .- 1438-4221. ; 307:7, s. 388-397
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Tidskriftsartikel (refereegranskat)abstract
- Staphylococcus aureus (S. aureus) is one of the most common pathogen causing septic arthritis. To colonize the joints and establish septic arthritis this bacterium needs to resist the host innate immune responses. Lysozyme secreted by neutrophils and macrophages is an important defense protein present in the joint synovial fluids. S. aureus is known to be resistant to lysozyme due to its peptidoglycan modification by O-acetylation of N-acetyl muramic acid. In this study we have investigated the role of O-acetylated peptidoglycan in septic arthritis. Using mouse models for both local and hematogenous S. aureus arthritis we compared the onset and progress of the disease induced by O-acetyl transferase mutant and the parenteral wild type SA113 strain. The disease progression was assessed by observing the clinical parameters including body weight, arthritis, and functionality of the affected limbs. Further X-ray and histopathological examinations were performed to monitor the synovitis and bone damage. In local S. aureus arthritis model, mice inoculated with the ΔoatA strain developed milder disease (in terms of knee swelling, motor and movement functionality) compared to mice inoculated with the wild type SA113 strain. X-ray and histopathological data revealed that ΔoatA infected mice knee joints had significantly lesser joint destruction, which was accompanied by reduced bacterial load in knee joints. Similarly, in hematogenous S. aureus arthritis model, ΔoatA mutant strain induced significantly less severe clinical septic arthritis compared to its parental strain, which is in accordance with radiological findings. Our data indicate that peptidoglycan O-acetylation plays an important role in S. aureus mediated septic arthritis.
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| 4. |
- Deshmukh, Megshree, et al.
(författare)
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Gene expression of S100a8/a9 predicts Staphylococcus aureus-induced septic arthritis in mice.
- 2023
-
Ingår i: Frontiers in microbiology. - 1664-302X. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Septic arthritis is the most aggressive joint disease associated with high morbidity and mortality. The interplay of the host immune system with the invading pathogens impacts the pathophysiology of septic arthritis. Early antibiotic treatment is crucial for a better prognosis to save the patients from severe bone damage and later joint dysfunction. To date, there are no specific predictive biomarkers for septic arthritis. Transcriptome sequencing analysis identified S100a8/a9 genes to be highly expressed in septic arthritis compared to non-septic arthritis at the early course of infection in an Staphylococcus aureus septic arthritis mouse model. Importantly, downregulation of S100a8/a9 mRNA expression at the early course of infection was noticed in mice infected with the S. aureus Sortase A/B mutant strain totally lacking arthritogenic capacity compared with the mice infected with parental S. aureus arthritogenic strain. The mice infected intra-articularly with the S. aureus arthritogenic strain significantly increased S100a8/a9 protein expression levels in joints over time. Intriguingly, the synthetic bacterial lipopeptide Pam2CSK4 was more potent than Pam3CSK4 in inducing S100a8/a9 release upon intra-articular injection of these lipopeptides into the mouse knee joints. Such an effect was dependent on the presence of monocytes/macrophages. In conclusion, S100a8/a9 gene expression may serve as a potential biomarker to predict septic arthritis, enabling the development of more effective treatment strategies.
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| 5. |
- Fatima, Farah, et al.
(författare)
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Radiological features of experimental staphylococcal septic arthritis by micro computed tomography scan.
- 2017
-
Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- Permanent joint dysfunction due to bone destruction occurs in up to 50% of patients with septic arthritis. Recently, imaging technologies such as micro computed tomography (μCT) scan have been widely used for preclinical models of autoimmune joint disorders. However, the radiological features of septic arthritis in mice are still largely unknown.NMRI mice were intravenously or intra-articularly inoculated with S. aureus Newman or LS-1 strain. The radiological and clinical signs of septic arthritis were followed for 10 days using μCT. We assessed the correlations between joint radiological changes and clinical signs, histological changes, and serum levels of cytokines.On days 5-7 after intravenous infection, bone destruction verified by μCT became evident in most of the infected joints. Radiological signs of bone destruction were dependent on the bacterial dose. The site most commonly affected by septic arthritis was the distal femur in knees. The bone destruction detected by μCT was positively correlated with histological changes in both local and hematogenous septic arthritis. The serum levels of IL-6 were significantly correlated with the severity of joint destruction.μCT is a sensitive method for monitoring disease progression and determining the severity of bone destruction in a mouse model of septic arthritis. IL-6 may be used as a biomarker for bone destruction in septic arthritis.
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| 6. |
- Fei, Ying, et al.
(författare)
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Commensal Bacteria Augment Staphylococcus aureus septic Arthritis in a Dose-Dependent Manner.
- 2022
-
Ingår i: Frontiers in cellular and infection microbiology. - : Frontiers Media SA. - 2235-2988. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- Septic arthritis is considered one of the most dangerous joints diseases and is mainly caused by the Gram-positive bacterium Staphylococcus aureus (S. aureus). Human skin commensals are known to augment S. aureus infections. The aim of this study was to investigate if human commensals could augment S. aureus-induced septic arthritis.NMRI mice were inoculated with S. aureus alone or with a mixture of S. aureus together with either of the human commensal Staphylococcus epidermidis (S. epidermidis) or Streptococcus mitis (S. mitis). The clinical, radiological and histopathological changes due to septic arthritis were observed. Furthermore, the serum levels of chemokines and cytokines were assessed.Mice inoculated with a mixture of S. aureus and S. epidermidis or S. mitis developed more severe and frequent clinical arthritis compared to mice inoculated with S. aureus alone. This finding was verified pathologically and radiologically. Furthermore, the ability of mice to clear invading bacteria in the joints but not in kidneys was hampered by the bacterial mixture compared to S. aureus alone. Serum levels of monocyte chemoattractant protein 1 were elevated at the early phase of disease in the mice infected with bacterial mixture compared with ones infected with S. aureus alone. Finally, the augmentation effect in septic arthritis development by S. epidermidis was bacterial dose-dependent.The commensal bacteria dose-dependently augment S. aureus-induced septic arthritis in a mouse model of septic arthritis.
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| 7. |
- Gupta, Priti, et al.
(författare)
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The impact of TLR2 and aging on the humoral immune response to Staphylococcus aureus bacteremia in mice.
- 2023
-
Ingår i: Scientific reports. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Aging alters immunoglobulin production, affecting the humoral immune response. Toll-like receptor 2 (TLR2) recognizes Staphylococcus aureus (S. aureus) which causes bacteremia with high mortality in the elderly. To understand how TLR2 and aging affect the humoral immune response in bacteremia, four groups of mice (wild type-young, wild type-old, TLR2-/--young, and TLR2-/--old) were used to analyze immunoglobulin levels in healthy conditions as well as 10days after intravenous injection with S. aureus. We found that aging increased the levels of both IgM and IgG. Increased IgG in aged mice was controlled by TLR2. In bacteremia infection, aged mice failed to mount proper IgM response in both wild-type (WT) and TLR2-/- mice, whereas IgG response was impaired in both aged and TLR2-/- mice. Aged mice displayed reduced IgG1 and IgG2a response irrespective of TLR2 expression. However, impaired IgG2b response was only found in agedWT mice and not in TLR2-/- mice. Both aging and TLR2-/- increased the levels of anti-staphylococcal IgM in bacteremia. Aging increased sialylated IgG in WT mice but not in TLR2-/- mice. IgG sialylation was not affected by the infection in neither of the mice. In summary, aging increases all immunoglobulins except IgG1. However, aged mice fail to mount a proper antibody response to S. aureus bacteremia. TLR2 plays the regulatory role in IgG but not IgM response to infection.
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| 8. |
- Hu, Zhicheng, et al.
(författare)
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Phenol-soluble modulin α and β display divergent roles in mice with staphylococcal septic arthritis.
- 2022
-
Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- Phenol-soluble modulin α (PSMα) is identified as potent virulence factors in Staphylococcus aureus (S. aureus) infections. Very little is known about the role of PSMβ which belongs to the same toxin family. Here we compared the role of PSMs in S. aureus-induced septic arthritis in a murine model using three isogenic S. aureus strains differing in the expression of PSMs (Newman, Δpsmα, and Δpsmβ). The effects of PSMs on neutrophil NADPH-oxidase activity were determined in vitro. We show that the PSMα activates neutrophils via the formyl peptide receptor (FPR) 2 and reduces their NADPH-oxidase activity in response to the phorbol ester PMA. Despite being a poor neutrophil activator, PSMβ has the ability to reduce the neutrophil activating effect of PSMα and to partly reverse the effect of PSMα on the neutrophil response to PMA. Mice infected with S. aureus lacking PSMα had better weight development and lower bacterial burden in the kidneys compared to mice infected with the parental strain, whereas mice infected with bacteria lacking PSMβ strain developed more severe septic arthritis accompanied with higher IL-6 and KC. We conclude that PSMα and PSMβ play distinct roles in septic arthritis: PSMα aggravates systemic infection, whereas PSMβ protects arthritis development.
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| 9. |
- Hu, Zhicheng, et al.
(författare)
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The impact of aging and TLR2 deficiency on the clinical outcomes of Staphylococcus aureus bacteremia.
- 2023
-
Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 228:3, s. 332-342
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Tidskriftsartikel (refereegranskat)abstract
- Staphylococcus aureus (S. aureus) causes a broad range of infections. TLR2 senses the S. aureus lipoproteins in S. aureus infections. Aging raises the risk of infection. Our aim was to understand how aging and TLR2 impact the clinical outcomes of S. aureus bacteremia. Four groups of mice (Wild type/young, Wild type/old, TLR2-/-/young, and TLR2-/-/old) were intravenously infected with S. aureus, and the infection course was followed. Both TLR2 deficiency and aging enhanced the susceptibility to disease. Increased age was the main contributing factor to mortality and changes in spleen weight, whereas other clinical parameters such as weight loss and kidney abscess formation were more TLR2 dependent. Importantly, aging increased mortality without relying on TLR2. In vitro, both aging and TLR2 deficiency downregulated cytokine/chemokine production of immune cells with distinct patterns. In summary, we demonstrate that aging and TLR2 deficiency impair the immune response to S. aureus bacteremia in distinct ways.
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| 10. |
- Jarneborn, Anders, et al.
(författare)
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Tofacitinib treatment aggravates Staphylococcus aureus septic arthritis, but attenuates sepsis and enterotoxin induced shock in mice
- 2020
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Tofacitinib, a janus kinase inhibitor, is a novel immunosuppressive drug for treatment of rheumatoid arthritis (RA). Septic arthritis (SA) and sepsis caused by Staphylococcus aureus (S. aureus), for which RA patients are at risk, are infections with high mortality. The aim of this study was to investigate the effect of tofacitinib on S. aureus infections using mouse models. In vitro tofacitinib treated mouse splenocytes were stimulated with S. aureus derived stimuli. Mice pre-treated with tofacitinib were inoculated intravenously with either arthritogenic- or septic doses of S. aureus. Arthritis severity and mortality were compared between groups. Additionally, pre-treated mice were challenged with staphylococcal toxin TSST-1 to induce shock. Tofacitinib inhibited splenocyte proliferation and IFN-gamma production in response to TSST-1 and dead S. aureus. In SA, tofacitinib treatment aggravated arthritis with more severe bone erosions. However, in sepsis, treated mice displayed significantly prolonged survival compared to controls. Similarly, in staphylococcal enterotoxin-induced shock tofacitinib pre-treatment, but not late treatment dramatically reduced mortality, which was accompanied by decreased levels of TNF-alpha and IFN-gamma. Our findings show that tofacitinib treatment increase susceptibility of SA in mice, but has a positive effect on survival in S. aureus-induced sepsis and a strong protective effect in toxin-induced shock.
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| 11. |
- Jin, Tao, 1973, et al.
(författare)
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A novel mouse model for septic arthritis induced by Pseudomonas aeruginosa
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Septic arthritis is one of the most aggressive joint diseases. Although caused predominantly by S. aureus, Gram-negative bacteria, Pseudomonas aeruginosa among them, account for a significant percentage of the causal agents of septic arthritis. However, septic arthritis caused by P. aeruginosa has not been studied thus far, due to lack of an animal model. NMRI mice were inoculated with different doses of P. aeruginosa. The clinical course of septic arthritis and radiological changes of joints were examined. Furthermore, the host molecular and cellular mechanisms involved in P. aeruginosa-induced septic arthritis were investigated. Inoculation of mice with P. aeruginosa caused septic arthritis in a dose-dependent manner. Neutrophil depletion led to higher mortality and more severe joint destruction (p < 0.01). In contrast, monocyte depletion resulted in higher mortality (p < 0.05) but similar arthritis severity compared to controls. Mice depleted of CD4+ T-cells inoculated with P. aeruginosa displayed less severe bone damage (p < 0.05). For the first time, a mouse model for P. aeruginosa septic arthritis is presented. Our data demonstrate that neutrophils play a protective role in P. aeruginosa septic arthritis. Monocytes/macrophages, on the other hand, are only essential in preventing P. aeruginosa-induced mortality. Finally, CD4+ T-cells are pathogenic in P. aeruginosa septic arthritis.
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| 12. |
- Jin, Tao, 1973, et al.
(författare)
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Bacteria and Host Interplay in Staphylococcus aureus Septic Arthritis and Sepsis.
- 2021
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Ingår i: Pathogens. - : MDPI AG. - 2076-0817. ; 10:2
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Forskningsöversikt (refereegranskat)abstract
- Staphylococcus aureus (S. aureus) infections are a major healthcare challenge and new treatment alternatives are needed. S. aureus septic arthritis, a debilitating joint disease, causes permanent joint dysfunction in almost 50% of the patients. S. aureus bacteremia is associated with higher mortalities than bacteremia caused by most other microbes and can develop to severe sepsis and death. The key to new therapies is understanding the interplay between bacterial virulence factors and host immune response, which decides the disease outcome. S. aureus produces numerous virulence factors that facilitate bacterial dissemination, invasion into joint cavity, and cause septic arthritis. Monocytes, activated by several components of S. aureus such as lipoproteins, are responsible for bone destructions. In S. aureus sepsis, cytokine storm induced by S. aureus components leads to the hyperinflammatory status, DIC, multiple organ failure, and later death. The immune suppressive therapies at the very early time point might be protective. However, the timing of treatment is crucial, as late treatment may aggravate the immune paralysis and lead to uncontrolled infection and death.
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| 13. |
- Kopparapu, Pradeep Kumar, et al.
(författare)
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Lipoproteins Are Responsible for the Pro-Inflammatory Property of Staphylococcus aureus Extracellular Vesicles
- 2021
-
Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067. ; 22:13
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Tidskriftsartikel (refereegranskat)abstract
- Staphylococcal aureus (S. aureus), a Gram-positive bacteria, is known to cause various infections. Extracellular vesicles (EVs) are a heterogeneous array of membranous structures secreted by cells from all three domains of life, i.e., eukaryotes, bacteria, and archaea. Bacterial EVs are implied to be involved in both bacteria-bacteria and bacteria-host interactions during infections. It is still unclear how S. aureus EVs interact with host cells and induce inflammatory responses. In this study, EVs were isolated from S. aureus and mutant strains deficient in either prelipoprotein lipidation (Delta lgt) or major surface proteins (Delta srtAB). Their immunostimulatory capacities were assessed both in vitro and in vivo. We found that S. aureus EVs induced pro-inflammatory responses both in vitro and in vivo. However, this activity was dependent on lipidated lipoproteins (Lpp), since EVs isolated from the Delta lgt showed no stimulation. On the other hand, EVs isolated from the Delta srtAB mutant showed full immune stimulation, indicating the cell wall anchoring of surface proteins did not play a role in immune stimulation. The immune stimulation of S. aureus EVs was mediated mainly by monocytes/macrophages and was TLR2 dependent. In this study, we demonstrated that not only free Lpp but also EV-imbedded Lpp had high pro-inflammatory activity.
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| 14. |
- Loni, Mohammad, et al.
(författare)
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DenseDisp : Resource-Aware Disparity Map Estimation by Compressing Siamese Neural Architecture
- 2020
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Ingår i: IEEE WORLD CONGRESS ON COMPUTATIONAL INTELLIGENCE (WCCI) 2020 IEEE WCCI. - Glasgow, United Kingdom.
-
Konferensbidrag (refereegranskat)abstract
- Stereo vision cameras are flexible sensors due to providing heterogeneous information such as color, luminance, disparity map (depth), and shape of the objects. Today, Convolutional Neural Networks (CNNs) present the highest accuracy for the disparity map estimation [1]. However, CNNs require considerable computing capacity to process billions of floating-point operations in a real-time fashion. Besides, commercial stereo cameras produce huge size images (e.g., 10 Megapixels [2]), which impose a new computational cost to the system. The problem will be pronounced if we target resource-limited hardware for the implementation. In this paper, we propose DenseDisp, an automatic framework that designs a Siamese neural architecture for disparity map estimation in a reasonable time. DenseDisp leverages a meta-heuristic multi-objective exploration to discover hardware-friendly architectures by considering accuracy and network FLOPS as the optimization objectives. We explore the design space with four different fitness functions to improve the accuracy-FLOPS trade-off and convergency time of the DenseDisp. According to the experimental results, DenseDisp provides up to 39.1x compression rate while losing around 5% accuracy compared to the state-of-the-art results.
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| 15. |
- Loni, Mohammad, et al.
(författare)
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Designing compact convolutional neural network for embedded stereo vision systems
- 2018
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Ingår i: Proceedings - 2018 IEEE 12th International Symposium on Embedded Multicore/Many-Core Systems-on-Chip, MCSoC 2018. - : Institute of Electrical and Electronics Engineers (IEEE). - 9781538666890 ; , s. 244-251
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Konferensbidrag (refereegranskat)abstract
- Autonomous systems are used in a wide range of domains from indoor utensils to autonomous robot surgeries and self-driving cars. Stereo vision cameras probably are the most flexible sensing way in these systems since they can extract depth, luminance, color, and shape information. However, stereo vision based applications suffer from huge image sizes and computational complexity leading system to higher power consumption. To tackle these challenges, in the first step, GIMME2 stereo vision system [1] is employed. GIMME2 is a high-throughput and cost efficient FPGA-based stereo vision embedded system. In the next step, we present a framework for designing an optimized Deep Convolutional Neural Network (DCNN) for time constraint applications and/or limited resource budget platforms. Our framework tries to automatically generate a highly robust DCNN architecture for image data receiving from stereo vision cameras. Our proposed framework takes advantage of a multi-objective evolutionary optimization approach to design a near-optimal network architecture for both the accuracy and network size objectives. Unlike recent works aiming to generate a highly accurate network, we also considered the network size parameters to build a highly compact architecture. After designing a robust network, our proposed framework maps generated network on a multi/many core heterogeneous System-on-Chip (SoC). In addition, we have integrated our framework to the GIMME2 processing pipeline such that it can also estimate the distance of detected objects. The generated network by our framework offers up to 24x compression rate while losing only 5% accuracy compare to the best result on the CIFAR-10 dataset.
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| 16. |
- Loni, Mohammad, PhD Candidate, 1991-, et al.
(författare)
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FastStereoNet : A Fast Neural Architecture Search for Improving the Inference of Disparity Estimation on Resource-Limited Platforms
- 2022
-
Ingår i: IEEE Transactions on Systems, Man & Cybernetics. Systems. - : Institute of Electrical and Electronics Engineers (IEEE). - 2168-2216 .- 2168-2232. ; 52:8, s. 5222-5234
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Tidskriftsartikel (refereegranskat)abstract
- Convolutional neural networks (CNNs) provide the best accuracy for disparity estimation. However, CNNs are computationally expensive, making them unfavorable for resource-limited devices with real-time constraints. Recent advances in neural architectures search (NAS) promise opportunities in automated optimization for disparity estimation. However, the main challenge of the NAS methods is the significant amount of computing time to explore a vast search space [e.g., 1.6x10(29)] and costly training candidates. To reduce the NAS computational demand, many proxy-based NAS methods have been proposed. Despite their success, most of them are designed for comparatively small-scale learning tasks. In this article, we propose a fast NAS method, called FastStereoNet, to enable resource-aware NAS within an intractably large search space. FastStereoNet automatically searches for hardware-friendly CNN architectures based on late acceptance hill climbing (LAHC), followed by simulated annealing (SA). FastStereoNet also employs a fine-tuning with a transferred weights mechanism to improve the convergence of the search process. The collection of these ideas provides competitive results in terms of search time and strikes a balance between accuracy and efficiency. Compared to the state of the art, FastStereoNet provides 5.25x reduction in search time and 44.4x reduction in model size. These benefits are attained while yielding a comparable accuracy that enables seamless deployment of disparity estimation on resource-limited devices. Finally, FastStereoNet significantly improves the perception quality of disparity estimation deployed on field-programmable gate array and Intel Neural Compute Stick 2 accelerator in a significantly less onerous manner.
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| 17. |
- Majd, Amin, et al.
(författare)
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A Cloud Based Super-Optimization Method to Parallelize the Sequential Code's Nested Loops
- 2019
-
Ingår i: Proceedings 2019 IEEE 13th International Symposium on Embedded Multicore/Many-Core Systems-on-Chip (MCSOC 2019). - : IEEE COMPUTER SOC. - 9781728148823 ; , s. 281-287
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Konferensbidrag (refereegranskat)abstract
- Advances in hardware architecture regarding multi-core processors make parallel computing ubiquitous. To achieve the maximum utilization of multi-core processors, parallel programming techniques are required. However, there are several challenges standing in front of parallel programming. These problems are mainly divided into three major groups. First, although recent advancements in parallel programming languages (e.g. MPI, OpenCL, etc.) assist developers, still parallel programming is not desirable for most programmers. The second one belongs to the massive volume of old software and applications, which have been written in serial mode. However, converting millions of line of serial codes to parallel codes is highly time-consuming and requiring huge verification effort. Third, the production of software and applications in parallel mode is very expensive since it needs knowledge and expertise. Super-optimization provided by super compilers is the process of automatically determine the dependent and independent instructions to find any data dependency and loop-free sequence of instructions. Super compiler then runs these instructions on different processors in the parallel mode, if it is possible. Super-optimization is a feasible solution for helping the programmer to get relaxed from parallel programming workload. Since the most complexity of the sequential codes is in the nested loops, we try to parallelize the nested loops by using the idea of super-optimization. One of the underlying stages in the super-optimization is scheduling tiled space for iterating nested loops. Since the problem is NP-Hard, using the traditional optimization methods are not feasible. In this paper, we propose a cloud-based super-optimization method as Software-as-a-Service (SaaS) to reduce the cost of parallel programming. In addition, it increases the utilization of the processing capacity of the multi-core processor. As the result, an intermediate programmer can use the whole processing capacity of his/her system without knowing anything about writing parallel codes or super compiler functions by sending the serial code to a cloud server and receiving the parallel version of the code from the cloud server. In this paper, an evolutionary algorithm is leveraged to solve the scheduling problem of tiles. Our proposed super-optimization method will serve as software and provided as a hybrid (public and private) deployment model.
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| 18. |
- Majd, A., et al.
(författare)
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Improving motion safety and efficiency of intelligent autonomous swarm of drones
- 2020
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Ingår i: Drones. - : MDPI AG. - 2504-446X. ; 4:3, s. 1-19
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Tidskriftsartikel (refereegranskat)abstract
- Interest is growing in the use of autonomous swarms of drones in various mission-physical applications such as surveillance, intelligent monitoring, and rescue operations. Swarm systems should fulfill safety and efficiency constraints in order to guarantee dependable operations. To maximize motion safety, we should design the swarm system in such a way that drones do not collide with each other and/or other objects in the operating environment. On other hand, to ensure that the drones have sufficient resources to complete the required task reliably, we should also achieve efficiency while implementing the mission, by minimizing the travelling distance of the drones. In this paper, we propose a novel integrated approach that maximizes motion safety and efficiency while planning and controlling the operation of the swarm of drones. To achieve this goal, we propose a novel parallel evolutionary-based swarm mission planning algorithm. The evolutionary computing allows us to plan and optimize the routes of the drones at the run-time to maximize safety while minimizing travelling distance as the efficiency objective. In order to fulfill the defined constraints efficiently, our solution promotes a holistic approach that considers the whole design process from the definition of formal requirements through the software development. The results of benchmarking demonstrate that our approach improves the route efficiency by up to 10% route efficiency without any crashes in controlling swarms compared to state-of-the-art solutions.
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| 19. |
- Mitander, Amanda, et al.
(författare)
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Complement Consumption in Systemic Lupus Erythematosus Leads to Decreased Opsonophagocytosis In Vitro.
- 2018
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Ingår i: The Journal of rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 45:11, s. 1557-1564
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Tidskriftsartikel (refereegranskat)abstract
- Infections remain a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). The high prevalence of infections in SLE is attributed to both the disease and its treatments. The complement system plays an important role in host immune responses against invading microorganisms. We sought to provide the experimental and clinical evidence supporting the hypothesis that low levels of complement factors cause defective complement-mediated opsonization in patients with SLE.Staphylococcus aureus was opsonized with sera from healthy individuals (n = 16), SLE patients with normal (n = 5) or low complement (n = 8) levels. Phagocytosis of S. aureus by healthy human neutrophils was analyzed by an imaging flow cytometry-based method. We retrospectively examined the infection incidence in relation to complement levels in a cohort of 165 patients with SLE during a 1.5-year period. The association was analyzed for infection incidence and disease-related variables.Uptake of S. aureus by neutrophils was decreased when S. aureus was opsonized with sera from SLE patients with low complement levels compared to sera from healthy individuals and SLE patients with normal complement. In our SLE cohort, 44% of patients had at least 1 infection during the 1.5 years. No significant association was observed between complement levels and infection risk. Importantly, high-dose glucocorticoids (GC; prednisone ≥ 10 mg/day) were the most important predictive factor for infections in patients with SLE.Low complement levels affect bacterial opsonization in SLE blood and lead to downregulated phagocytosis by neutrophils. High-dose GC increase the infection risk in patients with SLE.
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| 20. |
- Mohammad, Majd
(författare)
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Lipoproteins in Staphylococcus aureus infections
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Staphylococcus aureus (S. aureus) infections remain a major challenge for the healthcare system, and new treatment options are highly demanded. S. aureus is a pathogenic microorganism, responsible for a broad range of clinical infections in humans. Septic arthritis, a debilitating joint disease, is mainly due to S. aureus. Furthermore, the majority of skin and soft tissue infections are also caused by S. aureus. S. aureus expresses multiple bacterial molecules, including bacterial lipoproteins (Lpps), which play a role in the disease pathogenesis. S. aureus Lpps, the predominant ligands for TLR2, are important for bacterial survival due to their role in maintaining the metabolic activity of the bacteria. So far, their role in different staphylococcal infections have not been fully defined. The aim of this thesis was to explore the role of S. aureus Lpp in the mouse models for septic arthritis and skin infection. The severity of septic arthritis and skin inflammation/infection as well as the molecular and cellular response of the host upon S. aureus Lpp exposure was the main focus of the thesis. S. aureus Lpp, injected intra-articularly into murine knee joints, induced chronic macroscopic arthritis of a destructive character, which was mediated by monocytes/macrophages via TLR2. However, co-injection of purified S. aureus Lpp with S. aureus into mouse knees resulted in increased bacterial elimination. Mice intravenously infected with the S. aureus Lpp-expressing Newman parental strain, had increased mortality and weight reduction as well as impaired bacterial clearance in kidneys independent of TLR2 compared to those mice infected with Lpp-deficient strain. However, Lpp expression had no significant impact on the severity of bone destruction. Finally, in a skin infection model, expression of Lpp in S. aureus was associated with an enhanced inflammatory response and increased bacterial burden in the local infection site. In conclusion, S. aureus Lpps play differential roles depending on the route of infection. In the case of locally-induced arthritis, S. aureus Lpps play a dual role – on the one hand, Lpps contribute to joint inflammation and damage; on the other hand, Lpps elicit strong innate immune responses, resulting in efficient bacterial elimination. In haematogenous septic arthritis, Lpps have a limited impact on arthritis development. Finally, in the skin infection model, S. aureus Lpps contribute to local skin inflammation and enhance skin abscess formation.
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| 21. |
- Mohammad, Majd, et al.
(författare)
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RAGE Deficiency Impairs Bacterial Clearance in Murine Staphylococcal Sepsis, but Has No Significant Impact on Staphylococcal Septic Arthritis.
- 2016
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- Septic arthritis is a serious joint disease often caused by Staphylococcus aureus (S. aureus). Receptor for Advanced Glycation End products (RAGE) has an important role in several infections. We sought to investigate the role of RAGE in staphylococcal septic arthritis and sepsis in mice.Wild-type (WT) and RAGE deficient (RAGE-/-) mice were intra-articularly or intravenously inoculated with an arthritic or septic dose of S. aureus LS-1 strain. Clinical arthritis, weight development and mortality were monitored for 14 days. Serum levels of cytokines, kidney bacterial loads as well as micro-CT and histopathology of the joints were assessed.RAGE-/- mice with septic arthritis had significantly lower IL-17A and higher bone mineral density (BMD) compared to the control group. However, no significant differences between the groups were observed regarding the weight loss, the severity and frequency of arthritis, and bacterial loads in the kidneys. In mice with sepsis, the overall mortality rate was similar in RAGE-/- (39%) and in WT mice (45%). However, RAGE-/- mice with sepsis had significantly higher bacterial load in their kidneys compared to the WT controls. In line with data from hematogenous S. aureus arthritis, RAGE deficiency had no impact on arthritis severity in local joint infection.Our results indicate that lack of RAGE has no significant impact on septic arthritis. However, RAGE-/- mice had significantly higher BMD compared to WT mice, which coincided with lower IL-17A in RAGE-/- mice. In sepsis, RAGE deficiency impairs bacterial kidney clearance.
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| 22. |
- Mohammad, Majd, et al.
(författare)
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Staphylococcus aureus lipoproteins in infectious diseases.
- 2022
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Ingår i: Frontiers in microbiology. - : Frontiers Media SA. - 1664-302X. ; 13
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Forskningsöversikt (refereegranskat)abstract
- Infections with the Gram-positive bacterial pathogen Staphylococcus aureus remain a major challenge for the healthcare system and demand new treatment options. The increasing antibiotic resistance of S. aureus poses additional challenges, consequently inflicting a huge strain in the society due to enormous healthcare costs. S. aureus expresses multiple molecules, including bacterial lipoproteins (Lpps), which play a role not only in immune response but also in disease pathogenesis. S. aureus Lpps, the predominant ligands of TLR2, are important for bacterial survival as they maintain the metabolic activity of the bacteria. Moreover, Lpps possess many diverse properties that are of vital importance for the bacteria. They also contribute to host cell invasion but so far their role in different staphylococcal infections has not been fully defined. In this review, we summarize the current knowledge about S. aureus Lpps and their distinct roles in various infectious disease animal models, such as septic arthritis, sepsis, and skin and soft tissue infections. The molecular and cellular response of the host to S. aureus Lpp exposure is also a primary focus.
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| 23. |
- Mohammad, Majd, et al.
(författare)
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Staphylococcus aureus lipoproteins promote abscess formation in mice, shielding bacteria from immune killing.
- 2021
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- Despite being a major bacterial factor in alerting the human immune system, the role of Staphylococcus aureus (S. aureus) lipoproteins (Lpp) in skin infections remains largely unknown. Here, we demonstrated that subcutaneous injection of S. aureus Lpp led to infiltration of neutrophils and monocytes/macrophages and induced skin lesions in mice. Lipid-moiety of S. aureus Lpp and host TLR2 was responsible for such effect. Lpp-deficient S. aureus strains exhibited smaller lesion size and reduced bacterial loads than their parental strains; the altered phenotype in bacterial loads was TLR2-independent. Lpp expression in skin infections contributed to imbalanced local hemostasis toward hypercoagulable state. Depletion of leukocytes or fibrinogen abrogated the effects induced by Lpp in terms of skin lesions and bacterial burden. Our data suggest that S. aureus Lpp induce skin inflammation and promote abscess formation that protects bacteria from innate immune killing. This suggests an intriguing bacterial immune evasion mechanism.
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| 24. |
- Mohammad, Majd, et al.
(författare)
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The role of Staphylococcus aureus lipoproteins in hematogenous septic arthritis.
- 2020
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Permanent joint dysfunction is a devastating complication in patients with septic arthritis. Staphylococcus aureus (S. aureus) lipoproteins (Lpp), the predominant ligands for TLR2, are known to be arthritogenic and induce bone destruction when introduced directly into the joint. Here, we aim to investigate the importance of S. aureus Lpp and TLR2 in a hematogenous septic arthritis model, which is the most common route of infection in humans. C57BL/6 wild-type and TLR2 deficient mice were intravenously inoculated with S. aureus Newman parental strain or its lipoprotein-deficient Δlgt mutant strain. The clinical course of septic arthritis, radiological changes, and serum levels of cytokines and chemokines, were assessed. Newman strain induced more severe and frequent clinical septic polyarthritis compared to its Δlgt mutant in TLR2 deficient mice, but not in wild-type controls. Bone destruction, however, did not differ between groups. Lpp expression was associated with higher mortality, weight loss as well as impaired bacterial clearance in mouse kidneys independent of TLR2. Furthermore, Lpp expression induced increased systemic pro-inflammatory cytokine and neutrophil chemokine release. Staphylococcal Lpp are potent virulence factors in S. aureus systemic infection independent of host TLR2 signalling. However, they have a limited impact on bone erosion in hematogenous staphylococcal septic arthritis.
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| 25. |
- Mohammad, Majd, et al.
(författare)
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The YIN and YANG of lipoproteins in developing and preventing infectious arthritis by Staphylococcus aureus.
- 2019
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Ingår i: PLoS pathogens. - : Public Library of Science (PLoS). - 1553-7374. ; 15:6
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Tidskriftsartikel (refereegranskat)abstract
- Rapid bone destruction often leads to permanent joint dysfunction in patients with septic arthritis, which is mainly caused by Staphylococcus aureus (S. aureus). Staphylococcal cell wall components are known to induce joint inflammation and bone destruction. Here, we show that a single intra-articular injection of S. aureus lipoproteins (Lpps) into mouse knee joints induced chronic destructive macroscopic arthritis through TLR2. Arthritis was characterized by rapid infiltration of neutrophils and monocytes. The arthritogenic effect was mediated mainly by macrophages/monocytes and partially via TNF-α but not by neutrophils. Surprisingly, a S. aureus mutant lacking Lpp diacylglyceryl transferase (lgt) caused more severe joint inflammation, which coincided with higher bacterial loads of the lgt mutant in local joints than those of its parental strain. Coinjection of pathogenic S. aureus LS-1 with staphylococcal Lpps into mouse knee joints caused improved bacterial elimination and diminished bone erosion. The protective effect of the Lpps was mediated by their lipid moiety and was fully dependent on TLR2 and neutrophils. The blocking of CXCR2 on neutrophils resulted in total abrogation of the protective effect of the Lpps. Our data demonstrate that S. aureus Lpps elicit innate immune responses, resulting in a double-edged effect. On the one hand, staphylococcal Lpps boost septic arthritis. On the other hand, Lpps act as adjuvants and activate innate immunity, which could be useful for combating infections with multiple drug-resistant strains.
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