| 1. |
- Grinnemo, Karl-Henrik, et al.
(författare)
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Costimulation blockade induces tolerance to HESC transplanted to the testis and induces regulatory T-cells to HESC transplanted into the heart
- 2008
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Ingår i: Stem Cells. - : Oxford University Press (OUP). - 1549-4918 .- 1066-5099. ; 26:7, s. 1850-1857
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Tidskriftsartikel (refereegranskat)abstract
- In order to study the ability of costimulation blockade to induce tolerance to human embryonic stem cells (HESC), severe combined immunodeficient (SCID), and immunocompetent C57BL/6 mice treated with costimulation blockade received intratesticular and intramyocardial HESC transplants. All SCID mice with intratesticular HESC transplants developed teratoma. When SCID mice were transplanted intramyocardially, only two of five mice developed teratoma-like tumors. C57BL/6 mice transplanted intratesticularly and treated with costimulation blockade all developed teratoma and were surrounded by CD4(+)CD25(+)Foxp3(+) T-cells, while isotype control treated recipients rejected their grafts. Most C57BL/6 mice transplanted intramyocardially and treated with costimulation blockade demonstrated lymphocytic infiltrates 1 month after transplantation, whereas one maintained its graft. Isolation of regulatory T-cells from intramyocardial transplanted recipients treated with costimulation blockade demonstrated specificity toward undifferentiated HESC and down-regulated naive T-cell activation toward HESC. These results demonstrate that costimulation blockade is sufficiently robust to induce tolerance to HESC in the immune-privileged environment of the testis. HESC specific regulatory T-cells developed to HESC transplanted to the heart and the success of transplantation was similar to that seen in SCID mice.
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| 2. |
- Simonson, Oscar E., et al.
(författare)
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In Vivo Effects of Mesenchymal Stromal Cells in Two Patients With Severe Acute Respiratory Distress Syndrome
- 2015
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Ingår i: Stem Cells Translational Medicine. - : Oxford University Press (OUP). - 2157-6564 .- 2157-6580. ; 4:10, s. 1199-1213
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Tidskriftsartikel (refereegranskat)abstract
- Mesenchymal stromal cells (MSCs) have been investigated as a treatment for various inflammatory diseases because of their immunomodulatory and reparative properties. However, many basic questions concerning their mechanisms of action after systemic infusion remain unanswered. We performed a detailed analysis of the immunomodulatory properties and proteomic profile of MSCs systemically administered to two patients with severe refractory acute respiratory distress syndrome (ARDS) on a compassionate use basis and attempted to correlate these with in vivo anti-inflammatory actions. Both patients received 2 x 10(6) cells per kilogram, and each subsequently improved with resolution of respiratory, hemodynamic, and multiorgan failure. In parallel, a decrease was seen in multiple pulmonary and systemic markers of inflammation, including epithelial apoptosis, alveolar-capillary fluid leakage, and proinflammatory cytokines, microRNAs, and chemokines. In vitro studies of the MSCs demonstrated a broad anti-inflammatory capacity, including suppression of T-cell responses and induction of regulatory phenotypes in T cells, monocytes, and neutrophils. Some of these in vitro potency assessments correlated with, and were relevant to, the observed in vivo actions. These experiences highlight both the mechanistic information that can be gained from clinical experience and the value of correlating in vitro potency assessments with clinical effects. The findings also suggest, but do not prove, a beneficial effect of lung protective strategies using adoptively transferred MSCs in ARDS. Appropriate randomized clinical trials are required to further assess any potential clinical efficacy and investigate the effects on in vivo inflammation. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:1199-1213
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| 3. |
- Wedin, Johan O, et al.
(författare)
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Surgical Removal of a Detached Mitral Valve Repair Clip to Resolve Cardiogenic Shock
- 2022
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Ingår i: JACC. - : Elsevier. - 2666-0849. ; 4:11, s. 658-662
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Tidskriftsartikel (refereegranskat)abstract
- Transcatheter edge-to-edge mitral valve repair (TEER) with a clip device relieves symptoms and improves outcomes in patients not suitable for open heart surgery. Here, we present a patient in whom ventricular arrhythmias developed as a result of clip embolization shortly after TEER. He underwent successful emergent surgical clip removal and mitral valve replacement. (Level of Difficulty: Advanced.).
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| 4. |
- Ahlgren, Bengt, et al.
(författare)
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Are MIRCC and Rate-based Congestion Control in ICN READY for Variable Link Capacity?
- 2017
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Information-centric networking (ICN) has been introduced as a potential future networking architecture. ICN promises an architecture that makes information independent from lo- cation, application, storage, and transportation. Still, it is not without challenges. Notably, there are several outstanding issues regarding congestion control: Since ICN is more or less oblivious to the location of information, it opens up for a single application flow to have several sources, something which blurs the notion of transport flows, and makes it very difficult to employ traditional end-to-end congestion control schemes in these networks. Instead, ICN networks often make use of hop-by-hop congestion control schemes. How- ever, these schemes are also tainted with problems, e.g., several of the proposed ICN congestion controls assume fixed link capacities that are known beforehand. Since this seldom is the case, this paper evaluates the consequences in terms of latency, throughput, and link usage, variable link capacities have on a hop-by-hop congestion control scheme, such as the one employed by the Multipath-aware ICN Rate-based Congestion Control (MIRCC). The evaluation was carried out in the OMNeT++ simulator, and demonstrates how seemingly small variations in link capacity significantly deterio- rate both latency and throughput, and often result in inefficient network link usage.
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| 5. |
- Ahlgren, Bengt, et al.
(författare)
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ICN congestion control for wireless links
- 2018
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Ingår i: IEEE WCNC 2018 Conference Proceedings. - New York : IEEE.
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Konferensbidrag (refereegranskat)abstract
- Information-centric networking (ICN) with its design around named-based forwarding and in-network caching holds great promises to become a key architecture for the future Internet. Many proposed ICN hop-by-hop congestion control schemes assume a fixed and known link capacity, which rarely - if ever - holds true for wireless links. Firstly, we demonstrate that although these congestion control schemes are able to fairly well utilise the available wireless link capacity, they greatly fail to keep the delay low. In fact, they essentially offer the same delay as in the case with no hop-by-hop, only end-to-end, congestion control. Secondly, we show that by complementing these schemes with an easy-to-implement, packet-train capacity estimator, we reduce the delay to a level significantly lower than what is obtained with only end-to-end congestion control, while still being able to keep the link utilisation at a high level.
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| 6. |
- Ahlgren, Bengt, et al.
(författare)
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Latency-aware Multipath Scheduling inInformation-centric Networks
- 2019
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Ingår i: Proceedings of the Fifteenth Swedish National Computer Networking Workshop (SNCNW), Luleå, Sweden. 4-5 June 2019..
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Konferensbidrag (refereegranskat)abstract
- We present the latency-aware multipath schedulerZQTRTT that takes advantage of the multipath opportunities ininformation-centric networking. The goal of the scheduler is touse the (single) lowest latency path for transaction-oriented flows,and use multiple paths for bulk data flows. A new estimatorcalled zero queue time ratio is used for scheduling over multiplepaths. The objective is to distribute the flow over the paths sothat the zero queue time ratio is equal on the paths, that is,so that each path is ‘pushed’ equally hard by the flow withoutcreating unwanted queueing. We make an initial evaluation usingsimulation that shows that the scheduler meets our objectives.
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| 7. |
- Aldi, Silvia, et al.
(författare)
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Dual roles of heparanase in human carotid plaque calcification
- 2019
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Ingår i: Atherosclerosis. - : ELSEVIER IRELAND LTD. - 0021-9150 .- 1879-1484. ; 283, s. 127-136
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Calcification is a hallmark of advanced atherosclerosis and an active process akin to bone remodeling. Heparanase (HPSE) is an endo-beta-glucuronidase, which cleaves glycosaminoglycan chains of heparan sulfate proteoglycans. The role of HPSE is controversial in osteogenesis and bone remodeling while it is unexplored in vascular calcification. Previously, we reported upregulation of HPSE in human carotid endarterectomies from symptomatic patients and showed correlation of HPSE expression with markers of inflammation and increased thrombogenicity. The present aim is to investigate HPSE expression in relation to genes associated with osteogenesis and osteolysis and the effect of elevated HPSE expression on calcification and osteolysis in vitro.Methods: Transcriptomic and immunohistochemical analyses were performed using the Biobank of Karolinska Endarterectomies (BiKE). In vitro calcification and osteolysis were analysed in human carotid smooth muscle cells overexpressing HPSE and bone marrow-derived osteoclasts from HPSE-transgenic mice respectively.Results: HPSE expression correlated primarily with genes coupled to osteoclast differentiation and function in human carotid atheromas. HPSE was expressed in osteoclast-like cells in atherosclerotic lesions, and HPSE-transgenic bone marrow-derived osteoclasts displayed a higher osteolytic activity compared to wild-type cells. Contrarily, human carotid SMCs with an elevated HPSE expression demonstrated markedly increased mineralization upon osteogenic differentiation.Conclusions: We suggest that HPSE may have dual functions in vascular calcification, depending on the stage of the disease and presence of inflammatory cells. While HPSE plausibly enhances mineralization and osteogenic differentiation of vascular smooth muscle cells, it is associated with inflammation-induced osteoclast differentiation and activity in advanced atherosclerotic plaques.
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| 8. |
- Beljanski, Vladimir, et al.
(författare)
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Pleiotropic roles of autophagy in stem cell-based therapies
- 2019
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Ingår i: Cytotherapy. - : ELSEVIER SCI LTD. - 1465-3249 .- 1477-2566. ; 21:4, s. 380-392
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Forskningsöversikt (refereegranskat)abstract
- Stem cells (SCs) have been proven to possess regenerative and immunomodulatory properties and can be used to treat diseases that involve loss of cells due to tissue damage or inflammation. For this approach to succeed, SCs or their derivatives should be able to engraft in the target tissue at least for a short period of time. Unfortunately, once injected, therapeutic SCs will encounter a hostile environment, including hypoxia, lack of nutrients and stromal support, and cells may also be targeted and rejected by the immune system. Therefore, SC's stress-response mechanisms likely play a significant role in survival of injected cells and possibly contribute to their therapeutic efficacy. Autphagy, a stress-response pathway, is involved in many different cellular processes, such as survival during hypoxia and nutrient deprivation, cellular differentiation and de-differentiation, and it can also contribute to their immunovisibility by regulating antigen presentation and cytokine secretion. Autophagy machinery interacts with many proteins and signaling pathways that regulate SC properties, including PI3K/Akt, mammalian target of rapamycin (mTOR), Wnt, Hedgehog and Notch, and it is also involved in regulating intracellular reactive oxygen species (ROS) levels. In this review, we contend that autophagy is an important therapeutic target that can be used to improve the outcome of SC-based tissue repair and regeneration. Further research should reveal whether inhibition or stimulation of autophagy increases the therapeutic utility of SCs and it should also identify appropriate therapeutic regimens that can be applied in the clinic.
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| 9. |
- Beusch, Christian M., et al.
(författare)
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Analysis of local extracellular matrix identifies different aetiologies behind bicuspid and tricuspid aortic valve degeneration and suggests therapies
- 2023
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Ingår i: Cellular and Molecular Life Sciences (CMLS). - : Springer Nature. - 1420-682X .- 1420-9071. ; 80:9
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Tidskriftsartikel (refereegranskat)abstract
- Aortic valve degeneration (AVD) is a life-threatening condition that has no medical treatment and lacks individual therapies. Although extensively studied with standard approaches, aetiologies behind AVD are unclear. We compared abundances of extracellular matrix (ECM) proteins from excised valve tissues of 88 patients with isolated AVD of normal tricuspid (TAV) and congenital bicuspid aortic valves (BAV), quantified more than 1400 proteins per ECM sample by mass spectrometry, and demonstrated that local ECM preserves molecular cues of the pathophysiological processes. The BAV ECM showed enrichment with fibrosis markers, namely Tenascin C, Osteoprotegerin, and Thrombospondin-2. The abnormal physical stress on BAV may cause a mechanical injury leading to a continuous Tenascin C-driven presence of myofibroblasts and persistent fibrosis. The TAV ECM exhibited enrichment with Annexin A3 (p = 1.1 x 10(-16) and the fold change 6.5) and a significant deficit in proteins involved in high-density lipid metabolism. These results were validated by orthogonal methods. The difference in the ECM landscape suggests distinct aetiologies between AVD of BAV and TAV; warrants different treatments of the patients with BAV and TAV; elucidates the molecular basis of AVD; and implies possible new therapeutic approaches. Our publicly available database (human_avd_ecm.surgsci. uu.se) is a rich source for medical doctors and researchers who are interested in AVD or heart ECM in general. Systematic proteomic analysis of local ECM using the methods described here may facilitate future studies of various tissues and organs in development and disease.
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| 10. |
- Christoforidis, Christos, et al.
(författare)
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SCTPTrace : An Extension of TCPTrace for SCTP
- 2016
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Rapport (populärvet., debatt m.m.)abstract
- When it comes to analyzing TCP data and extracting the information in such a way that it becomes viewable, there are a couple of tools that can be used. One of them is TCPTrace. TCPTrace is used to analyze special dump files created from programs such as tcpdump, snoop and WinDump. TCPTrace became published for a broader public in the late 1996 by Shawn Ostermann. Since then functionalities, changes and fixes have been implemented for example the extension to create graphs and trace UDP packets. From the dump files a trace will be done, and depending on the input from the user, TCPTrace can present this information in a number of ways such as plain text, trace files and graphs, depending on the amount of information the user is looking for. The extensive information traced will be viewed and divided for each connection found. For each connection, information such as retransmits, throughput, round trip times, bytes and packets sent and received etc. can be presented.This project came to be, since there has been a desire to see a tool for SCTP that provides the same functionalities as TCPTrace. The project, called SCTPTrace, aimed to implement as much of the previous TCP functionalities as possible for the SCTP protocol.
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