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Sökning: WFRF:(Milosevic I)

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121.
  • Börjesson, Vanja, et al. (författare)
  • TC-hunter: identification of the insertion site of a transgenic gene within the host genome
  • 2022
  • Ingår i: Bmc Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Transgenic animal models are crucial for the study of gene function and disease, and are widely utilized in basic biological research, agriculture and pharma industries. Since the current methods for generating transgenic animals result in the random integration of the transgene under study, the phenotype may be compromised due to disruption of known genes or regulatory regions. Unfortunately, most of the tools that predict transgene insertion sites from high-throughput data are not publicly available or not properly maintained. Results: We implemented TC-hunter, Transgene-Construct hunter, an open tool that identifies transgene insertion sites and provides simple reports and visualization aids. It relies on common tools used in the analysis of high-throughput data and makes use of chimeric reads and discordant read pairs to identify and support the transgenic insertion site. To demonstrate its applicability, we applied TC-hunter to four transgenic mice samples harboring the human PPM1D gene, a model used in the study of malignant tumor development. We identified the transgenic insertion site in each sample and experimentally validated them with Touchdown-polymerase chain reaction followed by Sanger sequencing. Conclusions: TC-hunter is an accessible bioinformatics tool that can automatically identify transgene insertion sites from DNA sequencing data with high sensitivity (98%) and precision (92.45%). TC-hunter is a valuable tool that can aid in evaluating any potential phenotypic complications due to the random integration of the transgene and can be accessed at https://github.com/bcfgothenburg/SSF.
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122.
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123.
  • Ederle, Joerg, et al. (författare)
  • Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial
  • 2010
  • Ingår i: The Lancet. - 1474-547X. ; 375:9719, s. 985-997
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006), Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
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124.
  • Lopez-Garcia, SC, et al. (författare)
  • Treatment and long-term outcome in primary distal renal tubular acidosis
  • 2019
  • Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 34:6, s. 981-991
  • Tidskriftsartikel (refereegranskat)
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125.
  • Lukyanchuk, I., et al. (författare)
  • Rayleigh instability of confined vortex droplets in critical superconductors
  • 2015
  • Ingår i: Nature Physics. - 1745-2473 .- 1745-2481. ; 11:1, s. 21-25
  • Tidskriftsartikel (refereegranskat)abstract
    • Depending on the Ginzburg-Landau parameter kappa, superconductors can either be fully diamagnetic if kappa < 1/root 2 (type I superconductors) or allow magnetic flux to penetrate through Abrikosov vortices if kappa > 1/root 2 (type II superconductors; refs 1,2). At the Bogomolny critical point, kappa = kappa(c) = 1/root 2, a state that is infinitely degenerate with respect to vortex spatial configurations arises(3,4). Despite in-depth investigations of conventional type I and type II superconductors, a thorough understanding of the magnetic behaviour in the near-Bogomolny critical regime at kappa similar to kappa(c) remains lacking. Here we report that in confined systems the critical regime expands over a finite interval of kappa forming a critical superconducting state. We show that in this state, in a sample with dimensions comparable to the vortex core size, vortices merge into a multi-quanta droplet, which undergoes Rayleigh instability(5) on increasing kappa and decays by emitting single vortices. Superconducting vortices realize Nielsen-Olesen singular solutions of the Abelian Higgs model, which is pervasive in phenomena ranging from quantum electrodynamics to cosmology(6-9). Our study of the transient dynamics of Abrikosov-Nielsen-Olesen vortices in systems with boundaries promises access to non-trivial effects in quantum field theory by means of bench-top laboratory experiments.
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126.
  • Müller, Matias I., et al. (författare)
  • A Risk-Theoretical Approach to H2-Optimal Control under Covert Attacks
  • 2018
  • Ingår i: <em>57th IEEE Conference on Decision and Control</em>. - : IEEE. - 9781538613955 ; , s. 4553-4558
  • Konferensbidrag (refereegranskat)abstract
    • We consider the control design problem of optimizing the H-2 performance of a closed-loop system despite the presence of a malicious covert attacker. It is assumed that the attacker has incomplete knowledge on the true process we are controlling. To account for this uncertainty, we employ different measures of risk from the so called family of coherent measures of risk. In particular, we compare the closed-loop performance when a nominal value is used, with three different measures of risk: average risk, worst-case scenario and conditional valueat- risk (CVaR). Additionally, applying the approach from a previous work, we derive a convex formulation for the control design problem when CVaR is employed to quantify the risk. A numerical example illustrates the advantages of our approach.
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127.
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128.
  • Vidojkovic, Vojkan, et al. (författare)
  • RF and mm-Wave Systems and Circuits for Communications and Sensing
  • 2023
  • Ingår i: 2023 58th International Scientific Conference on Information, Communication and Energy Systems and Technologies, ICEST 2023 - Proceedings. ; , s. 83-92
  • Konferensbidrag (refereegranskat)abstract
    • In the last decade wireless communications experienced a nearly exponential growth. The number of connected devices exceeds the number of people on earth and the data rates can be as high as several GB/s. 5G already incorporates mm-wave frequencies. The next wave in wireless technology will be about sensing the environment and combining with communications. The applications are very versatile, like driver monitoring, autonomous driving, industry applications related to non-destructive material testing, food control and improving efficiency in agriculture. The future 6G standards will further extend the use of mm-wave bands for increasing data rates and incorporating sensing functionality. From semiconductor technology and design perspective significant progress has been made to gain speed, reliability and design flows that guarantee first-time right mm-wave circuits. This paper approaches mm-wave communications and sensing from application, system and circuit perspectives, while identifying challenges and finally showing examples how to address them from circuit perspective.
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129.
  • Wickstrom, Malin, et al. (författare)
  • Targeting the hedgehog signal transduction pathway at the level of GLI inhibits neuroblastoma cell growth in vitro and in vivo
  • 2013
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 132:7, s. 1516-1524
  • Tidskriftsartikel (refereegranskat)abstract
    • Hedgehog (HH) signaling is an important regulator of embryogenesis that has been associated with the development of several types of cancer. HH signaling is characterized by Smoothened (SMO)-dependent activation of the GLI transcription factors, which regulate the expression of critical developmental genes. Neuroblastoma, an embryonal tumor of the sympathetic nervous system, was recently shown to express high levels of key molecules in this signaling cascade. Using compounds blocking SMO (cyclopamine and SANT1) or GLI1/GLI2 (GANT61) activity revealed that inhibition of HH signaling at the level of GLI was most effective in reducing neuroblastoma growth. GANT61 sensitivity positively correlated to GLI1 and negatively to MYCN expression in the neuroblastoma cell lines tested. GANT61 downregulated GLI1, c-MYC, MYCN and Cyclin D1 expression and induced apoptosis of neuroblastoma cells. The effects produced by GANT61 were mimicked by GLI knockdown but not by SMO knockdown. Furthermore, GANT61 enhanced the effects of chemotherapeutic drugs used in the treatment of neuroblastoma in an additive or synergistic manner and reduced the growth of established neuroblastoma xenografts in nude mice. Taken together this study suggests that inhibition of HH signaling is a highly relevant therapeutic target for high-risk neuroblastoma lacking MYCN amplification and should be considered for clinical testing.
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130.
  • Wolmer-Solberg, N., et al. (författare)
  • Frequent detection of human cytomegalovirus in neuroblastoma: A novel therapeutic target?
  • 2013
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 133:10, s. 2351-2361
  • Tidskriftsartikel (refereegranskat)abstract
    • Neuroblastoma is the most common and deadly tumor of childhood, where new therapy options for patients with high-risk disease are highly warranted. Human cytomegalovirus (HCMV) is prevalent in the human population and has recently been implicated in different cancer forms where it may provide mechanisms for oncogenic transformation, oncomodulation and tumor cell immune evasion. Here we show that the majority of primary neuroblastomas and neuroblastoma cell lines are infected with HCMV. Our analysis show that HCMV immediate-early protein was expressed in 100% of 36 primary neuroblastoma samples, and HCMV late protein was expressed in 92%. However, no infectious virus was detected in primary neuroblastoma tissue extracts. Remarkably, all six human neuroblastoma cell lines investigated contained CMV DNA and expressed HCMV proteins. HCMV proteins were expressed in neuroblastoma cells expressing the proposed stem cell markers CD133 and CD44. When engrafted into NMRI nu/nu mice, human neuroblastoma cells expressed HCMV DNA, RNA and proteins but did not produce infectious virus. The HCMV-specific antiviral drug valganciclovir significantly reduced viral protein expression and cell growth both in vitro and in vivo. These findings indicate that HCMV is important for the pathogenesis of neuroblastoma and that anti-viral therapy may be a novel adjuvant treatment option for children with neuroblastoma. What's new? Relapse and invasiveness of neuroblastoma, a frequently fatal cancer of early childhood, may be linked to the presence of human cytomegalovirus (HCMV), one of the most common congenital viral infections known. In this study, HCMV was observed in primary neuroblastoma tumors and in six neuroblastoma cell lines. Although no infectious virus was isolated from tumors, the HCMV-specific drug valganciclovir significantly reduced viral protein expression and tumor cell growth both in vitro and in vivo. The results suggest that HCMV may be important in the pathogenesis of neuroblastoma and that antiviral therapy may represent a possible future treatment option for affected children. We have shown that all examined primary neuroblastoma tumors and six neuroblastoma cell lines were infected with HCMV, but no infectious virus was isolated from tumors. The HCMV-specific drug Valganciclovir significantly reduced viral protein expression and tumor cell growth in vitro and in vivo. Thus, HCMV may be important in the pathogenesis of neuroblastoma and anti-viral therapy may provide a novel treatment option for children with neuroblastoma.
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