| 191. |
- Nallapalli, Rajesh K, et al.
(författare)
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Targeting filamin A reduces K-RAS-induced lung adenocarcinomas and endothelial response to tumor growth in mice
- 2012
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Ingår i: Molecular Cancer. - : BioMed Central. - 1476-4598. ; 11:50
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Tidskriftsartikel (refereegranskat)abstract
- Background: Many human cancer cells express filamin A (FLNA), an actin-binding structural protein that interacts with a diverse set of cell signaling proteins, but little is known about the biological importance of FLNA in tumor development. FLNA is also expressed in endothelial cells, which may be important for tumor angiogenesis. In this study, we defined the impact of targeting Flna in cancer and endothelial cells on the development of tumors in vivo and on the proliferation of fibroblasts in vitro. less thanbrgreater than less thanbrgreater thanMethods: First, we used a Cre-adenovirus to simultaneously activate the expression of oncogenic K-RAS and inactivate the expression of Flna in the lung and in fibroblasts. Second, we subcutaneously injected mouse fibrosarcoma cells into mice lacking Flna in endothelial cells. less thanbrgreater than less thanbrgreater thanResults: Knockout of Flna significantly reduced K-RAS-induced lung tumor formation and the proliferation of oncogenic K-RAS-expressing fibroblasts, and attenuated the activation of the downstream signaling molecules ERK and AKT. Genetic deletion of endothelial FLNA in mice did not impact cardiovascular development; however, knockout of Flna in endothelial cells reduced subcutaneous fibrosarcoma growth and vascularity within tumors. less thanbrgreater than less thanbrgreater thanConclusions: We conclude that FLNA is important for lung tumor growth and that endothelial Flna impacts local tumor growth. The data shed new light on the biological importance of FLNA and suggest that targeting this protein might be useful in cancer therapeutics.
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| 192. |
- Nguyen, Long H., et al.
(författare)
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Antibiotic Therapy and Risk of Early-Onset Colorectal Cancer : A National Case-Control Study
- 2022
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Ingår i: Clinical and Translational Gastroenterology. - : Nature Publishing Group. - 2155-384X. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Antibiotic use has emerged as a risk factor for colorectal neoplasia and is hypothesized as a contributor to the rising incidence of colorectal cancer under age 50 years or early-onset colorectal cancer (EOCRC). However, the impact of antibiotic use and risk of EOCRC is unknown.METHODS: We conducted a population-based case-control study of CRC among individuals aged >= 18 years in the Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) cohort (2006-2016). The primary outcome was EOCRC. A secondary outcome was CRC at any age. Incident CRC was pathologically confirmed, and for each, up to 5 population-based controls were matched on age, sex, county of residence, and calendar year. We assessed prescriptions until 6 months before CRC diagnosis. Conditional logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs).RESULTS: We identified 54,804 cases of CRC (2,557 EOCRCs) and 261,089 controls. Compared with none, previous antibiotic use was not associated with EOCRC risk after adjustment for potential confounders (aOR 1.06, 95% CI: 0.96, 1.17) with similarly null findings when stratified by anatomic tumor site. In contrast, previous antibiotic use was weakly associated with elevated risk for CRC at any age (aOR 1.05, 95% CI: 1.02, 1.07). A potential but modest link between broad-spectrum antibiotic use and EOCRC was observed (aOR 1.13, 95% CI: 1.02, 1.26).DISCUSSION: We found no conclusive evidence that antibiotics are associated with EOCRC risk. Although antibiotic use was weakly associated with risk of CRC at any age, the magnitude of association was modest, and the study period was relatively short.
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| 193. |
- Nguyen, Long H., et al.
(författare)
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Antibiotic use and the development of inflammatory bowel disease : a national case-control study in Sweden
- 2020
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Ingår i: The Lancet Gastroenterology & Hepatology. - : Elsevier. - 2468-1253. ; 5:11, s. 986-995
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Tidskriftsartikel (refereegranskat)abstract
- Background: Use of antibiotics in early life has been linked with childhood inflammatory bowel disease (IBD), but data for adults are mixed, and based on smaller investigations that did not compare risk among siblings with shared genetic or environmental risk factors. We aimed to investigate the association between antibiotic therapy and IBD in a large, population-based study.Methods: In this prospective case-control study, we identified people living in Sweden aged 16 years or older, with a diagnosis of IBD based on histology and at least one diagnosis code for IBD or its subtypes (ulcerative colitis and Crohn's disease). We identified consecutive patients with incident IBD from the ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) study, cross-referenced with the Swedish Patient Register and the Prescribed Drug Register. We accrued data for cumulative antibiotic dispensations until 1 year before time of matching for patients and up to five general population controls per patient (matched on the basis of age, sex, county, and calendar year). We also included unaffected full siblings as a secondary control group. Conditional logistic regression was used to estimate multivariable-adjusted odds ratios (aORs) and 95% CIs for diagnosis of incident IBD.Findings: We identified 23 982 new patients with IBD (15 951 ulcerative colitis, 7898 Crohn's disease, 133 unclassified IBD) diagnosed between Jan 1, 2007, and Dec 31, 2016. 117 827 matched controls and 28 732 siblings were also identified. After adjusting for several risk factors, aOR in patients who had used antibiotics versus those who had never used antibiotics was 1.88 (95% CI 1.79-1.98) for diagnosis of incident IBD, 1.74 (1.64-1.85) for ulcerative colitis, and 2.27 (2.06-2.49) for Crohn's disease. aOR was higher in patients who had received one antibiotic dispensation (1.11, 1.07-1.15), two antibiotic dispensations (1.38, 1.32-1.44), and three or more antibiotic dispensations (1.55, 1.49-1.61) than patients who had none. Increased risk was noted for ulcerative colitis (aOR with three or more antibiotic dispensations 1.47, 95% CI 1.40-1.54) and Crohn's disease (1.64, 1.53-1.76) with higher estimates corresponding to broad-spectrum antibiotics. Similar but attenuated results were observed when siblings were used as the reference group, with an aOR of 1.35 (95% CI 1.28-1.43) for patients who had received three or more dispensations, compared with general population controls.Interpretation: Higher cumulative exposure to systemic antibiotic therapy, particularly treatments with greater spectrum of microbial coverage, may be associated with a greater risk of new-onset IBD and its subtypes. The association between antimicrobial treatment and IBD did not appear to differ when predisposed siblings were used as the reference controls. Our findings, if substantiated by longer-term prospective studies in humans or mechanistic preclinical investigations, suggest the need to further emphasise antibiotic stewardship to prevent the rise in dysbiosis-related chronic diseases, including IBD.
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| 194. |
- Osoegawa, Kazutoyo, et al.
(författare)
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Quality control project of NGS HLA genotyping for the 17th International HLA and Immunogenetics Workshop
- 2019
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Ingår i: Human Immunology. - : ELSEVIER SCIENCE INC. - 0198-8859 .- 1879-1166. ; 80:4, s. 228-236
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Tidskriftsartikel (refereegranskat)abstract
- The 17th International HLA and Immunogenetics Workshop (IHIW) organizers conducted a Pilot Study (PS) in which 13 laboratories (15 groups) participated to assess the performance of the various sequencing library preparation protocols, NGS platforms and software in use prior to the workshop. The organizers sent 50 cell lines to each of the 15 groups, scored the 15 independently generated sets of NGS HLA genotyping data, and generated "consensus" HLA genotypes for each of the 50 cell lines. Proficiency Testing (PT) was subsequently organized using four sets of 24 cell lines, selected from 48 of 50 PS cell lines, to validate the quality of NGS HLA typing data from the 34 participating IHIW laboratories. Completion of the PT program with a minimum score of 95% concordance at the HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 loci satisfied the requirements to submit NGS HLA typing data for the 17th IHIW projects. Together, these PS and PT efforts constituted the 17th IHIW Quality Control project. Overall PT concordance rates for HLA-A, HLA-B, HLA-C, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB3, HLA-DRB4 and HLA-DRB5 were 98.1%, 97.0% and 98.1%, 99.0%, 98.6%, 98.8%, 97.6%, 96.0%, 99.1%, 90.0% and 91.7%, respectively. Across all loci, the majority of the discordance was due to allele dropout. The high cost of NGS HLA genotyping per experiment likely prevented the retyping of initially failed HLA loci. Despite the high HLA genotype concordance rates of the software, there remains room for improvement in the assembly of more accurate consensus DNA sequences by NGS HLA genotyping software.
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| 195. |
- Papadimitriou, Nikos, et al.
(författare)
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Body size and risk of colorectal cancer molecular defined subtypes and pathways : mendelian randomization analyses
- 2024
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 101
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Tidskriftsartikel (refereegranskat)abstract
- Background: Obesity has been positively associated with most molecular subtypes of colorectal cancer (CRC); however, the magnitude and the causality of these associations is uncertain.Methods: We used Mendelian randomization (MR) to examine potential causal relationships between body size traits (body mass index [BMI], waist circumference, and body fat percentage) with risks of Jass classification types and individual subtypes of CRC (microsatellite instability [MSI] status, CpG island methylator phenotype [CIMP] status, BRAF and KRAS mutations). Summary data on tumour markers were obtained from two genetic consortia (CCFR, GECCO).Findings: A 1-standard deviation (SD:5.1 kg/m2) increment in BMI levels was found to increase risks of Jass type 1MSI-high,CIMP-high,BRAF-mutated,KRAS-wildtype (odds ratio [OR]: 2.14, 95% confidence interval [CI]: 1.46, 3.13; p-value = 9 × 10−5) and Jass type 2non-MSI-high,CIMP-high,BRAF-mutated,KRAS-wildtype CRC (OR: 2.20, 95% CI: 1.26, 3.86; p-value = 0.005). The magnitude of these associations was stronger compared with Jass type 4non-MSI-high,CIMP-low/negative,BRAF-wildtype,KRAS-wildtype CRC (p-differences: 0.03 and 0.04, respectively). A 1-SD (SD:13.4 cm) increment in waist circumference increased risk of Jass type 3non-MSI-high,CIMP-low/negative,BRAF-wildtype,KRAS-mutated (OR 1.73, 95% CI: 1.34, 2.25; p-value = 9 × 10−5) that was stronger compared with Jass type 4 CRC (p-difference: 0.03). A higher body fat percentage (SD:8.5%) increased risk of Jass type 1 CRC (OR: 2.59, 95% CI: 1.49, 4.48; p-value = 0.001), which was greater than Jass type 4 CRC (p-difference: 0.03).Interpretation: Body size was more strongly linked to the serrated (Jass types 1 and 2) and alternate (Jass type 3) pathways of colorectal carcinogenesis in comparison to the traditional pathway (Jass type 4).Funding: Cancer Research UK, National Institute for Health Research, Medical Research Council, National Institutes of Health, National Cancer Institute, American Institute for Cancer Research, Brigham and Women's Hospital, Prevent Cancer Foundation, Victorian Cancer Agency, Swedish Research Council, Swedish Cancer Society, Region Västerbotten, Knut and Alice Wallenberg Foundation, Lion's Cancer Research Foundation, Insamlingsstiftelsen, Umeå University. Full funding details are provided in acknowledgements.
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| 196. |
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| 197. |
- Pei, Xilong, et al.
(författare)
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RIS-Aided Wireless Communications : Prototyping, Adaptive Beamforming, and Indoor/Outdoor Field Trials
- 2021
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Ingår i: IEEE Transactions on Communications. - : Institute of Electrical and Electronics Engineers (IEEE). - 0090-6778 .- 1558-0857. ; 69:12, s. 8627-8640
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Tidskriftsartikel (refereegranskat)abstract
- The prospects of using a Reconfigurable Intelligent Surface (RIS) to aid wireless communication systems have recently received much attention from academia and industry. Most papers make theoretical studies based on elementary models, while the prototyping of RIS-aided wireless communication and real-world field trials are scarce. In this paper, we describe a new RIS prototype consisting of 1100 controllable elements working at 5.8 GHz band. We propose an efficient algorithm for configuring the RIS over the air by exploiting the geometrical array properties and a practical receiver-RIS feedback link. In our indoor test, where the transmitter and receiver are separated by a 30 cm thick concrete wall, our RIS prototype provides a 26 dB power gain compared to the baseline case where the RIS is replaced by a copper plate. A 27 dB power gain was observed in the short-distance outdoor measurement. We also carried out long-distance measurements and successfully transmitted a 32 Mbps data stream over 500 m. A 1080p video was live-streamed and it only played smoothly when the RIS was utilized. The power consumption of the RIS is around 1 W. Our paper is vivid proof that the RIS is a very promising technology for future wireless communications.
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| 198. |
- Shi, K. W., et al.
(författare)
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Observation of magnetic droplets in magnetic tunnel junctions
- 2022
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Ingår i: Science China-Physics Mechanics & Astronomy. - : Springer Science and Business Media LLC. - 1674-7348 .- 1869-1927. ; 65:2
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Tidskriftsartikel (refereegranskat)abstract
- Magnetic droplets, a class of highly nonlinear magnetodynamic solitons, can be nucleated and stabilized in nanocontact spin-torque nano-oscillators. Here we experimentally demonstrate magnetic droplets in magnetic tunnel junctions (MTJs). The droplet nucleation is accompanied by power enhancement compared with its ferromagnetic resonance modes. The nucleation and stabilization of droplets are ascribed to the double-CoFeB free-layer structure in the all-perpendicular MTJ, which provides a low Zhang-Li torque and a high pinning field. Our results enable better electrical sensitivity in fundamental studies of droplets and show that the droplets can be utilized in MTJ-based applications and materials science.
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| 199. |
- Tan, Zhifei, et al.
(författare)
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Constitutive modelling and systematic evaluation of asphalt concrete’s viscoelastic tension-compression asymmetry effect on pavement performance
- 2024
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Ingår i: The international journal of pavement engineering. - : Informa UK Limited. - 1029-8436 .- 1477-268X. ; 25:1
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Tidskriftsartikel (refereegranskat)abstract
- Asphalt concrete (AC) exhibits significant tension-compression (TC) asymmetry, which is currently not considered in pavement design. This study develops a novel temperature-dependent dual viscoelastic model to quantitatively capture the viscoelastic behaviour of AC. Unlike the conventional viscoelastic constitutive model, the proposed model decomposes strain into tensile and compressive components to characterise AC’s TC asymmetry. Additionally, a systematic modelling framework with intrinsic TC asymmetry is developed for the first time to predict the response of pavement under moving tire load. The results illustrate that implementing the proposed dual viscoelastic model enlarges both the vertical deformation of pavements and the tensile and shear strains in the AC layers, bringing it closer to the realistic scenario compared to the conventional model that only considers compression properties. Furthermore, high temperatures and low vehicular speeds exacerbate the substantial effects of AC’s TC asymmetry on asphalt pavement. This study provides a valuable method to capture AC’s TC asymmetry and predict pavement response more accurately, giving better insight into pavement response and enhancing pavement design and maintenance.
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| 200. |
- Thomas, Claire E., et al.
(författare)
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Epidemiologic factors in relation to colorectal cancer risk and survival by genotoxic colibactin mutational signature
- 2024
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association For Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 33:4, s. 534-546
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The genotoxin colibactin causes a tumor single-base substitution (SBS) mutational signature, SBS88. It is unknown whether epidemiologic factors' association with colorectal cancer risk and survival differs by SBS88.METHODS: Within the Genetic Epidemiology of Colorectal Cancer Consortium and Colon Cancer Family Registry, we measured SBS88 in 4,308 microsatellite stable/microsatellite instability low tumors. Associations of epidemiologic factors with colorectal cancer risk by SBS88 were assessed using multinomial regression (N = 4,308 cases, 14,192 controls; cohort-only cases N = 1,911), and with colorectal cancer-specific survival using Cox proportional hazards regression (N = 3,465 cases).RESULTS: 392 (9%) tumors were SBS88 positive. Among all cases, the highest quartile of fruit intake was associated with lower risk of SBS88-positive colorectal cancer than SBS88-negative colorectal cancer [odds ratio (OR) = 0.53, 95% confidence interval (CI) 0.37-0.76; OR = 0.75, 95% CI 0.66-0.85, respectively, Pheterogeneity = 0.047]. Among cohort studies, associations of body mass index (BMI), alcohol, and fruit intake with colorectal cancer risk differed by SBS88. BMI ≥30 kg/m2 was associated with worse colorectal cancer-specific survival among those SBS88-positive [hazard ratio (HR) = 3.40, 95% CI 1.47-7.84], but not among those SBS88-negative (HR = 0.97, 95% CI 0.78-1.21, Pheterogeneity = 0.066).CONCLUSIONS: Most epidemiologic factors did not differ by SBS88 for colorectal cancer risk or survival. Higher BMI may be associated with worse colorectal cancer-specific survival among those SBS88-positive; however, validation is needed in samples with whole-genome or whole-exome sequencing available.IMPACT: This study highlights the importance of identification of tumor phenotypes related to colorectal cancer and understanding potential heterogeneity for risk and survival.
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