| 41. |
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| 42. |
- Haycock, Philip C., et al.
(författare)
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Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases A Mendelian Randomization Study
- 2017
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Ingår i: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 3:5, s. 636-651
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. OBJECTIVE: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. DATA SOURCES: Genomewide association studies (GWAS) published up to January 15, 2015. STUDY SELECTION: GWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available. DATA EXTRACTION AND SYNTHESIS: Summary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population. MAIN OUTCOMES AND MEASURES: Odds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation. RESULTS: Summary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [ 95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [ 95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [ 95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [ 95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [ 95% CI, 0.05-0.15]). CONCLUSIONS AND RELEVANCE: It is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
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| 43. |
- Koul, R., et al.
(författare)
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The TACTIC atmospheric Cherenkov imaging telescope
- 2007
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 578:3, s. 548-564
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Tidskriftsartikel (refereegranskat)abstract
- The TACTIC (TeV Atomospheric Cherenkov Telescope with Imaging Camera) γγ-ray telescope, equipped with a light collector of area ∼9.5m2 and a medium resolution imaging camera of 349 pixels, has been in operation at Mt. Abu, India, since 2001. This paper describes the main features of its various subsystems and its overall performance with regard to (a) tracking accuracy of its two-axes drive system, (b) spot size of the light collector, (c) back-end signal processing electronics and topological trigger generation scheme, (d) data acquisition and control system and (e) relative and absolute gain calibration methodology. Using a trigger field-of-view of 11×1111×11 pixels (∼3.4∘×3.4∘)(∼3.4∘×3.4∘), the telescope records a cosmic ray event rate of ∼2.5Hz at a typical zenith angle of 15∘15∘. Monte Carlo simulation results are also presented in the paper for comparing the expected performance of the telescope with actual observational results. The consistent detection of a steady signal from the Crab Nebula above ∼1.2TeV energy, at a sensitivity level of ∼5.0σ∼5.0σ in ∼25h, alongwith excellent matching of its energy spectrum with that obtained by other groups, reassures that the performance of the TACTIC telescope is quite stable and reliable. Furthermore, encouraged by the detection of strong γγ-ray signals from Mrk 501 (during 1997 and 2006 observations) and Mrk 421 (during 2001 and 2005–2006 observations), we believe that there is considerable scope for the TACTIC telescope to monitor similar TeV γγ-ray emission activity from other active galactic nuclei on a long-term basis.
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| 44. |
- Tickoo, A. K., et al.
(författare)
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A generalized ray-tracing procedure for an atmospheric Cherenkov imaging telescope and optical characteristics of the TACTIC light collector
- 2005
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 539:1-2, s. 177-190
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Tidskriftsartikel (refereegranskat)abstract
- A generalized ray-tracing procedure has been developed, which facilitates the design of a multimirror-based light collector used in atmospheric Cherenkov telescopes. This procedure has been employed to study the optical characteristics of the 3.5 m diameter light collector of the TACTIC Imaging telescope. Comparison of the measured point-spread function of the light collector with the simulated performance of ideal Davies–Cotton and paraboloid designs has been made to determine an optimum arrangement of the 34 spherical mirror facets used in the telescope to obtain the best possible point-spread function. A description of the ray-tracing subroutine used for processing CORSIKA-generated Cherenkov data, required for carrying out Monte-Carlo simulation studies, is also discussed in the paper.
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| 45. |
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| 46. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 47. |
- Chakravarty, D, et al.
(författare)
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Association between Incidental Pelvic Inflammation and Aggressive Prostate Cancer
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:11
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Tidskriftsartikel (refereegranskat)abstract
- The impact of pelvic inflammation on prostate cancer (PCa) biology and aggressive phenotype has never been studied. Our study objective was to evaluate the role of pelvic inflammation on PCa aggressiveness and its association with clinical outcomes in patients following radical prostatectomy (RP). This study has been conducted on a retrospective single-institutional consecutive cohort of 2278 patients who underwent robot-assisted laparoscopic prostatectomy (RALP) between 01/2013 and 10/2019. Data from 2085 patients were analyzed to study the association between pelvic inflammation and adverse pathology (AP), defined as Gleason Grade Group (GGG) > 2 and ≥ pT3 stage, at resection. In a subset of 1997 patients, the association between pelvic inflammation and biochemical recurrence (BCR) was studied. Alteration in tumor transcriptome and inflammatory markers in patients with and without pelvic inflammation were studied using microarray analysis, immunohistochemistry, and culture supernatants derived from inflamed sites used in functional assays. Changes in blood inflammatory markers in the study cohort were analyzed by O-link. In univariate analyses, pelvic inflammation emerged as a significant predictor of AP. Multivariate cox proportional-hazards regression analyses showed that high pelvic inflammation with pT3 stage and positive surgical margins significantly affected the time to BCR (p ≤ 0.05). PCa patients with high inflammation had elevated levels of pro-inflammatory cytokines in their tissues and in blood. Genes involved in epithelial-to-mesenchymal transition (EMT) and DNA damage response were upregulated in patients with pelvic inflammation. Attenuation of STAT and IL-6 signaling decreased tumor driving properties of conditioned medium from inflamed sites. Pelvic inflammation exacerbates the progression of prostate cancer and drives an aggressive phenotype.
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| 48. |
- Coignard, J, et al.
(författare)
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A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 1078-
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers.
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| 49. |
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| 50. |
- Dhar, V. K., et al.
(författare)
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ANN based energy estimation procedure and energy spectrum of the Crab Nebula as measured by the TACTIC gamma-ray telescope
- 2005
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Ingår i: 29th International Cosmic Ray Conference Pune (2005). ; , s. 179-182
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Konferensbidrag (refereegranskat)abstract
- A novel energy reconstruction procedure based on the utilization of Articial Neural Network has been developedfor the TACTIC atmospheric Cerenkov imaging telescope to estimate the energy of the primary gammaraysin the TeV energy range. The procedure uses a 3:20:1 conguration of the ANN with resilient backpropagationtraining algorithm to estimate the energy of a-ray like event on the basis of its image SIZE,DISTANCE and zenith angle. The results obtained by using the CORSIKA code simulated data suggest theenergy resolution of the telescope is40for retaining90of the-ray events in a particular energybin which is comparable to the energy resolution of other single element imaging telescopes. Details of theenergy estimation procedure along with results obtained by determining the Crab Nebula energy spectrum inthe energy range 1-16 TeV as measured by the TACTIC telescope are presented in the paper.
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