| 1. |
- 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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| 2. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 3. |
- 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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| 4. |
- Al-Rabadi, Laith Farah, et al.
(författare)
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Serine Protease HTRA1 as a Novel Target Antigen in Primary Membranous Nephropathy
- 2021
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Ingår i: Journal of the American Society of Nephrology. - : American Society of Nephrology (ASN). - 1046-6673 .- 1533-3450. ; 32:7, s. 1666-1681
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Tidskriftsartikel (refereegranskat)abstract
- Background Identification of target antigens PLA2R, THSD7A, NELL1, or Semaphorin-3B can explain the majority of cases of primary membranous nephropathy (MN). However, target antigens remain unidentified in 15%-20% of patients. Methods A multipronged approach, using traditional and modern technologies, converged on a novel target antigen, and capitalized on the temporal variation in autoantibody titer for biomarker discovery. Immunoblotting of human glomerular proteins followed by differential immunoprecipitation and mass spectrometric analysis was complemented by laser-capture microdissection followed by mass spectrometry, elution of immune complexes from renal biopsy specimen tissue, and autoimmune profiling on a protein fragment microarray. Results These approaches identified serine protease HTRA1 as a novel podocyte antigen in a subset of patients with primary MN. Sera from two patients reacted by immunoblotting with a 51-kD protein within glomerular extract and with recombinant human HTRA1, under reducing and nonreducing conditions. Longitudinal serum samples from these patients seemed to correlate with clinical disease activity. As in PLA2R- and THSD7A- associated MN, anti-HTRA1 antibodies were predominantly IgG4, suggesting a primary etiology. Analysis of sera collected during active disease versus remission on protein fragment microarrays detected significantly higher titers of anti-HTRA1 antibody in active disease. HTRA1 was specifically detected within immune deposits of HTRA1-associated MN in 14 patients identified among three cohorts. Screening of 118 "quadruple-negative" (PLA2R-, THSD7A-, NELL1-, EXT2-negative) patients in a large repository of MN biopsy specimens revealed a prevalence of 4.2%. Conclusions Conventional and more modern techniques converged to identify serine protease HTRA1 as a target antigen in MN.
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| 5. |
- Bergstedt, Edwin, et al.
(författare)
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Gear micropitting initiation of ground and superfinished gears : Wrought versus pressed and sintered steel
- 2021
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Ingår i: Tribology International. - : Elsevier BV. - 0301-679X .- 1879-2464. ; 160
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Tidskriftsartikel (refereegranskat)abstract
- This paper investigates the resistance of micropitting on two materials, using an FZG back-to-back test rig with CPT gears. The materials are wrought steel (16MnCr5) and a commercial powder metallurgical material (AstaloyTM Mo). Two finishing methods were studied: grinding and superfinishing. Experimental results show that the superfinishing prevented micropitting, but led to premature failure due to cracks in the root caused by tip-to-root interference. Micropitting was initiated at a higher load stage for the powder metallurgical steel compared to the ground wrought steel. The failure mechanisms were similar between materials with the same surface finish. The powder metallurgical steel showed subsurface initiated fatigue compared to the wrought ground steel having surface-initiated fatigue. Testing new finishing methods and materials, one has to be aware of the influence of the gear micro geometry.
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| 6. |
- Bergstedt, Edwin, 1986-, et al.
(författare)
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Gear Micropitting Initiation of Ground and Superfinished Gears: Wrought versus Pressed and Sintered Steel
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Ingår i: Tribology International. - 0301-679X .- 1879-2464.
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Tidskriftsartikel (refereegranskat)abstract
- This paper investigates the resistance of micropitting on two materials, using an FZG back-to-back test rig with C-PT gears. The materials are wrought steel (16MnCr5) and a commercialpowder metallurgical material (AstaloyTM Mo). Two finishing methods were studied: grinding andsuperfinishing. Experimental results show that the superfinishing prevented micropitting, but ledto premature failure due to cracks in the root caused by tip-to-root interference. Micropitting wasinitiated at load stage 8, and 9 for the ground wrought, and powder metallurgical steel respectively.The failure mechanisms were similar between materials with the same surface finish. The powdermetallurgical steel showed subsurface initiated fatigue compared to the wrought groundsteel having surface-initiated fatigue. Testing new finishing methods and materials, onehas to be aware of the influence of the gear micro geometry.
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| 7. |
- Bergstedt, Edwin, et al.
(författare)
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Influence of gear surface roughness on the pitting and micropitting life
- 2020
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Ingår i: Proceedings of the Institution of mechanical engineers. Part C, journal of mechanical engineering science. - : SAGE Publications Ltd. - 0954-4062 .- 2041-2983. ; 234:24, s. 4953-4961
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Tidskriftsartikel (refereegranskat)abstract
- Pitting and micropitting are the two main gear rolling contact fatigue modes. It is widely accepted that micropitting will lead to pitting; however, the relationship between pitting and micropitting life needs further investigation. In this work, micropitting and pitting tests were performed on an FZG back-to-back test rig using standard FZG PT-C and GF-C gears. The gear tooth profile change due to micropitting and pitting damage was measured in situ in the gearbox using a profilometer after each test. The gear surface roughness parameters were calculated from the measured tooth profile. A Gaussian low pass filter with cut off length (Formula presented.) mm was applied to the measured tooth profile to obtain the waviness. The calculated roughness parameters and the obtained tooth profile with waviness for each test were imported into the KISSsoft software to calculate the contact stress and specific film thickness at the corresponding load stage. Experimental results show that smooth gear surface can reduce or even avoid micropitting damage, but could lead to a reduction in pitting life.
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| 8. |
- Brownstein, Catherine A., et al.
(författare)
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An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
- 2014
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:3, s. R53-
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
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| 9. |
- Hu, Bei, et al.
(författare)
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Timing of allogeneic hematopoietic cell transplantation (alloHCT) for chronic myeloid leukemia (CML) patients
- 2020
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Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 61:12, s. 2811-2820
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Tidskriftsartikel (refereegranskat)abstract
- While TKI are the preferred first-line treatment for chronic phase (CP) CML, alloHCT remains an important consideration. The aim is to estimate residual life expectancy (RLE) for patients initially diagnosed with CP CML based on timing of alloHCT or continuation of TKI in various settings: CP1 CML, CP2 + [after transformation to accelerated phase (AP) or blast phase (BP)], AP, or BP. Non-transplant cohort included single-institution patients initiating TKI and switched TKI due to failure. CIBMTR transplant cohort included CML patients who underwent HLA sibling matched (MRD) or unrelated donor (MUD) alloHCT. AlloHCT appeared to shorten survival in CP1 CML with overall mortality hazard ratio (HR) for alloHCT of 2.4 (95% CI 1.2-4.9;p = .02). In BP CML, there was a trend toward higher survival with alloHCT; HR = 0.7 (0.5-1.1;p = .099). AlloHCT in CP2 + [HR = 2.0 (0.8-4.9),p = .13] and AP [HR = 1.1 (0.6-2.1);p = .80] is less clear and should be determined on a case-by-case basis.
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| 10. |
- Lin, Jiachun, et al.
(författare)
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A quantitatively distributed wear-measurement method for spur gears during micro-pitting and pitting tests
- 2021
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Ingår i: Tribology International. - : Elsevier BV. - 0301-679X .- 1879-2464. ; 157
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Tidskriftsartikel (refereegranskat)abstract
- FZG gear testing is widely used to evaluate the performance of lubricants, gear materials, and gear-tooth geometries under different loads. During these tests, gear tooth wear results in the loss of gear profile in the form of micro-pitting, pitting and scuffing, can be observed. However, gear wear is usually measured by weighting. This method cannot be used to study the wear depth on a specific point on the gear-tooth surface. In this study, tooth profiles were measured via a profilometer during the FZG gear-pitting test. Moreover, an algorithm was developed to quantitatively evaluate the distributed cumulative wear and wear progress at a certain test stage. Simultaneously, the real tooth profile was obtained. Experiments were performed to validate the proposed method, and the results showed that gear-tooth-surface wear can be quantitatively determined. Thus, the proposed method can be used for further gear-failure-prediction experiments.
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