| 1. |
- Kang, E. Y., et al.
(författare)
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MCM3 is a novel proliferation marker associated with longer survival for patients with tubo-ovarian high-grade serous carcinoma
- 2022
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Ingår i: Virchows Archiv. - : Springer Science and Business Media LLC. - 0945-6317 .- 1432-2307. ; 480, s. 855-871
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Tidskriftsartikel (refereegranskat)abstract
- Tubo-ovarian high-grade serous carcinomas (HGSC) are highly proliferative neoplasms that generally respond well to platinum/taxane chemotherapy. We recently identified minichromosome maintenance complex component 3 (MCM3), which is involved in the initiation of DNA replication and proliferation, as a favorable prognostic marker in HGSC. Our objective was to further validate whether MCM3 mRNA expression and possibly MCM3 protein levels are associated with survival in patients with HGSC. MCM3 mRNA expression was measured using NanoString expression profiling on formalin-fixed and paraffin-embedded tissue (N = 2355 HGSC) and MCM3 protein expression was assessed by immunohistochemistry (N = 522 HGSC) and compared with Ki-67. Kaplan-Meier curves and the Cox proportional hazards model were used to estimate associations with survival. Among chemotherapy-naive HGSC, higher MCM3 mRNA expression (one standard deviation increase in the score) was associated with longer overall survival (HR = 0.87, 95% CI 0.81-0.92, p < 0.0001, N = 1840) in multivariable analysis. MCM3 mRNA expression was highest in the HGSC C5.PRO molecular subtype, although no interaction was observed between MCM3, survival and molecular subtypes. MCM3 and Ki-67 protein levels were significantly lower after exposure to neoadjuvant chemotherapy compared to chemotherapy-naive tumors: 37.0% versus 46.4% and 22.9% versus 34.2%, respectively. Among chemotherapy-naive HGSC, high MCM3 protein levels were also associated with significantly longer disease-specific survival (HR = 0.52, 95% CI 0.36-0.74, p = 0.0003, N = 392) compared to cases with low MCM3 protein levels in multivariable analysis. MCM3 immunohistochemistry is a promising surrogate marker of proliferation in HGSC.
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| 2. |
- Menkveld, Albert J., et al.
(författare)
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Nonstandard Errors
- 2024
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Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
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Tidskriftsartikel (refereegranskat)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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| 3. |
- Sintes, J, et al.
(författare)
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mTOR intersects antibody-inducing signals from TACI in marginal zone B cells
- 2017
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1, s. 1462-
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Tidskriftsartikel (refereegranskat)abstract
- Mechanistic target of rapamycin (mTOR) enhances immunity in addition to orchestrating metabolism. Here we show that mTOR coordinates immunometabolic reconfiguration of marginal zone (MZ) B cells, a pre-activated lymphocyte subset that mounts antibody responses to T-cell-independent antigens through a Toll-like receptor (TLR)-amplified pathway involving transmembrane activator and CAML interactor (TACI). This receptor interacts with mTOR via the TLR adapter MyD88. The resulting mTOR activation instigates MZ B-cell proliferation, immunoglobulin G (IgG) class switching, and plasmablast differentiation through a rapamycin-sensitive pathway that integrates metabolic and antibody-inducing transcription programs, including NF-κB. Disruption of TACI–mTOR interaction by rapamycin, truncation of the MyD88-binding domain of TACI, or B-cell-conditional mTOR deficiency interrupts TACI signaling via NF-κB and cooperation with TLRs, thereby hampering IgG production to T-cell-independent antigens but not B-cell survival. Thus, mTOR drives innate-like antibody responses by linking proximal TACI signaling events with distal immunometabolic transcription programs.
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| 4. |
- Li, K. -A, et al.
(författare)
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The Stellar β-decay Rate of 134Cs and Its Impact on the Barium Nucleosynthesis in the s-process
- 2021
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 919:2, s. L19-
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Tidskriftsartikel (refereegranskat)abstract
- We have calculated the stellar β-decay rate of the important s-process branching point 134Cs based on the state-of-the-art shell model calculations. At typical s-process temperatures (T ∼ 0.2-0.3 GK), our new rate is one order of magnitude lower than the widely used rate from Takahashi and Yokoi (hereafter TY87). The impact on the nucleosynthesis in AGB stars is investigated with various masses and metallicities. Our new decay rate leads to an overall decrease in the 134Ba/136Ba ratio, and well explains the measured ratio in meteorites without introducing the i-process. We also derive the elapsed time from the last AGB nucleosynthetic event that polluted the early solar system to be >28 Myr based on the 135Cs/133Cs ratio, which is consistent with the elapsed times derived from 107Pd and 182Hf. The s-process abundance sum of 135Ba and 135Cs is found to increase, resulting in a smaller r-process contribution of 135Ba in the solar system.
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| 5. |
- Unterkalmsteiner, Michael, et al.
(författare)
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Software startups-A research agenda
- 2016
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Ingår i: e-Informatica Software Engineering Journal. - : Politechnika Wroclawska. - 1897-7979 .- 2084-4840. ; 10:1, s. 89-123
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Tidskriftsartikel (refereegranskat)abstract
- Software startup companies develop innovative, software-intensive products within limited time frames and with few resources, searching for sustainable and scalable business models. Software startups are quite distinct from traditional mature software companies, but also from micro-, small-, and medium-sized enterprises, introducing new challenges relevant for software engineering research. This paper's research agenda focuses on software engineering in startups, identifying, in particular, 70+ research questions in the areas of supporting startup engineering activities, startup evolution models and patterns, ecosystems and innovation hubs, human aspects in software startups, applying startup concepts in non-startup environments, and methodologies and theories for startup research. We connect and motivate this research agenda with past studies in software startup research, while pointing out possible future directions. While all authors of this research agenda have their main background in Software Engineering or Computer Science, their interest in software startups broadens the perspective to the challenges, but also to the opportunities that emerge from multi-disciplinary research. Our audience is therefore primarily software engineering researchers, even though we aim at stimulating collaborations and research that crosses disciplinary boundaries. We believe that with this research agenda we cover a wide spectrum of the software startup industry current needs.
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