| 1. |
- Schweinsberg, Martin, et al.
(författare)
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Same data, different conclusions : Radical dispersion in empirical results when independent analysts operationalize and test the same hypothesis
- 2021
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Ingår i: Organizational Behavior and Human Decision Processes. - : Elsevier BV. - 0749-5978 .- 1095-9920. ; 165, s. 228-249
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Tidskriftsartikel (refereegranskat)abstract
- In this crowdsourced initiative, independent analysts used the same dataset to test two hypotheses regarding the effects of scientists' gender and professional status on verbosity during group meetings. Not only the analytic approach but also the operationalizations of key variables were left unconstrained and up to individual analysts. For instance, analysts could choose to operationalize status as job title, institutional ranking, citation counts, or some combination. To maximize transparency regarding the process by which analytic choices are made, the analysts used a platform we developed called DataExplained to justify both preferred and rejected analytic paths in real time. Analyses lacking sufficient detail, reproducible code, or with statistical errors were excluded, resulting in 29 analyses in the final sample. Researchers reported radically different analyses and dispersed empirical outcomes, in a number of cases obtaining significant effects in opposite directions for the same research question. A Boba multiverse analysis demonstrates that decisions about how to operationalize variables explain variability in outcomes above and beyond statistical choices (e.g., covariates). Subjective researcher decisions play a critical role in driving the reported empirical results, underscoring the need for open data, systematic robustness checks, and transparency regarding both analytic paths taken and not taken. Implications for orga-nizations and leaders, whose decision making relies in part on scientific findings, consulting reports, and internal analyses by data scientists, are discussed.
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| 2. |
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| 3. |
- Chen, Hu, et al.
(författare)
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Acene Ring Size Optimization in Fused Lactam Polymers Enabling High n-Type Organic Thermoelectric Performance
- 2021
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Ingår i: Journal of the American Chemical Society. - : AMER CHEMICAL SOC. - 0002-7863 .- 1520-5126. ; 143:1, s. 260-268
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Tidskriftsartikel (refereegranskat)abstract
- Three n-type fused lactam semiconducting polymers were synthesized for thermoelectric and transistor applications via a cheap, highly atom-efficient, and nontoxic transition-metal free aldol polycondensation. Energy level analysis of the three polymers demonstrated that reducing the central acene core size from two anthracenes (A-A), to mixed naphthalene-anthracene (A-N), and two naphthalene cores (N-N) resulted in progressively larger electron affinities, thereby suggesting an increasingly more favorable and efficient solution doping process when employing 4-(2,3-dihydro-1,3-dimethyl-1H-benzimidazol-2-yl)-N,N-dimethylbenzenamine (N-DMBI) as the dopant. Meanwhile, organic field effect transistor (OFET) mobility data showed the N-N and A-N polymers to feature the highest charge carrier mobilities, further highlighting the benefits of aryl core contraction to the electronic performance of the materials. Ultimately, the combination of these two factors resulted in N-N, A-N, and A-A to display power factors (PFs) of 3.2 mu W m(-1) K-2, 1.6 mu W m(-1 )K(-2), and 0.3 mu W m(-1) K-2, respectively, when doped with N-DMBI, whereby the PFs recorded for N-N and A-N are among the highest reported in the literature for n-type polymers. Importantly, the results reported in this study highlight that modulating the size of the central acene ring is a highly effective molecular design strategy to optimize the thermoelectric performance of conjugated polymers, thus also providing new insights into the molecular design guidelines for the next generation of high-performance n-type materials for thermoelectric applications.
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| 4. |
- Ghavami, Saeid, et al.
(författare)
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Mevalonate Cascade Regulation of Airway Mesenchymal Cell Autophagy and Apoptosis: A Dual Role for p53
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:1, s. 0016523-
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Tidskriftsartikel (refereegranskat)abstract
- Statins inhibit the proximal steps of cholesterol biosynthesis, and are linked to health benefits in various conditions, including cancer and lung disease. We have previously investigated apoptotic pathways triggered by statins in airway mesenchymal cells, and identified reduced prenylation of small GTPases as a primary effector mechanism leading to p53-mediated cell death. Here, we extend our studies of statin-induced cell death by assessing endpoints of both apoptosis and autophagy, and investigating their interplay and coincident regulation. Using primary cultured human airway smooth muscle (HASM) and human airway fibroblasts (HAF), autophagy, and autophagosome formation and flux were assessed by transmission electron microscopy, cytochemistry (lysosome number and co-localization with LC3) and immunoblotting (LC3 lipidation and Atg 12-5 complex formation). Chemical inhibition of autophagy increased simvastatin-induced caspase activation and cell death. Similarly, Atg5 silencing with shRNA, thus preventing Atg5-12 complex formation, increased proapoptotic effects of simvastatin. Simvastatin concomitantly increased p53-dependent expression of p53 up-regulated modulator of apoptosis (PUMA), NOXA, and damage-regulated autophagy modulator (DRAM). Notably both mevalonate cascade inhibition-induced autophagy and apoptosis were p53 dependent: simvastatin increased nuclear p53 accumulation, and both cyclic pifithrin-alpha and p53 shRNAi partially inhibited NOXA, PUMA expression and caspase-3/7 cleavage (apoptosis) and DRAM expression, Atg5-12 complex formation, LC3 lipidation, and autophagosome formation (autophagy). Furthermore, the autophagy response is induced rapidly, significantly delaying apoptosis, suggesting the existence of a temporally coordinated p53 regulation network. These findings are relevant for the development of statin-based therapeutic approaches in obstructive airway disease.
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| 5. |
- Ghavami, Saeid, et al.
(författare)
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S100A8/A9 induces autophagy and apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes that involves BNIP3
- 2010
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Ingår i: Cell Research. - : Springer Science and Business Media LLC. - 1001-0602 .- 1748-7838. ; 20:3, s. 314-331
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Tidskriftsartikel (refereegranskat)abstract
- The complex formed by two members of the S100 calcium-binding protein family, S100A8/A9, exerts apoptosis-inducing activity in various cells of different origins. Here, we present evidence that the underlying molecular mechanisms involve both programmed cell death I (PCD I, apoptosis) and PCD II (autophagy)-like death. Treatment of cells with S100A8/A9 caused the increase of Beclin-1 expression as well as Atg12-Atg5 formation. S100A8/A9-induced cell death was partially inhibited by the specific PI3-kinase class III inhibitor, 3-methyladenine (3-MA), and by the vacuole H+-ATPase inhibitor, bafilomycin-A1 (Baf-A1). S100A8/A9 provoked the translocation of BNIP3, a BH3 only pro-apoptotic Bcl2 family member, to mitochondria. Consistent with this finding, ΔTM-BNIP3 overexpression partially inhibited S100A8/A9-induced cell death, decreased reactive oxygen species (ROS) generation, and partially protected against the decrease in mitochondrial transmembrane potential in S100A8/A9-treated cells. In addition, either ΔTM-BNIP3 overexpression or N-acetyl-L-cysteine co-treatment decreased lysosomal activation in cells treated with S100A8/A9. Our data indicate that S100A8/A9-promoted cell death occurs through the cross-talk of mitochondria and lysosomes via ROS and the process involves BNIP3.
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| 6. |
- Ghavami, Saeid, et al.
(författare)
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Statin-triggered cell death in primary human lung mesenchyrnal cells involves p53-PUMA and release of Smac and Omi but not cytochrome c
- 2010
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Ingår i: Biochimica et Biophysica Acta. - : Elsevier. - 0006-3002 .- 1878-2434. ; 1803:4, s. 452-467
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Tidskriftsartikel (refereegranskat)abstract
- Statins inhibit 3-hydroxy-3-methyl-glutarylcoenzyme CoA (HMG-CoA) reductase, the proximal enzyme forcholesterol biosynthesis. They exhibit pleiotropic effects and are linked to health benefits for diseasesincluding cancer and lung disease. Understanding their mechanism of action could point to new therapies,thus we investigated the response of primary cultured human airway mesenchymal cells, which play aneffector role in asthma and chronic obstructive lung disease (COPD), to simvastatin exposure. Simvastatininduced apoptosis involving caspase-9, -3 and -7, but not caspase-8 in airway smooth muscle cells andfibroblasts. HMG-CoA inhibition did not alter cellular cholesterol content but did abrogate de novocholesterol synthesis. Pro-apoptotic effects were prevented by exogenous mevalonate, geranylgeranylpyrophosphate and farnesyl pyrophosphate, downstream products of HMG-CoA. Simvastatin increasedexpression of Bax, oligomerization of Bax and Bak, and expression of BH3-only p53-dependent genes, PUMAand NOXA. Inhibition of p53 and silencing of p53 unregulated modulator of apoptosis (PUMA) expressionpartly counteracted simvastatin-induced cell death, suggesting a role for p53-independent mechanisms.Simvastatin did not induce mitochondrial release of cytochrome c, but did promote release of inhibitor ofapoptosis (IAP) proteins, Smac and Omi. Simvastatin also inhibited mitochondrial fission with the loss ofmitochondrial Drp1, an essential component of mitochondrial fission machinery. Thus, simvastatin activatesnovel apoptosis pathways in lung mesenchymal cells involving p53, IAP inhibitor release, and disruption ofmitochondrial fission.
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| 7. |
- McNeill, Lisa C., et al.
(författare)
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Understanding Himalayan erosion and the significance of the Nicobar Fan
- 2017
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Ingår i: Earth and Planetary Science Letters. - : Elsevier BV. - 0012-821X .- 1385-013X. ; 475, s. 134-142
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Tidskriftsartikel (refereegranskat)abstract
- A holistic view of the Bengal-Nicobar Fan system requires sampling the full sedimentary section of the Nicobar Fan, which was achieved for the first time by International Ocean Discovery Program (IODP) Expedition 362 west of North Sumatra. We identified a distinct rise in sediment accumulation rate (SAR) beginning similar to 9.5 Ma and reaching 250-350 m/Myr in the 9.5-2 Ma interval, which equal or far exceed rates on the Bengal Fan at similar latitudes. This marked rise in SAR and a constant Himalayan-derived provenance necessitates a major restructuring of sediment routing in the Bengal-Nicobar submarine fan. This coincides with the inversion of the Eastern Himalayan Shillong Plateau and encroachment of the west-propagating Indo-Burmese wedge, which reduced continental accommodation space and increased sediment supply directly to the fan. Our results challenge a commonly held view that changes in sediment flux seen in the Bengal-Nicobar submarine fan were caused by discrete tectonic or climatic events acting on the Himalayan-Tibetan Plateau. Instead, an interplay of tectonic and climatic processes caused the fan system to develop by punctuated changes rather than gradual progradation.
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| 8. |
- Steffen, Will, et al.
(författare)
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Stratigraphic and Earth System approaches to defining the Anthropocene
- 2016
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Ingår i: Earth's Future. - 2328-4277. ; 4:8, s. 324-345
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Forskningsöversikt (refereegranskat)abstract
- Stratigraphy provides insights into the evolution and dynamics of the Earth System over its long history. With recent developments in Earth System science, changes in Earth System dynamics can now be observed directly and projected into the near future. An integration of the two approaches provides powerful insights into the nature and significance of contemporary changes to Earth. From both perspectives, the Earth has been pushed out of the Holocene Epoch by human activities, with the mid-20th century a strong candidate for the start date of the Anthropocene, the proposed new epoch in Earth history. Here we explore two contrasting scenarios for the future of the Anthropocene, recognizing that the Earth System has already undergone a substantial transition away from the Holocene state. A rapid shift of societies toward the UN Sustainable Development Goals could stabilize the Earth System in a state with more intense interglacial conditions than in the late Quaternary climate regime and with little further biospheric change. In contrast, a continuation of the present Anthropocene trajectory of growing human pressures will likely lead to biotic impoverishment and a much warmer climate with a significant loss of polar ice.
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| 9. |
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| 10. |
- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 11. |
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